A Thy-1-negative immunofibroblast population emerges as a key determinant of fibrotic outcomes to biomaterials.

Fibrosis-associated fibroblasts have been identified across various fibrotic disorders, but not in the context of biomaterials, fibrotic encapsulation, and the foreign body response. In other fibrotic disorders, a fibroblast subpopulation defined by Thy-1 loss is strongly correlated with fibrosis yet we do not know what promotes Thy-1 loss. We have previously shown that Thy-1 is an integrin regulator enabling normal fibroblast mechanosensing, and here, leveraging nonfibrotic microporous annealed particle (MAP) hydrogels versus classical fibrotic bulk hydrogels, we demonstrate that Thy1-/- mice mount a fibrotic response to MAP gels that includes inflammatory signaling. We found that a distinct and cryptic α-smooth muscle actin-positive Thy-1- fibroblast population emerges in response to interleuklin-1ß (IL-1ß) and tumor necrosis factor-α (TNFα). Furthermore, IL-1ß/TNFα-induced Thy-1- fibroblasts consist of two distinct subpopulations that are strongly proinflammatory. These findings illustrate the emergence of a unique proinflammatory, profibrotic fibroblast subpopulation that is central to fibrotic encapsulation of biomaterials.

Recruitment and Retention Issues in a Technology-Based Intervention Among Korean American Midlife Women With Depressive Symptoms'.

The number of health technology-based intervention studies has grown significantly. However, issues in the recruitment and retention for such studies, especially of Asian Americans, have rarely been discussed. The purpose of this paper was to discuss issues in the recruitment and retention of a specific group of Asian Americans-Korean American midlife women with depressive symptoms-into a technology-based intervention study using computers and mobile devices with a measurement device and to provide directions for future participant recruitment and retention in technology-based intervention studies. The written memos of research team members and the written records of research team meetings were analyzed using a content analysis. The issues in the recruitment and retention process included (1) low recruitment and retention rates; (2) the perceived long intervention period; (3) strict inclusion/exclusion criteria; (4) concerns related to the use of a measurement device; and (5) the perceived adequacy of monetary incentives. Based on the issues identified in the study, several suggestions are made for future recruitment and retention of racial/ethnic minorities in technology-based intervention studies (eg, appropriate intervention period, innovative and creative motivation strategies, acceptable measurement scales and devices, and adequate monetary reimbursement).

The Performance of ChatGPT on the American Society for Surgery of the Hand Self-Assessment Examination.

BACKGROUND: This study aims to compare the performance of ChatGPT-3.5 (GPT-3.5) and ChatGPT-4 (GPT-4) on the American Society for Surgery of the Hand (ASSH) Self-Assessment Examination (SAE) to determine their potential as educational tools. METHODS: This study assessed the proportion of correct answers to text-based questions on the 2021 and 2022 ASSH SAE between untrained ChatGPT versions. Secondary analyses assessed the performance of ChatGPT based on question difficulty and question category. The outcomes of ChatGPT were compared with the performance of actual examinees on the ASSH SAE. RESULTS: A total of 238 questions were included in the analysis. Compared with GPT-3.5, GPT-4 provided significantly more correct answers overall (58.0% versus 68.9%, respectively; P = 0.013), on the 2022 SAE (55.9% versus 72.9%; P = 0.007), and more difficult questions (48.8% versus 63.6%; P = 0.02). In a multivariable logistic regression analysis, correct answers were predicted by GPT-4 (odds ratio [OR], 1.66; P = 0.011), increased question difficulty (OR, 0.59; P = 0.009), Bone and Joint questions (OR, 0.18; P < 0.001), and Soft Tissue questions (OR, 0.30; P = 0.013). Actual examinees scored a mean of 21.6% above GPT-3.5 and 10.7% above GPT-4. The mean percentage of correct answers by actual examinees was significantly higher for correct (versus incorrect) ChatGPT answers. CONCLUSIONS: GPT-4 demonstrated improved performance over GPT-3.5 on the ASSH SAE, especially on more difficult questions. Actual examinees scored higher than both versions of ChatGPT, but the margin was cut in half by GPT-4.

