Although human epidermal growth factor receptor 2 (HER2)-targeted therapies have been approved for HER2-mutant NSCLC, real-world outcome data especially in the second-line setting remains limited. This non-interventional study utilized the Center for Cancer Genomics and Advanced Therapeutics national database to identify patients with HER2-mutant NSCLC who received second-line treatment in Japan. The primary objective was to characterize this population. Secondary objectives included describing second-line treatments and clinical outcomes (overall response rate [ORR], disease control rate [DCR], time on treatment [ToT] and reasons for second-line treatment termination). Among 3012 NSCLC patients identified, 168 (5.6%) had a HER2 mutation. In all NSCLC and HER2-mutant patients, median age was 66.0 years; 38.1% and 53.6% were female; 68.2% and 42.3% had a history of smoking; and 25.8% and 31.0% had brain metastases. In HER2-mutant patients, use of molecular targeted therapy (MTT, 44.6%) and chemotherapy (36.9%) as second-line treatment were comparable, followed by immunotherapy (15.5%), and immunochemotherapy (3.0%). Overall, median ToT with second-line treatment was 4.8 months (95% CI: 4.1-6.2). The longest median ToT was observed with MTT (8.1 months, 95% CI: 4.8-9.7), followed by chemotherapy (3.9 months, 95% CI: 2.5-5.2), immunochemotherapy (3.2 months, 95% CI: 0.4-not reached) and immunotherapy (5.5 months, 95% CI: 3.8-8.5). The ORR was 33.1% (95% CI: 25.4-41.6) and DCR was 78.4% (95% CI: 70.6-84.9). MTT was the most common second-line treatment, however, outcomes were generally poor, emphasizing the unmet need for effective second-line treatments for HER2-mutant NSCLC.
Patients with advanced hepatocellular carcinoma (HCC) who progress after first-line systemic therapy face a poor prognosis. This study evaluated the prognostic value of the baseline systemic immune-inflammation index (SII) in patients with unresectable HCC receiving second-line regorafenib, immune checkpoint inhibitors (ICIs), and transarterial chemoembolization (TACE). This multicenter, retrospective study included a cohort of 118 patients with unresectable HCC who experienced disease progression on first-line systemic treatment. To avoid the optimism bias and overfitting associated with data-derived binary cut-offs, the baseline SII was log-transformed and rigorously evaluated as a continuous variable. Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were analyzed using multivariate Cox proportional hazards models adjusted for key clinical confounders. In the multivariate analysis, the continuous log-transformed SII emerged as an independent prognostic factor. Each 1-unit increase in the log-SII was significantly associated with a 33% increased risk of disease progression (Adjusted Hazard Ratio [HR] = 1.33, 95% CI: 1.06-1.68, P = 0.015) and a 50% increased risk of overall mortality (Adjusted HR = 1.50, 95% CI: 1.08-2.09, P = 0.017). Subgroup analyses confirmed the consistency of these prognostic trends regardless of the regorafenib starting dose or the specific type of ICI administered. Notably, while baseline SII levels were not associated with objective response rates (ORR), they were significantly associated with an increased risk of severe treatment-related adverse events, underscoring its role as both a prognostic biomarker and a potential indicator of treatment tolerance. Baseline SII, when evaluated as a continuous variable, is a statistically significant and non-invasive prognostic biomarker for patients with unresectable HCC receiving second-line triple therapy. While its discriminatory ability as a standalone tool is modest, it serves as a useful clinical parameter for risk stratification when integrated with established hepatic and tumor burden indices.
