Diabetic retinopathy is a ceramidopathy reversible by anti-ceramide immunotherapy.

Diabetic retinopathy is a microvascular disease that causes blindness. Using acid sphingomyelinase knockout mice, we reported that ceramide generation is critical for diabetic retinopathy development. Here, in patients with proliferative diabetic retinopathy, we identify vitreous ceramide imbalance with pathologic long-chain C16-ceramides increasing and protective very long-chain C26-ceramides decreasing. C16-ceramides generate pro-inflammatory/pro-apoptotic ceramide-rich platforms on endothelial surfaces. To geo-localize ceramide-rich platforms, we invented a three-dimensional confocal assay and showed that retinopathy-producing cytokines TNFα and IL-1ß induce ceramide-rich platform formation on retinal endothelial cells within seconds, with volumes increasing 2-logs, yielding apoptotic death. Anti-ceramide antibodies abolish these events. Furthermore, intravitreal and systemic anti-ceramide antibodies protect from diabetic retinopathy in standardized rodent ischemia reperfusion and streptozotocin models. These data support (1) retinal endothelial ceramide as a diabetic retinopathy treatment target, (2) early-stage therapy of non-proliferative diabetic retinopathy to prevent progression, and (3) systemic diabetic retinopathy treatment; and they characterize diabetic retinopathy as a "ceramidopathy" reversible by anti-ceramide immunotherapy.

Orthopaedic Research Consortiums: A Review of Scope, Sex and Racial Representation.

Introduction The creation of research groups and consortiums has become more common in all medical and surgical specialities. The purpose of this investigation was to assess and describe collaborative research groups and consortiums within orthopaedic surgery. In addition, we aimed to define the demographics of the research consortium members with particular attention to female and minority members. Methods  Journals with a musculoskeletal/orthopaedic focus and a few medical journals were selected to identify articles published by research groups and consortiums. Articles published from 2020 to 2022 were manually reviewed. Bibliographic information, author information and level of evidence (LOE) were recorded. For identified consortium members, sex and race were defined in a binary manner. Results A total of 92 research consortiums were identified. A list of members was identified for 77 groups (83.7%), totalling 2,260 researchers. The remaining group members were not able to be identified due to the lack of information in the included publications, research group websites or after communicating with the corresponding author for respective articles. Most researchers were male (n=1,748, 77.3%) and white (n=1,694, 75%). Orthopaedic surgeons comprised 1,613 (71.4%) identified researchers. The most common fellowship training for orthopaedic surgeons was paediatrics (n=370, 16.4%), trauma (n=266, 11.8%) and sports medicine (n=229, 10.1%). The consortiums published 261 articles: women were lead (first) authors in 23% and senior (last) authors in 11.1%. Non-white researchers were lead authors in 24.5% (n=64) and senior authors in 17.2% (n=45). The most common level of evidence was level 3, accounting for 45.6% (n=119) of all publications. Level 1 evidence accounted for 12.6% (n=33) of published articles. Discussion Representation of women in orthopaedic research consortiums exceeds their representation in almost every orthopaedic professional society. There is less publicly available data to compare the involvement of under-represented minorities (URMs) in research consortiums to general practice. Further investigations should analyse possible avenues in which gender and racial disparity could be improved within orthopaedic surgery research.

Surgeon Factors and Trends Associated With the Use of Subacromial Decompression at the Time of Rotator Cuff Repair.

