Citations

Noncirrhotic portal hypertension has historically been described using heterogeneous and region-specific terminology—such as idiopathic portal hypertension (IPH), noncirrhotic portal fibrosis (NCPF), obliterative portal venopathy, and nodular regenerative hyperplasia—leading to substantial variability in diagnosis, reporting, and international research collaboration. Differences in guideline definitions from major societies (AASLD, EASL, and APASL), together with the presence of characteristic histologic lesions in patients without clinically overt portal hypertension, have further complicated disease classification. To address these challenges, a large, multisociety, international initiative was convened to harmonize nomenclature and diagnostic criteria. Representatives from liver, pathology, and pediatric hepatology societies across the Americas, Europe, and Asia participated in a structured consensus process that included specialized working groups and external Delphi validation. The initiative produced a globally harmonized and implementable diagnostic framework. Consensus was reached that the terms porto-sinusoidal vascular disorder (PSVD) and NCPF may be used interchangeably when identical diagnostic criteria are applied, and that they should be written as PSVD or NCPF . The diagnosis was defined as fundamentally clinicopathological, requiring integrated assessment. Core principles include the need for a high-quality liver biopsy (≥10 mm), mandatory exclusion of cirrhosis, and systematic exclusion of specific alternative conditions. Importantly, the consensus recognizes that PSVD or NCPF may be diagnosed even without clinical portal hypertension and may coexist with other liver diseases, provided cirrhosis is excluded. Standardized major and minor histologic criteria were developed collaboratively by expert pathologists and externally validated. Features of portal hypertension were harmonized into specific and nonspecific categories applicable to routine clinical practice. An integrated diagnostic scoring system incorporating histology, clinical features, associated conditions, and concommitant etiologies was developed and validated using the Delphi method. This consensus provides the first internationally endorsed, unified framework for the diagnosis of PSVD or NCPF. Its global implementation is expected to reduce diagnostic variability, improve comparability across regions, and facilitate the development of robust, internationally harmonized clinical and translational research cohorts.

Abstract Background Lumbar puncture is a routinely performed procedure, yet it presents significant challenges in patients with abnormal spinal anatomy, such as severe scoliosis or obesity. Conventional ultrasound-assisted neuraxial techniques, while superior to landmark-based methods, are constrained by two fundamental limitations: inaccurate projection of the probe’s geometric center onto the skin when the probe is tilted or rocked, and the difficulty of consistently replicating the exact probe angle during needle insertion. These limitations contribute to multiple needle passes, prolonged procedure time, and increased patient discomfort and complication risk. To address these issues, we developed a novel angle-free ultrasound-assisted technique designed to eliminate the need for replicating probe angulation during needle insertion. Case presentation: This angle-free approach was utilized for serial lumbar punctures in two patients with spinal muscular atrophy requiring repeated intrathecal nusinersen administration. Both patients presented with extreme anatomical complexity, including high body mass index (30 and 35.1 kg/m²) and severe scoliosis (Cobb angles 90° and 83°). The technique follows a three-step protocol: (1) Preprocedural imaging to select the optimal interlaminar space; (2) Ultrasound-guided postural adjustment until the probe could be held perpendicular to the bed edge and parallel to the floor while maintaining target visualization; (3) Needle insertion along this orthogonal trajectory. All 22 procedures (11 per patient) were completed successfully without persistent neurological complications. Procedural outcomes demonstrated a first-attempt success rate of 81.8% (Case 1) and 100% (Case 2), with first-pass success rates of 45.5% and 54.5%, respectively. Longitudinal analysis across sequential procedures revealed a consistent reduction in both the number of needle passes and needling time, reflecting a favorable learning curve. Conclusions The angle-free ultrasound-assisted neuraxial technique offers a valuable alternative for patients with complex spinal anatomy. By using real-time postural adjustments to achieve a needle trajectory, it enhances procedural precision and eliminates the technical hurdle of replicating probe angulation. The structured "4P" framework (Planning, Positioning, Perpendicular, Parallel) offers a practical guide for clinical adoption. The observed learning curve suggests that clinicians can readily acquire and apply this technique to manage such challenging cases.

