Citations

Abstract Background The expanding use of biologic and small-molecule therapies for ulcerative colitis (UC) has raised concerns regarding perioperative safety. We conducted a network meta-analysis to compare short-term postoperative complications associated with preoperative exposure to these agents in patients undergoing colorectal surgery. Methods We systematically searched PubMed, Web of Science, and the Cochrane Library through September 15, 2025, for cohort studies of adults with UC who were exposed to biologic or small-molecule therapy within 12 weeks prior to surgery. Interventions included biologic therapy, small-molecule therapy, and no biologic or small-molecule therapy (control). The primary outcome was overall postoperative complications at 30 and 90 days. Venous thromboembolism (VTE) was assessed as a key secondary outcome. Random-effects network meta-analysis was performed using risk ratios (RRs) with 95% confidence intervals (CIs). Results Sixteen retrospective cohort studies involving 3235 patients were included. At 30 days, ustekinumab and tofacitinib were associated with lower overall postoperative complication rates than control (RR: 0.29; 95% CI: 0.09-0.96; and RR: 0.66; 95% CI: 0.46-0.96, respectively). Anti-tumor necrosis factor (TNF) therapy was associated with higher complication rates compared with vedolizumab, ustekinumab, and tofacitinib at 30 days (RR: 1.27; 95% CI: 1.00-1.63; RR: 3.67; 95% CI: 1.12-12.03; and RR: 1.61; 95% CI: 1.14-2.27, respectively). At 90 days, anti-TNF therapy was associated with higher complication rates than control (RR 1.20, 95% CI 1.03-1.40), although the 90-day analysis was based on limited data. VTE rates were similar across treatments at both time points. Conclusion Preoperative ustekinumab and tofacitinib were associated with fewer 30-day postoperative complications than control or anti-TNF therapy, while vedolizumab was associated with fewer complications than anti-TNF therapy. At 90 days, anti-TNF therapy was associated with higher complication rates compared with control. These findings, particularly at 90 days based on limited data, should be interpreted with caution and require confirmation in well-designed prospective studies with rigorous adjustment for confounding factors.

Cardiac arrest is a leading cause of global mortality, with low survival rates despite advances in resuscitation science. Reported survival ranges from 8% to 34% for out-of-hospital and in-hospital cardiac arrest. Extracorporeal cardiopulmonary resuscitation (ECPR) has emerged as a rescue therapy for patients unresponsive to conventional CPR, leveraging veno-arterial extracorporeal membrane oxygenation (ECMO) to provide artificial circulation, gas exchange, and maintenance of organ perfusion in the absence of spontaneous native circulation. Successful ECPR depends on minimizing time to ECMO initiation and selecting appropriate patients. While several aspects are consistent across countries, ECPR protocols vary in logistics, team composition, cannulation methods, and monitoring, which may influence patient-important outcomes such as survival and neurological recovery. This narrative review explores current global practices in ECPR, and identifies opportunities for standardization while recognizing elements that should remain context specific.

Abstract Background: amyotrophic lateral sclerosis is the most common adult-onset motor neuron disease, characterised by the progressive degeneration of upper and lower motor neurons in the brain and spinal cord. Despite substantial advances in the understanding of underlying disease mechanisms, effective therapies remain lacking. Methods: we generated spinal cord organoids from patient-derived induced pluripotent stem cells and matched isogenic controls to model in vitro the molecular pathology associated with the hexanucleotide repeat expansion within the C9orf72 gene. Results: C9orf72 organoids displayed delayed neuronal maturation, axonal degeneration, mitochondrial abnormalities, enhanced apoptotic signaling, and accumulation of dipeptide repeat proteins. Integrated multi-omics analyses revealed a consistent down-regulation of Netrin-1 at both the transcript and protein levels across patient-derived organoids, suggesting that its loss may contribute to impaired neuronal connectivity, compromised axonal integrity, and increased motor neuron vulnerability in C9orf72 amyotrophic lateral sclerosis. Conclusions: together, these findings establish patient-derived spinal cord organoids as a biologically relevant and in vitro model that recapitulates key cellular and molecular hallmarks of C9orf72-associated amyotrophic lateral sclerosis. This platform provides a valuable framework to deepen disease mechanisms, toward the development of new effective therapeutic strategies.

