Citations

Abstract Background The evaluation of gastrointestinal (GI) bleeding is frequently negative despite a prolonged workup involving several different radiologic and endoscopic tests. Ferumoxytol, a superparamagnetic iron oxide agent used for treatment of iron deficiency anemia, can be used off-label as a blood pool contrast agent at MRI. Purpose To perform a proof-of-concept study to determine if ferumoxytol-enhanced MRI (FeMRI) can be performed to assist in detecting the presence and location of GI bleeding in patients who have undergone a negative standard evaluation. Methods A retrospective convenience cohort of patients examined with FeMRI at a single center over a 2-year period was evaluated. Inclusion criteria included clinical suspicion for slow or intermittent, active GI bleeding not localized following conventional testing. Exclusion criteria included any allergy to ferumoxytol or iron-containing agents, additional MRI scans scheduled within the following 72 hours, current pregnancy or breastfeeding, history of medication-related hypotensive episodes not related to an acute illness, syncopal events, arrhythmia, or low resting blood pressure. The patient’s clinical characteristics, examination results, and outcome during their hospital stay were examined. Results Five males and 1 female with average age of 66 years (range, 37-79 years) were imaged with FeMRI. All had undergone full diagnostic evaluation of the GI tract including upper and lower endoscopy and small bowel evaluation with imaging and/or endoscopic testing; in all patients, repeated rounds of testing were performed. Diagnostic images were obtained in all patients who underwent FeMRI. In 4/6 (67%) patients, FeMRI demonstrated active bleeding in the small bowel (n = 3) and colon (n = 1). Conclusion FeMRI was able to demonstrate the presence and location of active GI bleeding in hospitalized patients with previous extensive negative evaluation. FeMRI should be further evaluated to determine its performance characteristics as an examination in evaluating patients with GI bleeding.

Background: Tendon-bone healing after rotator cuff injury is, or remains, a clinical challenge. Purpose: To examine the role of intraoperative use of purified exosome products (PEPs) in the treatment of rotator cuff injuries and to assess the effect of PEP on supraspinatus tendon-bone healing after rotator cuff repair in a rat model. Study Design: Controlled laboratory study. Methods: This study used 120 Sprague-Dawley rats that underwent an acute supraspinatus tendon transection from the insertion, followed by repair using a single transosseous suture. They were divided into 3 groups: a control group that received only sutures, a TISSEEL group that used a commercially available fibrin sealant patch (TISSEEL) of approximately 0.5 cm 2 , and a PEP-TISSEEL group that used a similarly sized TISSEEL patch combined with PEP. Autopsies were performed at 1, 3, 6, and 8 weeks after surgery. Analyses were performed using molecular biological, biomechanical, and histological techniques. Results: At 6 weeks, the PEP-TISSEEL group achieved greater failure load (mean, 27.5 ± 5.3 N) than the control (mean, 16.4 ± 4.2 N; P = .012) and TISSEEL (mean, 23.4 ± 5.0 N; P = .041) groups, with superiority persisting at 12 weeks (27.2 ± 6.5 N vs 13.1 ± 2.6 N [ P = .002] for the control group and 21.1 ± 5.8 N [ P = .037] for the TISSEEL group). DigiGait showed earlier recovery of stride length and paw angle. Histology revealed organized collagen and reduced scarring, while molecular assays demonstrated early inflammatory modulation with subsequent upregulation of collagen type 1 or 3 and TGF-β, supporting accelerated tendon-bone healing. Conclusion: Intraoperative application of PEP-TISSEEL enhanced tendon-bone healing in a rat model by improving biomechanical strength, promoting enthesis-specific histological regeneration, and accelerating functional recovery as evidenced by gait analysis. Clinical Relevance: The intraoperative application of PEP combined with TISSEEL significantly enhances rotator cuff tendon healing by modulating early inflammation, promoting collagen synthesis, and improving biomechanical properties in a rat model. These findings suggest that PEP-based therapies could offer a promising adjunct in surgical repair, potentially reducing retear rates and improving functional outcomes in patients with rotator cuff injuries. Further clinical studies are warranted to translate these benefits into human applications.

