Annals of Translational Medicine

Background The high mortality of septic shock demands novel adjunctive therapies. Shenfu Injection (SFI), a traditional Chinese medicine, shows potential but its mechanism remains unclear. Method s We conducted an open-label, randomized trial in 80 patients with septic shock. Patients received standard care with or without adjunctive SFI for 7 days. The primary outcome was 28-day mortality. Key secondary outcomes included inflammatory markers, lactate clearance, and vasopressor duration. Concurrently, network pharmacology analyzed SFIs bioactive components, predicted targets, and enriched pathways, with validation by molecular docking. Results The 28-day mortality was significantly lower in the SFI group (20.0% vs. 42.5%, P=0.030). SFI accelerated clinical improvement, evidenced by greater reductions in IL-6 and procalcitonin, higher 6-hour lactate clearance (35.2% vs. 18.5%, P<0.001), shorter vasopressor duration (48 vs. 72 hours, P<0.001), and more rapid SOFA score decline. Network pharmacology identified 145 SFI-septic shock common targets, with IL-6, SRC, and MAPK3 as central hubs. Pathway analysis revealed significant enrichment in TNF, PI3K-Akt, and IL-17 signaling pathways. Molecular docking confirmed strong binding of key SFI components (e.g., Ginsenoside Rh2) to core targets like IL-6. Conclusion s Adjunctive Shenfu Injection reduces mortality and improves clinical recovery in septic shock, potentially through a multi-target mechanism involving modulation of inflammatory and cellular signaling pathways. This integrative study provides both clinical evidence and a mechanistic framework supporting SFI's use. Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800020435.

Objectives: Among surgically resected non-small cell lung cancer (NSCLC) patients with similar stage and histopathological characteristics, there is variability in patient outcomes which highlights urgency of identifying biomarkers to predict recurrence. The goal of this study was to systematically develop a pre-surgical CT-based habitat-based radiomics classifier to predict recurrence-of-risk in NSCLC. Methods: This study included 293 NSCLC patients with surgically resected stage IA-IIIA disease that were randomly divided into a training (n = 195) and test cohorts (n = 98). From pre-surgical CT images, tumor habitats were generated using two-level unsupervised clustering and then radiomic features were calculated from the intratumoral region and habitat-defined subregions. Using ridge-regularized logistic regression, separate classifiers were developed to predict 3-year recurrence using intratumoral radiomics, habitat-based radiomics, and a combined model (intratumoral and habitat) which was generated using a stacked learning framework. For each classifier, probability of recurrence was calculated for each patient then numerous statistical and machine learning approaches were utilized to stratify patients for recurrence-free survival. Results: The combined radiomics classifier yielded a superior AUC (0.82) compared to the intratumoral (AUC = 0.75) and habitat radiomics (AUC = 0.81) models. When the classifiers were used to stratify high- versus low-risk patients utilizing a cut-point identified by decision tree analysis, high-risk patients were yielded the largest risk estimate (HR = 8.43; 95% CI 2.47 - 28.81) compared to the habitat (HR = 5.41; 95% CI 2.08 - 14.09) and intratumoral radiomics (HR = 3.54; 95% CI 1.45 - 8.66) models. SHAP analyses indicated that habitat-derived information contributed most strongly to recurrence prediction. Conclusions: This study revealed that habitat-based radiomics provided superior statistical performance than intratumoral radiomics for predicting recurrence in NSCLC.

After rejection, resubmission of scientific manuscripts often requires substantial journal-specific reformatting. We compared systematic review submission policies across high-impact ophthalmology journals and quantified policy similarity to support resubmission planning. We identified the top 50 ophthalmology journals by SCImago Journal Rank that publish systematic reviews and are not invite-only, extracted policies from author instructions using an a priori data dictionary, and computed pairwise similarity on a 0 to 1 scale using the Gower coefficient across mixed policy variables with available-case denominators for unstated fields. Policies were heterogeneous and frequently unstated. Only 29 of 50 journals (58%) stated a main-text word limit; among journals with numeric limits, the median was 4000 words (interquartile range 3500 to 5500; n = 23). Preferred Reporting Items for Systematic Reviews and Meta-Analyses compliance was explicitly required by 35 of 50 journals (70%), and prospective registration by 6 of 50 journals (12%). Across 1225 journal pairs, similarity was modest, with a median of 0.64 (interquartile range 0.57 to 0.71; range 0.05 to 0.98). Similarity among the top 5 highest-ranking journals ranged from 0.62 to 0.90 (median 0.75). Systematic review submission policies vary widely across high-impact ophthalmology journals, and most journal pairs show only modest similarity. Similarity-based guidance may help identify policy-aligned resubmission targets while anticipating common sources of reformatting burden.