PURPOSE: Subacromial decompression (SAD) has historically been described as an essential part of the surgical treatment of rotator cuff disorders. However, investigations throughout the 21st century have increasingly questioned the need for routine SAD during rotator cuff repair (RCR). Our purpose was to assess for changes in the incidence of SAD performed during RCR over a 12-year period. In addition, we aimed to characterize surgeon and practice factors associated with SAD use. METHODS: Records from two large tertiary referral systems in the United States from 2010 to 2021 were reviewed. All cases of RCR with and without SAD were identified. The outcome of interest was the proportion of SAD performed during RCR across years and by surgeon. Surgeon-specific characteristics included institution, fellowship training, surgical volume, academic practice, and years in practice. Yearly trends were assessed using binomial logistic regression modeling, with a random effect accounting for surgeon-specific variability. RESULTS: During the study period, 37,165 RCR surgeries were performed by 104 surgeons. Of these cases, 71% underwent SAD during RCR. SAD use decreased by 11%. The multivariable model found that surgeons in academic practice, those with lower surgical volume, and those with increasing years in practice were significantly associated with increased odds of performing SAD. Surgeons with fellowship training were significantly more likely to use SAD over time, with the greatest odds of SAD noted for sports medicine surgeons (odds ratio = 3.04). CONCLUSIONS: Although SAD use during RCR appears to be decreasing, multiple surgeon and practice factors (years in practice, fellowship training, volume, and academic practice) are associated with a change in SAD use. CLINICAL RELEVANCE: These data suggest that early-career surgeons entering practice are likely driving the trend of declining SAD. Despite evidence suggesting limited clinical benefits, SAD remains commonly performed; future studies should endeavor to determine factors associated with practice changes among surgeons.

Mice with renal-specific alterations of stem cell-associated signaling develop symptoms of chronic kidney disease but surprisingly no tumors.

Previously, we found that Wnt and Notch signaling govern stem cells of clear cell kidney cancer (ccRCC) in patients. To mimic stem cell responses in the normal kidney in vitro in a marker-unbiased fashion, we have established tubular organoids (tubuloids) from total single adult mouse kidney epithelial cells in Matrigel and serum-free conditions. Deep proteomic and phosphoproteomic analyses revealed that tubuloids resembled renewal of adult kidney tubular epithelia, since tubuloid cells displayed activity of Wnt and Notch signaling, long-term proliferation and expression of markers of proximal and distal nephron lineages. In our wish to model stem cell-derived human ccRCC, we have generated two types of genetic double kidney mutants in mice: Wnt-ß-catenin-GOF together with Notch-GOF and Wnt-ß-catenin-GOF together with a most common alteration in ccRCC, Vhl-LOF. An inducible Pax8-rtTA-LC1-Cre was used to drive recombination specifically in adult kidney epithelial cells. We confirmed mutagenesis of ß-catenin, Notch and Vhl alleles on DNA, protein and mRNA target gene levels. Surprisingly, we observed symptoms of chronic kidney disease (CKD) in mutant mice, but no increased proliferation and tumorigenesis. Thus, the responses of kidney stem cells in the tubuloid and genetic systems produced different phenotypes, i.e. enhanced renewal versus CKD.

Tuning mono-divalent cation water composition by the capacitive ion-exchange mechanism.

Soil salinization poses a significant challenge to agricultural activities. To address this, the agricultural industry seeks an irrigation water solution that reduces both ionic conductivity and sodium adsorption rate (SAR), thereby diminishing the risks of soil sodification and fostering sustainable crop production. Capacitive deionization (CDI) is an attractive electrochemical technology to advance this search. Recently, a one-dimensional transient CDI model unveiled a capacitive ion-exchange mechanism presenting the potential to adjust the treated water composition by modifying monovalent and divalent cation concentrations, thereby influencing the SAR index. This behavior would be achieved by using electrodes rich in surface functional groups able to efficiently capture divalent cations during conditioning and releasing them during charging while capturing monovalent ions. Beyond the theoretical modelling, the current experimental research demonstrates, for the first time, the effectiveness of the capacitive ion-exchange mechanism in a CDI pilot plant using real water samples spiked with solutions containing specific mono and divalent ions. Electrosorption experiments and computational modeling, specifically Density-Functional Theory (DFT), were used along with the analysis of the surface functional groups present in the electrodes to describe the capacitive ion-exchange phenomenon and validate the steps involved on it, highlighting the conditioning as a critical step. Various operational and flow modes confirm the versatility of CDI technology, achieving separation factors (RMg/Na) of 5-6 in batch, raising production from 0.5 to 0.8 L m-2 h-1 (batch) to 8.0-8.1 L m-2 h-1 when using single pass although reducing RMg/Na to 2. The reliability of the CDI technology in reducing SAR was also successfully tested with different influent compositions, including magnesium and calcium. Finally, the robustness of the capacitive ion-exchange mechanism was validated by a second CDI laboratory 9-cell stack cycled over 350 cycles. Our results confirm the reported theoretical model and expands the conclusions through the experiments in a pilot plant showing direct implications for employing CDI in agricultural applications.

