A Recurrent Schwannoma in the Left Distal Ulnar Nerve.

While peripheral nerve schwannomas have a relatively low incidence, schwannomatosis, the condition in which one forms multiple recurring schwannomas, is an even rarer phenomenon and can be hard to detect given its ability to mimic other conditions. We report a case of a 35-year-old male who presented with a mass in his left wrist and forearm, volar pain in his forearm, and numbness in his fingers. Magnetic resonance imaging (MRI) revealed a bilobed heterogeneous neural sheath tumor in the distal left ulnar nerve. The tumor was resected including extensive internal neurolysis using a Zeiss operative microscope. Post-operative biopsy confirmed an encapsulated schwannoma. The patient did well initially but developed worsening pain in his forearm and weakness. He had persistent paresthesias in the ulnar nerve distribution. He underwent a repeat MRI almost one year later, which showed thickening of the ulnar nerve proximal to the area of resection with an 8.5 mm hyperintense nodule. The patient underwent a subsequent resection with extensive neurolysis, which confirmed that the mass was a benign non-invasive schwannoma. At six weeks post-surgery, the patient's forearm pain was significantly improved and his range of motion returned to baseline. Our case demonstrates the importance of post-operative follow-up in schwannomas with appropriate imaging if symptoms persist or recur.

Loss of ß-cell identity and dedifferentiation, not an irreversible process?

Type 2 diabetes (T2D) is a polygenic metabolic disorder characterized by insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While the decline in insulin production and secretion was previously attributed to apoptosis of insulin-producing ß-cells, recent studies indicate that ß-cell apoptosis rates are relatively low in diabetes. Instead, ß-cells primarily undergo dedifferentiation, a process where they lose their specialized identity and transition into non-functional endocrine progenitor-like cells, ultimately leading to ß-cell failure. The underlying mechanisms driving ß-cell dedifferentiation remain elusive due to the intricate interplay of genetic factors and cellular stress. Understanding these mechanisms holds the potential to inform innovative therapeutic approaches aimed at reversing ß-cell dedifferentiation in T2D. This review explores the proposed drivers of ß-cell dedifferentiation leading to ß-cell failure, and discusses current interventions capable of reversing this process, thus restoring ß-cell identity and function.

Renal-Limited Thrombotic Microangiopathy in a Patient Who Received Gemcitabine, Ramucirumab, and Pembrolizumab: A Case Report and Literature Review.

Cancer drug-induced thrombotic microangiopathy (DITMA) is an important and serious cause of kidney disease in cancer patients. In addition to classical chemotherapy, the increasing use of targeted therapy and immunotherapy has led to more oncotherapy-associated thrombotic microangiopathy (TMA). It is important for clinicians to recognize this potentially life-threatening adverse effect and gain knowledge of the patient's clinical course and treatment response. In this paper, we report a patient with lung cancer, who was treated with three different classes of anti-neoplastic agents, gemcitabine, ramucirumab, and pembrolizumab. This patient subsequently developed renal-limited thrombotic microangiopathy(rTMA) requiring hemodialysis. The varying features of TMA caused by these therapies were discussed. We also described the clinical course, diagnostic challenges, and management of this patient.

Intermittent fasting protects ß-cell identity and function in a type-2 diabetes model.

