Risk of Amyloidosis and Heart Failure Among Patients Undergoing Surgery for Trigger Digit or Carpal Tunnel Syndrome: A Nationwide Cohort Study With Implications for Screening.

PURPOSE: Tenosynovial biopsy during carpal tunnel release (CTR) leads to an earlier diagnosis of amyloidosis. Surgery for trigger digit-trigger release (TR)-may provide a similar opportunity. We sought to characterize the risk of amyloidosis diagnosis after TR and/or CTR. METHODS: We conducted a retrospective cohort study of adults without diagnosed amyloidosis undergoing TR and/or CTR in the Veterans Health Administration from 1999 to 2019, including matched controls. We used competing-risks methodology to estimate the cumulative incidence and adjusted subdistribution hazard ratios (sHRs) of amyloidosis, heart failure, and death after TR and/or CTR. RESULTS: Among the 126,788 patients undergoing TR and/or CTR, amyloidosis was diagnosed in 52 of 26,757 patients undergoing TR alone at a median of 4.7 years after surgery (10-year cumulative incidence: 0.26%, 95% CI: 0.18% to 0.34%), 396 of 91,384 patients undergoing CTR alone at a median of 5.1 years after surgery (10-year cumulative incidence: 0.60%, 95% CI: 0.53% to 0.67%), 50 of 8,647 patients undergoing both TR and CTR at a median of 3.1 years after surgery (10-year cumulative incidence: 0.80%, 95% CI: 0.54% to 1.1%), and 54 of 113,452 controls at a median of 5.0 years after the index date (10-year cumulative incidence 0.053%, 95% CI: 0.037% to 0.070%). In the adjusted analysis, patients who underwent TR and/or CTR had a higher risk of amyloidosis (TR: sHRadj 4.80, 95% CI: 3.33-6.92; CTR: sHRadj 10.2, 95% CI: 7.74-13.6; TR and CTR: sHRadj 14.9, 95% CI: 9.87-22.5) and heart failure (TR: sHRadj 1.91, 95% CI: 1.83-1.99; CTR: sHRadj 2.02, 95% CI: 1.97-2.07; TR and CTR: sHRadj 2.18, 95% CI: 2.04-2.33) but not death compared with the controls. Among the patients who underwent TR, age, Black race, prior CTR, heart failure, and the number of digits released were independent risk factors for amyloidosis. CONCLUSIONS: Patients undergoing TR and/or CTR are at increased risk of incident amyloidosis and heart failure compared to controls. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Fibroadipose Vascular Anomaly in the Upper Extremity: A Distinct Entity With Characteristic Clinical, Radiological, and Histopathological Findings.

PURPOSE: Fibroadipose vascular anomaly (FAVA) is an intramuscular vascular malformation that has been recently described as a distinct clinical entity. The clinical, radiological, and histopathological characteristics of FAVA in the upper extremity are reviewed. METHODS: This was a retrospective case series of upper-extremity FAVA lesions. RESULTS: We reviewed 19 patients with FAVA of the upper limb. Pain, stiffness, swelling, and flexion contractures were the most common presentations. Except for one lesion confined to the hand, all lesions either presented with or developed a contracture within 10 years. Ten patients underwent surgical debulking. Six required tendon transfer reconstruction and 3 necessitated a free functional muscle transfer. CONCLUSIONS: Fibroadipose vascular anomaly in the upper extremity requires an accurate diagnosis and may benefit from early referral to a multidisciplinary vascular anomaly center with experienced hand surgeons. Compression garments, propranolol, and sclerotherapy seem to be ineffective. Surgical resection focused on symptomatic regions with appropriate reconstruction may have benefit in salvage of limbs with compromised function. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Longitudinal Microsurgery Laboratory Training during Hand Surgery Fellowship.

