Citations

Abstract Background and Aims Truncating variants in the TTN gene (TTNtv) are the most common genetic cause of dilated cardiomyopathy (DCM) but also occur as incidental findings in the general population. This study investigated factors associated with the clinical manifestation of TTNtv. Methods An international multicentre retrospective observational study was performed in families with TTNtv-related DCM. Shared frailty models were used to estimate associations of variant characteristics with lifetime risk of DCM, and logistic regression to estimate odds ratios (ORs) for individual-level clinical risk factor profiles (cardiac conditions, cardiovascular comorbidities, lifestyle) and DCM. Results A total of 3158 subjects in 1043 families with TTNtv-related DCM were studied. TTNtv-positive subjects were 21-fold more likely to develop DCM [OR, 21.21; 95% confidence interval (CI), 14.80–30.39]. Disease onset was earlier in males, but was similar for TTNtv of different types and locations. The presence of clinical risk factors was associated with earlier DCM onset (OR, 3.41; 95% CI, 2.06–5.64), with a prior history of atrial fibrillation having a two-fold increased odds of DCM (OR, 2.05; 95% CI, 1.27–3.32). The prevalence of clinical risk factors increased with age; however, the strength of the DCM association was greatest for young-onset (<30 years) disease (OR, 4.75; 95% CI, 2.35–9.60). Administration of beta-adrenergic receptor or renin-angiotensin system-blocking drugs prior to overt DCM was associated with 87% reduced odds of DCM (OR, .13; 95% CI, .08–.23). Conclusions Disease onset in TTNtv-associated familial DCM is dependent on individual patient context and is potentially modifiable by risk factor management and prophylactic therapeutic intervention.

Background: Orthopaedic surgeons routinely delay surgical management of femoral neck fractures in patients taking direct oral anticoagulants (DOACs) to decrease perioperative bleeding and associated complications. However, this practice contradicts the principles of hip fracture management, as early surgery is associated with morbidity and mortality benefits. The purpose of this study was to quantify the association of DOAC use and perioperative outcomes in patients who underwent hemiarthroplasty (HA) or total hip arthroplasty (THA) for femoral neck fractures. We hypothesized that early surgical intervention on a patient taking a DOAC medication would not lead to worse perioperative outcomes. Methods: A retrospective cohort study was conducted on 2,833 patients who underwent primary THA or HA for femoral neck fractures between December 31, 2017, and January 29, 2024, across our hospital system. The patients taking a DOAC were divided into 3 groups based on the time since the last DOAC intake: 1 day, 2 days, and ≥3 days. Propensity matching was performed 1:1, accounting for age, sex, Elixhauser Comorbidity Index, preoperative chronic kidney disease stage, preoperative hemoglobin, body mass index, and hospital type. Subanalyses utilizing linear and conditional logistic regression models were performed to assess differences in outcomes between the groups that had a DOAC withheld and the control groups. Results: The mean age of all patients was 81 ± 10 years, 1,805 patients (64%) were women, and 207 patients (7%) were taking a DOAC prior to surgery. Despite comparable preoperative and postoperative hemoglobin levels between the groups that had a DOAC withheld and the control groups (all p > 0.05), the patients who had a DOAC withheld for 1 day were more likely to receive a postoperative blood transfusion (23.1% compared with 0%; p = 0.002). This difference in transfusion rate was not observed in other cohorts. There were no differences in medical complications, reoperation, discharge disposition, or mortality between the groups that had a DOAC withheld and the matched controls at any time point. Conclusions: Delaying surgical management due to DOAC medications may be unnecessary in patients undergoing arthroplasty for femoral neck fractures. Consideration should be given to adjusting transfusion triggers to reduce unwarranted blood transfusions in patients taking a DOAC. Level of Evidence: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Pancreatogenic or type 3c diabetes, which occurs as a consequence of pancreatitis, may have several mechanisms. Mechanisms overlapping with those of type 2 diabetes have been explored, including insulin resistance and insulin deficiency. However, autoimmune mechanisms in response to unmasking β-cell antigens, similar to those of type 1 diabetes (T1D), have not been thoroughly examined. We performed cross-sectional T1D autoantibody profiling in a large prospective cohort (N = 927) of adults with acute, recurrent acute, or chronic pancreatitis. We examined correlations of prevalence of autoantibodies against GAD (GAD antibody), IA-2 (IA-2 antibody), zinc transporter 8 (ZnT8; ZnT8 antibody), and insulin (insulin autoantibody [IAA]) with clinical and demographic features, including presence of diabetes, diabetes treatment, and family history of diabetes. Diabetes was present in 11 (12%) of 94 participants with acute pancreatitis, 69 (27%) of 273 with recurrent acute pancreatitis, and 235 (43%) of 560 with chronic pancreatitis. Among these groups, islet autoantibodies were respectively found in five (5.3%) of 94, 48 (17.6%) of 273, and 127 (22.6%) of 560. The proportions of individuals with diabetes who were autoantibody positive were 45%, 70%, and 54%, respectively (most commonly IAA, which may reflect exogenous insulin use). However, across the entire cohort, 27 participants (2.9%) had two, two (0.2%) had three, and one (0.1%) had four T1D-associated autoantibodies, respectively, suggesting a potential pathogenic link that should be further explored. ARTICLE HIGHLIGHTS Type 1 diabetes–associated autoimmune mechanisms have not been thoroughly examined in pancreatitis-associated diabetes. We assessed the prevalence of four islet autoantibodies in serum from a large prospective cohort of patients with acute, recurrent acute, or chronic pancreatitis. Diabetes was present in 11 (12%) of 94 participants with acute pancreatitis, 69 (27%) of 273 with recurrent acute pancreatitis, and 235 (43%) of 560 with chronic pancreatitis. Excluding those with only insulin autoantibody positivity, which is confounded by insulin treatment, islet autoantibodies were identified in 51 (5.5%) of 927 participants, and 30 (3.2%) of 297 were positive for two or more autoantibodies. Our findings suggest pancreatitis may elicit islet autoimmunity in a subset of patients, necessitating prospective longitudinal follow-up.

