LOX-1 and MMP-9 Inhibition Attenuates the Detrimental Effects of Delayed rt-PA Therapy and Improves Outcomes After Acute Ischemic Stroke.

BACKGROUND: Acute ischemic stroke triggers endothelial activation that disrupts vascular integrity and increases hemorrhagic transformation leading to worsened stroke outcomes. rt-PA (recombinant tissue-type plasminogen activator) is an effective treatment; however, its use is limited due to a restricted time window and hemorrhagic transformation risk, which in part may involve activation of MMPs (matrix metalloproteinases) mediated through LOX-1 (lectin-like oxLDL [oxidized low-density lipoprotein] receptor 1). This study's overall aim was to evaluate the therapeutic potential of novel MMP-9 (matrix metalloproteinase 9) ± LOX-1 inhibitors in combination with rt-PA to improve stroke outcomes. METHODS: A rat thromboembolic stroke model was utilized to investigate the impact of rt-PA delivered 4 hours poststroke onset as well as selective MMP-9 (JNJ0966) ±LOX-1 (BI-0115) inhibitors given before rt-PA administration. Infarct size, perfusion, and hemorrhagic transformation were evaluated by 9.4-T magnetic resonance imaging, vascular and parenchymal MMP-9 activity via zymography, and neurological function was assessed using sensorimotor function testing. Human brain microvascular endothelial cells were exposed to hypoxia plus glucose deprivation/reperfusion (hypoxia plus glucose deprivation 3 hours/R 24 hours) and treated with ±tPA and ±MMP-9 ±LOX-1 inhibitors. Barrier function was assessed via transendothelial electrical resistance, MMP-9 activity was determined with zymography, and LOX-1 and barrier gene expression/levels were measured using qRT-PCR (quantitative reverse transcription PCR) and Western blot. RESULTS: Stroke and subsequent rt-PA treatment increased edema, hemorrhage, MMP-9 activity, LOX-1 expression, and worsened neurological outcomes. LOX-1 inhibition improved neurological function, reduced edema, and improved endothelial barrier integrity. Elevated MMP-9 activity correlated with increased edema, infarct volume, and decreased neurological function. MMP-9 inhibition reduced MMP-9 activity and LOX-1 expression. In human brain microvascular endothelial cells, LOX-1/MMP-9 inhibition differentially attenuated MMP-9 levels, inflammation, and activation following hypoxia plus glucose deprivation/R. CONCLUSIONS: Our findings indicate that LOX-1 inhibition and ± MMP-9 inhibition attenuate negative aspects of ischemic stroke with rt-PA therapy, thus resulting in improved neurological function. While no synergistic effect was observed with simultaneous LOX-1 and MMP-9 inhibition, a distinct interaction is evident.

Repositioning the Early Pathology of Type 1 Diabetes to the Extraislet Vasculature.

Type 1 diabetes (T1D) is a prototypic T cell-mediated autoimmune disease. Because the islets of Langerhans are insulated from blood vessels by a double basement membrane and lack detectable lymphatic drainage, interactions between endocrine and circulating T cells are not permitted. Thus, we hypothesized that initiation and progression of anti-islet immunity required islet neolymphangiogenesis to allow T cell access to the islet. Combining microscopy and single cell approaches, the timing of this phenomenon in mice was situated between 5 and 8 wk of age when activated anti-insulin CD4 T cells became detectable in peripheral blood while peri-islet pathology developed. This "peri-insulitis," dominated by CD4 T cells, respected the islet basement membrane and was limited on the outside by lymphatic endothelial cells that gave it the attributes of a tertiary lymphoid structure. As in most tissues, lymphangiogenesis seemed to be secondary to local segmental endothelial inflammation at the collecting postcapillary venule. In addition to classic markers of inflammation such as CD29, V-CAM, and NOS, MHC class II molecules were expressed by nonhematopoietic cells in the same location both in mouse and human islets. This CD45- MHC class II+ cell population was capable of spontaneously presenting islet Ags to CD4 T cells. Altogether, these observations favor an alternative model for the initiation of T1D, outside of the islet, in which a vascular-associated cell appears to be an important MHC class II-expressing and -presenting cell.