Background While randomized trials have demonstrated that middle meningeal artery embolization (MMAE) reduces subdural hematoma recurrence over several months, its effect on immediate hospitalization outcomes remains unclear. Purpose To evaluate the impact of first-line stand-alone MMAE on immediate hospitalization outcomes for patients admitted with nontraumatic nonacute subdural hematoma (NASDH). Materials and Methods In this retrospective cohort study of the Nationwide Readmissions Database (2019-2022), nonelectively hospitalized patients with NASDH with clinically significant mass effect who did not undergo urgent decompression within 3 days were included. Those with multicompartment hemorrhage, cerebrovascular malformations, intracranial tumors, or embolization performed after delayed surgery were excluded. First-line stand-alone MMAE was compared with conservative management (CM) alone, and 3:1 propensity score matching was used to balance groups according to baseline characteristics. The primary outcome was functional independence at discharge. The secondary outcome was in-hospital mortality. Patients were followed up through the end of their hospital stays. Results A total of 5829 patients were included (median age, 74 years [IQR, 65-83 years]; 3949 male patients); 896 (15.4%) underwent MMAE. After propensity score matching, 850 and 2257 patients remained in the MMAE and CM groups, respectively. MMAE was associated with a higher functional independence rate (52.8% vs 42.2%, P = .001), lower mortality (3.1% vs 8.3%, P < .001), lower rate of need for rescue surgery (12.9% vs 31.7%, P < .001), and lower respiratory complication rate (10.5% vs 15.5%, P < .001). In exploratory subgroup analysis, functional independence rates were higher for early MMAE (within 3 days) versus CM (59.0% vs 42.2%, P < .001) but not for late MMAE versus CM (41.3% vs 42.2%, P = .81). Conclusion First-line stand-alone MMAE for patients nonelectively hospitalized for NASDH who did not require urgent decompression was associated with a higher early functional independence rate and lower in-hospital mortality, rescue surgery, and in-hospital complication rates than CM, particularly when MMAE was performed early. © RSNA, 2026 Supplemental material is available for this article.
Wound microbial burden and infection can delay wound healing, increase complications and rapidly progress to spreading or systemic infection, particularly in high-risk patients. Early diagnosis and appropriate treatment are essential for improved outcomes and reduced antimicrobial resistance (AMR). AMR is a growing concern in wound care due to reported inappropriate use of topical antiseptics, as well as systemic antibiotics. A recent survey found 41.8% of healthcare professionals used antimicrobial prophylactically, against recommendations, while 37.2% did not follow antimicrobial stewardship (AMS) guidance, indicating a potential gap in best-practice treatment. The primary aim of this document was to provide evidence-based guidance on the role of microbial-binding dressings (MBDs) in managing microbial burden, preventing infection and reducing the need for antimicrobial intervention in both surgical incisions and hard-to-heal wounds. The secondary aim was to summarise key findings in four clinical pathways. This guideline was developed according to AGREE II with a pragmatic literature review with GRADE assessments and a modified Delphi process for developing evidence-based statements. The literature search asked: 'In adults with a wound or surgical incision, do MBDs, compared with standard care, reduce surgical site infections, microbial burden, signs of infection, antibiotic use, antiseptic dressing use, time to healing or complication rates?'. For the statements, a 10-member expert panel scored agreement from 1 to 5, over three rounds (two remote and one in person), with acceptance at a mean score of ≥4.00 (SD ≤1.00). The literature review returned 12 studies on surgical incisions and 17 on hard-to-heal wounds, varying in evidence level and certainty. From 13 original statements, strong agreement was reached for 14; nine in round one, two in round two and three in round three (in-person meeting), with one statement split into two prior to agreement. The statements fit three themes: challenges of wound infection and AMR; benefits of MBDs for infection prevention and control (IPC); and early IPC in future AMS strategies. The guideline presents each statement with supporting evidence and detailed guidance for implementation in practice. This is followed by four easy-to-use AMS clinical pathways to support practical implementation, decision-making and consistency in care, currently under evaluation, with further validation studies expected. This guideline identifies and aims to meet a clear need for evidence-based best practice to enhance AMS in wound care. A paradigm shift towards infection prevention, early intervention and first-line treatment using MBDs should be considered an opportunity in everyday practice to minimise progression of infection, limit antimicrobial requirements and thus tackle the global threat of AMR.
