Weight history of individuals with and without physical disability in the International Weight Control Registry.

Background: People with physical disabilities (PWD) have an increased risk of obesity and related comorbidities compared with people without physical disabilities (PWoD). Previously identified contributors to weight loss maintenance pose challenges to PWD. However, it is not known if PWD experience less success in weight management. Methods: Six hundred and nine participants in the International Weight Control Registry (IWCR) were eligible for this analysis (PWD, n = 174; PWoD, n = 435). Self-reported weight history metrics were compared using general linear models. Perceived weight history category was compared using Chi-squared tests. Importance of diet and physical activity strategies for weight management were compared using Wilcoxon rank-signed tests. Results: PWD reported higher current body mass index (BMI) (36.1 ± 0.7 vs. 31.0 ± 0.5; p < 0.0001) and more weight loss attempts (9.1 ± 0.7 vs. 7.1 ± 0.4; p = 0.01) than PWoD. Current weight loss percentage (PWD 13.0 ± 1.0; PWoD, 13.0 ± 0.6; p = 0.97) and weight loss category (χ 2 [3, N = 609] = 2.9057, p = 0.41) did not differ between the groups. There were no differences in any weight strategy between PWD who were successful and those who regained. Conclusions: PWD and PWoD in the IWCR achieved similar levels of weight maintenance success. However, higher BMI and more weight loss attempts suggest that PWD may face challenges with weight management. More research is needed to identify strategies leading to success for PWD.

Reliability and Validity of the International Physical Activity Questionnaire Adapted to Include Adults With Physical Disability.

BACKGROUND: People with physical disabilities (PWD) participate in less physical activity than people without physical disabilities (PWoD), which increases the risk for several negative health consequences. Comparing physical activity between PWD and PWoD remains a challenge since no reliable and valid survey exists to measure physical activity in both populations. The International Physical Activity Questionnaire (IPAQ) was adapted to be inclusive of PWD using a recently developed survey adaption framework; however, the adapted IPAQ has not been assessed for reliability and validity. The objective of this study was to assess the reliability and validity of the adapted IPAQ. METHODS: To assess test-retest reliability, the adapted IPAQ was completed twice within a 72-hour period by 172 individuals (PWD: n = 102, PWoD: n = 70) and compared using intraclass correlation coefficients. Using Spearman rho, convergent validity and construct validity were assessed in 62 individuals by comparing the adapted IPAQ against the original instrument and activity monitor measured step count, respectively. RESULTS: The adapted IPAQ demonstrated moderate test-retest reliability, with intraclass correlation coefficients of total scores for the total sample of .690 (95% confidence interval [CI] .581-.770) and among subgroup analysis (PWD, .640, 95% CI, .457-.761; PWoD, .758, 95% CI, .610-.850). Correlation coefficients were also good for the assessment of convergent validity of total score (.727; 95% CI, .579-.829; P < .001). Construct validity assessment yielded moderate coefficient (.406; 95% CI, .166-.596; P = .001). CONCLUSIONS: The adapted IPAQ demonstrated acceptable reliability and validity and is appropriate for use in PWD and PWoD.

Technical report: an online international weight control registry to inform precision approaches to healthy weight management.

BACKGROUND: Personalizing approaches to prevention and treatment of obesity will be a crucial aspect of precision health initiatives. However, in considering individual susceptibility to obesity, much remains to be learned about how to support healthy weight management in different population subgroups, environments and geographical locations. SUBJECTS/METHODS: The International Weight Control Registry (IWCR) has been launched to facilitate a deeper and broader understanding of the spectrum of factors contributing to success and challenges in weight loss and weight loss maintenance in individuals and across population groups. The IWCR registry aims to recruit, enroll and follow a diverse cohort of adults with varying rates of success in weight management. Data collection methods include questionnaires of demographic variables, weight history, and behavioral, cultural, economic, psychological, and environmental domains. A subset of participants will provide objective measures of physical activity, weight, and body composition along with detailed reports of dietary intake. Lastly, participants will be able to provide qualitative information in an unstructured format on additional topics they feel are relevant, and environmental data will be obtained from public sources based on participant zip code. CONCLUSIONS: The IWCR will be a resource for researchers to inform improvements in interventions for weight loss and weight loss maintenance in different countries, and to examine environmental and policy-level factors that affect weight management in different population groups. This large scale, multi-level approach aims to inform efforts to reduce the prevalence of obesity worldwide and its associated comorbidities and economic impacts. TRIAL REGISTRATION: NCT04907396 (clinicaltrials.gov) sponsor SB Roberts; Tufts University IRB #13075.