BackgroundEpidermal Growth Factor Receptor (EGFR) inhibitors, while effective in oncology, are associated with under-characterized ocular adverse events (AEs). Prior studies have been limited in scope, lacking a comprehensive, class-wide analysis of the full spectrum of ocular toxicity, particularly for newer agents. MethodsWe conducted a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS) (2001-2025). Twelve EGFR-targeted agents were evaluated against a pre-specified set of ocular MedDRA Preferred Terms. To ensure robust signal detection, a significant association was defined by [&ge;]3 co-reported cases, a Proportional Reporting Ratio (PRR) [&ge;]2.0, and a false-discovery-rate adjusted p-value <0.05. ResultsAmong 6,976,462 drug-event combinations, 20 met all signal criteria for Eyelash Abnormalities, Ocular Surface Disease, or Vision-Threatening and Intraocular Events. Trichomegaly demonstrated extreme disproportionality (e.g., panitumumab PRR= 465.3, 95% Confidence Interval [CI], 247.7-874.3). A consistent pattern of ocular surface toxicity (conjunctivitis, keratitis, blepharitis) was observed across multiple tyrosine kinase inhibitors and monoclonal antibodies, indicating a class-wide effect. Signals for serious events included corneal perforation (erlotinib, n= 7, PRR=13.9, 95% CI= 6.6-29.4) and optic neuropathy (erlotinib, n= 6, PRR= 2.9, 95% CI= 1.3-6.4). ConclusionThis analysis confirms a strong, class-wide signal for ocular toxicity across the spectrum of EGFR inhibitors, from characteristic eyelid changes to sight-threatening complications. These findings underscore the necessity for proactive ophthalmologic monitoring, including baseline assessment, in patients receiving these therapies to preserve vision and maintain quality of life during cancer treatment.

PurposeTo evaluate the three-year efficacy and safety of compound trabeculectomy for uveitic glaucoma (UG). MethodsThis retrospective study enrolled 51 patients (53 eyes) requiring compound trabeculectomy, divided into UG (25 eyes) and non-UG groups (28 eyes). Outcomes including intraocular pressure (IOP), medication use, surgical success rates, and complications were analyzed over 3 years. ResultsBaseline characteristics including age, sex, preoperative IOP and medication use were comparable (all P>0.05). At 36 months, postoperative IOP was showed no significant differences, which was 15.4{+/-}8.4 mmHg and 14.6{+/-}3.3 mmHg (P=0.73) with 54% and 55% reduction (P=0.88) in UG and non-UG groups respectively. The qualified success rate was 76.0% and 85.7% at 36 months in UG and non-UG group, and Kaplan-Meier analysis showed no significant difference. Medication reduction of UG group was significant lower than non-UG group (P=0.0058). Comparable complication rates were observed between groups (all P>0.05), yet bleb scarring and cataract progression showed elevated incidence in both cohort. ConclusionCompound trabeculectomy effectively reduced IOP and medications use in UG and non-UG. There was no significant difference in both qualified and completed success rate between UG and non-UG. Complications of filtering bleb fibrosis and cataract progression should be pay close attention for both groups.