Accessing Highly Substituted Indoles via B(C6F5)3-Catalyzed Secondary Alkyl Group Transfer.

Herein, we report a synthetic method to access a range of highly substituted indoles via the B(C6F5)3-catalyzed transfer of 2° alkyl groups from amines. The transition-metal-free catalytic approach has been demonstrated across a broad range of indoles and amine 2° alkyl donors, including various substituents on both reacting components, to access useful C(3)-alkylated indole products. The alkyl transfer process can be performed using Schlenk line techniques in combination with commercially available B(C6F5)3·nH2O and solvents, which obviates the requirement for specialized equipment (e.g., glovebox).

A Comparison of Amyloid Deposition in Endoscopic and Open Carpal Tunnel Release.

PURPOSE: Previous investigations assessing the incidence of amyloidosis detected with biopsy during carpal tunnel release (CTR) have focused on open CTR (OCTR). Prior authors have suggested that biopsy may be more technically challenging during endoscopic carpal tunnel release (ECTR). Our purpose was to compare differences in the incidence of amyloid deposition detected during ECTR versus OCTR. METHODS: We reviewed all primary ECTR and OCTR during which a biopsy for amyloid was obtained between February 2022 and June 2023. All procedures were performed by five upper-extremity surgeons from a single institution. Congo red staining was used to determine the presence of amyloid deposition in either the transverse carpal ligament (TCL) or tenosynovium. All positive cases underwent subtype analysis and protein identification through liquid chromatography-tandem mass spectrometry. Baseline demographics were recorded for each case, and the incidence of positive biopsy was compared between ECTR and OCTR cases. RESULTS: A total of 282 cases were included for analysis (143 ECTR and 139 OCTR). The mean age was 67 years, and 45% of cases were women. Baseline demographics were similar except for a significantly higher incidence of diabetes in OCTR cases (13% vs 33%). Overall, 13% of CTR cases had a positive biopsy. There was a statistically significant difference in the incidence of amyloid deposition detected during biopsy in ECTR cases (3.5%) compared with OCTR cases (23%). CONCLUSIONS: Biopsy performed during ECTR may result in a lower incidence of amyloid detection. Future basic science investigation may be necessary to determine histologic differences between tenosynovium proximal and distal to the leading edge of the TCL. When surgeons plan a biopsy during surgical release of the carpal tunnel, an open approach may be advantageous. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Characterization of Demographical Histologic Diversity in Small Renal Masses With the Clear Cell Likelihood Score.

OBJECTIVE: This study aimed to develop a diagnostic model to estimate the distribution of small renal mass (SRM; ≤4 cm) histologic subtypes for patients with different demographic backgrounds and clear cell likelihood score (ccLS) designations. MATERIALS AND METHODS: A bi-institution retrospective cohort study was conducted where 347 patients (366 SRMs) underwent magnetic resonance imaging and received a ccLS before pathologic confirmation between June 2016 and November 2021. Age, sex, race, ethnicity, socioeconomic status, body mass index (BMI), and the ccLS were tabulated. The socioeconomic status for each patient was determined using the Area Deprivation Index associated with their residential address. The magnetic resonance imaging-derived ccLS assists in the characterization of SRMs by providing a likelihood of clear cell renal cell carcinoma (ccRCC). Pathological subtypes were grouped into four categories (ccRCC, papillary renal cell carcinoma, other renal cell carcinomas, or benign). Generalized estimating equations were used to estimate probabilities of the pathological subtypes across different patient subgroups. RESULTS: Race and ethnicity, BMI, and ccLS were significant predictors of histology (all P < 0.001). Obese (BMI, ≥30 kg/m 2 ) Hispanic patients with ccLS of ≥4 had the highest estimated rate of ccRCC (97.1%), and normal-weight (BMI, <25 kg/m 2 ) non-Hispanic Black patients with ccLS ≤2 had the lowest (0.2%). The highest estimated rates of papillary renal cell carcinoma were found in overweight (BMI, 25-30 kg/m 2 ) non-Hispanic Black patients with ccLS ≤2 (92.3%), and the lowest, in obese Hispanic patients with ccLS ≥4 (<0.1%). CONCLUSIONS: Patient race, ethnicity, BMI, and ccLS offer synergistic information to estimate the probabilities of SRM histologic subtypes.