BACKGROUND: Laboratory training courses have traditionally offered an attractive method to learn microsurgery in a low-risk environment. However, courses are often limited by cost, accessibility, and their one-time, nonlongitudinal nature. Our aims were to (1) describe our institution's microsurgical training course for hand surgery fellows, which is longitudinal and integrated within our fellowship curriculum and (2) investigate how this course affects the microsurgical confidence and competence of trainees throughout their fellowship year. METHODS: All hand fellows who trained in our 1-year combined hand surgery fellowship from 2016 through 2018 participated in this study. Baseline data on the type and duration of residency training, previous microsurgery experience and self-reported confidence, knowledge, and interest in microsurgery were recorded. Self-reported scores were documented using a continuous scale ranging from 0 to 10. An initial 3-day laboratory course combining the use of didactic teaching, a nonliving synthetic model, and a live rat model was conducted. Repeat laboratory training occurred thereafter at 6 and 12 months. At the end of each session, fellows repeated the baseline questionnaire and faculty assessed their microsurgical competence using a standardized global rating scale (GRS). RESULTS: A total of six fellows (2 years) were enrolled. At the end of the initial course, there was a statistically significant increase in mean self-reported confidence in microsurgery from 4.3 to 6.2 and knowledge from 4.7 to 6.5. Mean scores in interest were unchanged, from 9.2 to 9.3. There was also an increase in mean GRS score from day 3 to months 6 and 12. CONCLUSION: A longitudinal microsurgical training course integrated within a hand surgery fellowship is associated with increased confidence and microsurgical skill. This study describes our approach and its feasibility.

MC1R gene polymorphisms are associated with dysfunctional immune responses and wound infection after burn injury.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is associated with organ failure and infectious complications after major burn injury. Recent evidence has linked melanocortin signaling to anti-inflammatory and wound-repair functions, with mutations in the melanocortin 1 receptor (MC1R) gene leading to increased inflammatory responses. Our group has previously demonstrated that MC1R gene polymorphisms are associated with postburn hypertrophic scarring. Thus, we hypothesized that MC1R single nucleotide polymorphisms (SNPs) would be associated with increased burn-induced SIRS and increased infectious complications. METHODS: We performed a retrospective cohort study of adults (>18 y of age) admitted to our burn center with >20% total body surface area (TBSA) partial/full thickness burns between 2006 and 2013. We screened for five MC1R SNPs (V60L, V92M, R151C, R163Q, T314T) by polymerase chain reaction from genomic DNA isolated from blood samples. We performed a detailed review of each patient chart to identify age, sex, race, ethnicity, %TBSA burned, burn wound infections (BWIs), and 72-hr intravenous fluid volume, the latter a surrogate for a dysfunctional inflammatory response to injury. Association testing was based on multivariable regression. RESULTS: Of 106 subjects enrolled, 82 had complete data for analysis. Of these, 64 (78%) were male, with a median age of 39 and median burn size of 30% TBSA. A total of 36 (44%) subjects developed BWIs. The median total administered IV crystalloid in first 72h was 24.6 L. In multivariate analysis, the R151C variant allele was a significant independent risk factor for BWI (adjusted prevalence ratio 2.03; 95% CI: 1.21-3.39; P = 0.007), and the V60L variant allele was independently associated with increased resuscitation fluid volume (P = 0.021). CONCLUSIONS: This is the first study to demonstrate a significant association between genetic polymorphisms and a nonfatal burn-induced SIRS complication. Our findings suggest that MC1R polymorphisms contribute to dysfunctional responses to burn injury that may predict infectious and inflammatory complications.

RIG-I-like receptor LGP2 protects tumor cells from ionizing radiation.

An siRNA screen targeting 89 IFN stimulated genes in 14 different cancer cell lines pointed to the RIG-I (retinoic acid inducible gene I)-like receptor Laboratory of Genetics and Physiology 2 (LGP2) as playing a key role in conferring tumor cell survival following cytotoxic stress induced by ionizing radiation (IR). Studies on the role of LGP2 revealed the following: (i) Depletion of LGP2 in three cancer cell lines resulted in a significant increase in cell death following IR, (ii) ectopic expression of LGP2 in cells increased resistance to IR, and (iii) IR enhanced LGP2 expression in three cell lines tested. Studies designed to define the mechanism by which LGP2 acts point to its role in regulation of IFNß. Specifically (i) suppression of LGP2 leads to enhanced IFNß, (ii) cytotoxic effects following IR correlated with expression of IFNß inasmuch as inhibition of IFNß by neutralizing antibody conferred resistance to cell death, and (iii) mouse embryonic fibroblasts from IFN receptor 1 knockout mice are radioresistant compared with wild-type mouse embryonic fibroblasts. The role of LGP2 in cancer may be inferred from cumulative data showing elevated levels of LGP2 in cancer cells are associated with more adverse clinical outcomes. Our results indicate that cytotoxic stress exemplified by IR induces IFNß and enhances the expression of LGP2. Enhanced expression of LGP2 suppresses the IFN stimulated genes associated with cytotoxic stress by turning off the expression of IFNß.

