Citations

Objectives: To compare thresholds and accuracies of FIB-4, vibration-controlled transient elastography (VCTE), point shear wave elastography (pSWE), 2D shear wave elastography (2D-SWE), and MR elastography (MRE) for detecting hepatic fibrosis in patients with MASLD. Materials and Methods: Systematic searching of MEDLINE, EMBASE, Cochrane Library, Scopus, and the gray literature from inception to March 2024 was performed. Studies evaluating accuracies of FIB-4, VCTE, 2D-SWE, pSWE, and/or MRE for detecting significant (≥F2) and/or advanced (≥F3) hepatic fibrosis in MASLD patients compared to histology were identified. Full-text review and data extraction were performed independently by two reviewers. Multivariate meta-analysis and subgroup analyses were performed using index test and fibrosis grading. Risk of bias was assessed using QUADAS-2. Results: 207 studies with over 80,000 patient investigations were included. FIB-4 1.3 threshold sensitivity was 71% (95% CI 66–75%) for detecting advanced hepatic fibrosis, which improved to 88% (85–91%) using a <0.75 threshold. FIB-4 specificity using a 2.67 threshold was 96% (94–97%). Sensitivities of 88–91% were achieved using thresholds of 3.2 kPa for pSWE, 4.92 kPa for 2D-SWE, 7.18 kPa for VCTE, and 2.32 kPa for MRE. No significant differences were identified for sensitivities in subgroup analysis with thresholds between 7 and 9 kPa. Most imaging-based studies were high risk of bias for the index test. Conclusions: A FIB-4 threshold of <0.75 and modality-dependent thresholds (VCTE < 7 kPa; pSWE <3 kPa; 2D-SWE <5 kPa; and MRE <2.5 kPa) would achieve sensitivities of around 90% when defining low-risk MASLD in population screening. A modified two-tier algorithm aligning with existing Society of Radiologists in Ultrasound guidelines would improve risk stratification accuracies compared to existing guidelines by European and American liver societies.

Abstract Background Inadvertent temporary transvenous pacing (TTVP) of left ventricle (LV) is rare and likely underreported, posing significant embolic risk. We present a case of TTVP with atypical trajectory identified on computed tomography (CT) imaging. Summary A 62-year-old male with metastatic renal cell carcinoma on chemotherapy and bifascicular block presented with symptomatic bradycardia and non–ST-elevation myocardial infarction (NSTEMI), raising concerns for complete heart block on ECG. Intermittent asystole occurred during TTVP placement with appropriate capture. Post-procedure, ECG showed ventricular-paced rhythm with pseudo-right bundle branch block, and chest X-ray suggested lead placement in right ventricle; however, suboptimal echocardiography limited lead visualization. Coronary angiography revealed non-obstructive coronary artery disease. Positron emission tomography–computed tomography (PET-CT), performed to evaluate immune checkpoint inhibitor myocarditis, incidentally noted TTVP wire entering right subclavian artery and traversing to LV. Patient underwent TTVP removal, endovascular repair, and pacemaker implantation; however, course was unfortunately complicated by embolic stroke and haemorrhagic conversion. Discussion Early detection and management of lead malposition remain critical to minimizing complications. Management strategies for inadvertent lead malposition (ILM) depend on duration of implantation, clinical presentation, and associated risks. This case highlights importance of recognizing this high-risk complication, preventive strategies, and evidence-based management. While existing data primarily focus on ILM in permanent devices, further research is needed to elucidate incidence, predictors, and outcomes of ILM in TTVP, particularly in resource-limited settings.

Abstract Objective Allergic fungal rhinosinusitis (AFRS) is characterized by type I immunoglobulin E (IgE)‐mediated hypersensitivity reactions to fungal antigens. This systematic review and meta‐analysis assessed the efficacy of biologics in the management of refractory AFRS. Data Sources PubMed, SCOPUS, Embase, Web of Science, and Cochrane. Review Methods Changes in Sino‐Nasal Outcome Test (SNOT)‐22 scores, endoscopic findings, serum eosinophil count, and total IgE levels were assessed in patients with refractory AFRS after receiving biologic therapy. Subgroup analyses were conducted to evaluate the individual efficacy of each biologic agent, including dupilumab, mepolizumab, and omalizumab. Results A total of 60 patients from 6 studies were analyzed. Biologics showed a significant improvement in SNOT‐22 scores (standard mean difference 1.1607 [95% CI 0.5549; 1.7664]), endoscopic scores (2.1953 [1.4181; 2.9725]), serum eosinophil count (1.1649 [0.7735; 1.5563]), and total IgE level (1.0700 [0.4052; 1.7348]). Dupilumab, mepolizumab, and omalizumab all enhanced SNOT‐22 and endoscopic scores. Additionally, dupilumab significantly reduced total IgE levels (1.2981 [0.4063; 2.1900]), whereas both dupilumab (0.9274 [0.1592; 1.6957]) and mepolizumab (1.2324 [0.9215; 1.5433]) significantly lowered the serum eosinophil counts. Conclusion The agents significantly improved nasal symptoms, laboratory findings, and endoscopic scores. These findings support the potential role of biologics as a therapeutic option for patients with AFRS who are unresponsive to conventional treatments.