Predicting academic productivity among American Shoulder and Elbow Surgeons fellowship faculty from publications acquired before and during surgical training.

BACKGROUND: Orthopedic residency and fellowship applicants with a strong research record are highly valued for their potential in continuing academic excellence. Despite this, the association between research productivity during training and future academic productivity as an attending orthopedic surgeon is not well-established. We assess the effects of research output during different periods of surgical training as well as residency location on long-term academic productivity as an attending shoulder and elbow surgeon. METHODS: A search of the 2022-2023 American Shoulder and Elbow Surgeons Fellowship Directory was conducted to identify a list of orthopedic shoulder and elbow fellowship faculty members. Each surgeon's residency, fellowship and current institution of practice were determined and stratified by geographic location. Total publication counts acquired before residency, during residency, during fellowship, and after fellowship were collected for each faculty member. Attending publication rates and H-indices were calculated. A multivariate linear regression model was created, and significance was set at a P value <.05. RESULTS: A total of 149 shoulder and elbow fellowship faculty members representing 34 fellowship programs were identified. The average number of total publications per surgeon was 88.8 ± 102. The average attending publication rate was 5.29 ± 6.89 publications per year. The average H-index for included surgeons was 27.8 ± 24.4. The number of publications acquired before residency (ß = 0.293; P < .001), during residency (ß = 0.110; P = .025) and during fellowship (ß = 0.593; P < .001) were significantly associated with an increased attending publication rate, but no association was observed with the H-index [before residency (ß = -0.221; P = .574), during residency (ß = 0.045; P = .866), during fellowship (ß = 0.198; P = .678)]. There were no significant differences in total publication count (P = .397), attending publication rate (P = .237), or H-index (P = .364) based on location of residency training. DISCUSSION: Research output before and during surgical training is predictive of continued academic productivity as a shoulder and elbow surgeon. In particular, greater productivity during surgical fellowship was most predictive of academic output as an attending. While long-term academic productivity does not seem to be influenced by the geographic location of residency training, attending surgeons practicing in the Midwest had significantly greater total publication counts and H-indices but similar annual publication rates.

Association between blood markers and the progression of osseointegration in percutaneous prostheses patients-A pilot study.

Patients implanted with osseointegrated (OI) prosthetic systems have reported vastly improved upper and lower extremity prosthetic function compared with their previous experience with socket-suspension systems. However, OI systems have been associated with superficial and deep-bone infections and implant loosening due, in part, to a failure of the osseointegration process. Although monitoring the osseointegration using circulating biomarkers has clinical relevance for understanding the progression of osseointegration with these devices, it has yet to be established. Ten patients were enrolled in this study. Blood samples were collected at pre-selected times, starting before implantation surgery, and continuing to 12 months after the second surgery. Bone formation markers, bone resorption markers, and circulating amino acids were measured from blood samples. A linear mixed model was generated for each marker, incorporating patient ID and age with the normalized marker value as the response variable. Post hoc comparisons were made between 1 week before Stage 1 Surgery and all subsequent time points for each marker, followed by multiple testing corrections. Serial radiographic imaging of the residual limb containing the implant was obtained during follow-up, and the cortical index (CI) was calculated for the bone at the porous region of the device. Two markers of bone formation, specifically bone-specific alkaline phosphatase (Bone-ALP) and amino-terminal propeptide of type I procollagen (PINP), exhibited significant increases when compared with the baseline levels of unloaded residual bone prior to the initial surgery, and they subsequently returned to their baseline levels by the 12-month mark. Patients who experienced clinically robust osseointegration experienced increased cortical bone thickness at the porous coated region of the device. A medium correlation was observed between Bone-ALP and the porous CI values up to PoS2-M1 (p = .056), while no correlation was observed for PINP. An increase in bone formation markers and the lack of change observed in bone resorption markers likely reflect increased cortical bone formation induced by the end-loading design of the Utah OI device used in this study. A more extensive study is required to validate the correlation observed between Bone-ALP and porous CI values.

