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Blood test could aid steroid decision in alcoholic hepatitis
AMSTERDAM – Determining the ratio of neutrophils to leukocytes in the blood could help identify patients with alcoholic hepatitis that would and would not benefit from steroid treatment.
Patients who had a neutrophil to lymphocyte ratio (NLR) of between 5 and 8 before being treated with the corticosteroid prednisolone appeared to obtain a benefit versus no-steroid treatment (P = .007) while those with higher and lower NLR values did not, in an analysis presented at the International Liver Congress.
This could potentially help clinicians avoid putting some patients through a futile trial of steroid therapy, study author Ewan H. Forrest, MD, explained in an interview at the meeting, which is sponsored by the European Association for the Study of the Liver (EASL).
“The traditional approach would be to give steroids to patients with severe alcoholic hepatitis, wait 7 days, see if they are getting better, and if so, keep them on the steroids,” Dr. Forrest of the liver unit at Glasgow Royal Infirmary observed. Conversely, if patients are not doing better then steroids should be stopped.
“What we are increasingly aware of is that not only do some people not do well with steroids but also they actually do considerably more badly,” Dr. Forrest cautioned.
Usually, the response to steroid treatment in alcoholic hepatitis is measured by changes in serum bilirubin after a week of treatment, but this, of course, exposes patients to a “futile course of treatment with a risk of complication such as sepsis,” Dr. Forrest and his coauthors noted in a a late-breaking poster.
Determining the NLR has already been shown to help predict the prognosis of patients with several diseases with an underlying inflammatory component, such as cardiovascular diseases and several types of cancer. It also has proven useful in patients with liver disease, although not specifically in alcoholic hepatitis before this study, Dr. Forrest observed.
Data on patients with alcoholic hepatitis who had participated in the multicenter, double-blind, randomized STOPAH trial were used to see if the baseline NLR could help stratify patients who would benefit from steroid therapy.
STOPAH had compared the use of prednisolone or pentoxifylline for the treatment of alcoholic hepatitis but found no benefit for the latter, although there was a possible benefit of steroids for improving overall survival, at least in the short term (N Engl J Med. 2015 Apr;372:1619-28).
Dr. Forrest noted that measurement of the lymphocyte count was not part of the original study design, so data to calculate the NLR were obtained retrospectively. As there had been little or no response to pentoxifylline in the trial, patients who had taken this drug were regarded as having had no treatment in the analysis.
In all, baseline NLR values could be worked out for 630 patients from the STOPAH trial, but 113 were excluded from further analysis as they met the prespecified exclusion criteria of gastrointestinal bleeding or sepsis.
Overall, a NLR of 5 or less, indicating milder liver disease, was associated with significantly better survival at 3 months than if the NLR was 5 or more (85.5% vs. 67.3%; P less than .0001), study findings suggested.
Dr. Forest noted that 29% of patients fell into the “sweet spot” of the NLR of between 5 and 8, where patients did benefit from steroids, but that the 23% of study subjects who had an NLR ratio above 8 did not. These patients may have had disease too severe to benefit from the prednisolone, he suggested, and tended to have a worse prognosis regardless. A baseline NLR greater than 8 was associated with acute kidney infection but not sepsis, the team found.
There was also no great effect of the steroid in the 48% of patients who had an NLR ratio less than 5, suggesting that maybe they had disease that was too mild to warrant such treatment and did well regardless.
Of course, these findings still need further validation, but they are “not far off” from clinical application, Dr. Forrest offered. Calculating the ratio is simple, can be done during a routine whole-blood cell count, and is potentially cost saving because it reduces the standard practice in the United Kingdom of giving “all-comers” 7 days of corticosteroid therapy as a trial to see if they get better, he said.
Dr. Forrest had no conflicts of interest to disclose.
AMSTERDAM – Determining the ratio of neutrophils to leukocytes in the blood could help identify patients with alcoholic hepatitis that would and would not benefit from steroid treatment.
Patients who had a neutrophil to lymphocyte ratio (NLR) of between 5 and 8 before being treated with the corticosteroid prednisolone appeared to obtain a benefit versus no-steroid treatment (P = .007) while those with higher and lower NLR values did not, in an analysis presented at the International Liver Congress.
This could potentially help clinicians avoid putting some patients through a futile trial of steroid therapy, study author Ewan H. Forrest, MD, explained in an interview at the meeting, which is sponsored by the European Association for the Study of the Liver (EASL).
“The traditional approach would be to give steroids to patients with severe alcoholic hepatitis, wait 7 days, see if they are getting better, and if so, keep them on the steroids,” Dr. Forrest of the liver unit at Glasgow Royal Infirmary observed. Conversely, if patients are not doing better then steroids should be stopped.
“What we are increasingly aware of is that not only do some people not do well with steroids but also they actually do considerably more badly,” Dr. Forrest cautioned.
Usually, the response to steroid treatment in alcoholic hepatitis is measured by changes in serum bilirubin after a week of treatment, but this, of course, exposes patients to a “futile course of treatment with a risk of complication such as sepsis,” Dr. Forrest and his coauthors noted in a a late-breaking poster.
Determining the NLR has already been shown to help predict the prognosis of patients with several diseases with an underlying inflammatory component, such as cardiovascular diseases and several types of cancer. It also has proven useful in patients with liver disease, although not specifically in alcoholic hepatitis before this study, Dr. Forrest observed.
Data on patients with alcoholic hepatitis who had participated in the multicenter, double-blind, randomized STOPAH trial were used to see if the baseline NLR could help stratify patients who would benefit from steroid therapy.
STOPAH had compared the use of prednisolone or pentoxifylline for the treatment of alcoholic hepatitis but found no benefit for the latter, although there was a possible benefit of steroids for improving overall survival, at least in the short term (N Engl J Med. 2015 Apr;372:1619-28).
Dr. Forrest noted that measurement of the lymphocyte count was not part of the original study design, so data to calculate the NLR were obtained retrospectively. As there had been little or no response to pentoxifylline in the trial, patients who had taken this drug were regarded as having had no treatment in the analysis.
In all, baseline NLR values could be worked out for 630 patients from the STOPAH trial, but 113 were excluded from further analysis as they met the prespecified exclusion criteria of gastrointestinal bleeding or sepsis.
Overall, a NLR of 5 or less, indicating milder liver disease, was associated with significantly better survival at 3 months than if the NLR was 5 or more (85.5% vs. 67.3%; P less than .0001), study findings suggested.
Dr. Forest noted that 29% of patients fell into the “sweet spot” of the NLR of between 5 and 8, where patients did benefit from steroids, but that the 23% of study subjects who had an NLR ratio above 8 did not. These patients may have had disease too severe to benefit from the prednisolone, he suggested, and tended to have a worse prognosis regardless. A baseline NLR greater than 8 was associated with acute kidney infection but not sepsis, the team found.
There was also no great effect of the steroid in the 48% of patients who had an NLR ratio less than 5, suggesting that maybe they had disease that was too mild to warrant such treatment and did well regardless.
Of course, these findings still need further validation, but they are “not far off” from clinical application, Dr. Forrest offered. Calculating the ratio is simple, can be done during a routine whole-blood cell count, and is potentially cost saving because it reduces the standard practice in the United Kingdom of giving “all-comers” 7 days of corticosteroid therapy as a trial to see if they get better, he said.
Dr. Forrest had no conflicts of interest to disclose.
AMSTERDAM – Determining the ratio of neutrophils to leukocytes in the blood could help identify patients with alcoholic hepatitis that would and would not benefit from steroid treatment.
Patients who had a neutrophil to lymphocyte ratio (NLR) of between 5 and 8 before being treated with the corticosteroid prednisolone appeared to obtain a benefit versus no-steroid treatment (P = .007) while those with higher and lower NLR values did not, in an analysis presented at the International Liver Congress.
This could potentially help clinicians avoid putting some patients through a futile trial of steroid therapy, study author Ewan H. Forrest, MD, explained in an interview at the meeting, which is sponsored by the European Association for the Study of the Liver (EASL).
“The traditional approach would be to give steroids to patients with severe alcoholic hepatitis, wait 7 days, see if they are getting better, and if so, keep them on the steroids,” Dr. Forrest of the liver unit at Glasgow Royal Infirmary observed. Conversely, if patients are not doing better then steroids should be stopped.
“What we are increasingly aware of is that not only do some people not do well with steroids but also they actually do considerably more badly,” Dr. Forrest cautioned.
Usually, the response to steroid treatment in alcoholic hepatitis is measured by changes in serum bilirubin after a week of treatment, but this, of course, exposes patients to a “futile course of treatment with a risk of complication such as sepsis,” Dr. Forrest and his coauthors noted in a a late-breaking poster.
Determining the NLR has already been shown to help predict the prognosis of patients with several diseases with an underlying inflammatory component, such as cardiovascular diseases and several types of cancer. It also has proven useful in patients with liver disease, although not specifically in alcoholic hepatitis before this study, Dr. Forrest observed.
Data on patients with alcoholic hepatitis who had participated in the multicenter, double-blind, randomized STOPAH trial were used to see if the baseline NLR could help stratify patients who would benefit from steroid therapy.
STOPAH had compared the use of prednisolone or pentoxifylline for the treatment of alcoholic hepatitis but found no benefit for the latter, although there was a possible benefit of steroids for improving overall survival, at least in the short term (N Engl J Med. 2015 Apr;372:1619-28).
Dr. Forrest noted that measurement of the lymphocyte count was not part of the original study design, so data to calculate the NLR were obtained retrospectively. As there had been little or no response to pentoxifylline in the trial, patients who had taken this drug were regarded as having had no treatment in the analysis.
In all, baseline NLR values could be worked out for 630 patients from the STOPAH trial, but 113 were excluded from further analysis as they met the prespecified exclusion criteria of gastrointestinal bleeding or sepsis.
Overall, a NLR of 5 or less, indicating milder liver disease, was associated with significantly better survival at 3 months than if the NLR was 5 or more (85.5% vs. 67.3%; P less than .0001), study findings suggested.
Dr. Forest noted that 29% of patients fell into the “sweet spot” of the NLR of between 5 and 8, where patients did benefit from steroids, but that the 23% of study subjects who had an NLR ratio above 8 did not. These patients may have had disease too severe to benefit from the prednisolone, he suggested, and tended to have a worse prognosis regardless. A baseline NLR greater than 8 was associated with acute kidney infection but not sepsis, the team found.
There was also no great effect of the steroid in the 48% of patients who had an NLR ratio less than 5, suggesting that maybe they had disease that was too mild to warrant such treatment and did well regardless.
Of course, these findings still need further validation, but they are “not far off” from clinical application, Dr. Forrest offered. Calculating the ratio is simple, can be done during a routine whole-blood cell count, and is potentially cost saving because it reduces the standard practice in the United Kingdom of giving “all-comers” 7 days of corticosteroid therapy as a trial to see if they get better, he said.
Dr. Forrest had no conflicts of interest to disclose.
Key clinical point: Calculating the neutrophil to leukocyte ratio (NLR) could save some patients with alcoholic hepatitis from having steroid therapy.
Major finding: 90-day survival was 85.5% vs. 67.3%, (P less than .0001), comparing an NLR less than 5 with an NLR of 5 or greater in all patients.
Data source: 513 patients with alcoholic hepatitis who had participated in the multicenter, double-blind, randomized STOPAH trial.
Disclosures: Dr. Forrest had no conflicts of interest to disclose.
SMILE, Your Myopia Has Just Been Treated Faster!
Fort Belvoir Community Hospital surgeons have performed the first small-incision lenticule extraction (SMILE) in the DoD, according to Health.mil News. The procedure to reduce or eliminate nearsightedness has been performed since 2011; the FDA recently approved it for the U.S.
The very fast and short-pulsed (femtosecond) laser creates a thin disc within the cornea, which is removed through a cut on the corneal surface. Removing the tissue changes the shape of the cornea.
The procedure takes 15 to 20 minutes with the laser activated for about 90 seconds per eye. Both eyes can be treated in the same session. With SMILE, unlike LASIK, no tissue is vaporized, meaning wound recovery time is faster, and with no corneal flap created, there is no risk of flap dislocation.
A clinical study found complications were rare, and by month 12 postsurgery there were only 4 reports of moderate or severe glare and 1 of moderate or severe halos. The most commonly reported effects were starbursts, blurred vision, and difficulty judging distance or depth perception, but at 12 months, more patients reported improvement than worsening. At the 6-month follow-up, 287 of 328 patients were seeing 20/20 or better without glasses.
“We are thrilled to extend this treatment option to active duty service members under the Warfighter Refractive Eye Surgery Program,” said U.S. Army Lt. Col. Bruce Rivers, director of the program at Belvoir Hospital.
The surgery will make a difference for patients. One of the first to have it done, Navy Petty Officer 1st Class Christopher Mahmood, a submarine mechanic, said, “On a submarine we have to be able to put our breathing equipment on in approximately 30 seconds, in case of emergency. Glasses make this difficult. Getting this surgery means I have one less thing to worry about while deployed and can focus 100 percent on the mission.”
The SMILE procedure will be available at Belvoir Hospital, San Diego Naval Medical Center, and Wilford Hall in San Antonio.
Fort Belvoir Community Hospital surgeons have performed the first small-incision lenticule extraction (SMILE) in the DoD, according to Health.mil News. The procedure to reduce or eliminate nearsightedness has been performed since 2011; the FDA recently approved it for the U.S.
The very fast and short-pulsed (femtosecond) laser creates a thin disc within the cornea, which is removed through a cut on the corneal surface. Removing the tissue changes the shape of the cornea.
The procedure takes 15 to 20 minutes with the laser activated for about 90 seconds per eye. Both eyes can be treated in the same session. With SMILE, unlike LASIK, no tissue is vaporized, meaning wound recovery time is faster, and with no corneal flap created, there is no risk of flap dislocation.
A clinical study found complications were rare, and by month 12 postsurgery there were only 4 reports of moderate or severe glare and 1 of moderate or severe halos. The most commonly reported effects were starbursts, blurred vision, and difficulty judging distance or depth perception, but at 12 months, more patients reported improvement than worsening. At the 6-month follow-up, 287 of 328 patients were seeing 20/20 or better without glasses.
“We are thrilled to extend this treatment option to active duty service members under the Warfighter Refractive Eye Surgery Program,” said U.S. Army Lt. Col. Bruce Rivers, director of the program at Belvoir Hospital.
The surgery will make a difference for patients. One of the first to have it done, Navy Petty Officer 1st Class Christopher Mahmood, a submarine mechanic, said, “On a submarine we have to be able to put our breathing equipment on in approximately 30 seconds, in case of emergency. Glasses make this difficult. Getting this surgery means I have one less thing to worry about while deployed and can focus 100 percent on the mission.”
The SMILE procedure will be available at Belvoir Hospital, San Diego Naval Medical Center, and Wilford Hall in San Antonio.
Fort Belvoir Community Hospital surgeons have performed the first small-incision lenticule extraction (SMILE) in the DoD, according to Health.mil News. The procedure to reduce or eliminate nearsightedness has been performed since 2011; the FDA recently approved it for the U.S.
The very fast and short-pulsed (femtosecond) laser creates a thin disc within the cornea, which is removed through a cut on the corneal surface. Removing the tissue changes the shape of the cornea.
The procedure takes 15 to 20 minutes with the laser activated for about 90 seconds per eye. Both eyes can be treated in the same session. With SMILE, unlike LASIK, no tissue is vaporized, meaning wound recovery time is faster, and with no corneal flap created, there is no risk of flap dislocation.