Type 2 diabetes (T2DM) is caused by the interaction of multiple genes and environmental factors. T2DM is characterized by hyperglycemia, insulin secretion deficiency and insulin resistance. Chronic hyperglycemia induces ß-cell dysfunction, loss of ß-cell mass/identity and ß-cell dedifferentiation. Intermittent fasting (IF) a commonly used dietary regimen for weight-loss, also induces metabolic benefits including reduced blood glucose, improved insulin sensitivity, reduced adiposity, inflammation, oxidative-stress and increased fatty-acid oxidation; however, the mechanisms underlying these effects in pancreatic ß-cells remain elusive. KK and KKAy, mouse models of polygenic T2DM spontaneously develop hyperglycemia, glucose intolerance, glucosuria, impaired insulin secretion and insulin resistance. To determine the long-term effects of IF on T2DM, 6-weeks old KK and KKAy mice were subjected to IF for 16 weeks. While KKAy mice fed ad-libitum demonstrated severe hyperglycemia (460 mg/dL) at 6 weeks of age, KK mice showed blood glucose levels of 230 mg/dL, but progressively became severely diabetic by 22-weeks. Strikingly, both KK and KKAy mice subjected to IF showed reduced blood glucose and plasma insulin levels, decreased body weight gain, reduced plasma triglycerides and cholesterol, and improved insulin sensitivity. They also demonstrated enhanced expression of the ß-cell transcription factors NKX6.1, MAFA and PDX1, and decreased expression of ALDH1a3 suggesting protection from loss of ß-cell identity by IF. IF normalized glucose stimulated insulin secretion in islets from KK and KKAy mice, demonstrating improved ß-cell function. In addition, hepatic steatosis, gluconeogenesis and inflammation was decreased particularly in KKAy-IF mice, indicating peripheral benefits of IF. These results have important implications as an optional intervention for preservation of ß-cell identity and function in T2DM.

High Tidal Volume, High Positive End Expiratory Pressure and Apneic Breath Hold Strategies (Lung Navigation Ventilation Protocol) With Cone Beam Computed Tomography Bronchoscopic Biopsy of Peripheral Lung Lesions: Results in 100 Patients.

BACKGROUND: A dedicated anesthesia protocol for bronchoscopic lung biopsy-lung navigation ventilation protocol (LNVP)-specifically designed to mitigate atelectasis and reduce unnecessary respiratory motion, has been recently described. LNVP demonstrated significantly reduced dependent ground glass, sublobar/lobar atelectasis, and atelectasis obscuring target lesions compared with conventional ventilation. METHODS: In this retrospective, single-center study, we examine the impact of LNVP on 100 consecutive patients during peripheral lung lesion biopsy. We report the incidence of atelectasis using cone beam computed tomography imaging, observed ventilatory findings, anesthesia medications, and outcomes, including diagnostic yield, radiation exposure, and complications. RESULTS: Atelectasis was observed in a minority of subjects: ground glass opacity atelectasis was seen in 30 patients by reader 1 (28%) and in 18 patients by reader 2 (17%), with good agreement between readers (κ = 0.78). Sublobar/lobar atelectasis was observed in 23 patients by reader 1 and 26 patients by reader 2, also demonstrating good agreement (κ = 0.67). Atelectasis obscured target lesions in very few cases: 0 patients (0%, reader 1) and 3 patients (3%, reader 2). Diagnostic yield was 85.9% based on the AQuIRE definition. Pathology demonstrated 57 of 106 lesions (54%) were malignant, 34 lesions (32%) were benign, and 15 lesions (14%) were nondiagnostic. CONCLUSION: Cone beam computed tomography images confirmed low rates of atelectasis, high tool-in-lesion confirmation rate, and high diagnostic yield. LNVP has a similar safety profile to conventional bronchoscopy. Most patients will require intravenous fluid and vasopressor support. Further study of LNVP and other ventilation protocols are necessary to understand the impact of ventilation protocols on bronchoscopic peripheral lung biopsy.

Pearls and pitfalls of PROMIS clinically significant outcomes in orthopaedic surgery.