INTRODUCTION: This study used the novel C-reactive protein-albumin-lymphocyte (CALLY) index to explore its relationship with the risk of developing gallstones. METHODS: This study conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey data from 2017 to 2020; multivariable logistic regression examined the CALLY-gallstone association. Restricted cubic splines tested nonlinearity. Subgroup and mediation analyses explored population variations and mediating effects (Conicity, lipid accumulation product, and a body shape index). Receiver operating characteristic curves compared CALLY, systemic immune inflammation index, systemic inflammatory response index, and aggregate index of systemic inflammation predictive performance. RESULTS: After comprehensive adjustments, the highest CALLY quartile had significantly lower gallstone risk vs the lowest (odds ratio 0.56, 95% confidence interval 0.34–0.94). Restricted cubic splines revealed a linear inverse correlation. Subgroup analyses generally supported this inverse relationship. Mediation analysis identified the Conicity index as the strongest mediator (21.47%, P < 0.001), followed by lipid accumulation product and a body shape index (10.72% each, P < 0.001). Receiver operating characteristic analysis showed CALLY (area under the curve = 0.604) outperformed systemic immune inflammation index (0.540), systemic inflammatory response index (0.550), and aggregate index of systemic inflammation (0.546). DISCUSSION: A significant inverse association exists between the CALLY index and gallstone prevalence. The CALLY index demonstrates superior predictive ability compared with other indices, suggesting its potential utility as an objective biomarker for early gallstone risk identification.

Radiation-induced brain injury (RIBI) is a debilitating sequela after radiotherapy to treat head and neck cancer, and 20 to 30% of patients with RIBI fail to respond to or have contraindications to the first-line treatments of bevacizumab and corticosteroids. Here, we reported a Simon’s minmax two-stage, single-arm, phase 2 clinical trial (NCT03208413) to assess the efficacy of thalidomide in patients with RIBI who were unresponsive to or had contraindications to bevacizumab and corticosteroid therapies. The trial met its primary endpoint, with 27 of 58 patients enrolled showing ≥25% reduction in the volume of cerebral edema on fluid-attenuated inversion recovery–magnetic resonance imaging (FLAIR-MRI) after treatment (overall response rate, 46.6%; 95% CI, 33.3 to 60.1%). Twenty-five (43.1%) patients demonstrated a clinical improvement based on the Late Effects Normal Tissues–Subjective, Objective, Management, Analytic (LENT/SOMA) scale, and 36 (62.1%) experienced cognitive improvement based on the Montreal Cognitive Assessment (MoCA) scores. In a mouse model of RIBI, thalidomide restored the blood-brain barrier and cerebral perfusion, which were attributed to the functional rescue of pericytes secondary to elevation of platelet-derived growth factor receptor β (PDGFRβ) expression by thalidomide. Our data thus demonstrate the therapeutic potential of thalidomide for the treatment of radiation-induced cerebral vasculature impairment.

Abstract Lineage-ambiguous leukemias are high-risk malignancies of poorly understood genetic basis. Here, we describe a distinct subgroup of acute leukemia with expression of myeloid, T lymphoid, and stem cell markers driven by aberrant allele-specific deregulation of BCL11B, a master transcription factor responsible for thymic T-lineage commitment and specification. Mechanistically, this deregulation was driven by chromosomal rearrangements that juxtapose BCL11B to superenhancers active in hematopoietic progenitors, or focal amplifications that generate a superenhancer from a noncoding element distal to BCL11B. Chromatin conformation analyses demonstrated long-range interactions of rearranged enhancers with the expressed BCL11B allele and association of BCL11B with activated hematopoietic progenitor cell cis-regulatory elements, suggesting BCL11B is aberrantly co-opted into a gene regulatory network that drives transformation by maintaining a progenitor state. These data support a role for ectopic BCL11B expression in primitive hematopoietic cells mediated by enhancer hijacking as an oncogenic driver of human lineage-ambiguous leukemia. Significance: Lineage-ambiguous leukemias pose significant diagnostic and therapeutic challenges due to a poorly understood molecular and cellular basis. We identify oncogenic deregulation of BCL11B driven by diverse structural alterations, including de novo superenhancer generation, as the driving feature of a subset of lineage-ambiguous leukemias that transcend current diagnostic boundaries. This article is highlighted in the In This Issue feature, p. 2659