Genome-wide Association Study of Postburn Scarring Identifies a Novel Protective Variant.

OBJECTIVE: To identify genetic variants associated with the severity of postburn hypertrophic scarring (HTS) using a genome-wide approach. BACKGROUND: Risk of severe postburn HTS is known to depend on race, but the genetic determinants of HTS are unknown. METHODS: We conducted a genome-wide association study (GWAS) in a prospective cohort of adults admitted with deep-partial-thickness burns from 2007 through 2014. Scar severity was assessed over time using the Vancouver Scar Scale (VSS), and DNA was genotyped with a >500,000-marker array. We performed association testing of single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) >0.01 using linear regression of VSS height score on genotype adjusted for patient and injury characteristics as well as population genetic structure. Array-wide significance was based on Bonferroni correction for multiple testing. RESULTS: Of 538 patients (median age 40 years, median burn size 6.0% of body surface area), 71% were men and 76% were White. The mean VSS height score was 1.2 (range: 0-3). Of 289,639 SNPs tested, a variant in the CUB and Sushi multiple domains 1 (CSMD1) gene (rs11136645; MAF = 0.49), was significantly associated with decreased scar height (regression coefficient = -0.23, P = 7.9 × 10). CONCLUSIONS: In the first published GWAS of HTS, we report that a common intronic variant in the CSMD1 gene is associated with reduced severity of postburn HTS. If this association is confirmed in an independent cohort, investigating the potential role of CSMD1 in wound healing may elucidate HTS pathophysiology.

Targeted metabolic profiling of wounds in diabetic and nondiabetic mice.

While cellular metabolism is known to regulate a number of key biological processes such as cell growth and proliferation, its role in wound healing is unknown. We hypothesized that cutaneous injury would induce significant metabolic changes and that the impaired wound healing seen in diabetes would be associated with a dysfunctional metabolic response to injury. We used a targeted metabolomics approach to characterize the metabolic profile of uninjured skin and full-thickness wounds at day 7 postinjury in nondiabetic (db/-) and diabetic (db/db) mice. By liquid chromatography mass spectrometry, we identified 129 metabolites among all tissue samples. Principal component analysis demonstrated that uninjured skin and wounds have distinct metabolic profiles and that diabetes alters the metabolic profile of both uninjured skin and wounds. Examining individual metabolites, we identified 62 with a significantly altered response to injury in the diabetic mice, with many of these, including glycine, kynurenate, and OH-phenylpyruvate, implicated in wound healing for the first time. Thus, we report the first comprehensive analysis of wound metabolic profiles, and our results highlight the potential for metabolomics to identify novel biomarkers and therapeutic targets for improved wound healing outcomes.

Complications Within 30 Days of Hand Surgery: An Analysis of 10,646 Patients.

