Citations

A three year old male neutered mixed breed dog presented with a mass on the right carpus and accompanying lameness. A Jamshidi bone biopsy was performed, and histopathology results were consistent with a sarcoma. The dog received oncolytic virotherapy (OV) with vesicular stomatitis virus (VSV) as part of a clinical trial in dogs with osteosarcoma (OSA). Ten days after VSV treatment, the affected limb was amputated, and histopathology was consistent with intramedullary HSA. Considering the new diagnosis, standard doxorubicin chemotherapy was prescribed. With this combination of therapies, the dog had an extended survival of more than seven years and remains alive at the time of writing. This is the first case report documenting OV given in conjunction with the standard of care for canine appendicular HSA.

Objective To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework. Methods Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD‐related cognitive decline was estimated primarily by baseline cognitive symptoms plus SVD risk factors. Adjudicated risk status was estimated by cognitive symptoms plus presence of moderate‐to‐severe white matter hyperintensities, microbleeds, or lacunes on baseline MRI. Results MarkVCID2 enrolled 1883 individuals age 73.4 ± 7.5 years, 65.0% female, 24.2% Hispanic, and 27.1% non‐Hispanic Black. Among enrollees, 44.8% were provisionally designated high‐risk. After baseline MRI, 48.5% were categorized as adjudicated high‐risk status, with substantial recategorization both from low‐ to high‐risk (primarily because of MRI lesions without SVD risk factors) and high‐ to low‐risk (primarily suspected cognitive impairment at screening not confirmed by baseline testing). Interpretation MarkVCID2 baseline data indicate successful enrollment of diverse individuals enriched in factors associated with SVD‐related cognitive decline. Changes over 3 years of longitudinal follow‐up will be analyzed to validate the candidate biomarkers for 2 projected contexts of use: subject selection (identifying likelihood of future SVD progression) and study outcome (efficiently measuring SVD progression). ANN NEUROL 2026;99:449–458

ImportanceStudies suggest that everolimus may reduce the risk of rejection, cardiac allograft vasculopathy (CAV), chronic kidney disease (CKD), and cytomegalovirus (CMV) after heart transplant. Everolimus use is controversial because of data demonstrating higher infection deaths when everolimus is introduced de novo after transplant. It is unclear whether everolimus is safe and effective when initiated at 6 months posttransplant in children, a population in which median graft survival is limited to 15 years and randomized clinical trials are lacking.ObjectiveTo evaluate the safety and efficacy of everolimus combined with low-dose tacrolimus to prevent major adverse transplant events (MATEs) in children after heart transplant.Design, Setting, and ParticipantsMulticenter, randomized, open-label, clinical trial enrolling 211 patients who were alive 6 months after pediatric heart transplant at 25 US sites from February 2018 to August 2020. The last date of follow-up was April 17, 2023.InterventionsParticipants were randomized to receive everolimus and low-dose tacrolimus (n = 107) or standard-dose tacrolimus and mycophenolate mofetil (n = 104) for 30 months.Main Outcomes and MeasuresThe primary efficacy end point was the MATE-3 score at 30 months, a validated composite ordinal end point including acute cellular rejection, CAV, and CKD. The primary safety end point was the MATE-6 score, encompassing the MATE-3 score plus antibody-mediated rejection, infection, and posttransplant lymphoproliferative disorder.ResultsAmong 211 children randomized, the mean age was 8.2 (SD, 6.3) years, 97 (46%) underwent transplant for congenital heart disease, and 49 (23%) were treated for rejection before 6 months. At 30 months, the mean MATE-3 score did not differ between the 2 treatment groups (mean difference, −0.32; 95% CI, −0.90 to 0.20; P = .16). The mean MATE-6 score was no higher in the everolimus group than in the mycophenolate group (baseline-adjusted mean difference, −0.40; 95% CI, −1.81 to 0.93), meeting the success criterion for safety (noninferiority margin <3). There were no differences in graft survival, MATE-free survival, or freedom from any individual MATE. Everolimus was associated with greater improvement in estimated glomerular filtration rate at 12 months (mean difference, 10.5 mL/min/1.73 m2; 95% CI, 1.09-19.91 mL/min/1.73 m2) and a lower incidence of CMV infection (hazard ratio, 0.50; 95% CI, 0.26-0.93).Conclusions and RelevanceAmong 6-month pediatric heart transplant survivors, everolimus and low-dose tacrolimus did not differ from tacrolimus and mycophenolate in preventing the composite of cellular rejection, CAV, and CKD at 30 months. However, everolimus and low-dose tacrolimus appear to be safe based on the total burden of 6 MATEs and may be associated with improved kidney function and less CMV infection.Trial RegistrationClinicalTrials.gov Identifier: NCT03386539