BackgroundLung transplantation remains the ultimate treatment option for patients with end-stage lung disease, but has many limitations. This underlines the urgent need of developing alternative approaches to treat lung disorders. Among the emergent strategies, gene therapy holds great potential for the treatment of monogenic lung diseases. However, so far, aerosolized viral vector-based delivery for gene therapy has failed likely because of difficulties in accessing the target cells. Combined gene and cell therapy approaches could be a promising alternative. Trials using basal cell transplantation already showed encouraging results. Moreover, the induced pluripotent stem cell (iPSC) technology broadens the scope of personalized therapies by paving the way for autologous approaches. Our group previously derived iPSC lines from patients with Primary Ciliary Dyskinesia (PCD) and found that their correction by gene conversion allows functional recovery. This study aimed to identify the best progenitors and airway conditioning technique to develop an autologous cell replacement strategy for PCD. MethodsAirway epithelial cells were differentiated from induced pluripotent stem cell (iPSC) lines from a healthy donor (parental Hy03) and Hy03 in which MCIDAS was knocked out (PCD model) and maintained in air-liquid interface (iALI). The engraftment of GFP+ ventral Anterior Foregut Endoderm (vAFE) cells, differentiated from GFP-expressing Hy03 iPSCs, was assessed after conditioning of the recipient iALI. The efficacy (epithelial cell shedding) and toxicity (cell death) of different conditioning strategies were compared. Cilia functional repair was assessed using microbead motion tracking. ResultsGFP+ vAFE cells can successfully integrate and repair trypsin- or EDTA-conditioned airway epithelia derived from the parental and MCIDAS-/- Hy03 iPSC lines. EDTA showed optimal efficacy/safety balance. Progenitor integration and differentiation were confirmed by E-cadherin, tubulin-IV, KRT5 and MUC5AC co-expression in GFP+ engrafted cells at day 35 post-graft (immunofluorescence analysis). The engrafted GFP+ population reached 35-45% of the total epithelial population, as indicated by flow cytometry quantification of EpCAM+/GFP+ cells. Functional analysis demonstrated cilia motion restoration after GFP+ cell engraftment onto MCIDAS-/- iALI. ConclusionsOur study shows that vAFE cells can integrate and differentiate to repair epithelial models of PCD. EDTA conditioning is promising for the clinical application of this therapeutic strategy.

Rapid prediction of the severity of acute coronary syndrome (ACS) is crucial for appropriate intervention in emergency department. Neutrophils (Neu), lymphocytes (Lym) and monocytes (Mon) and their ratios (Neu/Lym, NLR; Mon/Lym, MLR NeuxMon/Lym, SIRI) are acknowledged to be associated with the prediction of the severity and adverse outcome of ACS patients. Here, we analysed retrospectively eosinophils (Eos) and Eos-derived novel ratios (Neu/Eos, NER; Mon/Eos, MER; Neu x Mon/Eos, SIII; Neu/Eos x Lym, NEL; Mon/Eos x Lym, MEL; Neu x Mon/Eos x Lym, SV) of first admitted 1053 ACS patients within 24 hours of symptom onset to predict ST-segment elevation of myocardial infarction (STEMI), high Gensini score (H) and cardiac dysfunction (Killip Classification l to III grades). Results showed that Eos was significantly decreased in ST (n=227), Gensini (H) (n=311) and Killip I group (n=237) (P<0.05). All Eos-derived ratios (NER, MER, SIII, NEL, MEL, SV) were significantly higher with diagnostic severity (ST, Gensini (H), and Killip I group (P<0.05). ROC analysis revealed that SIII and SV predicted ST and Gensini (H) with high specificity and sensitivity, which were similar to that of NLR, MLR and SIRI. Conclusion: Eos and Eos-derived ratios, SIII and SV in particular, are strongly linked to the prediction of the severity of ACS, along with those of well-established leukocyte ratios. The new ratios of Eos hold significant importance in emergency department for quick evaluation of ACS patients.