A clinical study found complications were rare, and by month 12 postsurgery there were only 4 reports of moderate or severe glare and 1 of moderate or severe halos. The most commonly reported effects were starbursts, blurred vision, and difficulty judging distance or depth perception, but at 12 months, more patients reported improvement than worsening. At the 6-month follow-up, 287 of 328 patients were seeing 20/20 or better without glasses.
“We are thrilled to extend this treatment option to active duty service members under the Warfighter Refractive Eye Surgery Program,” said U.S. Army Lt. Col. Bruce Rivers, director of the program at Belvoir Hospital.
The surgery will make a difference for patients. One of the first to have it done, Navy Petty Officer 1st Class Christopher Mahmood, a submarine mechanic, said, “On a submarine we have to be able to put our breathing equipment on in approximately 30 seconds, in case of emergency. Glasses make this difficult. Getting this surgery means I have one less thing to worry about while deployed and can focus 100 percent on the mission.”
The SMILE procedure will be available at Belvoir Hospital, San Diego Naval Medical Center, and Wilford Hall in San Antonio.
5 Points on Pyogenic Flexor Tenosynovitis of the Hand
Pyogenic flexor tenosynovitis (PFT) is a common closed space infection of the flexor tendon sheaths of the hand and remains one of the most challenging problems encountered in orthopedic and hand surgery (Figure 1). PFT also is known as septic flexor tenosynovitis and suppurative flexor tenosynovitis.
Kanavel1 initially described 4 cardinal signs that characterize infection of the flexor tendon sheath: symmetric fusiform swelling of the entire digit, exquisite tenderness to palpation along the course of the tendon sheath, semiflexed posture at rest, and pain with attempted passive extension of the digit. The prevalence of this infection ranges from 2.5% to 9.4%.2 Once the infection is established in a patient, it can cause significant morbidity and disability and produce an economic burden. It can also present a significant treatment dilemma for the treating surgeon, as there is no standardized protocol for managing this common but challenging hand infection. For treatment, many surgeons combine surgical decompression, sheath irrigation, and empiric intravenous (IV) antibiotic administration. However, despite prompt treatment, and regardless of the protocol used, complication rates as high as 38% have been reported.3 Moreover, even after infection eradication, a significant proportion of patients continue to have pain, swelling, stiffness, loss of composite flexion, weakness, and recurrence that potentially requires amputation.
1. What Causes Pyogenic Flexor Tenosynovitis?
PFT can result from hematogenous spread, but local inoculation by a laceration, a puncture, or a bite also is common4-7 (Figure 1). As a consequence of these mechanisms of injury, the most common source of PFT is skin flora. Staphylococcus aureus has been found in up to 75% of positive cultures in several studies.2,5,6,8,9 Methicillin-resistant S aureus (MRSA) has been found in up to 29% of cases, and the incidence continues to increase, particularly in urban areas.2,9-12 Other common bacteria are Staphylococcus epidermidis, β-hemolytic Streptococcus species, and Pseudomonas aeruginosa.5,6,10 Infection by more than 1 species of bacteria is also fairly prevalent. Of 62 patients in a study, 38% had infections with 1 organism, and 62% with 2 or more.6 Twenty-six percent of cultures grew mixed anaerobic and aerobic organisms.6 PFT is seldom caused by Eikenella corrodens from a human bite or Pasteurella multocida from an animal bite.10 Other rare causes of PFT are Listeria monocytogenes13 and Clostridium difficile from a gastrointestinal source.14Neisseria gonorrhea can cause acute tenosynovitis, usually in the setting of disseminated gonococcal infection.15,16 Also reported is mycobacterial tenosynovitis, most commonly caused by Mycobacterium kansasii and Mycobacterium marinum.17
2. Which Antibiotics Are Best Suited to Empirical Management of PFT?
Management of PFT, regardless of the pathogen, includes prompt administration of empiric IV antibiotics, usually followed by surgical drainage.7,18-20 While cultures are being tested, antibiotics should be selected—including antibiotics for empiric coverage against common gram-positive organisms, including Staphylococcus and Streptococcus species.12 The Centers for Disease Control and Prevention recommends empiric coverage for MRSA if the local prevalence exceeds 10% to 15%. Recommended empiric antibiotics are trimethoprim-sulfamethoxazole (TMP-SMX) and clindamycin (both oral) and clindamycin, vancomycin, and daptomycin (all IV).
In addition, institutional and local antibiotic resistance patterns of bacteria should guide treatment and antibiotic selection. First-generation cephalosporins have long been the cornerstone of treatment for infections caused by S aureus, but increasing methicillin resistance has reduced their role in the treatment, particularly the empiric treatment, of MRSA infections. Methicillin resistance first appeared as nosocomial S aureus infections in 1961, only 1 year after the introduction of the semisynthetic penicillin class that includes methicillin. Over the past 2 decades, MRSA has emerged in the community in otherwise young and healthy individuals with no healthcare-associated risk factors. Fortunately, several readily available antibiotics have maintained their efficacy in managing these “community-acquired” MRSA hand infections. TMP-SMX provides adequate coverage for MRSA and is a relatively inexpensive medication, and clindamycin is an equally effective and cost-effective alternative.
Presumptive antibiotics should also cover gram-negative rods and anaerobes, including Clostridium species, especially in immunocompromised patients.7,9 These patients may require additional antibiotics for presumptive coverage of other rarer bacterial causes, especially when unique mechanisms of injury (eg, aquatic injury, farm injury) are involved. Once culture results are ready, antibiotic regimens should be narrowed to cover the specific organisms identified.
3. What Are the Timing and Indications for Surgery?
Nonoperative treatment may be appropriate for PFT patients who present early, typically within 48 hours after penetrating trauma to the hand.21 In a 4-patient series, Neviaser and Gunther19 successfully treated PFT nonoperatively, with IV antibiotics, splinting, and elevation. During nonoperative treatment, the affected hand should be regularly examined. If this treatment is to be successful, clinical symptoms should improve within 48 hours; if they do not, surgical irrigation and débridement should be performed.
Regardless of timing and type of irrigation, surgical treatment remains the treatment of choice for the majority of PFT cases. Michon22 developed a 3-tier PFT classification system that is based on intraoperative findings (Table). 
4. What Are the Surgical Techniques for PFT Drainage?
Several surgical methods have been developed to decompress and irrigate the flexor sheaths of the hand. However, debates about optimal timing of surgical intervention, surgery type (open surgery or closed catheter irrigation only), and irrigation method continue.
Open Irrigation and Débridement
Open irrigation and débridement procedures were originally described for surgical management of PFT.1 Midaxial and palmar (Bruner zigzag) incisions can be used to expose and open the entire sheath for complete drainage and washout. Both incisions afford good access to the flexor sheath, but the midaxial approach may provide more coverage of the sheath after surgery. Open irrigation and débridement is the treatment of choice for the most advanced cases of PFT and for atypical or chronic tenosynovial infections.4,23,24 The Bruner zigzag incision affords ease of surgical dissection, extension, and more exposure of the flexor tendon sheath at the expense of possible difficulty in closure or flap necrosis in the setting of a swollen digit. Alternatively, the midaxial incision has the advantage of a large, more robust skin flap for more reliable closure.
Closed Tendon Sheath Irrigation
In 1943, Dickson-Wright25 first described catheter irrigation of tendon sheath infections. Later, Neviaser4 described this technique in detail. A proximal incision is made over the metacarpal neck. The tendon sheath is cut transversely at the proximal edge of the A1 pulley. An angiocatheter is inserted 1 cm to 2 cm antegrade into the flexor tendon sheath. Then, a distal midaxial incision is made dorsal to the neurovascular bundle at the level of the distal interphalangeal joint on the ulnar aspect of the finger or the radial aspect of the thumb. The distal edge of the flexor sheath is exposed and resected distal to the distal-most pulley. A Penrose drain can be threaded into the tendon sheath beneath the A4 pulley to keep the wound open and allow for fluid drainage. The sheath is flushed gently in the operating room. After surgery, intermittent bedside irrigation can be continued on the floor.
Neviaser4 reported excellent initial results with this technique; 18 of 20 patients regained complete active and passive range of motion (ROM) by 1 week after surgery. Similarly, Juliano and Eglseder,26 using a similar method, reported 100% excellent results for mild PFT and 88.4% excellent results for more severe infection.
Gutowski and colleagues23 reviewed 47 PFT cases to determine if there is a difference in outcomes between PFT treated with open irrigation and débridement and PFT treated with closed catheter irrigation. Between these groups, they found no significant differences in early postoperative outcomes, including resolution of infection, need for additional surgery, and hospital length of stay.
There are also many differing opinions regarding the best irrigation method. Some authors have asserted that normal saline is sufficient,4,5,23 and others that local antibiotics provide added benefit.27-29 Recently, Draeger and colleagues30 reported promising results with local injection of antibiotics into the tendon sheath and the addition of locally administered corticosteroids in the treatment of PFT in an animal model.
Continuous Closed Irrigation
A continuous closed irrigation system with inlet and outlet tubes has yielded successful results.8,31,32 This system consists of 2 fenestrated tubes placed within the infected space, with the tip of the smaller caliber inlet tube positioned just inside the larger outlet tube. Advantages of this system include the patient’s ability to participate in hand therapy with the system in place and avoidance of pain caused by the high pressures involved in intermittent closed irrigation. Duration of this system has ranged from 2 days to 3 weeks, and results have been good.5,8
Postoperative Irrigation
Use of postoperative irrigation on the floor or at home is controversial, as leaving an indwelling catheter in the tendon sheath can lead to complications. Catheters may increase digital stiffness by decreasing the patient’s ability to participate in therapy or may cause additional injury and irritation to the sheath itself if left in place too long. Lille and colleagues6 retrospectively compared the results of intraoperative closed tendon sheath irrigation alone with those of intraoperative and postoperative closed tendon sheath irrigation. There were no significant differences in mean hospital length of stay, follow-up complication rates, or postoperative ROM—which suggests that postoperative intermittent or continuous irrigation is not necessary.
Our Preferred Technique
We recommend a palmar approach that begins with outlining a Bruner zigzag incision along the entire finger. Then, only the distal-most and proximal-most incision lines are opened, thereby exposing the A5 and A1 pulleys, respectively (Figure 2). 
5. What Are the Long-Term Outcomes of PFT?
The principal complication associated with PFT is stiffness with loss of ROM, which can be caused by flexor tendon adhesions, joint capsular thickening, or destruction of the sheath and pulley system.24 In several studies, up to one-fourth of patients with PFT did not obtain full ROM, despite adequate treatment.4-6,27 Therefore, full active ROM exercises should be initiated immediately after surgery to counteract the development of stiffness.
The most severe complication of PFT is amputation of the affected digit (Figures 3A, 3B).
Pang and colleagues2 identified 5 factors associated with increased risk of amputation in patients with PFT: (1) age >43 years; (2) diabetes mellitus, peripheral vascular disease, or renal failure; (3) subcutaneous purulence; (4) signs of digital ischemia at presentation; and (5) growth of more than 1 bacteria species on culture of specimens obtained at time of surgery.
Pang and colleagues2 classified these patients into 3 groups with distinct clinical features and reported each group’s outcomes. The authors based their PFT classification system on increasingly severe clinical presentation, which potentially predicts amputation risk. Patients in stage 1 presented with Kanavel signs of tenosynovitis but no evidence of subcutaneous purulence or ischemia; patients in stage 2 had concurrent localized subcutaneous purulence but no ischemia; and patients in stage 3 had concurrent extensive subcutaneous purulence involving more than 1 phalangeal segment or spreading circumferentially as well as signs of ischemia. These PFT stages were found to correlate with worse patient outcomes. In patients with stage 1 infection, amputation was not required, and average functional return was 80% of total active ROM of the affected digit. In patients with stage 2 infection, the amputation rate was 8%, and return of total active ROM in the remaining digits was 72%. The outcomes for the patients with stage 3 infection were the worst. The amputation rate for patients with all 3 classification criteria (Kanavel signs, subcutaneous purulence, digital ischemia) was 59%, and return of total active ROM in the remaining digits was only 49%. Use of this clinical classification system makes it possible to guide treatment and predict outcome and return to function.
Conclusion
PFT is a common hand infection that can cause significant morbidity. Early treatment is crucial: this requires use of IV antibiotics, or surgical irrigation and débridement in more advanced cases. However, despite prompt and thorough treatment, severe infection can lead to long-term impaired function and even amputation of the affected digit. More research is needed to determine optimal timing and technique for surgical intervention and to elucidate the role of local antibiotics and corticosteroids in treating this infection and potentially preventing the morbid outcomes we currently see.
Am J Orthop. 2017;46(3):E207-E212. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.
1. Kanavel AB. The symptoms, signs, and diagnosis of tenosynovitis and major fascial-space abscesses. In: Kanavel AB, ed. Infections of the Hand. 6th ed. Philadelphia, PA: Lea & Febiger; 1933:364-395.
2. Pang HN, Teoh LC, Yam AK, Lee JY, Puhaindran ME, Tan AB. Factors affecting the prognosis of pyogenic flexor tenosynovitis. J Bone Joint Surg Am. 2007;89(8):1742-1748.
3. Stern PJ, Staneck JL, McDonough JJ, Neale HW, Tyler G. Established hand infections: a controlled, prospective study. J Hand Surg Am. 1983;8(5 pt 1):553-559.
4. Neviaser RJ. Closed tendon sheath irrigation for pyogenic flexor tenosynovitis. J Hand Surg Am. 1978;3(5):462-466.
5. Harris PA, Nanchahal J. Closed continuous irrigation in the treatment of hand infections. J Hand Surg Br. 1999;24(3):328-333.
6. Lille S, Hayakawa T, Neumeister MW, Brown RE, Zook EG, Murray K. Continuous postoperative catheter irrigation is not necessary for the treatment of suppurative flexor tenosynovitis. J Hand Surg Br. 2000;25(3):304-307.
7. Boles SD, Schmidt CC. Pyogenic flexor tenosynovitis. Hand Clin. 1998;14(4):567-578.
8. Nemoto K, Yanagida M, Nemoto T. Closed continuous irrigation as a treatment for infection in the hand. J Hand Surg Br. 1993;18(6):783-789.
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18. Abrams RA, Botte MJ. Hand infections: treatment recommendations for specific types. J Am Acad Orthop Surg. 1996;4(4):219-230.
19. Neviaser RJ, Gunther SF. Tenosynovial infections in the hand: diagnosis and management. Instr Course Lect. 1980;29:108-128.
20. Szabo R, Palumbo C. Infections of the hand. In: Chapman M, ed. Chapman’s Orthopedic Surgery. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:1989-2008.
21. Neviaser R. Acute infections. In: Green D, Hotchkiss R, Pederson W, eds. Green’s Operative Hand Surgery. 4th ed. New York, NY: Churchill Livingstone; 1999:1033-1047.
22. Michon J. Phlegmon of the tendon sheaths [in French]. Ann Chir. 1974;28(4):277-280.
23. Gutowski KA, Ochoa O, Adams WP Jr. Closed-catheter irrigation is as effective as open drainage for treatment of pyogenic flexor tenosynovitis. Ann Plast Surg. 2002;49(4):350-354.
24. Stern PJ. Selected acute infections. Instr Course Lect. 1990;39:539-546.
25. Dickson-Wright A. Tendon sheath infection. Proc R Soc Med. 1943-1944;37:504-505.
26. Juliano PJ, Eglseder WA. Limited open-tendon-sheath irrigation in the treatment of pyogenic flexor tenosynovitis. Orthop Rev. 1991;20(12):1065-1069.
