This supplement includes 2 CME credits. (scroll down)

Topics include:

• Biologics, Biosimilars, and Generics
• Community-Acquired Bacterial Pneumonia
• Cardiovascular Safety of Medications for Type 2 Diabetes Mellitus
• Dual therapy for Type 2 Diabetes Mellitus
• GLP-1R Agonists
• Medication Adherence in Type 2 Diabetes Mellitus
• NSAIDs
• Sublingual Immunotherapy

This supplement offers the opportunity to earn a total of 2 CME credits. 

Credit is awarded for successful completion of the online evaluations at the links below; these links may also be found within the supplement on the first page of each article.

• Diagnosis of Cirrhosis and Evaluation of Hepatic Encephalopathy: Common Errors and Their Significance for the PCP
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to http://www.pceconsortium.org/liver.
• Role of the Microbiome in Disease: Implications for Treatment of Irritable Bowel Syndrome
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to http://www.pceconsortium.org/microbiome.

This supplement includes 2 CME credits. (scroll down)

Topics include:

• Biologics, Biosimilars, and Generics
• Community-Acquired Bacterial Pneumonia
• Cardiovascular Safety of Medications for Type 2 Diabetes Mellitus
• Dual therapy for Type 2 Diabetes Mellitus
• GLP-1R Agonists
• Medication Adherence in Type 2 Diabetes Mellitus
• NSAIDs
• Sublingual Immunotherapy

This supplement offers the opportunity to earn a total of 2 CME credits. 

Credit is awarded for successful completion of the online evaluations at the links below; these links may also be found within the supplement on the first page of each article.

• Diagnosis of Cirrhosis and Evaluation of Hepatic Encephalopathy: Common Errors and Their Significance for the PCP
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to http://www.pceconsortium.org/liver.
• Role of the Microbiome in Disease: Implications for Treatment of Irritable Bowel Syndrome
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to http://www.pceconsortium.org/microbiome.

This supplement includes 2 CME credits. (scroll down)

Topics include:

• Biologics, Biosimilars, and Generics
• Community-Acquired Bacterial Pneumonia
• Cardiovascular Safety of Medications for Type 2 Diabetes Mellitus
• Dual therapy for Type 2 Diabetes Mellitus
• GLP-1R Agonists
• Medication Adherence in Type 2 Diabetes Mellitus
• NSAIDs
• Sublingual Immunotherapy

This supplement offers the opportunity to earn a total of 2 CME credits. 

Credit is awarded for successful completion of the online evaluations at the links below; these links may also be found within the supplement on the first page of each article.

• Diagnosis of Cirrhosis and Evaluation of Hepatic Encephalopathy: Common Errors and Their Significance for the PCP
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to http://www.pceconsortium.org/liver.
• Role of the Microbiome in Disease: Implications for Treatment of Irritable Bowel Syndrome
  • To complete the online evaluation and receive 1 CME credit for this article: please click on the link at the end of the article or go to http://www.pceconsortium.org/microbiome.

NATIONAL HARBOR, MD – Cancer of the vulva is becoming more common, and as incidence is rising, so are death rates from the relatively rare malignancy. A new examination of women with early-stage vulvar cancer showed that recurrence was common, and carried a poor prognosis.

Cancer in “nearly 25% of women with stage IB squamous cell carcinoma of the vulva will recur within 3 years of initial diagnosis,” said the study’s lead author, Rebecca Stone, MD, at the annual meeting of the Society of Gynecologic Oncology. Although most (85%) of the cancers that recur do so locally, salvage rates for patients with recurrences are poor, she said in a video interview.

Dr. Stone of Johns Hopkins University, Baltimore, said that the study looked at the subset of 59 patients with recurrence of their stage IB vulvar cancer, drawing from a total of 244 stage IB patients for whom complete data were available.

Current National Comprehensive Cancer Network (NCCN) guidelines for the treatment of early-stage vulvar squamous cell carcinoma (meaning T1 or 4 cm or smaller T2 lesions) call for adjuvant radiotherapy for patients with positive margins or unresectable lesions. For patients with negative margins after the primary procedure or re-excision, the guidelines say that radiotherapy decisions should be guided by risk factors including margin width, tumor size, the presence of lymphovascular invasion, and the pattern and depth of invasion.

However, Dr. Stone said, “There’s a knowledge gap in our current management of early-stage disease.” Some unknowns include what the threshold should be for tumor recurrence in terms of depth of invasion and size of tumor, whether perineural invasion is a risk factor, and whether adverse clinical factors are important. Also, she said, it’s not known how risk factors combine to increase recurrence risk.

Tumor size, invasion depth over 6 mm, and patient age were all risk factors identified by the study; perineural and lymphovascular invasion were also potential risk factors for recurrence.

The retrospective study, said Dr. Stone, is the largest multi-institutional cohort study examining stage IB vulvar cancer that has been completed, and it accomplished a detailed examination of which patients have recurrences, factors associated with recurrence, and postrecurrence salvage rates.

Dr. Stone reported no disclosures.

[email protected]

On Twitter @karioakes

NATIONAL HARBOR, MD – Cancer of the vulva is becoming more common, and as incidence is rising, so are death rates from the relatively rare malignancy. A new examination of women with early-stage vulvar cancer showed that recurrence was common, and carried a poor prognosis.

Cancer in “nearly 25% of women with stage IB squamous cell carcinoma of the vulva will recur within 3 years of initial diagnosis,” said the study’s lead author, Rebecca Stone, MD, at the annual meeting of the Society of Gynecologic Oncology. Although most (85%) of the cancers that recur do so locally, salvage rates for patients with recurrences are poor, she said in a video interview.

Dr. Stone of Johns Hopkins University, Baltimore, said that the study looked at the subset of 59 patients with recurrence of their stage IB vulvar cancer, drawing from a total of 244 stage IB patients for whom complete data were available.

Current National Comprehensive Cancer Network (NCCN) guidelines for the treatment of early-stage vulvar squamous cell carcinoma (meaning T1 or 4 cm or smaller T2 lesions) call for adjuvant radiotherapy for patients with positive margins or unresectable lesions. For patients with negative margins after the primary procedure or re-excision, the guidelines say that radiotherapy decisions should be guided by risk factors including margin width, tumor size, the presence of lymphovascular invasion, and the pattern and depth of invasion.

However, Dr. Stone said, “There’s a knowledge gap in our current management of early-stage disease.” Some unknowns include what the threshold should be for tumor recurrence in terms of depth of invasion and size of tumor, whether perineural invasion is a risk factor, and whether adverse clinical factors are important. Also, she said, it’s not known how risk factors combine to increase recurrence risk.

Tumor size, invasion depth over 6 mm, and patient age were all risk factors identified by the study; perineural and lymphovascular invasion were also potential risk factors for recurrence.

The retrospective study, said Dr. Stone, is the largest multi-institutional cohort study examining stage IB vulvar cancer that has been completed, and it accomplished a detailed examination of which patients have recurrences, factors associated with recurrence, and postrecurrence salvage rates.

Dr. Stone reported no disclosures.

[email protected]

On Twitter @karioakes

NATIONAL HARBOR, MD – Cancer of the vulva is becoming more common, and as incidence is rising, so are death rates from the relatively rare malignancy. A new examination of women with early-stage vulvar cancer showed that recurrence was common, and carried a poor prognosis.

Cancer in “nearly 25% of women with stage IB squamous cell carcinoma of the vulva will recur within 3 years of initial diagnosis,” said the study’s lead author, Rebecca Stone, MD, at the annual meeting of the Society of Gynecologic Oncology. Although most (85%) of the cancers that recur do so locally, salvage rates for patients with recurrences are poor, she said in a video interview.

Dr. Stone of Johns Hopkins University, Baltimore, said that the study looked at the subset of 59 patients with recurrence of their stage IB vulvar cancer, drawing from a total of 244 stage IB patients for whom complete data were available.

Current National Comprehensive Cancer Network (NCCN) guidelines for the treatment of early-stage vulvar squamous cell carcinoma (meaning T1 or 4 cm or smaller T2 lesions) call for adjuvant radiotherapy for patients with positive margins or unresectable lesions. For patients with negative margins after the primary procedure or re-excision, the guidelines say that radiotherapy decisions should be guided by risk factors including margin width, tumor size, the presence of lymphovascular invasion, and the pattern and depth of invasion.

However, Dr. Stone said, “There’s a knowledge gap in our current management of early-stage disease.” Some unknowns include what the threshold should be for tumor recurrence in terms of depth of invasion and size of tumor, whether perineural invasion is a risk factor, and whether adverse clinical factors are important. Also, she said, it’s not known how risk factors combine to increase recurrence risk.

Tumor size, invasion depth over 6 mm, and patient age were all risk factors identified by the study; perineural and lymphovascular invasion were also potential risk factors for recurrence.

The retrospective study, said Dr. Stone, is the largest multi-institutional cohort study examining stage IB vulvar cancer that has been completed, and it accomplished a detailed examination of which patients have recurrences, factors associated with recurrence, and postrecurrence salvage rates.

Dr. Stone reported no disclosures.

[email protected]

On Twitter @karioakes

Take-Home Points

• According to the orthopedic literature, ST and LTO for a TSA produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.
• Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions.
• ST and LTO approaches for a TSA result in similar Constant scores, pain scores, radiographic outcomes, and complication rates.

During total shoulder arthroplasty (TSA) exposure, the subscapularis muscle must be mobilized; its repair is crucial to the stability of the arthroplasty. The subscapularis is the largest rotator cuff muscle and has a contractile force equal to that of the other 3 muscles combined.^1,2 Traditionally it is mobilized with a tenotomy just medial to the tendon’s insertion onto the lesser tuberosity. Over the past 15 years, however, numerous authors have reported dysfunction after subscapularis tenotomy (ST). In 2003, Miller and colleagues³ reported that, at 2-year follow-up, almost 70% of patients had abnormal belly-press and liftoff tests, surrogate markers of subscapularis function. Other authors have found increased rates of anterior instability after subscapularis rupture.^4,5

In 2005, Gerber and colleagues⁶ introduced a technique for circumventing surgical division of the subscapularis. They described a lesser tuberosity osteotomy (LTO), in which the subscapularis tendon is detached with a bone fragment 5 mm to 10 mm in thickness and 3 cm to 4 cm in length. This approach was based on the premise that bone-to-bone healing is more reliable than tendon-to-tendon healing. Initial studies reported successful osteotomy healing, improved clinical outcome scores, and fewer abnormalities with belly-press and liftoff tests.^2,6 More recent literature, however, has questioned the necessity of LTO.^2,4,7-9We performed a systematic review to evaluate the literature, describe ST and LTO, and summarize the radiographic and clinical outcomes of both techniques. We hypothesized there would be no significant clinical differences between these approaches.