Eye of the Carpenter: How Well do Orthopaedic Surgeons Estimate Angular Measurements in Derotational Osteotomies?

BACKGROUND: Femoral derotational osteotomies are used by orthopaedic surgeons to decrease version in a variety of pathologies. Intraoperatively, the goal of the surgery is to decrease the rotation of the femur to within physiological range. Surgeons generally visually estimate the angle of correction based on bone markers at the rotating cylindrical portion of the femur. This study sought first to assess the accuracy and inter-rater reliability of surgeons with respect to angle creation, and then to implement a training intervention. METHODS: A rotational femur model was constructed and tested among surgeons and nonsurgeons. Surgeons were then randomized into an experimental and control cohort with training on the model as the intervention. Subjects were asked to create target angles of 15, 30, 45, and 60 degrees using only Kirschner wires and then only bone marks for reference. Independent and paired t -tests were performed to determine variability between cohorts. RESULTS: The mean angle creation error and range of the surgeon cohort were significantly lower than those of the nonsurgeon cohort. Within the nonsurgeon cohort, the mean angle creation error and range of the wire modality were significantly lower than that of the mark modality. The mean angle creation error and range of the trained cohort were significantly lower than the untrained cohort. CONCLUSIONS: The considerable inter-subject range within the surgeon cohort highlights a need for the reinforcement of basic geometric principles within orthopaedic instruction. This model allows for immediate, accurate feedback on angle creation, and training appears to be both time and cost-effective. The physiological range allows for a level of variability between surgical outcomes without consequence. However, the more than 20 degree range determined by this study does not fall within those bounds and should be addressed. CLINICAL RELEVANCE: Moving forward, rotational estimation as a surgical skill should increase in prominence within orthopaedic instruction to maximize future joint health, and additional emphasis should be placed on fundamental spatial orientation during training.

Postoperative Elbow Instability: Options for Revision Stabilization.

Persistent and recurrent postoperative elbow instability includes a spectrum of pathologies ranging from joint incongruity and subluxation to dislocation. Restoration of osseous anatomy, particularly the coronoid, is a priority in restoring elbow alignment and maintaining ulnohumeral joint stability. After managing bony deficiencies, soft-tissue and ligamentous structures are typically addressed. When required, both static and dynamic adjunctive stabilization procedures have been described, which aid in maintaining a concentric reduction. In these complex procedures, both complication avoidance and early recognition of postoperative complications assist in obtaining a good result. In this review, we discuss current treatment options for revision stabilization for patients with persistent and recurrent elbow subluxation or dislocation after primary stabilization.

Refractory primary and secondary headache disorders that dramatically responded to combined treatment of ultrasound-guided percutaneous suprazygomatic pterygopalatine ganglion blocks and non-invasive vagus nerve stimulation: a case series.

In 1981, Devoghel achieved an 85.6% success rate in treating patients with treatment-refractory cluster headaches with alcoholization of the pterygopalatine ganglion (PPG) via the percutaneous suprazygomatic approach. Devoghel's study led to the theory that interrupting the parasympathetic pathway by blocking its transduction at the PPG could prevent or treat symptoms related to primary headache disorders (PHDs). Furthermore, non-invasive vagus nerve stimulation (nVNS) has proven to treat PHDs and has been approved by national regulatory bodies to treat, among others, cluster headaches and migraines.In this case series, nine desperate patients who presented with 11 longstanding treatment-refractory primary headache disorders and epidural blood patch-resistant postdural puncture headache (PDPH) received ultrasound-guided percutaneous suprazygomatic pterygopalatine ganglion blocks (PPGB), and seven also received nVNS. The patients were randomly selected and were not part of a research study. They experienced dramatic, immediate, satisfactory, and apparently lasting symptom resolution (at the time of the writing of this report). The report provides the case descriptions, briefly reviews the trigeminovascular and neurogenic inflammatory theories of the pathophysiology, outlines aspects of these PPGB and nVNS interventions, and argues for adopting this treatment regime as a first-line or second-line treatment rather than desperate last-line treatment of PDPH and PHDs.