Patient-Reported Activity Levels Correlate With Early Cartilage Degeneration After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: The association between activity level after anterior cruciate ligament (ACL) reconstruction (ACLR) and development of posttraumatic osteoarthritis (PTOA) remains unclear. This study investigated the relationship of patient-reported outcomes and progressive cartilage degenerative changes at 3 years after ACLR. HYPOTHESIS: Higher activity levels, as measured by Marx scores, are significantly correlated with early cartilage degeneration after ACLR. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 35 patients (16 women; mean age, 31.0 ± 7.6 years) with isolated ACLR and without pre-existing arthritis were prospectively enrolled. Patients reported Marx activity scores and Knee injury and Osteoarthritis Outcome Score (KOOS) scores and underwent T1ρ magnetic resonance imaging (MRI) preoperatively, 6 months, 1 year, 2 years, and 3 years after ACLR with soft tissue graft (22 autograft). The change in cartilage relaxation times between preoperative and 3-year imaging was used to identify cartilage degeneration, defined as an increase in T1ρ values by 14.3%. Correlation between Marx activity levels, KOOS scores, and T1ρ degeneration was performed with the Spearman rank test. The Fisher exact test was used to test for association between Marx activity score cutoffs and degeneration. The Student t test was used to compare Whole-Organ Magnetic Resonance Imaging Score (WORMS) and T1ρ relaxation times. Significance was defined as P < .05. RESULTS: Sixteen patients (45.7%) showed evidence of cartilage degeneration at 3 years, most frequently in the medial compartment (n = 12; 34%). Higher Marx activity scores at 3 years correlated with cartilage degeneration in the medial femur (rho = 0.34; P = .045), and medial tibia (rho = 0.43; P = .01). A Marx score of 11 or greater at 3 years was significantly associated with medial compartment degeneration (P = .03), with a positive predictive value of 52.6%. No Marx score cutoff at years 1 or 2 predicted future cartilage degeneration. The KOOS Quality of Life score was inversely correlated with cartilage degeneration (rho = 0.38; P = .02). WORMS did not correlate with degeneration of the medial compartment. CONCLUSION: Increased activity at 3 years after ACLR was significantly associated with increased risk of medial compartment PTOA. While further research is needed to fully define these relationships, patients may be counseled that return to Marx activity levels of greater than 11 may be associated with a higher risk of medial compartment cartilage degeneration.

Prior Bone Marrow Stimulation Surgery Influences Outcomes After Cell-Based Cartilage Restoration: A Systematic Review and Meta-analysis.

BACKGROUND: Cell-based cartilage restoration with autologous chondrocyte implantation (ACI) is a safe and effective treatment for symptomatic cartilage lesions. Many patients undergoing ACI have a history of prior surgery, including bone marrow stimulation (BMS). There is mounting evidence that a history of prior BMS may impede healing of the ACI graft. PURPOSE/HYPOTHESIS: The purpose of this study was to compare the failure rates of primary ACI with ACI after prior BMS. We hypothesized that ACI after BMS would have a significantly higher failure rate (defined as reoperation, conversion to arthroplasty, and/or imaging-based failure) compared with primary ACI. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A literature search was performed by use of PubMed and Embase databases for relevant articles published through October 2, 2020, to identify studies evaluating outcomes and failures rates of ACI after prior BMS in the knee. RESULTS: Included were 11 studies comprising 1479 ACI procedures. The mean age at surgery ranged from 18.3 to 39.1 years, and the mean follow-up ranged from 3 to 20.6 years. All studies reported failure rates. The overall failure rate was significantly higher in the patients who underwent ACI after BMS, at 26.4% compared with 14.8% in the ACI group (P < .001). Meta-analysis demonstrated an increased risk of failure in patients with a history of prior BMS (log odds ratio = -0.90 [95% confidence interval, -1.38 to -0.42]). CONCLUSION: This systematic review demonstrated that failure rates were significantly higher for patients treated with ACI after BMS relative to patients undergoing ACI without prior BMS. This finding has important implications when considering the use of BMS for defects that are amenable to cell-based restoration and when determining treatment options after failed BMS. REGISTRATION: PROSPERO (CRD42020180387).