PURPOSE: The American College of Surgeons Surgical Quality Improvement Program database collects detailed and validated data on demographics, comorbidities, and 30-day postoperative outcomes of patients undergoing operations in most subspecialties. This dataset has been previously used to quantify complications and identify risk factors in other surgical subspecialties. We sought to determine the incidence of postoperative complications following hand surgery and to identify factors associated with increased risk of complications in order to focus preventive strategies. METHODS: National Surgical Quality Improvement Program data from 2006 to 2011 were queried using 302 hand-specific Current Procedural Technology codes. Descriptive statistics were calculated for the population, and potential risk factors and patient characteristics were analyzed for their association with complications in the 30-day postoperative period using both univariate and multivariate analyses. RESULTS: There were 208 hand-specific Current Procedural Technology codes represented in the data, and of these, 84 were associated with at least 1 complication. The overall incidence of complications within 30 days of hand surgery was 2.5% (95% confidence interval, 2.2%-2.8%). In univariate analysis, older age, diabetes, chronic obstructive pulmonary disease, congestive heart failure, atherosclerosis, steroids, bleeding disorder, increasing American Society of Anesthesiologists class, increasing wound class, emergency procedure, longer operative time, and preoperative transfusion were associated with significantly higher risk of complications, and local anesthesia and outpatient surgery were associated with lower risk. In the multivariate model, male sex, increasing American Society of Anesthesiologists class, wound class 4, and preoperative transfusion were associated with significantly higher risk, and outpatient surgery was associated with significantly lower risk. The most common complication was surgical-site infection (1.2%). CONCLUSIONS: The incidence of complications was low, with overall health status being more important than specific comorbidities in predicting complication risk. This information may be valuable in counseling patients before surgery and in identifying patients at higher risk for complications following hand surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic III.

Revision Carpal Tunnel Release Following Endoscopic Compared With Open Decompression.

Importance: Carpal tunnel release (CTR) technique may influence the likelihood of revision surgery. Prior studies of revision CTR following endoscopic CTR (ECTR) compared with open CTR (OCTR) have been limited by sample size and duration of follow-up. Objective: To estimate the incidence of revision CTR following ECTR compared with OCTR in a national cohort. Design, Setting, and Participants: This retrospective cohort study used data from the US Veterans Health Administration. Participants included all adults (age ≥18 years) undergoing at least 1 outpatient CTR from October 1, 1999, to May 20, 2021. Data were analyzed from May 21, 2021, to November 27, 2023. Exposure: Index CTR technique. Main Outcomes and Measures: The primary outcome was time to revision CTR, defined as repeat ipsilateral CTR during the study period. Secondary outcomes were indications for revision, findings during revision, and additional procedures performed during revision. Results: Among 134 851 wrists from 103 455 patients (92 510 [89.4%] male; median [IQR] age, 62 [53-70] years) undergoing at least 1 CTR, 1809 wrists underwent at least 1 revision at a median (IQR) of 2.5 (1.0-3.8) years. In competing-risks analysis, the cumulative incidence of revision was 1.06% (95% CI, 0.99%-1.12%) at 5 years and 1.59% (95% CI, 1.51%-1.67%) at 10 years. ECTR was associated with increased hazard of revision CTR compared with OCTR (adjusted hazard ratio [aHR], 1.56; 95% CI, 1.34-1.81; P < .001). The risk difference for revision CTR associated with ECTR compared with OCTR was 0.57% (95% CI, 0.31%-0.84%) at 5 years (number needed to harm, 176) and 0.72% (95% CI, 0.36%-1.07%) at 10 years (number needed to harm, 139). Regardless of index CTR technique, the most common indication for revision was symptom recurrence (1062 wrists [58.7%]). A reconstituted transverse carpal ligament (TCL) was more common after ECTR compared with OCTR, whereas scarring of the overlying tissues and of the median nerve itself were more common following OCTR. Incomplete transverse-carpal-ligament release was observed in 251 of the wrists undergoing revision CTR (13.94%) and was more common among revisions following ECTR (odds ratio, 1.62; 95% CI, 1.11-2.37; P = .01). Conclusions and Relevance: In this cohort study of revision CTR in the Veterans Health Administration, ECTR was associated with increased risk of revision compared with OCTR, but the absolute risk was low regardless of technique. Intraoperative findings at revision varied significantly according to index CTR technique.

Syndactyly Release in the Hand: Surgical Technique.

SUMMARY: Syndactyly is one of the most common congenital differences treated by hand surgeons. Although dozens of techniques for syndactyly release have been described, a reliable method is based on a dorsal rectangular flap for commissure construction and a combination of interdigitating zigzag flaps and skin grafts for digital coverage. In this article, the authors present a detailed description of syndactyly release emphasizing principles integral to successful outcomes.