Methods

Search Strategy and Study Selection

Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we systematically reviewed the literature.¹⁰ Searches were completed in September 2014 using the PubMed Medline database and the Cochrane Central Register of Clinical Trials. Two reviewers (Dr. Louie, Dr. Levy) independently performed the search and assessed eligibility of all relevant studies based on predetermined inclusion criteria. Disagreements between reviewers were resolved by discussion. Key word selection was designed to capture all English-language studies with clinical and/or radiographic outcomes and level I to IV evidence. We used an electronic search algorithm with key words and a series of NOT phrases to match certain exclusion criteria:

(((((((((((((((((((((((((((((((((((((total[Text Word]) AND shoulder[Title]) AND arthroplasty[Title] AND (English[lang]))) NOT reverse[Title/Abstract]) NOT hemiarthroplasty[Title]) NOT nonoperative[Title]) NOT nonsurgical[Title] AND (English[lang]))) NOT rheumatoid[Title/Abstract]) NOT inflammatory[Title/Abstract]) NOT elbow[Title/Abstract]) NOT wrist[Title/Abstract]) NOT hip[Title/Abstract]) NOT knee[Title/Abstract]) NOT ankle[Title/Abstract] AND (English[lang]))) NOT biomechanic[Title/Abstract]) NOT biomechanics[Title/Abstract]) NOT biomechanical [Title/Abstract]) NOT cadaveric[Title/Abstract]) NOT revision[Title]) NOT resurfacing[Title/Abstract]) NOT surface[Title/Abstract]) NOT interphalangeal[Title/Abstract] AND (English[lang]))) NOT radiostereometric[Title/Abstract] AND (English[lang]))) NOT cmc[Title/Abstract]) NOT carpometacarpal[Title/Abstract]) NOT cervical[Title/Abstract]) NOT histology[Title/Abstract]) NOT histological[Title/Abstract]) NOT collagen[Title/Abstract] AND (English[lang]))) NOT kinematic[Title/Abstract]) NOT kinematics[Title/Abstract] AND (English[lang]))) NOT vitro[Title/Abstract] AND (English[lang]))) NOT inverted[Title/Abstract]) NOT grammont[Title/Abstract]) NOT arthrodesis[Title/Abstract]) NOT fusion[Title/Abstract]) NOT reverse[Title/Abstract] AND (English[lang]))

Study exclusion criteria consisted of cadaveric, biomechanical, histologic, and kinematic results as well as analyses of nonoperative management, hemiarthroplasty, or reverse TSA. Studies were excluded if they did not report clinical and/or radiographic data. Minimum mean follow-up was 2 years. To discount the effect of other TSA technical innovations, we evaluated the same period for the 2 surgical approaches. The first study with clinical outcomes after LTO was published in early 2005,⁶ so all studies published before 2005 were excluded.

We reviewed all references within the studies included by the initial search algorithm: randomized control trials, retrospective and prospective cohort designs, case series, and treatment studies. Technical notes, review papers, letters to the editor, and level V evidence reviews were excluded. To avoid counting patients twice, we compared each study’s authors and data collection period with those of the other studies. If there was overlap in authorship, period, and place, only the study with the longer follow-up or more comprehensive data was included. All trials comparing ST and LTO were included. If the authors of a TSA study did not describe the approach used, that study was excluded from our review.

Data Extraction

We collected details of study design, sample size, and patient demographics (sex, age, hand dominance, primary diagnosis). We also abstracted surgical factors about the glenoid component (cemented vs uncemented; pegged vs keeled; all-polyethylene vs metal-backed) and the humeral component (cemented vs press-fit; stemmed vs stemless). Clinical outcomes included pain scores, functional scores, number of revisions, range of motion (ROM), and subscapularis-specific tests (eg, belly-press, liftoff). As pain scales varied between studies, all values were converted to a 10-point scoring scale (0 = no pain; 10 = maximum pain) for comparisons. Numerous functional outcome scores were reported, but the Constant score was the only one consistently used across studies, making it a good choice for comparisons. One study used Penn Shoulder Scores (PSSs) and directly compared ST and LTO groups, so its data were included. In addition, radiographic data were compiled: radiolucencies around the humeral stem and glenoid component, humeral head subluxation/migration, and osteotomy healing. The only consistent radiographic parameter available for comparisons between groups was the presence of radiolucencies.

The Modified Coleman Methodology Score (MCMS), described by Cowan and colleagues,¹¹ was used to evaluate the methodologic quality of each study. The MCMS is a 15-item instrument that has been used to assess both randomized and nonrandomized trials.^12,13 It has a scaled score ranging from 0 to 100 (85-100, excellent; 70-84, good; 55-69, fair; <55, poor). Study quality was not factored into the data synthesis analysis.

Statistical Analysis

Data are reported as weighted means and standard deviations. A mean was calculated for each study reporting on a respective data point and was then weighed according to the study sample size. The result was that the nonweighted means from studies with smaller samples did not carry as much weight as those from studies with larger samples. Student t tests and 2-way analysis of variance were used to compare the ST and LTO groups and assess differences over time (SPSS Version 18; IBM). An α of 0.05 was set as statistically significant.

Results

Twenty studies (1420 shoulders, 1392 patients) were included in the final dataset (Figure).^2,6,8,14-30 

The youngest patients in the ST and LTO groups were 22 years and 19 years of age, respectively.

Discussion

Our goal in this systematic review was to analyze outcomes associated with ST and LTO in a heterogenous TSA population. We hypothesized TSA with ST or LTO would produce similar clinical and radiographic outcomes. There were no significant differences in Constant scores, pain scores, radiolucencies, or complications between the 2 groups. The ST group showed trends toward wider ROM improvements and fewer revisions, but only the change in forward elevation was significant. The components used in the 2 groups were similar with the exception of a lack of keeled glenoids and cemented humeral stems in the LTO group; data stratification controlling for these differences revealed no change in outcomes.

The optimal method of subscapularis mobilization for TSA remains a source of debate. Jackson and colleagues²³ found significant improvements in Neer and DASH scores after ST. However, 7 of 15 patients ruptured the subscapularis after 6 months and had significantly lower DASH scores. In 2005, Gerber and colleagues⁶ first described the LTO technique as an alternative to ST. After a mean of 39 months, 89% of their patients had a negative belly-press test, and 75% had a normal liftoff test. Radiographic evaluation revealed that the osteotomized fragment had healed in an anatomical position in all shoulders. In a large case series, Small and colleagues²⁰ used radiographs and computed tomography to further investigate LTO healing rates and found that 89% of patients had bony union by 6 months and that smoking was a significant risk factor for nonunion.

Biomechanical studies comparing ST and LTO approaches have shown mixed results. Ponce and colleagues² found decreased cyclic displacement and increased maximum load to failure with LTO, but Giuseffi and colleagues³² showed less cyclic displacement with ST and no difference in load to failure. Others authors have found no significant differences in stiffness or maximum load to failure.³³ Van den Berghe and colleagues⁷ reported a higher failure rate in bone-to-bone repairs compared with tendon-to-tendon constructs. Moreover, they found that suture cut-out through bone tunnels is the primary mode of LTO failure, so many LTO surgeons now pass sutures around the humeral stem instead.

Three TSA studies directly compared ST and LTO approaches. Buckley and colleagues¹⁴ analyzed 60 TSAs and found no significant differences in WOOS, DASH, or Constant scores between groups. The authors described an ST subgroup with subscapularis attenuation on ultrasound but did not report the group as having any inferior functional outcome. Scalise and colleagues¹⁵ showed improved strength and PSSs in both groups after 2 years. However, the LTO group had a lower rate of subscapularis tears and significantly higher PSSs. Finally, Jandhyala and colleagues¹⁶ reported more favorable outcomes with LTO, which trended toward wider ROM and significantly higher belly-press test grades. Lapner and colleagues³⁴ conducted a randomized, controlled trial (often referenced) and found no significant differences between the 2 groups in terms of strength or functional outcome at 2-year follow-up. Their study, however, included hemiarthroplasties and did not substratify the TSA population, so we did not include it in our review.

Our systematic review found significantly more forward elevation improvement for the ST group than the LTO group, which may suggest improved ROM with a soft-tissue approach than a bony approach. At the same time, the ST group trended toward better passive external rotation relative to the LTO group. This trend indicates fewer constraints to external rotation in the ST group, possibly attributable to a more attenuated subscapularis after tenotomy. Subscapularis tear or attenuation was more commonly reported in the ST group than in the LTO group, though not significantly so. This may indicate that more ST studies than LTO studies specially emphasized postoperative subscapularis function, but these data also highlight some authors’ concerns regarding subscapularis dysfunction after tenotomy.^6,15,16The study populations’ complication rates were similar, just over 17%. The LTO group trended toward a higher revision rate, but it was not statistically significant. The LTO group also had significantly fewer patients with osteoarthritis and more patients with posttraumatic arthritis, so this group may have had more complex patients predisposed to a higher likelihood of revision surgery. Revisions were most commonly performed for aseptic loosening; theoretically, if osteotomies heal less effectively than tenotomies, the LTO approach could produce component instability and aseptic loosening. However, no prior studies or other clinical findings from this review suggest LTO predisposes to aseptic loosening. Overall, the uneven revision rates represent a clinical concern that should be monitored as larger samples of patients undergo ST and LTO procedures.

Glenoid radiolucencies were the only radiographic parameter consistently reported in the included studies. Twelve ST studies had radiolucency data—compared with only 2 LTO studies. Thus, our ability to compare radiographic outcomes was limited. Our data revealed similar rates of glenoid radiolucencies between the 2 approaches. The clinical relevance of radiolucencies is questioned by some authors, and, indeed, Razmjou and colleagues²⁵ found no correlation of radiolucencies with patient satisfaction. Nevertheless, early presence of radiolucencies may raise concerns about progressive loss of fixation,^35,36 so this should be monitored.

Limitations of this systematic review reflect the studies analyzed. We minimized selection bias by including level I to IV evidence, but most studies were level IV, and only 1 was level I. As such, there was a relative paucity of consistent clinical and radiographic data. For instance, although many ST studies reported patient satisfaction as an outcomes measure, only 1 LTO study commented on it. Perhaps the relative novelty of the LTO approach has prompted some authors to focus more on technical details and less on reporting a variety of outcome measures. As mentioned earlier, the significance of radiolucency data is controversial, and determination of their presence or absence depends on the observer. A radiolucency found in one study may not qualify as one in a study that uses different criteria. However, lucency data were the most frequently and reliably reported radiographic parameter, so we deemed it the most appropriate method for comparing radiographic outcomes. Finally, the baseline differences in diagnosis between the ST and LTO groups complicated comparisons. We stratified the groups by component design because use of keeled or pegged implants or humeral cemented or press-fit stems was usually a uniform feature of each study—enabling removal of certain studies for data stratification. However, we were unable to stratify by original diagnosis because these groups were not stratified within the individual studies.