Aims Total elbow arthroplasty (TEA) has shown favourable outcomes in the management of severely comminuted distal humeral fractures in low-demand elderly patients, leading to its increased use in recent years. Less is known about the outcomes of TEA when used for the failure of either internal fixation or conservative management, particularly whether not performing TEA acutely influences the options for further management if fixation fails. This systematic review aimed to assess the clinical and functional outcomes following TEA when used for the post-traumatic sequelae of a distal humeral fracture, and to compare these outcomes with those in patients with a distal humeral fracture who undergo TEA acutely. Methods MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus databases were searched from January 2000 to September 2024 for studies reporting complications, reoperations, the range of motion of the elbow, or functional outcomes following the use of TEA in the management of the post-traumatic sequelae of distal humeral fractures, including those due to failed fixation, nonunion, and post-traumatic arthritis. Demographic and clinical data were collected, descriptive statistics were summarized, and meta-analyses were undertaken to compare the outcomes between salvage and acute TEA. Results A total of 16 studies were included, with a total of 380 patients who underwent salvage TEA and 251 who underwent TEA as the initial management. Salvage TEA was associated with a significantly higher overall risk of complications (odds ratio (OR) 2.5 (95% CI 1.0 to 5.9)), though the rate of reoperations did not differ from those who underwent TEA acutely (OR 1.4 (95% CI 0.8 to 2.4)). Pooled analyses revealed a similar postoperative range of flexion (mean difference (MD) -2.4° (95% CI -9.1 to 4.3)) and extension of the elbow (MD 1.1° (95% CI -2.3 to 4.5)) and pronation (MD 0.0° (95% CI -1.1 to 1.1)) and supination (MD -0.0° (95% CI -1.0 to 0.9)) of the forearm. However, salvage TEA showed significantly inferior functional outcomes, as assessed by the Mayo Elbow Performance Score (MD 9.7 (95% CI -18.8 to -0.6)). Conclusion These findings indicate that salvage TEA represents a viable option for the management of post-traumatic sequelae following the teatment of a distal humeral fracture, although patients who underwent salvage TEA had a significantly increased rate of complications and significantly inferior functional outcomes compared with those who underwent TEA acutely. Cite this article: Bone Joint J 2026;108-B(1):21–29.

ABSTRACT Introduction Positron emission tomography (PET) myocardial flow reserve (MFR) is a robust indicator of coronary vascular health and a strong predictor of cardiovascular risk. Clinical guidelines typically use fixed MFR thresholds (e.g., <2.0) to stratify risk, yet this approach overlooks individual variation, particularly by age and sex. We aimed to establish age- and sex-adjusted MFR percentiles and to evaluate their prognostic and predictive performance for cardiovascular risk assessment, in comparison with conventional fixed-threshold MFR approach. Methods Using data from the REFINE PET registry (24,820 patients from 12 sites), we measured PET MFR and derived age- and sex-adjusted MFR reference percentiles using quantile regression in patients without known coronary artery disease. All patients were categorized into percentile-based quartile groups. The primary outcome for prognostic and prediction analyses was major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, or heart-failure hospitalization. Time-to-event associations were evaluated using covariate-adjusted survival models, with cumulative incidence and hazard ratios (HR) estimated at 1 and 5 years in the derivation dataset, an independent but similar validation dataset A, and a high-risk validation dataset B. Predictive performance for MACE was assessed using discrimination, calibration, and reclassification metrics, comparing percentile-based models with models using a fixed MFR threshold (<2.0). Results Among participants (mean age 66.5 years; median follow-up 3.6 years), age- and sex-adjusted MFR quartile groups were strong independent predictors of MACE, with adjusted HR increasing stepwise across quartile groups at both early and later follow-up. At 1 year, HR (95% CI) comparing the lowest to the highest quartile group were 4.06 (3.41–4.82) in the derivation cohort, 3.31 (2.32–4.71) in validation cohort A, and 2.35 (2.05–2.70) in validation cohort B. At 5 years, the corresponding HR were 2.18 (1.86–2.56), 1.77 (1.31–2.40), and 1.59 (1.36–1.86). Percentile-based models demonstrated consistently higher discrimination, better calibration, and greater net reclassification for MACE at both time points compared with fixed-threshold MFR models. Although 67.2% of patients had preserved MFR (>2.0), cardiovascular risk increased steadily across MFR percentiles even within this range. Conclusion Age- and sex-adjusted MFR percentiles provide a reliable, clinically actionable measure of vascular health, improving cardiovascular risk stratification by better capturing age- and sex-related heterogeneity in vascular risk. Compared with traditional fixed-threshold approaches, MFR percentiles demonstrate improved predictive performance for cardiovascular risk assessment across diverse patient populations. CLINICAL PERSPECTIVE What is new? In a large, multinational real-world registry of more than 24,000 patients undergoing PET MPI, we derived age- and sex-adjusted myocardial flow reserve (MFR) percentiles, establishing a lifespan-based reference framework with age-specific reference values. Age- and sex-adjusted MFR percentiles showed a strong, graded association with 1- and 5-year cardiovascular risk and demonstrated improved prognostic and predictive performance compared with fixed MFR thresholds and models without MFR across independent derivation and validation datasets, including a higher-risk cohort. Lower adjusted MFR percentiles were consistently associated with higher risk of major adverse cardiovascular events, including all-cause mortality, myocardial infarction, and heart-failure hospitalization. What are the clinical implications? Age- and sex-adjusted MFR percentiles provide a personalized, dynamic measure of coronary vascular health that improves cardiovascular risk stratification by accounting for age- and sex-related heterogeneity. A percentile-based approach may help clinicians better identify patients at elevated cardiovascular risk who may warrant closer monitoring or intensified preventive strategies, while avoiding unnecessary intervention in lower-risk individuals. By integrating macrovascular and microvascular dysfunction, age- and sex-adjusted MFR percentiles offer a clinically interpretable marker of vascular aging that may inform future research on aging biomarkers, novel therapeutics and cardiovascular risk assessment across the spectrum of atherosclerotic and microvascular disease.