Trends in the Adoption of Outpatient Joint Arthroplasties and Patient Risk: A Retrospective Analysis of 2019 to 2021 Medicare Claims Data.

INTRODUCTION: Total joint arthroplasties (TJAs) have recently been shifting toward outpatient arthroplasty. This study aims to explore recent trends in outpatient total joint arthroplasty (TJA) procedures and examine whether patients with a higher comorbidity burden are undergoing outpatient arthroplasty. METHODS: Medicare fee-for-service claims were screened for patients who underwent total hip, knee, or shoulder arthroplasty procedures between January 2019 and December 2022. The procedure was considered to be outpatient if the patient was discharged on the same date of the procedure. The Hierarchical Condition Category Score (HCC) and the Charlson Comorbidity Index (CCI) scores were used to assess patient comorbidity burden. Patient adverse outcomes included all-cause hospital readmission, mortality, and postoperative complications. Logistic regression analyses were used to evaluate if higher HCC/CCI scores were associated with adverse patient outcomes. RESULTS: A total of 69,520, 116,411, and 41,922 respective total knee, hip, and shoulder arthroplasties were identified, respectively. Despite earlier removal from the inpatient-only list, outpatient knee and hip surgical volume did not markedly increase until the pandemic started. By 2022Q4, 16%, 23%, and 36% of hip, knee, and shoulder arthroplasties were discharged on the same day of surgery, respectively. Both HCC and CCI risk scores in outpatients increased over time (P < 0.001). DISCUSSION: TJA procedures are shifting toward outpatient surgery over time, largely driven by the COVID-19 pandemic. TJA outpatients' HCC and CCI risk scores increased over this same period, and additional research to determine the effects of this should be pursued. LEVEL OF EVIDENCE: Level III, therapeutic retrospective cohort study.

Neonatal Graves disease with persistent hypoglycemia: A case report.

Neonatal Graves disease is the most common cause of hyperthyroidism during the newborn period. Maternal Graves disease increases the risk of intrauterine growth restriction, small for gestational age, and neonatal Graves disease. Intrauterine growth restriction and small for gestational age are associated with hypoglycemia and transient neonatal hyperinsulinism. Neonatal Graves disease with severe persistent hypoglycemia has not been well described. We present the case of a female patient born at 34 weeks and 3 days with a birth weight of 1.6 kg (fifth percentile) to a mother with recent treatment for Graves disease. Prenatal ultrasounds were significant for intrauterine growth restriction and small for gestational age. The mother did not begin hyperthyroidism medical therapy until 23 weeks and 2 days of gestation. After the infant was born, the infant not only had symptoms of hyperthyroidism such as tachycardia and abnormal thyroid values but also had persistent hypoglycemia, which could be due to maternal propranolol usage, prematurity, IUGR, increased metabolism due to neonatal Graves, and transient stress-induced hyperinsulinism. The infant was started on methimazole for hyperthyroidism and propranolol for tachycardia. She was also started on diazoxide for persistent hypoglycemia. By 6 months of age, the hyperthyroidism and hypoglycemia had resolved. This is an interesting case of neonatal Graves disease with severe persistent hypoglycemia which we suspect is due to transient neonatal hyperinsulinism induced by multiple stress responses.

The Top 100 Classical and Contemporary Papers on Elbow Surgery: A Trend Analysis of Elbow Surgery Literature.

