There should be no hesitation in administering the routine vaccination schedule for 13-valent pneumococcal conjugate vaccine (PCV13) on account of gestational age or birth weight in preterm infants, researchers concluded.

In a phase IV study, researchers compared 100 term with 100 preterm infants; both groups were vaccinated on the routine schedule at ages 2, 3, 4, and 12 months. After the 12-month (toddler) dose of the PCV13, the infants were evaluated for serum antibody persistence at 12 and 24 months. “To date, no studies have examined the long-term persistence of immune responses to PCV13 in formerly preterm infants,” noted Federico Martinón-Torres, MD, PhD, of Hospital Clínico Universitario de Santiago de Compostela, Spain, and his coauthors.

copyright luiscar/Thinkstock

CDC/Dr. Mike Miller

[email protected]

There should be no hesitation in administering the routine vaccination schedule for 13-valent pneumococcal conjugate vaccine (PCV13) on account of gestational age or birth weight in preterm infants, researchers concluded.

In a phase IV study, researchers compared 100 term with 100 preterm infants; both groups were vaccinated on the routine schedule at ages 2, 3, 4, and 12 months. After the 12-month (toddler) dose of the PCV13, the infants were evaluated for serum antibody persistence at 12 and 24 months. “To date, no studies have examined the long-term persistence of immune responses to PCV13 in formerly preterm infants,” noted Federico Martinón-Torres, MD, PhD, of Hospital Clínico Universitario de Santiago de Compostela, Spain, and his coauthors.

copyright luiscar/Thinkstock

CDC/Dr. Mike Miller

[email protected]

There should be no hesitation in administering the routine vaccination schedule for 13-valent pneumococcal conjugate vaccine (PCV13) on account of gestational age or birth weight in preterm infants, researchers concluded.

In a phase IV study, researchers compared 100 term with 100 preterm infants; both groups were vaccinated on the routine schedule at ages 2, 3, 4, and 12 months. After the 12-month (toddler) dose of the PCV13, the infants were evaluated for serum antibody persistence at 12 and 24 months. “To date, no studies have examined the long-term persistence of immune responses to PCV13 in formerly preterm infants,” noted Federico Martinón-Torres, MD, PhD, of Hospital Clínico Universitario de Santiago de Compostela, Spain, and his coauthors.

copyright luiscar/Thinkstock

CDC/Dr. Mike Miller

[email protected]

To the Editor:

Anti–tumor necrosis factor (TNF) α treatments have radically improved the management of chronic inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, and bowel diseases (eg, Crohn disease, ulcerative colitis [UC]). Because the number of patients treated with these agents has increased, uncommon adverse reactions have increasingly occurred. Cutaneous adverse reactions that have been reported with anti-TNF agents include immediate injection-site reaction, systemic infusion reactions, and delayed reactions.¹ Among the delayed adverse reactions, psoriatic and eczematous eruptions as well as cutaneous infections are the most common, while cutaneous adverse effects related to an immune imbalance syndrome including vasculitis; lupuslike, lichenlike, and granulomatous eruptions; and skin cancer rarely are observed.¹ Although most of the cutaneous adverse effects do not require anti-TNF treatment discontinuation and are resolved with symptomatic treatment, anti-TNF therapy must be stopped in more severe cases. We report the case of severe Henoch-Schönlein purpura (HSP) following treatment with infliximab.

A 46-year-old man who was a nonsmoker with quiescent UC on infliximab for 30 months presented with palpable necrotic purpura on both legs (Figure) and arms as well as the abdomen of 10 days’ duration, along with diffuse joint pain and swelling. He had no history of infectious or gastrointestinal symptoms. The last infliximab infusion was performed 6 weeks prior to developing the purpura. His UC was diagnosed 10 years prior to the current presentation and was not associated with any extragastrointestinal manifestations. Since diagnosis, UC had failed to respond to therapies such as azathioprine, cyclosporine, and purinethol. The complete blood cell count was normal. The C-reactive protein level was 18.7 mg/L (reference range, <5 mg/L) and the erythrocyte sedimentation rate was 30 mm/h (reference range, 0–20 mm/h). Electrolytes, urea, creatinine clearance, and liver function were normal, and a chest radiograph and radiographs of the swollen joints were unremarkable. The total IgA level was elevated at 4 g/L (reference range, 0.7–4 g/L), with IgG and IgM levels within reference range. There was no hematuria or proteinuria on urinalysis. Tests for antinuclear antibodies, rheumatoid factor, circulating immune complexes, and antineutrophil cytoplasmic antibody were negative. Total complement, C3, and C4 levels also were normal. A skin biopsy confirmed a leukocytoclastic vasculitis of small vessels with C3 deposition. Serologic tests for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative. Based on these findings, the diagnosis of HSP was made. Systemic corticosteroids—120 mg daily of intravenous methylprednisolone for 3 days, followed by 1 mg/kg daily of oral prednisone for 2 weeks—were then introduced with rapid clinical improvement. Henoch-Schönlein purpura and joint symptoms completely resolved, but UC relapsed with bloody diarrhea and severe abdominal pain. Oral prednisone was maintained (1 mg/kg daily). Because of the severity of cutaneous vasculitis (HSP), a multidisciplinary decision was taken to definitively stop the anti-TNF agents and to first add azathioprine (2 mg/kg daily for 2 months), then subcutaneous methotrexate (25 mg weekly). Colonoscopy did not show any dysplasia or adenocarcinoma and confirmed the diagnosis of UC. After 6 months of combined therapy, UC was still active and we decided to perform a total colectomy with ileostomy formation. Complete remission of UC was obtained and maintained after 28 months of follow-up.

Henoch-Schönlein purpura is a multisystem small vessel leukocytoclastic vasculitis with the deposition of immune complexes containing IgA. Clinical manifestations may include palpable purpura, arthritis, enteritis, and nephritis. Henoch-Schönlein purpura usually affects children. Adult onset is rare but associated with more severe symptoms and a poor prognosis.² The criteria for HSP, as defined by the American College of Rheumatology,³ include palpable purpura, 20 years or younger at disease onset, bowel angina, and presence of vascular wall granulocytes on biopsy. At least 2 of these criteria are required for HSP diagnosis. Various viral or bacterial infections and drugs can trigger HSP, which also can be associated with autoinflammatory or autoimmune diseases. The association of HSP and UC is a rare event, as demonstrated by de Oliveira et al.⁴ Although only 2 cases of cutaneous vasculitis mimicking HSP have been described in UC,⁴ we cannot exclude a possible association between HSP and UC. However, our patient had UC for 10 years and never had clinical manifestations of vasculitis.

There are 5 reports of HSP following etanercept^5,6 or adalimumab^7-9 therapy and 1 following infliximab therapy.¹⁰ In all cases, HSP occurred after several months of anti-TNF therapy. However, there also are reports of cutaneous vasculitis associated with arthralgia and glomerulonephritis that resolved after withdrawal of anti-TNF agents.^11,12 It is possible that some of these reactions may have been manifestations of undiagnosed HSP. In a series of 113 patients who developed cutaneous vasculitis after anti-TNF agents, visceral vasculitis was observed in 24% of patients. Treatment of vasculitis involved withdrawal of the anti-TNF therapy in 101 cases (89%).¹³ In these UC patients with few therapeutic alternatives, the continuation of anti-TNF agents should be discussed. In the previous series,¹³ of 16 patients who were rechallenged with the same or a different TNF antagonist, 12 (75%) experienced vasculitis relapse, suggesting a class effect of TNF inhibition. Because of the severity of cutaneous vasculitis and as previously suggested in a recent analytical and comprehensive overview on paradoxical reactions under TNF blockers,¹ we decided not to re-expose our patient to infliximab or to other anti-TNF agents.

In conclusion, HSP may occur during anti-TNF therapy and physicians need to be aware of this potentially serious complication.

To the Editor:

Anti–tumor necrosis factor (TNF) α treatments have radically improved the management of chronic inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, and bowel diseases (eg, Crohn disease, ulcerative colitis [UC]). Because the number of patients treated with these agents has increased, uncommon adverse reactions have increasingly occurred. Cutaneous adverse reactions that have been reported with anti-TNF agents include immediate injection-site reaction, systemic infusion reactions, and delayed reactions.¹ Among the delayed adverse reactions, psoriatic and eczematous eruptions as well as cutaneous infections are the most common, while cutaneous adverse effects related to an immune imbalance syndrome including vasculitis; lupuslike, lichenlike, and granulomatous eruptions; and skin cancer rarely are observed.¹ Although most of the cutaneous adverse effects do not require anti-TNF treatment discontinuation and are resolved with symptomatic treatment, anti-TNF therapy must be stopped in more severe cases. We report the case of severe Henoch-Schönlein purpura (HSP) following treatment with infliximab.

A 46-year-old man who was a nonsmoker with quiescent UC on infliximab for 30 months presented with palpable necrotic purpura on both legs (Figure) and arms as well as the abdomen of 10 days’ duration, along with diffuse joint pain and swelling. He had no history of infectious or gastrointestinal symptoms. The last infliximab infusion was performed 6 weeks prior to developing the purpura. His UC was diagnosed 10 years prior to the current presentation and was not associated with any extragastrointestinal manifestations. Since diagnosis, UC had failed to respond to therapies such as azathioprine, cyclosporine, and purinethol. The complete blood cell count was normal. The C-reactive protein level was 18.7 mg/L (reference range, <5 mg/L) and the erythrocyte sedimentation rate was 30 mm/h (reference range, 0–20 mm/h). Electrolytes, urea, creatinine clearance, and liver function were normal, and a chest radiograph and radiographs of the swollen joints were unremarkable. The total IgA level was elevated at 4 g/L (reference range, 0.7–4 g/L), with IgG and IgM levels within reference range. There was no hematuria or proteinuria on urinalysis. Tests for antinuclear antibodies, rheumatoid factor, circulating immune complexes, and antineutrophil cytoplasmic antibody were negative. Total complement, C3, and C4 levels also were normal. A skin biopsy confirmed a leukocytoclastic vasculitis of small vessels with C3 deposition. Serologic tests for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative. Based on these findings, the diagnosis of HSP was made. Systemic corticosteroids—120 mg daily of intravenous methylprednisolone for 3 days, followed by 1 mg/kg daily of oral prednisone for 2 weeks—were then introduced with rapid clinical improvement. Henoch-Schönlein purpura and joint symptoms completely resolved, but UC relapsed with bloody diarrhea and severe abdominal pain. Oral prednisone was maintained (1 mg/kg daily). Because of the severity of cutaneous vasculitis (HSP), a multidisciplinary decision was taken to definitively stop the anti-TNF agents and to first add azathioprine (2 mg/kg daily for 2 months), then subcutaneous methotrexate (25 mg weekly). Colonoscopy did not show any dysplasia or adenocarcinoma and confirmed the diagnosis of UC. After 6 months of combined therapy, UC was still active and we decided to perform a total colectomy with ileostomy formation. Complete remission of UC was obtained and maintained after 28 months of follow-up.

Henoch-Schönlein purpura is a multisystem small vessel leukocytoclastic vasculitis with the deposition of immune complexes containing IgA. Clinical manifestations may include palpable purpura, arthritis, enteritis, and nephritis. Henoch-Schönlein purpura usually affects children. Adult onset is rare but associated with more severe symptoms and a poor prognosis.² The criteria for HSP, as defined by the American College of Rheumatology,³ include palpable purpura, 20 years or younger at disease onset, bowel angina, and presence of vascular wall granulocytes on biopsy. At least 2 of these criteria are required for HSP diagnosis. Various viral or bacterial infections and drugs can trigger HSP, which also can be associated with autoinflammatory or autoimmune diseases. The association of HSP and UC is a rare event, as demonstrated by de Oliveira et al.⁴ Although only 2 cases of cutaneous vasculitis mimicking HSP have been described in UC,⁴ we cannot exclude a possible association between HSP and UC. However, our patient had UC for 10 years and never had clinical manifestations of vasculitis.

There are 5 reports of HSP following etanercept^5,6 or adalimumab^7-9 therapy and 1 following infliximab therapy.¹⁰ In all cases, HSP occurred after several months of anti-TNF therapy. However, there also are reports of cutaneous vasculitis associated with arthralgia and glomerulonephritis that resolved after withdrawal of anti-TNF agents.^11,12 It is possible that some of these reactions may have been manifestations of undiagnosed HSP. In a series of 113 patients who developed cutaneous vasculitis after anti-TNF agents, visceral vasculitis was observed in 24% of patients. Treatment of vasculitis involved withdrawal of the anti-TNF therapy in 101 cases (89%).¹³ In these UC patients with few therapeutic alternatives, the continuation of anti-TNF agents should be discussed. In the previous series,¹³ of 16 patients who were rechallenged with the same or a different TNF antagonist, 12 (75%) experienced vasculitis relapse, suggesting a class effect of TNF inhibition. Because of the severity of cutaneous vasculitis and as previously suggested in a recent analytical and comprehensive overview on paradoxical reactions under TNF blockers,¹ we decided not to re-expose our patient to infliximab or to other anti-TNF agents.

In conclusion, HSP may occur during anti-TNF therapy and physicians need to be aware of this potentially serious complication.

To the Editor:

Anti–tumor necrosis factor (TNF) α treatments have radically improved the management of chronic inflammatory conditions, including rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, and bowel diseases (eg, Crohn disease, ulcerative colitis [UC]). Because the number of patients treated with these agents has increased, uncommon adverse reactions have increasingly occurred. Cutaneous adverse reactions that have been reported with anti-TNF agents include immediate injection-site reaction, systemic infusion reactions, and delayed reactions.¹ Among the delayed adverse reactions, psoriatic and eczematous eruptions as well as cutaneous infections are the most common, while cutaneous adverse effects related to an immune imbalance syndrome including vasculitis; lupuslike, lichenlike, and granulomatous eruptions; and skin cancer rarely are observed.¹ Although most of the cutaneous adverse effects do not require anti-TNF treatment discontinuation and are resolved with symptomatic treatment, anti-TNF therapy must be stopped in more severe cases. We report the case of severe Henoch-Schönlein purpura (HSP) following treatment with infliximab.

A 46-year-old man who was a nonsmoker with quiescent UC on infliximab for 30 months presented with palpable necrotic purpura on both legs (Figure) and arms as well as the abdomen of 10 days’ duration, along with diffuse joint pain and swelling. He had no history of infectious or gastrointestinal symptoms. The last infliximab infusion was performed 6 weeks prior to developing the purpura. His UC was diagnosed 10 years prior to the current presentation and was not associated with any extragastrointestinal manifestations. Since diagnosis, UC had failed to respond to therapies such as azathioprine, cyclosporine, and purinethol. The complete blood cell count was normal. The C-reactive protein level was 18.7 mg/L (reference range, <5 mg/L) and the erythrocyte sedimentation rate was 30 mm/h (reference range, 0–20 mm/h). Electrolytes, urea, creatinine clearance, and liver function were normal, and a chest radiograph and radiographs of the swollen joints were unremarkable. The total IgA level was elevated at 4 g/L (reference range, 0.7–4 g/L), with IgG and IgM levels within reference range. There was no hematuria or proteinuria on urinalysis. Tests for antinuclear antibodies, rheumatoid factor, circulating immune complexes, and antineutrophil cytoplasmic antibody were negative. Total complement, C3, and C4 levels also were normal. A skin biopsy confirmed a leukocytoclastic vasculitis of small vessels with C3 deposition. Serologic tests for hepatitis B virus, hepatitis C virus, and human immunodeficiency virus were negative. Based on these findings, the diagnosis of HSP was made. Systemic corticosteroids—120 mg daily of intravenous methylprednisolone for 3 days, followed by 1 mg/kg daily of oral prednisone for 2 weeks—were then introduced with rapid clinical improvement. Henoch-Schönlein purpura and joint symptoms completely resolved, but UC relapsed with bloody diarrhea and severe abdominal pain. Oral prednisone was maintained (1 mg/kg daily). Because of the severity of cutaneous vasculitis (HSP), a multidisciplinary decision was taken to definitively stop the anti-TNF agents and to first add azathioprine (2 mg/kg daily for 2 months), then subcutaneous methotrexate (25 mg weekly). Colonoscopy did not show any dysplasia or adenocarcinoma and confirmed the diagnosis of UC. After 6 months of combined therapy, UC was still active and we decided to perform a total colectomy with ileostomy formation. Complete remission of UC was obtained and maintained after 28 months of follow-up.

Henoch-Schönlein purpura is a multisystem small vessel leukocytoclastic vasculitis with the deposition of immune complexes containing IgA. Clinical manifestations may include palpable purpura, arthritis, enteritis, and nephritis. Henoch-Schönlein purpura usually affects children. Adult onset is rare but associated with more severe symptoms and a poor prognosis.² The criteria for HSP, as defined by the American College of Rheumatology,³ include palpable purpura, 20 years or younger at disease onset, bowel angina, and presence of vascular wall granulocytes on biopsy. At least 2 of these criteria are required for HSP diagnosis. Various viral or bacterial infections and drugs can trigger HSP, which also can be associated with autoinflammatory or autoimmune diseases. The association of HSP and UC is a rare event, as demonstrated by de Oliveira et al.⁴ Although only 2 cases of cutaneous vasculitis mimicking HSP have been described in UC,⁴ we cannot exclude a possible association between HSP and UC. However, our patient had UC for 10 years and never had clinical manifestations of vasculitis.