A randomized proof-of-mechanism trial of TNF antagonism for motivational anhedonia and related corticostriatal circuitry in depressed patients with high inflammation.

Chronic, low-grade inflammation has been associated with motivational deficits in patients with major depression (MD). In turn, impaired motivation has been linked to poor quality of life across psychiatric disorders. We thus determined effects of the anti-inflammatory drug infliximab-a potent tumor necrosis factor (TNF) antagonist-on behavioral and neural measures of motivation in 42 medically stable, unmedicated MD patients with a C-reactive protein > 3mg/L. All patients underwent a double-blind, placebo-controlled, single-dose, randomized clinical trial with infliximab (5mg/kg) versus placebo. Behavioral performance on an effort-based decision-making task, self-report questionnaires, and neural responses during event-related functional magnetic resonance imaging were assessed at baseline and 2 weeks following infusion. We found that relative to placebo, patients receiving infliximab were more willing to expend effort for rewards. Moreover, increase in effortful choices was associated with reduced TNF signaling as indexed by decreased soluble TNF receptor type 2 (sTNFR2). Changes in effort-based decision-making and sTNFR2 were also associated with changes in task-related activity in a network of brain areas, including dmPFC, ventral striatum, and putamen, as well as the functional connectivity between these regions. Changes in sTNFR2 also mediated the relationships between drug condition and behavioral and neuroimaging measures. Finally, changes in self-reported anhedonia symptoms and effort-discounting behavior were associated with greater responses of an independently validated whole-brain predictive model (aka "neural signature") sensitive to monetary rewards. Taken together, these data support the use of anti-inflammatory treatment to improve effort-based decision-making and associated brain circuitry in depressed patients with high inflammation.

Higher return to sport and lower revision rates when performing arthroscopic Bankart repair with remplissage for anterior shoulder instability with a Hill-Sachs lesion: a meta-analysis.

BACKGROUND: Recurrent anterior shoulder instability remains the most common complication from a prior shoulder dislocation, especially among young and active individuals who engage in athletic activities. This instability can lead to repeated subluxation or dislocations of the humeral head from the glenoid fossa. The purpose of this study is to compare postoperative recurrence rates, instability-related revision and return to sport (RTS) rates between isolated arthroscopic Bankart repair (ABR) and ABR with remplissage (ABR + R) for anterior shoulder instability with subcritical glenoid bone loss (GBL) and a Hill-Sachs lesion (HSL). METHODS: PubMed, Embase, and Web of Science were searched on June 2022. Studies sought were those comparing postoperative outcomes of ABR + R versus isolated ABR for subcritical GBL and an HSL. Study quality was evaluated using the revised Cochrane tool. Redislocations, instability-related revisions, and RTS rates were extracted and pooled estimates were calculated using the random-effect model. RESULTS: Twelve studies were included with a mean follow-up of 48.2 months for isolated ABR and 43.2 months for ABR + R. The meta-analytic comparison demonstrated that ABR + R resulted in statistically significant improvement in Rowe and American Shoulder and Elbow Surgeons scores by 6.5 and 2.2 points, respectively; however, the improvements in patient-reported outcomes were not clinically meaningful. ABR + R resulted in reduced external rotation at the side by 1° which was not clinically meaningful and there was no significant difference in terms of forward elevation. ABR + R resulted in a statistically significant reduction of overall postoperative recurrences (odds ratio [OR]: 9.36), postoperative dislocations (OR: 6.28), instability-related revision (OR: 3.46), and RTS to any level (OR: 2.85). CONCLUSION: The addition of remplissage to ABR for recurrent anterior shoulder instability with subcritical GBL and HSL results in significantly lower postoperative instability recurrence, lower instability-related revisions, and higher RTS to any level.