Background. Chronic kidney disease (CKD) is a common complication of nonrenal transplantation, influencing recipients’ morbidity and mortality. The incidence of CKD varies depending on the transplanted organ. Recipients of vascularized composite allotransplantation (VCA) need lifelong immunosuppression similar to that of solid organ transplantation. This study investigated renal function in VCA recipients. Methods. We studied 70 recipients from 17 centers (median follow-up: 8 y): 59 upper extremity, 10 face, and 1 penis transplant. Pretransplant and posttransplant clinical data and sera were collected to calculate the estimated glomerular filtration rate (eGFR) using the CKD Epidemiology collaboration 2021 formula. Results. Pretransplantation, the median eGFR was 105.36 mL/min (range, 71.39–155.39 mL/min). By 3 mo posttransplant, the eGFR had significantly decreased to 78.42 mL/min (range, 32.49–130.74 mL/min; P = 0.001) before stabilizing. Despite higher tacrolimus levels at 3 mo, no correlation with eGFR was found. During follow-up, 17.1% of patients experienced a ≥50% eGFR decline, 10.9% progressed to CKD, and 4.7% developed end-stage kidney disease. Some risk factors were identified, but their responsibility could not be established with certainty because of the low number of severe renal outcomes. Conclusions. Renal function declines in the majority of VCA recipients, but the function loss is lower compared with nonrenal solid organ transplantation recipients. Although no statistically significant correlation could be established between tacrolimus exposure and renal function decline, strategies aiming at minimizing calcineurin inhibitor exposure and avoiding other nephrotoxic causes are recommended to preserve long-term kidney function.

Immune-mediated epilepsies represent an etiologically unique category defined by immune activation within the central nervous system that initiates a pathophysiological cascade resulting in seizures, encephalopathy, and sometimes epileptogenesis with long-term epilepsy. Once considered rare and largely confined to paraneoplastic or postinfectious syndromes, immune-mediated and inflammatory mechanisms are now recognized across a broad spectrum ranging from acute autoimmune encephalitis with reversible seizures, new-onset refractory status epilepticus, or febrile illness-related refractory status epilepticus, to chronic autoimmune-associated epilepsy and drug-refractory structural epilepsies. This review integrates historical perspectives, mechanistic insights from animal and human studies, and contemporary clinical frameworks. It synthesizes advances in neuroimmunology, clinical phenotyping, diagnostics, immunomodulatory and antiseizure therapies, neuromodulation, and patient and family centered outcomes, and outlines future directions focused on biomarker-driven precision medicine, disease-modifying strategies, and interdisciplinary care models.

Abstract Objective The upper frequency limit of human brain activity remains unknown. Using ultrahigh sampling rate (≥20 kHz) intracranial microelectroencephalography, this study aimed to systematically explore and quantitatively characterize brain field oscillations beyond the established high‐frequency oscillation range (>2 kHz), and to determine their relationship to epileptogenic tissue. Methods We analyzed intracranial electroencephalographic recordings from 15 patients with drug‐resistant epilepsy, comprising 466 microcontacts and 434 macrocontacts implanted in mesiotemporal structures across four international epilepsy centers. A custom spectrogram‐based detector optimized for ultrahigh frequencies was developed to identify ultrafast oscillations (UFOs; >2 kHz). UFO rates were assessed in epileptic (successfully resected) and nonepileptic hippocampi and compared with established electrophysiological biomarkers, including interictal epileptiform discharges, ripples, and fast ripples. Statistical comparisons were performed using mixed‐effects models to account for intersubject and interelectrode variability. Results We identified a previously undescribed class of short‐duration oscillatory events spanning 2–8 kHz. UFOs occurred at significantly higher rates in epileptic compared with nonepileptic mesiotemporal regions, with the strongest differentiation observed in the 2–3‐kHz band. Two distinct UFO phenotypes were consistently observed: (1) spindlelike, narrow‐band oscillations and (2) sharp‐onset, rapidly decaying bursts. Both forms were prevalent within epileptic hippocampi but were exceedingly rare in nonepileptic structures. UFOs exhibited pronounced temporal intermittency and spatial focality and frequently arose independently of ripples, fast ripples, and very high‐frequency oscillations, indicating that they represent a distinct electrophysiological phenomenon. Macrocontacts detected UFOs only exceptionally, highlighting the necessity of microelectrode recordings to capture activity in this ultrahigh‐frequency regime. Significance These findings substantially extend the known frequency range of human brain field activity and identify ultrafast oscillations as a novel biomarker of neuronal hyperexcitability. UFOs likely reflect pathological microcircuit dynamics inaccessible to conventional clinical recordings and provide new insights into the organization and pathophysiology of epileptogenic networks.