There are 5 reports of HSP following etanercept^5,6 or adalimumab^7-9 therapy and 1 following infliximab therapy.¹⁰ In all cases, HSP occurred after several months of anti-TNF therapy. However, there also are reports of cutaneous vasculitis associated with arthralgia and glomerulonephritis that resolved after withdrawal of anti-TNF agents.^11,12 It is possible that some of these reactions may have been manifestations of undiagnosed HSP. In a series of 113 patients who developed cutaneous vasculitis after anti-TNF agents, visceral vasculitis was observed in 24% of patients. Treatment of vasculitis involved withdrawal of the anti-TNF therapy in 101 cases (89%).¹³ In these UC patients with few therapeutic alternatives, the continuation of anti-TNF agents should be discussed. In the previous series,¹³ of 16 patients who were rechallenged with the same or a different TNF antagonist, 12 (75%) experienced vasculitis relapse, suggesting a class effect of TNF inhibition. Because of the severity of cutaneous vasculitis and as previously suggested in a recent analytical and comprehensive overview on paradoxical reactions under TNF blockers,¹ we decided not to re-expose our patient to infliximab or to other anti-TNF agents.

In conclusion, HSP may occur during anti-TNF therapy and physicians need to be aware of this potentially serious complication.

Adjuvant chemotherapy may be overused among younger patients with colon cancer, without clear evidence of survival benefit over surgery alone, according to a report in JAMA Surgery.

Using data from 3,143 patients with histologically confirmed primary colon adenocarcinoma in the U.S. Department of Defense’s Central Cancer Registry and Military Heath System medical claims databases, researchers compared overall survival in those who underwent surgery and adjuvant chemotherapy to those who underwent surgery alone.

They found patients aged 18-49 years were up to eight times more likely to receive postoperative systemic chemotherapy across all tumor stages compared to patients aged 65-75 years. The odds ratios ranged from 7.98 for stage I tumors to 2.30 for stage III tumors (JAMA Surgery 2017, Jan 25. doi:10.1001/jamasurg.2016.5050).

“Furthermore, young and middle-aged adults were 2.5 times more likely to receive multiagent chemotherapy regimens and most patients with information on chemotherapy regimens underwent multiagent regimens, suggesting a tendency toward more intense treatments,” wrote Janna Manjelievskaia, MPH, of Walter Reed National Military Medical Center, and coauthors.*

However, they found that there was no significant difference in survival between those who had surgery and chemotherapy compared to those who had surgery alone, across age groups and tumor stage.

They did note greater overall survival among middle-aged patients with stage I and stage IV disease who were treated with surgery alone, compared to their older counterparts. Younger patients with stage III disease who received surgery alone also had slightly better survival than did older patients.

“The study suggests that more use of chemotherapy in younger patients did not result in additional survival benefits,” the authors wrote.

While national guidelines advise that selected patients with stage II disease – those with inadequately sampled nodes, T3 lesions or poorly differentiated histology – can be considered for adjuvant chemotherapy, the authors argued there is no solid evidence for the effectiveness of chemotherapy in these patients.

“Patients with cancer who receive chemotherapy are vulnerable to its toxicity and adverse effects and may have reduced quality of life,” they wrote. “As a result, patients may undergo decreased physical, functional, emotional, and social well-being, although these changes might be mitigated over time.”

Given the additional economic and financial cost of adjuvant chemotherapy, the authors called for further research to evaluate the appropriate use of chemotherapy in colon cancer.

The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, and the National Cancer Institute supported the study. No conflicts of interest were declared.

* This story was updated on 2/6/2107

Adjuvant chemotherapy may be overused among younger patients with colon cancer, without clear evidence of survival benefit over surgery alone, according to a report in JAMA Surgery.

Using data from 3,143 patients with histologically confirmed primary colon adenocarcinoma in the U.S. Department of Defense’s Central Cancer Registry and Military Heath System medical claims databases, researchers compared overall survival in those who underwent surgery and adjuvant chemotherapy to those who underwent surgery alone.

They found patients aged 18-49 years were up to eight times more likely to receive postoperative systemic chemotherapy across all tumor stages compared to patients aged 65-75 years. The odds ratios ranged from 7.98 for stage I tumors to 2.30 for stage III tumors (JAMA Surgery 2017, Jan 25. doi:10.1001/jamasurg.2016.5050).

“Furthermore, young and middle-aged adults were 2.5 times more likely to receive multiagent chemotherapy regimens and most patients with information on chemotherapy regimens underwent multiagent regimens, suggesting a tendency toward more intense treatments,” wrote Janna Manjelievskaia, MPH, of Walter Reed National Military Medical Center, and coauthors.*

However, they found that there was no significant difference in survival between those who had surgery and chemotherapy compared to those who had surgery alone, across age groups and tumor stage.

They did note greater overall survival among middle-aged patients with stage I and stage IV disease who were treated with surgery alone, compared to their older counterparts. Younger patients with stage III disease who received surgery alone also had slightly better survival than did older patients.

“The study suggests that more use of chemotherapy in younger patients did not result in additional survival benefits,” the authors wrote.

While national guidelines advise that selected patients with stage II disease – those with inadequately sampled nodes, T3 lesions or poorly differentiated histology – can be considered for adjuvant chemotherapy, the authors argued there is no solid evidence for the effectiveness of chemotherapy in these patients.

“Patients with cancer who receive chemotherapy are vulnerable to its toxicity and adverse effects and may have reduced quality of life,” they wrote. “As a result, patients may undergo decreased physical, functional, emotional, and social well-being, although these changes might be mitigated over time.”

Given the additional economic and financial cost of adjuvant chemotherapy, the authors called for further research to evaluate the appropriate use of chemotherapy in colon cancer.

The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, and the National Cancer Institute supported the study. No conflicts of interest were declared.

* This story was updated on 2/6/2107

Adjuvant chemotherapy may be overused among younger patients with colon cancer, without clear evidence of survival benefit over surgery alone, according to a report in JAMA Surgery.

Using data from 3,143 patients with histologically confirmed primary colon adenocarcinoma in the U.S. Department of Defense’s Central Cancer Registry and Military Heath System medical claims databases, researchers compared overall survival in those who underwent surgery and adjuvant chemotherapy to those who underwent surgery alone.

They found patients aged 18-49 years were up to eight times more likely to receive postoperative systemic chemotherapy across all tumor stages compared to patients aged 65-75 years. The odds ratios ranged from 7.98 for stage I tumors to 2.30 for stage III tumors (JAMA Surgery 2017, Jan 25. doi:10.1001/jamasurg.2016.5050).

“Furthermore, young and middle-aged adults were 2.5 times more likely to receive multiagent chemotherapy regimens and most patients with information on chemotherapy regimens underwent multiagent regimens, suggesting a tendency toward more intense treatments,” wrote Janna Manjelievskaia, MPH, of Walter Reed National Military Medical Center, and coauthors.*

However, they found that there was no significant difference in survival between those who had surgery and chemotherapy compared to those who had surgery alone, across age groups and tumor stage.

They did note greater overall survival among middle-aged patients with stage I and stage IV disease who were treated with surgery alone, compared to their older counterparts. Younger patients with stage III disease who received surgery alone also had slightly better survival than did older patients.

“The study suggests that more use of chemotherapy in younger patients did not result in additional survival benefits,” the authors wrote.

While national guidelines advise that selected patients with stage II disease – those with inadequately sampled nodes, T3 lesions or poorly differentiated histology – can be considered for adjuvant chemotherapy, the authors argued there is no solid evidence for the effectiveness of chemotherapy in these patients.

“Patients with cancer who receive chemotherapy are vulnerable to its toxicity and adverse effects and may have reduced quality of life,” they wrote. “As a result, patients may undergo decreased physical, functional, emotional, and social well-being, although these changes might be mitigated over time.”

Given the additional economic and financial cost of adjuvant chemotherapy, the authors called for further research to evaluate the appropriate use of chemotherapy in colon cancer.

The John P. Murtha Cancer Center, Walter Reed National Military Medical Center, and the National Cancer Institute supported the study. No conflicts of interest were declared.

* This story was updated on 2/6/2107

CHICAGO – Catheter dependence is often the final option available for hemodialysis patients who have exhausted upper extremity access because of central venous obstruction. But an alternative device that combines a standard expanded polytetrafluoroethylene (ePTFE) arterial graft component with an entirely internalized central venous catheter component may provide an additional option that can help avoid catheters in selected patients, according to pooled results reported at a symposium on vascular surgery sponsored by Northwestern University.

Virginia L. Wong, MD, of University Hospitals Cleveland Medical Center, reported on her group’s and others’ experience using the Hemodialysis Reliable Outflow (HeRO) graft (Merit Medical) to gain access to the superior vena cava (SVC), thus allowing for further upper extremity access options. The device has its limitations in patients with CVO, Dr. Wong noted, “but it can be an important tool for the dedicated access surgeon who is likely to be referred the most complicated patients who have run out of just about every other option.”

The Food and Drug Administration approved the HeRO graft for CVO in 2008, but a recent pooled analysis (Eur J Vasc Endovasc Surg. 2015;50[1]:108-13), which showed a 1-year primary patency rate of 22% and a secondary patency rate of 60%, may provide clarity on how the device can be used to treat CVO in end-stage renal disease (ESRD) patients when the care team desires an alternative to femoral arteriovenous graft, Dr. Wong said. “The 1-year primary patency rate overall was not very good, but with aggressive thrombectomy programs the 1-year patency rate was decent,” she said.

The pooled analysis involved eight series from 2009 to 2015, but the largest series, which involved 164 patients, reported primary and secondary patency rates of 48.8% and 90.8%, respectively (Eur J Vasc Endovasc Surg. 2012;44[1]:93-9). “Patency for these alternative accesses may not be quite what we can achieve with standard upper-extremity access,” Dr. Wong said, “but these patients do not have the standard access as an option.”

Dr. Wong explained where the HeRO fits into the existing vascular practice. “The current data suggest that we should try to exhaust all traditional upper extremity access options before considering anything else, but the HeRO could be considered as an acceptable option for suitable patients,” she said. However, to achieve those outcomes, “you need to have an aggressive thrombectomy program.”

HeRO may be an option for salvage of an existing arm access, plagued by recalcitrant CVO, while still preserving the femoral sites and for future hemodialysis access and/or renal transplantation, Dr. Wong said.

The HeRO also has been used in alternative configurations, taking advantage of axillary or subclavian routes to the SVC when both internal jugular veins are occluded. Dr. Wong has used the femoral route to the inferior vena cava (IVC) for salvaging the femoral AV graft in which iliofemoral venous outflow has been compromised.

Anatomically, the patient must be able to accept a large-bore (19-Fr) access catheter into the central vein. Physiologically, the patient must be able to maintain patency of the long, low-resistance HeRO circuit, which can be up to 50 cm in length, she said. The protocol at Dr. Wong’s institution recommends an inflow arterial diameter of at least 3 mm, along with a left ventricular ejection fraction of 20% or greater and a minimum systolic blood pressure of 100 mm Hg for HeRO on the right side, and possibly higher when coming from the left.

Chronic hypotension is a frequent disqualifier, although some of these patients may benefit from midodrine hydrochloride, she said. In any event, a review of medications and consultation with nephrology and the dialysis unit are mandatory elements of patient screening. “I usually request hemodialysis run sheets from the last three sessions to see what systolic blood pressure excursion is like over the course of treatment,” she said.

The basic principles of hemo-access care are important when considering the HeRO for CVO patients, Dr. Wong said. These include site/side preservation, catheter avoidance and “not to burn any bridges” for future access. “Individualization of care and careful patient selection are probably the best bets if you’re just starting out,” she said. “Choose good patients before resorting to HeRO as the last option for a fairly marginal candidate.”

Dr. Wong had no relevant financial relationships to disclose.

CHICAGO – Catheter dependence is often the final option available for hemodialysis patients who have exhausted upper extremity access because of central venous obstruction. But an alternative device that combines a standard expanded polytetrafluoroethylene (ePTFE) arterial graft component with an entirely internalized central venous catheter component may provide an additional option that can help avoid catheters in selected patients, according to pooled results reported at a symposium on vascular surgery sponsored by Northwestern University.

Virginia L. Wong, MD, of University Hospitals Cleveland Medical Center, reported on her group’s and others’ experience using the Hemodialysis Reliable Outflow (HeRO) graft (Merit Medical) to gain access to the superior vena cava (SVC), thus allowing for further upper extremity access options. The device has its limitations in patients with CVO, Dr. Wong noted, “but it can be an important tool for the dedicated access surgeon who is likely to be referred the most complicated patients who have run out of just about every other option.”

The Food and Drug Administration approved the HeRO graft for CVO in 2008, but a recent pooled analysis (Eur J Vasc Endovasc Surg. 2015;50[1]:108-13), which showed a 1-year primary patency rate of 22% and a secondary patency rate of 60%, may provide clarity on how the device can be used to treat CVO in end-stage renal disease (ESRD) patients when the care team desires an alternative to femoral arteriovenous graft, Dr. Wong said. “The 1-year primary patency rate overall was not very good, but with aggressive thrombectomy programs the 1-year patency rate was decent,” she said.

The pooled analysis involved eight series from 2009 to 2015, but the largest series, which involved 164 patients, reported primary and secondary patency rates of 48.8% and 90.8%, respectively (Eur J Vasc Endovasc Surg. 2012;44[1]:93-9). “Patency for these alternative accesses may not be quite what we can achieve with standard upper-extremity access,” Dr. Wong said, “but these patients do not have the standard access as an option.”

Dr. Wong explained where the HeRO fits into the existing vascular practice. “The current data suggest that we should try to exhaust all traditional upper extremity access options before considering anything else, but the HeRO could be considered as an acceptable option for suitable patients,” she said. However, to achieve those outcomes, “you need to have an aggressive thrombectomy program.”

HeRO may be an option for salvage of an existing arm access, plagued by recalcitrant CVO, while still preserving the femoral sites and for future hemodialysis access and/or renal transplantation, Dr. Wong said.

The HeRO also has been used in alternative configurations, taking advantage of axillary or subclavian routes to the SVC when both internal jugular veins are occluded. Dr. Wong has used the femoral route to the inferior vena cava (IVC) for salvaging the femoral AV graft in which iliofemoral venous outflow has been compromised.

Anatomically, the patient must be able to accept a large-bore (19-Fr) access catheter into the central vein. Physiologically, the patient must be able to maintain patency of the long, low-resistance HeRO circuit, which can be up to 50 cm in length, she said. The protocol at Dr. Wong’s institution recommends an inflow arterial diameter of at least 3 mm, along with a left ventricular ejection fraction of 20% or greater and a minimum systolic blood pressure of 100 mm Hg for HeRO on the right side, and possibly higher when coming from the left.

Chronic hypotension is a frequent disqualifier, although some of these patients may benefit from midodrine hydrochloride, she said. In any event, a review of medications and consultation with nephrology and the dialysis unit are mandatory elements of patient screening. “I usually request hemodialysis run sheets from the last three sessions to see what systolic blood pressure excursion is like over the course of treatment,” she said.

The basic principles of hemo-access care are important when considering the HeRO for CVO patients, Dr. Wong said. These include site/side preservation, catheter avoidance and “not to burn any bridges” for future access. “Individualization of care and careful patient selection are probably the best bets if you’re just starting out,” she said. “Choose good patients before resorting to HeRO as the last option for a fairly marginal candidate.”

Dr. Wong had no relevant financial relationships to disclose.

CHICAGO – Catheter dependence is often the final option available for hemodialysis patients who have exhausted upper extremity access because of central venous obstruction. But an alternative device that combines a standard expanded polytetrafluoroethylene (ePTFE) arterial graft component with an entirely internalized central venous catheter component may provide an additional option that can help avoid catheters in selected patients, according to pooled results reported at a symposium on vascular surgery sponsored by Northwestern University.

Virginia L. Wong, MD, of University Hospitals Cleveland Medical Center, reported on her group’s and others’ experience using the Hemodialysis Reliable Outflow (HeRO) graft (Merit Medical) to gain access to the superior vena cava (SVC), thus allowing for further upper extremity access options. The device has its limitations in patients with CVO, Dr. Wong noted, “but it can be an important tool for the dedicated access surgeon who is likely to be referred the most complicated patients who have run out of just about every other option.”

The Food and Drug Administration approved the HeRO graft for CVO in 2008, but a recent pooled analysis (Eur J Vasc Endovasc Surg. 2015;50[1]:108-13), which showed a 1-year primary patency rate of 22% and a secondary patency rate of 60%, may provide clarity on how the device can be used to treat CVO in end-stage renal disease (ESRD) patients when the care team desires an alternative to femoral arteriovenous graft, Dr. Wong said. “The 1-year primary patency rate overall was not very good, but with aggressive thrombectomy programs the 1-year patency rate was decent,” she said.

The pooled analysis involved eight series from 2009 to 2015, but the largest series, which involved 164 patients, reported primary and secondary patency rates of 48.8% and 90.8%, respectively (Eur J Vasc Endovasc Surg. 2012;44[1]:93-9). “Patency for these alternative accesses may not be quite what we can achieve with standard upper-extremity access,” Dr. Wong said, “but these patients do not have the standard access as an option.”

Dr. Wong explained where the HeRO fits into the existing vascular practice. “The current data suggest that we should try to exhaust all traditional upper extremity access options before considering anything else, but the HeRO could be considered as an acceptable option for suitable patients,” she said. However, to achieve those outcomes, “you need to have an aggressive thrombectomy program.”