Purpose: To identify the ocular biometric parameters associated with refractive outcomes in Chinese Primary angle closure glaucoma (PACG) patients receiving phacoemulsification and intraocular lens (IOL) implantation (PEI) surgery. Methods: 165 Chinese PACG patients receiving PEI and goniosynechialysis (GSL) and 53 cataract patients as controls only receiving PEI surgery were recruited. The prediction accuracy of IOL power calculation was assessed by the prediction error (PE), mean absolute error (MAE), median absolute error (MedAE), and proportions of eyes with a PE within {+/-} 0.25 diopters (D), {+/-} 0.50 D, {+/-} 0.75 D, and {+/-} 1.00 D. The association of different ocular biometric parameters with the PE of IOL calculation were evaluated. Results: The PACG patients had significantly higher absolute of PE as compared to the control subjects, especially the acute PACG patients. The axial length (AL), changes in aqueous depth pre- and post-surgery ({bigtriangleup}AD), and the ratio of {bigtriangleup}AD/AL were significantly associated with the PE in acute PACG patients. The association of {bigtriangleup}AD with the PE of IOL power calculation was found in PACG patients with AL [&ge;] 22 mm. Conclusions: This study revealed the association of AL and {bigtriangleup}AD with the PE of IOL calculation in Chinese PACG patients. Precisely predict the {bigtriangleup}AD is necessary for acute PACG patients, especially for those with AL [&ge;] 22 mm, to improve the refractive outcomes.

Bubble continuous positive airway pressure (bCPAP) is a low-cost respiratory support device that has demonstrated different outcomes for children with severe pneumonia in different settings. Some differences in outcomes may be attributable to implementation factors (e.g., patient monitoring and feeding practices). We aimed to characterize bCPAP reach, implementation fidelity, and safety outcomes for children with severe pneumonia in Pakistan. We conducted a prospective cohort study at Aga Khan University Hospital and Abbasi Shaheed Hospital from February through May 2025. We enrolled children 1-59 months who met WHO criteria for severe pneumonia within 24 hours of presentation to the emergency department. Participants were followed daily via chart review, caregiver survey, and physical exam through discharge, transfer, or death. We reported the proportion of children receiving bCPAP ("reach") and constructed a mixed-effects, multinomial logistic regression model with robust standard errors to report: fidelity (child location in a highly monitored area, continuous monitoring, avoidance of unplanned disruptions to bCPAP, and avoidance of oral feeding); safety (aspiration events and pneumothorax); bCPAP failure (death, respiratory support escalation, or leaving against medical advice); and in-hospital mortality. Of 165 children with severe pneumonia, 88 (53%) received bCPAP over 141 bCPAP days. The average predicted probabilities (95% CI) of our fidelity measures were: 85% (78-92%) for location in a highly monitored area; 56% (51-60%) for continuous monitoring; 66% (57-75%) for continuous bCPAP without disruptions; 46% (36-55%) for avoidance of oral feeding while on bCPAP. Among children receiving bCPAP, 9 (10%) experienced an aspiration event, 1 (2.2%) experienced a pneumothorax; 19 (22%) experienced bCPAP treatment failure. One child (1.1%) died; 6 (6.8%) required respiratory support escalation; 14 (16%) left against medical advice. We identified several gaps in bCPAP reach and fidelity. These may be modifiable by individual-and team-targeted strategies to reduce bCPAP-related complications and pneumonia-related child deaths.

Background: To investigate the safety and efficacy of CTguided lung nodule localization needles for the preoperative localization of small pulmonary nodules. Methods: A retrospective study was conducted on 102 patients with a total of 113 small pulmonary nodules who underwent preoperative localization at Jinan Fourth People's Hospital from January 2024 to December 2025. Nodule diameter and depth, localization time, the number of pleural punctures, the localization success rate, and postoperative complications (hook dislodgement, hemorrhage, and pneumothorax) were recorded. All patients underwent video assisted thoracoscopic surgery (VATS) after localization. Results: The mean nodule diameter was 0.97{+/-}0.36 cm, the mean depth was 1.26{+/-}0.48 cm, and the mean localization time was 9.8{+/-}3.65 minutes. The hook dislodgement rate was 0.98% (1/102), the intrapulmonary hemorrhage rate was 14.71% (15/102), and the pneumothorax rate was 16.67% (17/102). All pulmonary nodules were successfully resected by VATS at 73.82{+/-}13.83 minutes after localization, and no severe complications occurred. Conclusions: The use of a CTguided lung nodule localization needle for the preoperative localization of small pulmonary nodules decreases the time needed for intraoperative nodule detection and operation time. This strategy is a simple, safe, and accurate preoperative localization method that is worthy of increased clinical use.