Conclusion

Our systematic review found similar Constant scores, pain scores, radiographic outcomes, and complication rates for the ST and LTO approaches. Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions. Although not definitive, these data suggest the ST approach may provide more stability over the long term, but additional comprehensive studies are needed to increase the sample size and the power of the trends elucidated in this review. According to the orthopedic literature, both techniques produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.

Am J Orthop. 2017;46(2):E131-E138. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• According to the orthopedic literature, ST and LTO for a TSA produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.
• Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions.
• ST and LTO approaches for a TSA result in similar Constant scores, pain scores, radiographic outcomes, and complication rates.

During total shoulder arthroplasty (TSA) exposure, the subscapularis muscle must be mobilized; its repair is crucial to the stability of the arthroplasty. The subscapularis is the largest rotator cuff muscle and has a contractile force equal to that of the other 3 muscles combined.^1,2 Traditionally it is mobilized with a tenotomy just medial to the tendon’s insertion onto the lesser tuberosity. Over the past 15 years, however, numerous authors have reported dysfunction after subscapularis tenotomy (ST). In 2003, Miller and colleagues³ reported that, at 2-year follow-up, almost 70% of patients had abnormal belly-press and liftoff tests, surrogate markers of subscapularis function. Other authors have found increased rates of anterior instability after subscapularis rupture.^4,5

In 2005, Gerber and colleagues⁶ introduced a technique for circumventing surgical division of the subscapularis. They described a lesser tuberosity osteotomy (LTO), in which the subscapularis tendon is detached with a bone fragment 5 mm to 10 mm in thickness and 3 cm to 4 cm in length. This approach was based on the premise that bone-to-bone healing is more reliable than tendon-to-tendon healing. Initial studies reported successful osteotomy healing, improved clinical outcome scores, and fewer abnormalities with belly-press and liftoff tests.^2,6 More recent literature, however, has questioned the necessity of LTO.^2,4,7-9We performed a systematic review to evaluate the literature, describe ST and LTO, and summarize the radiographic and clinical outcomes of both techniques. We hypothesized there would be no significant clinical differences between these approaches.

Methods

Search Strategy and Study Selection

Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we systematically reviewed the literature.¹⁰ Searches were completed in September 2014 using the PubMed Medline database and the Cochrane Central Register of Clinical Trials. Two reviewers (Dr. Louie, Dr. Levy) independently performed the search and assessed eligibility of all relevant studies based on predetermined inclusion criteria. Disagreements between reviewers were resolved by discussion. Key word selection was designed to capture all English-language studies with clinical and/or radiographic outcomes and level I to IV evidence. We used an electronic search algorithm with key words and a series of NOT phrases to match certain exclusion criteria:

(((((((((((((((((((((((((((((((((((((total[Text Word]) AND shoulder[Title]) AND arthroplasty[Title] AND (English[lang]))) NOT reverse[Title/Abstract]) NOT hemiarthroplasty[Title]) NOT nonoperative[Title]) NOT nonsurgical[Title] AND (English[lang]))) NOT rheumatoid[Title/Abstract]) NOT inflammatory[Title/Abstract]) NOT elbow[Title/Abstract]) NOT wrist[Title/Abstract]) NOT hip[Title/Abstract]) NOT knee[Title/Abstract]) NOT ankle[Title/Abstract] AND (English[lang]))) NOT biomechanic[Title/Abstract]) NOT biomechanics[Title/Abstract]) NOT biomechanical [Title/Abstract]) NOT cadaveric[Title/Abstract]) NOT revision[Title]) NOT resurfacing[Title/Abstract]) NOT surface[Title/Abstract]) NOT interphalangeal[Title/Abstract] AND (English[lang]))) NOT radiostereometric[Title/Abstract] AND (English[lang]))) NOT cmc[Title/Abstract]) NOT carpometacarpal[Title/Abstract]) NOT cervical[Title/Abstract]) NOT histology[Title/Abstract]) NOT histological[Title/Abstract]) NOT collagen[Title/Abstract] AND (English[lang]))) NOT kinematic[Title/Abstract]) NOT kinematics[Title/Abstract] AND (English[lang]))) NOT vitro[Title/Abstract] AND (English[lang]))) NOT inverted[Title/Abstract]) NOT grammont[Title/Abstract]) NOT arthrodesis[Title/Abstract]) NOT fusion[Title/Abstract]) NOT reverse[Title/Abstract] AND (English[lang]))

Study exclusion criteria consisted of cadaveric, biomechanical, histologic, and kinematic results as well as analyses of nonoperative management, hemiarthroplasty, or reverse TSA. Studies were excluded if they did not report clinical and/or radiographic data. Minimum mean follow-up was 2 years. To discount the effect of other TSA technical innovations, we evaluated the same period for the 2 surgical approaches. The first study with clinical outcomes after LTO was published in early 2005,⁶ so all studies published before 2005 were excluded.

We reviewed all references within the studies included by the initial search algorithm: randomized control trials, retrospective and prospective cohort designs, case series, and treatment studies. Technical notes, review papers, letters to the editor, and level V evidence reviews were excluded. To avoid counting patients twice, we compared each study’s authors and data collection period with those of the other studies. If there was overlap in authorship, period, and place, only the study with the longer follow-up or more comprehensive data was included. All trials comparing ST and LTO were included. If the authors of a TSA study did not describe the approach used, that study was excluded from our review.

Data Extraction

We collected details of study design, sample size, and patient demographics (sex, age, hand dominance, primary diagnosis). We also abstracted surgical factors about the glenoid component (cemented vs uncemented; pegged vs keeled; all-polyethylene vs metal-backed) and the humeral component (cemented vs press-fit; stemmed vs stemless). Clinical outcomes included pain scores, functional scores, number of revisions, range of motion (ROM), and subscapularis-specific tests (eg, belly-press, liftoff). As pain scales varied between studies, all values were converted to a 10-point scoring scale (0 = no pain; 10 = maximum pain) for comparisons. Numerous functional outcome scores were reported, but the Constant score was the only one consistently used across studies, making it a good choice for comparisons. One study used Penn Shoulder Scores (PSSs) and directly compared ST and LTO groups, so its data were included. In addition, radiographic data were compiled: radiolucencies around the humeral stem and glenoid component, humeral head subluxation/migration, and osteotomy healing. The only consistent radiographic parameter available for comparisons between groups was the presence of radiolucencies.

The Modified Coleman Methodology Score (MCMS), described by Cowan and colleagues,¹¹ was used to evaluate the methodologic quality of each study. The MCMS is a 15-item instrument that has been used to assess both randomized and nonrandomized trials.^12,13 It has a scaled score ranging from 0 to 100 (85-100, excellent; 70-84, good; 55-69, fair; <55, poor). Study quality was not factored into the data synthesis analysis.

Statistical Analysis

Data are reported as weighted means and standard deviations. A mean was calculated for each study reporting on a respective data point and was then weighed according to the study sample size. The result was that the nonweighted means from studies with smaller samples did not carry as much weight as those from studies with larger samples. Student t tests and 2-way analysis of variance were used to compare the ST and LTO groups and assess differences over time (SPSS Version 18; IBM). An α of 0.05 was set as statistically significant.

Results

Twenty studies (1420 shoulders, 1392 patients) were included in the final dataset (Figure).^2,6,8,14-30 

The youngest patients in the ST and LTO groups were 22 years and 19 years of age, respectively.

Discussion

Our goal in this systematic review was to analyze outcomes associated with ST and LTO in a heterogenous TSA population. We hypothesized TSA with ST or LTO would produce similar clinical and radiographic outcomes. There were no significant differences in Constant scores, pain scores, radiolucencies, or complications between the 2 groups. The ST group showed trends toward wider ROM improvements and fewer revisions, but only the change in forward elevation was significant. The components used in the 2 groups were similar with the exception of a lack of keeled glenoids and cemented humeral stems in the LTO group; data stratification controlling for these differences revealed no change in outcomes.

The optimal method of subscapularis mobilization for TSA remains a source of debate. Jackson and colleagues²³ found significant improvements in Neer and DASH scores after ST. However, 7 of 15 patients ruptured the subscapularis after 6 months and had significantly lower DASH scores. In 2005, Gerber and colleagues⁶ first described the LTO technique as an alternative to ST. After a mean of 39 months, 89% of their patients had a negative belly-press test, and 75% had a normal liftoff test. Radiographic evaluation revealed that the osteotomized fragment had healed in an anatomical position in all shoulders. In a large case series, Small and colleagues²⁰ used radiographs and computed tomography to further investigate LTO healing rates and found that 89% of patients had bony union by 6 months and that smoking was a significant risk factor for nonunion.

Biomechanical studies comparing ST and LTO approaches have shown mixed results. Ponce and colleagues² found decreased cyclic displacement and increased maximum load to failure with LTO, but Giuseffi and colleagues³² showed less cyclic displacement with ST and no difference in load to failure. Others authors have found no significant differences in stiffness or maximum load to failure.³³ Van den Berghe and colleagues⁷ reported a higher failure rate in bone-to-bone repairs compared with tendon-to-tendon constructs. Moreover, they found that suture cut-out through bone tunnels is the primary mode of LTO failure, so many LTO surgeons now pass sutures around the humeral stem instead.

Three TSA studies directly compared ST and LTO approaches. Buckley and colleagues¹⁴ analyzed 60 TSAs and found no significant differences in WOOS, DASH, or Constant scores between groups. The authors described an ST subgroup with subscapularis attenuation on ultrasound but did not report the group as having any inferior functional outcome. Scalise and colleagues¹⁵ showed improved strength and PSSs in both groups after 2 years. However, the LTO group had a lower rate of subscapularis tears and significantly higher PSSs. Finally, Jandhyala and colleagues¹⁶ reported more favorable outcomes with LTO, which trended toward wider ROM and significantly higher belly-press test grades. Lapner and colleagues³⁴ conducted a randomized, controlled trial (often referenced) and found no significant differences between the 2 groups in terms of strength or functional outcome at 2-year follow-up. Their study, however, included hemiarthroplasties and did not substratify the TSA population, so we did not include it in our review.