Arthroscopic Single-Portal Subscapularis Tendon Repair.

Tears of the subscapularis tendon can be challenging to diagnose and treat. Because the subscapularis plays an important role in shoulder function, careful arthroscopic evaluation and treatment are necessary to restore function. Previous surgical techniques have ranged from full open repairs to complex arthroscopic procedures needing suture passer and/or retriever devices. We describe an arthroscopic surgical technique of subscapularis repair through a single anterior portal using only penetrating graspers. This approach can be used for partial upper-border subscapularis tears, as well as complete and retracted subscapularis tendon tears.

Patellar tendon reconstruction with hamstring autograft for the treatment of chronic irreparable patellar tendon injuries.

BACKGROUND: Patellar tendon injuries not amenable to primary repair present a challenging problem for surgeons and patients alike. No standard surgical technique exists for these injuries and few studies report outcomes after surgical treatment. METHODS: A retrospective analysis was conducted for patients undergoing surgical treatment for irreparable patellar tendon tears. Patients were treated with an indirect tendon reconstruction technique using high-strength suture to set initial patellar height and hamstring autograft for biologic augmentation. Patients who underwent this procedure between 2012 and 2018 and met minimum two-year follow-up with completion of all outcome measurements including KOOS, PROMIS, VAS pain and satisfaction scores were included. RESULTS: Eleven patients met inclusion criteria. Ten of eleven patients (91%) had intact repairs and final patient outcomes were collected at a mean of 54.9 ± 23.1 months after surgery. Only one patient experienced extensor lag at final follow-up (p < 0.001). The preoperative Caton-Dechamps ratio was 1.77 ± 0.58, which decreased to 0.98 ± 0.25 after surgery (p < 0.001). The mean postoperative KOOS ADL score was 61.5. The mean postoperative PROMIS Global Mental and Physical Health scores were 46.9 ± 8.7 and 42.0 ± 9.8. Post-operative mean VAS satisfaction score was 5.6 ± 3.4. CONCLUSIONS: Patellar tendon reconstruction with autologous hamstring tendon graft and suture augmentation allows for acceptable outcomes in the setting of patellar tendon disruption with segmental defects when direct repair is not possible.

The Learning Curve for Hip Arthroscopic Surgery: A Prospective Evaluation With 2-Year Outcomes in Patients With Femoroacetabular Impingement.

BACKGROUND: The use of hip arthroscopic surgery in the treatment of femoroacetabular impingement (FAI) is increasing, but it is universally known as a technically demanding procedure with a "steep" learning curve. There are limited data investigating the correlation between surgeon experience and patient-reported outcomes (PROs) as well as procedure and traction times. PURPOSE: To prospectively evaluate the relationship between surgeon experience and PROs after hip arthroscopic surgery for the treatment of FAI. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: A total of 190 patients undergoing primary hip arthroscopic surgery for FAI were prospectively enrolled during a sports medicine fellowship-trained surgeon's first 36 months of practice. A radiographic evaluation as well as PRO surveys including the 12-Item Short Form Health Survey (SF-12), the modified Harris Hip Score (mHHS), and the Hip disability and Osteoarthritis Outcome Score (HOOS) were administered preoperatively and at 2 years postoperatively. Logistic regression as well as analysis of variance was performed to evaluate for correlations between surgical experience and PROs, procedure time, and traction time. RESULTS: Of the 190 patients, 168 (88%; mean age, 35.3 ± 9.6 years; mean body mass index, 25.07 ± 3.98) completed a 2-year follow-up and were included for analysis. The mean procedure time was 91.5 ± 23.9 minutes, and the mean traction time was 54.0 ± 17.7 minutes. Patients demonstrated significant improvements at 2 years after surgery for all PRO scores (mHHS, HOOS, and SF-12 physical component summary; P < .001), except the SF-12 mental component summary, which had no change (P = .43). The procedure time significantly decreased after 70 cases, while the traction time continued to decrease until 110 cases (R 2 = 0.99; P < .0001). There was no correlation between increasing case volume and 2-year PRO scores (P > .2 for mHHS, HOOS, and SF-12). There was also no difference with increasing case volume and amount of improvement from preoperative to 2-year postoperative PRO scores for the SF-12 and HOOS. Case volume did not affect the complication rate, as this cohort experienced 4 minor cases of neurapraxia. CONCLUSION: Surgical efficiency in hip arthroscopic surgery for the treatment of FAI was maximized after 110 cases in this cohort. However, significant PRO improvements can be achieved early in a surgeon's practice prior to maximizing surgical efficiency.