BackgroundA critical radiologist shortage exists in India, leading to delayed chest radiograph (CXR) interpretation. This leads to disease progression, higher morbidity, and mortality. Artificial intelligence-based CXR interpretation by Lenek Intelligent Radiology Assistant (LIRA) is a promising solution. This study aims to establish the screening and triaging capabilities of LIRA by assessing its accuracy in detecting abnormalities and pathologies in CXRs from geographically diverse institutions. MethodsWe conducted a retrospective multi-source validation of the diagnostic accuracy of LIRA for the detection of general abnormalities, tuberculosis, consolidation, pleural effusion, pneumothorax, and cardiomegaly. De-identified chest radiographs were input into LIRA models. The obtained interpretations were compared to the established ground truth reporting for the calculation of sensitivity, specificity, and AUROC with 95% CI for individual pathologies across varying probability thresholds. ResultsLIRA demonstrated high sensitivity for general abnormality detection (AUROC 0.93-0.986, 84.4-97.1% sensitivity, 88.9-92.4% specificity) and tuberculosis triaging (Shenzhen & Montgomery: 88.5-89.7% sensitivity, 89.9-90.5% specificity; Jaypee: 98.7% sensitivity, 63.6% specificity). For consolidation (AUROC 0.884-0.895, 96.4-96.9% sensitivity, 70.8-77.1% specificity), pleural effusion (AUROC 0.942-0.967, 79.7-99.1% sensitivity, 81.2-87.7% specificity), pneumothorax (AUROC 0.87, 90.6-94.8% sensitivity, 79.5-82.7% specificity) and cardiomegaly (AUROC 0.883, 95.1% sensitivity, 81.6% specificity), the model exhibited commendable accuracy as well. ConclusionsThe diagnostic performance of LIRA was consistent across various pathologies and chest radiographs from diverse geographic locations, with particular strengths in abnormality detection and tuberculosis screening. The risk-stratified triaging and high sensitivity of LIRA make it a reliable adjunct solution to address radiologist shortages, reduce turnaround times, and support Indias tuberculosis elimination goals.

This study investigates the therapeutic potential of secretomes derived from Adipose-derived Mesenchymal Stem Cells (ADMSC-CM) and Limbal-derived Mesenchymal Stem Cells (LMSC-CM) against oxidative stress-induced damage in Retinal Pigment Epithelium (RPE-1) cells. RPE dysfunction, often triggered by oxidative stress, is a hallmark of various retinal degenerations. Here, we induced RPE-1 injury using H2O2 and evaluated the restorative effects of both MSC-conditioned media (CM). Our results demonstrated that both ADMSC-CM and LMSC-CM significantly enhanced cell viability and successfully reversed H2O2-induced G2/M phase cell cycle arrest. While oxidative stress triggered a pro-inflammatory response characterized by elevated IL-1{beta}, IL-6, and IL-10 expression, MSC-CM treatment, particularly ADMSC-CM, effectively modulated these levels and suppressed the p38 MAPK signaling pathway. Furthermore, MSC-CM reduced the Bax/Bcl-2 ratio, indicating an anti-apoptotic effect, and appeared to stabilize autophagic flux. To investigate the impact of oxidative-stress induced alterations in retinal pigment epithelial cells on angiogenesis, the effects of RPE-derived secreted factors on endothelial cell function were evaluated. Crucially, in terms of safety and secondary complications, neither secretome exhibited pro-angiogenic tendencies; instead, they significantly inhibited HUVEC migration and invasion compared to the H2O2 damaged group. These findings suggest that both ADMSC and LMSC secretomes provide a potent multi-targeted therapeutic effect, making them promising candidates for cell-free therapies in retinal diseases.