OBJECTIVE The Centers for Medicare & Medicaid Services (CMS) requires a low C-peptide level for insulin pump coverage unless the individual is β-cell autoantibody positive, which precludes coverage of automated insulin delivery (AID) systems for many people with type 2 diabetes. RESEARCH DESIGN AND METHODS In the Randomized Trial Evaluating the Efficacy and Safety of Control-IQ+ Technology in Adults With Type 2 Diabetes Using Basal-Bolus Insulin Therapy study evaluating the t:slim X2 insulin pump with Control-IQ+ technology, adults with insulin-treated type 2 diabetes were categorized into high C-peptide (n = 195) and low C-peptide (n = 59) groups based on CMS criteria. RESULTS In the AID group, mean HbA1c decreased from baseline by 0.8%, which was significantly greater than in the control group with both high (P < 0.001) and low (P = 0.02) C-peptide levels. Results were similar in participants ≥65 years old. CONCLUSIONS The benefit of AID is present with high and low C-peptide levels. Thus, requiring a low C-peptide level as a prerequisite for AID therapy is not warranted.

Abstract Repetitive head impacts are associated with structural brain changes and an increased risk for chronic traumatic encephalopathy, a progressive neurodegenerative disease that can only be diagnosed after death. Chronic traumatic encephalopathy is defined by the abnormal accumulation of phosphorylated tau protein, particularly at the depths of the superior frontal sulci, suggesting that sulcal morphology may serve as a relevant structural biomarker. Contact sport athletes, such as former football players, are at elevated risk due to their prolonged exposure to repetitive head impacts. Cortical atrophy linked to underlying tau accumulation may result in shallower and wider sulci, potentially making sulcal morphology an imaging marker for identifying individuals at risk for this disease. This study investigated sulcal morphological differences in former football players and examined associations with age, football-related exposure, clinical diagnosis of traumatic encephalopathy syndrome, levels of certainty for chronic traumatic encephalopathy pathology, neuropsychological performance, and positron emission tomography imaging using flortaucipir. We analysed structural magnetic resonance imaging data from 169 male former football players (mean age 57.2 (8.2) years, range 45–74) and 54 age-matched, unexposed asymptomatic male controls (mean age 59.4 (8.5) years, range 45–74). Sulcal depth and width were quantified using the CalcSulc, focusing on two regions in each hemisphere commonly affected by chronic traumatic encephalopathy pathology: the superior frontal and occipitotemporal sulci. Generalized least squares models were used to assess group differences and interactions with age and football exposure variables, including age of first exposure, total years played, and cumulative head impact exposure. An analysis of covariance evaluated relationships between sulcal morphology, clinical measures, and flortaucipir uptake, adjusting for age, race, body mass index, education, imaging site, apolipoprotein E4 status, and total intracranial volume. Former football players demonstrated significantly shallower sulcal depth in the left superior frontal sulcus compared to unexposed controls. Earlier age of first exposure and longer football careers were associated with greater widening of the left occipitotemporal sulcus. Higher cumulative head impact exposure was linked to reduced sulcal depth in the left superior frontal region. However, sulcal morphology was not associated with clinical diagnosis, levels of certainty, neuropsychological test performance, or flortaucipir imaging. These findings suggest that sulcal morphology may reflect cumulative exposure to repetitive head impacts, particularly in brain regions vulnerable to chronic traumatic encephalopathy pathology. Future ante- and post-mortem validation studies are needed to determine whether sulcal morphology can serve as a reliable in vivo biomarker of risk.

The COVID-19 pandemic necessitated a triad of therapies for patients: oxygen, nutrition, and patient positioning. In the progressive care units, patients were placed in a prone position while receiving continuous enteral nutrition (EN) to optimize healing and oxygenation. The study aimed to identify the rate of aspiration pneumonia in non-ventilated COVID-19 patients placed in a prone position while receiving continuous EN. This was a single-group, descriptive retrospective study. The study was conducted at a two-time Magnet ® designated academic medical and health science center in the Southwestern United States. The sample included 97 electronic health records (EHRs) of patients diagnosed with COVID-19, receiving continuous EN, and placed in a prone position from March 15, 2020 to June 1, 2022. Data were extracted from EHRs using ICD-10 codes, including patient demographics, EN frequency, gastric tube placement, patient positioning, and incidence of aspiration pneumonia. Descriptive statistics and non-parametric tests were used. The Kruskal–Wallis rank sum test and Fisher’s exact test were employed for comparisons. Statistical significance was set at p ≤ .05. Out of 97 patients, 8 (8.25%) developed aspiration pneumonia. The majority of patients (75%) had post-pyloric feeding tubes. All patients who developed aspiration pneumonia had post-pyloric tubes. Placing COVID-19 patients in a prone position while receiving continuous EN may be a safe practice. Diligent nursing assessment is crucial to minimize aspiration risk and optimize patient outcomes.