HeRO may be an option for salvage of an existing arm access, plagued by recalcitrant CVO, while still preserving the femoral sites and for future hemodialysis access and/or renal transplantation, Dr. Wong said.

The HeRO also has been used in alternative configurations, taking advantage of axillary or subclavian routes to the SVC when both internal jugular veins are occluded. Dr. Wong has used the femoral route to the inferior vena cava (IVC) for salvaging the femoral AV graft in which iliofemoral venous outflow has been compromised.

Anatomically, the patient must be able to accept a large-bore (19-Fr) access catheter into the central vein. Physiologically, the patient must be able to maintain patency of the long, low-resistance HeRO circuit, which can be up to 50 cm in length, she said. The protocol at Dr. Wong’s institution recommends an inflow arterial diameter of at least 3 mm, along with a left ventricular ejection fraction of 20% or greater and a minimum systolic blood pressure of 100 mm Hg for HeRO on the right side, and possibly higher when coming from the left.

Chronic hypotension is a frequent disqualifier, although some of these patients may benefit from midodrine hydrochloride, she said. In any event, a review of medications and consultation with nephrology and the dialysis unit are mandatory elements of patient screening. “I usually request hemodialysis run sheets from the last three sessions to see what systolic blood pressure excursion is like over the course of treatment,” she said.

The basic principles of hemo-access care are important when considering the HeRO for CVO patients, Dr. Wong said. These include site/side preservation, catheter avoidance and “not to burn any bridges” for future access. “Individualization of care and careful patient selection are probably the best bets if you’re just starting out,” she said. “Choose good patients before resorting to HeRO as the last option for a fairly marginal candidate.”

Dr. Wong had no relevant financial relationships to disclose.

Take-Home Points

• DVT and PE are uncommon complications following osteotomies about the knee.
• Use of oral contraceptives can increase the risk of a patient sustaining a postoperative DVT and PE following osteotomies about the knee.
• In the absence of significant risk factors, postoperative chemical DVT prophylaxis may be unnecessary in patients undergoing osteotomies about the knee.

High tibial osteotomy (HTO), distal femoral osteotomy (DFO), and tibial tubercle osteotomy (TTO) are viable treatment options for deformities about the knee and patella maltracking.^1-4 Although TTO can be performed in many ways (eg, anteriorization, anteromedialization, medialization), the basic idea is to move the tibial tubercle to improve patellar tracking or to offload a patellar facet that has sustained trauma or degenerated.² DFO is a surgical option for treating a valgus knee deformity (the lateral tibiofemoral compartment is offloaded) or for protecting a knee compartment after cartilage or meniscal restoration (medial closing wedge or lateral opening wedge).¹ Similarly, HTO is an option for treating a varus knee deformity or isolated medial compartment arthritis; the diseased compartment is offloaded, and any malalignment is corrected. Akin to DFO, HTO is often performed to protect a knee compartment, typically the medial tibiofemoral compartment, after cartilage or meniscal restoration.^2-4

Compared to most arthroscopic knee surgeries, these osteotomies are much more involved, have longer operative times, and restrict postoperative weight-bearing and range of motion.^2-4 The rates of deep vein thrombosis (DVT) and pulmonary embolism (PE) after these osteotomies are not well documented. In addition, there is no documentation of the risks in patients who smoke, are obese, or are using oral contraceptives (OCs) at time of surgery, despite the increased DVT and PE risks posed by smoking, obesity, and OC use in other surgical procedures.^5-7 Although the American Academy of Orthopaedic Surgeons (AAOS) issued clinical practice guidelines for DVT/PE prophylaxis after hip and knee arthroplasty, there is no standard prophylaxis guidelines for DVT/PE prevention after HTO, DFO, or TTO.^8,9 Last, rates of DVT after total knee arthroplasty (TKA) are well defined; they range from 2% to 12%.^10,11 These rates may be surrogates for osteotomies about the knee, but this is only conjecture.

We conducted a study to determine the rates of symptomatic DVT and PE after HTO, DFO, or TTO in patients who did not receive postoperative DVT/PE prophylaxis. We also wanted to determine if age, body mass index (BMI), and smoking status have associations with the risk of developing either DVT or PE after HTO, DFO, or TTO. We hypothesized that the DVT and PE rates would both be <1%.

Methods

After this study was approved by our university’s Institutional Review Board, we searched the surgical database of Dr. Cole, a sports medicine fellowship–trained surgeon, to identify all patients who had HTO, DFO, or TTO performed between September 1, 2009 and September 30, 2014. Current Procedural Terminology (CPT) codes were used for the search. The code for HTO was 27457: osteotomy, proximal tibia, including fibular excision or osteotomy (includes correction of genu varus [bowleg] or genu valgus [knock-knee]); after epiphyseal closure). The code for DFO was 27450: osteotomy, femur, shaft or supracondylar; with fixation. Last, the code for TTO was 27418: anterior tibial tubercleplasty (eg, Maquet-type procedure). The 141 patients identified in the search were treated by Dr. Cole at a single institution and were included in the study. Study inclusion did not require a minimum follow-up. Follow-up duration was defined as the time between surgery and the final clinic note in the patient chart. No patient was excluded for lack of follow-up clinic visits, and none was lost to follow-up.

Age, BMI, smoking status, and OC use were recorded for all patients. For each procedure, the surgeon’s technique remained the same throughout the study period: HTO, medial opening-wedge osteotomy with plate-and-screw fixation; DFO, lateral opening-wedge osteotomy with plate-and-screw fixation; and TTO, mostly anteromedialization with screw fixation (though this was dictated by patellar contact pressures). A tourniquet was used in all cases. Each patient’s hospital electronic medical record and outpatient office notes were reviewed to determine if symptomatic DVT or PE developed after surgery. The diagnosis of symptomatic DVT was based on clinical symptoms and confirmatory ultrasound, and the PE diagnosis was based on computed tomography. Doppler ultrasound was performed only in symptomatic patients (ie, it was not routinely performed).

Per surgeon protocol, postoperative DVT prophylaxis was not administered. Patients were encouraged to begin dorsiflexion and plantar flexion of the ankle (ankle pumps) immediately and to mobilize as soon as comfortable. Each patient received a cold therapy machine with compression sleeve. Patients were allowed toe-touch weight-bearing for 6 weeks, and then progressed 25% per week for 4 weeks to full weight-bearing by 10 weeks. After surgery, each patient was placed in a brace, which was kept locked in extension for 10 days; when the brace was unlocked, the patient was allowed to range the knee.

Continuous variable data are reported as weighted means and weighted standard deviations. Categorical variable data are reported as frequencies and percentages.

Results

Our database search identified 141 patients (44% male, 56% female) who underwent HTO (47 patients, 33.3%), DFO (13 patients, 9.2%), or TTO (81 patients, 57.5%). Mean (SD) age was 34.28 (9.86) years, mean (SD) BMI was 26.88 (5.11) kg/m², and mean (SD) follow-up was 17.1 (4.1) months. Of the female patients, 36.7% were using OCs at time of surgery. Of all patients, 13.48% were smokers.

Two patients (1.42%) had clinical symptoms consistent with DVT. In each case, the diagnosis was confirmed with Doppler ultrasound. The below-knee DVT was unilateral in 1 case and bilateral in the other.

Discussion

As the rates of DVT and PE after osteotomies about the knee have not been well studied, we wanted to determine these rates after HTO, DFO, and TTO in patients who did not receive postoperative DVT prophylaxis. We hypothesized that DVT and PE rates would both be <1%, and this hypothesis was partly confirmed: The rate of PE after HTO, DFO, and TTO was <1%, and the rate of symptomatic DVT was >1%. Similarly, the patients who developed these complications were nonsmokers and had a BMI no higher than that of the patients who did not develop DVT or PE. In addition, only 1 patient developed DVT and PE, and she was using OCs and had a family history of DVT. Last, the patients who developed these complications were on average 14 years older than the patients who did not develop DVT or PE.

Although there is a plethora of reports on the incidence of DVT and PE after TKA, there is little on the incidence after osteotomies about the knee.^8,12 The rate of DVT after TKA varies, but many studies place it between 2% and 12%, and routinely find a PE rate of <0.5%.^10,11,13,14 Although the AAOS issued a clinical practice guideline for postoperative DVT prophylaxis after TKA, and evaluated the best available evidence, it could not reach consensus on a specific type of DVT prophylaxis, though the workgroup did recommend that patients be administered postoperative DVT prophylaxis of some kind.^8,9 Similarly, the American College of Chest Physicians (ACCP) issued clinical practice guidelines for preventing DVT and PE after elective TKA and total hip arthroplasty.¹⁵ According to the ACCP guidelines, patients should receive prophylaxis—LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, low-dose unfractionated heparin, adjusted-dose vitamin K antagonist, aspirin, or an intermittent pneumatic compression device—for a minimum of 14 days. Unfortunately, though there are similarities between TKAs and peri-knee osteotomies, these procedures are markedly different, and it is difficult to extrapolate and adapt recommendations and produce a consensus statement for knee arthroplasties. In addition, guidelines exist for hospitalized patients who are being treated for medical conditions or have undergone surgery, but all the patients in the present study had their osteotomies performed on an outpatient basis.

Martin and colleagues¹⁶ reviewed 323 cases of medial opening-wedge HTO and found a DVT rate of 1.4% in the absence of routine DVT prophylaxis, except in patients with a history of DVT. Their rate is almost identical to ours, but we also included other osteotomies in our study. Miller and colleagues¹⁷ reviewed 46 cases of medial opening-wedge HTO and found a 4.3% DVT rate, despite routine prophylaxis with once-daily 325-mg aspirin and ankle pumps. This finding contrasts with our 1.42% DVT rate in the absence of postoperative chemical DVT prophylaxis. Motycka and colleagues¹⁸ reviewed 65 HTO cases in which DVT prophylaxis (oral anticoagulant) was given for 6 weeks, and they found a DVT rate of 9.7%. Turner and colleagues¹⁹ performed venous ultrasound on 81 consecutive patients who underwent HTO and received DVT prophylaxis (twice-daily subcutaneous heparin), and they found a DVT rate of 41% and a PE rate of 1.2%, though only 8.6% of the DVT cases were symptomatic. Of note, whereas the lowest postoperative DVT rate was for patients who did not receive postoperative DVT prophylaxis, the rate of symptomatic DVT after these osteotomies ranged from 1.4% to 8.6% in patients who received prophylaxis.^16,19 Given this evidence and our study results, it appears routine chemical DVT prophylaxis after osteotomies about the knee may not be necessary, though higher level evidence is needed in order to make definitive recommendations.

In the present study, the 2 patients who developed symptomatic DVT (1 subsequently developed PE) were nonsmokers in good health. The female patient (DVT plus PE) was using OCs at time of surgery. Studies have shown that patients who smoke and who use OCs are at increased risk for developing DVT or PE after surgery.^5,6,12 Given that only 2 of our patients developed DVT/PE, and neither was a smoker, smoking was not associated with increased DVT or PE risk in this study population, in which 13.48% of patients were smokers at time of surgery. In addition, given that the 1 female patient who developed DVT/PE was using OCs and that 36.7% of all female patients in the study were using OCs, it is difficult to conclude whether OC use increased the female patient’s risk for DVT or PE. Furthermore, neither the literature nor the AAOS consensus statement supports discontinuing OCs for this surgical procedure.

Patients in this study did not receive chemical or mechanical DVT prophylaxis after surgery. Regarding various post-TKA DVT prophylaxis regimens, aspirin is as effective as LMWH in preventing DVT, and the risk for postoperative blood loss and wound complications is lower with aspirin than with rivaroxaban.^20,21 Given that the present study’s postoperative rates of DVT (1.42%) and PE (0.71%) are equal to or less than rates already reported in the literature, routine DVT prophylaxis after osteotomies about the knee may be unnecessary in the absence of other significant risk factors.^16,19 However, our study considered only symptomatic DVT and PE, so it is possible that the number of asymptomatic DVT cases is higher in this patient population. Definitively answering our study’s clinical question will require a multicenter registry study (prospective cohort study).

Study Limitations

The strengths of this study include the large number of patients treated by a single surgeon using the same postoperative protocol. Limitations of this study include the lack of a control group. Although we found a DVT rate of 1.42% and a PE rate of 0.71%, the literature on the accepted risks for DVT and PE after HTO, DFO, and TTO is unclear. With our results stratified by procedure, the DVT rate was 2% in the HTO group, 0% in the DFO group, and 1% in the TTO group. However, we were unable to reliably stratify these results by each specific procedure, as the number of patients in each group would be too low. This study involved reviewing charts; as patients were not contacted, it is possible a patient developed DVT or PE, was treated at an outside facility, and then never followed up with the treating surgeon. Patients were identified by CPT codes, so, if a patient underwent HTO, DFO, or TTO that was recorded under a different CPT code, it is possible the patient was missed by our search. All patients were seen after surgery, and we reviewed the outpatient office notes that were taken, so unless the DVT or PE occurred after a patient’s final postoperative visit, it would have been recorded. Similarly, the DVT and PE rates reported here cannot be extrapolated to overall risks for DVT and PE after osteotomies about the knee in all patients—only in patients who did not receive DVT prophylaxis after surgery.

Conclusion

The rates of DVT and PE after HTO, DFO, and TTO in patients who did not receive chemical prophylaxis are low: 1.42% and 0.71%, respectively. After these osteotomies, DVT/PE prophylaxis in the absence of known risk factors may not be warranted.

Am J Orthop. 2017;46(1):E23-E27. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• DVT and PE are uncommon complications following osteotomies about the knee.
• Use of oral contraceptives can increase the risk of a patient sustaining a postoperative DVT and PE following osteotomies about the knee.
• In the absence of significant risk factors, postoperative chemical DVT prophylaxis may be unnecessary in patients undergoing osteotomies about the knee.

High tibial osteotomy (HTO), distal femoral osteotomy (DFO), and tibial tubercle osteotomy (TTO) are viable treatment options for deformities about the knee and patella maltracking.^1-4 Although TTO can be performed in many ways (eg, anteriorization, anteromedialization, medialization), the basic idea is to move the tibial tubercle to improve patellar tracking or to offload a patellar facet that has sustained trauma or degenerated.² DFO is a surgical option for treating a valgus knee deformity (the lateral tibiofemoral compartment is offloaded) or for protecting a knee compartment after cartilage or meniscal restoration (medial closing wedge or lateral opening wedge).¹ Similarly, HTO is an option for treating a varus knee deformity or isolated medial compartment arthritis; the diseased compartment is offloaded, and any malalignment is corrected. Akin to DFO, HTO is often performed to protect a knee compartment, typically the medial tibiofemoral compartment, after cartilage or meniscal restoration.^2-4

Compared to most arthroscopic knee surgeries, these osteotomies are much more involved, have longer operative times, and restrict postoperative weight-bearing and range of motion.^2-4 The rates of deep vein thrombosis (DVT) and pulmonary embolism (PE) after these osteotomies are not well documented. In addition, there is no documentation of the risks in patients who smoke, are obese, or are using oral contraceptives (OCs) at time of surgery, despite the increased DVT and PE risks posed by smoking, obesity, and OC use in other surgical procedures.^5-7 Although the American Academy of Orthopaedic Surgeons (AAOS) issued clinical practice guidelines for DVT/PE prophylaxis after hip and knee arthroplasty, there is no standard prophylaxis guidelines for DVT/PE prevention after HTO, DFO, or TTO.^8,9 Last, rates of DVT after total knee arthroplasty (TKA) are well defined; they range from 2% to 12%.^10,11 These rates may be surrogates for osteotomies about the knee, but this is only conjecture.

We conducted a study to determine the rates of symptomatic DVT and PE after HTO, DFO, or TTO in patients who did not receive postoperative DVT/PE prophylaxis. We also wanted to determine if age, body mass index (BMI), and smoking status have associations with the risk of developing either DVT or PE after HTO, DFO, or TTO. We hypothesized that the DVT and PE rates would both be <1%.

Methods

After this study was approved by our university’s Institutional Review Board, we searched the surgical database of Dr. Cole, a sports medicine fellowship–trained surgeon, to identify all patients who had HTO, DFO, or TTO performed between September 1, 2009 and September 30, 2014. Current Procedural Terminology (CPT) codes were used for the search. The code for HTO was 27457: osteotomy, proximal tibia, including fibular excision or osteotomy (includes correction of genu varus [bowleg] or genu valgus [knock-knee]); after epiphyseal closure). The code for DFO was 27450: osteotomy, femur, shaft or supracondylar; with fixation. Last, the code for TTO was 27418: anterior tibial tubercleplasty (eg, Maquet-type procedure). The 141 patients identified in the search were treated by Dr. Cole at a single institution and were included in the study. Study inclusion did not require a minimum follow-up. Follow-up duration was defined as the time between surgery and the final clinic note in the patient chart. No patient was excluded for lack of follow-up clinic visits, and none was lost to follow-up.

Age, BMI, smoking status, and OC use were recorded for all patients. For each procedure, the surgeon’s technique remained the same throughout the study period: HTO, medial opening-wedge osteotomy with plate-and-screw fixation; DFO, lateral opening-wedge osteotomy with plate-and-screw fixation; and TTO, mostly anteromedialization with screw fixation (though this was dictated by patellar contact pressures). A tourniquet was used in all cases. Each patient’s hospital electronic medical record and outpatient office notes were reviewed to determine if symptomatic DVT or PE developed after surgery. The diagnosis of symptomatic DVT was based on clinical symptoms and confirmatory ultrasound, and the PE diagnosis was based on computed tomography. Doppler ultrasound was performed only in symptomatic patients (ie, it was not routinely performed).