ABSTRACT Objective To comprehensively evaluate the validity of ICD-10-CM codes for both prevalent diagnoses and less common diseases, and to assess the performance of a large language model (LLM)-based system in validating these codes. Materials and Methods This retrospective study analyzed hospital admissions from the Medical Information Mart for Intensive Care (MIMIC-IV) database. We developed a validated LLM-based system using GPT-4o, refined through iterative prompt engineering, to assess ICD-10-CM code validity. We measured the PPV of ICD-10-CM codes, PPV of principal and secondary diagnoses, and the performance of an LLM-based system in code validation. Results Among 865,079 assigned codes, the PPV was 84.6% (95% CI, 84.5%-84.6%). Principal diagnoses had a PPV of 93.9% (95% CI, 93.7%-94.1%), while secondary diagnoses had a PPV of 83.8% (95% CI, 83.7%-83.9%). The LLM system demonstrated high performance in validating ICD codes, achieving 93.6% accuracy, 95.4% sensitivity and 85.2% specificity. Among correctly assigned secondary diagnoses, the majority (67.9%) represented historical or baseline conditions, while 32.1% reflected active conditions that deviated from baseline status; 22.3% of these emerged after hospital admission. PPV decreases with later diagnosis positions, with the largest decline occurring between principal and secondary diagnoses. Discussion and Conclusion In this large-scale evaluation, ICD-10-CM codes exhibited generally high accuracy, though variability existed by position and condition type. A validated LLM system performed comparably to physician review and offers a scalable means to improve coding accuracy. These findings support the potential for integrating LLM-based auditing into routine workflows to strengthen the quality of administrative and research data.

Abstract Objective Perimenopause is an under-recognized life stage that may be accompanied by complex and fluctuating symptoms. We aimed to quantify the prevalence of perimenopause uncertainty and explore the underlying drivers. Methods We conducted a mixed-methods study based on a cross-sectional survey of U.S. women aged 35 years and above (N=7,640). Closed-ended responses were analyzed to estimate the prevalence of perimenopause uncertainty with subgroup differences investigated by age and symptom severity. Content analysis of free-text responses (n=409) was conducted to identify the main uncertainty drivers. Results Overall, 34% of participants reported being unsure of their reproductive stage. Uncertainty peaked among those aged 40-44 (42%) and was highest among those with severe symptom burden (37%). The content analysis revealed three main uncertainty drivers. Symptom confusion and attribution was the most common (56%), reflecting difficulties interpreting bodily changes and distinguishing perimenopause from other causes. Knowledge gaps and information seeking accounted for 28% of responses, highlighting limited health literacy, assumptions about age, and active searches for evidence. Barriers to confirmation and care (16%) described dismissive healthcare encounters and reluctance to acknowledge perimenopause. Younger women (35-39 years) were more likely to cite knowledge gaps, while healthcare barriers peaked in the 40-44 age group. Conclusion Perimenopause uncertainty is a prevalent and clinically meaningful challenge. This uncertainty is conceptually distinct from illness-focused models: it is a universal transition with ambiguity and often lack of validation. Better symptom recognition and targeted communication is a crucial first step toward improving women’s awareness and support during perimenopause.