INTRODUCTION: Bibliometric analyses provide an aggregate of the most frequently cited literature in a given field. The purpose of this study was to analyze the top 100 most-cited classical and contemporary papers relating to elbow surgery to serve as a reference for surgeons and trainees for educational and research purposes. METHODS: A search was conducted for all papers containing the term "elbow" in the categories Orthopedics, Surgery, and Sports Science in the Clarivate Web of Science. Classical papers were those published from 1980 to 2009, and contemporary papers were those published from 2010 to 2019. Articles were assessed by country of origin, authors and their credentials, parent journal, level of evidence, and topic. RESULTS: Citation frequency ranged from 86 to 867. Among the classical group, there were more level IV papers compared with level I papers; however, the opposite was true in the contemporary group. The most common topic in the classical group was elbow anatomy and function, and the most common topic in the contemporary group was lateral epicondylitis and medial epicondylitis and associated therapies. DISCUSSION: This bibliometric analysis serves to help guide surgeons and trainees on the highly cited articles and important topics in elbow surgery, demonstrating a shift to prospective randomized controlled trials in recent years. LEVEL OF EVIDENCE: Level V (Systematic Review with Level V as Lowest LOE).

Mixed-Reality Improves Execution of Templated Glenoid Component Positioning in Shoulder Arthroplasty: A CT Imaging Analysis.

INTRODUCTION: Glenoid placement is critical for successful outcomes in total shoulder arthroplasty (TSA). Preoperative templating with three-dimensional (3D) imaging has improved implant positioning, but deviations from the planned inclination and version still occur. Mixed-Reality (MR) is a novel technology that allows surgeons intra-operative access to 3D imaging and templates, capable of overlaying the surgical field to help guide component positioning. The purpose of this study was to compare the execution of preoperative templates using MR versus standard instruments (SI). METHODS: Retrospective review of 97 TSAs (18 anatomic, 79 reverse) from a single high-volume shoulder surgeon between January 2021 and February 2023, including only primary diagnoses of osteoarthritis, rotator cuff arthropathy, or a massive irreparable rotator cuff tear. To be included, patients needed a templated preoperative plan and then a postoperative computed tomography scan. Allocation to MR vs. SI was based on availability of the MR headset, industry technical personnel, and the templated preoperative plan loaded into the software, but preoperative or intraoperative patient factors did not contribute to the allocation decision. Postoperative inclination and version were measured by two independent, blinded physicians and compared to the preoperative template. From these measurements, we calculated the mean difference, standard deviation (SD), and variance to compare MR and SI. RESULTS: Comparing 25 MR to 72 SI cases, MR significantly improved both inclination (p<0.001) and version (p<0.001). Specifically, MR improved the mean difference from preoperative templates (by 1.9º inclination, 2.4º version), narrowed the SD (by 1.7o inclination, 1.8o version), and decreased the variance (11.7 to 3.0 inclination, 14.9 to 4.3 version). A scatterplot of the data demonstrates a concentration of MR cases within 5° of plan relative to SI cases typically within 10° of plan. There was no difference in operative time. CONCLUSION: MR improved the accuracy and precision of glenoid positioning. Although it is unlikely that 2o makes a detectable clinical difference, our results demonstrate the potential ability for technology like MR to narrow the bell curve and decrease the outliers in glenoid placement. This will be particularly relevant as MR and other similar technologies continue to evolve into more effective methods in guiding surgical execution.

Methylprednisolone taper is an effective addition to multimodal pain regimens after total shoulder arthroplasty: results of a randomized controlled trial: 2022 Neer Award winner.