Our systematic review found significantly more forward elevation improvement for the ST group than the LTO group, which may suggest improved ROM with a soft-tissue approach than a bony approach. At the same time, the ST group trended toward better passive external rotation relative to the LTO group. This trend indicates fewer constraints to external rotation in the ST group, possibly attributable to a more attenuated subscapularis after tenotomy. Subscapularis tear or attenuation was more commonly reported in the ST group than in the LTO group, though not significantly so. This may indicate that more ST studies than LTO studies specially emphasized postoperative subscapularis function, but these data also highlight some authors’ concerns regarding subscapularis dysfunction after tenotomy.^6,15,16The study populations’ complication rates were similar, just over 17%. The LTO group trended toward a higher revision rate, but it was not statistically significant. The LTO group also had significantly fewer patients with osteoarthritis and more patients with posttraumatic arthritis, so this group may have had more complex patients predisposed to a higher likelihood of revision surgery. Revisions were most commonly performed for aseptic loosening; theoretically, if osteotomies heal less effectively than tenotomies, the LTO approach could produce component instability and aseptic loosening. However, no prior studies or other clinical findings from this review suggest LTO predisposes to aseptic loosening. Overall, the uneven revision rates represent a clinical concern that should be monitored as larger samples of patients undergo ST and LTO procedures.

Glenoid radiolucencies were the only radiographic parameter consistently reported in the included studies. Twelve ST studies had radiolucency data—compared with only 2 LTO studies. Thus, our ability to compare radiographic outcomes was limited. Our data revealed similar rates of glenoid radiolucencies between the 2 approaches. The clinical relevance of radiolucencies is questioned by some authors, and, indeed, Razmjou and colleagues²⁵ found no correlation of radiolucencies with patient satisfaction. Nevertheless, early presence of radiolucencies may raise concerns about progressive loss of fixation,^35,36 so this should be monitored.

Limitations of this systematic review reflect the studies analyzed. We minimized selection bias by including level I to IV evidence, but most studies were level IV, and only 1 was level I. As such, there was a relative paucity of consistent clinical and radiographic data. For instance, although many ST studies reported patient satisfaction as an outcomes measure, only 1 LTO study commented on it. Perhaps the relative novelty of the LTO approach has prompted some authors to focus more on technical details and less on reporting a variety of outcome measures. As mentioned earlier, the significance of radiolucency data is controversial, and determination of their presence or absence depends on the observer. A radiolucency found in one study may not qualify as one in a study that uses different criteria. However, lucency data were the most frequently and reliably reported radiographic parameter, so we deemed it the most appropriate method for comparing radiographic outcomes. Finally, the baseline differences in diagnosis between the ST and LTO groups complicated comparisons. We stratified the groups by component design because use of keeled or pegged implants or humeral cemented or press-fit stems was usually a uniform feature of each study—enabling removal of certain studies for data stratification. However, we were unable to stratify by original diagnosis because these groups were not stratified within the individual studies.

Conclusion

Our systematic review found similar Constant scores, pain scores, radiographic outcomes, and complication rates for the ST and LTO approaches. Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions. Although not definitive, these data suggest the ST approach may provide more stability over the long term, but additional comprehensive studies are needed to increase the sample size and the power of the trends elucidated in this review. According to the orthopedic literature, both techniques produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.

Am J Orthop. 2017;46(2):E131-E138. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• According to the orthopedic literature, ST and LTO for a TSA produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.
• Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions.
• ST and LTO approaches for a TSA result in similar Constant scores, pain scores, radiographic outcomes, and complication rates.

During total shoulder arthroplasty (TSA) exposure, the subscapularis muscle must be mobilized; its repair is crucial to the stability of the arthroplasty. The subscapularis is the largest rotator cuff muscle and has a contractile force equal to that of the other 3 muscles combined.^1,2 Traditionally it is mobilized with a tenotomy just medial to the tendon’s insertion onto the lesser tuberosity. Over the past 15 years, however, numerous authors have reported dysfunction after subscapularis tenotomy (ST). In 2003, Miller and colleagues³ reported that, at 2-year follow-up, almost 70% of patients had abnormal belly-press and liftoff tests, surrogate markers of subscapularis function. Other authors have found increased rates of anterior instability after subscapularis rupture.^4,5

In 2005, Gerber and colleagues⁶ introduced a technique for circumventing surgical division of the subscapularis. They described a lesser tuberosity osteotomy (LTO), in which the subscapularis tendon is detached with a bone fragment 5 mm to 10 mm in thickness and 3 cm to 4 cm in length. This approach was based on the premise that bone-to-bone healing is more reliable than tendon-to-tendon healing. Initial studies reported successful osteotomy healing, improved clinical outcome scores, and fewer abnormalities with belly-press and liftoff tests.^2,6 More recent literature, however, has questioned the necessity of LTO.^2,4,7-9We performed a systematic review to evaluate the literature, describe ST and LTO, and summarize the radiographic and clinical outcomes of both techniques. We hypothesized there would be no significant clinical differences between these approaches.

Methods

Search Strategy and Study Selection

Using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we systematically reviewed the literature.¹⁰ Searches were completed in September 2014 using the PubMed Medline database and the Cochrane Central Register of Clinical Trials. Two reviewers (Dr. Louie, Dr. Levy) independently performed the search and assessed eligibility of all relevant studies based on predetermined inclusion criteria. Disagreements between reviewers were resolved by discussion. Key word selection was designed to capture all English-language studies with clinical and/or radiographic outcomes and level I to IV evidence. We used an electronic search algorithm with key words and a series of NOT phrases to match certain exclusion criteria:

(((((((((((((((((((((((((((((((((((((total[Text Word]) AND shoulder[Title]) AND arthroplasty[Title] AND (English[lang]))) NOT reverse[Title/Abstract]) NOT hemiarthroplasty[Title]) NOT nonoperative[Title]) NOT nonsurgical[Title] AND (English[lang]))) NOT rheumatoid[Title/Abstract]) NOT inflammatory[Title/Abstract]) NOT elbow[Title/Abstract]) NOT wrist[Title/Abstract]) NOT hip[Title/Abstract]) NOT knee[Title/Abstract]) NOT ankle[Title/Abstract] AND (English[lang]))) NOT biomechanic[Title/Abstract]) NOT biomechanics[Title/Abstract]) NOT biomechanical [Title/Abstract]) NOT cadaveric[Title/Abstract]) NOT revision[Title]) NOT resurfacing[Title/Abstract]) NOT surface[Title/Abstract]) NOT interphalangeal[Title/Abstract] AND (English[lang]))) NOT radiostereometric[Title/Abstract] AND (English[lang]))) NOT cmc[Title/Abstract]) NOT carpometacarpal[Title/Abstract]) NOT cervical[Title/Abstract]) NOT histology[Title/Abstract]) NOT histological[Title/Abstract]) NOT collagen[Title/Abstract] AND (English[lang]))) NOT kinematic[Title/Abstract]) NOT kinematics[Title/Abstract] AND (English[lang]))) NOT vitro[Title/Abstract] AND (English[lang]))) NOT inverted[Title/Abstract]) NOT grammont[Title/Abstract]) NOT arthrodesis[Title/Abstract]) NOT fusion[Title/Abstract]) NOT reverse[Title/Abstract] AND (English[lang]))

Study exclusion criteria consisted of cadaveric, biomechanical, histologic, and kinematic results as well as analyses of nonoperative management, hemiarthroplasty, or reverse TSA. Studies were excluded if they did not report clinical and/or radiographic data. Minimum mean follow-up was 2 years. To discount the effect of other TSA technical innovations, we evaluated the same period for the 2 surgical approaches. The first study with clinical outcomes after LTO was published in early 2005,⁶ so all studies published before 2005 were excluded.

We reviewed all references within the studies included by the initial search algorithm: randomized control trials, retrospective and prospective cohort designs, case series, and treatment studies. Technical notes, review papers, letters to the editor, and level V evidence reviews were excluded. To avoid counting patients twice, we compared each study’s authors and data collection period with those of the other studies. If there was overlap in authorship, period, and place, only the study with the longer follow-up or more comprehensive data was included. All trials comparing ST and LTO were included. If the authors of a TSA study did not describe the approach used, that study was excluded from our review.

Data Extraction

We collected details of study design, sample size, and patient demographics (sex, age, hand dominance, primary diagnosis). We also abstracted surgical factors about the glenoid component (cemented vs uncemented; pegged vs keeled; all-polyethylene vs metal-backed) and the humeral component (cemented vs press-fit; stemmed vs stemless). Clinical outcomes included pain scores, functional scores, number of revisions, range of motion (ROM), and subscapularis-specific tests (eg, belly-press, liftoff). As pain scales varied between studies, all values were converted to a 10-point scoring scale (0 = no pain; 10 = maximum pain) for comparisons. Numerous functional outcome scores were reported, but the Constant score was the only one consistently used across studies, making it a good choice for comparisons. One study used Penn Shoulder Scores (PSSs) and directly compared ST and LTO groups, so its data were included. In addition, radiographic data were compiled: radiolucencies around the humeral stem and glenoid component, humeral head subluxation/migration, and osteotomy healing. The only consistent radiographic parameter available for comparisons between groups was the presence of radiolucencies.

The Modified Coleman Methodology Score (MCMS), described by Cowan and colleagues,¹¹ was used to evaluate the methodologic quality of each study. The MCMS is a 15-item instrument that has been used to assess both randomized and nonrandomized trials.^12,13 It has a scaled score ranging from 0 to 100 (85-100, excellent; 70-84, good; 55-69, fair; <55, poor). Study quality was not factored into the data synthesis analysis.

Statistical Analysis

Data are reported as weighted means and standard deviations. A mean was calculated for each study reporting on a respective data point and was then weighed according to the study sample size. The result was that the nonweighted means from studies with smaller samples did not carry as much weight as those from studies with larger samples. Student t tests and 2-way analysis of variance were used to compare the ST and LTO groups and assess differences over time (SPSS Version 18; IBM). An α of 0.05 was set as statistically significant.

Results

Twenty studies (1420 shoulders, 1392 patients) were included in the final dataset (Figure).^2,6,8,14-30 

The youngest patients in the ST and LTO groups were 22 years and 19 years of age, respectively.

Discussion

Our goal in this systematic review was to analyze outcomes associated with ST and LTO in a heterogenous TSA population. We hypothesized TSA with ST or LTO would produce similar clinical and radiographic outcomes. There were no significant differences in Constant scores, pain scores, radiolucencies, or complications between the 2 groups. The ST group showed trends toward wider ROM improvements and fewer revisions, but only the change in forward elevation was significant. The components used in the 2 groups were similar with the exception of a lack of keeled glenoids and cemented humeral stems in the LTO group; data stratification controlling for these differences revealed no change in outcomes.