Assessment of SOX10 expression in 437 canine neoplasms of different embryologic origins.

Several members of the SRY-related HMG-box (SOX) protein family are implicated in tumorigenesis, metastasis, and regulation of the tumor microenvironment. SOX10, which is involved in neural crest cell migration and differentiation, has long been recognized a sensitive and specific immunohistochemical (IHC) marker in the diagnosis of melanoma in humans. However, expression of SOX10 in other tumor types has infrequently been evaluated in humans until recently and has not been thoroughly investigated in the dog. Our aim was to characterize the expression of SOX10 in canine neoplasms to objectively assess its value as a diagnostic IHC marker. Immunohistochemistry for SOX10 was performed on 437 archived, formalin-fixed paraffin-embedded tissues from representative canine neoplasms of ectodermal (15 tumor types), mesodermal (13 tumor types), endodermal (8 tumor types), and mixed/unknown (7 tumor types) embryologic origin. Oral and cutaneous tumors of melanocytic origin were used as positive controls. Intense SOX10 immunolabeling was observed in most tumors of ectodermal origin, including consistent expression in mammary carcinomas, and gliomas. Embryonal and hair follicle neoplasms inconsistently exhibited strong nuclear immunolabeling. Oral fibrosarcomas and undifferentiated oral sarcomas both inconsistently exhibited moderate to strong nuclear immunolabeling. Neoplasms of mesodermal and endodermal origin lacked immunolabeling. Salivary carcinomas, representing an unknown/mixed embryologic origin, were strongly labeled. SOX10 expression is not limited to melanomas, but is expressed by canine tumors of diverse tissues and embryologic derivation. Importantly, expression of SOX10 by a subset of oral sarcomas impairs its value as a marker for spindle cell oral melanomas.

Validation of Temperature Sensors to Monitor Thermoplastic Splint Wear in Hand Surgery Patients.

BACKGROUND: The aim of this study was to validate the use of temperature sensors to accurately measure thermoplastic volar forearm splint wear in a healthy cohort of volunteers using 5- and 15-minute temperature measurement intervals. METHODS: A prospective diagnostic study was performed to evaluate the diagnostic accuracy of temperature sensors in monitoring splint wear in 8 healthy volunteers between December 2022 and June 2023. Temperature sensors were molded into thermoplastic volar forearm splints. Volunteers who were familiar with the study aims were asked to keep an exact log of the time spent wearing the splint ("actual wear time"). Sensors recorded temperatures every 5 or 15 minutes, and separate algorithms were developed to determine the sensor-detected wear time compared with the actual wear time as the gold standard. The algorithms were then externally validated with the total population. RESULTS: The 5-minute and 15-minute algorithms demonstrated excellent sensitivity (99.1% vs 96.6%), specificity (99.9% vs 99.9%), positive (99.4% vs 99.5%) and negative (99.9% vs 99.3%) predictive value, and diagnostic accuracy (99.8% vs 99.3%), respectively. The 5-minute algorithm recorded 99.5% of the total splint hours, whereas the 15-minute algorithm recorded 96.1%. There was no significant difference between the actual time per wear session (5.4 ± 2.7 hours) and the time estimated by the 5-minute algorithm (5.4 ± 2.6 hours; P = .40), but there was a significant difference for the 15-minute algorithm (5.2 ± 2.6 hours; P < .001). CONCLUSION: Temperature sensors can be used to accurately monitor thermoplastic volar forearm splint wear. LEVEL OF EVIDENCE: Diagnostic II.

Effects of autolysis and prolonged formalin fixation on histomorphology and immunohistochemistry of normal canine brain tissue: an experimental study.