27. Pollen AG. Acute infection of the tendon sheaths. Hand. 1974;6(1):21-25.
28. Besser MI. Digital flexor tendon irrigation. Hand. 1976;8(1):72.
29. Carter SJ, Burman SO, Mersheimer WL. Treatment of digital tenosynovitis by irrigation with peroxide and oxytetracycline: review of nine cases. Ann Surg. 1966;163(4):645-650.
30. Draeger RW, Singh B, Bynum DK, Dahners LE. Corticosteroids as an adjunct to antibiotics and surgical drainage for the treatment of pyogenic flexor tenosynovitis. J Bone Joint Surg Am. 2010;92(16):2653-2662.
31. Delsignore JL, Ritland D, Becker DR, Watson HK. Continuous catheter irrigation for the treatment of suppurative flexor synovitis. Conn Med. 1986;50(8):503-506.
32. Gosain AK, Markisson RE. Catheter irrigation for treatment of pyogenic closed space infections of the hand. Br J Plast Surg. 1991;44(4):270-273.
Pyogenic flexor tenosynovitis (PFT) is a common closed space infection of the flexor tendon sheaths of the hand and remains one of the most challenging problems encountered in orthopedic and hand surgery (Figure 1). PFT also is known as septic flexor tenosynovitis and suppurative flexor tenosynovitis.
Kanavel1 initially described 4 cardinal signs that characterize infection of the flexor tendon sheath: symmetric fusiform swelling of the entire digit, exquisite tenderness to palpation along the course of the tendon sheath, semiflexed posture at rest, and pain with attempted passive extension of the digit. The prevalence of this infection ranges from 2.5% to 9.4%.2 Once the infection is established in a patient, it can cause significant morbidity and disability and produce an economic burden. It can also present a significant treatment dilemma for the treating surgeon, as there is no standardized protocol for managing this common but challenging hand infection. For treatment, many surgeons combine surgical decompression, sheath irrigation, and empiric intravenous (IV) antibiotic administration. However, despite prompt treatment, and regardless of the protocol used, complication rates as high as 38% have been reported.3 Moreover, even after infection eradication, a significant proportion of patients continue to have pain, swelling, stiffness, loss of composite flexion, weakness, and recurrence that potentially requires amputation.
1. What Causes Pyogenic Flexor Tenosynovitis?
PFT can result from hematogenous spread, but local inoculation by a laceration, a puncture, or a bite also is common4-7 (Figure 1). As a consequence of these mechanisms of injury, the most common source of PFT is skin flora. Staphylococcus aureus has been found in up to 75% of positive cultures in several studies.2,5,6,8,9 Methicillin-resistant S aureus (MRSA) has been found in up to 29% of cases, and the incidence continues to increase, particularly in urban areas.2,9-12 Other common bacteria are Staphylococcus epidermidis, β-hemolytic Streptococcus species, and Pseudomonas aeruginosa.5,6,10 Infection by more than 1 species of bacteria is also fairly prevalent. Of 62 patients in a study, 38% had infections with 1 organism, and 62% with 2 or more.6 Twenty-six percent of cultures grew mixed anaerobic and aerobic organisms.6 PFT is seldom caused by Eikenella corrodens from a human bite or Pasteurella multocida from an animal bite.10 Other rare causes of PFT are Listeria monocytogenes13 and Clostridium difficile from a gastrointestinal source.14Neisseria gonorrhea can cause acute tenosynovitis, usually in the setting of disseminated gonococcal infection.15,16 Also reported is mycobacterial tenosynovitis, most commonly caused by Mycobacterium kansasii and Mycobacterium marinum.17
2. Which Antibiotics Are Best Suited to Empirical Management of PFT?
Management of PFT, regardless of the pathogen, includes prompt administration of empiric IV antibiotics, usually followed by surgical drainage.7,18-20 While cultures are being tested, antibiotics should be selected—including antibiotics for empiric coverage against common gram-positive organisms, including Staphylococcus and Streptococcus species.12 The Centers for Disease Control and Prevention recommends empiric coverage for MRSA if the local prevalence exceeds 10% to 15%. Recommended empiric antibiotics are trimethoprim-sulfamethoxazole (TMP-SMX) and clindamycin (both oral) and clindamycin, vancomycin, and daptomycin (all IV).
In addition, institutional and local antibiotic resistance patterns of bacteria should guide treatment and antibiotic selection. First-generation cephalosporins have long been the cornerstone of treatment for infections caused by S aureus, but increasing methicillin resistance has reduced their role in the treatment, particularly the empiric treatment, of MRSA infections. Methicillin resistance first appeared as nosocomial S aureus infections in 1961, only 1 year after the introduction of the semisynthetic penicillin class that includes methicillin. Over the past 2 decades, MRSA has emerged in the community in otherwise young and healthy individuals with no healthcare-associated risk factors. Fortunately, several readily available antibiotics have maintained their efficacy in managing these “community-acquired” MRSA hand infections. TMP-SMX provides adequate coverage for MRSA and is a relatively inexpensive medication, and clindamycin is an equally effective and cost-effective alternative.
Presumptive antibiotics should also cover gram-negative rods and anaerobes, including Clostridium species, especially in immunocompromised patients.7,9 These patients may require additional antibiotics for presumptive coverage of other rarer bacterial causes, especially when unique mechanisms of injury (eg, aquatic injury, farm injury) are involved. Once culture results are ready, antibiotic regimens should be narrowed to cover the specific organisms identified.
3. What Are the Timing and Indications for Surgery?
Nonoperative treatment may be appropriate for PFT patients who present early, typically within 48 hours after penetrating trauma to the hand.21 In a 4-patient series, Neviaser and Gunther19 successfully treated PFT nonoperatively, with IV antibiotics, splinting, and elevation. During nonoperative treatment, the affected hand should be regularly examined. If this treatment is to be successful, clinical symptoms should improve within 48 hours; if they do not, surgical irrigation and débridement should be performed.
Regardless of timing and type of irrigation, surgical treatment remains the treatment of choice for the majority of PFT cases. Michon22 developed a 3-tier PFT classification system that is based on intraoperative findings (Table).
4. What Are the Surgical Techniques for PFT Drainage?
Several surgical methods have been developed to decompress and irrigate the flexor sheaths of the hand. However, debates about optimal timing of surgical intervention, surgery type (open surgery or closed catheter irrigation only), and irrigation method continue.
Open Irrigation and Débridement
Open irrigation and débridement procedures were originally described for surgical management of PFT.1 Midaxial and palmar (Bruner zigzag) incisions can be used to expose and open the entire sheath for complete drainage and washout. Both incisions afford good access to the flexor sheath, but the midaxial approach may provide more coverage of the sheath after surgery. Open irrigation and débridement is the treatment of choice for the most advanced cases of PFT and for atypical or chronic tenosynovial infections.4,23,24 The Bruner zigzag incision affords ease of surgical dissection, extension, and more exposure of the flexor tendon sheath at the expense of possible difficulty in closure or flap necrosis in the setting of a swollen digit. Alternatively, the midaxial incision has the advantage of a large, more robust skin flap for more reliable closure.
Closed Tendon Sheath Irrigation
In 1943, Dickson-Wright25 first described catheter irrigation of tendon sheath infections. Later, Neviaser4 described this technique in detail. A proximal incision is made over the metacarpal neck. The tendon sheath is cut transversely at the proximal edge of the A1 pulley. An angiocatheter is inserted 1 cm to 2 cm antegrade into the flexor tendon sheath. Then, a distal midaxial incision is made dorsal to the neurovascular bundle at the level of the distal interphalangeal joint on the ulnar aspect of the finger or the radial aspect of the thumb. The distal edge of the flexor sheath is exposed and resected distal to the distal-most pulley. A Penrose drain can be threaded into the tendon sheath beneath the A4 pulley to keep the wound open and allow for fluid drainage. The sheath is flushed gently in the operating room. After surgery, intermittent bedside irrigation can be continued on the floor.
Neviaser4 reported excellent initial results with this technique; 18 of 20 patients regained complete active and passive range of motion (ROM) by 1 week after surgery. Similarly, Juliano and Eglseder,26 using a similar method, reported 100% excellent results for mild PFT and 88.4% excellent results for more severe infection.
Gutowski and colleagues23 reviewed 47 PFT cases to determine if there is a difference in outcomes between PFT treated with open irrigation and débridement and PFT treated with closed catheter irrigation. Between these groups, they found no significant differences in early postoperative outcomes, including resolution of infection, need for additional surgery, and hospital length of stay.
There are also many differing opinions regarding the best irrigation method. Some authors have asserted that normal saline is sufficient,4,5,23 and others that local antibiotics provide added benefit.27-29 Recently, Draeger and colleagues30 reported promising results with local injection of antibiotics into the tendon sheath and the addition of locally administered corticosteroids in the treatment of PFT in an animal model.
Continuous Closed Irrigation
A continuous closed irrigation system with inlet and outlet tubes has yielded successful results.8,31,32 This system consists of 2 fenestrated tubes placed within the infected space, with the tip of the smaller caliber inlet tube positioned just inside the larger outlet tube. Advantages of this system include the patient’s ability to participate in hand therapy with the system in place and avoidance of pain caused by the high pressures involved in intermittent closed irrigation. Duration of this system has ranged from 2 days to 3 weeks, and results have been good.5,8
Postoperative Irrigation
Use of postoperative irrigation on the floor or at home is controversial, as leaving an indwelling catheter in the tendon sheath can lead to complications. Catheters may increase digital stiffness by decreasing the patient’s ability to participate in therapy or may cause additional injury and irritation to the sheath itself if left in place too long. Lille and colleagues6 retrospectively compared the results of intraoperative closed tendon sheath irrigation alone with those of intraoperative and postoperative closed tendon sheath irrigation. There were no significant differences in mean hospital length of stay, follow-up complication rates, or postoperative ROM—which suggests that postoperative intermittent or continuous irrigation is not necessary.
Our Preferred Technique
We recommend a palmar approach that begins with outlining a Bruner zigzag incision along the entire finger. Then, only the distal-most and proximal-most incision lines are opened, thereby exposing the A5 and A1 pulleys, respectively (Figure 2).
5. What Are the Long-Term Outcomes of PFT?
The principal complication associated with PFT is stiffness with loss of ROM, which can be caused by flexor tendon adhesions, joint capsular thickening, or destruction of the sheath and pulley system.24 In several studies, up to one-fourth of patients with PFT did not obtain full ROM, despite adequate treatment.4-6,27 Therefore, full active ROM exercises should be initiated immediately after surgery to counteract the development of stiffness.
The most severe complication of PFT is amputation of the affected digit (Figures 3A, 3B).
Pang and colleagues2 identified 5 factors associated with increased risk of amputation in patients with PFT: (1) age >43 years; (2) diabetes mellitus, peripheral vascular disease, or renal failure; (3) subcutaneous purulence; (4) signs of digital ischemia at presentation; and (5) growth of more than 1 bacteria species on culture of specimens obtained at time of surgery.
Pang and colleagues2 classified these patients into 3 groups with distinct clinical features and reported each group’s outcomes. The authors based their PFT classification system on increasingly severe clinical presentation, which potentially predicts amputation risk. Patients in stage 1 presented with Kanavel signs of tenosynovitis but no evidence of subcutaneous purulence or ischemia; patients in stage 2 had concurrent localized subcutaneous purulence but no ischemia; and patients in stage 3 had concurrent extensive subcutaneous purulence involving more than 1 phalangeal segment or spreading circumferentially as well as signs of ischemia. These PFT stages were found to correlate with worse patient outcomes. In patients with stage 1 infection, amputation was not required, and average functional return was 80% of total active ROM of the affected digit. In patients with stage 2 infection, the amputation rate was 8%, and return of total active ROM in the remaining digits was 72%. The outcomes for the patients with stage 3 infection were the worst. The amputation rate for patients with all 3 classification criteria (Kanavel signs, subcutaneous purulence, digital ischemia) was 59%, and return of total active ROM in the remaining digits was only 49%. Use of this clinical classification system makes it possible to guide treatment and predict outcome and return to function.
Conclusion
PFT is a common hand infection that can cause significant morbidity. Early treatment is crucial: this requires use of IV antibiotics, or surgical irrigation and débridement in more advanced cases. However, despite prompt and thorough treatment, severe infection can lead to long-term impaired function and even amputation of the affected digit. More research is needed to determine optimal timing and technique for surgical intervention and to elucidate the role of local antibiotics and corticosteroids in treating this infection and potentially preventing the morbid outcomes we currently see.
Am J Orthop. 2017;46(3):E207-E212. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.
Pyogenic flexor tenosynovitis (PFT) is a common closed space infection of the flexor tendon sheaths of the hand and remains one of the most challenging problems encountered in orthopedic and hand surgery (Figure 1). PFT also is known as septic flexor tenosynovitis and suppurative flexor tenosynovitis.
Kanavel1 initially described 4 cardinal signs that characterize infection of the flexor tendon sheath: symmetric fusiform swelling of the entire digit, exquisite tenderness to palpation along the course of the tendon sheath, semiflexed posture at rest, and pain with attempted passive extension of the digit. The prevalence of this infection ranges from 2.5% to 9.4%.2 Once the infection is established in a patient, it can cause significant morbidity and disability and produce an economic burden. It can also present a significant treatment dilemma for the treating surgeon, as there is no standardized protocol for managing this common but challenging hand infection. For treatment, many surgeons combine surgical decompression, sheath irrigation, and empiric intravenous (IV) antibiotic administration. However, despite prompt treatment, and regardless of the protocol used, complication rates as high as 38% have been reported.3 Moreover, even after infection eradication, a significant proportion of patients continue to have pain, swelling, stiffness, loss of composite flexion, weakness, and recurrence that potentially requires amputation.
1. What Causes Pyogenic Flexor Tenosynovitis?
PFT can result from hematogenous spread, but local inoculation by a laceration, a puncture, or a bite also is common4-7 (Figure 1). As a consequence of these mechanisms of injury, the most common source of PFT is skin flora. Staphylococcus aureus has been found in up to 75% of positive cultures in several studies.2,5,6,8,9 Methicillin-resistant S aureus (MRSA) has been found in up to 29% of cases, and the incidence continues to increase, particularly in urban areas.2,9-12 Other common bacteria are Staphylococcus epidermidis, β-hemolytic Streptococcus species, and Pseudomonas aeruginosa.5,6,10 Infection by more than 1 species of bacteria is also fairly prevalent. Of 62 patients in a study, 38% had infections with 1 organism, and 62% with 2 or more.6 Twenty-six percent of cultures grew mixed anaerobic and aerobic organisms.6 PFT is seldom caused by Eikenella corrodens from a human bite or Pasteurella multocida from an animal bite.10 Other rare causes of PFT are Listeria monocytogenes13 and Clostridium difficile from a gastrointestinal source.14Neisseria gonorrhea can cause acute tenosynovitis, usually in the setting of disseminated gonococcal infection.15,16 Also reported is mycobacterial tenosynovitis, most commonly caused by Mycobacterium kansasii and Mycobacterium marinum.17
2. Which Antibiotics Are Best Suited to Empirical Management of PFT?
Management of PFT, regardless of the pathogen, includes prompt administration of empiric IV antibiotics, usually followed by surgical drainage.7,18-20 While cultures are being tested, antibiotics should be selected—including antibiotics for empiric coverage against common gram-positive organisms, including Staphylococcus and Streptococcus species.12 The Centers for Disease Control and Prevention recommends empiric coverage for MRSA if the local prevalence exceeds 10% to 15%. Recommended empiric antibiotics are trimethoprim-sulfamethoxazole (TMP-SMX) and clindamycin (both oral) and clindamycin, vancomycin, and daptomycin (all IV).