Per surgeon protocol, postoperative DVT prophylaxis was not administered. Patients were encouraged to begin dorsiflexion and plantar flexion of the ankle (ankle pumps) immediately and to mobilize as soon as comfortable. Each patient received a cold therapy machine with compression sleeve. Patients were allowed toe-touch weight-bearing for 6 weeks, and then progressed 25% per week for 4 weeks to full weight-bearing by 10 weeks. After surgery, each patient was placed in a brace, which was kept locked in extension for 10 days; when the brace was unlocked, the patient was allowed to range the knee.

Continuous variable data are reported as weighted means and weighted standard deviations. Categorical variable data are reported as frequencies and percentages.

Results

Our database search identified 141 patients (44% male, 56% female) who underwent HTO (47 patients, 33.3%), DFO (13 patients, 9.2%), or TTO (81 patients, 57.5%). Mean (SD) age was 34.28 (9.86) years, mean (SD) BMI was 26.88 (5.11) kg/m², and mean (SD) follow-up was 17.1 (4.1) months. Of the female patients, 36.7% were using OCs at time of surgery. Of all patients, 13.48% were smokers.

Two patients (1.42%) had clinical symptoms consistent with DVT. In each case, the diagnosis was confirmed with Doppler ultrasound. The below-knee DVT was unilateral in 1 case and bilateral in the other.

Discussion

As the rates of DVT and PE after osteotomies about the knee have not been well studied, we wanted to determine these rates after HTO, DFO, and TTO in patients who did not receive postoperative DVT prophylaxis. We hypothesized that DVT and PE rates would both be <1%, and this hypothesis was partly confirmed: The rate of PE after HTO, DFO, and TTO was <1%, and the rate of symptomatic DVT was >1%. Similarly, the patients who developed these complications were nonsmokers and had a BMI no higher than that of the patients who did not develop DVT or PE. In addition, only 1 patient developed DVT and PE, and she was using OCs and had a family history of DVT. Last, the patients who developed these complications were on average 14 years older than the patients who did not develop DVT or PE.

Although there is a plethora of reports on the incidence of DVT and PE after TKA, there is little on the incidence after osteotomies about the knee.^8,12 The rate of DVT after TKA varies, but many studies place it between 2% and 12%, and routinely find a PE rate of <0.5%.^10,11,13,14 Although the AAOS issued a clinical practice guideline for postoperative DVT prophylaxis after TKA, and evaluated the best available evidence, it could not reach consensus on a specific type of DVT prophylaxis, though the workgroup did recommend that patients be administered postoperative DVT prophylaxis of some kind.^8,9 Similarly, the American College of Chest Physicians (ACCP) issued clinical practice guidelines for preventing DVT and PE after elective TKA and total hip arthroplasty.¹⁵ According to the ACCP guidelines, patients should receive prophylaxis—LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, low-dose unfractionated heparin, adjusted-dose vitamin K antagonist, aspirin, or an intermittent pneumatic compression device—for a minimum of 14 days. Unfortunately, though there are similarities between TKAs and peri-knee osteotomies, these procedures are markedly different, and it is difficult to extrapolate and adapt recommendations and produce a consensus statement for knee arthroplasties. In addition, guidelines exist for hospitalized patients who are being treated for medical conditions or have undergone surgery, but all the patients in the present study had their osteotomies performed on an outpatient basis.

Martin and colleagues¹⁶ reviewed 323 cases of medial opening-wedge HTO and found a DVT rate of 1.4% in the absence of routine DVT prophylaxis, except in patients with a history of DVT. Their rate is almost identical to ours, but we also included other osteotomies in our study. Miller and colleagues¹⁷ reviewed 46 cases of medial opening-wedge HTO and found a 4.3% DVT rate, despite routine prophylaxis with once-daily 325-mg aspirin and ankle pumps. This finding contrasts with our 1.42% DVT rate in the absence of postoperative chemical DVT prophylaxis. Motycka and colleagues¹⁸ reviewed 65 HTO cases in which DVT prophylaxis (oral anticoagulant) was given for 6 weeks, and they found a DVT rate of 9.7%. Turner and colleagues¹⁹ performed venous ultrasound on 81 consecutive patients who underwent HTO and received DVT prophylaxis (twice-daily subcutaneous heparin), and they found a DVT rate of 41% and a PE rate of 1.2%, though only 8.6% of the DVT cases were symptomatic. Of note, whereas the lowest postoperative DVT rate was for patients who did not receive postoperative DVT prophylaxis, the rate of symptomatic DVT after these osteotomies ranged from 1.4% to 8.6% in patients who received prophylaxis.^16,19 Given this evidence and our study results, it appears routine chemical DVT prophylaxis after osteotomies about the knee may not be necessary, though higher level evidence is needed in order to make definitive recommendations.

In the present study, the 2 patients who developed symptomatic DVT (1 subsequently developed PE) were nonsmokers in good health. The female patient (DVT plus PE) was using OCs at time of surgery. Studies have shown that patients who smoke and who use OCs are at increased risk for developing DVT or PE after surgery.^5,6,12 Given that only 2 of our patients developed DVT/PE, and neither was a smoker, smoking was not associated with increased DVT or PE risk in this study population, in which 13.48% of patients were smokers at time of surgery. In addition, given that the 1 female patient who developed DVT/PE was using OCs and that 36.7% of all female patients in the study were using OCs, it is difficult to conclude whether OC use increased the female patient’s risk for DVT or PE. Furthermore, neither the literature nor the AAOS consensus statement supports discontinuing OCs for this surgical procedure.

Patients in this study did not receive chemical or mechanical DVT prophylaxis after surgery. Regarding various post-TKA DVT prophylaxis regimens, aspirin is as effective as LMWH in preventing DVT, and the risk for postoperative blood loss and wound complications is lower with aspirin than with rivaroxaban.^20,21 Given that the present study’s postoperative rates of DVT (1.42%) and PE (0.71%) are equal to or less than rates already reported in the literature, routine DVT prophylaxis after osteotomies about the knee may be unnecessary in the absence of other significant risk factors.^16,19 However, our study considered only symptomatic DVT and PE, so it is possible that the number of asymptomatic DVT cases is higher in this patient population. Definitively answering our study’s clinical question will require a multicenter registry study (prospective cohort study).

Study Limitations

The strengths of this study include the large number of patients treated by a single surgeon using the same postoperative protocol. Limitations of this study include the lack of a control group. Although we found a DVT rate of 1.42% and a PE rate of 0.71%, the literature on the accepted risks for DVT and PE after HTO, DFO, and TTO is unclear. With our results stratified by procedure, the DVT rate was 2% in the HTO group, 0% in the DFO group, and 1% in the TTO group. However, we were unable to reliably stratify these results by each specific procedure, as the number of patients in each group would be too low. This study involved reviewing charts; as patients were not contacted, it is possible a patient developed DVT or PE, was treated at an outside facility, and then never followed up with the treating surgeon. Patients were identified by CPT codes, so, if a patient underwent HTO, DFO, or TTO that was recorded under a different CPT code, it is possible the patient was missed by our search. All patients were seen after surgery, and we reviewed the outpatient office notes that were taken, so unless the DVT or PE occurred after a patient’s final postoperative visit, it would have been recorded. Similarly, the DVT and PE rates reported here cannot be extrapolated to overall risks for DVT and PE after osteotomies about the knee in all patients—only in patients who did not receive DVT prophylaxis after surgery.

Conclusion

The rates of DVT and PE after HTO, DFO, and TTO in patients who did not receive chemical prophylaxis are low: 1.42% and 0.71%, respectively. After these osteotomies, DVT/PE prophylaxis in the absence of known risk factors may not be warranted.

Am J Orthop. 2017;46(1):E23-E27. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• DVT and PE are uncommon complications following osteotomies about the knee.
• Use of oral contraceptives can increase the risk of a patient sustaining a postoperative DVT and PE following osteotomies about the knee.
• In the absence of significant risk factors, postoperative chemical DVT prophylaxis may be unnecessary in patients undergoing osteotomies about the knee.

High tibial osteotomy (HTO), distal femoral osteotomy (DFO), and tibial tubercle osteotomy (TTO) are viable treatment options for deformities about the knee and patella maltracking.^1-4 Although TTO can be performed in many ways (eg, anteriorization, anteromedialization, medialization), the basic idea is to move the tibial tubercle to improve patellar tracking or to offload a patellar facet that has sustained trauma or degenerated.² DFO is a surgical option for treating a valgus knee deformity (the lateral tibiofemoral compartment is offloaded) or for protecting a knee compartment after cartilage or meniscal restoration (medial closing wedge or lateral opening wedge).¹ Similarly, HTO is an option for treating a varus knee deformity or isolated medial compartment arthritis; the diseased compartment is offloaded, and any malalignment is corrected. Akin to DFO, HTO is often performed to protect a knee compartment, typically the medial tibiofemoral compartment, after cartilage or meniscal restoration.^2-4

Compared to most arthroscopic knee surgeries, these osteotomies are much more involved, have longer operative times, and restrict postoperative weight-bearing and range of motion.^2-4 The rates of deep vein thrombosis (DVT) and pulmonary embolism (PE) after these osteotomies are not well documented. In addition, there is no documentation of the risks in patients who smoke, are obese, or are using oral contraceptives (OCs) at time of surgery, despite the increased DVT and PE risks posed by smoking, obesity, and OC use in other surgical procedures.^5-7 Although the American Academy of Orthopaedic Surgeons (AAOS) issued clinical practice guidelines for DVT/PE prophylaxis after hip and knee arthroplasty, there is no standard prophylaxis guidelines for DVT/PE prevention after HTO, DFO, or TTO.^8,9 Last, rates of DVT after total knee arthroplasty (TKA) are well defined; they range from 2% to 12%.^10,11 These rates may be surrogates for osteotomies about the knee, but this is only conjecture.

We conducted a study to determine the rates of symptomatic DVT and PE after HTO, DFO, or TTO in patients who did not receive postoperative DVT/PE prophylaxis. We also wanted to determine if age, body mass index (BMI), and smoking status have associations with the risk of developing either DVT or PE after HTO, DFO, or TTO. We hypothesized that the DVT and PE rates would both be <1%.

Methods

After this study was approved by our university’s Institutional Review Board, we searched the surgical database of Dr. Cole, a sports medicine fellowship–trained surgeon, to identify all patients who had HTO, DFO, or TTO performed between September 1, 2009 and September 30, 2014. Current Procedural Terminology (CPT) codes were used for the search. The code for HTO was 27457: osteotomy, proximal tibia, including fibular excision or osteotomy (includes correction of genu varus [bowleg] or genu valgus [knock-knee]); after epiphyseal closure). The code for DFO was 27450: osteotomy, femur, shaft or supracondylar; with fixation. Last, the code for TTO was 27418: anterior tibial tubercleplasty (eg, Maquet-type procedure). The 141 patients identified in the search were treated by Dr. Cole at a single institution and were included in the study. Study inclusion did not require a minimum follow-up. Follow-up duration was defined as the time between surgery and the final clinic note in the patient chart. No patient was excluded for lack of follow-up clinic visits, and none was lost to follow-up.

Age, BMI, smoking status, and OC use were recorded for all patients. For each procedure, the surgeon’s technique remained the same throughout the study period: HTO, medial opening-wedge osteotomy with plate-and-screw fixation; DFO, lateral opening-wedge osteotomy with plate-and-screw fixation; and TTO, mostly anteromedialization with screw fixation (though this was dictated by patellar contact pressures). A tourniquet was used in all cases. Each patient’s hospital electronic medical record and outpatient office notes were reviewed to determine if symptomatic DVT or PE developed after surgery. The diagnosis of symptomatic DVT was based on clinical symptoms and confirmatory ultrasound, and the PE diagnosis was based on computed tomography. Doppler ultrasound was performed only in symptomatic patients (ie, it was not routinely performed).

Per surgeon protocol, postoperative DVT prophylaxis was not administered. Patients were encouraged to begin dorsiflexion and plantar flexion of the ankle (ankle pumps) immediately and to mobilize as soon as comfortable. Each patient received a cold therapy machine with compression sleeve. Patients were allowed toe-touch weight-bearing for 6 weeks, and then progressed 25% per week for 4 weeks to full weight-bearing by 10 weeks. After surgery, each patient was placed in a brace, which was kept locked in extension for 10 days; when the brace was unlocked, the patient was allowed to range the knee.

Continuous variable data are reported as weighted means and weighted standard deviations. Categorical variable data are reported as frequencies and percentages.

Results

Our database search identified 141 patients (44% male, 56% female) who underwent HTO (47 patients, 33.3%), DFO (13 patients, 9.2%), or TTO (81 patients, 57.5%). Mean (SD) age was 34.28 (9.86) years, mean (SD) BMI was 26.88 (5.11) kg/m², and mean (SD) follow-up was 17.1 (4.1) months. Of the female patients, 36.7% were using OCs at time of surgery. Of all patients, 13.48% were smokers.

Two patients (1.42%) had clinical symptoms consistent with DVT. In each case, the diagnosis was confirmed with Doppler ultrasound. The below-knee DVT was unilateral in 1 case and bilateral in the other.

Discussion

As the rates of DVT and PE after osteotomies about the knee have not been well studied, we wanted to determine these rates after HTO, DFO, and TTO in patients who did not receive postoperative DVT prophylaxis. We hypothesized that DVT and PE rates would both be <1%, and this hypothesis was partly confirmed: The rate of PE after HTO, DFO, and TTO was <1%, and the rate of symptomatic DVT was >1%. Similarly, the patients who developed these complications were nonsmokers and had a BMI no higher than that of the patients who did not develop DVT or PE. In addition, only 1 patient developed DVT and PE, and she was using OCs and had a family history of DVT. Last, the patients who developed these complications were on average 14 years older than the patients who did not develop DVT or PE.

Although there is a plethora of reports on the incidence of DVT and PE after TKA, there is little on the incidence after osteotomies about the knee.^8,12 The rate of DVT after TKA varies, but many studies place it between 2% and 12%, and routinely find a PE rate of <0.5%.^10,11,13,14 Although the AAOS issued a clinical practice guideline for postoperative DVT prophylaxis after TKA, and evaluated the best available evidence, it could not reach consensus on a specific type of DVT prophylaxis, though the workgroup did recommend that patients be administered postoperative DVT prophylaxis of some kind.^8,9 Similarly, the American College of Chest Physicians (ACCP) issued clinical practice guidelines for preventing DVT and PE after elective TKA and total hip arthroplasty.¹⁵ According to the ACCP guidelines, patients should receive prophylaxis—LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, low-dose unfractionated heparin, adjusted-dose vitamin K antagonist, aspirin, or an intermittent pneumatic compression device—for a minimum of 14 days. Unfortunately, though there are similarities between TKAs and peri-knee osteotomies, these procedures are markedly different, and it is difficult to extrapolate and adapt recommendations and produce a consensus statement for knee arthroplasties. In addition, guidelines exist for hospitalized patients who are being treated for medical conditions or have undergone surgery, but all the patients in the present study had their osteotomies performed on an outpatient basis.

Martin and colleagues¹⁶ reviewed 323 cases of medial opening-wedge HTO and found a DVT rate of 1.4% in the absence of routine DVT prophylaxis, except in patients with a history of DVT. Their rate is almost identical to ours, but we also included other osteotomies in our study. Miller and colleagues¹⁷ reviewed 46 cases of medial opening-wedge HTO and found a 4.3% DVT rate, despite routine prophylaxis with once-daily 325-mg aspirin and ankle pumps. This finding contrasts with our 1.42% DVT rate in the absence of postoperative chemical DVT prophylaxis. Motycka and colleagues¹⁸ reviewed 65 HTO cases in which DVT prophylaxis (oral anticoagulant) was given for 6 weeks, and they found a DVT rate of 9.7%. Turner and colleagues¹⁹ performed venous ultrasound on 81 consecutive patients who underwent HTO and received DVT prophylaxis (twice-daily subcutaneous heparin), and they found a DVT rate of 41% and a PE rate of 1.2%, though only 8.6% of the DVT cases were symptomatic. Of note, whereas the lowest postoperative DVT rate was for patients who did not receive postoperative DVT prophylaxis, the rate of symptomatic DVT after these osteotomies ranged from 1.4% to 8.6% in patients who received prophylaxis.^16,19 Given this evidence and our study results, it appears routine chemical DVT prophylaxis after osteotomies about the knee may not be necessary, though higher level evidence is needed in order to make definitive recommendations.

In the present study, the 2 patients who developed symptomatic DVT (1 subsequently developed PE) were nonsmokers in good health. The female patient (DVT plus PE) was using OCs at time of surgery. Studies have shown that patients who smoke and who use OCs are at increased risk for developing DVT or PE after surgery.^5,6,12 Given that only 2 of our patients developed DVT/PE, and neither was a smoker, smoking was not associated with increased DVT or PE risk in this study population, in which 13.48% of patients were smokers at time of surgery. In addition, given that the 1 female patient who developed DVT/PE was using OCs and that 36.7% of all female patients in the study were using OCs, it is difficult to conclude whether OC use increased the female patient’s risk for DVT or PE. Furthermore, neither the literature nor the AAOS consensus statement supports discontinuing OCs for this surgical procedure.