INTRODUCTION: Patient-Reported Outcome Measurement Information System (PROMIS) was developed as a uniform and generalizable PROM system using item response theory and computer adaptive testing. We aimed to assess the utilization of PROMIS for clinically significant outcomes (CSOs) measurements and provide insights into its use in orthopaedic research. MATERIALS AND METHODS: We reviewed PROMIS CSO reports for orthopaedic procedures via PubMed, Cochrane Library, Embase, CINAHL, and Web of Science from inception to 2022, excluding abstracts and missing measurements. Bias was assessed using the Newcastle-Ottawa Scale (NOS) and questionnaire compliance. PROMIS domains, CSO measures, and study populations were described. A meta-analysis compared distribution and anchor-based MCIDs in low-bias (NOS ≥ 7) studies. RESULTS: Overall, 54 publications from 2016 to 2022 were reviewed. PROMIS CSO studies were observational with increasing publication rates. Evidence-level was II in 10/54, bias low in 51/54, and compliance ≥ 86% in 46/54. Most (28/54) analysed lower extremity procedures. PROMIS domains examined Pain Function (PF) in 44/54, Pain Interference (PI) in 36/54, and Depression (D) in 18/54. Minimal clinically important difference (MCID) was reported in 51/54 and calculated based on distribution in 39/51 and anchor in 29/51. Patient acceptable symptom state (PASS), substantial clinical benefit (SCB), and minimal detectable change (MDC) were reported in ≤ 10/54. MCIDs were not significantly greater than MDCs. Anchor-based MCIDs were greater than distribution based MCIDs (standardized mean difference = 0.44, p < 0.001). CONCLUSIONS: PROMIS CSOs are increasingly utilized, especially for lower extremity procedures assessing the PF, PI, and D domains using distribution-based MCID. Using more conservative anchor-based MCIDs and reporting MDCs may strengthen results. Researchers should consider unique pearls and pitfalls when assessing PROMIS CSOs.

Megadose Vitamin C Prescription Through Alternative Medicine Leading to End-Stage Renal Disease: Case Study and Literature Review.

Modern medicine has made tremendous advancements and succeeded in increasing longevity through adequate screening and diagnosis and various new therapeutic approaches. However, alternative medicine is a branch of health care practicing different traditional and unconventional, potentially hazardous therapies to treat commonly known ailments. Standard low-dose vitamin C, ie, 500-1000 mg, is approved in medical conditions like methemoglobinemia, scurvy, burns and also helps iron absorption in anemia. However, toxic doses carry high nephrotoxicity potential like in our case. We present a 74-year-old Caucasian female falling victim to one such alternative therapy leading to acute kidney injury requiring lifelong hemodialysis. She had endometrial cancer and received 100 gm of intravenous vitamin C weekly through a provider for the last 6 weeks as part of this alternate approach to cure her cancer. Upon admission, the serum creatinine level was elevated at 8.2 mg/dl, which subsequently did not improve with conservative management. Renal biopsy revealed diffuse acute tubular injury with polarized microscopy demonstrating calcium oxalate crystals. While her blood vitamin C levels were high, the serum oxalate level was normal. She ended up requiring renal replacement therapy permanently. Alternative medicine continues to be a significant health care hazard with the potential to cause unwanted irreversible nephrotoxicity. Public attention is necessary at various social levels to counter the detrimental outcomes of alternative medicine.

Risk Factors for Nonunion Following Ankle Arthrodesis: A Systematic Review and Meta-analysis.

BACKGROUND: Nonunion is a postoperative complication after ankle arthrodesis (AA), which leads to increased morbidity and revision rates. Previous studies have identified risk factors for nonunion following AA, but no meta-analysis has been performed to stratify risk factors based on strength of evidence. METHODS: Abstracts and full-text articles were screened by 2 independent reviewers. Relevant data were extracted from the included studies. Random effects meta-analyses were summarized as forest plots of individual study and pooled random effect results. RESULTS: Database search yielded 13 studies involving 987 patients were included, and 37 potential risk factors for nonunion. Meta-analysis found 5 significant risk factors for nonunion post-AA. Strong evidence supports male gender (OR: 1.96; 95% CI: 1.13-3.41), smoking (OR: 2.89; 95% CI: 1.23-6.76), and history of operative site infection prior to arthrodesis (OR: 2.40; 95% CI: 1.13-5.09) as predictors for nonunion following AA. There was moderate evidence supporting history of open injury (OR: 5.95; 95% CI: 2.31-15.38) and limited evidence for preoperative avascular necrosis (OR: 13.16; 95% CI: 2.17-79.61) as possible risk factors for nonunion. CONCLUSION: The results of our meta-analysis suggest that male gender, smoking, and history of operative site infection have strong evidence and that history of open injury and avascular necrosis also have evidence as risk factors for nonunion. Surgeons should be cognizant of these risks when performing AA and closely follow up with patients with the aforementioned risk factors to ensure postoperative success. LEVELS OF EVIDENCE: Level V: Systematic review of cohort and case-control studies.