In addition, institutional and local antibiotic resistance patterns of bacteria should guide treatment and antibiotic selection. First-generation cephalosporins have long been the cornerstone of treatment for infections caused by S aureus, but increasing methicillin resistance has reduced their role in the treatment, particularly the empiric treatment, of MRSA infections. Methicillin resistance first appeared as nosocomial S aureus infections in 1961, only 1 year after the introduction of the semisynthetic penicillin class that includes methicillin. Over the past 2 decades, MRSA has emerged in the community in otherwise young and healthy individuals with no healthcare-associated risk factors. Fortunately, several readily available antibiotics have maintained their efficacy in managing these “community-acquired” MRSA hand infections. TMP-SMX provides adequate coverage for MRSA and is a relatively inexpensive medication, and clindamycin is an equally effective and cost-effective alternative.
Presumptive antibiotics should also cover gram-negative rods and anaerobes, including Clostridium species, especially in immunocompromised patients.7,9 These patients may require additional antibiotics for presumptive coverage of other rarer bacterial causes, especially when unique mechanisms of injury (eg, aquatic injury, farm injury) are involved. Once culture results are ready, antibiotic regimens should be narrowed to cover the specific organisms identified.
3. What Are the Timing and Indications for Surgery?
Nonoperative treatment may be appropriate for PFT patients who present early, typically within 48 hours after penetrating trauma to the hand.21 In a 4-patient series, Neviaser and Gunther19 successfully treated PFT nonoperatively, with IV antibiotics, splinting, and elevation. During nonoperative treatment, the affected hand should be regularly examined. If this treatment is to be successful, clinical symptoms should improve within 48 hours; if they do not, surgical irrigation and débridement should be performed.
Regardless of timing and type of irrigation, surgical treatment remains the treatment of choice for the majority of PFT cases. Michon22 developed a 3-tier PFT classification system that is based on intraoperative findings (Table).
4. What Are the Surgical Techniques for PFT Drainage?
Several surgical methods have been developed to decompress and irrigate the flexor sheaths of the hand. However, debates about optimal timing of surgical intervention, surgery type (open surgery or closed catheter irrigation only), and irrigation method continue.
Open Irrigation and Débridement
Open irrigation and débridement procedures were originally described for surgical management of PFT.1 Midaxial and palmar (Bruner zigzag) incisions can be used to expose and open the entire sheath for complete drainage and washout. Both incisions afford good access to the flexor sheath, but the midaxial approach may provide more coverage of the sheath after surgery. Open irrigation and débridement is the treatment of choice for the most advanced cases of PFT and for atypical or chronic tenosynovial infections.4,23,24 The Bruner zigzag incision affords ease of surgical dissection, extension, and more exposure of the flexor tendon sheath at the expense of possible difficulty in closure or flap necrosis in the setting of a swollen digit. Alternatively, the midaxial incision has the advantage of a large, more robust skin flap for more reliable closure.
Closed Tendon Sheath Irrigation
In 1943, Dickson-Wright25 first described catheter irrigation of tendon sheath infections. Later, Neviaser4 described this technique in detail. A proximal incision is made over the metacarpal neck. The tendon sheath is cut transversely at the proximal edge of the A1 pulley. An angiocatheter is inserted 1 cm to 2 cm antegrade into the flexor tendon sheath. Then, a distal midaxial incision is made dorsal to the neurovascular bundle at the level of the distal interphalangeal joint on the ulnar aspect of the finger or the radial aspect of the thumb. The distal edge of the flexor sheath is exposed and resected distal to the distal-most pulley. A Penrose drain can be threaded into the tendon sheath beneath the A4 pulley to keep the wound open and allow for fluid drainage. The sheath is flushed gently in the operating room. After surgery, intermittent bedside irrigation can be continued on the floor.
Neviaser4 reported excellent initial results with this technique; 18 of 20 patients regained complete active and passive range of motion (ROM) by 1 week after surgery. Similarly, Juliano and Eglseder,26 using a similar method, reported 100% excellent results for mild PFT and 88.4% excellent results for more severe infection.
Gutowski and colleagues23 reviewed 47 PFT cases to determine if there is a difference in outcomes between PFT treated with open irrigation and débridement and PFT treated with closed catheter irrigation. Between these groups, they found no significant differences in early postoperative outcomes, including resolution of infection, need for additional surgery, and hospital length of stay.
There are also many differing opinions regarding the best irrigation method. Some authors have asserted that normal saline is sufficient,4,5,23 and others that local antibiotics provide added benefit.27-29 Recently, Draeger and colleagues30 reported promising results with local injection of antibiotics into the tendon sheath and the addition of locally administered corticosteroids in the treatment of PFT in an animal model.
Continuous Closed Irrigation
A continuous closed irrigation system with inlet and outlet tubes has yielded successful results.8,31,32 This system consists of 2 fenestrated tubes placed within the infected space, with the tip of the smaller caliber inlet tube positioned just inside the larger outlet tube. Advantages of this system include the patient’s ability to participate in hand therapy with the system in place and avoidance of pain caused by the high pressures involved in intermittent closed irrigation. Duration of this system has ranged from 2 days to 3 weeks, and results have been good.5,8
Postoperative Irrigation
Use of postoperative irrigation on the floor or at home is controversial, as leaving an indwelling catheter in the tendon sheath can lead to complications. Catheters may increase digital stiffness by decreasing the patient’s ability to participate in therapy or may cause additional injury and irritation to the sheath itself if left in place too long. Lille and colleagues6 retrospectively compared the results of intraoperative closed tendon sheath irrigation alone with those of intraoperative and postoperative closed tendon sheath irrigation. There were no significant differences in mean hospital length of stay, follow-up complication rates, or postoperative ROM—which suggests that postoperative intermittent or continuous irrigation is not necessary.
Our Preferred Technique
We recommend a palmar approach that begins with outlining a Bruner zigzag incision along the entire finger. Then, only the distal-most and proximal-most incision lines are opened, thereby exposing the A5 and A1 pulleys, respectively (Figure 2).
5. What Are the Long-Term Outcomes of PFT?
The principal complication associated with PFT is stiffness with loss of ROM, which can be caused by flexor tendon adhesions, joint capsular thickening, or destruction of the sheath and pulley system.24 In several studies, up to one-fourth of patients with PFT did not obtain full ROM, despite adequate treatment.4-6,27 Therefore, full active ROM exercises should be initiated immediately after surgery to counteract the development of stiffness.
The most severe complication of PFT is amputation of the affected digit (Figures 3A, 3B).
Pang and colleagues2 identified 5 factors associated with increased risk of amputation in patients with PFT: (1) age >43 years; (2) diabetes mellitus, peripheral vascular disease, or renal failure; (3) subcutaneous purulence; (4) signs of digital ischemia at presentation; and (5) growth of more than 1 bacteria species on culture of specimens obtained at time of surgery.
Pang and colleagues2 classified these patients into 3 groups with distinct clinical features and reported each group’s outcomes. The authors based their PFT classification system on increasingly severe clinical presentation, which potentially predicts amputation risk. Patients in stage 1 presented with Kanavel signs of tenosynovitis but no evidence of subcutaneous purulence or ischemia; patients in stage 2 had concurrent localized subcutaneous purulence but no ischemia; and patients in stage 3 had concurrent extensive subcutaneous purulence involving more than 1 phalangeal segment or spreading circumferentially as well as signs of ischemia. These PFT stages were found to correlate with worse patient outcomes. In patients with stage 1 infection, amputation was not required, and average functional return was 80% of total active ROM of the affected digit. In patients with stage 2 infection, the amputation rate was 8%, and return of total active ROM in the remaining digits was 72%. The outcomes for the patients with stage 3 infection were the worst. The amputation rate for patients with all 3 classification criteria (Kanavel signs, subcutaneous purulence, digital ischemia) was 59%, and return of total active ROM in the remaining digits was only 49%. Use of this clinical classification system makes it possible to guide treatment and predict outcome and return to function.
Conclusion
PFT is a common hand infection that can cause significant morbidity. Early treatment is crucial: this requires use of IV antibiotics, or surgical irrigation and débridement in more advanced cases. However, despite prompt and thorough treatment, severe infection can lead to long-term impaired function and even amputation of the affected digit. More research is needed to determine optimal timing and technique for surgical intervention and to elucidate the role of local antibiotics and corticosteroids in treating this infection and potentially preventing the morbid outcomes we currently see.
Am J Orthop. 2017;46(3):E207-E212. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.
1. Kanavel AB. The symptoms, signs, and diagnosis of tenosynovitis and major fascial-space abscesses. In: Kanavel AB, ed. Infections of the Hand. 6th ed. Philadelphia, PA: Lea & Febiger; 1933:364-395.
2. Pang HN, Teoh LC, Yam AK, Lee JY, Puhaindran ME, Tan AB. Factors affecting the prognosis of pyogenic flexor tenosynovitis. J Bone Joint Surg Am. 2007;89(8):1742-1748.
3. Stern PJ, Staneck JL, McDonough JJ, Neale HW, Tyler G. Established hand infections: a controlled, prospective study. J Hand Surg Am. 1983;8(5 pt 1):553-559.
4. Neviaser RJ. Closed tendon sheath irrigation for pyogenic flexor tenosynovitis. J Hand Surg Am. 1978;3(5):462-466.
5. Harris PA, Nanchahal J. Closed continuous irrigation in the treatment of hand infections. J Hand Surg Br. 1999;24(3):328-333.
6. Lille S, Hayakawa T, Neumeister MW, Brown RE, Zook EG, Murray K. Continuous postoperative catheter irrigation is not necessary for the treatment of suppurative flexor tenosynovitis. J Hand Surg Br. 2000;25(3):304-307.
7. Boles SD, Schmidt CC. Pyogenic flexor tenosynovitis. Hand Clin. 1998;14(4):567-578.
8. Nemoto K, Yanagida M, Nemoto T. Closed continuous irrigation as a treatment for infection in the hand. J Hand Surg Br. 1993;18(6):783-789.
9. Dailiana ZH, Rigopoulos N, Varitimidis S, Hantes M, Bargiotas K, Malizos KN. Purulent flexor tenosynovitis: factors influencing the functional outcome. J Hand Surg Eur Vol. 2008;33(3):280-285.
10. Small LN, Ross JJ. Suppurative tenosynovitis and septic bursitis. Infect Dis Clin North Am. 2005;19(4):991-1005, xi.
11. Katsoulis E, Bissell I, Hargreaves DG. MRSA pyogenic flexor tenosynovitis leading to digital ischaemic necrosis and amputation. J Hand Surg Br. 2006;31(3):350-352.
12. Fowler JR Greenhill D, Schaffer AA, Thoder JJ, Ilyas AM. Evolving incidence of MRSA in urban hand infections. Orthopedics. 2013;36(6):796-800.
13. Aubert JP, Stein A, Raoult D, Magalon G. Flexor tenosynovitis in the hand: an unusual aetiology. J Hand Surg Br. 1995;20(4):509-510.
14. Wright TW, Linscheid RL, O’Duffy JD. Acute flexor tenosynovitis in association with Clostridium difficile infection: a case report. J Hand Surg Am. 1996;21(2):304-306.
15. Schaefer RA, Enzenauer RJ, Pruitt A, Corpe RS. Acute gonococcal flexor tenosynovitis in an adolescent male with pharyngitis: a case report and literature review. Clin Orthop Relat Res. 1992;(281):212-215.
16. Mamane W, Falcone MO, Doursounian L, Nourissat G. Isolated gonococcal tenosynovitis. Case report and review of literature [in French]. Chir Main. 2010;29(5):335-337.
17. Regnard PJ, Barry P, Isselin J. Mycobacterial tenosynovitis of the flexor tendons of the hand. A report of five cases. J Hand Surg Br. 1996;21(3):351-354.
18. Abrams RA, Botte MJ. Hand infections: treatment recommendations for specific types. J Am Acad Orthop Surg. 1996;4(4):219-230.
19. Neviaser RJ, Gunther SF. Tenosynovial infections in the hand: diagnosis and management. Instr Course Lect. 1980;29:108-128.
20. Szabo R, Palumbo C. Infections of the hand. In: Chapman M, ed. Chapman’s Orthopedic Surgery. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:1989-2008.
21. Neviaser R. Acute infections. In: Green D, Hotchkiss R, Pederson W, eds. Green’s Operative Hand Surgery. 4th ed. New York, NY: Churchill Livingstone; 1999:1033-1047.
22. Michon J. Phlegmon of the tendon sheaths [in French]. Ann Chir. 1974;28(4):277-280.
23. Gutowski KA, Ochoa O, Adams WP Jr. Closed-catheter irrigation is as effective as open drainage for treatment of pyogenic flexor tenosynovitis. Ann Plast Surg. 2002;49(4):350-354.
24. Stern PJ. Selected acute infections. Instr Course Lect. 1990;39:539-546.
25. Dickson-Wright A. Tendon sheath infection. Proc R Soc Med. 1943-1944;37:504-505.
26. Juliano PJ, Eglseder WA. Limited open-tendon-sheath irrigation in the treatment of pyogenic flexor tenosynovitis. Orthop Rev. 1991;20(12):1065-1069.
27. Pollen AG. Acute infection of the tendon sheaths. Hand. 1974;6(1):21-25.
28. Besser MI. Digital flexor tendon irrigation. Hand. 1976;8(1):72.
29. Carter SJ, Burman SO, Mersheimer WL. Treatment of digital tenosynovitis by irrigation with peroxide and oxytetracycline: review of nine cases. Ann Surg. 1966;163(4):645-650.
30. Draeger RW, Singh B, Bynum DK, Dahners LE. Corticosteroids as an adjunct to antibiotics and surgical drainage for the treatment of pyogenic flexor tenosynovitis. J Bone Joint Surg Am. 2010;92(16):2653-2662.
31. Delsignore JL, Ritland D, Becker DR, Watson HK. Continuous catheter irrigation for the treatment of suppurative flexor synovitis. Conn Med. 1986;50(8):503-506.
32. Gosain AK, Markisson RE. Catheter irrigation for treatment of pyogenic closed space infections of the hand. Br J Plast Surg. 1991;44(4):270-273.
1. Kanavel AB. The symptoms, signs, and diagnosis of tenosynovitis and major fascial-space abscesses. In: Kanavel AB, ed. Infections of the Hand. 6th ed. Philadelphia, PA: Lea & Febiger; 1933:364-395.
2. Pang HN, Teoh LC, Yam AK, Lee JY, Puhaindran ME, Tan AB. Factors affecting the prognosis of pyogenic flexor tenosynovitis. J Bone Joint Surg Am. 2007;89(8):1742-1748.
3. Stern PJ, Staneck JL, McDonough JJ, Neale HW, Tyler G. Established hand infections: a controlled, prospective study. J Hand Surg Am. 1983;8(5 pt 1):553-559.
4. Neviaser RJ. Closed tendon sheath irrigation for pyogenic flexor tenosynovitis. J Hand Surg Am. 1978;3(5):462-466.
5. Harris PA, Nanchahal J. Closed continuous irrigation in the treatment of hand infections. J Hand Surg Br. 1999;24(3):328-333.
6. Lille S, Hayakawa T, Neumeister MW, Brown RE, Zook EG, Murray K. Continuous postoperative catheter irrigation is not necessary for the treatment of suppurative flexor tenosynovitis. J Hand Surg Br. 2000;25(3):304-307.