CNS tumor diagnosis in dogs often relies on immunohistochemistry (IHC) given similar histologic features among tumors. Most CNS tissue samples encountered by diagnostic pathologists are collected during autopsy, and postmortem specimens can be susceptible to autolysis and prolonged formalin fixation, both of which have the potential to influence IHC results and interpretation. Here we evaluated the effects of experimentally controlled autolysis induced by delayed tissue fixation (sections of brain held for 2, 4, 8, 12, 24, 48, and 72 h in 0.9% NaCl at either room temperature or 37°C prior to fixation) as well as the effects of prolonged formalin fixation times (1 wk, 1 mo, 2 mo) on a panel of 8 IHC markers (CNPase, GFAP, Iba1, OLIG2, PGP9.5, MAP2, NeuN, synaptophysin) relevant to brain tumor diagnosis. Prolonged fixation of up to 2 mo had no detrimental effect on any immunomarker except NeuN, which had reduced immunolabeling intensity. Delayed fixation led to autolytic changes as expected, on a gradient of severity corresponding to increased time in saline prior to fixation. Several immunomarkers should be used with caution (CNPase, OLIG2) or avoided entirely (MAP2, NeuN) in markedly autolyzed brain and brain tumor tissues. Our results suggest that autolysis has minimal effect on most immunomarkers, but that advanced autolysis may cause a loss of specificity for GFAP, MAP2, and PGP9.5, a loss of intensity of CNPase and OLIG2, and loss of labeling with MAP2 and NeuN. Prolonged fixation affected only NeuN, with mildly decreased intensity.

Diagnostic immunohistochemistry of primary and secondary central nervous system neoplasms of dogs and cats.

The diagnosis of primary and secondary CNS neoplasms of dogs and cats relies on histologic examination of autopsy or biopsy samples. In addition, many neoplasms must be further characterized by immunohistochemistry (IHC) for a more refined diagnosis in specific cases. Given the many investigations assessing the diagnostic and prognostic IHC profile of CNS neoplasms in the veterinary literature, it may be difficult for the diagnostic pathologist or pathology trainee to narrow the list of reliable diagnostic IHCs when facing a challenging case. Here we compile a comprehensive list of the most diagnostically relevant immunomarkers that should be utilized for the diagnostic support or confirmation of the most common primary and secondary CNS neoplasms of dogs and cats.

Inflammatory markers for differentiation of endometritis in the mare.

BACKGROUND: Endometrial biopsy is required to diagnose mares with chronic endometritis and endometrial degenerative fibrosis. An increase in understanding of equine reproductive immunology could be utilised to create less-invasive, time-efficient diagnostic tools especially when evaluating mares for chronic endometritis. OBJECTIVES: To evaluate inflammatory cytokine and chemokine concentrations in uterine fluid samples collected by low-volume lavage (LVL) as a potential screening diagnostic biomarker for endometritis. STUDY DESIGN: Prospective cross-sectional clinical study. METHODS: Forty-six mares underwent a LVL and subsequently endometrial biopsy. Mares were split in three groups: healthy, acute endometritis, and chronic endometrial fibrosis (CEF) based on cytological and histological evaluation. A fluorescent bead-based multiplex assay for IFN-γ, IFN-α, IL-1ß, IL-4, IL-10, IL-17, sCD14, TNF-α, CCL2, CCL3, CCL5 and CCL11 were carried out on the LVL fluid. The endometrial biopsy was utilised for histology and qPCR of IFN-γ, IL-1ß, IL-6, IL-8, IL-17, TNF-α, CCL2 and CCL3 genes. Statistical analyses examined differences in inflammatory markers and predictive modelling for diseased endometrium. RESULTS: Secreted concentrations of IFN-γ were lower in LVL fluid from reproductively healthy mares compared with acute endometritis (p = 0.04) and CEF (p = 0.006). Additionally, IL-17, IL-10, IL-1ß, TNF-α, CCL2, CCL3, CCL5 and CCL11 were significantly increased (p ≤ 0.04) in LVL from CEF mares compared with healthy mares. Mares with CCL2 concentrations ≥550 pg/mL (14/14) had 100% probability of having CEF and/or acute endometritis. Healthy mares had lower relative abundance of IL-17 mRNA compared with mares in CEF group [median (interquartile rage) = 14.76 (13.3, 15.3) and 12.4 (10.54, 13.81)], respectively (p = 0.02). MAIN LIMITATIONS: Limited sample size: larger numbers of mares with and without endometritis are required and reference intervals in LVL samples have to be established. CONCLUSIONS: Inflammatory chemokines and cytokines concentrations differed between healthy mares and mares with acute endometritis or CEF in LVL.