Fast Starters and Slow Starters After Hip Arthroscopy for Femoroacetabular Impingement: Correlation of Early Postoperative Pain and 2-Year Outcomes.

BACKGROUND: Patients experience varying degrees of pain and symptoms during the early recovery period after hip arthroscopy for femoroacetabular impingement (FAI). Some "fast starters" report minimal discomfort and are eager to advance activities, while "slow starters" describe severe pain and limitations. The relationship between these early postoperative symptoms and 2-year outcomes after hip arthroscopy is unknown. PURPOSE: To analyze the relationship between early postoperative pain and 2-year patient-reported outcomes (PROs) after hip arthroscopy for FAI. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Patients without arthritis or dysplasia who were undergoing primary hip arthroscopy for FAI were prospectively enrolled and completed validated PROs. Scores for visual analog scale (VAS) for pain were collected preoperatively and at 1 week, 6 weeks, and 2 years postoperatively. Scores for the modified Harris Hip Score (mHHS), Hip disability and Osteoarthritis Outcome Score (HOOS), and 12-Item Short Form Health Survey (SF-12) were collected preoperatively and 2 years postoperatively. Paired t tests were used to evaluate PRO score changes, and correlation analyses were used to assess relationships between early postoperative pain and 2-year postoperative outcomes. RESULTS: A total of 166 patients were included (55% female; mean ± SD age, 35.29 ± 9.6 years; mean body mass index, 25.07 ± 3.98 kg/m2). Patients demonstrated significant improvements in PRO scores (VAS, SF-12 Physical Component Score, mHHS, and all HOOS subscales) at 2 years after hip arthroscopy for FAI (P < .001). There was a significant correlation between lower 1-week VAS pain level (fast starters) and lower 2-year VAS pain level (R = 0.31; P < .001) as well as higher 2-year PRO scores (SF-12 Physical Component Score, mHHS, and all HOOS subscales: R = -0.21 to -0.3; P < .001). There was no correlation between 1-week VAS pain and 2-year SF-12 Mental Component Score (P = .17). Preoperative VAS pain levels showed positive correlations with 1-week postoperative pain scores (R = 0.39; P < .001) and negative correlations with 2-year patient outcomes (R = -0.15 to -0.33, P < .01). There was no correlation between 6-week postoperative pain scores and 2-year PRO scores. CONCLUSION: Fast starters after hip arthroscopy for FAI experience sustained improvements in outcomes at 2 years after surgery. Patient pain levels before surgery may delineate potential fast starters and slow starters.

Experiences of left ventricular assist device-destination therapy recipients: A systematic review and meta-synthesis.

Left ventricular assist device-destination therapy (LVAD-DT) represents a powerful technology capable of prolonging and significantly altering recipients' lives. The objective of this systematic review is to analyze the experiences of LVAD-DT recipients and recommend directions of further study. This is a qualitative research project; a systematic review, using thematic meta-synthesis. Six studies were reviewed. Three over-arching themes supported by seven conceptual categories were recognized across the six studies. The three overarching themes are that LVAD-DT recipients continue to struggle with complex support needs post implantation; the motivations for accepting LVAD-DT is death avoidance, and symptom relief; and, that recipients often believe the device will reverse or fix their heart failure. Although elemental, these themes suggest LVAD-DT recipients' interests may not be well served by the informed consent process. The number of LVAD-DT recipients continues to grow and age, presenting significant implications for healthcare providers as a result of this finding.

Development and Validation of a Prognostic, Risk-Adjusted Scoring System for Operative Upper-Extremity Infections.