A Comparison of Early Complication Rates of Endoscopic Carpal Tunnel Release With and Without Resident Involvement.

PURPOSE: The purpose of this study was to compare the complication rates of endoscopic carpal tunnel release (ECTR) relative to orthopedic resident trainee involvement in the procedure. METHODS: All patients undergoing isolated, elective ECTR by two attending surgeons within a 59-month period were analyzed. Cases were categorized as the following according to the degree of resident involvement: ECTR performed by attending with either no resident or a resident as an assistant (group 1), resident performing a portion of the procedure (group 2), and resident performing the entire procedure (group 3). Early postoperative complications and/or intraoperative conversion to an open procedure were the outcomes of interest. We used a noninferiority design, hypothesizing that resident involvement would not be associated with inferior outcomes compared with cases without resident involvement. Multiple logistic regression models, adjusted for patient demographic and surgical characteristics, were fit to assess the relationship between resident involvement groups and complication/conversion outcomes. RESULTS: A total of 1,167 ECTR cases (895 patients) were performed and returned for postoperative follow-up for at least 2 weeks after surgery. Operative time was significantly shorter for group 1 cases versus group 2 and 3 cases. The early postoperative complication and conversion rates were 1.7% and 1.0%, respectively. Superficial infection (1.2%), deep infection (0.3%), and transient neuropraxia (0.3%) occurred infrequently and did not differ relative to resident involvement. No differences in the odds of complication and/or conversion relative to resident involvement were observed. CONCLUSIONS: The results of ECTR performed entirely or in part by attending-supervised resident trainees were not inferior to ECTR performed by an attending surgeon regarding the odds of experiencing complications or conversion to an open procedure. With appropriate supervision, ECTR can be performed safely by orthopedic and plastic surgery residents. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Quantitative iron-neuromelanin MRI associates with motor severity in Parkinson's disease and matches radiological disease classification.

Background: Neuromelanin- and iron-sensitive MRI studies in Parkinson's disease (PD) are limited by small sample sizes and lack detailed clinical correlation. In a large case-control PD cohort, we evaluated the diagnostic accuracy of quantitative iron-neuromelanin MRI parameters from the substantia nigra (SN), their radiological utility, and clinical association. Methods: PD patients and age-matched controls were prospectively recruited for motor assessment and midbrain neuromelanin- and iron-sensitive [quantitative susceptibility mapping (QSM) and susceptibility map-weighted imaging (SMWI)] MRI. Quantitative neuromelanin-iron parameters from the SN were assessed for their discriminatory performance in PD classification using ROC analysis compared to those of qualitative visual classification by radiological readers of differential experience and used to predict motor severity. Results: In total, 191 subjects (80 PD, mean age 65.0 years; 111 controls, 65.6) were included. SN masks showed (a) higher mean susceptibility (p < 0.0001) and smaller sizes after thresholding for low susceptibility (p < 0.0001) on QSM and (b) lower contrast range (p < 0.0001) and smaller sizes after thresholding for high-signal voxels (p < 0.0001) on neuromelanin-sensitive MRI in patients than in controls. Quantitative iron and neuromelanin parameters showed a moderate correlation with motor dysfunction (87.5%: 0.4< | r | <0.6, p < 0.0001), respectively. A composite quantitative neuromelanin-iron marker differentiated the groups with excellent performance (AUC 0.94), matching the diagnostic accuracy of the best-performing reader (accuracy 97%) using SMWI. Conclusion: Quantitative neuromelanin-iron MRI is associated with PD motor severity and matched best-performing radiological PD classification using SMWI, with the potential to improve diagnostic confidence in the clinics and track disease progression and response to neuroprotective therapies.

Statistical Literacy in Hand and Upper-Extremity Patients.

