Citations

Expert consensus recommendations from 21 academic centers were established for appropriate radiography utilization at 12 potentially low-yield anatomic sites through a multidisciplinary process endorsed by six major American medical societies.

Purpose: To compare reported intraoperative failure-mode profiles between preloaded and manually loaded intraocular lens (IOL) delivery systems using U.S. Food and Drug Administration (FDA) device reports. Setting: FDA Manufacturer and User Facility Device Experience (MAUDE) database, United States. Design: Retrospective cross-sectional study. Methods: MAUDE reports from January 1, 2016 through December 31, 2025 were reviewed. Reports describing intraoperative IOL loading, delivery, or positioning issues were included when injector type was specified. Structured MAUDE fields served as the primary data source, and free-text narratives were analyzed using automated natural language processing to supplement classification when consistent with structured fields. Comparisons were performed using within-group proportions, and multivariable logistic regression estimated adjusted odds ratios (aORs) controlling for report year, manufacturer, lens platform, and reporting entity. Results: Of 57,435 FDA device reports, 14,460 intraoperative reports met inclusion criteria; 10,567 (73.1%) involved preloaded systems and 3,893 (26.9%) manually loaded systems. Manually loaded systems showed higher reporting of IOL damage (66.0% vs 45.4%; aOR 3.06, 95% CI 2.78–3.37; p<0.001) and loading issues (aOR 5.53, 95% CI 3.99–7.66; p<0.001). Preloaded systems showed higher reporting of delivery failures (40.5% vs 21.8%; aOR 3.91, 95% CI 3.51–4.35; p<0.001), lens positioning issues (aOR 1.27, 95% CI 1.01–1.62; p=0.041), and material or optics abnormalities (aOR 3.53, 95% CI 1.96–6.35; p<0.001). Conclusions: Preloaded and manually loaded IOL delivery systems demonstrated distinct failure-mode profiles within FDA device reports. These findings characterized reporting patterns rather than population-level risk and may inform device design and post-market surveillance priorities.

We describe the case of a man in his 60s with metastatic melanoma on encorafenib/binimetinib and nivolumab/relatlimab, with a history of immune checkpoint inhibitor (ICI)-induced acute interstitial nephritis, who presented with acute-onset nausea, vomiting and profuse watery diarrhoea. Investigations excluded infectious causes, and flexible sigmoidoscopy with biopsy demonstrated lymphocytic colitis. His symptoms persisted despite discontinuation of Braftovi-Mektovi (BRAF–MEK) therapy and required escalation of corticosteroid therapy and budesonide initiation. This case highlights the diagnostic challenges of differentiating ICI-mediated colitis from adverse events of targeted therapy and underscores the importance of endoscopic and histological confirmation in guiding treatment.

Background Early-life dysbiosis associated with Cesarean section (C-section) delivery is increasingly recognized as a modifiable risk factor influencing short- and long-term health outcomes. This multidisciplinary expert consensus summarizes the clinical implications of C-section on infant gut microbiota. It proposes evidence-based strategies to mitigate these effects, with a focus on the critical window of the first 1,000 days of life. Methods A multidisciplinary panel of 16 pediatricians, neonatologists, pediatric gastroenterologists, and nutrition experts conducted a targeted narrative review of the literature to inform a structured expert consensus process and participated in an online structured consensus process. Seventeen consensus statements were developed and validated through discussion, expert voting, and commentary, supported by a targeted review of current scientific evidence. Results The expert panel reached consensus on the impact of C-section delivery on early microbiota composition and its clinical relevance, emphasizing that the rising prevalence of C-sections worldwide demands urgent attention. Experts unanimously emphasized the importance of exclusive breastfeeding as the primary strategy to support healthy microbiota development in infants born by cesarean section. When exclusive breastfeeding is not possible, evidence-based nutritional approaches, including selected prebiotics and probiotic strains with documented clinical efficacy, are recognized as promising alternatives for supporting microbial balance. Notably, the panel underscored that not all probiotics are equally effective and recommended shifting toward evidence-based strains shown to help restore gut dysbiosis in this population. Also, experts advocated for continuing microbiota-targeted support throughout the first 1,000 days of life, viewing this developmental window as a critical continuum rather than a limited early-life phase, while acknowledging the need for more long-term data. Additionally, education for healthcare professionals and parents about the long-term implications of C-section delivery was emphasized as a key enabler of the broader adoption of eubiosis-targeted strategies. Conclusions Optimizing microbial colonization in infants born by cesarean section requires a multifaceted approach that prioritizes breastfeeding, supports judicious use of evidence-based nutritional interventions when needed, and emphasizes education and continuity of care across early life. By aligning clinical practice with emerging microbiome science, early-life interventions may reduce dysbiosis-associated risks and improve long-term health outcomes.