Patients in this study did not receive chemical or mechanical DVT prophylaxis after surgery. Regarding various post-TKA DVT prophylaxis regimens, aspirin is as effective as LMWH in preventing DVT, and the risk for postoperative blood loss and wound complications is lower with aspirin than with rivaroxaban.^20,21 Given that the present study’s postoperative rates of DVT (1.42%) and PE (0.71%) are equal to or less than rates already reported in the literature, routine DVT prophylaxis after osteotomies about the knee may be unnecessary in the absence of other significant risk factors.^16,19 However, our study considered only symptomatic DVT and PE, so it is possible that the number of asymptomatic DVT cases is higher in this patient population. Definitively answering our study’s clinical question will require a multicenter registry study (prospective cohort study).

Study Limitations

The strengths of this study include the large number of patients treated by a single surgeon using the same postoperative protocol. Limitations of this study include the lack of a control group. Although we found a DVT rate of 1.42% and a PE rate of 0.71%, the literature on the accepted risks for DVT and PE after HTO, DFO, and TTO is unclear. With our results stratified by procedure, the DVT rate was 2% in the HTO group, 0% in the DFO group, and 1% in the TTO group. However, we were unable to reliably stratify these results by each specific procedure, as the number of patients in each group would be too low. This study involved reviewing charts; as patients were not contacted, it is possible a patient developed DVT or PE, was treated at an outside facility, and then never followed up with the treating surgeon. Patients were identified by CPT codes, so, if a patient underwent HTO, DFO, or TTO that was recorded under a different CPT code, it is possible the patient was missed by our search. All patients were seen after surgery, and we reviewed the outpatient office notes that were taken, so unless the DVT or PE occurred after a patient’s final postoperative visit, it would have been recorded. Similarly, the DVT and PE rates reported here cannot be extrapolated to overall risks for DVT and PE after osteotomies about the knee in all patients—only in patients who did not receive DVT prophylaxis after surgery.

Conclusion

The rates of DVT and PE after HTO, DFO, and TTO in patients who did not receive chemical prophylaxis are low: 1.42% and 0.71%, respectively. After these osteotomies, DVT/PE prophylaxis in the absence of known risk factors may not be warranted.

Am J Orthop. 2017;46(1):E23-E27. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

CHICAGO – Bioresorbable scaffolds, new drugs, adjuvant interventions, and stem and progenitor cell therapy will change how vascular surgeons treat peripheral artery disease in the next 5 years, so they must embrace these emerging treatments or run the risk of being displaced by other specialists, according to a presentation at a symposium on vascular surgery sponsored by Northwestern University.

“Vascular surgeons must position their practices to be the nexus for the evaluation and treatment of the patient and proactively engage in the critical trials of these new technologies,” said Patrick J. Geraghty, MD, of Washington University, St. Louis. “If our specialty fails to adapt to new treatment options, we risk getting sidelined as critical limb ischemia (CLI) treatment moves into a multimodality model.”

CHICAGO – Bioresorbable scaffolds, new drugs, adjuvant interventions, and stem and progenitor cell therapy will change how vascular surgeons treat peripheral artery disease in the next 5 years, so they must embrace these emerging treatments or run the risk of being displaced by other specialists, according to a presentation at a symposium on vascular surgery sponsored by Northwestern University.

“Vascular surgeons must position their practices to be the nexus for the evaluation and treatment of the patient and proactively engage in the critical trials of these new technologies,” said Patrick J. Geraghty, MD, of Washington University, St. Louis. “If our specialty fails to adapt to new treatment options, we risk getting sidelined as critical limb ischemia (CLI) treatment moves into a multimodality model.”

CHICAGO – Bioresorbable scaffolds, new drugs, adjuvant interventions, and stem and progenitor cell therapy will change how vascular surgeons treat peripheral artery disease in the next 5 years, so they must embrace these emerging treatments or run the risk of being displaced by other specialists, according to a presentation at a symposium on vascular surgery sponsored by Northwestern University.

“Vascular surgeons must position their practices to be the nexus for the evaluation and treatment of the patient and proactively engage in the critical trials of these new technologies,” said Patrick J. Geraghty, MD, of Washington University, St. Louis. “If our specialty fails to adapt to new treatment options, we risk getting sidelined as critical limb ischemia (CLI) treatment moves into a multimodality model.”

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. The classic presentation of BP is a generalized, pruritic, bullous eruption in elderly patients, which is occasionally preceded by an urticarial prodrome. Immunopathologically, BP is characterized by IgG and sometimes IgE autoantibodies that target basement membrane zone proteins BP180 and BP230 of the epidermis.¹

The diagnosis of BP should be suspected when an elderly patient presents with tense blisters and can be confirmed via diagnostic testing, including tissue histology and direct immunofluorescence (DIF) as the gold standard, as well as indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and most recently biochip technology as supportive tests.² Since its advent, ELISA has gained popularity as a trustworthy diagnostic test for BP. The specificity of ELISA for BP diagnosis is reported to be 98% to 100%, which leads clinicians to believe that a positive ELISA equals certain diagnosis of BP; however, misdiagnosis of BP based on a positive ELISA result can occur.^3-13 The treatment of BP often involves lifelong immunosuppressive therapy. Complications of immunosuppressive therapy contribute to morbidity and mortality in these patients, thus an accurate diagnosis is paramount before introducing therapy.¹⁴

We present the case of a 74-year-old man with a history of a pruritic nonbullous eruption who was diagnosed with BP and treated for 3 years based on positive ELISA results in the absence of confirmatory histology or DIF.

Case Report

A 74-year-old man with diabetes mellitus, hypertension, hyperlipidemia, benign prostatic hypertrophy, and obstructive sleep apnea presented for further evaluation and confirmation of a prior diagnosis of BP by an outside dermatologist. He reported a pruritic rash on the trunk, back, and extremities of 3 years’ duration. He denied occurrence of blisters at any time.

On presentation to an outside dermatologist 3 years ago, a biopsy was performed along with serologic studies due to the patient’s age and the possibility of an urticarial prodrome in BP. The biopsy revealed epidermal acanthosis, subepidermal separation, and a perivascular and interstitial infiltrate of lymphocytes and eosinophils in the papillary dermis. Direct immunofluorescence was nondiagnostic with a weak discontinuous pattern of IgG and IgA linearly along the basement membrane zone as well as few scattered and clumped cytoid bodies of IgM and IgA. Indirect immunofluoresence revealed a positive IgG titer of 1:40 on monkey esophagus substrate and a positive epidermal pattern on human split-skin substrate with a titer of 1:80. An ELISA for IgG autoantibodies against BP180 and BP230 yielded 15 U and 6 U, respectively (cut off value, 9 U). Based on the positive ELISA for IgG against BP180, a diagnosis of BP was made.

Over the following 3 years, the treatment included prednisone, tetracycline, nicotinamide, doxycycline, and dapsone. Therapy was suboptimal due to the patient’s comorbidities and socioeconomic status. Poorly controlled diabetes mellitus precluded consistent use of prednisone as recommended for BP. Tetracycline and nicotinamide were transiently effective in controlling the patient’s symptoms but were discontinued due to changes in his health insurance. Doxycycline and dapsone were ineffective. Throughout this 3-year period, the patient remained blister free, but the pruritic eruption was persistent.

The patient presented to our clinic due to his frustration with the lack of improvement and doubts about the BP diagnosis given the persistent absence of bullous lesions. Physical examination revealed numerous eroded, scaly, crusted papules on erythematous edematous plaques on all extremities, trunk, and back (Figure 1). The head, neck, face, and oral mucosa were spared. His history and clinical findings were atypical for BP and skin biopsies were performed. Histology revealed epidermal erosion with parakeratosis, spongiosis, and superficial perivascular lymphocytic inflammation with rare eosinophils without subepidermal split (Figure 2). Direct immunofluorescence was negative for IgG, IgA, IgM, C3, and C1q. Additionally, further review of the initial histology by another dermatopathologist revealed that the subepidermal separation reported was more likely artifactual clefts. These findings were not consistent with BP.

Given the patient’s clinical history, lack of bullae, and twice-negative DIF, the diagnosis was determined to be more consistent with eczematous spongiotic dermatitis. He refused a referral for phototherapy due to scheduling inconvenience. The patient was started on cyclosporine 0.5 mg/kg twice daily. After 10 days of treatment, he returned for follow-up and reported notable improvement in the pruritus. On physical examination, his dermatitis was improved with decreased erythema and inflammation.

The patient is being continued on extensive dry skin care with thick moisturizers and additional topical corticosteroid application on an as-needed basis.

Comment

Chronic immunosuppression contributes to morbidity and mortality in patients with BP; therefore, accurate diagnosis of BP is of utmost importance.¹⁴ A meta-analysis described ELISA as a test with high sensitivity and specificity (87% and 98%–100%, respectively) for diagnosis of BP.³ Nevertheless, there are opportunities for misdiagnosis using ELISA, as demonstrated in our case. To determine if the reported sensitivity and specificity of ELISA is accurate and reliable for clinical use, individual studies from the meta-analysis were reviewed.^{4,5,7-10,13,15} Issues identified in our review included dissimilar diagnostic procedures and patient populations among individual studies, several reports of positive ELISA in patients without BP, and a lack of explanation for these false-positive results.

There are notable differences in diagnostic procedures and patient populations among reports that establish the sensitivity and specificity of ELISA for BP diagnosis.^3-13 Studies have detected IgG that targets the NC16A domain of the BP180 kD antigen, the C-terminal of the BP180 kD antigen, or the entire ectodomain of the BP180 kD antigen. Study patient populations varied in disease activity, stage, and treatment. Control patients included healthy patients as well as those with many dermatoses, including pemphigus vulgaris, systemic scleroderma, systemic lupus erythematosus, rheumatoid arthritis, lichen planus, and discoid lupus erythematosus.^3-13 Due to these differences between individual studies, we believe the results that determine the overall sensitivity and specificity of ELISA for BP diagnosis must be interpreted with caution. For ELISA statistics to be clinically applicable to a specific patient, he/she should be similar to the patients studied. Therefore, we believe each study must be evaluated individually for applicability, given the differences that exist between them.

Furthermore, there have been several reports of false-positive ELISA results in patients with other dermatologic disorders, specifically in elderly patients with pruritus who do not fulfill clinical criteria for diagnosis with BP.^16-18 In a population of elderly patients with pruritus for which no specific dermatological or systemic cause was identified, Hofmann et al¹⁸ found that 12% (3/25) of patients showed IgG reactivity to BP180 despite having negative DIF results. In another study of elderly patients with pruritic dermatoses, Feliciani et al¹⁷ found that 33% (5/15) of patients had IgG reactivity against BP230 or BP180, though they did not fulfill BP criteria based on clinical presentation and showed negative DIF and IIF results. These findings suggest that IgG reactivity against BP autoantibodies as determined by ELISA is not uncommon in pruritic diseases of the elderly.

Explanations for false-positive ELISA results were rare. A few authors suggested that false-positives could be attributed to an excessively low cutoff value,^7-9 which was consistent with reports that the titer of autoantibodies to BP180 correlates with disease severity, suggesting that the higher titer of antibodies correlates with more severe disease and likely more accurate diagnosis.^10,19,20 It is important to consider that patients who have low titers of BP180 autoantibodies with inconsistent clinical characteristics and DIF results may not truly have BP. Furthermore, to determine the clinical value of ELISA in identifying patients in the initial phase of BP, sera of BP patients should be compared with sera of elderly patients with pruritic skin disorders because they comprise the patient population that often requires diagnosis.¹⁸

Given the issues identified in our review of the literature, the published sensitivity and specificity of ELISA for BP diagnosis are likely overstated. In conclusion, ELISA should not be relied on as a single criterion adequate for diagnosis of BP.^12,21 Rather, the diagnosis of BP can be obtained with a positive predictive value of 95% when a patient meets 3 of 4 clinical criteria (ie, absence of atrophic scars, absence of head and neck involvement, absence of mucosal involvement, and older than 70 years) and demonstrates linear deposits of predominantly IgG and/or C3 along the basement membrane zone of a perilesional biopsy on DIF.¹⁵ The gold standard for diagnosis of BP remains clinical presentation along with DIF, which can be supported by histology, IIF, and ELISA.²²

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. The classic presentation of BP is a generalized, pruritic, bullous eruption in elderly patients, which is occasionally preceded by an urticarial prodrome. Immunopathologically, BP is characterized by IgG and sometimes IgE autoantibodies that target basement membrane zone proteins BP180 and BP230 of the epidermis.¹

The diagnosis of BP should be suspected when an elderly patient presents with tense blisters and can be confirmed via diagnostic testing, including tissue histology and direct immunofluorescence (DIF) as the gold standard, as well as indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and most recently biochip technology as supportive tests.² Since its advent, ELISA has gained popularity as a trustworthy diagnostic test for BP. The specificity of ELISA for BP diagnosis is reported to be 98% to 100%, which leads clinicians to believe that a positive ELISA equals certain diagnosis of BP; however, misdiagnosis of BP based on a positive ELISA result can occur.^3-13 The treatment of BP often involves lifelong immunosuppressive therapy. Complications of immunosuppressive therapy contribute to morbidity and mortality in these patients, thus an accurate diagnosis is paramount before introducing therapy.¹⁴

We present the case of a 74-year-old man with a history of a pruritic nonbullous eruption who was diagnosed with BP and treated for 3 years based on positive ELISA results in the absence of confirmatory histology or DIF.

Case Report

A 74-year-old man with diabetes mellitus, hypertension, hyperlipidemia, benign prostatic hypertrophy, and obstructive sleep apnea presented for further evaluation and confirmation of a prior diagnosis of BP by an outside dermatologist. He reported a pruritic rash on the trunk, back, and extremities of 3 years’ duration. He denied occurrence of blisters at any time.

On presentation to an outside dermatologist 3 years ago, a biopsy was performed along with serologic studies due to the patient’s age and the possibility of an urticarial prodrome in BP. The biopsy revealed epidermal acanthosis, subepidermal separation, and a perivascular and interstitial infiltrate of lymphocytes and eosinophils in the papillary dermis. Direct immunofluorescence was nondiagnostic with a weak discontinuous pattern of IgG and IgA linearly along the basement membrane zone as well as few scattered and clumped cytoid bodies of IgM and IgA. Indirect immunofluoresence revealed a positive IgG titer of 1:40 on monkey esophagus substrate and a positive epidermal pattern on human split-skin substrate with a titer of 1:80. An ELISA for IgG autoantibodies against BP180 and BP230 yielded 15 U and 6 U, respectively (cut off value, 9 U). Based on the positive ELISA for IgG against BP180, a diagnosis of BP was made.

Over the following 3 years, the treatment included prednisone, tetracycline, nicotinamide, doxycycline, and dapsone. Therapy was suboptimal due to the patient’s comorbidities and socioeconomic status. Poorly controlled diabetes mellitus precluded consistent use of prednisone as recommended for BP. Tetracycline and nicotinamide were transiently effective in controlling the patient’s symptoms but were discontinued due to changes in his health insurance. Doxycycline and dapsone were ineffective. Throughout this 3-year period, the patient remained blister free, but the pruritic eruption was persistent.

The patient presented to our clinic due to his frustration with the lack of improvement and doubts about the BP diagnosis given the persistent absence of bullous lesions. Physical examination revealed numerous eroded, scaly, crusted papules on erythematous edematous plaques on all extremities, trunk, and back (Figure 1). The head, neck, face, and oral mucosa were spared. His history and clinical findings were atypical for BP and skin biopsies were performed. Histology revealed epidermal erosion with parakeratosis, spongiosis, and superficial perivascular lymphocytic inflammation with rare eosinophils without subepidermal split (Figure 2). Direct immunofluorescence was negative for IgG, IgA, IgM, C3, and C1q. Additionally, further review of the initial histology by another dermatopathologist revealed that the subepidermal separation reported was more likely artifactual clefts. These findings were not consistent with BP.

Given the patient’s clinical history, lack of bullae, and twice-negative DIF, the diagnosis was determined to be more consistent with eczematous spongiotic dermatitis. He refused a referral for phototherapy due to scheduling inconvenience. The patient was started on cyclosporine 0.5 mg/kg twice daily. After 10 days of treatment, he returned for follow-up and reported notable improvement in the pruritus. On physical examination, his dermatitis was improved with decreased erythema and inflammation.

The patient is being continued on extensive dry skin care with thick moisturizers and additional topical corticosteroid application on an as-needed basis.

Comment

Chronic immunosuppression contributes to morbidity and mortality in patients with BP; therefore, accurate diagnosis of BP is of utmost importance.¹⁴ A meta-analysis described ELISA as a test with high sensitivity and specificity (87% and 98%–100%, respectively) for diagnosis of BP.³ Nevertheless, there are opportunities for misdiagnosis using ELISA, as demonstrated in our case. To determine if the reported sensitivity and specificity of ELISA is accurate and reliable for clinical use, individual studies from the meta-analysis were reviewed.^{4,5,7-10,13,15} Issues identified in our review included dissimilar diagnostic procedures and patient populations among individual studies, several reports of positive ELISA in patients without BP, and a lack of explanation for these false-positive results.