Purpose: Statistical literacy is the ability of a patient to apply basic statistical concepts to their health care. Understanding statistics is a critical component of shared decision making. The purpose of this investigation was to define levels of statistical literacy in an upper-extremity (UE) patient population. We aimed to determine if patient demographics would be associated with statistical literacy. Methods: An electronic survey was administered to a consecutive series of UE patients at a single institution. We recorded baseline demographics, Single Assessment Numeric Evaluation scores, the Berlin Numeracy Test (BNT), and General Health Numeracy Test. We also included a surgical risk question, which asked: "Approximately 3% of patients who get carpal tunnel surgery develop an infection. If 100 patients get this surgery, how many would you expect to develop an infection?" A covariate-controlled adjusted odds ratio reflecting the association between each statistical literacy outcome measure and patient characteristics was reported. Results: A total 254 surveys were administered, 148 of which were completed and included. Fifty percent of respondents had a high-school education or less. For the BNT, 78% scored in the bottom quartile, and 52% incorrectly answered all questions. For the General Health Numeracy Test, 34% answered 0 or 1/6 questions correctly. For the surgical risk question, 24% of respondents answered incorrectly. Respondents who had a college or graduate degree had 2.62 times greater odds (95% confidence interval, 1.09-6.32) of achieving a BNT score in a higher quartile than patients who did not have a college or graduate degree. Conclusions: Overall levels of statistical literacy are low for UE patients. Clinical relevance: When engaging in management discussions and shared decision making, UE surgeons should assume low levels of statistical literacy. Consideration of alternative formats, such as frequencies, video-based materials, and pictographs, may be warranted when discussing outcomes and risks of surgical procedures.

Adherence to Complication Reporting for Randomized Controlled Trials Contained in Clinical Practice Guidelines for the Management of Carpal Tunnel Syndrome.

Purpose: Randomized controlled trials (RCTs) are frequently used in creating recommendations contained within clinical practice guidelines (CPGs). However, investigations outside of hand surgery have reported that RCTs within CPGs infrequently report complications and harms-related data. Our purpose was to assess adherence to complication reporting and harms-related outcomes contained in the Consolidated Standards for Reporting (CONSORT) Extension of Harms and Standards for Reporting of Diagnostic Accuracy Studies (STARD) reporting checklists for RCTs within the American Academy of Orthopaedic Surgery (AAOS) CPGs for carpal tunnel syndrome (CTS). Methods: We identified all RCTs within the AAOS CTS CPGs. All therapeutic RCTs and diagnostic studies were included. We used the CONSORT Harms Checklist criteria to assess adherence to the reporting of adverse events for therapeutic RCTs and the STARD criteria to assess the diagnostic accuracy of the articles. We defined adequate compliance as adherence to ≥50% of the checklist items. Results: We identified 82 therapeutic RCTs and 90 diagnostic accuracy articles within the AAOS CTS CPG. For therapeutic RCTs, we found that the average compliance with the published checklists was 19%. For diagnostic studies, the average compliance with checklists was found to be 55%. Eleven therapeutic RCTs (13%) and 60 diagnostic studies (67%) were determined to have adequate compliance for the CONSORT and STARD checklists, respectively. Conclusions: Randomized controlled trials in the AAOS CPGs for CTS have low compliance with the CONSORT Extension for Harms Checklist. Although the overall adherence to the items published in the STARD statement for diagnostic accuracy evaluation remains higher, future efforts should be made to improve the adherence rates to both checklists. Clinical relevance: Improved standardization of complication reporting may aid in comparing outcomes across multiple clinical investigations of upper-extremity procedures.

Defining Nonunion for Metacarpal Fractures: A Systematic Review.