BACKGROUND: Perioperative corticosteroids have shown potential as nonopioid analgesic adjuncts for various orthopedic pathologies, but there is a lack of research on their use in the postoperative setting after total shoulder arthroplasty (TSA). The purpose of this study was to assess the effect of a methylprednisolone taper on a multimodal pain regimen after TSA. METHODS: This study was a randomized controlled trial (clinicaltrials.gov NCT03661645) of opioid-naive patients undergoing TSA. Patients were randomly assigned to receive intraoperative dexamethasone only (control group) or intraoperative dexamethasone followed by a 6-day oral methylprednisolone (Medrol) taper course (treatment group). All patients received the same standardized perioperative pain management protocol. Standardized pain journal entries were used to record visual analog pain scores (VAS-pain), VAS-nausea scores, and quantity of opioid tablet consumption during the first 7 postoperative days (POD). Patients were followed for at least one year postoperatively for clinical evaluation, collection of patient-reported outcomes, and observation of complications. RESULTS: A total of 67 patients were enrolled in the study; 32 in the control group and 35 in the treatment group. The groups had similar demographics and comorbidities. The treatment group demonstrated a reduction in mean VAS pain scores over the first 7 POD. Between POD 1 and POD 7, patients in the control group consumed an average of 17.6 oxycodone tablets while those in the treatment group consumed an average of 5.5 tablets. This equated to oral morphine equivalents of 132.1 and 41.1 for the control and treatment groups, respectively. There were fewer opioid-related side effects during the first postoperative week in the treatment group. The treatment group reported improved VAS pain scores at 2-week, 6-week, and 12-week postoperatively. There were no differences in Europe Quality of Life, shoulder subjective value (SSV), at any time point between groups, although American Shoulder and Elbow Surgeons questionnaire scores showed a slight improvement at 6-weeks in the treatment group. At mean follow-up, (control group: 23.4 months; treatment group:19.4 months), there was 1 infection in the control group and 1 postoperative cubital tunnel syndrome in the treatment group. No other complications were reported. CONCLUSIONS: A methylprednisolone taper course shows promise in reducing acute pain and opioid consumption as part of a multimodal regimen following TSA. As a result of this study, we have included this 6-day methylprednisolone taper course in our multimodal regimen for all primary shoulder arthroplasties. We hope this trial serves as a foundation for future studies on the use of low-dose oral corticosteroids and other nonnarcotic modalities to control pain after shoulder surgeries.

Upper Extremity Fractures in the Emergency Department: A Database Analysis of National Trends in the United States.

BACKGROUND: Upper extremity (UE) fractures are a common reason for emergency department (ED) visits, but recent data on their epidemiology are lacking. This study aimed to describe the incidence, demographics, patient characteristics, and associated health care factors of UE fractures, hypothesizing that they would remain prevalent in the ED setting. METHODS: Using the Nationwide ED Sample database, patients presenting to the ED with UE fractures in 2016 were identified, and population estimates were used to calculate incidence rates. Data on insurance status, trauma designation, cost, and teaching status were analyzed. RESULTS: The study identified 2 118 568 patients with UE fractures, representing 1.5% of all ED visits in 2016. Men accounted for 54.2% of UE fractures, with phalangeal fractures being most common. Distal radius and/or ulna fractures were most common in women (30.4%). The greatest proportion of UE fractures (23.2%) occurred in patients aged 5 to 14 years (1195.5 per 100 000). Nontrauma centers were the most common treating institutions (50.4%), followed by level I (19.5%), II (15.3%), and III (12.8%) centers. The greatest proportion of fractures (38.3%) occurred in the southern United States. Emergency department cost of treatment was almost 2-fold in patients with open UE fractures compared with closed. CONCLUSION: This study provides important epidemiological information on UE fractures in 2016. The incidence rate of UE fractures in the ED has remained high, with most occurring in the distal radius, phalanges, and clavicle. In addition, UE fractures were most common in younger patients, men, and those in the southern United States during the summer. These findings can be useful for health care providers and policymakers when evaluating and treating patients with UE fractures.

A Changing Landscape in the Surgical Management of Wrist Arthritis: An Analysis of National Trends From 2009 to 2019.