BackgroundVertebral artery calcification (VAC), a critical indicator of cerebrovascular disease, is often overlooked in head-and-neck imaging. Manual detection is time-consuming and prone to inter-observer variability. This study aimed to develop and validate a deep learning model for automated detection and quantitative risk assessment of VAC in non-contrast head-and-neck computed tomography (CT) images, bridging the diagnostic gap between dentistry and vascular medicine. MethodsWe developed a deep learning model based on the ResNet-18 architecture, designated as Grayscale ResNet, optimized for single-channel CT images. The development followed a two-phase strategy: initial training on 539 axial images from head-and-neck CT image followed by iterative refinement (fine-tuning) using a targeted dataset of clinically significant cases to ensure generalizability. The models performance was evaluated using patient-level Receiver Operating Characteristic (ROC) analysis and saliency map visualization for clinical interpretability. ResultsThe optimized model demonstrated a robust performance in distinguishing between cases with and without VAC. In the independent cohort, the model achieved an area under the curve (AUC) of 0.846. At a specific threshold value (98.6%), the system yielded a sensitivity of 80.0% and a specificity of 90.6%. A saliency map analysis confirmed that the model consistently focused on anatomically relevant vascular regions. ConclusionsThe proposed automated system provides an accurate and reliable method for VAC screening using routine head-and-neck CT scans. By transforming incidental imaging findings into a quantifiable risk index, this tool can serve as a vital decision-support system for dentists and radiologists, facilitating early patient referrals and contributing to global stroke prevention.

BackgroundOsteoarthritis (OA) is a chronic degenerative joint disease characterized by the progressive deterioration of articular cartilage, significantly impacting the quality of life in middle-aged and elderly populations. The Ras and Hippo signaling pathways play critical roles in regulating cell proliferation, differentiation, and stress responses; however, their interactive mechanisms in OA remain unclear. This study aimed to identify key genes associated with these two pathways using bioinformatic approaches and to elucidate their potential mechanisms in OA. MethodsTranscriptomic data of OA along with Ras signaling pathway-related genes (RSPRGs) and Hippo signaling pathway-related genes (HSPRGs) were obtained from public databases. Differentially expressed genes (DEGs) were identified, and key genes were screened through machine learning, expression validation, and receiver operating characteristic (ROC) curve analysis. Functional insights were further explored via gene set enrichment analysis (GSEA), subcellular localization, immune infiltration analysis, regulatory network construction, and drug prediction. Finally, the expression of key genes was validated in clinical samples. ResultsKIT and CSF1R were identified as key genes. GSEA indicated their involvement in pathways such as the lysosome pathway. Subcellular localization predicted that KIT and CSF1R are distributed in the nucleus, extracellular region, and plasma membrane. Immune infiltration analysis revealed that KIT showed a positive correlation with eosinophils and a negative correlation with immature dendritic cells, while CSF1R was positively correlated with macrophages and negatively correlated with CD56 natural killer cells. Drug prediction suggested interactions between the key genes and several therapeutic agents, including avapritinib and IMC-CS4. Subsequently, we validated our findings in cartilage tissue samples and discovered that compared to the control group, both CSF1R mRNA and protein expression was significantly upregulated in OA tissue, while KIT expression was significantly downregulated.The same results were also validated in immunofluorescence staining of chondrocytes. ConclusionThis study identified KIT and CSF1R as key genes in OA, providing new theoretical insights and potential targets for mechanistic research and targeted therapy.