Purpose: Our purpose was to assess how nonunion of the metacarpals has been defined in prior investigations with respect to both clinical and radiographic criteria. We hypothesized that the definitions of nonunion would be highly variable. Methods: A systematic review was conducted using MEDLINE and Embase databases for clinical articles related to the treatment of metacarpal fractures (surgical and nonsurgical) from 2010 to 2021. Included articles were searched to assess how nonunion was defined based on clinical and radiographic criteria. We assessed the treatment type, method of union assessment, time to union, and incidence of union as well as article factors such as the following: date of publication, level of evidence, and publishing journal. Results: A total of 641 articles were identified, of which 102 were included for a definition of nonunion and 97 were included for the assessment of clinical management and outcomes. Of the included articles, 62% contained level IV evidence. A definition of nonunion was provided in 47% of the articles. Radiographic criteria alone, clinical criteria alone, or a combination of the 2 was used in 22%, 6%, and 19% of the cases, respectively, to define nonunion. The most common definition of nonunion was presence of fracture-site tenderness (with no time defined) in 20 articles (20%), followed by lack of radiographic healing at 6 months (15%). In the 97 included articles, the total number of fracture cases was 4,435 and nonunion was reported in 0.45%. Cases with nonunion were reported in a total of six articles that used a variety of treatment modalities. Conclusions: The definition of metacarpal nonunion remains highly variable and lacks standardization with respect to clinical and radiographic criteria. Clinical relevance: Standardizing the definition of nonunion for metacarpal fractures would allow for more accurate assessments of the incidence of this complication and may aid in improving diagnostic and management strategies.

Fifty Most-Cited Research Articles in Elbow Surgery: A Modern Reading List.

Purpose: Bibliometric analysis is a common method for evaluating current trends within a scientific field. The primary aim of this study was to define and analyze the 50 most frequently cited articles in the field of elbow surgery, both of all time and those published during the 21st century. Methods: We searched the Journal Citation Report to identify articles related to elbow surgery within academic journals. Articles were sorted by total citations. The overall top 50 articles and those published since 2000 were identified, and data were collected, including title, journal of publication, publication year, country of publication, citation density, level of evidence, article type, institution, and sex of the lead and senior authors, and inclusion on the reference list for the Orthopaedic In-Training Examination within the last 5 years. Descriptive statistics were reported, and correlation analysis was performed using Spearman test. Results: For the most-cited elbow surgery articles, "fracture" was overall the most reported topic, whereas "lateral epicondylosis" and "fracture" were equal for those published since 2000. The United States was the most represented overall and for articles published since 2000. Women comprised 1/50 (2%) of lead authors overall, increasing to 8/50 (16%) for articles published during the 21st century. Most articles in during both periods contained level IV evidence, with level I evidence appearing infrequently (4%). Six percent of the most-cited articles of all time had appeared on the reference list of the Orthopaedic In-Training Examination within the past 5 years. Conclusions: The top 50 most-cited elbow surgery articles often assess fracture and lateral epicondylosis, most commonly originating from the United States. Level IV retrospective series comprises over half of the articles on this list. Women remain underrepresented as authors. Clinical Relevance: This study provides a modern reading list for upper-extremity surgeons about impactful elbow surgery articles.

Analysis of Terminated Hand and Wrist-Related Clinical Trials.

Purpose: While clinical trials provide high-quality evidence guiding medical decision-making, early trial termination can result in both lost time and resources. Our purpose was to investigate the rate of and reasons for clinical trial termination for hand and wrist-related conditions and identify study characteristics associated with early trial termination. Methods: The ClinicalTrials.gov database was queried for all hand and wrist-related clinical trials. All terminated and completed trials were reviewed, with characteristics and reasons for termination recorded. Study characteristics included type, purpose, intervention assessed, enrollment, group allocation, blinding, trial phase, sponsor type, and geographic region. Chi-square test was used to identify associations between trial characteristics and terminated versus completed status. Results: A total of 793 hand and wrist-related clinical trials were identified, with 77 trials (10%) terminated prior to completion. The most common reason for termination was "recruitment/retention difficulty," reported in 37 (48%) terminated trials. In comparing competed versus terminated trials, primary purpose (nonobservational studies), enrollment (<50 patients), and geographic region (North America) were all significantly more likely to be terminated. Terminated trials were more likely to have an intervention type investigating a specific device or drug. Conclusions: Early trial termination for hand and wrist-related conditions is common (10%), with patient recruitment and retention identified as the leading cause of termination. Trials involving potential commercial incentives (those investigating a device or drug) were associated with an increased rate of trial termination. Clinical relevance: An emphasis on patient enrollment during study design may aid in mitigating the most common cause of early clinical trial termination.