7. Boles SD, Schmidt CC. Pyogenic flexor tenosynovitis. Hand Clin. 1998;14(4):567-578.
8. Nemoto K, Yanagida M, Nemoto T. Closed continuous irrigation as a treatment for infection in the hand. J Hand Surg Br. 1993;18(6):783-789.
9. Dailiana ZH, Rigopoulos N, Varitimidis S, Hantes M, Bargiotas K, Malizos KN. Purulent flexor tenosynovitis: factors influencing the functional outcome. J Hand Surg Eur Vol. 2008;33(3):280-285.
10. Small LN, Ross JJ. Suppurative tenosynovitis and septic bursitis. Infect Dis Clin North Am. 2005;19(4):991-1005, xi.
11. Katsoulis E, Bissell I, Hargreaves DG. MRSA pyogenic flexor tenosynovitis leading to digital ischaemic necrosis and amputation. J Hand Surg Br. 2006;31(3):350-352.
12. Fowler JR Greenhill D, Schaffer AA, Thoder JJ, Ilyas AM. Evolving incidence of MRSA in urban hand infections. Orthopedics. 2013;36(6):796-800.
13. Aubert JP, Stein A, Raoult D, Magalon G. Flexor tenosynovitis in the hand: an unusual aetiology. J Hand Surg Br. 1995;20(4):509-510.
14. Wright TW, Linscheid RL, O’Duffy JD. Acute flexor tenosynovitis in association with Clostridium difficile infection: a case report. J Hand Surg Am. 1996;21(2):304-306.
15. Schaefer RA, Enzenauer RJ, Pruitt A, Corpe RS. Acute gonococcal flexor tenosynovitis in an adolescent male with pharyngitis: a case report and literature review. Clin Orthop Relat Res. 1992;(281):212-215.
16. Mamane W, Falcone MO, Doursounian L, Nourissat G. Isolated gonococcal tenosynovitis. Case report and review of literature [in French]. Chir Main. 2010;29(5):335-337.
17. Regnard PJ, Barry P, Isselin J. Mycobacterial tenosynovitis of the flexor tendons of the hand. A report of five cases. J Hand Surg Br. 1996;21(3):351-354.
18. Abrams RA, Botte MJ. Hand infections: treatment recommendations for specific types. J Am Acad Orthop Surg. 1996;4(4):219-230.
19. Neviaser RJ, Gunther SF. Tenosynovial infections in the hand: diagnosis and management. Instr Course Lect. 1980;29:108-128.
20. Szabo R, Palumbo C. Infections of the hand. In: Chapman M, ed. Chapman’s Orthopedic Surgery. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2001:1989-2008.
21. Neviaser R. Acute infections. In: Green D, Hotchkiss R, Pederson W, eds. Green’s Operative Hand Surgery. 4th ed. New York, NY: Churchill Livingstone; 1999:1033-1047.
22. Michon J. Phlegmon of the tendon sheaths [in French]. Ann Chir. 1974;28(4):277-280.
23. Gutowski KA, Ochoa O, Adams WP Jr. Closed-catheter irrigation is as effective as open drainage for treatment of pyogenic flexor tenosynovitis. Ann Plast Surg. 2002;49(4):350-354.
24. Stern PJ. Selected acute infections. Instr Course Lect. 1990;39:539-546.
25. Dickson-Wright A. Tendon sheath infection. Proc R Soc Med. 1943-1944;37:504-505.
26. Juliano PJ, Eglseder WA. Limited open-tendon-sheath irrigation in the treatment of pyogenic flexor tenosynovitis. Orthop Rev. 1991;20(12):1065-1069.
27. Pollen AG. Acute infection of the tendon sheaths. Hand. 1974;6(1):21-25.
28. Besser MI. Digital flexor tendon irrigation. Hand. 1976;8(1):72.
29. Carter SJ, Burman SO, Mersheimer WL. Treatment of digital tenosynovitis by irrigation with peroxide and oxytetracycline: review of nine cases. Ann Surg. 1966;163(4):645-650.
30. Draeger RW, Singh B, Bynum DK, Dahners LE. Corticosteroids as an adjunct to antibiotics and surgical drainage for the treatment of pyogenic flexor tenosynovitis. J Bone Joint Surg Am. 2010;92(16):2653-2662.
31. Delsignore JL, Ritland D, Becker DR, Watson HK. Continuous catheter irrigation for the treatment of suppurative flexor synovitis. Conn Med. 1986;50(8):503-506.
32. Gosain AK, Markisson RE. Catheter irrigation for treatment of pyogenic closed space infections of the hand. Br J Plast Surg. 1991;44(4):270-273.
Clinician Reviews: What’s In It for You
Intensive chemo upfront means DHL patients can skip HSCT
A new study suggests that patients with double-hit lymphoma (DHL) in first remission only benefit from an autologous hematopoietic stem cell transplant (auto-HSCT) if they received standard frontline chemotherapy.
Researchers looked at long-term outcomes for DHL patients who achieved remission and, overall, found that auto-HSCT did not significantly prolong remission or survival.
However, patients who received standard chemotherapy as frontline treatment did appear to benefit from auto-HSCT, as these patients had worse outcomes than patients who received intensive frontline chemotherapy.
This finding led the researchers to recommend that DHL patients receive intensive chemotherapy upfront and forgo subsequent auto-HSCT.
Daniel J. Landsburg, MD, of the University of Pennsylvania in Philadelphia, and his colleagues made these recommendations in the Journal of Clinical Oncology.
“A major dilemma for oncologists who treat [DHL] was whether or not to recommend the potentially harmful therapy of auto-[H]SCT to patients with this disease as a strategy to help keep them in remission,” Dr Landsburg said.
To gain some insight into the issue, Dr Landsburg and his colleagues looked at data on 159 patients from 19 academic medical centers across the US.
Patients were diagnosed with DHL between 2006 and 2015, and all achieved remission following frontline chemotherapy.
Thirty-five patients received standard frontline therapy—R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone).
The remaining patients received intensive frontline chemotherapy:
- 81 received DA-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab)
- 32 received R-hyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine)
- 11 received R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high-dose cytarabine).
Sixty-two patients underwent auto-HSCT, and 97 patients did not. There were no significant differences between these 2 patient groups at baseline.
“Our result is not explained by differences in patients’ overall health or disease features,” Dr Landsburg said. “The transplant and non-transplant arms of this study were very well-matched.”
Relapse and survival
For the entire patient cohort, the 3-year relapse-free survival (RFS) rate was 80%, and the 3-year overall survival (OS) rate was 87%.
There was no significant difference in RFS or OS between patients who underwent auto-HSCT and those who did not.
The RFS rate was 89% in patients who underwent auto-HSCT and 75% in patients who did not (P=0.12). The OS rate was 91% and 85%, respectively (P=0.74).
“Once these patients achieve remission, the data show they are likely to stay in remission,” Dr Landsburg said.
“In the absence of a large, randomized, controlled trial, which would be very challenging to carry out in this case, this is the best evidence we have, and it shows there’s no clear benefit to these patients undergoing auto-[H]SCT.”
Impact of frontline therapy
Patients who received R-CHOP upfront had worse RFS and OS than those who received intensive chemotherapy, although the OS difference was not significant.
RFS rates were 56% in patients who received R-CHOP, 88% in those who received DA-EPOCH-R, 87% in those who received R-hyperCVAD, and 91% in those who received R-CODOX-M/IVAC (P=0.003).
OS rates were 77% in patients who received R-CHOP, 87% in those who received DA-EPOCH-R, 90% in those who received R-hyperCVAD, and 100% in those who received R-CODOX-M/IVAC, respectively (P=0.36).
When the 3 intensive regimens were combined, the RFS rate was 88% (vs 56% for R-CHOP, P=0.002), and the OS rate was 90% (vs 77% for R-CHOP, P=0.13).
Frontline therapy and HSCT
Patients who received R-CHOP upfront benefited from auto-HSCT, but patients who received intensive chemotherapy did not.
The RFS was 51% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 75% for patients who received R-CHOP followed by auto-HSCT.
The OS was 75% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 83% for patients who received R-CHOP followed by auto-HSCT.
The RFS was 86% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 91% for patients who received intensive chemotherapy followed by auto-HSCT.
The OS was 89% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 92% for patients who received intensive chemotherapy followed by auto-HSCT.
An intergroup comparison showed a significant difference in RFS (P=0.003), which was driven by a significantly lower rate of RFS for patients who received R-CHOP without auto-HSCT, compared with patients who received intensive chemotherapy without auto-HSCT (P=0.003) or intensive chemotherapy with auto-HSCT (P=0.001).
“[I]f patients do go into remission with R-CHOP, it appears to be less durable, so, in these cases, going forward with auto-[H]SCT may still make sense,” Dr Landsburg said.
On the other hand, there was no significant difference between the groups with regard to OS (P=0.50).
Dr Landsburg said the next step for this research will be to study features of patients who don’t go into remission in order to understand why their disease is resistant to therapy and if that can be overcome with different treatment strategies. He also said it’s important to try to find more effective therapies for DHL patients who relapse. 
A new study suggests that patients with double-hit lymphoma (DHL) in first remission only benefit from an autologous hematopoietic stem cell transplant (auto-HSCT) if they received standard frontline chemotherapy.
Researchers looked at long-term outcomes for DHL patients who achieved remission and, overall, found that auto-HSCT did not significantly prolong remission or survival.
However, patients who received standard chemotherapy as frontline treatment did appear to benefit from auto-HSCT, as these patients had worse outcomes than patients who received intensive frontline chemotherapy.
This finding led the researchers to recommend that DHL patients receive intensive chemotherapy upfront and forgo subsequent auto-HSCT.
Daniel J. Landsburg, MD, of the University of Pennsylvania in Philadelphia, and his colleagues made these recommendations in the Journal of Clinical Oncology.
“A major dilemma for oncologists who treat [DHL] was whether or not to recommend the potentially harmful therapy of auto-[H]SCT to patients with this disease as a strategy to help keep them in remission,” Dr Landsburg said.
To gain some insight into the issue, Dr Landsburg and his colleagues looked at data on 159 patients from 19 academic medical centers across the US.
Patients were diagnosed with DHL between 2006 and 2015, and all achieved remission following frontline chemotherapy.
Thirty-five patients received standard frontline therapy—R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone).
The remaining patients received intensive frontline chemotherapy:
- 81 received DA-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab)
- 32 received R-hyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine)
- 11 received R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high-dose cytarabine).
Sixty-two patients underwent auto-HSCT, and 97 patients did not. There were no significant differences between these 2 patient groups at baseline.
“Our result is not explained by differences in patients’ overall health or disease features,” Dr Landsburg said. “The transplant and non-transplant arms of this study were very well-matched.”
Relapse and survival
For the entire patient cohort, the 3-year relapse-free survival (RFS) rate was 80%, and the 3-year overall survival (OS) rate was 87%.
There was no significant difference in RFS or OS between patients who underwent auto-HSCT and those who did not.
The RFS rate was 89% in patients who underwent auto-HSCT and 75% in patients who did not (P=0.12). The OS rate was 91% and 85%, respectively (P=0.74).
“Once these patients achieve remission, the data show they are likely to stay in remission,” Dr Landsburg said.
“In the absence of a large, randomized, controlled trial, which would be very challenging to carry out in this case, this is the best evidence we have, and it shows there’s no clear benefit to these patients undergoing auto-[H]SCT.”
Impact of frontline therapy
Patients who received R-CHOP upfront had worse RFS and OS than those who received intensive chemotherapy, although the OS difference was not significant.
RFS rates were 56% in patients who received R-CHOP, 88% in those who received DA-EPOCH-R, 87% in those who received R-hyperCVAD, and 91% in those who received R-CODOX-M/IVAC (P=0.003).
OS rates were 77% in patients who received R-CHOP, 87% in those who received DA-EPOCH-R, 90% in those who received R-hyperCVAD, and 100% in those who received R-CODOX-M/IVAC, respectively (P=0.36).
When the 3 intensive regimens were combined, the RFS rate was 88% (vs 56% for R-CHOP, P=0.002), and the OS rate was 90% (vs 77% for R-CHOP, P=0.13).
Frontline therapy and HSCT
Patients who received R-CHOP upfront benefited from auto-HSCT, but patients who received intensive chemotherapy did not.
The RFS was 51% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 75% for patients who received R-CHOP followed by auto-HSCT.
The OS was 75% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 83% for patients who received R-CHOP followed by auto-HSCT.
The RFS was 86% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 91% for patients who received intensive chemotherapy followed by auto-HSCT.
The OS was 89% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 92% for patients who received intensive chemotherapy followed by auto-HSCT.
An intergroup comparison showed a significant difference in RFS (P=0.003), which was driven by a significantly lower rate of RFS for patients who received R-CHOP without auto-HSCT, compared with patients who received intensive chemotherapy without auto-HSCT (P=0.003) or intensive chemotherapy with auto-HSCT (P=0.001).
“[I]f patients do go into remission with R-CHOP, it appears to be less durable, so, in these cases, going forward with auto-[H]SCT may still make sense,” Dr Landsburg said.
On the other hand, there was no significant difference between the groups with regard to OS (P=0.50).
Dr Landsburg said the next step for this research will be to study features of patients who don’t go into remission in order to understand why their disease is resistant to therapy and if that can be overcome with different treatment strategies. He also said it’s important to try to find more effective therapies for DHL patients who relapse.
A new study suggests that patients with double-hit lymphoma (DHL) in first remission only benefit from an autologous hematopoietic stem cell transplant (auto-HSCT) if they received standard frontline chemotherapy.
Researchers looked at long-term outcomes for DHL patients who achieved remission and, overall, found that auto-HSCT did not significantly prolong remission or survival.
However, patients who received standard chemotherapy as frontline treatment did appear to benefit from auto-HSCT, as these patients had worse outcomes than patients who received intensive frontline chemotherapy.
This finding led the researchers to recommend that DHL patients receive intensive chemotherapy upfront and forgo subsequent auto-HSCT.
Daniel J. Landsburg, MD, of the University of Pennsylvania in Philadelphia, and his colleagues made these recommendations in the Journal of Clinical Oncology.
“A major dilemma for oncologists who treat [DHL] was whether or not to recommend the potentially harmful therapy of auto-[H]SCT to patients with this disease as a strategy to help keep them in remission,” Dr Landsburg said.
To gain some insight into the issue, Dr Landsburg and his colleagues looked at data on 159 patients from 19 academic medical centers across the US.
Patients were diagnosed with DHL between 2006 and 2015, and all achieved remission following frontline chemotherapy.
Thirty-five patients received standard frontline therapy—R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone).
The remaining patients received intensive frontline chemotherapy:
- 81 received DA-EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab)
- 32 received R-hyperCVAD (rituximab, cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, and cytarabine)
- 11 received R-CODOX-M/IVAC (rituximab, cyclophosphamide, doxorubicin, vincristine, methotrexate/ifosfamide, etoposide, high-dose cytarabine).
Sixty-two patients underwent auto-HSCT, and 97 patients did not. There were no significant differences between these 2 patient groups at baseline.
“Our result is not explained by differences in patients’ overall health or disease features,” Dr Landsburg said. “The transplant and non-transplant arms of this study were very well-matched.”
Relapse and survival
For the entire patient cohort, the 3-year relapse-free survival (RFS) rate was 80%, and the 3-year overall survival (OS) rate was 87%.
There was no significant difference in RFS or OS between patients who underwent auto-HSCT and those who did not.
The RFS rate was 89% in patients who underwent auto-HSCT and 75% in patients who did not (P=0.12). The OS rate was 91% and 85%, respectively (P=0.74).
