Citations

Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease marked by cholestasis and progressive fibrosis. While ursodeoxycholic acid (UDCA) remains the first-line therapy, approximately 30–40% of patients have an inadequate biochemical response, increasing the risk of disease progression. Obeticholic acid (OCA), a potent farnesoid X receptor (FXR) agonist, was the first second-line agent approved by the only Food and Drug Administration (FDA) and has demonstrated moderate biochemical efficacy but limited tolerability due to dose-dependent pruritus and safety concerns in cirrhosis. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPAR-α) agonist, showed substantial alkaline phosphatase (ALP) reductions when added to UDCA, although its long-term benefit remains unconfirmed in large-scale trials and its use remains off-label in the United States, unlike FDA-approved agents. Seladelpar, a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist, and elafibranor, a dual PPAR-α/δ agonist, have both recently received FDA accelerated approval after demonstrating significant improvements in ALP, biochemical response rates, and pruritus relief in phase 3 trials. This review summarizes these second-line therapies’ mechanisms, efficacy, safety, and limitations emphasizing the need for individualized treatment decisions and ongoing research into long-term clinical outcomes.

Objective Inflammatory bowel disease (IBD) is increasingly recognised in the Middle East, but limited regional data hinder a clear understanding of its burden. We aimed to examine trends in IBD diagnoses, disease phenotypes and predictors of poor outcomes at a major tertiary referral centre in the United Arab Emirates (UAE). Methods In this retrospective observational study, we evaluated diagnostic trends in a cohort of 600 Arab patients between 2002 and June 2025 and analysed detailed phenotypes in a subcohort of 414 patients diagnosed since 2012. Results We observed a nearly 13-fold increase in new IBD diagnoses among Arab patients at our centre between 2002 and 2024. This cohort (median age at diagnosis 25 years; 65% Crohn’s disease (CD; n=269), 35% ulcerative colitis (UC; n=145)) demonstrated a sharper rise in CD compared with UC, with CD being diagnosed at a significantly younger age (median 25 years vs 30 years, p=0.001). A substantial proportion of patients with CD presented with complicated disease defined as stricturing (B2; 22%, n=59), penetrating (B3; 17%, n=46) and perianal (34%, n=92) disease. Ileocolonic (L3) disease was a significant predictor for presenting with a complicated phenotype (OR 3.89). Penetrating (OR 13.9), stricturing (OR 3.38) and perianal (OR 2.22) disease were significant predictors for requiring surgery. 84% of patients with CD and 62% of patients with UC were exposed to advanced therapy. A diagnosis of CD and younger age at diagnosis were associated with a higher likelihood of needing advanced therapy. Conclusions This study provides the most comprehensive data set on IBD diagnoses and phenotypes in the UAE to date, highlighting a pronounced rise in IBD overall and of aggressive disease presentations in CD in particular.

Abstract Deconvolution models are a powerful tool for extracting cell-type-specific information from bulk gene expression profiles. Current methods leverage advanced machine learning models and high-resolution sequencing, like single-cell RNA-sequencing, showing promising results across diverse tissues and conditions. However, they still present important limitations: First, many depend on selecting a robust reference, which can strongly affect the deconvolution. Second, pseudobulk data used for training and real bulk RNA-seq samples often exhibit strong distribution shifts, which are currently unaccounted for. Finally, most deconvolution approaches behave as black boxes, which can compromise the reliability of the results. Here, we present Sweetwater, an adaptive and interpretable autoencoder that efficiently deconvolves bulk samples leveraging multiple classes of reference data. Moreover, we propose an improved way of generating training data from a mixture of FACS-sorted FASTQ files, reducing platform-specific biases and outperforming current single-cell-based references. Furthermore, we introduce a gold standard dataset to facilitate fair and accurate evaluation of deconvolution approaches. Finally, we demonstrate that Sweetwater adapts effectively to deconvolved samples during training, uncovering biologically meaningful patterns and enhancing result’s reliability. Sweetwater is available at https://doi.org/10.6084/m9.figshare.29609180, and we anticipate it will expedite the accurate examination of high-throughput clinical data across diverse applications.

Background and objectives Arteriovenous malformations (AVMs) with perinidal aneurysms and single draining vein are associated with an elevated risk of rupture and increased procedural complexity. The role of preoperative embolization in this high-risk anatomical subset remains unclear. This study aimed to evaluate the safety and efficacy of microsurgery with preoperative embolization, compared with microsurgery alone in patients with such AVMs. Methods We conducted a multicenter retrospective analysis of an AVM registry from the MISTA (Multicenter International Study for Treatment of Brain AVMs) consortium and included AVMs with perinidal aneurysms and a single draining vein. Baseline characteristics, angiographic outcomes, functional outcomes, and complication rates were compared. Propensity score weighting (PSW) using the covariate balancing method was applied to adjust for baseline differences. Results Out of a total of 1919 patients, 65 met the inclusion criteria; 45 patients underwent preoperative embolization followed by microsurgery, and 20 underwent microsurgery alone. After adjustment, complete obliteration rates were similar between groups (OR 0.87, 95% CI 0.04 to 16.33, P=0.92), as were rates of functional independence at discharge and follow-up. Overall complication, symptomatic complication, and mortality rates did not differ significantly between groups. However, permanent complications were significantly lower in patients with preoperative embolization (OR 0.06, 95% CI 0.004 to 0.84, P=0.03). Discussion In patients with AVMs featuring perinidal aneurysms and single draining vein, preoperative embolization followed by microsurgery was associated with fewer permanent complications and no increase in adverse outcomes compared with microsurgery alone. However, given the small number of events, this finding should be interpreted cautiously.