Index Finger Pollicization for Hypoplastic Thumb: Surgical Technique.

SUMMARY: Pollicization can be performed for secondary thumb reconstruction after traumatic injury or for primary thumb construction in cases of congenital thumb hypoplasia. Given the complexity of this operation, intimate familiarity with the involved anatomy and surgical principles is key to successful surgical outcomes. In this Video Plus article, the authors present a step-by-step approach to pollicization in case of Blauth type IIIB thumb hypoplasia.

Diagnosing Systemic Amyloidosis Presenting as Carpal Tunnel Syndrome: A Risk Nomogram to Guide Biopsy at Time of Carpal Tunnel Release.

BACKGROUND: As carpal tunnel syndrome often precedes other signs of systemic amyloidosis, tenosynovial biopsy at the time of carpal tunnel release may facilitate early diagnosis and treatment. However, evidence-based guidelines for amyloidosis screening during carpal tunnel release have not been established. We sought to develop a predictive model for amyloidosis after carpal tunnel release to inform screening efforts. METHODS: We performed a retrospective cohort study of adults without known amyloidosis undergoing at least 1 carpal tunnel release from 2000 to 2019 with use of the national Veterans Health Administration database. After estimating the cumulative incidence of amyloidosis after carpal tunnel release, we identified risk factors, constructed a predictive nomogram based on a multivariable subdistribution-hazard competing-risks model, and performed cross-validation. RESULTS: Among 89,981 patients undergoing at least 1 carpal tunnel release, 310 were subsequently diagnosed with amyloidosis at a median interval of 4.5 years, corresponding to a cumulative incidence of 0.55% (95% confidence interval [CI]: 0.47% to 0.63%) at 10 years. Amyloidosis diagnosis following carpal tunnel release was associated with an increased hazard of heart failure (hazard ratio [HR], 4.68; 95% CI: 4.26 to 5.55) and death (HR, 1.27; 95% CI: 1.07 to 1.51) after adjustment for potential confounders. Age, male sex, Black race, monoclonal gammopathy of undetermined significance or multiple myeloma, rheumatoid arthritis, atrial fibrillation, spinal stenosis, and bilateral carpal tunnel syndrome were independently associated with increased risk of amyloidosis diagnosis and were included in the risk nomogram. CONCLUSIONS: Amyloidosis diagnosis after carpal tunnel release is rare but is associated with poor outcomes. We present an amyloidosis-risk nomogram to help guide tenosynovial biopsy at time of carpal tunnel release. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Surgery for lower extremity symptomatic neuroma: Long-term outcomes.

INTRODUCTION: Traumatic neuroma caused by injuries or surgery can result in neuropathic pain, functional impairment, and psychological distress, which has an impact on quality of life. The aim of this study was to identify the factors related to successful treatment of symptomatic lower extremity symptomatic neuromas using patient-reported outcome measures (PROMs). METHODS: Thirty-two patients with 48 symptomatic neuromas completed the PROMIS mobility, PROMIS pain interference (PI), Numeric Rating Scale (NRS) for pain (0-10) for both pre- and post-operative pain, and the PROMIS depression at a mean of 8.9±4.5 years following neuroma surgery. Neuromas were located around the foot and ankle (n=18, 38%), leg (n=14, 29%), around the knee (n=13, 27%), and in the thigh (n=3, 6.3%). Surgical treatment included neuroma excision and implantation (n=29, 60%) followed by neuroma excision alone or excision with placement in the subcutaneous tissue (n=12, 25%). We performed multivariable analysis to identify the factors influencing the PROMs. RESULTS: Patients reported significant reduction in mean NRS pain after surgery (7.3 vs 4.9, p=0.0013). Higher PROMIS depression scores were independently associated with inferior PROMIS mobility scores (ß=-0.38, p=0.001), higher PROMIS PI scores (ß=0.68, p<0.001), and higher NRS pain scores (ß=0.1, p=0.001). Additionally, smoking was independently associated with higher NRS pain scores (ß=1.59, p=0.049) CONCLUSION: Surgical treatment of symptomatic neuromas of the lower extremity provides a long-term improvement in 59% of patients, but 19% of patients still reported severe persistent pain despite surgical treatment. Smoking and negative mood have negative effects on patient-reported outcomes after neuroma surgery.