Part 2 of the guideline addresses the updates on treatment recommendations in immunocompetent as well as immunosuppressed patients with invasive cutaneous squamous cell carcinoma (CSCC), based on current literature and expert consensus. A multidisciplinary panel of experts from the European Association of Dermato-Oncology (EADO), the European Dermatology Forum (EDF), the European Society for Radiotherapy and Oncology (ESTRO), the European Union of Medical Specialists (UEMS)-Dermatology Venereology and the European Organization of Research and Treatment of Cancer (EORTC), was formed to update the previous guideline on CSCC (version 2023). For common primary CSCC, first-line treatment is surgical excision with post-operative margin assessment or micrographically controlled surgery. Achieving clear histological margins is key for patients with CSCC amenable to surgery. Radiotherapy should be considered for non-surgical candidates/tumors. For patients with macroscopic regional lymph node metastases, individualized treatment should be discussed in the multidisciplinary tumor board. For patients with metastatic or locally advanced CSCC who are not candidates for curative surgery or radiotherapy, anti-PD-1 agents are the first-line systemic treatment, with cemiplimab being the approved systemic agent for advanced CSCC by the EMA. Second-line systemic treatments for advanced CSCC, include clinical trials, EGFR inhibitors (cetuximab) combined with anti-PD-1 immunotherapy, or chemotherapy or radiotherapy. The decision for adjuvant cemiplimab for CSCC at high risk of recurrence after surgery and radiotherapy should be discussed in the multidisciplinary tumor board. In addition, multidisciplinary board decisions are mandatory for all patients with advanced CSCC, considering the risks of toxicity, the age and frailty of patients and co-morbidities, including immunosuppression. Patients should be engaged in informed, shared decision-making on management and be provided with best supportive care to improve symptom management and quality of life. Frequency of follow-up visits and investigations for subsequent new CSCC depend on underlying risk characteristics.
Klinefelter syndrome (KS), the most common sex chromosome aneuploidy (affecting approximately 1 in 650 live male births), causes severe infertility. The extra X chromosome can impair the development of fetal germ cells, but its effects on somatic cells, especially the Leydig cells, are still not well known. We performed single-cell transcriptome analysis of fetal KS and control testicular cells, and found that two clusters of KS Sertoli cells with the XIST-negative cluster showing distinct gene expression pattern and abnormally increased G2/M ratio. Fetal KS Leydig cells showed increased proliferation and immature differentiation with high level of MAPK signaling pathway and X-linked EIF1AX. Inhibition of MAPK signaling partially rescued overproliferation and defective differentiation and androgen secretion in KS Leydig cells, while overexpression of EIF1AX recapitulated the phenotype of increased proliferation and decline in testosterone synthesis capacity in the Leydig cell line. These findings revealed the early pathological mechanisms of KS somatic cells, and lay the groundwork for developing novel early intervention strategies.
Immunotherapy has significantly improved outcomes in advanced hepatocellular carcinoma (HCC). However, most patients eventually progress, and second-line options remain limited. Fostrox, a liver targeted prodrug, was administered in combination with lenvatinib, aiming at enhancing antitumour activity while avoiding further deterioration of residual liver function. This multicentre, single arm Phase 1b/2a study evaluated safety, PK/PD and efficacy of fostrox (orally for 5 days in 21-day cycles), plus lenvatinib (standard doses), in locally advanced unresectable or metastatic HCC progressed on 1L/2L therapy (NCT03781934). A 3+3 dose escalation design was used to determine the recommended Phase2 dose. Twenty-one patients were enrolled and the median follow-up was 10.5 months. No dose limiting toxicities were observed and the RP2D of fostrox was established at 30 mg. All patients had adverse events (AEs); 81% grade ≥3 with possible relation to fostrox in 52.5% and lenvatinib in 66.7%. Fostrox related AEs were mainly transient neutropenia and thrombocytopenia. Other AEs, mainly attributed to lenvatinib, were grade I/II and consistent with monotherapy use. Fostrox dose reduction and/or discontinuation was 29% and 5%, and for lenvatinib 52% and 14%, respectively. There were no signs of treatment related liver function deterioration. ORR was 24%, DCR 81%, median TTP 10.9 months, median PFS 6.7 months and median OS 13.7 months. Fostrox PK analyses confirmed dose proportionality, and liver biopsies showed tumour selective DNA-damage. The combination of fostrox and lenvatinib demonstrated promising preliminary efficacy and tolerability post-immunotherapy, supporting further investigation as a second-line option in advanced HCC.