The Doppler twinkling artifact (TA) plays a crucial role in detecting some biopsy markers including those made of polymethyl methacrylate (PMMA), facilitating precise lymph node localization in diagnostic and therapeutic procedures. This study presents comprehensive signal processing analysis methods to quantify and characterize the TA phenomenon using raw, per-channel radiofrequency (RF) data acquired from PMMA markers scanned with an L7-4 linear array transducer. We evaluated signals at different stages along the image reconstruction pipeline including (1) beamforming, (2) beamformed RF signal conversion into in-phase/quadrature (IQ) signals, and (3) Doppler velocity calculations and image reconstruction. We analyzed changes of pulses within an ensemble and between ensembles (i.e., frames). We also evaluated the impact of wall filters with various cutoff frequencies on color and power Doppler image reconstruction. Comparative analysis between PMMA markers and a non-twinkling control sample demonstrated distinct TA signatures or lack thereof in color and power Doppler images. The IQ data from PMMA marker locations exhibiting TA signatures showed substantially higher variability compared to non-twinkling samples, with standard deviations approximately 20 times higher between ensembles and 5 times higher within ensembles. This quantitative analysis framework provides valuable insight into the TA signal, potentially leading to more reliable and accurate diagnostic interpretations.

Purpose: Atrial fibrillation (AF), the most common arrhythmia in older adults, is often treated with cryoballoon ablation (CBA) or laser balloon ablation (LBA) when refractory to medication. We used real-world patient data to investigate differences in arrhythmia-free survival, procedure and fluoroscopy times, and complications between these techniques. Methods: In this single-center, retrospective study of 178 patients with symptomatic paroxysmal AF referred for first-time pulmonary vein isolation (PVI), 103 underwent CBA, and 75 underwent LBA. Recurrence was defined as any atrial arrhythmia of > 30 seconds’ duration after a three-month blanking period. Complications at 30 days were recorded. Kaplan-Meier analysis was used to estimate arrhythmia-free survival at one year for both groups. Categorical variables were expressed as n (%) and continuous variables as mean ± standard deviation or median (Q1, Q3). Results: Baseline characteristics were similar between groups, with exception to left atrial volume index (CBA 32.2 ± 10.9 ml/m2; LBA 36.0 ± 11.0 ml/m2, p = 0.047). History of stroke was higher in CBA (13.6% vs 2.7%; p = 0.012), as was coronary artery disease (35.0% vs 14.7%, p = 0.002). Median fluoroscopy and procedure times (min) were significantly shorter in LBA (24.2 vs 31.6, p = 0.004; 141.0 vs 210.0, p < 0.0001, respectively). One-year arrhythmia-free survival rates were similar (CBA 79.1% vs LBA 78.7%, p = 0.934), as were total complication rates (21.4% vs 16.0%, p = 0.289), including rates of transient ischemic attack/stroke and vascular complications. Conclusions: In patients with paroxysmal AF undergoing PVI, CBA and LBA were equally efficacious at one year and demonstrated acceptably low complication rates. LBA was associated with reduced procedure time and fluoroscopy exposure.

Background and Objectives: Heart failure (HF) represents a major public health challenge worldwide, with rising prevalence, high morbidity and mortality rates, and substantial healthcare costs. Non-invasive telemonitoring has emerged as a promising adjunct in HF management, yet its clinical effectiveness remains unclear. Materials and Methods: In this systematic review, we summarize randomized controlled trials (RCTs) between 2004 and 2024 examining the efficacy of non-invasive telemonitoring on mortality, readmission, and quality of life (QoL) in HF. In addition, we characterize the heterogeneity of features of different telemonitoring interventions. Results: In total, 32 RCTs were included, comprising 13,294 participants. While some individual studies reported benefits, non-invasive telemonitoring demonstrated mixed effects on mortality, readmission rates, and QoL. The most common modality for interfacing with patients was by mobile application (53%), followed by web portals (22%), and stand-alone devices (19%). Periodic feedback (63%) was more common than continuous feedback (31%) or on-demand feedback (6%). Clinician reviews of patient telemonitoring data was event-triggered (44%) more commonly than based on a prespecified timeline (38%). In most designs (90%), patients played a passive role in telemonitoring. Conclusions: Non-invasive telemonitoring interventions for HF exhibited considerable variation in duration and system design and had a low rate of patient engagement. Future work should focus on identifying telemonitoring-responsive subgroups and refining telemonitoring strategies to complement traditional HF care.