As an emerging tire wear-derived environmental contaminant, 6PPD-quinone (6PPDQ) has raised significant concerns regarding its neurotoxic potential, particularly for children exposed to recycled tire crumb rubber in playgrounds. However, the molecular mechanisms by which 6PPDQ influences neurological disorders such as epilepsy remain poorly understood. In this study, we employed an integrative framework combining network toxicology, bulk analysis of human epileptic brain tissues, Mendelian randomization, and molecular dynamics simulations to elucidate these mechanisms. Our findings, validated through CETSA-WB and SPR, identify 6PPDQ as a direct ligand that binds to and stabilizes neuronal TP53. Through a synergistic double-hit mechanism, 6PPDQ directly engages the TP53 pathway while simultaneously triggering microglial interleukin-6 secretion. These converging pathways lead to the suppression of the master antioxidant regulator Nrf2, resulting in glutathione depletion, excessive reactive oxygen species accumulation, and exacerbated neuronal damage under excitotoxic stress. Experimental validation using glutamate-induced HT22 cell models and microglia–neuron crosstalk systems confirmed that targeting the TP53/Nrf2 axis or scavenging ROS significantly attenuates 6PPDQ-induced neurotoxicity. Our findings highlight critical risks to pediatric neurological health posed by tire-derived contaminants and identify the TP53/Nrf2 axis as a promising therapeutic target. Furthermore, this work provides a robust scientific basis for refining risk assessment frameworks and developing regulatory strategies to mitigate environmental exposure to 6PPDQ.

Abstract We are interested in artificial gene regulation by exploiting principles learned from lactose repressor (lacI) control of the Escherichia coli lac operon through the formation of tight DNA loops on the order of 100–200 base pairs. We previously showed that appropriately designed DNA target-programmable Transcription Activator-Like Effector dimer (TALED) proteins can produce DNA-looping-dependent gene repression comparable to lacI. Here, we demonstrate regulation of such switches by the principle of controlled repressor autoinhibition. Thus, TALEDs are inhibited by controlled cyclization, dependent on small molecules. Cyclized TALEDs poorly participate in DNA looping. We fit DNA loop length-dependent data with an established thermodynamic model to quantitate these effects. We further demonstrate the ability of small molecules to induce gene expression using this system in actively growing E. coli cells. The resulting designed systems demonstrate regulated gene expression by DNA looping, emulating the lac system but with entirely different molecular components.

Abstract Background Several bispecific antibodies (BsAbs), including mosunetuzumab, glofitamab, and epcoritamab, are approved for non-Hodgkin lymphoma (NHL). However, real-world patient-centered data evaluating treatment-related time burden and preferences are lacking. Methods We conducted an online survey of 120 patients with relapsed/refractory follicular lymphoma (FL; N = 60) and diffuse large B-cell lymphoma (DLBCL; N = 60) receiving BsAbs. Participants reported all-cause healthcare visits and time spent on cancer-related healthcare resource utilization over the past 30 days, including travel, treatment administration, recovery, and impact on daily activities. Participants also evaluated two hypothetical treatment profiles to assess preference for fixed-duration versus treat-to-progression therapy. Results Participants with FL reported a mean of 2.5 healthcare visits in the past 30 days, with significantly fewer visits for mosunetuzumab versus epcoritamab (1.7 vs 3.3, respectively; P &lt; .01). In DLBCL, the mean was 2.6 visits, with fewer visits for glofitamab versus epcoritamab (2.2 vs 3.0; P =.01). Although epcoritamab visits were shorter in FL, more frequent visits and longer recovery time resulted in significantly lower monthly time burden with mosunetuzumab versus epcoritamab (31.2 vs 61.9 hours; P &lt; .05). Similarly, monthly time burden was also lower with glofitamab than epcoritamab in DLBCL (43.0 vs 87.7 hours; P &lt; .05). Most participants reported little to moderate impact on daily activities. Across treatment groups, ≥92% preferred a hypothetical fixed-duration regimen over a treat-to-progression therapy. Conclusion Our real-world data, including novel aspects of time toxicity, demonstrate clinically meaningful differences in time burden associated with BsAbs and emphasize the importance of incorporating patient convenience and preference into shared decision-making in NHL.

Summary Achalasia is a motility condition defined by failure of relaxation of the lower esophageal sphincter and loss of peristalsis in the distal esophagus. Per-oral endoscopic myotomy (POEM) is a technique to reduce lower esophageal sphincter pressure. We performed a systematic review and meta-analysis to assess the association between POEM and the clinical outcomes. We performed a systematic review and a meta-analysis (CRD420251052240). Literature search was done on PubMed and Embase (up to 8 June 2025). Original studies involving achalasia patients who underwent esophageal POEM with impedance planimetry using 8-cm balloon at 30 or 40 mL filling volumes with 325 catheter only (not the 322-N catheter) were included. The outcomes of interest were the clinical response groups (responders’ Eckardt score [ES] &lt; 3 and non-responders’ ES &gt; 3), reflux esophagitis, cross-sectional area (CSA), distensibility index (DI), and diameter. Nineteen studies with 1215 patients were included. The responders (ES &lt; 3) showed a statistically significantly greater increase in DI due to POEM (post-op minus pre-op) (mean difference [MD] = 1.92 mm2/mmHg [0.32, 3.53], P = 0.02) as well as a higher postoperative DI (MD = 1.87 mm2/mmHg [0.04, 3.70], P = 0.05) (40 mL). Reflux esophagitis group had statistically significantly higher CSA and diameter values (CSA MD = 15.68 mm2 [6.91, 24.24], P = 0.0005) (diameter MD = 0.96 mm [0.58, 1.33], P &lt; 0.00001) but no statistically significant difference for DI as compared to the non-reflux esophagitis group (DI MD = 0.19 mm2/mmHg [−0.51, 0.89], P = 0.59). In achalasia patients undergoing esophageal POEM, a greater interval increase in the DI as well as a higher post-procedural DI absolute value predicts a favorable clinical response. Higher postoperative CSA and diameter were linked to reflux esophagitis.