Patient-selection algorithm for outpatient shoulder arthroplasty in ambulatory surgery center: a retrospective update.

BACKGROUND: Outpatient total shoulder arthroplasty (TSA) presents a safe alternative to inpatient arthroplasty, while helping meet the rapidly rising volume of shoulder arthroplasty needs and minimizing health care costs. Identifying the correct patient for outpatient surgery is critical to maintaining the safety standards with TSA. This study sought to update an ambulatory surgery center (ASC) TSA patient-selection algorithm previously published by our institution. METHODS: A retrospective chart review of TSAs was performed in an ASC at a single institution to collect patient demographics, perioperative risk factors, and postoperative outcomes with regard to reoperations, hospital admissions, and complications. The existing ASC algorithm for outpatient TSA was altered based on collected perioperative information, review of pertinent literature, and anesthesiology recommendations. RESULTS: A total of 319 TSAs were performed in an ASC in 298 patients over 7 years. Medically related complications occurred in 3 patients (0.9%) within 90 days of surgery, 2 of whom required hospital admission (0.6%) for acute kidney injury and pulmonary embolus. There were no instances of major cardiac events. Orthopedic-related complications occurred in 11 patients (3.4%), with hematoma development requiring evacuation and instability requiring revision being the most common causes. CONCLUSIONS: There was a low rate of perioperative complications and hospital admissions, confirming the safety of TSAs in an ASC setting. Based on prior literature and the population included, a pre-existing patient-selection algorithm was updated to better reflect increased comfort, knowledge, and data regarding safe patient selection for TSA in an ASC.

Social determinants of health disparities impact postoperative complications in patients undergoing total shoulder arthroplasty.

BACKGROUND: Understanding the role of social determinants of health disparities (SDHDs) in surgical outcomes can better prepare providers to improve postoperative care. In this study, we use International Classification of Diseases (ICD) codes to identify SDHDs and investigate the risk of postoperative complication rates among patients undergoing total shoulder arthroplasty (TSA). METHODS: A retrospective cohort analysis was conducted using a national insurance claims database. Using ICD and Current Procedural Terminology (CPT) codes, patients who underwent primary TSA with at least 2 years of follow-up in the database were identified. Patients with a history of SDHDs were identified using appropriate ICD-9 and ICD-10 codes. Patients were grouped in one of 2 cohorts: (1) patients with no history of SDHDs (control) and (2) patients with a history of SDHDs (SDHD group) prior to TSA. The SDHD and control groups were matched 1:1 for comorbidities and demographics prior to conducting multivariable analysis for 90-day medical complications and 2-year surgical complications. RESULTS: After matching, there were 8023 patients in the SDHD group and 8023 patients in the control group. The SDHD group had significantly higher odds for 90-day medical complications including heart failure, cerebrovascular accident, renal failure, deep vein thrombosis, pneumonia, sepsis, and urinary tract infection. Additionally, the SDHD group had significantly higher odds for revision surgery within 2 years following TSA. Patients in the SDHD group also had a significantly longer length of hospital stay following TSA. DISCUSSION: This study highlights the association between SDHDs and postoperative complications following TSA. Quantifying the risk of complications and differences in length of stay for TSA patients with a history of SDHDs is important in determining value-based payment models and risk stratifying to optimize patient care.

In situ hybridization to detect Escherichia coli in canine granulomatous colitis.