PURPOSE: The purpose of this study was to analyze the trends in the annual volume and incidence of proximal row carpectomy (PRC), four-corner fusion (4CF), total wrist arthrodesis (TWF), and total wrist arthroplasty (TWA) from 2009 to 2019 in the United States. METHODS: The IBM Watson Health MarketScan databases were queried to identify annual case volumes for PRC, 4CF, TWF, and TWA from 2009 to 2019. The annual incidence of these procedures was then calculated based on the population estimates from the US Census Bureau. Trends in annual volume and incidence over the study period were evaluated using regression line analysis. Further subgroup analysis was conducted based on age and region. RESULTS: From 2009 to 2019, the total case volumes for the four procedures increased by 3.4%, but the incidence decreased by 2.8%. However, PRC case volume and incidence trends significantly increased (38.2% and 29.7%, respectively), whereas 4CF remained constant. Conversely, the case volume and incidence of TWA significantly decreased (-52.2% and -54.5%, respectively), whereas TWF remained constant. When stratified by age, all four procedures decreased in the <45-year-old cohort (combined -35.1%) significantly for 4CF, TWF, and TWA. TWA decreased significantly in the <45-year-old and 45- to 65-year-old cohorts (53.6% and 63.2%, respectively). For age >65 years, the total case incidence increased by 98.9%, including a significant positive trend in TWF (175%). CONCLUSIONS: Surgical management of wrist arthritis remains a controversial issue. However, PRC has gained recent support in the literature, and our results reflect this shift, even for the <45-year-old cohort. Furthermore, TWA declined, despite reports of positive early outcomes for fourth-generation implants. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Cell-based versus corticosteroid injections for knee pain in osteoarthritis: a randomized phase 3 trial.

Various types of cellular injection have become a popular and costly treatment option for patients with knee osteoarthritis despite a paucity of literature establishing relative efficacy to each other or corticosteroid injections. Here we aimed to identify the safety and efficacy of cell injections from autologous bone marrow aspirate concentrate, autologous adipose stromal vascular fraction and allogeneic human umbilical cord tissue-derived mesenchymal stromal cells, in comparison to corticosteroid injection (CSI). The study was a phase 2/3, four-arm parallel, multicenter, single-blind, randomized, controlled clinical trial with 480 patients with a diagnosis of knee osteoarthritis (Kellgren-Lawrence II-IV). Participants were randomized to the three different arms with a 3:1 distribution. Arm 1: autologous bone marrow aspirate concentrate (n = 120), CSI (n = 40); arm 2: umbilical cord tissue-derived mesenchymal stromal cells (n = 120), CSI (n = 40); arm 3: stromal vascular fraction (n = 120), CSI (n = 40). The co-primary endpoints were the visual analog scale pain score and Knee injury and Osteoarthritis Outcome Score pain score at 12 months versus baseline. Analyses of our primary endpoints, with 440 patients, revealed that at 1 year post injection, none of the three orthobiologic injections was superior to another, or to the CSI control. In addition, none of the four groups showed a significant change in magnetic resonance imaging osteoarthritis score compared to baseline. No procedure-related serious adverse events were reported during the study period. In summary, this study shows that at 1 year post injection, there was no superior orthobiologic as compared to CSI for knee osteoarthritis. ClinicalTrials.gov Identifier: NCT03818737.

Preoperative Depression Is Associated With Increased Complications Following Distal Radius Fracture Surgery.

BACKGROUND: Depression is a known risk factor for inferior outcomes after orthopedic procedures, but its specific relationship with distal radius fractures remains unknown. This study investigates the relationship between preoperative diagnosed depression and common postoperative complications occurring within the first year after open reduction internal fixation (ORIF) for distal radius fractures. METHODS: This retrospective study used Truven MarketScan database and the Current Procedural Terminology (CPT) codes to identify distal radius fracture patients who underwent ORIF in the United States between January 1, 2009, and December 31, 2019. International Classification of Diseases (ICD) codes were used to identify patients with and without a diagnosis of preoperative depression. Univariate, multivariate, t test, and χ2 analyses were performed to determine the association between preoperative depression and postoperative complications following a distal radius fracture surgery. RESULTS: Of the 75 098 eligible patients, 9.9% had at least one ICD code associated with preoperative depression. Preoperative depression was associated with increased odds for surgical site infection (odds ratio [OR] 1.25, confidence interval [CI] 1.14-1.37), emergency department visits for postoperative pain (OR 1.28, CI 1.15-1.36), hardware complication (OR 1.18, CI 1.07-1.30), removal of hardware within 1 year (OR 1.16, CI 1.09-1.27), wound complication (OR 1.17, CI 1.08-1.27), and 30-day readmission (OR 1.21, CI 1.07-1.31). CONCLUSIONS: Preoperative diagnosed depression is associated with increased complications following distal radius fracture surgery. These results can help guide preoperative and postoperative protocols in these higher risk patients. More research is needed to investigate if depression is a modifiable risk factor, as depression treatment could potentially improve postsurgical outcomes.