“Once these patients achieve remission, the data show they are likely to stay in remission,” Dr Landsburg said.
“In the absence of a large, randomized, controlled trial, which would be very challenging to carry out in this case, this is the best evidence we have, and it shows there’s no clear benefit to these patients undergoing auto-[H]SCT.”
Impact of frontline therapy
Patients who received R-CHOP upfront had worse RFS and OS than those who received intensive chemotherapy, although the OS difference was not significant.
RFS rates were 56% in patients who received R-CHOP, 88% in those who received DA-EPOCH-R, 87% in those who received R-hyperCVAD, and 91% in those who received R-CODOX-M/IVAC (P=0.003).
OS rates were 77% in patients who received R-CHOP, 87% in those who received DA-EPOCH-R, 90% in those who received R-hyperCVAD, and 100% in those who received R-CODOX-M/IVAC, respectively (P=0.36).
When the 3 intensive regimens were combined, the RFS rate was 88% (vs 56% for R-CHOP, P=0.002), and the OS rate was 90% (vs 77% for R-CHOP, P=0.13).
Frontline therapy and HSCT
Patients who received R-CHOP upfront benefited from auto-HSCT, but patients who received intensive chemotherapy did not.
The RFS was 51% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 75% for patients who received R-CHOP followed by auto-HSCT.
The OS was 75% for patients who received R-CHOP and did not undergo auto-HSCT, and it was 83% for patients who received R-CHOP followed by auto-HSCT.
The RFS was 86% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 91% for patients who received intensive chemotherapy followed by auto-HSCT.
The OS was 89% for patients who received intensive chemotherapy and did not undergo auto-HSCT, and it was 92% for patients who received intensive chemotherapy followed by auto-HSCT.
An intergroup comparison showed a significant difference in RFS (P=0.003), which was driven by a significantly lower rate of RFS for patients who received R-CHOP without auto-HSCT, compared with patients who received intensive chemotherapy without auto-HSCT (P=0.003) or intensive chemotherapy with auto-HSCT (P=0.001).
“[I]f patients do go into remission with R-CHOP, it appears to be less durable, so, in these cases, going forward with auto-[H]SCT may still make sense,” Dr Landsburg said.
On the other hand, there was no significant difference between the groups with regard to OS (P=0.50).
Dr Landsburg said the next step for this research will be to study features of patients who don’t go into remission in order to understand why their disease is resistant to therapy and if that can be overcome with different treatment strategies. He also said it’s important to try to find more effective therapies for DHL patients who relapse.
Antibody shows potential for treating AML, B-ALL
Endoglin may be a promising therapeutic target in acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL), according to researchers.
The group identified endoglin expression on the majority of blasts from patients with AML and B-ALL.
The team also found that an endoglin antibody, TRC105 (carotuximab), exhibited activity against AML and B-ALL in vivo, and combining the drug with chemotherapeutic agents enhanced this activity.
Rita Perlingeiro, PhD, of the University of Minnesota in Minneapolis, and her colleagues reported these findings in Blood.
The researchers first discovered that endoglin, which is also known as CD105, was “highly expressed” in leukemic blasts.
In samples from AML patients, 47.6% to 98.5% of blasts were CD105+. In samples from B-ALL patients, 92.6% to 99% of blasts were CD105+.
“We have been studying the function of endoglin in hematopoiesis for more than a decade, and the consistent expression of this receptor in the majority of acute leukemias was intriguing,” Dr Perlingeiro said.
She and her colleagues also found that CD105+ blasts had superior leukemogenic activity and reduced survival in mice when compared to CD105- blasts.
Mice injected with AML CD105+ blasts had all died at day 110 after injection, but mice injected with CD105- AML blasts survived until day 140.
Mice injected with CD105+ ALL blasts died 3 months after injection, but mice injected with CD105- ALL blasts were still alive and showed no signs of disease at the time of sacrifice, which was 5 months after injection.
TRC105 monotherapy
Several experiments showed that TRC105 could reduce leukemic activity in vivo.
TRC105 reduced blast counts in the peripheral blood of mice that had been injected with AML blasts. The drug also reduced blasts in the bone marrow initially, though blast counts were comparable in treated mice and controls by week 12.
On the other hand, mice treated with TRC105 did not experience the weight loss and splenomegaly observed in control mice. And TRC105 suppressed the ability of AML blasts to give rise to leukemia in secondary recipient mice.
In mice injected with ALL blasts, TRC105 initially decreased blast counts. However, by week 8, blast counts in the peripheral blood, bone marrow, and spleen of treated mice were similar to those observed in controls. The researchers said this suggests that TRC105 only slows the development of ALL.
The team then evaluated the effects of TRC105 after disease had been established. Mice with established AML received TRC105 for 8 weeks, and mice with established ALL received TRC105 for 4 weeks.
In mice with AML, TRC105 reduced blasts in the peripheral blood and spleen but not the bone marrow. The treatment also prevented splenomegaly and weight loss and prolonged survival.
“Our hypothesis that endoglin expression was linked to leukemia-forming activity was proven to be true, and it was even more rewarding to witness the robust anti-leukemogenic effect of blocking endoglin signaling with TRC105, even when leukemia had already been established in the mouse,” Dr Perlingeiro said.
However, in mice with established ALL, TRC105 had no effect on leukemia progression.
The researchers said this could be due to expression of soluble endoglin (sENG), which would titrate the TRC105 antibody, limiting its ability to bind to membrane-bound endoglin on leukemic cells. Results of additional experiments supported this idea.
TRC105 in combination
The researchers also tested TRC105 in combination with chemotherapy in the mouse models. The team combined the antibody with cytarabine to treat AML and cyclophosphamide to treat ALL.
In mice with AML, cytarabine and TRC105 significantly reduced levels of leukemic cells in the peripheral blood.
In mice with ALL, cyclophosphamide and TRC105 suppressed leukemia development more effectively and more quickly than cyclophosphamide alone.
The researchers detected high levels of sENG in untreated mice with ALL, but levels were lower in the TRC105-treated mice. And there was “no significant detection” of sENG in mice that received cyclophosphamide and TRC105 or cyclophosphamide alone.
Dr Perlingeiro and her colleagues said this suggests the inhibitory effects of sENG can be circumvented by suppressing tumor burden, which results in the combination therapy demonstrating potent antileukemic activity.
Endoglin may be a promising therapeutic target in acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL), according to researchers.
The group identified endoglin expression on the majority of blasts from patients with AML and B-ALL.
The team also found that an endoglin antibody, TRC105 (carotuximab), exhibited activity against AML and B-ALL in vivo, and combining the drug with chemotherapeutic agents enhanced this activity.
Rita Perlingeiro, PhD, of the University of Minnesota in Minneapolis, and her colleagues reported these findings in Blood.
The researchers first discovered that endoglin, which is also known as CD105, was “highly expressed” in leukemic blasts.
In samples from AML patients, 47.6% to 98.5% of blasts were CD105+. In samples from B-ALL patients, 92.6% to 99% of blasts were CD105+.
“We have been studying the function of endoglin in hematopoiesis for more than a decade, and the consistent expression of this receptor in the majority of acute leukemias was intriguing,” Dr Perlingeiro said.
She and her colleagues also found that CD105+ blasts had superior leukemogenic activity and reduced survival in mice when compared to CD105- blasts.
Mice injected with AML CD105+ blasts had all died at day 110 after injection, but mice injected with CD105- AML blasts survived until day 140.
Mice injected with CD105+ ALL blasts died 3 months after injection, but mice injected with CD105- ALL blasts were still alive and showed no signs of disease at the time of sacrifice, which was 5 months after injection.
TRC105 monotherapy
Several experiments showed that TRC105 could reduce leukemic activity in vivo.
TRC105 reduced blast counts in the peripheral blood of mice that had been injected with AML blasts. The drug also reduced blasts in the bone marrow initially, though blast counts were comparable in treated mice and controls by week 12.
On the other hand, mice treated with TRC105 did not experience the weight loss and splenomegaly observed in control mice. And TRC105 suppressed the ability of AML blasts to give rise to leukemia in secondary recipient mice.
In mice injected with ALL blasts, TRC105 initially decreased blast counts. However, by week 8, blast counts in the peripheral blood, bone marrow, and spleen of treated mice were similar to those observed in controls. The researchers said this suggests that TRC105 only slows the development of ALL.
The team then evaluated the effects of TRC105 after disease had been established. Mice with established AML received TRC105 for 8 weeks, and mice with established ALL received TRC105 for 4 weeks.
In mice with AML, TRC105 reduced blasts in the peripheral blood and spleen but not the bone marrow. The treatment also prevented splenomegaly and weight loss and prolonged survival.
“Our hypothesis that endoglin expression was linked to leukemia-forming activity was proven to be true, and it was even more rewarding to witness the robust anti-leukemogenic effect of blocking endoglin signaling with TRC105, even when leukemia had already been established in the mouse,” Dr Perlingeiro said.
However, in mice with established ALL, TRC105 had no effect on leukemia progression.
The researchers said this could be due to expression of soluble endoglin (sENG), which would titrate the TRC105 antibody, limiting its ability to bind to membrane-bound endoglin on leukemic cells. Results of additional experiments supported this idea.
TRC105 in combination
The researchers also tested TRC105 in combination with chemotherapy in the mouse models. The team combined the antibody with cytarabine to treat AML and cyclophosphamide to treat ALL.
In mice with AML, cytarabine and TRC105 significantly reduced levels of leukemic cells in the peripheral blood.
In mice with ALL, cyclophosphamide and TRC105 suppressed leukemia development more effectively and more quickly than cyclophosphamide alone.
The researchers detected high levels of sENG in untreated mice with ALL, but levels were lower in the TRC105-treated mice. And there was “no significant detection” of sENG in mice that received cyclophosphamide and TRC105 or cyclophosphamide alone.
Dr Perlingeiro and her colleagues said this suggests the inhibitory effects of sENG can be circumvented by suppressing tumor burden, which results in the combination therapy demonstrating potent antileukemic activity.
Endoglin may be a promising therapeutic target in acute myeloid leukemia (AML) and B-cell acute lymphoblastic leukemia (B-ALL), according to researchers.
The group identified endoglin expression on the majority of blasts from patients with AML and B-ALL.
The team also found that an endoglin antibody, TRC105 (carotuximab), exhibited activity against AML and B-ALL in vivo, and combining the drug with chemotherapeutic agents enhanced this activity.
Rita Perlingeiro, PhD, of the University of Minnesota in Minneapolis, and her colleagues reported these findings in Blood.
The researchers first discovered that endoglin, which is also known as CD105, was “highly expressed” in leukemic blasts.
In samples from AML patients, 47.6% to 98.5% of blasts were CD105+. In samples from B-ALL patients, 92.6% to 99% of blasts were CD105+.
“We have been studying the function of endoglin in hematopoiesis for more than a decade, and the consistent expression of this receptor in the majority of acute leukemias was intriguing,” Dr Perlingeiro said.
She and her colleagues also found that CD105+ blasts had superior leukemogenic activity and reduced survival in mice when compared to CD105- blasts.
Mice injected with AML CD105+ blasts had all died at day 110 after injection, but mice injected with CD105- AML blasts survived until day 140.
Mice injected with CD105+ ALL blasts died 3 months after injection, but mice injected with CD105- ALL blasts were still alive and showed no signs of disease at the time of sacrifice, which was 5 months after injection.
TRC105 monotherapy
Several experiments showed that TRC105 could reduce leukemic activity in vivo.
TRC105 reduced blast counts in the peripheral blood of mice that had been injected with AML blasts. The drug also reduced blasts in the bone marrow initially, though blast counts were comparable in treated mice and controls by week 12.
On the other hand, mice treated with TRC105 did not experience the weight loss and splenomegaly observed in control mice. And TRC105 suppressed the ability of AML blasts to give rise to leukemia in secondary recipient mice.
In mice injected with ALL blasts, TRC105 initially decreased blast counts. However, by week 8, blast counts in the peripheral blood, bone marrow, and spleen of treated mice were similar to those observed in controls. The researchers said this suggests that TRC105 only slows the development of ALL.
The team then evaluated the effects of TRC105 after disease had been established. Mice with established AML received TRC105 for 8 weeks, and mice with established ALL received TRC105 for 4 weeks.
In mice with AML, TRC105 reduced blasts in the peripheral blood and spleen but not the bone marrow. The treatment also prevented splenomegaly and weight loss and prolonged survival.
“Our hypothesis that endoglin expression was linked to leukemia-forming activity was proven to be true, and it was even more rewarding to witness the robust anti-leukemogenic effect of blocking endoglin signaling with TRC105, even when leukemia had already been established in the mouse,” Dr Perlingeiro said.
However, in mice with established ALL, TRC105 had no effect on leukemia progression.
The researchers said this could be due to expression of soluble endoglin (sENG), which would titrate the TRC105 antibody, limiting its ability to bind to membrane-bound endoglin on leukemic cells. Results of additional experiments supported this idea.
TRC105 in combination
The researchers also tested TRC105 in combination with chemotherapy in the mouse models. The team combined the antibody with cytarabine to treat AML and cyclophosphamide to treat ALL.
In mice with AML, cytarabine and TRC105 significantly reduced levels of leukemic cells in the peripheral blood.
In mice with ALL, cyclophosphamide and TRC105 suppressed leukemia development more effectively and more quickly than cyclophosphamide alone.
The researchers detected high levels of sENG in untreated mice with ALL, but levels were lower in the TRC105-treated mice. And there was “no significant detection” of sENG in mice that received cyclophosphamide and TRC105 or cyclophosphamide alone.
Dr Perlingeiro and her colleagues said this suggests the inhibitory effects of sENG can be circumvented by suppressing tumor burden, which results in the combination therapy demonstrating potent antileukemic activity.
Maternal education can reduce risk of childhood malaria
One way to reduce the risk of malaria infection in children is to educate their mothers, according to a study published in Pathogens and Global Health.
The study suggested that educating mothers can be more effective in preventing childhood malaria than the malaria vaccine candidate RTS,S (Mosquirix).
Researchers said this finding can be explained by the fact that educated mothers know of ways to prevent malaria infection, such as using bed nets and taking their children for treatment if they develop a fever.
For this study, the researchers performed malaria testing in 647 children in the Democratic Republic of Congo (DRC) who were between the ages of 2 months and 5 years.
The team also had the children’s parent or guardian fill out a survey related to demographics, socioeconomic status, maternal education, bed net use, and recent illness involving fever.
Results showed that mothers with a higher education level had children with a lower risk of malaria infection.
“This was not a small effect,” said study author Michael Hawkes, MD, PhD, of the University of Alberta in Edmonton, Alberta, Canada.
“Maternal education had an enormous effect—equivalent to or greater than the leading biomedical vaccine against malaria.”
Overall, 19% of the children studied (123/647) tested positive for malaria.
The prevalence of malaria was 30% in children of mothers with no education, 17% in children of mothers with primary education, and 15% in children of mothers with education beyond primary school (P=0.001).
In a multivariate analysis adjusted for the effect of a child’s age and the study site, maternal education was still a significant predictor of malaria antigenemia.
“It doesn’t take a lot of education to teach a mom how to take simple precautions to prevent malaria in her child,” said study author Cary Ma, a medical student at the University of Alberta.
“All it takes is knowing the importance of using a bed net and knowing the importance of seeking care when your child has a fever. These are fairly straightforward, simple messages in the context of health and hygiene that can easily be conveyed, usually at an elementary or primary school level.”