Canine granulomatous colitis (histiocytic ulcerative colitis) is an uncommon disease, predominantly of young French Bulldogs and Boxer dogs, that manifests from a dysregulated immune response, primarily to adherent-invasive Escherichia coli (AIEC). In conjunction with histopathology and periodic acid-Schiff staining, the diagnosis of granulomatous colitis currently relies on fluorescence in situ hybridization (ISH) or immunohistochemistry to identify and localize AIEC organisms within macrophages in the mucosa and/or submucosa. We investigated the utility of ISH for E. coli using formalin-fixed, paraffin-embedded specimens collected from 29 cases of suspected granulomatous colitis. Most confirmed cases of granulomatous colitis were in French Bulldogs (12 of 20; 60%) and Boxers (3 of 20; 15%), and the mean age was 25 ± 6 mo with no sex predilection. E. coli ISH signal localized bacterial genetic material within the mucosa in 20 of 29 (69%) cases, supporting the diagnosis. ISH signal was limited to the lumen in 8 of 29 (28%) cases, which did not support the identification of these organisms as AIEC. The remaining case had no hybridization signal, and the diagnosis of granulomatous colitis was not supported. Our results revealed that ISH is a quick and specific detection method that can effectively confirm the diagnosis of canine granulomatous colitis.

Association of the FGF4L2 retrogene with fibrocartilaginous embolic myelopathy in dogs.

BACKGROUND: Fibrocartilaginous embolic myelopathy (FCE) is a well-documented condition in dogs although rarely reported in chondrodystrophic breeds. Genetic associations have not been defined. OBJECTIVES: Define the association of the chondrodystrophy-associated FGF4L2 retrogene with histopathologically confirmed cases of FCE. ANIMALS: Ninety-eight dogs with a histopathologic diagnosis of FCE. METHODS: Retrospective multicenter study. Dogs were genotyped for the FGF4L2 and FGF4L1 retrogenes using DNA extracted from formalin-fixed, paraffin-embedded tissue. Associations between breed, FCE and retrogene status were investigated with reference to a hospital population and known breed and general population allele frequencies. RESULTS: FGF4L2 genotype was defined in 89 FCE cases. Fibrocartilaginous embolic myelopathy was present in 22 dogs from FGF4L2-segregating breeds with allele frequencies of ≥5%; however, all dogs were wild type. Two Labrador retrievers with FCE carried FGF4L2 alleles. Frequency of the FGF4L2 allele was significantly (P < .001) and negatively associated with FCE relative to predicted hospital-population dogs. FCE was overrepresented in Boxer, Great Dane, Yorkshire Terrier, Bernese Mountain Dog, Miniature Schnauzer, Rottweiler, and Shetland Sheepdog breeds. CONCLUSIONS AND CLINICAL IMPORTANCE: Study data based on genotypically and histopathologically defined cases support the historical observation that FCE is uncommon in chondrodystrophic dog breeds. FGF4 plays an important role in angiogenesis and vascular integrity; anatomical studies comparing chondrodystrophic and non-chondrodystrophic dogs might provide insight into the pathogenesis of FCE.

Primary and secondary leptomeningeal gliomatosis in dogs.

Leptomeningeal gliomatosis (LG) is characterized by extensive dissemination of neoplastic glial cells in the subarachnoid space either without an intraparenchymal glioma (primary LG or PLG) or secondary to an intraparenchymal glioma (secondary LG or SLG). Given the low frequency of LG in human and veterinary medicine, specific diagnostic criteria are lacking. Here, we describe 14 cases of canine LG that were retrospectively identified from 6 academic institutions. The mean age of affected dogs was 7.3 years and over 90% of patients were brachycephalic. Clinical signs were variable and progressive. Relevant magnetic resonance image findings in 7/14 dogs included meningeal enhancement of affected areas and/or intraparenchymal masses. All affected dogs were euthanized because of the poor prognosis. Gross changes were reported in 12/14 cases and consisted mainly of gelatinous leptomeningeal thickening in the brain (6/12 cases) or spinal cord (2/12 cases) and 1 or multiple, gelatinous, gray to red intraparenchymal masses in the brain (6/12 cases). Histologically, all leptomeningeal neoplasms and intraparenchymal gliomas were morphologically consistent with oligodendrogliomas. Widespread nuclear immunolabeling for OLIG2 was observed in all neoplasms. The absence of an intraparenchymal glioma was consistent with PLG in 3 cases. The remaining 11 cases were diagnosed as SLG.