The optimal method of subscapularis mobilization for TSA remains a source of debate. Jackson and colleagues²³ found significant improvements in Neer and DASH scores after ST. However, 7 of 15 patients ruptured the subscapularis after 6 months and had significantly lower DASH scores. In 2005, Gerber and colleagues⁶ first described the LTO technique as an alternative to ST. After a mean of 39 months, 89% of their patients had a negative belly-press test, and 75% had a normal liftoff test. Radiographic evaluation revealed that the osteotomized fragment had healed in an anatomical position in all shoulders. In a large case series, Small and colleagues²⁰ used radiographs and computed tomography to further investigate LTO healing rates and found that 89% of patients had bony union by 6 months and that smoking was a significant risk factor for nonunion.

Biomechanical studies comparing ST and LTO approaches have shown mixed results. Ponce and colleagues² found decreased cyclic displacement and increased maximum load to failure with LTO, but Giuseffi and colleagues³² showed less cyclic displacement with ST and no difference in load to failure. Others authors have found no significant differences in stiffness or maximum load to failure.³³ Van den Berghe and colleagues⁷ reported a higher failure rate in bone-to-bone repairs compared with tendon-to-tendon constructs. Moreover, they found that suture cut-out through bone tunnels is the primary mode of LTO failure, so many LTO surgeons now pass sutures around the humeral stem instead.

Three TSA studies directly compared ST and LTO approaches. Buckley and colleagues¹⁴ analyzed 60 TSAs and found no significant differences in WOOS, DASH, or Constant scores between groups. The authors described an ST subgroup with subscapularis attenuation on ultrasound but did not report the group as having any inferior functional outcome. Scalise and colleagues¹⁵ showed improved strength and PSSs in both groups after 2 years. However, the LTO group had a lower rate of subscapularis tears and significantly higher PSSs. Finally, Jandhyala and colleagues¹⁶ reported more favorable outcomes with LTO, which trended toward wider ROM and significantly higher belly-press test grades. Lapner and colleagues³⁴ conducted a randomized, controlled trial (often referenced) and found no significant differences between the 2 groups in terms of strength or functional outcome at 2-year follow-up. Their study, however, included hemiarthroplasties and did not substratify the TSA population, so we did not include it in our review.

Our systematic review found significantly more forward elevation improvement for the ST group than the LTO group, which may suggest improved ROM with a soft-tissue approach than a bony approach. At the same time, the ST group trended toward better passive external rotation relative to the LTO group. This trend indicates fewer constraints to external rotation in the ST group, possibly attributable to a more attenuated subscapularis after tenotomy. Subscapularis tear or attenuation was more commonly reported in the ST group than in the LTO group, though not significantly so. This may indicate that more ST studies than LTO studies specially emphasized postoperative subscapularis function, but these data also highlight some authors’ concerns regarding subscapularis dysfunction after tenotomy.^6,15,16The study populations’ complication rates were similar, just over 17%. The LTO group trended toward a higher revision rate, but it was not statistically significant. The LTO group also had significantly fewer patients with osteoarthritis and more patients with posttraumatic arthritis, so this group may have had more complex patients predisposed to a higher likelihood of revision surgery. Revisions were most commonly performed for aseptic loosening; theoretically, if osteotomies heal less effectively than tenotomies, the LTO approach could produce component instability and aseptic loosening. However, no prior studies or other clinical findings from this review suggest LTO predisposes to aseptic loosening. Overall, the uneven revision rates represent a clinical concern that should be monitored as larger samples of patients undergo ST and LTO procedures.

Glenoid radiolucencies were the only radiographic parameter consistently reported in the included studies. Twelve ST studies had radiolucency data—compared with only 2 LTO studies. Thus, our ability to compare radiographic outcomes was limited. Our data revealed similar rates of glenoid radiolucencies between the 2 approaches. The clinical relevance of radiolucencies is questioned by some authors, and, indeed, Razmjou and colleagues²⁵ found no correlation of radiolucencies with patient satisfaction. Nevertheless, early presence of radiolucencies may raise concerns about progressive loss of fixation,^35,36 so this should be monitored.

Limitations of this systematic review reflect the studies analyzed. We minimized selection bias by including level I to IV evidence, but most studies were level IV, and only 1 was level I. As such, there was a relative paucity of consistent clinical and radiographic data. For instance, although many ST studies reported patient satisfaction as an outcomes measure, only 1 LTO study commented on it. Perhaps the relative novelty of the LTO approach has prompted some authors to focus more on technical details and less on reporting a variety of outcome measures. As mentioned earlier, the significance of radiolucency data is controversial, and determination of their presence or absence depends on the observer. A radiolucency found in one study may not qualify as one in a study that uses different criteria. However, lucency data were the most frequently and reliably reported radiographic parameter, so we deemed it the most appropriate method for comparing radiographic outcomes. Finally, the baseline differences in diagnosis between the ST and LTO groups complicated comparisons. We stratified the groups by component design because use of keeled or pegged implants or humeral cemented or press-fit stems was usually a uniform feature of each study—enabling removal of certain studies for data stratification. However, we were unable to stratify by original diagnosis because these groups were not stratified within the individual studies.

Conclusion

Our systematic review found similar Constant scores, pain scores, radiographic outcomes, and complication rates for the ST and LTO approaches. Compared with the LTO approach, the ST approach produced significantly more forward elevation improvement and trended toward more external rotation and abduction and fewer revisions. Although not definitive, these data suggest the ST approach may provide more stability over the long term, but additional comprehensive studies are needed to increase the sample size and the power of the trends elucidated in this review. According to the orthopedic literature, both techniques produce excellent clinical outcomes, and technique selection should be based on surgeon discretion and expertise.

Am J Orthop. 2017;46(2):E131-E138. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

PHILADELPHIA – Despite combination therapies for hepatitis C virus (HCV) that are now showing high rates of sustained viral remission (SVR) across all genotypes, a one-size-fits-all treatment will not be practical in the near future, according to a review of current and coming HCV therapies at Digestive Diseases: New Advances meeting held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.

The focus for improving HCV care is “now shifting, I think, from this one-size-fits-all treatment to identifying, really, the one-size-fits all provider,” reported Kimberly A. Brown, MD, division head of gastroenterology/hepatology at Henry Ford Health System, Detroit.

Courtesy US. Dept of Veterans Affairs

PHILADELPHIA – Despite combination therapies for hepatitis C virus (HCV) that are now showing high rates of sustained viral remission (SVR) across all genotypes, a one-size-fits-all treatment will not be practical in the near future, according to a review of current and coming HCV therapies at Digestive Diseases: New Advances meeting held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.

The focus for improving HCV care is “now shifting, I think, from this one-size-fits-all treatment to identifying, really, the one-size-fits all provider,” reported Kimberly A. Brown, MD, division head of gastroenterology/hepatology at Henry Ford Health System, Detroit.

Courtesy US. Dept of Veterans Affairs

PHILADELPHIA – Despite combination therapies for hepatitis C virus (HCV) that are now showing high rates of sustained viral remission (SVR) across all genotypes, a one-size-fits-all treatment will not be practical in the near future, according to a review of current and coming HCV therapies at Digestive Diseases: New Advances meeting held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.

The focus for improving HCV care is “now shifting, I think, from this one-size-fits-all treatment to identifying, really, the one-size-fits all provider,” reported Kimberly A. Brown, MD, division head of gastroenterology/hepatology at Henry Ford Health System, Detroit.

Courtesy US. Dept of Veterans Affairs

Paraneoplastic palmoplantar keratoderma (PPK) is an acquired dermatosis that presents with hyperkeratosis of the palms and soles in association with visceral malignancies, such as esophageal, gastric, pulmonary, and bladder carcinomas. This condition may either be acquired or inherited.¹

Case Report

A 72-year-old woman was referred to our dermatology clinic for evaluation of a nonpruritic hyperkeratotic eruption predominantly on the palms and soles of 2 to 3 months’ duration (Figure 1A). Review of systems was remarkable for chronic anxiety, unintentional weight loss of 10 lb over the last 6 months, and a mild cough of 10 days’ duration. The differential diagnosis included eczematous dermatitis, tinea manuum, new-onset palmoplantar psoriasis, and PPK.

A punch biopsy of the medial hypothenar eminence of the left hand was performed, revealing notable lichenified hyperkeratosis with vascular ectasia (Figure 2). Periodic acid–Schiff staining was negative for fungal elements. Given the suspicion of PPK, multiple carcinoma markers were ordered. Cancer antigen 125 measured at 68 U/mL (reference range upper limit, 21 U/mL). Cancer antigen 27-29 was 50 U/mL (reference range, <38 U/mL) and cancer antigen 19-9 was 24 U/mL (reference range, <37 U/mL). Computed tomography of the chest revealed a large mass in the left lower lung associated with hilar lymphadenopathy. The patient was referred to oncology for further evaluation. Computed tomography–guided biopsy revealed metastatic uterine adenocarcinoma, which prompted subsequent chemotherapy. The combination of visceral malignancy with PPK led to the diagnosis of acquired PPK secondary to uterine cancer. After the completion of chemotherapy, the palmar dermatosis notably decreased (Figure 1B).

Comment

Paraneoplastic PPK is not uncommon. Ninety percent of acquired diffuse PPK is secondary to cancer,² which occurs more frequently in male patients. Associated visceral malignancies include localized esophageal,³ myeloma,⁴ pulmonary, urinary/bladder,⁵ and gastric carcinoma.⁶ Paraneoplastic PPK in women is rare but has been linked to ovarian and breast carcinoma.⁷

The findings under light microscopy include thickening of any or all of the cell layers of the epidermis, which can include hyperkeratosis, acanthosis, and papillomatosis (Figure 2). A moderate amount of mononuclear cell infiltrates also can be visualized.