Patellar fracture among elite-level European soccer players: 4-year case-control cohort analysis of return to play, re-injury, and player performance.

OBJECTIVES: There is a paucity of literature investigating the relationship between patellar fracture and player performance of professional soccer players following return to play (RTP). Our goal is to determine the rate of RTP, time to RTP, and effect on player performance following patellar fracture. METHODS: Twenty-one elite-level European professional soccer players who sustained a patellar fracture between 1999 and 2018 were identified via a publicly accessible database. Athletes with patellar fracture were matched to controls by age, height, years played in the league, season of injury, and position. Change in performance metrics between one season prior to injury and the following four seasons after injury were compared. RESULTS: Players with patellar fracture were absent for a mean 207.95 ± 135.55 days and 16.81 ± 31.79 games. Fifteen (71%) players returned to play after injury with 67% returning within 1 season after injury. Injured players did not demonstrate significant change in performance metrics at any of the follow-up timepoints compared to control. Subgroup analysis showed that attackers recorded approximately 1200 fewer minutes played per season than pre-injury levels 2 seasons following injury, significantly fewer (p < 0.05) than the control cohort recording similar minutes per season throughout the study period. Midfielders and defenders demonstrated similar fluctuations in performance to the control cohort for both field time and performance metrics (p > 0.05). CONCLUSION: Seventy-one percent of players RTP after patellar fracture with an associated absence of 7 months and 17 missed games. Overall, injured players did not demonstrate a significant decline in performance as demonstrated by games played, total minutes played per season, minutes per game, assists, and goals 1 season after injury. Attackers played fewer minutes during the season of and 2 seasons after the initial injury.

Increasing Patient Age, Ambulatory Surgery Center Setting, and Surgeon Experience Are Associated With Shorter Operative Duration for Anterior Cruciate Ligament Reconstruction.

Purpose: To identify variables associated with operative duration and intraoperative or perioperative complications after primary anterior cruciate ligament reconstruction (ACLR). Methods: Surgeons who performed a minimum of 20 arthroscopic cases per month were recruited for participation through the Arthroscopy Association of North America from 2011 through 2013. All participants agreed to voluntarily submit data for 6 months of consecutive knee and shoulder arthroscopy cases. Only subjects coded for ACLR were analyzed, whereas revision cases were excluded. ACLRs were subdivided into isolated ACLR, ACLR with minor concomitant procedures, and ACLR with major concomitant procedures. Patient, surgeon, and surgical variables were analyzed for their effect on operative duration and complications. Results: One hundred thirty-five orthopaedic surgeons participated, providing 1,180 primary ACLRs (399 isolated ACLRs, 441 ACLRs plus minor procedures, and 340 ACLRs plus major procedures). Most surgeons were in private practice (72.8%). Most patients were male patients (58.8%), and the mean body mass index (BMI) was 26.2 ± 5.1. The overall mean operative duration was 95.9 ± 42.0 minutes (isolated ACLRs, 88.4 ± 36.8 minutes; ACLRs plus minor concomitant procedures, 90.1 ± 37.6 minutes; and ACLRs plus major concomitant procedures, 118.5 ± 112.4 minutes; P < .001). Patient age was inversely correlated with operative duration (ρ = -0.221, P < .001). Surgical procedures performed in an ambulatory surgery center had a shorter mean operative duration (91.5 ± 40.4 minutes) compared with those performed in a hospital setting (105.0 ± 43.8 minutes, P < .001). There were 22 intraoperative and 47 early postoperative complications, with the most common being deep vein thrombosis (n = 15). Surgical volume (knee arthroscopy cases per month) correlated inversely with operative time (ρ = -0.200, P = .001) and complication rate (ρ = -0.112, P < .001). Patient BMI was associated with increased odds of early postoperative complications on multivariate analysis (odds ratio, 1.060; P = .044; 95% confidence interval, 1.002-1.121). Conclusions: Increasing patient age, private practice, ambulatory surgery center setting, and surgeon experience are associated with a shorter operative duration for ACLR. Although an increasing number of arthroscopic knee procedures performed by surgeons correlated with fewer complications, only increasing patient BMI significantly predicted odds of complications. Level of Evidence: Level IV, prognostic case series.