Tramadol use before total shoulder arthroplasty: patients have lower risk of complications and resource utilization than those using traditional opioids.

BACKGROUND: Evidence continues to mount for the deleterious effects of preoperative opioid use in the setting of total shoulder arthroplasty (TSA). Tramadol, a synthetic opioid with concomitant neurotransmitter effects, has become a popular alternative to traditional opioids, but it has not been well studied in the preoperative setting of TSA. The purpose of this study is to evaluate postsurgical outcomes in TSA for patients with preoperative tramadol use compared with patients using traditional opioids and those who were opioid naïve. METHODS: Using the IBM Watson Health MarketScan databases, a retrospective cohort study was performed for patients who underwent TSA from 2009 to 2018. Filled pain prescriptions were collected, and prescribing trends were analyzed. Outcomes were compared between 4 patient cohorts defined by preoperative analgesia use-opioid naïve, tramadol, traditional opioids, and combination (opioids and tramadol). Multivariate analysis was used to account for small variations in cohort demographics and comorbidities. Analysis focused on resource utilization and complications. Revision rates at 1 and 3 years postoperatively were also compared. RESULTS: A total of 29,454 TSA patients were studied, with 8959 available for 3-year postoperative follow-up. Of these, 10,462 (35.5%) were prescribed traditional opioids and 2214 (7.5%) tramadol only. From 2009 to 2018, prescribing trends in the United States demonstrated a significant decrease in the number of patients prescribed preoperative narcotics, whereas the number of patients prescribed preoperative tramadol and those who were opioid naïve significantly increased. Compared with opioid-naïve patients, the traditional opioid cohort had significantly increased odds of resource utilization and complications, whereas the tramadol cohort did not. Specifically, the traditional opioid cohort had an increased risk of prosthetic joint infection compared with both opioid-naïve and tramadol cohorts. The traditional opioid cohort had higher revision rates than opioid-naïve patients at 1 and 3 years, whereas the tramadol cohort did not. CONCLUSION: Despite a decrease in opioid prescriptions over the study period, many patients in the United States remain on opioids. Although tramadol is not without its own risks, our results suggest that patients taking preoperative tramadol as an alternative to traditional opioids for glenohumeral arthritic pain had a lesser postoperative risk profile, comparable with opioid-naïve patients.

Total Wrist Arthroplasty as a Motion-Sparing Option for Distal Radius Malunion in a Patient of Advanced Age: A Case Report.

CASE: A 62-year-old woman presented with wrist pain secondary to a distal radius fracture malunion 4 months after a fall onto an outstretched hand. She was not an ideal candidate for osteotomy and bone graft because of the degree of displacement and osteoporosis, so after nonoperative treatment was unsuccessful, she was offered total wrist arthroplasty (TWA) or arthrodesis and opted for TWA. CONCLUSION: At 14-month follow-up, the patient reported significant improvement in her pain and function. The current generation of TWA implants may allow use in the management of symptomatic distal radius malunions in older, low-demand patients.

Trends and outcomes of outpatient total shoulder arthroplasty after its removal from CMS's inpatient-only list.