Palmoplantar keratoderma associated with uterine malignancy is rare. However, many other paraneoplastic dermatoses resulting from uterine cancer have been described as well as nonuterine gynecological malignancies (Table).^8-17

The first step in managing acquired PPK is to determine its etiology via a complete history and a total-body skin examination. If findings are consistent with a hereditary PPK, then genetic workup is advised. Other suspected etiologies should be investigated via imaging and laboratory analysis.¹⁸

The first approach in managing acquired PPK is to treat the underlying cause. In prior cases, complete resolution of skin findings resulted once the malignancy or associated dermatosis had been treated.^8-17 Adjunctive medication includes topical keratolytics (eg, urea, salicylic acid, lactic acid), topical retinoids, topical psoralen plus UVA, and topical corticosteroids.¹⁸ Vitamin A analogues have been found to be an effective treatment of many hyperkeratotic dermatoses.¹⁹ Isotretinoin and etretinate have been used to treat the cutaneous findings and prevent the onset and progression of esophageal malignancy of the inherited forms of PPK. The oral retinoid acitretin has been shown to rapidly resolve lesions, have persistent effects after 5 months of cessation, and have minimal side effects. Thus, it has been suggested as the first-line treatment of chronic PPK.¹⁹ One study found no response to topical keratolytics (urea cream and salicylic acid ointment) and a 2-week course of oral prednisone; however, low-dose oral acitretin 10 mg once daily resulted in notable improvement over several weeks.⁷ Physical debridement also may be necessary.¹⁸

Conclusion

Palmoplantar keratoderma is a condition that presents with hyperkeratosis of the palms and soles. Acquired PPK often occurs as a paraneoplastic response as well as a stigma of other dermatoses. It occurs more frequently in male patients. Reports of PPK secondary to uterine cancer are not common in the literature. Management of PPK includes a complete history and total-body skin examination. After appropriate imaging and laboratory analysis, treatment of the underlying cause is the best approach. Adjunctive medications include topical keratolytics, topical retinoids, topical psoralen plus UVA, and topical corticosteroids. Oral isotretinoin and etretinate have demonstrated promising results.

Paraneoplastic palmoplantar keratoderma (PPK) is an acquired dermatosis that presents with hyperkeratosis of the palms and soles in association with visceral malignancies, such as esophageal, gastric, pulmonary, and bladder carcinomas. This condition may either be acquired or inherited.¹

Case Report

A 72-year-old woman was referred to our dermatology clinic for evaluation of a nonpruritic hyperkeratotic eruption predominantly on the palms and soles of 2 to 3 months’ duration (Figure 1A). Review of systems was remarkable for chronic anxiety, unintentional weight loss of 10 lb over the last 6 months, and a mild cough of 10 days’ duration. The differential diagnosis included eczematous dermatitis, tinea manuum, new-onset palmoplantar psoriasis, and PPK.

A punch biopsy of the medial hypothenar eminence of the left hand was performed, revealing notable lichenified hyperkeratosis with vascular ectasia (Figure 2). Periodic acid–Schiff staining was negative for fungal elements. Given the suspicion of PPK, multiple carcinoma markers were ordered. Cancer antigen 125 measured at 68 U/mL (reference range upper limit, 21 U/mL). Cancer antigen 27-29 was 50 U/mL (reference range, <38 U/mL) and cancer antigen 19-9 was 24 U/mL (reference range, <37 U/mL). Computed tomography of the chest revealed a large mass in the left lower lung associated with hilar lymphadenopathy. The patient was referred to oncology for further evaluation. Computed tomography–guided biopsy revealed metastatic uterine adenocarcinoma, which prompted subsequent chemotherapy. The combination of visceral malignancy with PPK led to the diagnosis of acquired PPK secondary to uterine cancer. After the completion of chemotherapy, the palmar dermatosis notably decreased (Figure 1B).

Comment

Paraneoplastic PPK is not uncommon. Ninety percent of acquired diffuse PPK is secondary to cancer,² which occurs more frequently in male patients. Associated visceral malignancies include localized esophageal,³ myeloma,⁴ pulmonary, urinary/bladder,⁵ and gastric carcinoma.⁶ Paraneoplastic PPK in women is rare but has been linked to ovarian and breast carcinoma.⁷

The findings under light microscopy include thickening of any or all of the cell layers of the epidermis, which can include hyperkeratosis, acanthosis, and papillomatosis (Figure 2). A moderate amount of mononuclear cell infiltrates also can be visualized.

Palmoplantar keratoderma associated with uterine malignancy is rare. However, many other paraneoplastic dermatoses resulting from uterine cancer have been described as well as nonuterine gynecological malignancies (Table).^8-17

The first step in managing acquired PPK is to determine its etiology via a complete history and a total-body skin examination. If findings are consistent with a hereditary PPK, then genetic workup is advised. Other suspected etiologies should be investigated via imaging and laboratory analysis.¹⁸

The first approach in managing acquired PPK is to treat the underlying cause. In prior cases, complete resolution of skin findings resulted once the malignancy or associated dermatosis had been treated.^8-17 Adjunctive medication includes topical keratolytics (eg, urea, salicylic acid, lactic acid), topical retinoids, topical psoralen plus UVA, and topical corticosteroids.¹⁸ Vitamin A analogues have been found to be an effective treatment of many hyperkeratotic dermatoses.¹⁹ Isotretinoin and etretinate have been used to treat the cutaneous findings and prevent the onset and progression of esophageal malignancy of the inherited forms of PPK. The oral retinoid acitretin has been shown to rapidly resolve lesions, have persistent effects after 5 months of cessation, and have minimal side effects. Thus, it has been suggested as the first-line treatment of chronic PPK.¹⁹ One study found no response to topical keratolytics (urea cream and salicylic acid ointment) and a 2-week course of oral prednisone; however, low-dose oral acitretin 10 mg once daily resulted in notable improvement over several weeks.⁷ Physical debridement also may be necessary.¹⁸

Conclusion

Palmoplantar keratoderma is a condition that presents with hyperkeratosis of the palms and soles. Acquired PPK often occurs as a paraneoplastic response as well as a stigma of other dermatoses. It occurs more frequently in male patients. Reports of PPK secondary to uterine cancer are not common in the literature. Management of PPK includes a complete history and total-body skin examination. After appropriate imaging and laboratory analysis, treatment of the underlying cause is the best approach. Adjunctive medications include topical keratolytics, topical retinoids, topical psoralen plus UVA, and topical corticosteroids. Oral isotretinoin and etretinate have demonstrated promising results.

Paraneoplastic palmoplantar keratoderma (PPK) is an acquired dermatosis that presents with hyperkeratosis of the palms and soles in association with visceral malignancies, such as esophageal, gastric, pulmonary, and bladder carcinomas. This condition may either be acquired or inherited.¹

Case Report

A 72-year-old woman was referred to our dermatology clinic for evaluation of a nonpruritic hyperkeratotic eruption predominantly on the palms and soles of 2 to 3 months’ duration (Figure 1A). Review of systems was remarkable for chronic anxiety, unintentional weight loss of 10 lb over the last 6 months, and a mild cough of 10 days’ duration. The differential diagnosis included eczematous dermatitis, tinea manuum, new-onset palmoplantar psoriasis, and PPK.

A punch biopsy of the medial hypothenar eminence of the left hand was performed, revealing notable lichenified hyperkeratosis with vascular ectasia (Figure 2). Periodic acid–Schiff staining was negative for fungal elements. Given the suspicion of PPK, multiple carcinoma markers were ordered. Cancer antigen 125 measured at 68 U/mL (reference range upper limit, 21 U/mL). Cancer antigen 27-29 was 50 U/mL (reference range, <38 U/mL) and cancer antigen 19-9 was 24 U/mL (reference range, <37 U/mL). Computed tomography of the chest revealed a large mass in the left lower lung associated with hilar lymphadenopathy. The patient was referred to oncology for further evaluation. Computed tomography–guided biopsy revealed metastatic uterine adenocarcinoma, which prompted subsequent chemotherapy. The combination of visceral malignancy with PPK led to the diagnosis of acquired PPK secondary to uterine cancer. After the completion of chemotherapy, the palmar dermatosis notably decreased (Figure 1B).

Comment

Paraneoplastic PPK is not uncommon. Ninety percent of acquired diffuse PPK is secondary to cancer,² which occurs more frequently in male patients. Associated visceral malignancies include localized esophageal,³ myeloma,⁴ pulmonary, urinary/bladder,⁵ and gastric carcinoma.⁶ Paraneoplastic PPK in women is rare but has been linked to ovarian and breast carcinoma.⁷

The findings under light microscopy include thickening of any or all of the cell layers of the epidermis, which can include hyperkeratosis, acanthosis, and papillomatosis (Figure 2). A moderate amount of mononuclear cell infiltrates also can be visualized.

Palmoplantar keratoderma associated with uterine malignancy is rare. However, many other paraneoplastic dermatoses resulting from uterine cancer have been described as well as nonuterine gynecological malignancies (Table).^8-17

The first step in managing acquired PPK is to determine its etiology via a complete history and a total-body skin examination. If findings are consistent with a hereditary PPK, then genetic workup is advised. Other suspected etiologies should be investigated via imaging and laboratory analysis.¹⁸

The first approach in managing acquired PPK is to treat the underlying cause. In prior cases, complete resolution of skin findings resulted once the malignancy or associated dermatosis had been treated.^8-17 Adjunctive medication includes topical keratolytics (eg, urea, salicylic acid, lactic acid), topical retinoids, topical psoralen plus UVA, and topical corticosteroids.¹⁸ Vitamin A analogues have been found to be an effective treatment of many hyperkeratotic dermatoses.¹⁹ Isotretinoin and etretinate have been used to treat the cutaneous findings and prevent the onset and progression of esophageal malignancy of the inherited forms of PPK. The oral retinoid acitretin has been shown to rapidly resolve lesions, have persistent effects after 5 months of cessation, and have minimal side effects. Thus, it has been suggested as the first-line treatment of chronic PPK.¹⁹ One study found no response to topical keratolytics (urea cream and salicylic acid ointment) and a 2-week course of oral prednisone; however, low-dose oral acitretin 10 mg once daily resulted in notable improvement over several weeks.⁷ Physical debridement also may be necessary.¹⁸

Conclusion

Palmoplantar keratoderma is a condition that presents with hyperkeratosis of the palms and soles. Acquired PPK often occurs as a paraneoplastic response as well as a stigma of other dermatoses. It occurs more frequently in male patients. Reports of PPK secondary to uterine cancer are not common in the literature. Management of PPK includes a complete history and total-body skin examination. After appropriate imaging and laboratory analysis, treatment of the underlying cause is the best approach. Adjunctive medications include topical keratolytics, topical retinoids, topical psoralen plus UVA, and topical corticosteroids. Oral isotretinoin and etretinate have demonstrated promising results.

A new low-cost rotavirus gastroenteritis vaccine that does not require cold storage showed a vaccine efficacy of 67% in a per-protocol test of 3,508 Nigerien infants, according to a study by Sheila Isanaka of the department of research at Epicentre, Paris, and her associates.

In a double blind, placebo-controlled test of the oral bovine rotavirus pentavalent vaccine (BRV-PV), 31 severe cases of rotavirus were found in the vaccinated group of 1,780, while 87 cases were found in the placebo group of 1,728 (2.14 vs. 6.44 cases per 100 person-years, respectively), according to Ms. Isanaka and her colleagues (N Engl J Med. 2017 Mar 23;376[12]:1121-30).