Ship trajectory prediction plays a crucial role in ensuring the safety of inland waterway transportation and enabling intelligent scheduling. To address the limitations of traditional models in capturing long-term dependencies and extracting salient features, this study proposes a novel prediction model-TDV-TTCN-BiGRU-integrating a Temporal-Dependent Variable (TDV) attention mechanism with an improved TCN-BiGRU architecture. The model employs a hierarchical Temporal Convolutional Network (TTCN) to extract multi-scale temporal features in parallel, incorporates the TDV attention mechanism to adaptively adjust the weights of speed and heading features, and uses BiGRU to model bidirectional dependencies, thereby enhancing prediction accuracy and stability. Experiments based on real AIS data include both comparative and ablation studies. Results show that the proposed TCN-BiGRU outperforms CNN, BiGRU, CNN-BiLSTM, and CNN-BiGRU models, achieving the lowest prediction errors. Compared to CNN-BiGRU, the TDV-TTCN-BiGRU model reduces MSE of predicted longitude and latitude by 14.47% and 18.83%, respectively; MAE by 22.41% and 21.25%; and ADE by 21.46%, with trajectory plots showing closer alignment with actual vessel tracks. Furthermore, to address the risk of vessels deviating from navigable channels, a multi-level yaw warning mechanism is developed and validated in typical cross-river scenarios. The system achieves a warning accuracy of over 96%, significantly improving the responsiveness to unexpected yaw behavior. The proposed method provides technical support for intelligent ship navigation, maritime safety management, and the protection of overhead transmission lines.
A digital in-line holography technique (DIH) is applied to measure non-invasively the three-dimensional motion of micrometric bubbles in an acoustic field. In addition to the components of the bubble displacements, DIH also allows the measurement of the temporal evolution of the bubble radii. It is shown that the knowledge of these four variables allow assessing the various forces that the bubbles experience. In the absence of the acoustic field, the buoyancy and drag forces are assessed. When the acoustic field is switched on, the primary radiation force acting on a single bubble is quantified. The order of the magnitude of the force, as well as its evolution along the bubble trajectory, are captured. It is demonstrated that the location of pressure nodes and antinodes in the cavity are recovered when compared with numerical simulations of the acoustic pressure field. When two bubbles nucleated in the cavity are investigated, they can attract and coalesce under the action of the secondary radiation force. DIH technique allows the quantification of this attractive force acting between the bubbles. The evolution of the secondary Bjerknes force with the interbubble distance is shown to be consistent with theoretical models.
This study examined the patient-reported outcomes (PROs) in the Asian subgroup of patients from the RATIONALE-305 (NCT03777657) trial. Adults with previously untreated, unresectable, or metastatic GC/GEJC were randomized (1:1) to receive either tislelizumab 200 mg or placebo IV once every 3 weeks, in combination with investigator-choice chemotherapy. PROs were evaluated using the EORTC QLQ-C30 and QLQ-STO22 questionnaires. Least-squares mean score changes from baseline to key clinical Cycles 4 and 6 were assessed using a mixed model for repeated measures. Time-to-deterioration (TTD) was also examined. This analysis included 748 Asian patients (376 in the tislelizumab arm; 372 in the placebo arm). At Cycle 4, both arms experienced clinically meaningful improvements in pain, with tislelizumab demonstrating significantly greater improvement than placebo. At Cycle 6, only the tislelizumab arm continued to show clinically meaningful improvement in pain. The mean treatment difference was significant for GHS/QoL, with the tislelizumab arm showing significantly greater improvement compared to the placebo arm. TTD analysis further showed that patients receiving tislelizumab had a lower risk of deterioration in QLQ-C30 physical functioning, QLQ-STO22 index score, and upper gastrointestinal symptoms. Asian patients receiving tislelizumab with chemotherapy reported better PRO outcomes compared to those receiving placebo with chemotherapy, particularly in GHS/QoL and pain/discomfort. Patients in the tislelizumab arm also experienced a lower risk of deterioration in overall gastric cancer symptoms, upper gastrointestinal symptoms, and physical functioning. These results, consistent with