PURPOSE: Acute infections of the distal upper extremity (UE) can require one and possibly multiple debridements. We aimed to develop and validate a prognostic scoring system based on patient, infection, and microbiology risk factors to help with operative planning and patient counseling. METHODS: We studied all acute surgical UE infections distal to the elbow joint over a 5-year period. A split-sample design was created with 1:1 randomization into development and validation samples. The primary outcome was infection persistence, defined as the need for additional operative drainage according to usual indications. Multivariable logistic regression identified risk factors for persistent infections in the development sample, which was translated to a simple clinical scoring system derived from regression coefficients. The model was then tested separately against the validation sample. RESULTS: A total of 602 patients were included; 31% of all infections exhibited persistence. Independent risk factors from the development sample included diabetes (3 points), smoking (2 points), leukocytosis at presentation (2 points), animal bite mechanism (3 points), osteomyelitis (4 points), tenosynovitis (7 points), pyarthrosis (3 points), necrotizing fasciitis (11 points), and methicillin-resistant Staphylococcus aureus (3 points). These were all confirmed in the validation sample. Infections were categorized into 3 groups based on risk for persistent infection: low (less than 8 points), medium (8-11 points), and high (12 points or more). In the validation sample, the probability of persistent infection for these 3 groups was 23%, 57%, and 79%, respectively. The c statistic for the model in the validation sample was 0.79. CONCLUSIONS: Persistence of acute surgical distal UE infections is mediated by patient and microbiology factors, as well as infection mechanism and type. Surgeons can use this risk-adjusted prognostic scoring system to anticipate which infections may require additional therapeutic debridement and plan operative schedules and counsel patients accordingly. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Quantifying the Effect of Diabetes on Surgical Hand and Forearm Infections.

PURPOSE: Diabetes has long been established as a risk factor for hand and forearm infections. The purpose of this study was to review the effect of glycemic factors on outcomes among diabetic patients with surgical upper-extremity infections. We hypothesized that diabetic inpatients may benefit from stronger peri-infection glycemic control. METHODS: A prospective cohort study enrolled diabetic and nondiabetic surgical hand and forearm infections over 3 years. Glycemic factors included baseline glycosylated hemoglobin, blood glucose (BG) at presentation, and inpatient BG. Poor baseline control was defined as glycosylated hemoglobin of 9.0% or greater and poor inpatient control as average BG of 180 mg/dL or greater. The main outcome of interest was the need for repeat therapeutic drainage. Multivariable logistic regression quantified the association between diabetic factors and this outcome. RESULTS: The study involved 322 patients: 76 diabetic and 246 nondiabetic. Diabetic infections were more likely than nondiabetic infections to result from idiopathic mechanisms, occur in the forearm, and present as osteomyelitis, septic arthritis, and necrotizing fasciitis. Diabetic microbiology was more likely polymicrobial and fungal. After first drainage, diabetic patients were more likely to require repeat drainage and undergo eventual amputation. Among diabetic patients, poor inpatient control was associated with need for repeat drainage. CONCLUSIONS: Diabetes exacerbates the burden of surgical upper-extremity infections: specifically, more proximal locations, deeper involved anatomy at presentation, broader pathogenic microbiology, increased need for repeat drainage, and higher risk for amputation. Among diabetic patients, poor inpatient glycemic control is associated with increased need for repeat drainage. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic I.

Comparison of Fixation Techniques of 3D-Woven Poly(ϵ-Caprolactone) Scaffolds for Cartilage Repair in a Weightbearing Porcine Large Animal Model.

Objective To test different fixation methods of a 3-dimensionally woven poly(ϵ-caprolactone) (PCL) scaffold within chondral defects of a weightbearing large animal model. Methods Full thickness chondral defects were made in the femoral condyles of 15 adult male Yucatan mini-pigs. Two surgical approaches were compared including total arthrotomy (traditional) and a retinaculum-sparing, minimally invasive surgery (MIS) approach. Following microfracture (MFX), scaffolds were placed without fixation or were fixed with fibrin glue, suture, or subchondral anchor. Experimental endpoints were between 1 and 6 weeks. Micro-computed tomography and histology were used to assess samples. Results The MIS approach was superior as the traditional approach caused medial condyle cartilage wear. One of 13 (7.7%) of scaffolds without fixation, 4 of 11 (36.3%) fibrin scaffolds, 1 of 4 (25%) of sutured scaffolds, and 9 of 9 (100%) of anchor-fixed scaffolds remained in place. Histology demonstrated tissue filling with some overgrowth of PCL scaffolds. Conclusions Of the methods tested, the MIS approach coupled with subchondral anchor fixation provided the best scaffold retention in a mini-pig chondral defect model. This finding has implications for fixation strategies in future animal studies and potential future human use.