Brevibacterium casei Induced Peritonitis in a Patient Undergoing Continuous Cycler Peritoneal Dialysis: Case Report and Literature Review.

Brevibacterium casei is an extremely rare organism that can lead to peritonitis in End-stage renal disease patients of peritoneal dialysis. Out of only five overall Brevibacterium species peritonitis reported worldwide, only two of them had B. casei subspecies peritonitis detected, with both needing peritoneal dialysis catheter removal and change in dialysis modality to hemodialysis. Our patient, an elderly 63-year-old Hispanic male, was on peritoneal dialysis at home and presented with features suggestive of peritonitis. He was diagnosed subsequently with B. casei and started on broad spectrum intraperitoneal antibiotics. However, he did not need dialysis modality change and recovered fully after 3 weeks of appropriate intraperitoneal antibiotics therapy. Longer antibiotics therapy and frequent clinical follow-up plus better clinician awareness are needed to prevent this rare infection.

Risk factors for nonunion following tibiotalocalcaneal arthrodesis: A systematic review and meta-analysis.

BACKGROUND: The goal of this study is to review the literature to identify risk factors for nonunion after tibiotalocalcaneal arthrodesis (TTCA) and stratify them based on strength of evidence. METHODS: Five databases were searched from inception to May 17th, 2020. Abstracts and full-text articles were screened for those that included risk factors predictive of nonunion following TTCA. RESULTS: Eight studies involving 624 patients were included and 33 potential risk factors for nonunion were identified. Strong evidence supported prior peripheral neuropathic conditions as risk factors for nonunion following surgery (OR: 2.86, 95% CI: 1.56-5.23). CONCLUSION: TTCA is an effective salvage procedure but is associated with high nonunion rates. The results of our meta-analysis suggest that prior peripheral neuropathic conditions have strong evidence for failure to achieve union. Surgeons should be cognizant of these risks when performing TTCA and carefully monitor patients with the aforementioned comorbidity to achieve successful results.

Do Outcomes of Meniscal Allograft Transplantation Differ Based on Age and Sex? A Comparative Group Analysis.