There are notable differences in diagnostic procedures and patient populations among reports that establish the sensitivity and specificity of ELISA for BP diagnosis.^3-13 Studies have detected IgG that targets the NC16A domain of the BP180 kD antigen, the C-terminal of the BP180 kD antigen, or the entire ectodomain of the BP180 kD antigen. Study patient populations varied in disease activity, stage, and treatment. Control patients included healthy patients as well as those with many dermatoses, including pemphigus vulgaris, systemic scleroderma, systemic lupus erythematosus, rheumatoid arthritis, lichen planus, and discoid lupus erythematosus.^3-13 Due to these differences between individual studies, we believe the results that determine the overall sensitivity and specificity of ELISA for BP diagnosis must be interpreted with caution. For ELISA statistics to be clinically applicable to a specific patient, he/she should be similar to the patients studied. Therefore, we believe each study must be evaluated individually for applicability, given the differences that exist between them.

Furthermore, there have been several reports of false-positive ELISA results in patients with other dermatologic disorders, specifically in elderly patients with pruritus who do not fulfill clinical criteria for diagnosis with BP.^16-18 In a population of elderly patients with pruritus for which no specific dermatological or systemic cause was identified, Hofmann et al¹⁸ found that 12% (3/25) of patients showed IgG reactivity to BP180 despite having negative DIF results. In another study of elderly patients with pruritic dermatoses, Feliciani et al¹⁷ found that 33% (5/15) of patients had IgG reactivity against BP230 or BP180, though they did not fulfill BP criteria based on clinical presentation and showed negative DIF and IIF results. These findings suggest that IgG reactivity against BP autoantibodies as determined by ELISA is not uncommon in pruritic diseases of the elderly.

Explanations for false-positive ELISA results were rare. A few authors suggested that false-positives could be attributed to an excessively low cutoff value,^7-9 which was consistent with reports that the titer of autoantibodies to BP180 correlates with disease severity, suggesting that the higher titer of antibodies correlates with more severe disease and likely more accurate diagnosis.^10,19,20 It is important to consider that patients who have low titers of BP180 autoantibodies with inconsistent clinical characteristics and DIF results may not truly have BP. Furthermore, to determine the clinical value of ELISA in identifying patients in the initial phase of BP, sera of BP patients should be compared with sera of elderly patients with pruritic skin disorders because they comprise the patient population that often requires diagnosis.¹⁸

Given the issues identified in our review of the literature, the published sensitivity and specificity of ELISA for BP diagnosis are likely overstated. In conclusion, ELISA should not be relied on as a single criterion adequate for diagnosis of BP.^12,21 Rather, the diagnosis of BP can be obtained with a positive predictive value of 95% when a patient meets 3 of 4 clinical criteria (ie, absence of atrophic scars, absence of head and neck involvement, absence of mucosal involvement, and older than 70 years) and demonstrates linear deposits of predominantly IgG and/or C3 along the basement membrane zone of a perilesional biopsy on DIF.¹⁵ The gold standard for diagnosis of BP remains clinical presentation along with DIF, which can be supported by histology, IIF, and ELISA.²²

Bullous pemphigoid (BP) is the most common autoimmune blistering disease. The classic presentation of BP is a generalized, pruritic, bullous eruption in elderly patients, which is occasionally preceded by an urticarial prodrome. Immunopathologically, BP is characterized by IgG and sometimes IgE autoantibodies that target basement membrane zone proteins BP180 and BP230 of the epidermis.¹

The diagnosis of BP should be suspected when an elderly patient presents with tense blisters and can be confirmed via diagnostic testing, including tissue histology and direct immunofluorescence (DIF) as the gold standard, as well as indirect immunofluorescence (IIF), enzyme-linked immunosorbent assay (ELISA), and most recently biochip technology as supportive tests.² Since its advent, ELISA has gained popularity as a trustworthy diagnostic test for BP. The specificity of ELISA for BP diagnosis is reported to be 98% to 100%, which leads clinicians to believe that a positive ELISA equals certain diagnosis of BP; however, misdiagnosis of BP based on a positive ELISA result can occur.^3-13 The treatment of BP often involves lifelong immunosuppressive therapy. Complications of immunosuppressive therapy contribute to morbidity and mortality in these patients, thus an accurate diagnosis is paramount before introducing therapy.¹⁴

We present the case of a 74-year-old man with a history of a pruritic nonbullous eruption who was diagnosed with BP and treated for 3 years based on positive ELISA results in the absence of confirmatory histology or DIF.

Case Report

A 74-year-old man with diabetes mellitus, hypertension, hyperlipidemia, benign prostatic hypertrophy, and obstructive sleep apnea presented for further evaluation and confirmation of a prior diagnosis of BP by an outside dermatologist. He reported a pruritic rash on the trunk, back, and extremities of 3 years’ duration. He denied occurrence of blisters at any time.

On presentation to an outside dermatologist 3 years ago, a biopsy was performed along with serologic studies due to the patient’s age and the possibility of an urticarial prodrome in BP. The biopsy revealed epidermal acanthosis, subepidermal separation, and a perivascular and interstitial infiltrate of lymphocytes and eosinophils in the papillary dermis. Direct immunofluorescence was nondiagnostic with a weak discontinuous pattern of IgG and IgA linearly along the basement membrane zone as well as few scattered and clumped cytoid bodies of IgM and IgA. Indirect immunofluoresence revealed a positive IgG titer of 1:40 on monkey esophagus substrate and a positive epidermal pattern on human split-skin substrate with a titer of 1:80. An ELISA for IgG autoantibodies against BP180 and BP230 yielded 15 U and 6 U, respectively (cut off value, 9 U). Based on the positive ELISA for IgG against BP180, a diagnosis of BP was made.

Over the following 3 years, the treatment included prednisone, tetracycline, nicotinamide, doxycycline, and dapsone. Therapy was suboptimal due to the patient’s comorbidities and socioeconomic status. Poorly controlled diabetes mellitus precluded consistent use of prednisone as recommended for BP. Tetracycline and nicotinamide were transiently effective in controlling the patient’s symptoms but were discontinued due to changes in his health insurance. Doxycycline and dapsone were ineffective. Throughout this 3-year period, the patient remained blister free, but the pruritic eruption was persistent.

The patient presented to our clinic due to his frustration with the lack of improvement and doubts about the BP diagnosis given the persistent absence of bullous lesions. Physical examination revealed numerous eroded, scaly, crusted papules on erythematous edematous plaques on all extremities, trunk, and back (Figure 1). The head, neck, face, and oral mucosa were spared. His history and clinical findings were atypical for BP and skin biopsies were performed. Histology revealed epidermal erosion with parakeratosis, spongiosis, and superficial perivascular lymphocytic inflammation with rare eosinophils without subepidermal split (Figure 2). Direct immunofluorescence was negative for IgG, IgA, IgM, C3, and C1q. Additionally, further review of the initial histology by another dermatopathologist revealed that the subepidermal separation reported was more likely artifactual clefts. These findings were not consistent with BP.

Given the patient’s clinical history, lack of bullae, and twice-negative DIF, the diagnosis was determined to be more consistent with eczematous spongiotic dermatitis. He refused a referral for phototherapy due to scheduling inconvenience. The patient was started on cyclosporine 0.5 mg/kg twice daily. After 10 days of treatment, he returned for follow-up and reported notable improvement in the pruritus. On physical examination, his dermatitis was improved with decreased erythema and inflammation.

The patient is being continued on extensive dry skin care with thick moisturizers and additional topical corticosteroid application on an as-needed basis.

Comment

Chronic immunosuppression contributes to morbidity and mortality in patients with BP; therefore, accurate diagnosis of BP is of utmost importance.¹⁴ A meta-analysis described ELISA as a test with high sensitivity and specificity (87% and 98%–100%, respectively) for diagnosis of BP.³ Nevertheless, there are opportunities for misdiagnosis using ELISA, as demonstrated in our case. To determine if the reported sensitivity and specificity of ELISA is accurate and reliable for clinical use, individual studies from the meta-analysis were reviewed.^{4,5,7-10,13,15} Issues identified in our review included dissimilar diagnostic procedures and patient populations among individual studies, several reports of positive ELISA in patients without BP, and a lack of explanation for these false-positive results.

There are notable differences in diagnostic procedures and patient populations among reports that establish the sensitivity and specificity of ELISA for BP diagnosis.^3-13 Studies have detected IgG that targets the NC16A domain of the BP180 kD antigen, the C-terminal of the BP180 kD antigen, or the entire ectodomain of the BP180 kD antigen. Study patient populations varied in disease activity, stage, and treatment. Control patients included healthy patients as well as those with many dermatoses, including pemphigus vulgaris, systemic scleroderma, systemic lupus erythematosus, rheumatoid arthritis, lichen planus, and discoid lupus erythematosus.^3-13 Due to these differences between individual studies, we believe the results that determine the overall sensitivity and specificity of ELISA for BP diagnosis must be interpreted with caution. For ELISA statistics to be clinically applicable to a specific patient, he/she should be similar to the patients studied. Therefore, we believe each study must be evaluated individually for applicability, given the differences that exist between them.

Furthermore, there have been several reports of false-positive ELISA results in patients with other dermatologic disorders, specifically in elderly patients with pruritus who do not fulfill clinical criteria for diagnosis with BP.^16-18 In a population of elderly patients with pruritus for which no specific dermatological or systemic cause was identified, Hofmann et al¹⁸ found that 12% (3/25) of patients showed IgG reactivity to BP180 despite having negative DIF results. In another study of elderly patients with pruritic dermatoses, Feliciani et al¹⁷ found that 33% (5/15) of patients had IgG reactivity against BP230 or BP180, though they did not fulfill BP criteria based on clinical presentation and showed negative DIF and IIF results. These findings suggest that IgG reactivity against BP autoantibodies as determined by ELISA is not uncommon in pruritic diseases of the elderly.

Explanations for false-positive ELISA results were rare. A few authors suggested that false-positives could be attributed to an excessively low cutoff value,^7-9 which was consistent with reports that the titer of autoantibodies to BP180 correlates with disease severity, suggesting that the higher titer of antibodies correlates with more severe disease and likely more accurate diagnosis.^10,19,20 It is important to consider that patients who have low titers of BP180 autoantibodies with inconsistent clinical characteristics and DIF results may not truly have BP. Furthermore, to determine the clinical value of ELISA in identifying patients in the initial phase of BP, sera of BP patients should be compared with sera of elderly patients with pruritic skin disorders because they comprise the patient population that often requires diagnosis.¹⁸

Given the issues identified in our review of the literature, the published sensitivity and specificity of ELISA for BP diagnosis are likely overstated. In conclusion, ELISA should not be relied on as a single criterion adequate for diagnosis of BP.^12,21 Rather, the diagnosis of BP can be obtained with a positive predictive value of 95% when a patient meets 3 of 4 clinical criteria (ie, absence of atrophic scars, absence of head and neck involvement, absence of mucosal involvement, and older than 70 years) and demonstrates linear deposits of predominantly IgG and/or C3 along the basement membrane zone of a perilesional biopsy on DIF.¹⁵ The gold standard for diagnosis of BP remains clinical presentation along with DIF, which can be supported by histology, IIF, and ELISA.²²

HOLLYWOOD, FLA. – Incompatible Type A plasma appears to be a safe and effective part of an initial resuscitation protocol for trauma patients who need a massive transfusion.

There were no increases in morbidity, mortality, or transfusion-related acute lung injury among 120 patients who received Type A plasma, compared with those who got compatible plasma, Bryan C. Morse, MD, said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Type AB blood products are preferred for initial transfusions for trauma patients with unknown blood type. While type AB blood products are universally acceptable to patients, they are also in short supply. In an attempt to mitigate this shortage, some trauma centers are relying on anecdotal data, much drawn from real-life combat experience dating from World War II to present times, suggesting that Type A plasma is safe for initial resuscitation protocols. But the body of data from well-constructed trials is small, said Dr. Morse of Emory University, Atlanta. Thus, EAST sponsored this retrospective registry study, which examined outcomes in 1,536 trauma patients who received plasma transfusions as part of a massive transfusion protocol from 2012 to 2016.

The primary endpoints were overall morbidity, and mortality at four time points: 6 and 24 hours, and 7 and 28 days. Eight trauma centers contributed data to the study.

The group was largely male (75%) with a mean age of 37 years. Patients were seriously injured, with a mean Injury Severity Score (ISS) of 25. About 60% suffered from blunt-force trauma. Among the entire group, 120 (8%) received incompatible type A plasma.

About 28% of patients (434) experienced an adverse event. These were numerically but not significantly more common among the incompatible A plasma group (35% vs. 28%; P = .14). Events included acute respiratory distress syndrome (6% vs. 7.6%), thromboembolism (9% vs. 7%), pneumonia (19% vs. 15%), and acute kidney injury (8% each).

There were two cases of transfusion-related acute lung injury, both of which occurred in the compatible type A group.

Mortality was similar at every time point: 6 hours (16% vs. 15%), 24 hours (25% vs. 22%), 7 days (35% vs. 32%), and 28 days (38% vs. 35%).

A multivariate regression model controlled for treatment center, ISS, units of packed red cells given by 4 hours, mechanism of injury, Type A plasma incompatibility, and age.

In the morbidity analysis, only ISS and units of red blood cells at 4 hours were associated with a significant increase in risk (odd ratio 1.02). Incompatible Type A plasma did not significantly increase the risk of morbidity.

In the mortality analysis, units of red cells, ISS, and age were significantly associated with increased risk. Again, incompatible Type A plasma did not significantly increase the risk of death.

Dr. Morse had no financial declaration.

[email protected]

On Twitter @Alz_Gal

HOLLYWOOD, FLA. – Incompatible Type A plasma appears to be a safe and effective part of an initial resuscitation protocol for trauma patients who need a massive transfusion.

There were no increases in morbidity, mortality, or transfusion-related acute lung injury among 120 patients who received Type A plasma, compared with those who got compatible plasma, Bryan C. Morse, MD, said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Type AB blood products are preferred for initial transfusions for trauma patients with unknown blood type. While type AB blood products are universally acceptable to patients, they are also in short supply. In an attempt to mitigate this shortage, some trauma centers are relying on anecdotal data, much drawn from real-life combat experience dating from World War II to present times, suggesting that Type A plasma is safe for initial resuscitation protocols. But the body of data from well-constructed trials is small, said Dr. Morse of Emory University, Atlanta. Thus, EAST sponsored this retrospective registry study, which examined outcomes in 1,536 trauma patients who received plasma transfusions as part of a massive transfusion protocol from 2012 to 2016.

The primary endpoints were overall morbidity, and mortality at four time points: 6 and 24 hours, and 7 and 28 days. Eight trauma centers contributed data to the study.

The group was largely male (75%) with a mean age of 37 years. Patients were seriously injured, with a mean Injury Severity Score (ISS) of 25. About 60% suffered from blunt-force trauma. Among the entire group, 120 (8%) received incompatible type A plasma.

About 28% of patients (434) experienced an adverse event. These were numerically but not significantly more common among the incompatible A plasma group (35% vs. 28%; P = .14). Events included acute respiratory distress syndrome (6% vs. 7.6%), thromboembolism (9% vs. 7%), pneumonia (19% vs. 15%), and acute kidney injury (8% each).

There were two cases of transfusion-related acute lung injury, both of which occurred in the compatible type A group.

Mortality was similar at every time point: 6 hours (16% vs. 15%), 24 hours (25% vs. 22%), 7 days (35% vs. 32%), and 28 days (38% vs. 35%).

A multivariate regression model controlled for treatment center, ISS, units of packed red cells given by 4 hours, mechanism of injury, Type A plasma incompatibility, and age.

In the morbidity analysis, only ISS and units of red blood cells at 4 hours were associated with a significant increase in risk (odd ratio 1.02). Incompatible Type A plasma did not significantly increase the risk of morbidity.

In the mortality analysis, units of red cells, ISS, and age were significantly associated with increased risk. Again, incompatible Type A plasma did not significantly increase the risk of death.

Dr. Morse had no financial declaration.

[email protected]

On Twitter @Alz_Gal

HOLLYWOOD, FLA. – Incompatible Type A plasma appears to be a safe and effective part of an initial resuscitation protocol for trauma patients who need a massive transfusion.

There were no increases in morbidity, mortality, or transfusion-related acute lung injury among 120 patients who received Type A plasma, compared with those who got compatible plasma, Bryan C. Morse, MD, said at the annual scientific assembly of the Eastern Association for the Surgery of Trauma.

Type AB blood products are preferred for initial transfusions for trauma patients with unknown blood type. While type AB blood products are universally acceptable to patients, they are also in short supply. In an attempt to mitigate this shortage, some trauma centers are relying on anecdotal data, much drawn from real-life combat experience dating from World War II to present times, suggesting that Type A plasma is safe for initial resuscitation protocols. But the body of data from well-constructed trials is small, said Dr. Morse of Emory University, Atlanta. Thus, EAST sponsored this retrospective registry study, which examined outcomes in 1,536 trauma patients who received plasma transfusions as part of a massive transfusion protocol from 2012 to 2016.

The primary endpoints were overall morbidity, and mortality at four time points: 6 and 24 hours, and 7 and 28 days. Eight trauma centers contributed data to the study.

The group was largely male (75%) with a mean age of 37 years. Patients were seriously injured, with a mean Injury Severity Score (ISS) of 25. About 60% suffered from blunt-force trauma. Among the entire group, 120 (8%) received incompatible type A plasma.

About 28% of patients (434) experienced an adverse event. These were numerically but not significantly more common among the incompatible A plasma group (35% vs. 28%; P = .14). Events included acute respiratory distress syndrome (6% vs. 7.6%), thromboembolism (9% vs. 7%), pneumonia (19% vs. 15%), and acute kidney injury (8% each).