BACKGROUND: In January 2021, the US Medicare program approved reimbursement of outpatient total shoulder arthroplasties (TSA), including anatomic and reverse TSAs. It remains unclear whether shifting TSAs from the inpatient to outpatient setting has affected clinical outcomes. Herein, we describe the rate of outpatient TSA growth and compare inpatient and outpatient TSA complications, readmissions, and mortality. METHODS: Medicare fee-for-service claims for 2019-2022Q1 were analyzed to identify the trends in outpatient TSAs and to compare 90-day postoperative complications, all-cause hospital readmissions, and mortality between outpatients and inpatients. Outpatient cases were defined as those discharged on the same day of the surgery. To reduce the COVID-19 pandemic's impact and selection bias, we excluded 2020Q2-Q4 data and used propensity scores to match 2021-2022Q1 outpatients with inpatients from the same period (the primary analysis) and from 2019-2020Q1 (the secondary analysis), respectively. We performed both propensity score-matched and -weighted multivariate analyses to compare outcomes between the two groups. Covariates included sociodemographics, preoperative diagnosis, comorbid conditions, the Hierarchical Condition Category risk score, prior year hospital/skilled nursing home admissions, annual surgeon volume, and hospital characteristics. RESULTS: Nationally, the proportion of outpatient TSAs increased from 3% (619) in 2019Q1 to 22% (3456) in 2021Q1 and 38% (6778) in 2022Q1. A total of 55,166 cases were identified for the primary analysis (14,540 outpatients and 40,576 inpatients). Overall, glenohumeral osteoarthritis was the most common indication for surgery (70.8%), followed by rotator cuff pathology (14.6%). The unadjusted rates of complications (1.3 vs 2.4%, P < .001), readmissions (3.7 vs 6.1%, P < .001), and mortality (0.2 vs 0.4%, P = .024) were significantly lower among outpatient TSAs than inpatient TSAs. Using 1:1 nearest matching, 12,703 patient pairs were identified. Propensity score-matched multivariate analyses showed similar rates of postoperative complications, hospital readmissions, and mortality between outpatients and inpatients. Propensity score-weighted multivariate analyses resulted in similar conclusions. The secondary analysis showed a lower hospital readmission rate in outpatients (odds ratio: 0.8, P < .001). CONCLUSIONS: There has been accelerated growth in outpatient TSAs since 2019. Outpatient and inpatient TSAs have similar rates of postoperative complication, hospital readmission, and mortality.

Cubital Tunnel Syndrome: Does a Consensus Exist for Diagnosis?

PURPOSE: Cubital tunnel syndrome (CuTS) is the second most common compressive neuropathy of the upper extremity. We aimed to determine a consensus among experts using the Delphi method for clinical criteria that could be validated further for the diagnosis of CuTS. METHODS: The Delphi method was used for establishing a consensus among a group of expert panelists, comprising 12 hand and upper-extremity surgeons, who ranked the diagnostic clinical importance of 55 items related to CuTS on a scale from 1 (least important) to 10 (most important). The average and SDs of each item were calculated, and Cronbach α was used to assess homogeneity among the panelist-ranked items. RESULTS: All panelists answered the 55-item questionnaire. A Cronbach α value of 0.963 was obtained on the first iteration. The top criteria that were considered most clinically relevant to the diagnosis of CuTS among the group were determined based on the most highly ranked and correlated items among the expert panelist group. The criteria based on which there was agreement were as follows: (1) paresthesias in ulnar nerve distribution, (2) symptoms precipitated by increased elbow flexion/positive elbow flexion tests, (3) positive Tinel sign at the medial elbow, (4) atrophy/weakness/ late findings (eg, claw hand of the ring/small finger and Wartenberg or Froment sign) of ulnar nerve-innervated muscles of the hand, (5) loss of two-point discrimination in ulnar nerve distribution, and (6) similar symptoms on the involved side after successful treatment on the contralateral side. CONCLUSIONS: Our study demonstrated a consensus among an expert panelist group of hand and upper-extremity surgeons on potential diagnostic criteria for CuTS. This consensus on diagnostic criteria may help clinicians readily diagnose CuTS in a standardized form; however, further weighting and validation are necessary prior to the development of a formal diagnostic scale. CLINICAL RELEVANCE: This study is the first step in producing a consensus on how to diagnose CuTS.