Benign heart murmurs as a predictor for complications following total joint arthroplasty.

BACKGROUND: There is scant literature examining the predictive role of heart murmurs in the absence of suspected structural heart disease on complications of non-cardiac surgery. We hypothesize the detection of heart murmurs in the absence of structural heart disease will help identify patients at risk for complications following total joint arthroplasty (TJA) surgery. METHOD: This was a prospective cohort of patients undergoing TJA over a twenty-month period. The study was performed at a single academic institution with four subspecialty surgeons. Patients undergoing primary TJA who were over eighteen years old, gave informed consent, and had adequate documentation were included in the study. Patients with a preoperative murmur or a newly discovered postoperative murmur were compared against patients with no murmur. Surgery-related complications, performance with physical therapy, and discharge to a non-home facility were measured in each group. FINDINGS: 345 (63%) eligible patients were included. 20 (5.8%) patients had a documented preoperative murmur and 36 (10.4%) patients had a new postoperative murmur. No patient had concern for major structural heart disease. Preoperative murmurs independently predicted development of acute kidney injury (OR 7.729, p < 0.001; RR 1.36). Preoperative murmurs also predicted likelihood to be discharged to a non-home facility (OR 2.97, p = 0.03; RR 1.87). New postoperative murmurs independently correlated with decreased performance with physical therapy (OR 0.466, p = 0.045; RR 0.664). INTERPRETATION: Detection of heart murmurs both preoperatively and postoperatively is a low cost strategy to identify post-TJA surgical patients at risk for postoperative acute kidney injury, decreased physical performance, and discharge to non-home facilities. These patients may benefit from early fluid resuscitation and renally-dosed post-operative medications.

Dyslipidemia, weight gain, and decreased growth velocity in a 14-year-old male.

A 14-year-old male was referred for dyslipidemia. His findings were consistent with metabolic syndrome. Although he lacked the typical physical appearance, his accelerated weight gain combined with a decreased linear growth velocity suggested Cushing syndrome. He was subsequently found to have adrenocorticotropic hormone-independent Cushing syndrome secondary to primary pigmented nodular adrenal disease without Carney Complex. After bilateral adrenalectomy, his lipid profile returned to normal. In this article, we discuss the role of glucocorticoids on lipid and lipoprotein metabolism.

A retinaculum-sparing surgical approach preserves porcine stifle joint cartilage in an experimental animal model of cartilage repair.

BACKGROUND: This study compares a traditional parapatellar retinaculum-sacrificing arthrotomy to a retinaculum-sparing arthrotomy in a porcine stifle joint as a cartilage repair model. FINDINGS: Surgical exposure of the femoral trochlea of ten Yucatan pigs stifle joint was performed using either a traditional medial parapatellar approach with retinaculum incision and luxation of the patella (n = 5) or a minimally invasive (MIS) approach which spared the patellar retinaculum (n = 5). Both classical and MIS approaches provided adequate access to the trochlea, enabling the creation of cartilage defects without difficulties. Four full thickness, 4 mm circular full-thickness cartilage defects were created in each trochlea. There were no intraoperative complications observed in either surgical approach. All pigs were allowed full weight-bearing and full range of motion immediately postoperatively and were euthanized between 2 and 3 weeks. The traditional approach was associated with increased cartilage wear compared to the MIS approach. Two blinded raters performed gross evaluation of the trochlea cartilage surrounding the defects according to the modified ICRS cartilage injury classification. The traditional approach cartilage received a significantly worse score than the MIS approach group from both scorers (3.2 vs 0.8, p = 0.01 and 2.8 vs 0, p = 0.005 respectively). CONCLUSION: The MIS approach results in less damage to the trochlear cartilage and faster return to load bearing activities. As an arthrotomy approach in the porcine model, MIS is superior to the traditional approach.