PURPOSE: To analyze the effect of patient age, sex, and associated preoperative factors on patient-reported outcome (PRO) measures and graft survival following primary meniscal allograft transplantation (MAT). METHODS: A prospectively collected database was retrospectively reviewed to identify patients who underwent primary MAT with a minimum of 2 years of follow up between 1999 and 2017. Demographic, intraoperative, and postoperative outcome data were collected for each patient. Postoperative outcomes were stratified based on age and sex, and comparative statistical analysis was performed between sexes, both >40 and <40. RESULTS: A total of 238 patients underwent primary MAT during the study period, of which 212 patients (mean age, 28.5 ± 9.0 years; range, 15.01-53.67 years) met the inclusion criteria with a mean follow-up of 5.1 ± 3.4 years (range 2.0-15.9 years). At final follow-up, patients ≥40 and <40 years of age demonstrated statistically significant improvements in nearly all PRO scores (P < .05 for both groups). There were no significant differences between either group for achievement of minimal clinically important difference for International Knee Documentation Committee (P = .48) or Knee Injury and Osteoarthritis Outcome Score symptoms (P = .76). Because of insufficient numbers, a statistically significant difference could not be demonstrated in reoperation rate (≥40: 1.49 ± 1.77 years, <40: 1.87 ± 1.98 years, P = .591), failure rate (≥40: 7/32 [21.9%], <40: 19/180 [10.6%], P = .072), or complication rate (≥40: 2/32 [6.3%], <40: 12/180 [6.7%], P = .930) based on age. Both sexes showed a significant improvement in PROs, whereas female patients were more likely to undergo revision surgery (P = .033), with no significant differences based on time to reoperation, failure, or complication rates. CONCLUSIONS: PROs similarly improved following MAT in both patients aged ≥40 and those <40 at final follow-up with no significant differences in minimal clinically important difference achievement rate, complication rate, reoperation rate, time to reoperation, or failure rate between groups. Female patients may be more likely to undergo revision surgery after MAT. LEVEL OF EVIDENCE: III; therapeutic retrospective comparison study.

Defining Clinically Significant Outcomes Following Superior Capsular Reconstruction With Acellular Dermal Allograft.

PURPOSE: To define clinically significant outcomes (CSO) thresholds for minimal clinically important difference (MCID), substantial clinical benefit (SCB), and patient-acceptable symptomatic state (PASS) in patients undergoing superior capsular reconstruction (SCR) with an acellular dermal allograft. We also evaluated patient-specific variables predictive of achieving CSO thresholds. METHODS: The American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES), Single Assessment Numeric Evaluation (SANE), and subjective Constant-Murley (Constant) scores were collected preoperatively and at the most recent follow up for patients undergoing SCR from 2010 to 2019. A distribution-based approach was used to calculate MCID, and an anchor-based approach was used to calculate SCB and PASS. Logistic regression was used to determine factors associated with CSO achievement. RESULTS: Fifty-eight patients were identified (n = 39 males; n = 19 females) with a mean age of 53.4 ± 14.1 years at surgery and an average follow-up of 23 months. The MCID, SCB, and PASS were 11.2, 18.02, and 68.82 for ASES, 14.5, 23.13, and 69.9 for SANE, and 3.6, 10, and 18 for Constant, respectively. Subscapularis tear, female sex, and workers compensation (WC) status reduced odds of achieving MCID. Reduced odds of achieving Constant SCB were associated with older age, female sex, and WC status, while concomitant distal clavicle excision during SCR and lower preoperative ASES increased odds of achieving ASES SCB. Reduced odds for achieving ASES PASS were associated with female sex and WC status, while reduced odds for achieving SANE PASS were associated with subscapularis tearing preoperatively. CONCLUSION: On the basis of calculated values for MCID, SCB, and PASS, subscapularis tearing, WC status, age, and sex are associated with failure to achieve clinically significant outcomes following SCR. Concomitant distal clavicle excision during SCR and lower preoperative ASES was predictive for achievement of MCID and SCB. By defining the thresholds and variables predictive of achieving CSOs following SCR, surgeons may better counsel patients prior to SCR. LEVEL OF EVIDENCE: Level IV, case series.

Successful Treatment of Calciphylaxis in a Young Female With End-Stage Renal Disease on Peritoneal Dialysis With Parathyroidectomy, Intensification of Dialysis, and Sodium Thiosulphate-A Case Report and Literature Review.