Researchers gathered infants with severe symptoms and administered three injections of either BRV-PV or the placebo from August 2014 through November 2015. The BRV-PV vaccine, manufactured by Serum Institute of India, contains the rotavirus serotypes G1, G2, G3, G4, and G9.

CDC/Dr. Erskine Palmer

[email protected]

On Twitter @EAZTweets

A new low-cost rotavirus gastroenteritis vaccine that does not require cold storage showed a vaccine efficacy of 67% in a per-protocol test of 3,508 Nigerien infants, according to a study by Sheila Isanaka of the department of research at Epicentre, Paris, and her associates.

In a double blind, placebo-controlled test of the oral bovine rotavirus pentavalent vaccine (BRV-PV), 31 severe cases of rotavirus were found in the vaccinated group of 1,780, while 87 cases were found in the placebo group of 1,728 (2.14 vs. 6.44 cases per 100 person-years, respectively), according to Ms. Isanaka and her colleagues (N Engl J Med. 2017 Mar 23;376[12]:1121-30).

Researchers gathered infants with severe symptoms and administered three injections of either BRV-PV or the placebo from August 2014 through November 2015. The BRV-PV vaccine, manufactured by Serum Institute of India, contains the rotavirus serotypes G1, G2, G3, G4, and G9.

CDC/Dr. Erskine Palmer

[email protected]

On Twitter @EAZTweets

A new low-cost rotavirus gastroenteritis vaccine that does not require cold storage showed a vaccine efficacy of 67% in a per-protocol test of 3,508 Nigerien infants, according to a study by Sheila Isanaka of the department of research at Epicentre, Paris, and her associates.

In a double blind, placebo-controlled test of the oral bovine rotavirus pentavalent vaccine (BRV-PV), 31 severe cases of rotavirus were found in the vaccinated group of 1,780, while 87 cases were found in the placebo group of 1,728 (2.14 vs. 6.44 cases per 100 person-years, respectively), according to Ms. Isanaka and her colleagues (N Engl J Med. 2017 Mar 23;376[12]:1121-30).

Researchers gathered infants with severe symptoms and administered three injections of either BRV-PV or the placebo from August 2014 through November 2015. The BRV-PV vaccine, manufactured by Serum Institute of India, contains the rotavirus serotypes G1, G2, G3, G4, and G9.

CDC/Dr. Erskine Palmer

[email protected]

On Twitter @EAZTweets

ORLANDO – A greasy hamburger and fries and a chocolate milkshake may all earn the finger of blame when teens fret over acne. But which of these foods is the real culprit?

A growing body of data suggests it may be the milk – especially if it’s fat-free milk, according to Andrea Zaenglein, MD, who spoke at the annual meeting of the American Academy of Dermatology. Skim milk has been at the center of a long-simmering acne controversy, said Dr. Zaenglein, professor of dermatology and pediatric dermatology at Pennsylvania State University, Hershey.

Wikimedia Commons

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On Twitter @alz_gal

ORLANDO – A greasy hamburger and fries and a chocolate milkshake may all earn the finger of blame when teens fret over acne. But which of these foods is the real culprit?

A growing body of data suggests it may be the milk – especially if it’s fat-free milk, according to Andrea Zaenglein, MD, who spoke at the annual meeting of the American Academy of Dermatology. Skim milk has been at the center of a long-simmering acne controversy, said Dr. Zaenglein, professor of dermatology and pediatric dermatology at Pennsylvania State University, Hershey.

Wikimedia Commons

[email protected]

On Twitter @alz_gal

ORLANDO – A greasy hamburger and fries and a chocolate milkshake may all earn the finger of blame when teens fret over acne. But which of these foods is the real culprit?

A growing body of data suggests it may be the milk – especially if it’s fat-free milk, according to Andrea Zaenglein, MD, who spoke at the annual meeting of the American Academy of Dermatology. Skim milk has been at the center of a long-simmering acne controversy, said Dr. Zaenglein, professor of dermatology and pediatric dermatology at Pennsylvania State University, Hershey.

Wikimedia Commons

[email protected]

On Twitter @alz_gal

PHILADELPHIA – The road to absolute cure of hepatitis B virus (HBV) is so well understood that the strategies now being actively pursued may conceivably eliminate this infection from the human population, according to a summary of progress presented at Digestive Diseases: New Advances.

“As in HIV and hepatitis C infections, combination therapies of drugs with different mechanisms of action will be the solution. Which combination will deliver the ultimate cure is yet to be determined, but within 5 years we should have a cure,” reported Vinod K. Rustgi, MD, chief of hepatology at Robert Wood Johnson Medical School, New Brunswick, N.J.

The biggest hurdle to cure may be clearing covalently closed circular DNA (cccDNA) from the hepatocytes of HBV-infected individuals. This structure is derived from cytoplasmic capsid–relaxed circular DNA (rcDNA) and creates a transcriptional template in the nucleus of hepatocytes. This HBV reservoir has been thus far resistant to therapy. According to Dr. Rustgi, eliminating cccDNA along with integrated HBV RNA sequences represents the final two milestones in the road to cure. There are at least theoretical approaches to eliminating both obstacles.

For many patients, available therapies already provide a functional cure of HBV, defined as viral loads below detection. Long-term data show that such patients can anticipate a lifespan equivalent to those without HBV infection, according to Dr. Rustgi, who listed this as one of the three milestones on the road to cure that have already been achieved. The first milestone was identified as a simple reduction in viral load. The second was anti-HBe seroconversion, which can be achieved in most with available treatments. Following functional cure, the fourth milestone, clearance of HBsAg antigen, is not yet reliably achieved, although this has been documented in a proportion of patients on the most effective long-term regimens.

Understanding these milestones is important, because each has prognostic relevance, according to Dr. Rustgi. Noting the direct correlation between increasing levels of serum HBV DNA and risk of hepatocellular carcinoma (HCC) over time, he indicated that reducing HBV DNA replication already reduces risk of complications. It is possible that virologic cure, which he defined as a stable off-drug suppression of HBV viremia and normalization of liver function tests, may be achieved in a larger proportion of patients with more potent versions of existing therapies. However, absolute cure, which includes complete clearance of cccDNA and other integrated HBV DNA, is the ultimate goal. It is expected that complete clearance will eliminate the threat of HCC or other liver complications.

Based on what is understood about HBV infection, increasing the potency of nucleoside analogues, which are the mainstay of current HBV therapy, will only go so far toward absolute cure. These drugs reduce viral replication to prevent liver damage. Although new drugs to prevent cccDNA formation and HBV life cycle events such as capsid assembly and HBeAg expression may further improve outcomes, they still may not be curative without better host defenses.

“One of the ways for trying to get rid of the virus is restoration of antiviral immunity, and there are several strategies to accomplish this,” reported Dr. Rustgi, citing active efforts to mobilize T cells that attack the virus and create toll-like receptor agonists, which play a key role in the innate immune response. He suggested that several strategies now demonstrating benefit in cancer, such as blocking proteins involved in the inhibition of the immune response, are being explored in the treatment of HBV. All of these strategies may be needed.

“No single approach will be sufficient to deliver a cure,” maintained Dr. Rustgi, outlining the many mechanisms HBV employs to defend against eradication. However, he provided a long list of HBV-targeted drugs and immunotherapies, including vaccines, which are now in clinical trials, enabling combinations to attack this infection from multiple fronts.

“A curative regimen might consist of an HBV antigen inhibitor, an immune activator, a cccDNA inhibitor, and a potent nucleoside analogue,” Dr. Rustgi said. Despite the multiple mechanisms that HBV now employs to evade eradication, there are now strategies being pursued to address most of the known vulnerabilities, he said. “I hope I have given you an idea where we are going.”

Digestive Diseases: New Advances was held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company. Dr. Rustgi reported financial relationships with AbbVie, Gilead, Innovimmune, Intercept, and Merck.

PHILADELPHIA – The road to absolute cure of hepatitis B virus (HBV) is so well understood that the strategies now being actively pursued may conceivably eliminate this infection from the human population, according to a summary of progress presented at Digestive Diseases: New Advances.

“As in HIV and hepatitis C infections, combination therapies of drugs with different mechanisms of action will be the solution. Which combination will deliver the ultimate cure is yet to be determined, but within 5 years we should have a cure,” reported Vinod K. Rustgi, MD, chief of hepatology at Robert Wood Johnson Medical School, New Brunswick, N.J.

The biggest hurdle to cure may be clearing covalently closed circular DNA (cccDNA) from the hepatocytes of HBV-infected individuals. This structure is derived from cytoplasmic capsid–relaxed circular DNA (rcDNA) and creates a transcriptional template in the nucleus of hepatocytes. This HBV reservoir has been thus far resistant to therapy. According to Dr. Rustgi, eliminating cccDNA along with integrated HBV RNA sequences represents the final two milestones in the road to cure. There are at least theoretical approaches to eliminating both obstacles.

For many patients, available therapies already provide a functional cure of HBV, defined as viral loads below detection. Long-term data show that such patients can anticipate a lifespan equivalent to those without HBV infection, according to Dr. Rustgi, who listed this as one of the three milestones on the road to cure that have already been achieved. The first milestone was identified as a simple reduction in viral load. The second was anti-HBe seroconversion, which can be achieved in most with available treatments. Following functional cure, the fourth milestone, clearance of HBsAg antigen, is not yet reliably achieved, although this has been documented in a proportion of patients on the most effective long-term regimens.

Understanding these milestones is important, because each has prognostic relevance, according to Dr. Rustgi. Noting the direct correlation between increasing levels of serum HBV DNA and risk of hepatocellular carcinoma (HCC) over time, he indicated that reducing HBV DNA replication already reduces risk of complications. It is possible that virologic cure, which he defined as a stable off-drug suppression of HBV viremia and normalization of liver function tests, may be achieved in a larger proportion of patients with more potent versions of existing therapies. However, absolute cure, which includes complete clearance of cccDNA and other integrated HBV DNA, is the ultimate goal. It is expected that complete clearance will eliminate the threat of HCC or other liver complications.

Based on what is understood about HBV infection, increasing the potency of nucleoside analogues, which are the mainstay of current HBV therapy, will only go so far toward absolute cure. These drugs reduce viral replication to prevent liver damage. Although new drugs to prevent cccDNA formation and HBV life cycle events such as capsid assembly and HBeAg expression may further improve outcomes, they still may not be curative without better host defenses.