findings from the overall intention-to-treat population, support tislelizumab with chemotherapy as a first-line treatment for GC/GEJC. Gastric cancer, including tumors of the gastroesophageal junction, remains one of the most common and serious cancers worldwide, with particularly high rates in Asia. The RATIONALE-305 study investigated whether tislelizumab, an immunotherapy medicine, could improve how patients feel and function during treatment compared with chemotherapy alone. This analysis focused on the Asian subgroup of patients, who represented approximately three-quarters of all study participants. Throughout treatment, patients filled out short patient-reported outcomes (PROs) questionnaires that asked about pain, how well they could do everyday activities, and how they felt overall. By the middle of treatment, both groups reported improvements in pain, but patients receiving tislelizumab experienced greater and longer-lasting relief. They also felt better overall, had fewer stomach-related symptoms, and were able to stay active longer than those who received placebo. These findings support the use of tislelizumab as a helpful first treatment for people in Asia with advanced stomach cancer, and they highlight how important it is to ask people directly about how they feel during cancer treatment.
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Stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a major fungal disease threatening global wheat production. Identifying resistance genes and breeding resistant cultivars represent the most sustainable and cost-effective strategies for disease control. Genetic analysis of F2 and F2:3 populations derived from the cross Xiaoyan 22/Hangmai 8 indicated that the resistance to the prevalent Chinese Pst race CYR32 in Hangmai 8 is controlled by a single dominant gene, temporarily designated as YrH8. By applying bulked segregant exome sequencing (BSE-Seq) combined with SNP-index and Euclidean distance (ED) analysis, the candidate region for YrH8 was predicted to be within a 680-720 Mb interval on chromosome 7BL. Kompetitive allele-specific PCR (KASP) markers developed from polymorphic SNPs within this interval mapped YrH8 to a 2.9 cM genetic interval. After extensive screening of 2531 F3 plants, the candidate interval was subsequently narrowed to 0.7 cM, spanning a 3.7 Mb physical region (689.7-693.4 Mb) on the Chinese Spring reference genome. These results not only provide a foundation for YrH8 map-based cloning, but also supply practical KASP markers for marker-assisted selection in wheat breeding programs.
Treatment of metastatic urothelial carcinoma (mUC) has evolved. The efficacy of chemotherapy (CT) and immune checkpoint inhibitors (ICI) against UC with Variant Differentiation (UC-VD) or pure variant histology (PVH) is rarely reported. This study assessed the clinical impact of first-line (1L) CT and/or ICI in patients with UC-VD or PVH. This retrospective study included patients treated with 1L palliative CT or ICI at the West German Tumor Center Essen (2006-2024). Treatment allocation reflected real-world clinical decision-making and was not randomized. Primary endpoint was objective response rate (ORR); secondary endpoints were progression-free survival (PFS) and overall survival (OS). Kaplan-Meier analysis, log-rank tests, and descriptive statistics were used. 42 patients were analyzed: 45.2% received ICI (73.6% monotherapy, 26.4% combination/maintenance), 54.8% CT. Median age was 67.7 years in ICI group und 61.2 in CT group. PVH was predominant in CT group (65.2%), while UC-VD with squamous differentiation was common in ICI group (42.1%). ORR of ICI was 52.7%. As secondary endpoints, median PFS and OS were 7.8 months (95% CI: 4.3-19.0) and 12.4 months in ICI group; for CT group, 6.3 months (95% CI: 4.5-11.6) and 10.4 months (95% CI: 1.9-58.2), respectively. ORR was 52.7% (ICI) vs. 39.1% (CT). No significant differences were observed in PFS (p = 0.316), OS (p = 0.318), or ORR (p = 0.515). 1L ICI demonstrated numerically higher response rates compared to 1L CT, however, these results are purely descriptive and serve only to inform hypothesis-building, without reaching statistical significance. Survival outcomes were also better in ICI group, albeit without statistical significance, however these should be interpreted cautiously given the retrospective design and limited sample size. Given emerging combination strategies involving ICI or targeted agents, these findings support further investigation of ICI in this diverse and underrepresented population. small sample size and retrospective design.