Abstract Optimal treatment of patients with various types of liver tumors or certain liver diseases frequently demands major liver resection, which remains a clinical challenge especially in children. Eighty seven consecutive pediatric liver resections including 51 (59%) major resections (resection of 3 or more hepatic segments) and 36 (41%) minor resections (resection of 1 or 2 segments) were analyzed. All patients were treated between January 2010 and March 2018. Perioperative outcomes were compared between major and minor hepatic resections. The male to female ratio was 1.72:1. The median age at operation was 20 months (range, 0.33–150 months). There was no significant difference in demographics including age, weight, ASA class, and underlying pathology. The surgical management included functional assessment of the future liver remnant, critical perioperative management, enhanced understanding of hepatic segmental anatomy, and bleeding control, as well as refined surgical techniques. The median estimated blood loss was 40 ml in the minor liver resection group, and 90 ml in major liver resection group (P < .001). Children undergoing major liver resection had a significantly longer median operative time (80 vs 140 minutes), anesthesia time (140 vs 205 minutes), as well as higher median intraoperative total fluid input (255 vs 450 ml) (P < .001 for all). Fourteen (16.1%) patients had postoperative complications. By Clavien-Dindo classification, there were 8 grade I, 4 grade II, and 2 grade III-a complications. There were no significant differences in complication rates between groups (P = .902). Time to clear liquid diet (P = .381) and general diet (P = .473) was not significantly different. There was no difference in hospital length of stay (7 vs 7 days, P = .450). There were no 90-day readmissions or mortalities. Major liver resection in children is not associated with an increased incidence of postoperative complications or prolonged postoperative hospital stay compared to minor liver resection. Techniques employed in this study offered good perioperative outcomes for children undergoing major liver resections.

ABSTRACTObjectivesTo determine how self-reported level of exposure to patients with novel coronavirus 2019 (COVID-19) affected the perceived safety, training and well-being of residents and fellows.MethodsWe administered an anonymous, voluntary, web-based survey to a convenience sample of trainees worldwide. The survey was distributed by email and social media posts from April 20th to May 11th, 2020. Respondents were asked to estimate the number of patients with COVID-19 they cared for in March and April 2020 (0, 1–30, 31–60, &gt;60). Survey questions addressed (1) safety and access to personal protective equipment (PPE), (2) training and professional development and (3) well-being and burnout.ResultsSurveys were completed by 1420 trainees (73% residents, 27% fellows), most commonly from the USA (n=670), China (n=150), Saudi Arabia (n=76) and Taiwan (n=75). Trainees who cared for a greater number of patients with COVID-19 were more likely to report limited access to PPE and COVID-19 testing and more likely to test positive for COVID-19. Compared with trainees who did not take care of patients with COVID-19 , those who took care of 1–30 patients (adjusted OR [AOR] 1.80, 95% CI 1.29 to 2.51), 31–60 patients (AOR 3.30, 95% CI 1.86 to 5.88) and &gt;60 patients (AOR 4.03, 95% CI 2.12 to 7.63) were increasingly more likely to report burnout. Trainees were very concerned about the negative effects on training opportunities and professional development irrespective of the number of patients with COVID-19 they cared for.ConclusionExposure to patients with COVID-19 is significantly associated with higher burnout rates in physician trainees.

PurposeBiomechanical properties can be used as biomarkers to diagnose tumors, monitor tumor development, and evaluate treatment efficacy. The purpose of this preliminary study is to characterize the biomechanical environment of two typical liver tumors, hemangiomas (HEMs) and hepatocellular carcinomas (HCCs), and to investigate the potential of using strain metrics as biomarkers for tumor diagnosis, based on a limited clinical dataset.MethodsMagnetic resonance (MR) tagging was used to quantify the motion and deformation of the two types of liver tumors. Displacements of the tumors arising from a heartbeat were measured over one cardiac cycle. Local biomechanical conditions of the tumors were characterized by estimating two principal strains (ε1 and ε2) and an octahedral shear strain (εsoct) of the tumor and its peripheral region. Biomechanical conditions of the tumors were compared with those of the arbitrarily selected regions from healthy volunteers.ResultsWe observed that the HCCs had significantly smaller strain values compared to their peripheral tissues. However, the HEMs did not have significantly different strains from those of the peripheral tissues, and were similar to healthy liver regions. The sensitivity of using ε1, ε2, and εsoct to diagnose HCC were all 1, while the sensitivity of using ε1, ε2, and εsoct to diagnose HEM were 0.67, 0.17, and 0.67, respectively.ConclusionsLagrangian strain metrics provide insight into the biomechanical conditions of certain liver tumors in the human body and may provide another perspective for tumor characterization and diagnosis.