Abstract Endoscopic bariatric and metabolic therapies (EBMTs) are increasingly recognized as valuable tools for managing obesity and related metabolic disorders. As the prevalence of obesity continues to rise globally, there is a growing demand for effective, safe, and less invasive treatment options. This review provides a comprehensive summary of the available EBMTs, including both stomach-targeted and small-bowel-targeted devices. The review details the various devices, outlines the techniques for their proper use, and discusses their indications. It also presents data on their efficacy and safety, and the management of adverse events and weight regain, as well as anticipated future developments. The paper emphasizes the necessity for additional high quality randomized controlled trials and long-term outcome data to better define the role of these therapies within obesity treatment protocols. Overall, this review serves as an authoritative resource for endoscopists, bariatric specialists, and the wider healthcare community involved in obesity care, promoting best practices and guiding the appropriate implementation of EBMTs in clinical settings.

Background: Kienböck disease most frequently affects 1 wrist and rarely occurs bilaterally. The purpose of this study is to describe the natural history and identify risk factors for development of bilateral Kienböck disease. Methods: After institutional review board approval, 350 patients with surgically managed Kienböck disease from 1976 to 2023 were identified. A retrospective review of the electronic medical record was used to collect demographic, clinical, and radiographic information. Two-tailed student t -test was used for continuous variable, and Fisher’s exact test was used for categorical variables with analysis of power. Results: Ten of 350 patients (2.9%) had bilateral disease. The mean age was 45 (range: 14-62) years, and 6 out of 10 patients were female. The mean follow-up time was 47 (range: 9-274) months. Three of the 10 patients were laborers. Antecedent trauma (n = 2), prior corticosteroid injection (n = 1), and concomitant autoimmune disease (n = 1) were rare events. There was no difference in Lichtman Stage comparing the dominant and nondominant hands, and 72.2% of wrists were ulnar negative. This was higher but not significantly different than the unilateral affected comparison cohort (60%). Sufficient power was demonstrated (0.99). Eighteen of 20 wrists were treated operatively. Two cases required operative revision due to progression of disease. Conclusions: The cause of bilateral versus unilateral Kienböck disease remains unclear. Bilateral disease was not associated with a higher incidence of autoimmune disease, systemic corticosteroid use, or exposure to heavy manual labor. However, thrombosis leading to avascular necrosis of the lunate may be influenced by hypercoagulable and inflammatory diseases. Surgeons should maintain a high index of suspicion for bilateral disease in patients with these comorbidities. Routine screening of the contralateral wrist is unjustified if the patient is asymptomatic.

Background: Trochlear dysplasia is important in recurrent patellofemoral instability (PFI); reliable metrics are essential to understand this condition and help define optimal treatment. One such measurement is the entry point to transition point (EP-TP) angle, which describes 2 components of patellar tracking from full knee extension to flexion: (1) mediodistal movement and (2) pure distal movement. Currently, measurement of this metric relies on 3-dimensional (3D) models. Purpose: To further develop the EP-TP angle metric to allow its digital measurement, to establish cohort and interrater reliability values, and to evaluate its appropriateness for clinical use. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: A data set composed of 30 recurrent PFI patient knees and 30 control knees was acquired. Each knee came with anterior views of the distal femur and curvature maps, which highlighted relevant structures such as the trochlear groove and the medial and proximal ridge. Three raters measured EP-TP angles utilizing a digital tool with and without the curvature maps. Significance of differences in means, presence of a TP, and interrater reliability with intraclass correlation coefficients were tested and evaluated according to an established guideline (<0.5, poor reliability; >0.5-0.75, moderate; >0.75-0.9, good; >0.9 excellent reliability). A significance level of .05 corrected with the Bonferroni method was assumed. Results: PFI knees had a significantly higher EP-TP angle than the control cohort (48.9° ± 10.8° vs 11.8° ± 14.6°; P < .001). Patients had a greater TP prevalence than controls (96.7% vs 10.0%). Interrater reliability for the EP-TP angle with curvature maps was significantly better than without (0.84 [95% CI, 0.76-0.89] vs 0.67 [95% CI, 0.55-0.78]; P < .001). Conclusion: The EP-TP angle is significantly different between PFI patients and controls. This study presents a digital approach for measuring the EP-TP angle, in contrast with the initially described method, which required 3D prints. This digital approach, when aided with curvature mapping, yields better reliability.