Modern Treatment of Neurogenic Thoracic Outlet Syndrome: Pathoanatomy, Diagnosis, and Arthroscopic Surgical Technique.

Compressive pathology in the supraclavicular and infraclavicular fossae is broadly termed "thoracic outlet syndrome," with the large majority being neurogenic in nature. These are challenging conditions for patients and physicians and require robust knowledge of thoracic outlet anatomy and scapulothoracic kinematics to elucidate neurogenic versus vascular disorders. The combination of repetitive overhead activity and scapular dyskinesia leads to contracture of the scalene muscles, subclavius, and pectoralis minor, creating a chronically distalized and protracted scapular posture. This decreases the volume of the scalene triangle, costoclavicular space, and retropectoralis minor space, with resultant compression of the brachial plexus causing neurogenic thoracic outlet syndrome. This pathologic cascade leading to neurogenic thoracic outlet syndrome is termed pectoralis minor syndrome when primary symptoms localize to the infraclavicular area. Making the correct diagnosis is challenging and requires the combination of complete history, physical examination, advanced imaging, and ultrasound-guided injections. Most patients improve with nonsurgical treatment incorporating pectoralis minor stretching and periscapular and postural retraining. Surgical decompression of the thoracic outlet is reserved for compliant patients who fail nonsurgical management and respond favorably to targeted injections. In addition to prior exclusively open procedures with supraclavicular, infraclavicular, and/or transaxillary approaches, new minimally invasive and targeted endoscopic techniques have been developed over the past decade. They involve the endoscopic release of the pectoralis minor tendon, with additional suprascapular nerve release, brachial plexus neurolysis, and subclavius and interscalene release depending on the preoperative work-up.

Modern Treatment of Cubital Tunnel Syndrome: Evidence and Controversy.

Cubital tunnel syndrome is the second most common peripheral mononeuropathy in the upper extremity. However, the diagnosis and treatment of cubital tunnel syndrome remains controversial without a standard algorithm. Although diagnosis can often be made from the patient's history and physical examination alone, electrodiagnostic studies, ultrasound, computed tomography (CT), and magnetic resonance image (MRI) can also be useful in diagnosing the disease and selecting the most appropriate treatment option. Treatment options include conservative nonoperative techniques as well as various surgical options, including in situ decompression with or without transposition, medial epicondylectomy, and nerve transfer in advanced disease. The purpose of this review is to summarize the most up-to-date literature regarding cubital tunnel syndrome and propose a treatment algorithm to provide clarity about the challenges of treating this complex patient population.

Measuring anti-islet autoimmunity in mouse and human by profiling peripheral blood antigen-specific CD4 T cells.

The endocrine pancreas is one of the most inaccessible organs of the human body. Its autoimmune attack leads to type 1 diabetes (T1D) in a genetically susceptible population and a lifelong need for exogenous insulin replacement. Monitoring disease progression by sampling peripheral blood would provide key insights into T1D immune-mediated mechanisms and potentially change preclinical diagnosis and the evaluation of therapeutic interventions. This effort has been limited to the measurement of circulating anti-islet antibodies, which despite a recognized diagnostic value, remain poorly predictive at the individual level for a fundamentally CD4 T cell-dependent disease. Here, peptide-major histocompatibility complex tetramers were used to profile blood anti-insulin CD4 T cells in mice and humans. While percentages of these were not directly informative, the state of activation of anti-insulin T cells measured by RNA and protein profiling was able to distinguish the absence of autoimmunity versus disease progression. Activated anti-insulin CD4 T cell were detected not only at time of diagnosis but also in patients with established disease and in some at-risk individuals. These results support the concept that antigen-specific CD4 T cells might be used to monitor autoimmunity in real time. This advance can inform our approach to T1D diagnosis and therapeutic interventions in the preclinical phase of anti-islet autoimmunity.