There were two cases of transfusion-related acute lung injury, both of which occurred in the compatible type A group.

Mortality was similar at every time point: 6 hours (16% vs. 15%), 24 hours (25% vs. 22%), 7 days (35% vs. 32%), and 28 days (38% vs. 35%).

A multivariate regression model controlled for treatment center, ISS, units of packed red cells given by 4 hours, mechanism of injury, Type A plasma incompatibility, and age.

In the morbidity analysis, only ISS and units of red blood cells at 4 hours were associated with a significant increase in risk (odd ratio 1.02). Incompatible Type A plasma did not significantly increase the risk of morbidity.

In the mortality analysis, units of red cells, ISS, and age were significantly associated with increased risk. Again, incompatible Type A plasma did not significantly increase the risk of death.

Dr. Morse had no financial declaration.

[email protected]

On Twitter @Alz_Gal

As pediatric and adolescent gynecologists, we are seeing an increasing number of adolescents with gender identity issues and have come to believe that all obstetrician-gynecologists need to have an understanding of varying gender identities, as well as their role in managing these patients’ care.

We had the honor to assist the American College of Obstetricians and Gynecologists’ (ACOG) Committee on Adolescent Health Care in the development of a new Committee Opinion to guide ob.gyns. in caring for transgender adolescents (Obstet Gynecol 2017;129:e11-6). As our culture grows more aware of the nuances and spectrum of gender identity, our health care practices must grow as well. Ob.gyns. are often uniquely positioned as being among the first people transgender adolescents present to – whether it’s signaling disassociation with their gender when answering routine medical questions or directly addressing gender with them as a trusted and private resource. Even when seeing a patient too young to consider hormone therapy, an ob.gyn. can offer vital early behavioral health support, educational and community resources, and specialist referrals.

Transgender adolescent patients have likely faced negative stereotypes and stigmas in social settings or through media that make them cautious and protective of their identity. They are also more likely to face social ostracism such as bullying and/or dissent and rejection from their parents, deepening the vulnerability of their situation. As a result, transgender adolescents can have increased instances of anxiety, depression, sexual harassment, homelessness, and risk-taking behavior. Medical practices can signal to transgender patients that they are safe and welcoming from the start by offering gender neutral forms, brochures, and information for LGBT patients in the waiting room, and having sensitive employees at every step – from the front desk onward.

As we’ve just outlined, transgender adolescent patients face unique challenges, including increased rates of social and mental health risks. In response, ob.gyns. must be prepared to have a comprehensive conversation about health and well-being beyond sexual and reproductive health. They must also be equipped to address the psychosocial issues associated with transgender adolescents. This includes knowledge of what to look for and offering patients resources, education, and referrals to guarantee their health and safety.

It is important that ob.gyns. are aware that transgender men have female reproductive organs and can present with common gynecological problems such as abnormal bleeding, ovarian cysts, and torsion, as well as pregnancy and pregnancy complications. Finally, ob.gyns. can serve a unique role in counseling about fertility and fertility preservation. Thus, not only do we provide essential health care, including ongoing primary care, but we can position ourselves as part of the support network for these adolescents and their families.

Most importantly, when addressing an adolescent transgender patient, we must understand there is no uniform transgender experience. Expressing gender, sexual identity, and behavior patterns will vary from patient to patient. There are a wide range of treatment options available for transgender patients, from hormone to surgical therapies. An ob.gyn.’s responsibility is to help each individual make an informed decision, and help that patient think ahead to the future.

While this all may seem like a lot, it’s important to remember the essential components of our role as health care providers do not change because an adolescent patient is transgender. Care should always include education about their bodies, safe sex, deliberate and thoughtful assessment of symptoms or concerns, and preventive care services such as STI screenings and contraception. We are simply adding more nuanced cultural and medical understanding to those practices.
 

Dr. Gomez-Lobo is director of pediatric and adolescent obstetrics and gynecology, Medstar Washington Hospital Center/Children’s National Health System, Washington, D.C. Dr. Sokkary is associate professor of ob.gyn. at Navicent Health Center/Mercer School of Medicine in Macon, Ga. They are members of the ACOG Committee on Adolescent Health Care. They reported having no relevant financial disclosures.

As pediatric and adolescent gynecologists, we are seeing an increasing number of adolescents with gender identity issues and have come to believe that all obstetrician-gynecologists need to have an understanding of varying gender identities, as well as their role in managing these patients’ care.

We had the honor to assist the American College of Obstetricians and Gynecologists’ (ACOG) Committee on Adolescent Health Care in the development of a new Committee Opinion to guide ob.gyns. in caring for transgender adolescents (Obstet Gynecol 2017;129:e11-6). As our culture grows more aware of the nuances and spectrum of gender identity, our health care practices must grow as well. Ob.gyns. are often uniquely positioned as being among the first people transgender adolescents present to – whether it’s signaling disassociation with their gender when answering routine medical questions or directly addressing gender with them as a trusted and private resource. Even when seeing a patient too young to consider hormone therapy, an ob.gyn. can offer vital early behavioral health support, educational and community resources, and specialist referrals.

Transgender adolescent patients have likely faced negative stereotypes and stigmas in social settings or through media that make them cautious and protective of their identity. They are also more likely to face social ostracism such as bullying and/or dissent and rejection from their parents, deepening the vulnerability of their situation. As a result, transgender adolescents can have increased instances of anxiety, depression, sexual harassment, homelessness, and risk-taking behavior. Medical practices can signal to transgender patients that they are safe and welcoming from the start by offering gender neutral forms, brochures, and information for LGBT patients in the waiting room, and having sensitive employees at every step – from the front desk onward.

As we’ve just outlined, transgender adolescent patients face unique challenges, including increased rates of social and mental health risks. In response, ob.gyns. must be prepared to have a comprehensive conversation about health and well-being beyond sexual and reproductive health. They must also be equipped to address the psychosocial issues associated with transgender adolescents. This includes knowledge of what to look for and offering patients resources, education, and referrals to guarantee their health and safety.

It is important that ob.gyns. are aware that transgender men have female reproductive organs and can present with common gynecological problems such as abnormal bleeding, ovarian cysts, and torsion, as well as pregnancy and pregnancy complications. Finally, ob.gyns. can serve a unique role in counseling about fertility and fertility preservation. Thus, not only do we provide essential health care, including ongoing primary care, but we can position ourselves as part of the support network for these adolescents and their families.

Most importantly, when addressing an adolescent transgender patient, we must understand there is no uniform transgender experience. Expressing gender, sexual identity, and behavior patterns will vary from patient to patient. There are a wide range of treatment options available for transgender patients, from hormone to surgical therapies. An ob.gyn.’s responsibility is to help each individual make an informed decision, and help that patient think ahead to the future.

While this all may seem like a lot, it’s important to remember the essential components of our role as health care providers do not change because an adolescent patient is transgender. Care should always include education about their bodies, safe sex, deliberate and thoughtful assessment of symptoms or concerns, and preventive care services such as STI screenings and contraception. We are simply adding more nuanced cultural and medical understanding to those practices.
 

Dr. Gomez-Lobo is director of pediatric and adolescent obstetrics and gynecology, Medstar Washington Hospital Center/Children’s National Health System, Washington, D.C. Dr. Sokkary is associate professor of ob.gyn. at Navicent Health Center/Mercer School of Medicine in Macon, Ga. They are members of the ACOG Committee on Adolescent Health Care. They reported having no relevant financial disclosures.

As pediatric and adolescent gynecologists, we are seeing an increasing number of adolescents with gender identity issues and have come to believe that all obstetrician-gynecologists need to have an understanding of varying gender identities, as well as their role in managing these patients’ care.

We had the honor to assist the American College of Obstetricians and Gynecologists’ (ACOG) Committee on Adolescent Health Care in the development of a new Committee Opinion to guide ob.gyns. in caring for transgender adolescents (Obstet Gynecol 2017;129:e11-6). As our culture grows more aware of the nuances and spectrum of gender identity, our health care practices must grow as well. Ob.gyns. are often uniquely positioned as being among the first people transgender adolescents present to – whether it’s signaling disassociation with their gender when answering routine medical questions or directly addressing gender with them as a trusted and private resource. Even when seeing a patient too young to consider hormone therapy, an ob.gyn. can offer vital early behavioral health support, educational and community resources, and specialist referrals.

Transgender adolescent patients have likely faced negative stereotypes and stigmas in social settings or through media that make them cautious and protective of their identity. They are also more likely to face social ostracism such as bullying and/or dissent and rejection from their parents, deepening the vulnerability of their situation. As a result, transgender adolescents can have increased instances of anxiety, depression, sexual harassment, homelessness, and risk-taking behavior. Medical practices can signal to transgender patients that they are safe and welcoming from the start by offering gender neutral forms, brochures, and information for LGBT patients in the waiting room, and having sensitive employees at every step – from the front desk onward.

As we’ve just outlined, transgender adolescent patients face unique challenges, including increased rates of social and mental health risks. In response, ob.gyns. must be prepared to have a comprehensive conversation about health and well-being beyond sexual and reproductive health. They must also be equipped to address the psychosocial issues associated with transgender adolescents. This includes knowledge of what to look for and offering patients resources, education, and referrals to guarantee their health and safety.

It is important that ob.gyns. are aware that transgender men have female reproductive organs and can present with common gynecological problems such as abnormal bleeding, ovarian cysts, and torsion, as well as pregnancy and pregnancy complications. Finally, ob.gyns. can serve a unique role in counseling about fertility and fertility preservation. Thus, not only do we provide essential health care, including ongoing primary care, but we can position ourselves as part of the support network for these adolescents and their families.

Most importantly, when addressing an adolescent transgender patient, we must understand there is no uniform transgender experience. Expressing gender, sexual identity, and behavior patterns will vary from patient to patient. There are a wide range of treatment options available for transgender patients, from hormone to surgical therapies. An ob.gyn.’s responsibility is to help each individual make an informed decision, and help that patient think ahead to the future.

While this all may seem like a lot, it’s important to remember the essential components of our role as health care providers do not change because an adolescent patient is transgender. Care should always include education about their bodies, safe sex, deliberate and thoughtful assessment of symptoms or concerns, and preventive care services such as STI screenings and contraception. We are simply adding more nuanced cultural and medical understanding to those practices.
 

Dr. Gomez-Lobo is director of pediatric and adolescent obstetrics and gynecology, Medstar Washington Hospital Center/Children’s National Health System, Washington, D.C. Dr. Sokkary is associate professor of ob.gyn. at Navicent Health Center/Mercer School of Medicine in Macon, Ga. They are members of the ACOG Committee on Adolescent Health Care. They reported having no relevant financial disclosures.

Clostridium difficile (C difficile) infection (CDI) is a leading cause of infectious diarrhea among hospitalized patients and, increasingly, in ambulatory patients.^1,2 The high prevalence of CDI and the high recurrence rates (15%-30%) led the CDC to categorize C difficile as an "urgent" threat (the highest category) in its 2013 Antimicrobial Resistance Threat Report.^3-5 The Infectious Diseases Society of America guideline recommended treatment for CDI is vancomycin or metronidazole; more recent studies also support fidaxomicin use.^4,6,7  

Patients experiencing recurrent CDI are at risk for further recurrences, such that after the third CDI episode, the risk of subsequent recurrences exceeds 50%.⁸ This recurrence rate has stimulated research into other treatments, including fecal microbiota transplantation (FMT). A recent systematic  review of FMT reports that 85% of patients have resolution of symptoms without recurrence after FMT, although this is based on data from case series and 2 small randomized clinical trials.⁹

A commonly cited barrier to FMT is patient acceptance. In response to this concern, a previous survey demonstrated that 81% of respondents would opt for FMT to treat a hypothetical case of recurrent CDI.¹⁰ However, the surveyed population did not have CDI, and the 48% response rate is concerning, since those with a favorable opinion of FMT might be more willing to complete a survey than would other patients. Accordingly, the authors systematically surveyed hospitalized veterans with active CDI to assess their knowledge, attitudes, and opinions about FMT as a treatment for CDI.

Methods

In-person patient interviews were conducted by one of the study authors at the Minneapolis VA Health Care System (MVAHCS), consisting of 13 to 18 questions. Questions addressed any prior CDI episodes and knowledge of the following: CDI, recurrence risk, and FMT; preferred route and location of FMT administration; concerns regarding FMT; likelihood of agreeing to undergo FMT (if available); and likelihood of enrollment in a hypothetical study comparing FMT to standard antibiotic treatment. The survey was developed internally and was not validated. Questions used the Likert-scale (Survey).

Patients with CDI were identified by monitoring for positive C difficile polymerase chain reaction (PCR) stool tests and then screened for inclusion by medical record review. Inclusion criteria were (1) MVAHCS hospitalization; and (2) written informed consent. Exclusion criteria were the inability to communicate or participate in an interview. Patient responses regarding their likelihood of agreeing to FMT for CDI treatment under different circumstances were compared using Wilcoxon rank sum test. These circumstances included FMT for their current episode of CDI, FMT for a subsequent episode, and FMT if recommended by their physician. Possible concerns regarding FMT also were solicited, including infection risk, effectiveness, and procedural aesthetics. The MVAHCS institutional review board approved the study.

Results

Stool PCR tests for CDI were monitored for 158 days from 2013 to 2014 (based on availability of study staff), yielding 106 positive results. Of those, 31 (29%) were from outpatients and not addressed further. Of the 75 positive CDI tests from 66 hospitalized patients (9 patients had duplicate tests), 18 of 66 (27%) were not able to provide consent and were excluded, leaving 48 eligible patients. Six (13%) were missed for logistic reasons (patient at a test or procedure, discharged before approached, etc), leaving 42 patients who were approached for participation. Among these, 34 (81%) consented to participate in the survey. Two subjects (6%) found the topic so unappealing that they terminated the interview.

The majority of enrolled subjects were men (32/34, 94%), with a mean age of 65.3 years (range, 31-89). Eleven subjects (32%) reported a prior CDI episode, with 10 reporting 1 such episode, and the other 2 episodes. Those with prior CDI reported the effect of CDI on their overall quality of life as 5.1 (1 = no limitation, 10 = severe limitation). Respondents were fairly accurate regarding the risk of recurrence after an initial episode of CDI, with the average expectedrecurrence rate estimated at 33%. In contrast, their estimation of the risk of recurrence after a second CDI episode was lower (28%), although the risk of recurrent episodes increases with each CDI recurrence.

Regarding FMT, 5 subjects indicated awareness of the procedure: 2 learning of it from a news source, 1 from family, 1 from a health care provider, and 1 was unsure of the source. After subjects received a description of FMT, their opinions regarding the procedure were elicited. When asked which route of delivery they would prefer if they were to undergo FMT, the 33 subjects who provided a response indicated a strong preference for either enema (15, 45%) or colonoscopy (10, 30%), compared with just 4 (12%) indicating no preference, 2 (6%) choosing nasogastric tube administration, and 2 (6%) indicating that they would not undergo FMT by any route (P < .001).

Regarding the location of FMT administration (hospital setting vs self-administered at home), 31 of 33 respondents (94%) indicated they would prefer FMT to occur in the hospital vs 2 (6%) preferring self-administration at home (P < .001). The preferred source of donor stool was more evenly distributed, with 14 of 32 respondents (44%) indicating a preference for an anonymous donor, 11 preferring a family member (34%), and 7 (21%) with no preference (P = .21).

Subjects were asked about concerns regarding FMT, and asked to rate each on a 5-point Likert scale (1 = not at all concerning; 5 = overwhelming concern). Concerns regarding risk of infection and effectiveness received an average score of 2.74 and 2.72, respectively, whereas concern regarding the aesthetics, or "yuck factor" was slightly lower (2.1: P = NS for all comparisons). Subjects also were asked to rate the likelihood of undergoing FMT, if it were available, for their current episode of CDI, a subsequent episode of CDI, or if their physician recommended undergoing FMT (10 point scale: 1 = not at all likely; 10 = certainly agree to FMT). The mean scores (SD) for agreeing to FMT for the current or a subsequent episode were 4.8 (SD 2.7) and 5.6 (SD 3.0); P = .12, but increased to 7.1 (SD 3.23) if FMT were recommended by their physician (P < .001 for FMT if physician recommended vs FMT for current episode; P = .001 for FMT if physician recommended vs FMT for a subsequent episode). Finally, subjects were asked about the likelihood of enrolling in a study comparing FMT to standard antimicrobial treatment, with answers ranging from 1 (almost certainly would not enroll) to 5 (almost certainly would enroll). Among the 32 respondents to this question, 17 (53%) answered either "probably would enroll" or "almost certainly would enroll," with a mean score of 3.2.  

Discussion

Overall, VA patients with a current episode of CDI were not aware of FMT, with just 15% knowing about the procedure. However, after learning about FMT, patients expressed clear opinions regarding the route and setting of FMT administration, with enema or colonoscopy being the preferred routes, and a hospital the preferred setting. In contrast, subjects expressed ambivalence with regard to the source of donor stool, with no clear preference for stool from an anonymous donor vs from a family member.