Background and aimTrauma healing with low-intensity ultrasound is effective for different types of injuries affecting both soft tissues and bones. The work aimed to disclose the healing potential of a new type of ultrasound, ultra-wideband low-intensity mechanical waves (UMUS), and to compare its effects with those of low-intensity pulsed ultrasound (LIPUS) in a model of trauma. Material and methodsThe work was performed on 2-to 3-month-old male Wistar rats. The model of tail amputation was created, and a transducer emitting UMUS (1-7 MHz, 0.22 mW/cm2) was applied daily for 10 days to the surface of the trauma site in animals that were timely immobilized. LIPUS (1.5 mHz, 30.0 mW/cm2) was used in a separate group of animals. Sham-stimulated rats were used as a control. The intensity of collagen expression in the subdermal tissue was assessed in van Gieson-stained sections, whereas in the UMUS group, expression of CD31, CD34, VEGF, and Ki67 was analyzed. ResultsStarting on the 20th day after trauma, UMUS-treated animals demonstrated a statistically significant decrease in the surface area of the traumatic zone compared to the control, whereas LIPUS-treated rats showed this difference on the 30th day of observation. Starting from the 30th day, a significantly greater reduction in the surface of trauma was observed in UMUS, with complete closure achieved in 6 out of 9 rats (P=0.019 vs control), whereas in LIPUS-treated animals, a similar result was observed in 2 out of 8 rats (P>0.05). In UMUS-treated rats, heightened expression of collagen in animals with LIPUS exceeded control data by 7.84% (P=0.034), while the expression in rats with UMUS exceeded data in LIPUS-treated rats by 14.71% (P=0.013). Increased expression of CD31, CD34, VEGF, and Ki67 was observed in UMUS-treated rats. ConclusionsUMUS treatment accelerated healing and reduced wound size, and increased the expression of collagen, CD31, VEGF, CD34, and Ki67, supporting angiogenesis and collagen formation. Effects are more pronounced compared to LIPUS treatment. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=176 HEIGHT=200 SRC="FIGDIR/small/717366v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@1b82f66org.highwire.dtl.DTLVardef@12ffd81org.highwire.dtl.DTLVardef@1ac385aorg.highwire.dtl.DTLVardef@1a7da17_HPS_FORMAT_FIGEXP M_FIG C_FIG

ObjectiveTo compare the efficacy and safety of etomidate versus ketamine as induction agents for rapid sequence intubation in critically ill adults, focusing on 28-day mortality and post-intubation hypotension. Data SourcesPubMed, Embase, and the Cochrane Library were systematically searched from inception to January 2026. Reference lists of included studies were also manually screened. Study SelectionWe included randomized controlled trials (RCTs) comparing single-dose intravenous ketamine versus etomidate for emergency rapid sequence intubation in critically ill adults ([&ge;] 18 years) in non-operating room settings (e.g., intensive care unit or emergency department). Data ExtractionTwo investigators independently screened records, extracted data using a standardized form and assessed the risk of bias using the RoB 2 tool. The certainty of evidence was evaluated using the GRADE framework. Data SynthesisSix RCTs comprising 4,108 patients (2,046 assigned to ketamine and 2,062 to etomidate) were included. The pooled analysis showed no statistically significant difference in 28-day mortality between the ketamine and etomidate groups (39.0% vs. 40.3%; relative risk [RR] 0.96; 95% CI, 0.89-1.03; p=0.29; I{superscript 2}=11%). In a prespecified subgroup analysis of patients with sepsis (n=1,546), mortality also did not differ significantly (RR 0.94; 95% CI, 0.86-1.03). However, ketamine was associated with a statistically significant increase in the incidence of post-intubation hypotension (14.2% vs. 11.3%; RR 1.25; 95% CI, 1.01-1.53; p=0.04; I{superscript 2}=0%). No significant differences were observed regarding peri-intubation cardiac arrest, first-attempt intubation success, or ventilator- and intensive care unit-free days. ConclusionsThere is no statistical difference in 28-day mortality between etomidate and ketamine for emergency intubation in critically ill adults, including those with sepsis. The higher incidence of post-intubation hypotension with ketamine suggests etomidate presents a more favorable hemodynamic safety profile in this setting. Key pointsO_ST_ABSQuestionC_ST_ABSDoes the choice between etomidate and ketamine for emergency intubation in critically ill patients impact 28-day mortality? FindingsIn this systematic review and meta-analysis of randomized controlled trials, there was no statistically significant difference in 28-day mortality between patients induced with ketamine (39.0%) and those induced with etomidate (40.3%). MeaningThe use of etomidate versus ketamine for rapid sequence intubation does not alter 28-day mortality, indicating that the choice of induction agent should be individualized.