Purpose of review To synthesize the current literature regarding the evaluation and management of genitourinary fistula in women. Recent findings Genitourinary fistula are aberrant communications between the urinary tract and genital tract that present with urinary leakage per the vagina. Initial management often involves conservative measures, such as urethral catheter or ureteral stent placement, progressing to surgical repair when needed. Key surgical principles include a tension-free, watertight closure with well-vascularized tissue including tissue interposition as appropriate, and postoperative urinary drainage. When surgical management of vesicovaginal fistula is necessary, a transvaginal repair is the most common. Other minimally invasive approaches are increasing and result in similarly high success rates with lower patient morbidity compared to open abdominal surgeries. The initial management of ureterovaginal fistula commonly includes ureteral stent placement. When not feasible or in persistent fistula, laparoscopic and robotic surgical repair with ureteral reconstruction offers high success rates with lower morbidity than an open approach. Summary Successful management of genitourinary fistula ranges from conservative urinary tract drainage to surgical interventions based on etiology, location, and complexity. Approaches to repair are shifting toward less invasive procedures. With optimal technique and surgical planning, high success rates can be achieved, particularly in primary repairs.

Abstract Aim The aim of this review was to synthesise qualitative research evidence on factors influencing the implementation of patient reported outcome measures (PROMs) in surgical population. Methods The following databases were searched: MEDLINE, Embase, Emcare, Allied and Complementary Medicine, Global Health, Health and Psychosocial Instruments, Health Management Information Consortium, APA PsycInfo, PubMed and Web of Science. Searches were carried out between 21st and 23rd February 2024. “Best fit” framework analysis was selected for evidence synthesis, necessitating two systematic reviews. The “Models review” focused on relevant theory, framework or conceptual model relating to implementation of PROMs. The “Primary research review” focused on studies describing factors affecting the implementation of PROMs. Case reports, editorial, reviews, meta-analysis, protocols, or studies, conducted in non-surgical or paediatric population, were excluded. Results 3,714 studies were identified in the Models review, of which 7 underwent full-text review and 2 were included in the analysis. Two relevant implementation frameworks were identified: the Theoretical Domains Framework (TDF) and the Consolidated Framework for Implementation Research. TDF was selected as a priori framework for the coding of evidence. Primary research review identified 1,293 studies, of which 50 underwent full-text review and 18 were included in the analysis. Extracted data were coded against TDF, revealing multiple patient-, clinician- and provider-factors affecting the implementation of PROMs, including: beliefs about consequences and capabilities, environmental context and resources, knowledge, skills, social influences, decision processes, emotional and identity factors. Conclusions Successful implementation of PROMs into routine surgical practice requires careful consideration of patient-, clinician- and provider-factors.

Background: Flexor pollicis longus (FPL) palsy following both-bone forearm fracture (BBFF) is a rare complication. Methods: A retrospective review of acute BBFF treated with open reduction internal fixation by a single surgeon from 2005 to 2023 was performed. Injury and surgical characteristics of patients with documented FPL palsy were reviewed. In addition, 10 cadaveric dissections were performed to evaluate the anatomy of the anterior interosseous nerve (AIN) and its branches. The distance of these branches from palpable elbow landmarks and variability in branching pattern were evaluated. Results: Twenty-nine patients underwent surgery for acute BBFF. Of these, 5 (17%) had evidence of an FPL palsy either at the time of injury presentation (n = 2) or immediately following surgery (n = 3). All patients with FPL palsy sustained fractures in the middle one-third of the radius. All palsies resolved after an average of 33 days of observation. In cadaveric dissections, the average distance from the lateral epicondyle to the AIN takeoff and branch to the FPL was 5.5 and 7.6 cm, respectively. The AIN takeoff and branch to the FPL were never less than 4 and 7 cm from the lateral epicondyle, respectively. Conclusion: Flexor pollicis longus palsy following BBFF can occur at the time of injury or following surgery. All FPL palsies involved midshaft radial fractures and were likely neurapraxia. The etiology of FPL palsy remains unclear, but cadaveric dissection suggests the FPL motor branch may be at risk from mid-to-proximal radius fracture fragments or excessive traction during surgery.