When asked about concerns regarding FMT, none of the presented options (risk of infection, uncertain effectiveness, or procedural aesthetics) emerged as significantly more important than did others, although the oft-cited concern regarding FMT aesthetics engendered the lowest overall level of concern. In terms of FMT acceptance, 4 subjects (12%) were opposed to the procedure, indicating that they were not at all likely to agree to FMT for all scenarios (defined as a score of 1 or 2 on the 10-point Likert scale) or by terminating the survey because of the questions. However, 15 (44%) indicated that they would certainly agree to FMT (defined as a score of 9 or 10 on the 10-point Likert scale) if their physician recommended it. Physician recommendation for FMT resulted in the highest overall likelihood of agreeing to FMT, a finding in agreement with a previous survey of FMT for CDI.¹⁰ Most subjects indicated likely enrollment in a potential study comparing FMT with standard antimicrobial therapy.

Strengths/Limitations

Study strengths included surveying patients with current CDI, such that patients had personal experience with the disease in question. Use of in-person interviews also resulted in a robust response rate of 81% and allowed subjects to clarify any unclear questions with study personnel. Weaknesses included a relatively small sample size, underrepresentation of women, and lack of detail regarding respondent characteristics. Additionally, capsule delivery of FMT was not assessed since this method of delivery had not been published at the time of survey administration.

Conclusion

This survey of VA patients with CDI suggests that aesthetic concerns are not a critical deterrent for this population, and interest in FMT for the treatment of recurrent CDI exists. Physician recommendation to undergo FMT seems to be the most influential factor affecting the likelihood of agreeing to undergo FMT. These results support the feasibility of conducting clinical trials of FMT in the VA system.

Clostridium difficile (C difficile) infection (CDI) is a leading cause of infectious diarrhea among hospitalized patients and, increasingly, in ambulatory patients.^1,2 The high prevalence of CDI and the high recurrence rates (15%-30%) led the CDC to categorize C difficile as an "urgent" threat (the highest category) in its 2013 Antimicrobial Resistance Threat Report.^3-5 The Infectious Diseases Society of America guideline recommended treatment for CDI is vancomycin or metronidazole; more recent studies also support fidaxomicin use.^4,6,7  

Patients experiencing recurrent CDI are at risk for further recurrences, such that after the third CDI episode, the risk of subsequent recurrences exceeds 50%.⁸ This recurrence rate has stimulated research into other treatments, including fecal microbiota transplantation (FMT). A recent systematic  review of FMT reports that 85% of patients have resolution of symptoms without recurrence after FMT, although this is based on data from case series and 2 small randomized clinical trials.⁹

A commonly cited barrier to FMT is patient acceptance. In response to this concern, a previous survey demonstrated that 81% of respondents would opt for FMT to treat a hypothetical case of recurrent CDI.¹⁰ However, the surveyed population did not have CDI, and the 48% response rate is concerning, since those with a favorable opinion of FMT might be more willing to complete a survey than would other patients. Accordingly, the authors systematically surveyed hospitalized veterans with active CDI to assess their knowledge, attitudes, and opinions about FMT as a treatment for CDI.

Methods

In-person patient interviews were conducted by one of the study authors at the Minneapolis VA Health Care System (MVAHCS), consisting of 13 to 18 questions. Questions addressed any prior CDI episodes and knowledge of the following: CDI, recurrence risk, and FMT; preferred route and location of FMT administration; concerns regarding FMT; likelihood of agreeing to undergo FMT (if available); and likelihood of enrollment in a hypothetical study comparing FMT to standard antibiotic treatment. The survey was developed internally and was not validated. Questions used the Likert-scale (Survey).

Patients with CDI were identified by monitoring for positive C difficile polymerase chain reaction (PCR) stool tests and then screened for inclusion by medical record review. Inclusion criteria were (1) MVAHCS hospitalization; and (2) written informed consent. Exclusion criteria were the inability to communicate or participate in an interview. Patient responses regarding their likelihood of agreeing to FMT for CDI treatment under different circumstances were compared using Wilcoxon rank sum test. These circumstances included FMT for their current episode of CDI, FMT for a subsequent episode, and FMT if recommended by their physician. Possible concerns regarding FMT also were solicited, including infection risk, effectiveness, and procedural aesthetics. The MVAHCS institutional review board approved the study.

Results

Stool PCR tests for CDI were monitored for 158 days from 2013 to 2014 (based on availability of study staff), yielding 106 positive results. Of those, 31 (29%) were from outpatients and not addressed further. Of the 75 positive CDI tests from 66 hospitalized patients (9 patients had duplicate tests), 18 of 66 (27%) were not able to provide consent and were excluded, leaving 48 eligible patients. Six (13%) were missed for logistic reasons (patient at a test or procedure, discharged before approached, etc), leaving 42 patients who were approached for participation. Among these, 34 (81%) consented to participate in the survey. Two subjects (6%) found the topic so unappealing that they terminated the interview.

The majority of enrolled subjects were men (32/34, 94%), with a mean age of 65.3 years (range, 31-89). Eleven subjects (32%) reported a prior CDI episode, with 10 reporting 1 such episode, and the other 2 episodes. Those with prior CDI reported the effect of CDI on their overall quality of life as 5.1 (1 = no limitation, 10 = severe limitation). Respondents were fairly accurate regarding the risk of recurrence after an initial episode of CDI, with the average expectedrecurrence rate estimated at 33%. In contrast, their estimation of the risk of recurrence after a second CDI episode was lower (28%), although the risk of recurrent episodes increases with each CDI recurrence.

Regarding FMT, 5 subjects indicated awareness of the procedure: 2 learning of it from a news source, 1 from family, 1 from a health care provider, and 1 was unsure of the source. After subjects received a description of FMT, their opinions regarding the procedure were elicited. When asked which route of delivery they would prefer if they were to undergo FMT, the 33 subjects who provided a response indicated a strong preference for either enema (15, 45%) or colonoscopy (10, 30%), compared with just 4 (12%) indicating no preference, 2 (6%) choosing nasogastric tube administration, and 2 (6%) indicating that they would not undergo FMT by any route (P < .001).

Regarding the location of FMT administration (hospital setting vs self-administered at home), 31 of 33 respondents (94%) indicated they would prefer FMT to occur in the hospital vs 2 (6%) preferring self-administration at home (P < .001). The preferred source of donor stool was more evenly distributed, with 14 of 32 respondents (44%) indicating a preference for an anonymous donor, 11 preferring a family member (34%), and 7 (21%) with no preference (P = .21).

Subjects were asked about concerns regarding FMT, and asked to rate each on a 5-point Likert scale (1 = not at all concerning; 5 = overwhelming concern). Concerns regarding risk of infection and effectiveness received an average score of 2.74 and 2.72, respectively, whereas concern regarding the aesthetics, or "yuck factor" was slightly lower (2.1: P = NS for all comparisons). Subjects also were asked to rate the likelihood of undergoing FMT, if it were available, for their current episode of CDI, a subsequent episode of CDI, or if their physician recommended undergoing FMT (10 point scale: 1 = not at all likely; 10 = certainly agree to FMT). The mean scores (SD) for agreeing to FMT for the current or a subsequent episode were 4.8 (SD 2.7) and 5.6 (SD 3.0); P = .12, but increased to 7.1 (SD 3.23) if FMT were recommended by their physician (P < .001 for FMT if physician recommended vs FMT for current episode; P = .001 for FMT if physician recommended vs FMT for a subsequent episode). Finally, subjects were asked about the likelihood of enrolling in a study comparing FMT to standard antimicrobial treatment, with answers ranging from 1 (almost certainly would not enroll) to 5 (almost certainly would enroll). Among the 32 respondents to this question, 17 (53%) answered either "probably would enroll" or "almost certainly would enroll," with a mean score of 3.2.  

Discussion

Overall, VA patients with a current episode of CDI were not aware of FMT, with just 15% knowing about the procedure. However, after learning about FMT, patients expressed clear opinions regarding the route and setting of FMT administration, with enema or colonoscopy being the preferred routes, and a hospital the preferred setting. In contrast, subjects expressed ambivalence with regard to the source of donor stool, with no clear preference for stool from an anonymous donor vs from a family member.

When asked about concerns regarding FMT, none of the presented options (risk of infection, uncertain effectiveness, or procedural aesthetics) emerged as significantly more important than did others, although the oft-cited concern regarding FMT aesthetics engendered the lowest overall level of concern. In terms of FMT acceptance, 4 subjects (12%) were opposed to the procedure, indicating that they were not at all likely to agree to FMT for all scenarios (defined as a score of 1 or 2 on the 10-point Likert scale) or by terminating the survey because of the questions. However, 15 (44%) indicated that they would certainly agree to FMT (defined as a score of 9 or 10 on the 10-point Likert scale) if their physician recommended it. Physician recommendation for FMT resulted in the highest overall likelihood of agreeing to FMT, a finding in agreement with a previous survey of FMT for CDI.¹⁰ Most subjects indicated likely enrollment in a potential study comparing FMT with standard antimicrobial therapy.

Strengths/Limitations

Study strengths included surveying patients with current CDI, such that patients had personal experience with the disease in question. Use of in-person interviews also resulted in a robust response rate of 81% and allowed subjects to clarify any unclear questions with study personnel. Weaknesses included a relatively small sample size, underrepresentation of women, and lack of detail regarding respondent characteristics. Additionally, capsule delivery of FMT was not assessed since this method of delivery had not been published at the time of survey administration.

Conclusion

This survey of VA patients with CDI suggests that aesthetic concerns are not a critical deterrent for this population, and interest in FMT for the treatment of recurrent CDI exists. Physician recommendation to undergo FMT seems to be the most influential factor affecting the likelihood of agreeing to undergo FMT. These results support the feasibility of conducting clinical trials of FMT in the VA system.

Clostridium difficile (C difficile) infection (CDI) is a leading cause of infectious diarrhea among hospitalized patients and, increasingly, in ambulatory patients.^1,2 The high prevalence of CDI and the high recurrence rates (15%-30%) led the CDC to categorize C difficile as an "urgent" threat (the highest category) in its 2013 Antimicrobial Resistance Threat Report.^3-5 The Infectious Diseases Society of America guideline recommended treatment for CDI is vancomycin or metronidazole; more recent studies also support fidaxomicin use.^4,6,7  

Patients experiencing recurrent CDI are at risk for further recurrences, such that after the third CDI episode, the risk of subsequent recurrences exceeds 50%.⁸ This recurrence rate has stimulated research into other treatments, including fecal microbiota transplantation (FMT). A recent systematic  review of FMT reports that 85% of patients have resolution of symptoms without recurrence after FMT, although this is based on data from case series and 2 small randomized clinical trials.⁹

A commonly cited barrier to FMT is patient acceptance. In response to this concern, a previous survey demonstrated that 81% of respondents would opt for FMT to treat a hypothetical case of recurrent CDI.¹⁰ However, the surveyed population did not have CDI, and the 48% response rate is concerning, since those with a favorable opinion of FMT might be more willing to complete a survey than would other patients. Accordingly, the authors systematically surveyed hospitalized veterans with active CDI to assess their knowledge, attitudes, and opinions about FMT as a treatment for CDI.

Methods

In-person patient interviews were conducted by one of the study authors at the Minneapolis VA Health Care System (MVAHCS), consisting of 13 to 18 questions. Questions addressed any prior CDI episodes and knowledge of the following: CDI, recurrence risk, and FMT; preferred route and location of FMT administration; concerns regarding FMT; likelihood of agreeing to undergo FMT (if available); and likelihood of enrollment in a hypothetical study comparing FMT to standard antibiotic treatment. The survey was developed internally and was not validated. Questions used the Likert-scale (Survey).

Patients with CDI were identified by monitoring for positive C difficile polymerase chain reaction (PCR) stool tests and then screened for inclusion by medical record review. Inclusion criteria were (1) MVAHCS hospitalization; and (2) written informed consent. Exclusion criteria were the inability to communicate or participate in an interview. Patient responses regarding their likelihood of agreeing to FMT for CDI treatment under different circumstances were compared using Wilcoxon rank sum test. These circumstances included FMT for their current episode of CDI, FMT for a subsequent episode, and FMT if recommended by their physician. Possible concerns regarding FMT also were solicited, including infection risk, effectiveness, and procedural aesthetics. The MVAHCS institutional review board approved the study.

Results

Stool PCR tests for CDI were monitored for 158 days from 2013 to 2014 (based on availability of study staff), yielding 106 positive results. Of those, 31 (29%) were from outpatients and not addressed further. Of the 75 positive CDI tests from 66 hospitalized patients (9 patients had duplicate tests), 18 of 66 (27%) were not able to provide consent and were excluded, leaving 48 eligible patients. Six (13%) were missed for logistic reasons (patient at a test or procedure, discharged before approached, etc), leaving 42 patients who were approached for participation. Among these, 34 (81%) consented to participate in the survey. Two subjects (6%) found the topic so unappealing that they terminated the interview.

The majority of enrolled subjects were men (32/34, 94%), with a mean age of 65.3 years (range, 31-89). Eleven subjects (32%) reported a prior CDI episode, with 10 reporting 1 such episode, and the other 2 episodes. Those with prior CDI reported the effect of CDI on their overall quality of life as 5.1 (1 = no limitation, 10 = severe limitation). Respondents were fairly accurate regarding the risk of recurrence after an initial episode of CDI, with the average expectedrecurrence rate estimated at 33%. In contrast, their estimation of the risk of recurrence after a second CDI episode was lower (28%), although the risk of recurrent episodes increases with each CDI recurrence.

Regarding FMT, 5 subjects indicated awareness of the procedure: 2 learning of it from a news source, 1 from family, 1 from a health care provider, and 1 was unsure of the source. After subjects received a description of FMT, their opinions regarding the procedure were elicited. When asked which route of delivery they would prefer if they were to undergo FMT, the 33 subjects who provided a response indicated a strong preference for either enema (15, 45%) or colonoscopy (10, 30%), compared with just 4 (12%) indicating no preference, 2 (6%) choosing nasogastric tube administration, and 2 (6%) indicating that they would not undergo FMT by any route (P < .001).

Regarding the location of FMT administration (hospital setting vs self-administered at home), 31 of 33 respondents (94%) indicated they would prefer FMT to occur in the hospital vs 2 (6%) preferring self-administration at home (P < .001). The preferred source of donor stool was more evenly distributed, with 14 of 32 respondents (44%) indicating a preference for an anonymous donor, 11 preferring a family member (34%), and 7 (21%) with no preference (P = .21).

Subjects were asked about concerns regarding FMT, and asked to rate each on a 5-point Likert scale (1 = not at all concerning; 5 = overwhelming concern). Concerns regarding risk of infection and effectiveness received an average score of 2.74 and 2.72, respectively, whereas concern regarding the aesthetics, or "yuck factor" was slightly lower (2.1: P = NS for all comparisons). Subjects also were asked to rate the likelihood of undergoing FMT, if it were available, for their current episode of CDI, a subsequent episode of CDI, or if their physician recommended undergoing FMT (10 point scale: 1 = not at all likely; 10 = certainly agree to FMT). The mean scores (SD) for agreeing to FMT for the current or a subsequent episode were 4.8 (SD 2.7) and 5.6 (SD 3.0); P = .12, but increased to 7.1 (SD 3.23) if FMT were recommended by their physician (P < .001 for FMT if physician recommended vs FMT for current episode; P = .001 for FMT if physician recommended vs FMT for a subsequent episode). Finally, subjects were asked about the likelihood of enrolling in a study comparing FMT to standard antimicrobial treatment, with answers ranging from 1 (almost certainly would not enroll) to 5 (almost certainly would enroll). Among the 32 respondents to this question, 17 (53%) answered either "probably would enroll" or "almost certainly would enroll," with a mean score of 3.2.  

Discussion

Overall, VA patients with a current episode of CDI were not aware of FMT, with just 15% knowing about the procedure. However, after learning about FMT, patients expressed clear opinions regarding the route and setting of FMT administration, with enema or colonoscopy being the preferred routes, and a hospital the preferred setting. In contrast, subjects expressed ambivalence with regard to the source of donor stool, with no clear preference for stool from an anonymous donor vs from a family member.

When asked about concerns regarding FMT, none of the presented options (risk of infection, uncertain effectiveness, or procedural aesthetics) emerged as significantly more important than did others, although the oft-cited concern regarding FMT aesthetics engendered the lowest overall level of concern. In terms of FMT acceptance, 4 subjects (12%) were opposed to the procedure, indicating that they were not at all likely to agree to FMT for all scenarios (defined as a score of 1 or 2 on the 10-point Likert scale) or by terminating the survey because of the questions. However, 15 (44%) indicated that they would certainly agree to FMT (defined as a score of 9 or 10 on the 10-point Likert scale) if their physician recommended it. Physician recommendation for FMT resulted in the highest overall likelihood of agreeing to FMT, a finding in agreement with a previous survey of FMT for CDI.¹⁰ Most subjects indicated likely enrollment in a potential study comparing FMT with standard antimicrobial therapy.

Strengths/Limitations

Study strengths included surveying patients with current CDI, such that patients had personal experience with the disease in question. Use of in-person interviews also resulted in a robust response rate of 81% and allowed subjects to clarify any unclear questions with study personnel. Weaknesses included a relatively small sample size, underrepresentation of women, and lack of detail regarding respondent characteristics. Additionally, capsule delivery of FMT was not assessed since this method of delivery had not been published at the time of survey administration.

Conclusion

This survey of VA patients with CDI suggests that aesthetic concerns are not a critical deterrent for this population, and interest in FMT for the treatment of recurrent CDI exists. Physician recommendation to undergo FMT seems to be the most influential factor affecting the likelihood of agreeing to undergo FMT. These results support the feasibility of conducting clinical trials of FMT in the VA system.