Pulmonary Complications and Mortality in Patients with SARS-CoV-2 Undergoing Elective and Emergent Hand Surgery.

Background Patients acutely infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have increased risk for postsurgical pulmonary complications and mortality, particularly with general anesthesia. Surgery is often delayed to mitigate risk; however, excessive delays may result in morbidity. Optimal criteria for delaying surgery in patients with or without symptoms are unknown. This study aimed to evaluate any complications following hand surgery in patients testing positive for SARS-CoV-2. Methods We retrospectively reviewed patients with a positive polymerase chain reaction test within 60 days before or after hand surgery between March 31, 2020 and March 31, 2021. Patients were telephoned also to supplement records. Type of surgery, type of anesthesia, comorbidities, timing of surgery, onset of symptoms, and complications were recorded. Results We identified 21 patients undergoing 26 procedures, of which 21 (81%) were emergency procedures and 5 (19%) were elective. Mean age was 37 years (range: 17-71). General anesthesia was used in 88% of cases, with mean duration of 110 minutes. SARS-CoV-2 was diagnosed on average 6 days preoperatively (range: 39 days preop-14 days postop). Positive tests were usually identified preoperatively (50%), versus day-of-surgery (25%) or postoperatively (25%). Patients were symptomatic in only 27% of cases, and completely asymptomatic in 73%. No asymptomatic patients developed complications. One patient suffered a fracture malunion after delayed surgery. Pulmonary complications were noted in 3 patients; all had prior pulmonary disease and underwent emergency surgeries under general anesthesia. Overall mortality rate was 0%. Conclusion Pulmonary complications and mortality are low following hand surgery in asymptomatic patients with a positive SARS-CoV-2 test.

Associations of differentially expressed genes with psychoneurological symptoms in patients with head and neck cancer: A longitudinal study.

OBJECTIVE: Patients with head and neck cancer (HNC) experience psychoneurological symptoms (PNS, i.e., depression, fatigue, sleep disturbance, pain, and cognitive dysfunction) during intensity-modulated radiotherapy (IMRT) that negatively impact their functional status, quality of life, and overall survival. The underlying mechanisms for PNS are still not fully understood. This study aimed to examine differentially expressed genes and pathways related to PNS for patients undergoing IMRT (i.e., before, end of, 6 months, and 12 months after IMRT). METHODS: Participants included 142 patients with HNC (mean age 58.9 ± 10.3 years, 72.5% male, 83.1% White). Total RNA extracted from blood leukocytes were used for genome-wide gene expression assays. Linear mixed effects model was used to examine the association between PNS and gene expression across time. Gene Ontology (GO) enrichment analysis was employed to identify pathways related to PNS. RESULTS: A total of 1352 genes (162 upregulated, 1190 downregulated) were significantly associated with PNS across time (false discovery rate (FDR) < 0.05). Among these genes, 112 GO terms were identified (FDR < 0.05). The top 20 GO terms among the significant upregulated genes were related to immune and inflammatory responses, while the top 20 GO terms among the significant downregulated genes were associated with telomere maintenance. CONCLUSION: This study is the first to identify genes and pathways linked to immune and inflammatory responses and telomere maintenance that are associated with PNS in patients with HNC receiving IMRT. Inflammation and aging markers may be candidate biomarkers for PNS. Understanding biological markers may produce targets for novel interventions.