Anaphylaxis is a time-critical, potentially fatal systemic hypersensitivity reaction. This narrative review summarizes recent advances in the diagnosis and management of anaphylaxis in children and adolescents, with emphasis on new diagnostic frameworks, improved self-management strategies, intranasal adrenaline, and disease-modifying therapies. A narrative review was conducted using PubMed and MEDLINE, focusing on articles and guidelines published between January 2020 and March 2026. Search terms included "anaphylaxis", "pediatric anaphylaxis", "adrenaline", "epinephrine", "autoinjector", "intranasal adrenaline", "food anaphylaxis", "omalizumab", and "oral immunotherapy". International guidelines, consensus documents, systematic reviews, pharmacokinetic studies, and pediatric studies were prioritized. Food remains the leading trigger in children, but drug, Hymenoptera venom, cofactor-dependent, and non-IgE-mediated mechanisms must be systematically considered. Adrenaline is underused in community settings despite being the only life-saving drug. Intranasal adrenaline represents the most visible delivery innovation: it may reduce needle-related barriers and simplify administration, but current evidence is largely based on pharmacokinetic/pharmacodynamic studies and limited pediatric clinical data. Omalizumab and oral immunotherapy are reshaping long-term risk reduction in food allergy but do not remove the need for emergency adrenaline.  The pragmatic management of anaphylaxis in children and adolescents entails self-management and hospital-based care. Intramuscular adrenaline is the first-line treatment when anaphylaxis is ongoing or recurrent, whereas adjunctive therapies should be considered on clinical grounds. Discharge recommendations should be individualized and include structured education, risk assessment, emergency planning and specialist follow-up. Intranasal adrenaline is a promising innovation, but its introduction requires clinical positioning, pharmacovigilance, cost-effectiveness evaluation, and continued emphasis on early treatment. • Intramuscular adrenaline is the first-line treatment for anaphylaxis and should not be delayed. • Food is the leading trigger in children, while drugs, venom, and cofactors become more relevant with age. • Intranasal adrenaline is a promising needle-free option, but pediatric evidence remains limited. • Omalizumab and oral immunotherapy may reduce risk but do not replace emergency preparedness.
To investigate the anatomical characteristics of the lateral skin region in valgus knee arthroplasty incisions, specifically the size and distribution of the lateral perforator Choke zone, in order to guide incision placement during knee arthroplasty and reduce the risk of compromised skin perfusion. From October 2019 to September 2024, 70 patients undergoing valgus knee arthroplasty with iliotibial band (ITB) release were followed to record the incidence of lateral skin perfusion impairment, including a detailed report of a typical case of lateral skin necrosis. Additionally, from October to November 2024, 10 knees from 5 adult cadavers were perfused via the femoral artery using red latex-lead oxide. The lateral superior genicular artery (LSGA) perforators, Choke zone, and surrounding skin and soft tissue perfusion were anatomically dissected, observed, and measured. Postoperatively, 10 patients (14.3%) showed lateral knee skin swelling with perfusion impairment. The distance from the center of the perfusion-compromised area to the joint line was 1.9 ± 0.6 cm, and the area of perfusion deficit was 15.0 ± 6.6 cm2; all cases healed with conservative treatment. One patient developed lateral skin necrosis, which was successfully treated with debridement and flap reconstruction. Cadaveric dissection revealed an average of 2.20 ± 0.75 LSGA perforators per knee. The origin of the perforators was 4.61 ± 1.16 cm from the joint line, with a diameter of 2.06 ± 0.35 mm, and the exit point located 4.24 ± 1.36 cm from the joint line. The perforator length averaged 7.36 ± 2.42 cm. Distal skin perfusion extended 2.45 ± 1.78 cm beyond the joint line, while proximal perfusion reached 13.56 ± 4.72 cm. The center of the Choke zone was 2.00 ± 1.12 cm from the joint line, with an area of 10.00 ± 3.51 cm2. The blood supply of the superior lateral genicular artery branches generally extends only about 2 cm up to the joint line. The Choke area formed with the inferior lateral genicular artery is small and poorly perfused, making it prone to intraoperative injury and localized ischemia. Therefore, iliotibial band release and lateral incisions should avoid the joint line and Choke area to minimize the risk of postoperative skin ischemia and necrosis.