AimsCompared to lymphovascular invasion (LVI), hilar soft tissue invasion (HSTI) is a relatively novel pT2 staging parameter in testicular germ cell tumours (GCT), associated with metastasis at the time of diagnosis and a risk factor for disease relapse. Given diagnostic variability in how pathologists interpret HSTI, herein we explore interobserver reproducibility among genitourinary (GU) pathologists.MethodsTwenty haematoxylin and eosin‐stained digitized slides from testicular GCTs were distributed to 30 GU pathologists to classify each as HSTI or not HSTI based on their respective clinical practices; slides with concomitant LVI were excluded. Slides were then evaluated for the following morphologic features: tumour invasion beyond prominent hilar vessels, tumour invasion beyond the rete, tumour invasion beyond the level parallel to hilar adipose tissue and tumour within (directly touching) hilar adipose tissue. Interobserver reproducibility was assessed, and the morphological features were correlated with HSTI. Relationships between pathologists' interpretations, morphological features and HSTI were evaluated using hierarchical clustering.ResultsAlthough the diagnosis of HSTI was relatively uniform with a majority agreement (>67%) reached in 17/20 slides, overall interobserver reproducibility was only moderate (kappa = 0.50). Morphological features such as invasion beyond the level parallel to hilar adipose tissue and invasion into fat were more sensitive and specific for HSTI, while features such as invasion beyond hilar vessels and invasion beyond rete were less useful.ConclusionsThese findings suggest that more specific defined diagnostic criteria for testicular GCT HSTI are needed.

Aortic stenosis (AS), the most common valvular heart disease, is traditionally graded based on several echocardiographic quantitative parameters, such as aortic valve area (AVA), mean pressure gradient (MPG), and peak jet velocity (Vmax). This systematic review evaluates the clinical significance and prognostic implications of discordant high-gradient AS (DHG-AS), a distinct hemodynamic phenotype characterized by elevated MPG despite a preserved AVA (>1.0 cm2). Although often overlooked, DHG-AS presents unique diagnostic and therapeutic challenges, as high gradients remain a strong predictor of adverse outcomes despite moderately reduced AVA. Sixty-three studies were included following rigorous selection and quality assessment of the key studies. Prognostic outcomes across five key studies were discrepant: some showed better survival in DHG-AS compared to concordant high-gradient AS (CHG-AS), while others reported similar or worse outcomes. For instance, a retrospective observational study including 3209 patients with AS found higher mortality in CHG-AS (unadjusted HR: 1.4; 95% CI: 1.1 to 1.7), whereas another retrospective multicenter study including 2724 patients with AS observed worse outcomes in DHG-AS (adjusted HR: 1.59; 95% CI: 1.04 to 2.56). These discrepancies may stem from delays in intervention or heterogeneity in study populations. Despite the diagnostic ambiguity, the presence of high gradients warrants careful evaluation, aggressive risk stratification, and timely management. Current guidelines recommend a multimodal approach combining echocardiography, computed tomography (CT) calcium scoring, transesophageal echocardiography (TEE) planimetry, and, when needed, catheterization. Anatomic AVA assessment by TEE, CT, and cardiac magnetic resonance imaging (CMR) can improve diagnostic accuracy by directly visualizing valve morphology and planimetry-based AVA, helping to clarify the true severity in discordant cases. However, these modalities are limited by factors such as image quality (especially with TEE), radiation exposure and contrast use (in CT), and availability or contraindications (in CMR). Management remains largely based on CHG-AS protocols, with intervention primarily guided by transvalvular gradient and symptom burden. The variability among the different guidelines in defining severity and therapeutic thresholds highlights the need for tailored approaches in DHG-AS. DHG-AS is clinically relevant and associated with substantial prognostic uncertainty. Timely recognition and individualized treatment could improve outcomes in this complex subgroup.

This study evaluated the effectiveness of using a traditional computed tomography (CT) simulation scan in the Leksell Gamma Knife® Icon™ workflow for stereotactic radiosurgery. We compared two workflows, one involving a traditional CT simulation co-registered with the magnetic resonance imaging (MRI) and cone-beam CT (CBCT) (MRI-CT-CBCT) and another without the CT scan, co-registering the MRI directly with CBCT (MRI-CBCT). The cohort included 50 frame-based (54 targets) and 55 frameless (124 targets) patients treated between August 2020 and December 2022. Target coverage was assessed by the percentage of each target covered by the prescription isodose line. The mean coverage differences for the frame-based and frameless cohorts were −1.20% ± 1.43% and −1.06% ± 1.51%, respectively, with 95% confidence intervals of −1.59, −0.81 and −1.32, −0.79. The MRI-CBCT workflow was deemed noninferior to the MRI-CT-CBCT workflow. Our data indicate that both workflows yield similar results, suggesting that a traditional CT simulation scan is unnecessary.