“One of the ways for trying to get rid of the virus is restoration of antiviral immunity, and there are several strategies to accomplish this,” reported Dr. Rustgi, citing active efforts to mobilize T cells that attack the virus and create toll-like receptor agonists, which play a key role in the innate immune response. He suggested that several strategies now demonstrating benefit in cancer, such as blocking proteins involved in the inhibition of the immune response, are being explored in the treatment of HBV. All of these strategies may be needed.

“No single approach will be sufficient to deliver a cure,” maintained Dr. Rustgi, outlining the many mechanisms HBV employs to defend against eradication. However, he provided a long list of HBV-targeted drugs and immunotherapies, including vaccines, which are now in clinical trials, enabling combinations to attack this infection from multiple fronts.

“A curative regimen might consist of an HBV antigen inhibitor, an immune activator, a cccDNA inhibitor, and a potent nucleoside analogue,” Dr. Rustgi said. Despite the multiple mechanisms that HBV now employs to evade eradication, there are now strategies being pursued to address most of the known vulnerabilities, he said. “I hope I have given you an idea where we are going.”

Digestive Diseases: New Advances was held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company. Dr. Rustgi reported financial relationships with AbbVie, Gilead, Innovimmune, Intercept, and Merck.

PHILADELPHIA – The road to absolute cure of hepatitis B virus (HBV) is so well understood that the strategies now being actively pursued may conceivably eliminate this infection from the human population, according to a summary of progress presented at Digestive Diseases: New Advances.

“As in HIV and hepatitis C infections, combination therapies of drugs with different mechanisms of action will be the solution. Which combination will deliver the ultimate cure is yet to be determined, but within 5 years we should have a cure,” reported Vinod K. Rustgi, MD, chief of hepatology at Robert Wood Johnson Medical School, New Brunswick, N.J.

The biggest hurdle to cure may be clearing covalently closed circular DNA (cccDNA) from the hepatocytes of HBV-infected individuals. This structure is derived from cytoplasmic capsid–relaxed circular DNA (rcDNA) and creates a transcriptional template in the nucleus of hepatocytes. This HBV reservoir has been thus far resistant to therapy. According to Dr. Rustgi, eliminating cccDNA along with integrated HBV RNA sequences represents the final two milestones in the road to cure. There are at least theoretical approaches to eliminating both obstacles.

For many patients, available therapies already provide a functional cure of HBV, defined as viral loads below detection. Long-term data show that such patients can anticipate a lifespan equivalent to those without HBV infection, according to Dr. Rustgi, who listed this as one of the three milestones on the road to cure that have already been achieved. The first milestone was identified as a simple reduction in viral load. The second was anti-HBe seroconversion, which can be achieved in most with available treatments. Following functional cure, the fourth milestone, clearance of HBsAg antigen, is not yet reliably achieved, although this has been documented in a proportion of patients on the most effective long-term regimens.

Understanding these milestones is important, because each has prognostic relevance, according to Dr. Rustgi. Noting the direct correlation between increasing levels of serum HBV DNA and risk of hepatocellular carcinoma (HCC) over time, he indicated that reducing HBV DNA replication already reduces risk of complications. It is possible that virologic cure, which he defined as a stable off-drug suppression of HBV viremia and normalization of liver function tests, may be achieved in a larger proportion of patients with more potent versions of existing therapies. However, absolute cure, which includes complete clearance of cccDNA and other integrated HBV DNA, is the ultimate goal. It is expected that complete clearance will eliminate the threat of HCC or other liver complications.

Based on what is understood about HBV infection, increasing the potency of nucleoside analogues, which are the mainstay of current HBV therapy, will only go so far toward absolute cure. These drugs reduce viral replication to prevent liver damage. Although new drugs to prevent cccDNA formation and HBV life cycle events such as capsid assembly and HBeAg expression may further improve outcomes, they still may not be curative without better host defenses.

“One of the ways for trying to get rid of the virus is restoration of antiviral immunity, and there are several strategies to accomplish this,” reported Dr. Rustgi, citing active efforts to mobilize T cells that attack the virus and create toll-like receptor agonists, which play a key role in the innate immune response. He suggested that several strategies now demonstrating benefit in cancer, such as blocking proteins involved in the inhibition of the immune response, are being explored in the treatment of HBV. All of these strategies may be needed.

“No single approach will be sufficient to deliver a cure,” maintained Dr. Rustgi, outlining the many mechanisms HBV employs to defend against eradication. However, he provided a long list of HBV-targeted drugs and immunotherapies, including vaccines, which are now in clinical trials, enabling combinations to attack this infection from multiple fronts.

“A curative regimen might consist of an HBV antigen inhibitor, an immune activator, a cccDNA inhibitor, and a potent nucleoside analogue,” Dr. Rustgi said. Despite the multiple mechanisms that HBV now employs to evade eradication, there are now strategies being pursued to address most of the known vulnerabilities, he said. “I hope I have given you an idea where we are going.”

Digestive Diseases: New Advances was held by Rutgers, the State University of New Jersey, and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company. Dr. Rustgi reported financial relationships with AbbVie, Gilead, Innovimmune, Intercept, and Merck.

It’s early days for research on the physical impact of robot-assisted surgery on operators. But a study of surgeons who regularly do this kind of work suggests that surgical robots can be the cause of workplace injuries, despite their reputation for good ergonomic design and low stress on surgeon hands, wrists, backs, and necks

More than half (236) of 432 surveyed surgeons with at least 10 robotic surgeries annually reported physical discomfort associated with robotics consoles, according to a study out of Johns Hopkins University, Baltimore.

Remains/Thinkstock

Researchers declared no relevant financial disclosures.

[email protected]

On Twitter @EAZTweets

It’s early days for research on the physical impact of robot-assisted surgery on operators. But a study of surgeons who regularly do this kind of work suggests that surgical robots can be the cause of workplace injuries, despite their reputation for good ergonomic design and low stress on surgeon hands, wrists, backs, and necks

More than half (236) of 432 surveyed surgeons with at least 10 robotic surgeries annually reported physical discomfort associated with robotics consoles, according to a study out of Johns Hopkins University, Baltimore.

Remains/Thinkstock

Researchers declared no relevant financial disclosures.

[email protected]

On Twitter @EAZTweets

It’s early days for research on the physical impact of robot-assisted surgery on operators. But a study of surgeons who regularly do this kind of work suggests that surgical robots can be the cause of workplace injuries, despite their reputation for good ergonomic design and low stress on surgeon hands, wrists, backs, and necks

More than half (236) of 432 surveyed surgeons with at least 10 robotic surgeries annually reported physical discomfort associated with robotics consoles, according to a study out of Johns Hopkins University, Baltimore.

Remains/Thinkstock

Researchers declared no relevant financial disclosures.

[email protected]

On Twitter @EAZTweets

NATIONAL HARBOR, MD – Start small, but anticipate growth. Engage your administration from the start. Be smart about resources, and consider using advanced practice providers to keep costs down. Above all, keep lines of communication open with physicians and other members of the care team.

In a video interview, Joanne Rash, PA-C, a certified physician assistant at the University of Wisconsin–Madison offers these and other tips. She explains her collaborative work with David Kushner, MD, director of the gynecologic oncology program and professor at the University of Wisconsin School of Medicine and Public Health, and a colleague to develop the Women’s Integrative Sexual Health (WISH) program.

WISH is modeled on the University of Chicago’s Program in Integrative Sex and Medicine for Women and Girls with Cancer (PRISM) and participates in the PRISM registry, which studies ways to prevent and treat sexual problems for women and girls with cancer.

“I think what makes the WISH program unique is that we carve time out,” said Ms. Rash. “Of course, we address some of these issues in my gynecologic oncology practice, but, when we do it in WISH, the format is different,” and there’s just more time for discussion.

Communication is key to the model’s success in safe integration of sexual health into cancer care, she said. “We certainly don’t want to do something that compromises cancer care, and so, it’s important that we have those conversations with that woman’s team. And now we get to be a part of that team, which is a real privilege.”

Ms. Rash reported no conflicts of interest.

[email protected]

On Twitter @karioakes

NATIONAL HARBOR, MD – Start small, but anticipate growth. Engage your administration from the start. Be smart about resources, and consider using advanced practice providers to keep costs down. Above all, keep lines of communication open with physicians and other members of the care team.

In a video interview, Joanne Rash, PA-C, a certified physician assistant at the University of Wisconsin–Madison offers these and other tips. She explains her collaborative work with David Kushner, MD, director of the gynecologic oncology program and professor at the University of Wisconsin School of Medicine and Public Health, and a colleague to develop the Women’s Integrative Sexual Health (WISH) program.

WISH is modeled on the University of Chicago’s Program in Integrative Sex and Medicine for Women and Girls with Cancer (PRISM) and participates in the PRISM registry, which studies ways to prevent and treat sexual problems for women and girls with cancer.

“I think what makes the WISH program unique is that we carve time out,” said Ms. Rash. “Of course, we address some of these issues in my gynecologic oncology practice, but, when we do it in WISH, the format is different,” and there’s just more time for discussion.

Communication is key to the model’s success in safe integration of sexual health into cancer care, she said. “We certainly don’t want to do something that compromises cancer care, and so, it’s important that we have those conversations with that woman’s team. And now we get to be a part of that team, which is a real privilege.”

Ms. Rash reported no conflicts of interest.

[email protected]

On Twitter @karioakes

NATIONAL HARBOR, MD – Start small, but anticipate growth. Engage your administration from the start. Be smart about resources, and consider using advanced practice providers to keep costs down. Above all, keep lines of communication open with physicians and other members of the care team.

In a video interview, Joanne Rash, PA-C, a certified physician assistant at the University of Wisconsin–Madison offers these and other tips. She explains her collaborative work with David Kushner, MD, director of the gynecologic oncology program and professor at the University of Wisconsin School of Medicine and Public Health, and a colleague to develop the Women’s Integrative Sexual Health (WISH) program.

WISH is modeled on the University of Chicago’s Program in Integrative Sex and Medicine for Women and Girls with Cancer (PRISM) and participates in the PRISM registry, which studies ways to prevent and treat sexual problems for women and girls with cancer.

“I think what makes the WISH program unique is that we carve time out,” said Ms. Rash. “Of course, we address some of these issues in my gynecologic oncology practice, but, when we do it in WISH, the format is different,” and there’s just more time for discussion.

Communication is key to the model’s success in safe integration of sexual health into cancer care, she said. “We certainly don’t want to do something that compromises cancer care, and so, it’s important that we have those conversations with that woman’s team. And now we get to be a part of that team, which is a real privilege.”

Ms. Rash reported no conflicts of interest.

[email protected]

On Twitter @karioakes