Introduction: Clostridioides difficile infection (CDI) is a major complication in patients with inflammatory bowel disease (IBD), contributing to increased morbidity, mortality, and health care burden. This study aimed to evaluate national trends and clinical outcomes associated with CDI in hospitalized IBD patients in the United States. Methods: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) from 2012 to 2021. Adult patients hospitalized with a primary or secondary diagnosis of IBD (Crohn’s disease or ulcerative colitis) were stratified into 2 groups by the status of CDI diagnosis (either primary or secondary diagnosis). Demographic characteristics, hospital outcomes, and complications were compared between CDI and non-CDI cohorts. Multivariable logistic regression was used to identify independent predictors of in-hospital mortality, septic shock, and venous thromboembolism (VTE). Results: Among 4,193,564 hospitalized IBD patients, 534,190 (12.7%) had CDI. CDI patients were older (mean: 68.8 vs 53.3 y, P < 0.001), with higher in-hospital mortality (3.6% vs 2.0%, P < 0.001), VTE (23.7% vs 6.2%, P < 0.001), septic shock (5.4% vs 4.0%, P < 0.001), and mechanical ventilation use (4.2% vs 2.8%, P < 0.001). Ulcerative colitis was more frequently associated with CDI than Crohn’s disease (30.3% vs 25.0%, P < 0.001) and independently predicted septic shock (OR: 1.09) and VTE (OR: 1.06) but was associated with lower mortality (OR: 0.81). Conclusion: The presence of CDI in hospitalized patients with IBD led to significantly worse outcomes. Ulcerative colitis is more commonly associated with CDI and increased risk of complications. These findings highlight the need for early detection, preventive strategies, and tailored management of CDI in the IBD population.

Background: Mastocytic enterocolitis has been proposed as a cause of chronic diarrhea and abdominal pain, characterized by increased mast cells in gastrointestinal mucosal biopsies. However, its clinical significance remains uncertain. Methods: We present a case report of a patient identified to have high levels of mast cells on gastrointestinal biopsies. We then reviewed cases at Mayo Clinic where patients had >20 mast cells per high-power field (HPF) on gastrointestinal biopsies. Patients with alternative explanations for mast cell elevation, including systemic mastocytosis were excluded. We analyzed demographics, clinical presentations, pathology reports, serum and urine mast cell mediators, inflammatory markers, bone marrow biopsies, motility testing, and treatment responses. Results: We identified 42 patients (30 female and 12 male) with elevated mast cells on biopsy (mean age: 41 y, range: 17 to 81). Mast cells were quantified using KIT (CD117) staining, with no abnormal clumping or morphology, and CD25 immunostaining was negative in all cases. Eosinophilic infiltration was absent in all but one case. Small intestinal bacterial overgrowth (SIBO) was found in 78% of patients tested. Treatments varied widely, with antihistamines and cromolyn being the most common. Among 21 patients with sufficient follow-up, only 5 (24%) reported partial or complete symptom improvement, while 76% experienced persistent symptoms. Conclusion: Routine assessment of mast cells on gastrointestinal biopsies is not supported by our findings. Elevated mucosal mast cells, in the absence of systemic mast cell disorders, may not indicate a distinct disease entity. Evaluation should focus on ruling out other inflammatory, allergic, infectious, and motility disorders, as well as SIBO. Further research is needed to determine the clinical significance of increased mucosal mast cells and their role in gastrointestinal symptomatology.

Background and Objectives: There are many well-described approaches to symptomatic ventral hernia management; however, there remains a significant patient population with limited options for a durable ventral hernia repair with a reasonable risk of infection and recurrence. Drawing from the orthopedic literature, we changed our approach to this clinical problem and developed a palliative ventral hernioplasty pathway. Materials and Methods: A retrospective review (2017–2019) of patients’ palliative ventral hernioplasty was performed. Results: In total, 43 patients included, with a female preponderance of 24 (58.6%) and a mean age 61.5 ± 11.5 years. The mean BMI was 38.1 kg/m2 (IQR: 25.4–62), and 28 patients (65.1%) had a history of prior wound/mesh infection. Urgent repair was performed in 14 patients. Overall polypropylene prosthetic was implanted in 26 patients, and bioprosthetic/absorbable mesh was used in the remaining. The mean surface area of the implanted mesh was 561 cm2. The most common wound complications identified were skin separation (30.2%) and seroma formation (48.8%). Hernia recurrence occurred in four (9.3%) patients, with a mean follow-up of 24.1 months (9–37). Three patients had central lightweight mesh rupture and one had a recurrence (bioprosthetic mesh); all were subsequently repaired. Conclusions: Despite the small number of patients, our palliative ventral hernia repair pathway offers durable repair with an acceptable risk of recurrence and mesh infection in patients who would otherwise be considered nonoperative.