Patient Transfer for Hand and Upper Extremity Injuries: Diagnostic Accuracy at the Time of Referral.

BACKGROUND: Local health care facilities are often unequipped to treat complex upper extremity injuries, and patients are therefore transferred to designated trauma centers. This study describes the characteristics of patients transferred to a Level I trauma center for hand and upper extremity injuries and to investigate the accuracy of the provided diagnosis at the time of referral. METHODS: Adult patients transferred from outside facilities to the authors' Level I trauma center by means of direct contract with the on-call fellow for the care of hand and upper extremity injuries were identified. Patient- and injury-related information was prospectively collected at the time of referral before patient transfer, and again following diagnostic evaluation by a hand surgeon at the authors' institution. RESULTS: Sixty-three patients were transferred to the authors' hand surgery service from outside facilities after direct contact with the on-call fellow. Most patients were referred by emergency medicine physicians [n = 47 (76 percent)], followed by midlevel emergency department providers (physician assistant or nurse practitioner) [n = 12 (19 percent)] or hand surgeons [n = 3 (5 percent)]. Six patients were transferred directly from a Level I trauma center. Twenty-one transferred patients (33 percent) had an inaccurate diagnosis at the time of referral. Factors associated with an inaccurate diagnosis included trauma level of the referring hospital and diagnoses of infection or dysvascularity. CONCLUSIONS: The diagnostic accuracy for hand injuries transferred from outside facilities by means of provider-to-provider communication is imperfect, and some injuries are misdiagnosed. Hand surgeons should continue to improve the triage and transfer process for patients with acute hand surgery injuries. CLINICAL QUESTION/LEVEL OF EVIDENCE: Diagnostic, IV.

Genetic Risk of Trigger Finger: Results of a Genomewide Association Study.

BACKGROUND: Trigger finger, or stenosing tenosynovitis, is one of the most common conditions affecting the hand, yet its pathophysiology remains poorly understood, and genetic association studies of trigger finger are lacking. The purpose of this study was to identify single-nucleotide polymorphisms associated with trigger finger through a genomewide approach. METHODS: The authors performed a case-control genomewide association study in the Partners HealthCare Biobank. Single-nucleotide polymorphism- and gene-based association analyses were carried out after quality control, imputation, and filtering. RESULTS: Among 942 trigger finger cases and 24,472 controls, the authors tested 7,846,471 single-nucleotide polymorphisms for association with trigger finger. In the single-nucleotide polymorphism-based analysis, a single locus on chromosome 13 corresponding to KLHL1 met the genomewide significance threshold (lead single-nucleotide polymorphism rs59988404; OR, 1.74; 95 percent CI, 1.47 to 2.07; p = 1.99 × 10). After mapping, gene-based analysis demonstrated a significant association with POLE2 (p = 7.53 × 10) on chromosome 14. Among trigger finger cases, rs59988404 genotype was significantly associated with the total number of trigger finger procedures performed (p = 0.026). CONCLUSIONS: In the first reported genomewide association study of trigger finger, the authors report significant associations of KLHL1 and POLE2 with risk of trigger finger. The authors' results may help to elucidate the pathophysiology of trigger finger and facilitate an individualized, precision-medicine treatment approach. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Five Essential Principles for First Web Space Reconstruction in the Burned Hand.