Calcific uremic arteriolopathy, commonly referred to as "calciphylaxis," is a rare life-threatening condition observed in patients with chronic kidney disease and end-stage renal disease on dialysis. This results in necrotic, ischemic, tender dermal lesions anywhere in the body, but mainly on the abdominal wall and lower extremities, where subcutaneous tissue is abundant. Histologically, it is defined by calcification in dermal capillaries, arterioles, and subcutaneous adipose tissues. It can occur in all advanced stages of chronic kidney disease as well as end-stage renal disease patients on hemodialysis or peritoneal dialysis. Our case highlights a successful case of calciphylaxis in a young female patient who underwent parathyroidectomy and intensification of peritoneal dialysis regimen along with the infusion of sodium thiosulphate injection resulting in complete resolution of the lesion in 3 months. With limited evidence of treatment options and increased frequency of this condition in a dialysis patient, our case highlights the key aspects of calciphylaxis management in a young end-stage renal disease patient who didn't need a change of dialysis modality. We also review the risk factors and current practiced management options of this condition in our article.

Roseomonas mucosa-Induced Peritonitis in a Patient Undergoing Continuous Cycler Peritoneal Dialysis: Case Report and Literature Analysis.

Roseomonas species, a rare Gram-negative microorganism, has seldom been reported to cause peritonitis in end-stage renal disease patients on peritoneal dialysis. Only seven cases of peritonitis by this rare microorganism have been reported worldwide. Treatment options can be challenging if not detected early and can lead to significant morbidity and mortality along with the switching of the dialysis modality to hemodialysis which is highly undesirable. Our patient is a 65-year-old Caucasian female who needed to be changed to emergency hemodialysis due to inability to perform peritoneal dialysis from suspected peritonitis and was subsequently discovered to have peritonitis from Roseomonas mucosa. She recovered with a prolonged antibiotics course and returned to peritoneal dialysis in 3 months following her treatment completion. Prompt diagnosis and prolonged antibiotics are a cornerstone in the management of this rare microorganism to prevent mortality and morbidity from peritonitis.

Traumatic Leg Fractures in UEFA Football Athletes: A Matched-Cohort Analysis of Return to Play, Reinjury, Player Retention, and Performance Outcomes.

BACKGROUND: The average professional soccer team experiences 1 to 2 traumatic leg fractures per season, with unknown effects on player performance. PURPOSE: To (1) determine the rate and time to return to play (RTP) following leg fracture, (2) investigate the rate of reinjury following RTP, and (3) investigate long-term effects that lower extremity (LE) fracture may have on elite soccer player performance. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Using publicly available records, we identified athletes sustaining a traumatic leg fracture across the 5 major European soccer leagues (English Premier League, Bundesliga, La Liga, Ligue 1, and Serie A) between 2000 and 2016. Athletes with leg fracture (femur, tibia, and/or fibula) were matched 1:2 to controls by demographic characteristics and performance metrics 1 season before the index timepoint. Investigations included the RTP rate, reinjury rate, player characteristics associated with RTP within 2 seasons, long-term player retention, performance metrics during the 4 following seasons, and subgroup analysis by player position. RESULTS: A total of 112 players with LE fracture and 224 controls were identified. Players with LE fractures were absent for a mean of 157 days (range, 24-601 days) and 21 games (range, 2-68 games). The rate of RTP within 1 season was 80%, with 4% experiencing subsequent refracture. Injured players remained active in the league at a higher rate than their uninjured counterparts. As compared with controls, injured athletes played 309 fewer total minutes (P < .05), scored 0.09 more assists per game (P < .01) 1 season after injury, and scored 0.12 more points per game 4 seasons after injury (P < .01). Defenders were most affected by an LE fracture, playing 5.24 fewer games (P < .05), 603 fewer total minutes (P < .01), and recording 0.19 more assists per 90 minutes of play as compared with controls 1 season after injury (P < .001). Attackers and midfielders demonstrated no significant difference in metrics after RTP when compared with controls. CONCLUSION: Most players sustaining an LE fracture returned to elite soccer at the same level after a significant loss of playing time, with a 4% rate of refracture. Player retention was higher for those sustaining an LE fracture versus uninjured controls. Overall, injured players did not experience a decline in performance after recovery from an LE fracture.