The Ponseti Method for Clubfoot Treatment in Low and Middle-Income Countries: A Systematic Review of Barriers and Solutions to Service Delivery.

BACKGROUND: Use of the minimally invasive Ponseti method has been increasing in low and middle-income countries, where most of the world's children with clubfoot are born. This method requires a system of service delivery involving screening, serial casting with or without a tenotomy to achieve correction, and long-term use of an orthosis to maintain correction. The goal of this systematic review is to evaluate the barriers to service delivery and the solutions that have been proposed or implemented to address these barriers. METHODS: A literature search of Medline, Embase, and SCOPUS produced 3251 results. Twenty-four papers were selected for final review. Barriers and their attempted solutions were organized into a previously described health barrier model. We reported on high-impact, sustainable solutions that are feasible for organizations to implement, as opposed to solutions that require major policy or country-wide infrastructure changes. RESULTS: Common barriers found to have the most impact on patient care included financial constraints, transportation, difficulties with brace and cast care, self-perceived health status, lack of physical resources, and provider's lack of knowledge and skill. The most common solutions detailed were education of the provider or patient and financial assistance for patients. CONCLUSIONS: Recognizing that contextually relevant solutions to the challenges of setting up a system for clubfoot service delivery are required, several common barriers have emerged within this systematic review of papers from multiple countries, including spatial accessibility, affordability, and availability. Programs can best prepare for challenges by placing clinics close to population centers and/or allocating funds to subsidize transportation, ensuring that an adequate supply of materials are available for the casting and tenotomy, and enhancing the education of families and health providers. Strengthening communication and establishing partnerships between individuals and organizations promoting the Ponseti method will improve systems for service delivery. LEVEL OF EVIDENCE: Level IV-prognostic study.

Rare and common variants in extracellular matrix gene Fibrillin 2 (FBN2) are associated with macular degeneration.

Neurodegenerative diseases affecting the macula constitute a major cause of incurable vision loss and exhibit considerable clinical and genetic heterogeneity, from early-onset monogenic disease to multifactorial late-onset age-related macular degeneration (AMD). As part of our continued efforts to define genetic causes of macular degeneration, we performed whole exome sequencing in four individuals of a two-generation family with autosomal dominant maculopathy and identified a rare variant p.Glu1144Lys in Fibrillin 2 (FBN2), a glycoprotein of the elastin-rich extracellular matrix (ECM). Sanger sequencing validated the segregation of this variant in the complete pedigree, including two additional affected and one unaffected individual. Sequencing of 192 maculopathy patients revealed additional rare variants, predicted to disrupt FBN2 function. We then undertook additional studies to explore the relationship of FBN2 to macular disease. We show that FBN2 localizes to Bruch's membrane and its expression appears to be reduced in aging and AMD eyes, prompting us to examine its relationship with AMD. We detect suggestive association of a common FBN2 non-synonymous variant, rs154001 (p.Val965Ile) with AMD in 10 337 cases and 11 174 controls (OR = 1.10; P-value = 3.79 × 10(-5)). Thus, it appears that rare and common variants in a single gene--FBN2--can contribute to Mendelian and complex forms of macular degeneration. Our studies provide genetic evidence for a key role of elastin microfibers and Bruch's membrane in maintaining blood-retina homeostasis and establish the importance of studying orphan diseases for understanding more common clinical phenotypes.

Update on the Kelch-like (KLHL) gene family.

The Kelch-like (KLHL) gene family encodes a group of proteins that generally possess a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. BTB domains facilitate protein binding and dimerization. The BACK domain has no known function yet is of functional importance since mutations in this domain are associated with disease. Kelch domains form a tertiary structure of ß-propellers that have a role in extracellular functions, morphology, and binding to other proteins. Presently, 42 KLHL genes have been classified by the HUGO Gene Nomenclature Committee (HGNC), and they are found across multiple human chromosomes. The KLHL family is conserved throughout evolution. Phylogenetic analysis of KLHL family members suggests that it can be subdivided into three subgroups with KLHL11 as the oldest member and KLHL9 as the youngest. Several KLHL proteins bind to the E3 ligase cullin 3 and are known to be involved in ubiquitination. KLHL genes are responsible for several Mendelian diseases and have been associated with cancer. Further investigation of this family of proteins will likely provide valuable insights into basic biology and human disease.