BACKGROUND: Burn injuries commonly affect the hand, and the development of adduction contractures of the first web space is frequent and deleterious, both functionally and aesthetically. Many corrective techniques and algorithmic approaches have been described to treat this problem, but there is no consensus on the optimal management. METHODS: A retrospective review at a single high-volume pediatric burn center was undertaken to evaluate the clinical course of these patients. All pediatric patients undergoing initial release of burn scar contracture of the first web space from 2005 through 2015 were included in a retrospective cohort study. RESULTS: The authors identified 40 patients with 57 burned hands. The initial approach to management was variable. Z-plasty or other local flap was the first technique used in 28 hands (49 percent), split-thickness skin graft in 19 hands (33 percent), full-thickness skin graft in seven hands (12 percent), groin flaps in two hands (4 percent), and a reverse radial forearm flap in one hand (2 percent). The mean numbers of total reconstructive procedures per hand including the initial procedure were as follows: groin flap, 4.0; full-thickness skin graft, 3.1; split-thickness skin graft, 2.1; Z-plasty, 1.4; and reverse radial forearm flap, 1.0. CONCLUSIONS: Successful reconstruction of the first web space must be addressed in the context of the entire hand. It is the authors' preference to use split-thickness skin grafting whenever a skin deficiency is present-only then should leading edge contractures be addressed with Z-plasty. Based on their experience, the authors recommend five principles that are essential to successfully treat postburn contractures of the first web space. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Patient-Reported Outcomes following Surgical Treatment of Symptomatic Digital Neuromas.

BACKGROUND: Many surgical techniques are used to treat symptomatic neuroma, but options are limited for digital neuromas because of a paucity of soft-tissue coverage and/or the absence of the terminal nerve end. The authors assessed factors that influence patient-reported outcomes after surgery for symptomatic digital neuroma. METHODS: The authors retrospectively identified 29 patients with 33 symptomatic digital neuromas that were treated surgically. Patients completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity and Pain Interference scales, a numeric rating scale for pain, and the PROMIS Depression scale at a median follow-up of 7.6 years postoperatively (range, 3.2 to 16.8 years). Surgical treatment for neuroma included excision with nerve repair/reconstruction (n =13; 39 percent), neuroma excision alone (n =10; 30 percent), and excision and implantation (n =10; 30 percent). Multivariable linear regression was performed to identify the factors that independently influenced patient-reported outcomes. RESULTS: The mean postoperative PROMIS Upper Extremity score was 45.2 ± 11.2, the mean Pain Interference score was 54.3 ± 10.7, and the mean numeric rating scale pain score was 3 (interquartile range, 1 to 5). Compared with other treatment techniques, neuroma excision with nerve repair/reconstruction was associated with lower numeric rating scale pain scores; lower Pain Interference scores, corresponding to less daily impact of pain; and higher Upper Extremity scores, reflecting better upper extremity function. Older age and higher Depression scores were associated with lower Upper Extremity scores and higher Pain Interference scores. Smoking was associated with higher Pain Interference and numeric rating scale pain scores. CONCLUSIONS: Neuroma excision followed by nerve repair/reconstruction resulted in better outcomes compared with neuroma excision alone with or without implantation. Patient age and psychosocial factors influenced patient-reported outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

STAT1-dependent expression of energy metabolic pathways links tumour growth and radioresistance to the Warburg effect.

BACKGROUND: The Signal Transducer and Activator of Transcription 1 (STAT1) has traditionally been regarded as a transmitter of interferon signaling and a pro-apoptotic tumour suppressor. Recent data have identified new functions of STAT1 associated with tumourigenesis and resistance to genotoxic stress, including ionizing radiation (IR) and chemotherapy. To investigate the mechanisms contributing to the tumourigenic functions of STAT1, we performed a combined transcriptomic-proteomic expressional analysis and found that STAT1 is associated with regulation of energy metabolism with potential implication in the Warburg effect. METHODS: We generated a stable knockdown of STAT1 in the SCC61 human squamous cell carcinoma cell line, established tumour xenografts in athymic mice, and compared transcriptomic and proteomic profiles of STAT1 wild-type (WT) and knockdown (KD) untreated or irradiated (IR) tumours. Transcriptional profiling was based on Affymetrix Human GeneChip(R) Gene 1.0 ST microarrays. Proteomes were determined from the tandem mass spectrometry (MS/MS) data by searching against the human subset of the UniProt database. Data were analysed using Significance Analysis of Microarrays for ribonucleic acid and Visualize software for proteins. Functional analysis was performed with Ingenuity Pathway Analysis with statistical significance measured by Fisher's exact test. RESULTS: Knockdown of STAT1 led to significant growth suppression in untreated tumours and radio sensitization of irradiated tumours. These changes were accompanied by alterations in the expression of genes and proteins of glycolysis/gluconeogenesis (GG), the citrate cycle (CC) and oxidative phosphorylation (OP). Of these pathways, GG had the most concordant changes in gene and protein expression and demonstrated a STAT1-dependent expression of genes and proteins consistent with tumour-specific glycolysis. In addition, IR drastically suppressed the GG pathway in STAT1 KD tumours without significant change in STAT1 WT tumours. CONCLUSION: Our results identify a previously uncharacterized function of STAT1 in tumours: expressional regulation of genes encoding proteins involved in glycolysis, the citrate cycle and mitochondrial oxidative phosphorylation, with predominant regulation of glycolytic genes. STAT1-dependent expressional regulation of glycolysis suggests a potential role for STAT1 as a transcriptional modulator of genes responsible for the Warburg effect.