Background/Objectives: Inflammatory bowel disease (IBD) is a chronic inflammatory condition encompassing ulcerative colitis (UC) and Crohn’s disease (CD). The role of environmental factors in the pathogenesis of IBD remains elusive. Nevertheless, evidence suggests a pivotal role of viruses, specifically Epstein–Barr virus (EBV), in the progression of IBD through mechanisms such as molecular mimicry and bystander activation. Our previous findings demonstrate EBV DNA’s significant role in exacerbating colitis symptoms and elevating the levels of the pro-autoimmune cytokine interleukin-17A (IL-17A) in an IBD mouse model via toll-like receptor 9 (TLR9). Therefore, we aimed to examine the role of EBV particles in the pathogenesis of IBD, and the potential role of TLR9 inhibition in ameliorating disease outcomes. Methods: Three days post colitis induction, EBV particles were intra-rectally injected into female C57BL/6J mice, followed by the intra-peritoneal administration of TLR9 inhibitor. Thereupon, mice were monitored daily and the disease activity index (DAI), colon lengths, and damage scores, as well as the number of cells, double-positive for IL-17A+ and IFN-γ+, and triple-positive for IL-17A+, IFN-γ+, and FOXP3+, were evaluated. Results: Our findings revealed a significant role of TLR9 inhibition in mitigating colitis features in an EBV-injected IBD mouse model compared to the control group. Conclusions: These results indicate an essential role of TLR9 in initiating immune responses against recurrent EBV reactivation events, which ultimately contributes to inflammation aggravation in IBD patients. Consequently, TLR9 could serve as a potential therapeutic target to alleviate the severe symptoms of IBD in EBV-infected individuals.

Purpose: Guidelines recommend serum estradiol concentrations of 100–200 pg/mL for transgender women prescribed oral, subcutaneous, or transdermal estradiol with or without adjunct antiandrogen as gender-affirming feminizing hormone therapy (HT). The purpose of this systematic review was to evaluate if the guideline range of 100–200 pg/mL for estradiol concentration is associated with indicators of adequate gender-affirming feminizing HT, specifically feminizing sufficiency, insufficiency, testosterone suppression, or toxicity in transgender women. Methods: The Populations/Intervention/Comparator/Outcome model was applied to the study question, whereby the target population included transgender, gender-diverse, and nonbinary adults using gender-affirming feminizing HT by any route of administration, with or without adjunct antiandrogen use. The comparator was defined as estradiol concentrations within (100–200 pg/mL or 367–734 pM) versus outside (</>100–200 pg/mL) the guideline range; evaluated outcomes were listed by the same clinical guidelines that recommend using the 100–200 pg/mL range. Embase, MEDLINE, and Web of Science were queried over a 24-year time frame (January 1, 1999–April 20, 2023); the search was restricted to English. The extracted outcomes were categorized as indicators of therapeutic insufficiency, sufficiency, toxicity, or hormone concentration. Results: There were 49 studies that met the inclusion criteria, of which 9, 42, 25, and 5 studies included indicators of therapeutic insufficiency, sufficiency, toxicity, or hormone concentration, respectively. The search did not identify articles demonstrating that the 100–200 pg/mL guideline range provides optimal feminizing outcomes or reduces adverse events. Conclusions : Evidence does not support using the guideline range of 100–200 pg/mL to indicate sufficient feminization in transgender women using gender-affirming feminizing HT.