We introduce Group Isolation Gauge Effect Metrics (GIGEM), a high-throughput software suite for Drosophila sleep analysis designed to manage large population datasets from multi-batch experiments. In this study, we characterized social isolation-induced sleep phenotypes across 38 Sleep Inbred Panel (SIP) lines after both acute and chronic social isolation. Beyond this specific study, GIGEM is broadly suited for diverse Drosophila sleep research involving large-scale and multi-batch datasets. GIGEM enabled an extensive analysis of sleep parameters and allowed systematic identification of sleep changes in response to social isolation. Following acute social isolation, SIP line animals showed heterogeneous responses, including sleep loss, sleep gain, and no change in sleep. In contrast, chronic social isolation led to significant sleep loss in nearly all lines, though to varying degrees. While most SIP lines were sensitive to chronic social isolation, a select few were resistant to it. These results were obtained across 38 SIP lines and wild-type controls (totaling 5687 animals). Collectively, our results demonstrate that chronic social isolation-induced sleep loss is a robust yet variable trait and establish GIGEM as a powerful, generalizable tool for Drosophila sleep phenotyping in large-scale, multi-batch studies.
The role of arterial blood gas (ABG) testing in the intensive care unit (ICU) remains debated within the "less is more" paradigm. While unnecessary testing may pose risks without benefit, timely ABGs provide critical information in unstable patients. Institutional variation in early ABG utilization and its association with outcomes remains unclear. We conducted a multicenter retrospective cohort study using the Japanese Intensive Care PAtient Database (JIPAD) between April 2015 and March 2023. Adult ICU patients with a stay ≥24 h and arterial line placement were included. The standardized number of ABGs (SNABGs) within the first 24 h was calculated as the ratio of observed to expected values, where expectations were derived from a multivariable model adjusting for patient covariates. ICUs were categorized into tertiles according to SNABG utilization. The primary outcome was in-hospital mortality, analyzed using multilevel logistic regression with ICU-level random intercepts. Restricted cubic splines were used to explore non-linear associations. Among 117,546 patients from 87 ICUs, the mean number of ABGs varied widely. After standardization, SNABGs ranged from 0.73-0.90 in the low tertile to 1.09-1.15 in the high tertile. In the multilevel model, SNABG was not significantly associated with in-hospital mortality (adjusted OR 0.942 [95% CI 0.807-1.100] for tertile 2; 0.874 [95% CI 0.751-1.017] for tertile 3). Flexible modeling suggested a non-linear trend toward better outcomes with higher utilization, but confidence intervals included unity. Early ABG utilization varied across ICUs, yet was not significantly associated with mortality. Sensitivity analysis suggested a non-linear relationship, with a tendency toward better outcomes at higher utilization. These findings warrant further investigation to clarify the role of early ABG utilization in critical care.
Gaps often exist between a therapy's performance in a controlled research setting and outcomes in routine clinical practice. A prescription binocular treatment delivered via head-mounted display has demonstrated efficacy for improving visual acuity in children with amblyopia in a pivotal randomized controlled trial (RCT). A retrospective patient registry has been established to collect real-world data on the treatment. To evaluate the real-world effectiveness of this treatment by benchmarking outcomes from a patient registry against those from the RCT. A retrospective analysis of a multicenter US patient registry was completed. The Registry was queried for patients who matched key eligibility criteria of the RCT with respect to age, amblyopia type and severity, and prior treatment exposure. The primary outcome was the change in amblyopic eye best-corrected visual acuity from baseline to the 12-week follow-up visit. These outcomes were compared with the historical intent-to-treat cohort (n = 45) from the RCT using a two one-sided tests procedure for equivalence with an equivalence margin of ±0.75 lines. Among the 40 registry patients meeting query criteria, mean age was 5.7 ± 1.0 years, and 21/40 (53%) had a history of prior treatment. Amblyopic eye best-corrected visual acuity improved a mean 1.7 lines (95% CI = 1.2-2.2), consistent with statistical equivalence within the prespecified ±0.75-line margin compared with RCT participants (1.8 lines; 95% CI = 1.4-2.3; two one-sided tests P = 0.038). No adverse safety events were reported. Patients prescribed this treatment for amblyopia in clinical practice achieved visual acuity improvements consistent with those observed in the RCT, indicating that effectiveness generalizes to real-world settings.