Abstract Background Ventricular arrhythmias (VA) are common complications of acute coronary syndromes (ACS) and can cause cardiac arrest and adverse outcomes. However, the prognostic impact of VA according to their timing in relation to percutaneous coronary intervention (PCI) remains unclear. Purpose To assess the prognostic significance of VA in patients with ACS undergoing PCI according to the timing of occurrence (before, during, or after PCI). Methods We performed a systematic review and meta-analysis of observational studies reporting all-cause mortality with and without VA (sustained VT/VF) in ACS patients undergoing PCI. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using random-effects models for short-term (30 days/in-hospital) and long-term (1 year) mortality. Between-study heterogeneity was assessed using the I² statistic. We conducted subgroup analyses for studies that stratified VA according to timing, defined as VA before PCI (prior to arrival in the catheterization laboratory), VA during PCI (in the catheterization laboratory or immediately after reperfusion), VA after PCI (following completion of PCI). Each timing category was compared to patients who did not develop VA within the same time window (before, during or after PCI). Results Twelve studies comprising 49306 patients were included, of whom 4320 (8.76%) experienced VA. The mean age of the patients ranged from 60 to 70 years, and the follow-up ranged from hospital discharge to 8 years. VA was associated with increased short-term (OR 5.02 [3.91-6.44]) and long-term mortality (OR 3.00 [2.86-3.82]). However, in patients alive at discharge/30 days, subsequent long-term mortality risk did not differ between those with and without VA (OR 1.21 [0.70-2.09]) (Figure 1). The subgroup analyses showed that patients with VA were associated with higher short-term mortality compared to patients without VA within each time window: before (OR 4.32 [3.29-5.66]), during (OR 4.29 [2.08-8.84]), and after PCI (OR 9.29 [3.12-27.63]) (Figure 2). VA after PCI was associated with the highest OR for short-term mortality. Conclusions VA significantly worsens short-term outcomes in ACS patients undergoing PCI. Subgroup analysis shows that VA increases mortality in each timing category, before, during and after PCI, with the poorest prognosis observed for arrhythmias developed after reperfusion, in whom reversible acute ischemia may play a lesser role and underlying arrhythmic substrate may predominate.Figure 1Figure 2

Abstract Myelodysplastic syndromes (MDS) are clinically and biologically diverse disorders, emphasizing the need for personalized treatment approaches. The International Working Group for Prognostication of MDS (IWG_PM) recently introduced a molecular classification, referred to as the MDS taxonomy, that categorizes patients into 16 subgroups based on 21 gene mutations, 6 cytogenetic abnormalities, and loss of heterozygosity (LOH) at TP53 and TET2 loci. This study sought to validate and enhance the clinical relevance of the MDS taxonomy by analyzing a large retrospective cohort ( n = 5136) and transcriptomic data from a prospective cohort ( n = 477). The taxonomy successfully identified subgroups with distinct clinical characteristics and disease progression patterns. However, incorporating gene interactions from taxonomy subgroups did not improve the prognostic performance of the Molecular International Prognostic Scoring System (IPSS‐M). We further assessed whether the taxonomy could guide management in patients receiving disease‐modifying therapies. Except for the “ TP53 ‐complex” subgroup, taxonomy classifications were not predictive of hypomethylating agent response or transplant outcomes. Nonetheless, they correlated with overall survival, suggesting that while both IPSS‐M and the taxonomy capture disease biology, other non‐genetic factors may influence treatment response. RNA sequencing confirmed the biological distinctiveness of the taxonomy groups. Transcriptomic profiling of CD34+ bone marrow cells revealed unique, homogeneous gene expression patterns, particularly within the AML‐like, bi TET2 , SF3B1 , and TP53 ‐complex subgroups. Further integration of multi‐omics data may refine MDS classification, improving clinical decision‐making and guiding the development of targeted therapies.

Abstract Background Dalbavancin is increasingly used off-label for chronic Gram-positive bone and joint infections (BJIs) requiring prolonged antimicrobial therapy, but optimal dosing strategies and the role of therapeutic drug monitoring (TDM) remain unclear. We evaluated the real-world implementation of a proactive TDM-guided dalbavancin workflow within an outpatient parenteral antimicrobial therapy (OPAT) programme. Methods Single-centre prospective observational implementation study including adult patients with BJIs consecutively treated with dalbavancin in OPAT service between July 2022 and August 2025. A multidisciplinary team developed a workflow incorporating TDM-guided pharmacokinetic modelling to individualize dosing intervals after fixed initial administrations (Days 1, 8 and 43). Target Cmin concentrations were ≥8 mg/L, later increased to ≥15 mg/L after European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint revision. Primary outcomes included implementation metrics (feasibility, fidelity and appropriateness). Secondary outcomes were clinical effectiveness, safety and overall workflow success. Results The workflow was applied to 101 patients accounting for 418 TDM-guided dalbavancin administrations (feasibility). Three patient-driven treatment discontinuations were observed (3/101, 3.0%), and scheduled administrations occurred within the predefined time window in 335/418 (83.5%) of cases (fidelity). Pharmacological target attainment was achieved in 285/342 (89.6%) of administrations without dosing delays (appropriateness). Clinical effectiveness was achieved in 55/73 (75.3%) patients completing therapy, with 28/101 (28%) still on treatment. Adverse events–related discontinuation occurred in 3/101 (3%) patients. Overall workflow success was observed in 74/101 (73.2%) patients. Conclusions A multidisciplinary TDM-guided dalbavancin workflow within an OPAT programme was feasible and safe, achieving high target attainment and favourable clinical outcomes. This approach supports individualized long-acting dalbavancin therapy for complex chronic BJIs.