Hyponatremia and Fever in a Patient on Ipilimumab and Nivolumab (Immune Checkpoint Inhibitors): A Case Report.

Immune checkpoint inhibitors (ICIs) are novel anticancer therapy approved in multiple tumors and their use is rapidly increasing. They are associated with various systemic side effects that are immune-mediated and clinically coined as "immune-related adverse effects" (irAE). Hyponatremia is a possible side effect in patients receiving ICIs. Fever is another side effect that is mostly non-infectious. There are different mechanisms leading to hyponatremia in patients on ICIs, which could be (1) hypovolemic hyponatremia due to hemodynamic disturbance secondary to volume depletion (eg, from irAE like colitis and enteritis) or hypervolemia due to congestive heart failure, cirrhosis, or nephrosis; (2) syndrome of inappropriate antidiuretic hormone (SIADH) secretion (especially from underlying lung cancer or neurological irAE like encephalitis and meningitis) with elevated urine sodium and urine osmolarity; and (3) irAE-related endocrinopathies such as hypophysitis, adrenal insufficiency, and hypothyroidism leading to euvolemic hyponatremia. We describe an interesting case of hyponatremia and fever in a patient receiving Ipilimumab and Nivolumab. The possible etiology of hyponatremia, in this case, was hypovolemia and volume depletion secondary to fever.

Identification of genetic modifiers of lifespan on a high sugar diet in the Drosophila Genetic Reference Panel.

Genome-wide association studies (GWAS) have become beneficial in identifying genetic variants underlying susceptibility to various complex diseases and conditions, including obesity. Utilizing the Drosophila Genetic Reference Panel (DGRP), we performed a GWAS of lifespan of 193 genetically distinct lines on a high sugar diet (HSD). The DGRP analysis pipeline determined the most significant lifespan associated polymorphisms were within loci of genes involved in: neural processes, behavior, development, and apoptosis, among other functions. Next, based on the relevance to obesity pathology, and the availability of transgenic RNAi lines targeting the genes we identified, whole-body in vivo knockdown of several candidate genes was performed. We utilized the GAL4-UAS binary expression system to independently validate the impacts of these loci on Drosophila lifespan during HSD. These loci were largely confirmed to affect lifespan in that HSD setting, as well as a normal diet setting. However, we also detected unexpected dietary effects of the HSD, including inconsistent diet effects on lifespan relative to a normal diet and a strong downregulation of feeding quantity.

Comparison of 4 tests' utility for predicting need for emergency department care in patients with alcohol-related complaints.

INTRODUCTION: Intoxication is a common presenting complaint in emergency departments (ED), but many patients with intoxication do not need emergency care. Three screens (BLINDED, Brown, and San Francisco) attempt to determine which intoxicated patients can be triaged to a lower level of care. METHODS: Observational multi-center cohort study of patients presenting to one of three ED with complaints consistent with acute intoxication. When a qualifying patient was brought to the emergency department, a team member interviewed the triaging provider. Interviews covered all three screens and the provider's gestalt. Receiver operating curve (ROC) analysis was used to determine which screen performed best. Cases were reviewed to determine need for emergency care. RESULTS: Of the 199 subjects studied, 91% (181/199) were male and were 50 years old on average (SD = 12 years). Of the 55 subjects tested (28%), their average alcohol level was 251 mg/dL (SD = 146 mg/dL). Only 117 subjects (59%) had complete information for inclusion in the final comparison of screens. Provider gestalt performed best (AUC = 0.69), but there were no meaningful differences between any of the screens (AUC = 0.62-0.66, p > 0.05 for all comparisons). Inability to sit up was sensitive for needing emergent care (88%), but it was non-specific (17%). Similarly, signs of trauma were specific (99%) for ED care, but insensitive (18%). CONCLUSIONS: The three formal screens and provider gestalt performed similarly.