Pulmonary wedge resection is a lung-sparing procedure, with mechanical staplers enhancing surgical safety. Staple line reinforcement reduces air leakage; however, its effect on preventing mechanical vascular injury remains unclear. Staple-related vascular injuries rarely cause life-threatening complications. Here, we report a rare case of hemorrhagic shock caused by intercostal artery perforation from a protruding staple leg following thoracoscopic wedge resection with a reinforced stapler, which was likely triggered by lung collapse and re-expansion. A 76-year-old man underwent thoracoscopic wedge resection of right segment 6 for suspected metachronous lung adenocarcinoma using a reinforced stapler with a gold cartridge. The surgery was uneventful. On postoperative day (POD) 1, accidental chest drain removal caused lung collapse. After drain reinsertion and lung re-expansion on POD 2, the patient developed hemorrhagic shock on POD 3. Emergency thoracotomy revealed massive intrathoracic hemorrhage from the eighth intercostal artery due to a staple leg protruding through the reinforcement and perforating the artery during lung inflation. Hemostasis was achieved using electrocautery and artery ligation, followed by removal of the protruding staple and additional staple line reinforcement. The postoperative course was uneventful, and the patient was discharged on POD 10. Mechanical vascular injury due to staple protrusion can occur despite reinforced staplers. Lung collapse and re-expansion may alter the spatial relationship between the staple line and adjacent chest wall vessels, thereby increasing arterial injury risk. Careful staple line inspection, appropriate cartridge selection based on tissue thickness, and chest drain management are essential for preventing this rare complication.
To evaluate the effectiveness, predictors, and durability of perceptual learning therapy using ReVitalVision in older children with amblyopia who had failed prolonged patching therapy. This prospective interventional study included children (≤18 years) and adults with amblyopia, with pediatric participants having failed ≥2 years of patching due to poor compliance or non-response. All participants completed a mandatory minimum of 40 ReVitalVision sessions; up to 80 sessions were optional. Vision (logMAR) and stereoacuity were assessed at baseline, after 40 and 80 sessions, and at 3, 6, and 12 months. Multivariable regression was performed to identify predictors of outcome. Seventy-three participants (mean age 14.6 ± 5.5 years; 67% male) were included: anisometropic (n=34), strabismic (n=20), isometropic (n=6), deprivational (n=4), and other causes (n=9). After 40 sessions, significant visual improvement was observed across subtypes, greatest in anisometropic amblyopia (0.50 to 0.32 logMAR), with 40% achieving 20/40 or better. Strabismic amblyopia showed slower recovery (0.54 to 0.38 logMAR) and greater variability, while deprivational amblyopia showed limited response. Stereoacuity improved significantly in anisometropic (175 to 67 arcsec) and strabismic amblyopia (214 to 48 arcsec). Baseline BCVA was the strongest predictor of outcome (β = 0.061 per line worsening; p < 0.001), independent of amblyopia subtype and age. Time taken to complete 40 sessions did not influence outcomes. Eighty sessions produced marginally better vision but significantly greater stereoacuity improvement (p = 0.002). A subtle trend toward regression was observed at 6-12 months. ReVitalVision therapy produces clinically meaningful visual and binocular improvements in patching-failed amblyopia. Baseline visual acuity strongly predicts response and durability, and extended therapy may benefit patients with denser amblyopia, supporting individualized treatment duration.