“The World Health Organization is rolling out a new vaccine [RTS,S] in countries across Africa that has an efficacy of about 30%,” Dr Hawkes added.
“But children whose mothers are educated beyond the primary level have a 53% reduction in their malaria rates. So educating the mom has as profound an effect on childhood malaria as hundreds of millions of dollars spent on a vaccine.”
The researchers said this work builds upon previous studies that have shown the importance of maternal education in reducing child mortality and disease in other countries around the world.
The team noted that maternal education isn’t a magic bullet by itself, but they do believe it is part of the solution. They hope the lessons learned via this study can help lead policymakers to strengthen efforts to educate girls and women in the DRC and other malaria hotspots around the world.
One way to reduce the risk of malaria infection in children is to educate their mothers, according to a study published in Pathogens and Global Health.
The study suggested that educating mothers can be more effective in preventing childhood malaria than the malaria vaccine candidate RTS,S (Mosquirix).
Researchers said this finding can be explained by the fact that educated mothers know of ways to prevent malaria infection, such as using bed nets and taking their children for treatment if they develop a fever.
For this study, the researchers performed malaria testing in 647 children in the Democratic Republic of Congo (DRC) who were between the ages of 2 months and 5 years.
The team also had the children’s parent or guardian fill out a survey related to demographics, socioeconomic status, maternal education, bed net use, and recent illness involving fever.
Results showed that mothers with a higher education level had children with a lower risk of malaria infection.
“This was not a small effect,” said study author Michael Hawkes, MD, PhD, of the University of Alberta in Edmonton, Alberta, Canada.
“Maternal education had an enormous effect—equivalent to or greater than the leading biomedical vaccine against malaria.”
Overall, 19% of the children studied (123/647) tested positive for malaria.
The prevalence of malaria was 30% in children of mothers with no education, 17% in children of mothers with primary education, and 15% in children of mothers with education beyond primary school (P=0.001).
In a multivariate analysis adjusted for the effect of a child’s age and the study site, maternal education was still a significant predictor of malaria antigenemia.
“It doesn’t take a lot of education to teach a mom how to take simple precautions to prevent malaria in her child,” said study author Cary Ma, a medical student at the University of Alberta.
“All it takes is knowing the importance of using a bed net and knowing the importance of seeking care when your child has a fever. These are fairly straightforward, simple messages in the context of health and hygiene that can easily be conveyed, usually at an elementary or primary school level.”
“The World Health Organization is rolling out a new vaccine [RTS,S] in countries across Africa that has an efficacy of about 30%,” Dr Hawkes added.
“But children whose mothers are educated beyond the primary level have a 53% reduction in their malaria rates. So educating the mom has as profound an effect on childhood malaria as hundreds of millions of dollars spent on a vaccine.”
The researchers said this work builds upon previous studies that have shown the importance of maternal education in reducing child mortality and disease in other countries around the world.
The team noted that maternal education isn’t a magic bullet by itself, but they do believe it is part of the solution. They hope the lessons learned via this study can help lead policymakers to strengthen efforts to educate girls and women in the DRC and other malaria hotspots around the world.
One way to reduce the risk of malaria infection in children is to educate their mothers, according to a study published in Pathogens and Global Health.
The study suggested that educating mothers can be more effective in preventing childhood malaria than the malaria vaccine candidate RTS,S (Mosquirix).
Researchers said this finding can be explained by the fact that educated mothers know of ways to prevent malaria infection, such as using bed nets and taking their children for treatment if they develop a fever.
For this study, the researchers performed malaria testing in 647 children in the Democratic Republic of Congo (DRC) who were between the ages of 2 months and 5 years.
The team also had the children’s parent or guardian fill out a survey related to demographics, socioeconomic status, maternal education, bed net use, and recent illness involving fever.
Results showed that mothers with a higher education level had children with a lower risk of malaria infection.
“This was not a small effect,” said study author Michael Hawkes, MD, PhD, of the University of Alberta in Edmonton, Alberta, Canada.
“Maternal education had an enormous effect—equivalent to or greater than the leading biomedical vaccine against malaria.”
Overall, 19% of the children studied (123/647) tested positive for malaria.
The prevalence of malaria was 30% in children of mothers with no education, 17% in children of mothers with primary education, and 15% in children of mothers with education beyond primary school (P=0.001).
In a multivariate analysis adjusted for the effect of a child’s age and the study site, maternal education was still a significant predictor of malaria antigenemia.
“It doesn’t take a lot of education to teach a mom how to take simple precautions to prevent malaria in her child,” said study author Cary Ma, a medical student at the University of Alberta.
“All it takes is knowing the importance of using a bed net and knowing the importance of seeking care when your child has a fever. These are fairly straightforward, simple messages in the context of health and hygiene that can easily be conveyed, usually at an elementary or primary school level.”
“The World Health Organization is rolling out a new vaccine [RTS,S] in countries across Africa that has an efficacy of about 30%,” Dr Hawkes added.
“But children whose mothers are educated beyond the primary level have a 53% reduction in their malaria rates. So educating the mom has as profound an effect on childhood malaria as hundreds of millions of dollars spent on a vaccine.”
The researchers said this work builds upon previous studies that have shown the importance of maternal education in reducing child mortality and disease in other countries around the world.
The team noted that maternal education isn’t a magic bullet by itself, but they do believe it is part of the solution. They hope the lessons learned via this study can help lead policymakers to strengthen efforts to educate girls and women in the DRC and other malaria hotspots around the world.
Racial, ethnic differences exist ADHD treatment of Medicaid-enrolled youth
, reported Janet R. Cummings, PhD, and her associates at the Rollins School of Public Health at Emory University, Atlanta.
Overall, quality of care for Medicaid-enrolled children receiving ADHD treatment is poor. Of those who initiated medications, 59% visited a provider within 30 days, 64% received at least two other doctor visits, and 38% received combined treatment with any psychotherapy visit. Sixty percent did not fill the ADHD prescription for enough days, 70% had no psychotherapy visit, and 42% stopped treatment.
The percentage that had any follow-up visit in the initiation phase was lower among African American children than among white children (56% vs. 61%, P less than .001), while Hispanic children were more likely than were white children to receive adequate follow-up in the initiation phase (63% vs. 61%; P less than .001) as well as in the C&M phase (71% vs. 63%; P less than .001). In children who continued medication, African American and Hispanic children were more likely than were white children to receive any psychotherapy (42% and 49% vs. 35%; P less than .001).
“The adjusted rate of discontinuing medication was 22.4% points higher (P less than .001) among African American versus white youth and 16.7% points higher (P less than .001) among Hispanic versus white youth,” Dr. Cummings and her associates said. “These findings are in line with research indicating that racial/ethnic minority parents may prefer psychosocial treatments over medication for ADHD.”
In terms of stopping treatment, the percentages were significantly higher among African American (51%) and Hispanic (45%) children than among white children at 36% (P less than .001).
“Higher rates of medication discontinuation among minority youth could be due to differences in cultural health beliefs and/or concerns about ADHD medication treatment. African American parents are less likely than white parents to conceptualize ADHD as a medical condition requiring treatment and may be less willing to administer psychotropic medication to a child due to beliefs about medication efficacy and side effects. ADHD medication is associated with an increased risk of adverse effects ... and a substantial proportion of treatment discontinuation is due to these adverse effects,” the researchers said.
Read more in Pediatrics (2017 May 16. doi: 10.1542/ peds. 2016-2444).
, reported Janet R. Cummings, PhD, and her associates at the Rollins School of Public Health at Emory University, Atlanta.
Overall, quality of care for Medicaid-enrolled children receiving ADHD treatment is poor. Of those who initiated medications, 59% visited a provider within 30 days, 64% received at least two other doctor visits, and 38% received combined treatment with any psychotherapy visit. Sixty percent did not fill the ADHD prescription for enough days, 70% had no psychotherapy visit, and 42% stopped treatment.
The percentage that had any follow-up visit in the initiation phase was lower among African American children than among white children (56% vs. 61%, P less than .001), while Hispanic children were more likely than were white children to receive adequate follow-up in the initiation phase (63% vs. 61%; P less than .001) as well as in the C&M phase (71% vs. 63%; P less than .001). In children who continued medication, African American and Hispanic children were more likely than were white children to receive any psychotherapy (42% and 49% vs. 35%; P less than .001).
“The adjusted rate of discontinuing medication was 22.4% points higher (P less than .001) among African American versus white youth and 16.7% points higher (P less than .001) among Hispanic versus white youth,” Dr. Cummings and her associates said. “These findings are in line with research indicating that racial/ethnic minority parents may prefer psychosocial treatments over medication for ADHD.”
In terms of stopping treatment, the percentages were significantly higher among African American (51%) and Hispanic (45%) children than among white children at 36% (P less than .001).
“Higher rates of medication discontinuation among minority youth could be due to differences in cultural health beliefs and/or concerns about ADHD medication treatment. African American parents are less likely than white parents to conceptualize ADHD as a medical condition requiring treatment and may be less willing to administer psychotropic medication to a child due to beliefs about medication efficacy and side effects. ADHD medication is associated with an increased risk of adverse effects ... and a substantial proportion of treatment discontinuation is due to these adverse effects,” the researchers said.
Read more in Pediatrics (2017 May 16. doi: 10.1542/ peds. 2016-2444).
, reported Janet R. Cummings, PhD, and her associates at the Rollins School of Public Health at Emory University, Atlanta.
Overall, quality of care for Medicaid-enrolled children receiving ADHD treatment is poor. Of those who initiated medications, 59% visited a provider within 30 days, 64% received at least two other doctor visits, and 38% received combined treatment with any psychotherapy visit. Sixty percent did not fill the ADHD prescription for enough days, 70% had no psychotherapy visit, and 42% stopped treatment.
The percentage that had any follow-up visit in the initiation phase was lower among African American children than among white children (56% vs. 61%, P less than .001), while Hispanic children were more likely than were white children to receive adequate follow-up in the initiation phase (63% vs. 61%; P less than .001) as well as in the C&M phase (71% vs. 63%; P less than .001). In children who continued medication, African American and Hispanic children were more likely than were white children to receive any psychotherapy (42% and 49% vs. 35%; P less than .001).
“The adjusted rate of discontinuing medication was 22.4% points higher (P less than .001) among African American versus white youth and 16.7% points higher (P less than .001) among Hispanic versus white youth,” Dr. Cummings and her associates said. “These findings are in line with research indicating that racial/ethnic minority parents may prefer psychosocial treatments over medication for ADHD.”
In terms of stopping treatment, the percentages were significantly higher among African American (51%) and Hispanic (45%) children than among white children at 36% (P less than .001).
“Higher rates of medication discontinuation among minority youth could be due to differences in cultural health beliefs and/or concerns about ADHD medication treatment. African American parents are less likely than white parents to conceptualize ADHD as a medical condition requiring treatment and may be less willing to administer psychotropic medication to a child due to beliefs about medication efficacy and side effects. ADHD medication is associated with an increased risk of adverse effects ... and a substantial proportion of treatment discontinuation is due to these adverse effects,” the researchers said.
Read more in Pediatrics (2017 May 16. doi: 10.1542/ peds. 2016-2444).
FROM PEDIATRICS
VIDEO: Care withdrawal becoming more common in ischemic stroke patients
BOSTON – U.S. physicians chose to withdraw life-sustaining care from critically ill ischemic stroke patients at much higher rates in 2011 than in 2006, according to results of a new study, although overall percentages remain low.
The trend was bolstered by big jumps in “withdrawal of care” among patients who underwent thrombolysis or both thrombolysis and endovascular treatment: Over the 5-year period, their likelihood of having care withdrawn increased fivefold.
The study authors don’t know whether the trends have continued over the past 6 years, and it’s not clear why the rates rose so much from 2006 to 2011. The researchers speculate that the increase could be linked to disease severity and the preferences of patients and their families.
Whatever the case, study lead author Malik Muhammad Adil, MD, a neurology resident at the Ochsner Clinic Foundation in New Orleans, cautioned that prematurely withdrawing care can throw off stroke prognostication estimates that are already fuzzy. In an interview, he said this can then lead to “significant consequences, including suboptimal outcomes and higher risk of short-term mortality.”
Dr. Adil defines withdrawal of care as “discontinuation of life-sustaining interventions from a patient who is expected to die without this support.” These interventions include such treatments as intubation, mechanical ventilation, feeding tubes, antibiotics, and brain surgery, he said.
For the new study, researchers examined the Nationwide Inpatient Survey database for the years 2006-2011. They reported their findings at the annual meeting of the American Academy of Neurology.
The study reports the following regarding withdrawal of care among ischemic stroke patients:
- The rate grew in those who received neither thrombolysis nor endovascular treatment from 0.8% in 2006 to 3.0% in 2011 (P less than or equal to .0001).
- In those who received thrombolysis alone, the rate rose from 0.9% to 5.5% (P less than or equal to .0001).
- In those who received endovascular treatment alone, the rate increased from 2.8% to 9.0% (P = .0006).
- In patients who received both thrombolysis and endovascular treatment, the rate grew from 2.0% to 10.3% (P = .0009).
Dr. Adil said several factors can affect rates of withdrawal of care in ischemic stroke patients, such as the level of illness (patients receiving aggressive treatment are sicker), advance directives, and the decisions of family members. Some institutions may be more likely to push for withdrawal of care, too, he said. “At my institution, we are not aggressive with withdrawal of care, and I have seen a few better outcomes than expected,” he said.
Also, the lack of useful data regarding prognosis for these patients may lead to premature decisions regarding withdrawal of care, he said.
“We have few prognostic models/scores that predict mortality, and these models are not very sensitive and specific,” Dr. Adil said. “Often, physicians make these decisions based on their previous experiences. All of this leads to premature withdrawal of care. On the other hand, because of premature withdrawal of care, we do not have the data on long-term outcomes on these patients, leading to errors in prognostication.”
In an interview, Adam G. Kelly, MD, a neurologist at the University of Rochester (N.Y.) and chief of neurology at Highland Hospital in Rochester, said the study is important but lacks crucial information such as the circumstances surrounding the care decisions. He hasn’t noticed trends in withdrawal of care among his patients.
“It’s possible that providers have become better at documenting discussions with patients and families which allowed this information to be better captured,” he said. “As the authors mention, it’s also possible that providers are consciously or unconsciously delivering prognoses that are biased towards negative outcomes, leading patients and families to be more apt to choose a palliative approach.”
Dr. Kelly added that neurologists need to objectively offer prognoses in stroke cases. “When the outcome is in doubt, I recommend time-limited trials of interventions of mechanical ventilation, artificial feeding, and other high-intensity interventions to allow patients and families to make the decision they feel is best,” he said.
What about trends in the years since 2011? Dr. Adil said information regarding the years since 2011 wasn’t available to him, but he hopes to analyze the period from 2012 to 2016.
Dr. Adil discussed his study and its implications in a video interview.
No funding is reported. Dr. Adil reports no relevant disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – U.S. physicians chose to withdraw life-sustaining care from critically ill ischemic stroke patients at much higher rates in 2011 than in 2006, according to results of a new study, although overall percentages remain low.
The trend was bolstered by big jumps in “withdrawal of care” among patients who underwent thrombolysis or both thrombolysis and endovascular treatment: Over the 5-year period, their likelihood of having care withdrawn increased fivefold.
The study authors don’t know whether the trends have continued over the past 6 years, and it’s not clear why the rates rose so much from 2006 to 2011. The researchers speculate that the increase could be linked to disease severity and the preferences of patients and their families.