11pt, fleqn, a4paper, ]LegrandOrangeBook Background: Early catheter ablation for atrial fibrillation (AF) improves outcomes, but the optimal timing, especially in heart failure (HF) subtypes, remains unclear. Objective: To evaluate the impact of ablation timing on outcomes in patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Methods: We used the TriNetX database (2010–2024) to identify HF patients with AF who underwent ablation. Patients were classified as early ablation (≤1 year of first AF diagnosis) or delayed ablation (1–3 years), with propensity score matching (PSM) applied to balance the baseline characteristics. The primary outcome was AF recurrence, defined by repeat ablation, direct current cardioversion (DCCV), or antiarrhythmic drug (AAD) use after a 3-month blanking period. Secondary outcomes included stroke, hospitalization, and mortality over 5 years. Results: After PSM, delayed ablation was associated with higher AF recurrence in both HFrEF (HR 1.25, p < 0.001) and HFpEF (HR 1.27, p = 0.01), as seen in multivariate analysis. In HFrEF, delayed ablation was associated with higher incidence of re-do ablation, AAD use, and DCCV, while in HFpEF, higher recurrence with delayed ablation was associated with increased AAD use. Both cohorts had similar stroke and mortality rates between early and delayed ablation. CONCLUSIONS: Delayed ablation in HFrEF and HFpEF was linked to higher AF recurrence, driven by increased redo ablations, DCCV, AAD use in HFrEF, and higher AAD use in HFpEF. Stroke and mortality rates were similar, suggesting earlier ablation may enhance rhythm control without affecting long-term survival. Condensed Abstract Delayed atrial fibrillation (AF) ablation was associated with higher (AF) recurrence in both HFrEF and HFpEF. In HFrEF, delayed ablation led to increased use of re-do ablation, cardioversion and antiarrhythmic drugs (AADs). In HFpEF, only AAD use was significantly higher with delayed ablation. Stroke and mortality rates were similar between early and delayed ablation groups.

Background Venous hematocrit (vHct) is commonly used to inform blood volume (BV) status and stratify cardiovascular risk. However, vHct defines a percentage of red blood cells (RBCs) to total BV; therefore, similar vHcts can reflect significantly different absolute BVs and RBC mass/plasma volume profiles. This analysis explores how quantitative measures of BV enhance vHct reliability as a biomarker in heart failure. Methods A retrospective analysis was undertaken in 395 patients stratified by vHcts reflecting clinically heart failure–relevant cut points (35% and 40%). BV was quantitated by the indicator‐dilution methodology using iodinated‐131 labeled albumin. Kaplan–Meier analyses compared outcomes. Results Quantitative absolute BVs on average did not differ between vHct subgroups above or below cut points; however, the distribution of RBC mass and plasma volume profiles varied significantly. A normal BV profile was measured in approximately one third of cohort patients and BV hypervolemia in 58%, driven largely by plasma volume expansions (72% of cohort), all with similar distributions above and below cut points. In contrast, profiles of deficits in RBC mass (anemia) and excess (erythrocythemia) were more frequent below and above cut points, respectively, but not exclusively, with 14% of patients demonstrating contrasting RBC mass profiles. Kaplan–Meier analyses provided aggregate support for vHct to stratify heart failure–related outcomes but do not account for misclassified patients. Conclusions VHcts lack capacity to discriminate absolute BVs or the variability in RBC mass and plasma volume profiles above or below cut points. Therefore, quantitative BV measurements are key to adding specificity to individual vHct values, which permits reliable identification of BV status, assignment of appropriate risk, and guidance in management.

Objective The Patient Experience with Treatment and Self-management (PETS) is a valid self-report measure of treatment burden. The objective of this analysis is to determine severity cut points for its scores. Methods Data from two survey studies of adults with multimorbidity were used to determine estimates of low, moderate, and high burden for twelve PETS scores. Anchor-based analyses were used to map mean PETS scores onto scores of other self-report measures, including physical and mental health, self-efficacy, and activity limitations. Low, medium, and high scores on the anchors were based on published thresholds or tertile splits of score distributions. Mean PETS scores were compared across levels of the anchor variable using analysis of variance (ANOVA) then summarized to produce burden severity cut points. Results Study 1 featured survey data from 332 adults with multimorbidity (mean age = 66 years, 56% female); study 2 featured survey data from 439 adults with multimorbidity (mean age = 60 years, 62% female). Anchor measures were correlated with PETS scores at rho≥ 0.30. ANOVAs comparing PETS scores across the levels of each anchor variable were all significant ( p s< .001). Estimates were placed into data tables. Cut scores for discriminating treatment burden severity levels were identified as the midpoint between the mean PETS scores associated with adjacent anchor categories (e.g., low vs. medium and medium vs. high burden), rounded to the nearest whole number. Conclusions Severity thresholds can improve the interpretability of PETS scores. The preliminary estimates derived require verification in future studies.