Respiratory Failure following Abdominal Wall Reconstruction: An Analysis of the Nationwide Inpatient Sample.

BACKGROUND: Patients undergoing abdominal wall reconstruction are at increased risk of postoperative respiratory failure. Understanding the epidemiology of this complication may guide preventive efforts. METHODS: The authors performed a population-based retrospective cohort study of adults undergoing elective abdominal wall reconstruction (ventral hernia repair with component separation) in the United States from 2004 through 2011 using the Nationwide Inpatient Sample. RESULTS: Of 2283 patients undergoing elective abdominal wall reconstruction, 57 percent were women, with a median age of 57 years, median hospital stay of 5 days, and mean total cost of $23,730. Postoperative respiratory failure occurred in 212 patients (9.3 percent), 164 patients (7.2 percent) were discharged to a skilled nursing facility, and 18 patients (0.8 percent) died. On multivariate analysis, age, male sex, congestive heart failure, lung disease, obesity, and obstructive sleep apnea were independently associated with increased risk of respiratory failure. Respiratory failure was associated with significantly increased risk of death and discharge to a skilled nursing facility as well as significantly increased total cost and hospital length of stay. CONCLUSIONS: Respiratory failure is an uncommon but devastating complication of abdominal wall reconstruction. The authors report clinical risk factors that may facilitate perioperative risk-reduction strategies to improve outcomes of elective abdominal wall reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Melanocortin-1 Receptor Polymorphisms and the Risk of Complicated Sepsis After Trauma: A Candidate Gene Association Study.

OBJECTIVE: The aim of the study was to determine if melanocortin-1 receptor (MC1R) single nucleotide polymorphisms (SNPs) are associated with complicated sepsis after trauma. BACKGROUND: Nosocomial infections are an important cause of morbidity and mortality after trauma. Several SNPs in inflammation-related genes have been associated with sepsis. MC1R is an anti-inflammatory mediator that may be involved in the immune response after trauma. PATIENTS AND METHODS: We genotyped eight common MC1R SNPs in genomic DNA from subjects enrolled in a previously reported prospective cohort study. Subjects were adult trauma patients admitted to the intensive care unit at a Level 1 trauma center (2003-2005). RESULTS: A total of 1,246 subjects were included in the analysis. The majority were male (70%), severely injured (81%), and injured by a blunt mechanism (89%). Forty percent developed sepsis, and 23% developed complicated sepsis, which was defined as sepsis with organ dysfunction. In logistic regression analysis, with adjustments for age, sex, body mass index, injury severity score, red blood cell transfusion requirement, and mechanism of injury, the MC1RR163Q variant (rs885479) was associated with a lower risk of developing complicated sepsis (adjusted odds ratio [ORadj] = 0.48, 95% confidence interval [CI]: 0.28-0.81, P = 0.006). In a subgroup of 511 subjects with genome-wide SNP data, the association between the MC1RR163Q variant and complicated sepsis remained significant after adjusting for genetic substructure (by principal components) and the above clinical factors (ORadj = 0.30, 95% CI: 0.13-0.70, P = 0.005). CONCLUSIONS: MC1RR163Q is associated with a lower risk of complicated sepsis after trauma. Therapeutic targeting of MC1R may be beneficial for trauma patients at risk for complicated sepsis.