Whatever the case, study lead author Malik Muhammad Adil, MD, a neurology resident at the Ochsner Clinic Foundation in New Orleans, cautioned that prematurely withdrawing care can throw off stroke prognostication estimates that are already fuzzy. In an interview, he said this can then lead to “significant consequences, including suboptimal outcomes and higher risk of short-term mortality.”
Dr. Adil defines withdrawal of care as “discontinuation of life-sustaining interventions from a patient who is expected to die without this support.” These interventions include such treatments as intubation, mechanical ventilation, feeding tubes, antibiotics, and brain surgery, he said.
For the new study, researchers examined the Nationwide Inpatient Survey database for the years 2006-2011. They reported their findings at the annual meeting of the American Academy of Neurology.
The study reports the following regarding withdrawal of care among ischemic stroke patients:
- The rate grew in those who received neither thrombolysis nor endovascular treatment from 0.8% in 2006 to 3.0% in 2011 (P less than or equal to .0001).
- In those who received thrombolysis alone, the rate rose from 0.9% to 5.5% (P less than or equal to .0001).
- In those who received endovascular treatment alone, the rate increased from 2.8% to 9.0% (P = .0006).
- In patients who received both thrombolysis and endovascular treatment, the rate grew from 2.0% to 10.3% (P = .0009).
Dr. Adil said several factors can affect rates of withdrawal of care in ischemic stroke patients, such as the level of illness (patients receiving aggressive treatment are sicker), advance directives, and the decisions of family members. Some institutions may be more likely to push for withdrawal of care, too, he said. “At my institution, we are not aggressive with withdrawal of care, and I have seen a few better outcomes than expected,” he said.
Also, the lack of useful data regarding prognosis for these patients may lead to premature decisions regarding withdrawal of care, he said.
“We have few prognostic models/scores that predict mortality, and these models are not very sensitive and specific,” Dr. Adil said. “Often, physicians make these decisions based on their previous experiences. All of this leads to premature withdrawal of care. On the other hand, because of premature withdrawal of care, we do not have the data on long-term outcomes on these patients, leading to errors in prognostication.”
In an interview, Adam G. Kelly, MD, a neurologist at the University of Rochester (N.Y.) and chief of neurology at Highland Hospital in Rochester, said the study is important but lacks crucial information such as the circumstances surrounding the care decisions. He hasn’t noticed trends in withdrawal of care among his patients.
“It’s possible that providers have become better at documenting discussions with patients and families which allowed this information to be better captured,” he said. “As the authors mention, it’s also possible that providers are consciously or unconsciously delivering prognoses that are biased towards negative outcomes, leading patients and families to be more apt to choose a palliative approach.”
Dr. Kelly added that neurologists need to objectively offer prognoses in stroke cases. “When the outcome is in doubt, I recommend time-limited trials of interventions of mechanical ventilation, artificial feeding, and other high-intensity interventions to allow patients and families to make the decision they feel is best,” he said.
What about trends in the years since 2011? Dr. Adil said information regarding the years since 2011 wasn’t available to him, but he hopes to analyze the period from 2012 to 2016.
Dr. Adil discussed his study and its implications in a video interview.
No funding is reported. Dr. Adil reports no relevant disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
BOSTON – U.S. physicians chose to withdraw life-sustaining care from critically ill ischemic stroke patients at much higher rates in 2011 than in 2006, according to results of a new study, although overall percentages remain low.
The trend was bolstered by big jumps in “withdrawal of care” among patients who underwent thrombolysis or both thrombolysis and endovascular treatment: Over the 5-year period, their likelihood of having care withdrawn increased fivefold.
The study authors don’t know whether the trends have continued over the past 6 years, and it’s not clear why the rates rose so much from 2006 to 2011. The researchers speculate that the increase could be linked to disease severity and the preferences of patients and their families.
Whatever the case, study lead author Malik Muhammad Adil, MD, a neurology resident at the Ochsner Clinic Foundation in New Orleans, cautioned that prematurely withdrawing care can throw off stroke prognostication estimates that are already fuzzy. In an interview, he said this can then lead to “significant consequences, including suboptimal outcomes and higher risk of short-term mortality.”
Dr. Adil defines withdrawal of care as “discontinuation of life-sustaining interventions from a patient who is expected to die without this support.” These interventions include such treatments as intubation, mechanical ventilation, feeding tubes, antibiotics, and brain surgery, he said.
For the new study, researchers examined the Nationwide Inpatient Survey database for the years 2006-2011. They reported their findings at the annual meeting of the American Academy of Neurology.
The study reports the following regarding withdrawal of care among ischemic stroke patients:
- The rate grew in those who received neither thrombolysis nor endovascular treatment from 0.8% in 2006 to 3.0% in 2011 (P less than or equal to .0001).
- In those who received thrombolysis alone, the rate rose from 0.9% to 5.5% (P less than or equal to .0001).
- In those who received endovascular treatment alone, the rate increased from 2.8% to 9.0% (P = .0006).
- In patients who received both thrombolysis and endovascular treatment, the rate grew from 2.0% to 10.3% (P = .0009).
Dr. Adil said several factors can affect rates of withdrawal of care in ischemic stroke patients, such as the level of illness (patients receiving aggressive treatment are sicker), advance directives, and the decisions of family members. Some institutions may be more likely to push for withdrawal of care, too, he said. “At my institution, we are not aggressive with withdrawal of care, and I have seen a few better outcomes than expected,” he said.
Also, the lack of useful data regarding prognosis for these patients may lead to premature decisions regarding withdrawal of care, he said.
“We have few prognostic models/scores that predict mortality, and these models are not very sensitive and specific,” Dr. Adil said. “Often, physicians make these decisions based on their previous experiences. All of this leads to premature withdrawal of care. On the other hand, because of premature withdrawal of care, we do not have the data on long-term outcomes on these patients, leading to errors in prognostication.”
In an interview, Adam G. Kelly, MD, a neurologist at the University of Rochester (N.Y.) and chief of neurology at Highland Hospital in Rochester, said the study is important but lacks crucial information such as the circumstances surrounding the care decisions. He hasn’t noticed trends in withdrawal of care among his patients.
“It’s possible that providers have become better at documenting discussions with patients and families which allowed this information to be better captured,” he said. “As the authors mention, it’s also possible that providers are consciously or unconsciously delivering prognoses that are biased towards negative outcomes, leading patients and families to be more apt to choose a palliative approach.”
Dr. Kelly added that neurologists need to objectively offer prognoses in stroke cases. “When the outcome is in doubt, I recommend time-limited trials of interventions of mechanical ventilation, artificial feeding, and other high-intensity interventions to allow patients and families to make the decision they feel is best,” he said.
What about trends in the years since 2011? Dr. Adil said information regarding the years since 2011 wasn’t available to him, but he hopes to analyze the period from 2012 to 2016.
Dr. Adil discussed his study and its implications in a video interview.
No funding is reported. Dr. Adil reports no relevant disclosures.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
Key clinical point:
Major finding: The percentages of ischemic stroke patients whose care was withdrawn grew from 0.8%-2.8% in 2006 to 3.0%-10.3% in 2011, depending on the kind of treatment they received (thrombolysis, endovascular treatment, both, or neither).
Data source: Nationwide Inpatient Survey database.
Disclosures: No funding is reported. Dr. Adil reports no relevant disclosures.
Long-term TNFi tapering possible for some with ankylosing spondylitis
BIRMINGHAM, ENGLAND – A proportion of patients with ankylosing spondylitis (AS) were able to remain on a reduced-dose regimen of a tumor necrosis factor inhibitor (TNFi) for almost 4 years, according to data from a small study presented at the British Society for Rheumatology annual conference.
In an extension of the ANSWERS (Ankylosing Spondylitis with Etanercept Regimens) trial, 4 of 12 patients receiving a once-weekly 25-mg dose of etanercept (Enbrel) had a sustained response as did 14 of 21 patients who remained on the usual once-weekly dose of 50 mg.
“Although a minority of patients maintained response to the lower dose of etanercept over the longer term, the costs savings are substantial,” said Lauren Steel and coauthors from the Norfolk and Norwich Hospitals NHS Foundation Trust in a poster presentation. Almost 18,000 pounds sterling ($23,000) could be saved per each patient who is able to stay on the lower dose for 50 months.
Further, patients who did not maintain a response on the lower dose were usually able to regain their responses when the higher dose therapy was reinstituted. On average, disease control was reestablished in three out of four patients within 14 months of reverting to standard therapy.
ANSWERS was an open-label, multicenter, randomized, pilot study that sought to determine if tapering the dose of etanercept from the recommended 50 mg to 25 mg was feasible in 47 patients with AS (J Rheumatol. 2015;42:1177–85). The premise was that dose tapering in patients who achieved a response would perhaps reduce the risk for side effects in the long term, as well as provide considerable cost savings.
About half of the patients studied achieved a response to full-dose etanercept and were able to reduce their dose. At 6 months, a clinical response was maintained by 52% of the patients taking 25 mg and 92% of the patients taking 50 mg (P = .003).
The current prospective extension of the study looked at the longer-term outcomes of the patients who successfully maintained a response to the lower dose of etanercept.
Maintenance of response was defined as no change in the primary outcome of a reduction of 50% or more or a fall of at least 2 units in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and at least a 2-unit reduction in spinal pain measured using a 10-point scale.
In all, 12 patients, 9 of them male, with a mean age of 52 years entered the extension study. The comparator group consisted of 21 patients who had continued taking the 50-mg dose, 20 of them male, with a mean age of 60 years.
Of the 12 patients in the 25-mg group, 1 discontinued treatment because of side effects and did not restart any further biologic treatment; 7 patients experienced a disease flare after a median of 16 months and were retreated with the 50-mg dose. Five of the seven patients who reverted to the higher dose of etanercept regained a good response; the other two patients were switched to adalimumab (Humira) because of a loss of efficacy.
Pfizer funded the original study. One author disclosed he had received research funding and acted as an adviser to Pfizer and other pharmaceutical companies.
BIRMINGHAM, ENGLAND – A proportion of patients with ankylosing spondylitis (AS) were able to remain on a reduced-dose regimen of a tumor necrosis factor inhibitor (TNFi) for almost 4 years, according to data from a small study presented at the British Society for Rheumatology annual conference.
In an extension of the ANSWERS (Ankylosing Spondylitis with Etanercept Regimens) trial, 4 of 12 patients receiving a once-weekly 25-mg dose of etanercept (Enbrel) had a sustained response as did 14 of 21 patients who remained on the usual once-weekly dose of 50 mg.
“Although a minority of patients maintained response to the lower dose of etanercept over the longer term, the costs savings are substantial,” said Lauren Steel and coauthors from the Norfolk and Norwich Hospitals NHS Foundation Trust in a poster presentation. Almost 18,000 pounds sterling ($23,000) could be saved per each patient who is able to stay on the lower dose for 50 months.
Further, patients who did not maintain a response on the lower dose were usually able to regain their responses when the higher dose therapy was reinstituted. On average, disease control was reestablished in three out of four patients within 14 months of reverting to standard therapy.
ANSWERS was an open-label, multicenter, randomized, pilot study that sought to determine if tapering the dose of etanercept from the recommended 50 mg to 25 mg was feasible in 47 patients with AS (J Rheumatol. 2015;42:1177–85). The premise was that dose tapering in patients who achieved a response would perhaps reduce the risk for side effects in the long term, as well as provide considerable cost savings.
About half of the patients studied achieved a response to full-dose etanercept and were able to reduce their dose. At 6 months, a clinical response was maintained by 52% of the patients taking 25 mg and 92% of the patients taking 50 mg (P = .003).
The current prospective extension of the study looked at the longer-term outcomes of the patients who successfully maintained a response to the lower dose of etanercept.
Maintenance of response was defined as no change in the primary outcome of a reduction of 50% or more or a fall of at least 2 units in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and at least a 2-unit reduction in spinal pain measured using a 10-point scale.
In all, 12 patients, 9 of them male, with a mean age of 52 years entered the extension study. The comparator group consisted of 21 patients who had continued taking the 50-mg dose, 20 of them male, with a mean age of 60 years.
Of the 12 patients in the 25-mg group, 1 discontinued treatment because of side effects and did not restart any further biologic treatment; 7 patients experienced a disease flare after a median of 16 months and were retreated with the 50-mg dose. Five of the seven patients who reverted to the higher dose of etanercept regained a good response; the other two patients were switched to adalimumab (Humira) because of a loss of efficacy.
Pfizer funded the original study. One author disclosed he had received research funding and acted as an adviser to Pfizer and other pharmaceutical companies.
BIRMINGHAM, ENGLAND – A proportion of patients with ankylosing spondylitis (AS) were able to remain on a reduced-dose regimen of a tumor necrosis factor inhibitor (TNFi) for almost 4 years, according to data from a small study presented at the British Society for Rheumatology annual conference.
In an extension of the ANSWERS (Ankylosing Spondylitis with Etanercept Regimens) trial, 4 of 12 patients receiving a once-weekly 25-mg dose of etanercept (Enbrel) had a sustained response as did 14 of 21 patients who remained on the usual once-weekly dose of 50 mg.
“Although a minority of patients maintained response to the lower dose of etanercept over the longer term, the costs savings are substantial,” said Lauren Steel and coauthors from the Norfolk and Norwich Hospitals NHS Foundation Trust in a poster presentation. Almost 18,000 pounds sterling ($23,000) could be saved per each patient who is able to stay on the lower dose for 50 months.
Further, patients who did not maintain a response on the lower dose were usually able to regain their responses when the higher dose therapy was reinstituted. On average, disease control was reestablished in three out of four patients within 14 months of reverting to standard therapy.
ANSWERS was an open-label, multicenter, randomized, pilot study that sought to determine if tapering the dose of etanercept from the recommended 50 mg to 25 mg was feasible in 47 patients with AS (J Rheumatol. 2015;42:1177–85). The premise was that dose tapering in patients who achieved a response would perhaps reduce the risk for side effects in the long term, as well as provide considerable cost savings.
About half of the patients studied achieved a response to full-dose etanercept and were able to reduce their dose. At 6 months, a clinical response was maintained by 52% of the patients taking 25 mg and 92% of the patients taking 50 mg (P = .003).
The current prospective extension of the study looked at the longer-term outcomes of the patients who successfully maintained a response to the lower dose of etanercept.
Maintenance of response was defined as no change in the primary outcome of a reduction of 50% or more or a fall of at least 2 units in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and at least a 2-unit reduction in spinal pain measured using a 10-point scale.
In all, 12 patients, 9 of them male, with a mean age of 52 years entered the extension study. The comparator group consisted of 21 patients who had continued taking the 50-mg dose, 20 of them male, with a mean age of 60 years.
Of the 12 patients in the 25-mg group, 1 discontinued treatment because of side effects and did not restart any further biologic treatment; 7 patients experienced a disease flare after a median of 16 months and were retreated with the 50-mg dose. Five of the seven patients who reverted to the higher dose of etanercept regained a good response; the other two patients were switched to adalimumab (Humira) because of a loss of efficacy.
Pfizer funded the original study. One author disclosed he had received research funding and acted as an adviser to Pfizer and other pharmaceutical companies.
AT RHEUMATOLOGY 2017
Key clinical point:
Major finding: Four of 12 patients treated with etanercept 25 mg once weekly maintained a response at 50 months.
Data source: An extension study of 33 patients in the open-label, multicenter, randomized Ankylosing Spondylitis with Etanercept Regimens (ANSWERS) trial.
Disclosures: Pfizer funded the original study. One author disclosed he had received research funding and acted as an adviser to Pfizer and other pharmaceutical companies.