BackgroundBronchiectasis is a debilitating respiratory condition characterized by chronic cough with expectoration of thick sputum. It accounts for significant morbidity and mortality, especially when associated with exacerbations. Assessing the health-related quality of life (HR-QoL) of patients with bronchiectasis is important to ascertain the impact of the disease on day-to-day life, as well as to gauge the effect of targeted interventions. Conventionally used methods for assessing HR-QoL such as the St. Georges Respiratory Questionnaire (SGRQ) are time-consuming and have limitations in day-to-day application. The Bronchiectasis Health Questionnaire (BHQ) is a novel, compact tool used for assessing the HR-QoL, and has been validated for use in Korean and Turkish populations. MethodsWe attempted to develop and validate the Hindi version of the Bronchiectasis Health Questionnaire (BHQ) in Indian adults with bronchiectasis. We assessed the correlation between the Hindi BHQ (H-BHQ) scores and other measures of lung health including the Hindi version of the COPD Assessment Tool (H-CAT), pulmonary function tests and the bronchiectasis severity index (BSI). In addition, we assessed the correlation between the H-BHQ scores and the number of exacerbations and hospital admissions in the previous year. ResultsA total of 145 subjects with bronchiectasis were included. The mean ({+/-} SD) H-BHQ total score was 49.10 {+/-} 10.3. The H-BHQ score correlated well with the H-CAT score (Correlation coefficient -0.6534, p value < 0.0001) and the mMRC scale (Correlation coefficient of -0.4459,p value < 0.0001). The H-BHQ score also had a moderate correlation with the number of exacerbations and low correlation with hospital admissions in the previous year, with correlation coefficients of -0.4193 (p < 0.0001) and -0.3030 (p < 0.0001), respectively. The correlation between the H-BHQ and the Bronchiectasis Severity Index (BSI) score was weak (Correlation coefficient of -0.3012, p value < 0.01). ConclusionThe H-BHQ offers a simple and convenient method to assess the HR-QoL in patients with bronchiectasis, and correlates well with other measures of respiratory health, including the H-CAT, the mMRC score and the number of exacerbations and hospital admissions in the previous year.

Mesenchymal stem cells (MSCs) cultured in hypoxic conditions have been suggested to have more therapeutic efficacy than those cultured under normoxic conditions, and there is growing interest in using hypoxic MSCs for clinical treatment, particularly human umbilical cord (hUC)-MSCs. We investigated how hUC-MSCs and human bone marrow (hBM)-MSCs change from normoxia to hypoxia (1% O2) for 2 weeks of culture. In the growth speed and population doubling time, hUC-MSCs cultured under hypoxia exhibited a significantly higher proliferation rate beyond cancerous cells, such as human glioblastoma and breast cancer cells, while hBM-MSCs did not show a significant difference between normoxia and hypoxia, and were statistically slower than these cancerous cells. Notably, hypoxic hUC-MSCs showed upregulation of genes related to metabolic reprogramming (cholesterol biosynthesis and fatty acid metabolism pathways) and cancer stem cell-like phenotype (factors related to Wnt and Hedgehog signaling pathways, cell proliferation drivers, and apoptosis-resistance), and lesser migration and homing to the traumatic brain injury than normoxic hUC-MSCs after intravenous injection. Thus, whether hUC-MSCs cultured under hypoxia offer clinical benefits and use are safe, given their extremely accelerated proliferation rate and partial cancer stem cell-like traits, requires comprehensive and careful investigation.

PurposeTo develop SCOPE (Small-lesion COntextual Pancreatic Evaluator), a deep learning model designed to improve CT detection of small pancreatic lesions--pancreatic ductal adenocarcinoma (PDAC), pancreatic neuroendocrine tumors (PanNETs), and cystic lesions--by integrating voxel-level features with global context. Materials and MethodsThis retrospective study used three independent datasets. A development cohort of 4,065 contrast-enhanced CT scans was used to train a deep neural network that performs pancreas, ductal, and lesion segmentation with an integrated classification head. A metamodel combined segmentation-derived and global contextual signals for case-level prediction. Performance was assessed on (1) an internal holdout test set (n = 605), (2) an external multi-institutional PDAC dataset from the PANORAMA challenge (n = 2,238), and (3) an expert-curated small-lesion reader study (n = 200). Areas under the receiver operating characteristic curve (AUCs) were compared using DeLong test; sensitivities and specificities using McNemars test. ResultsOn the internal test set, SCOPE improved lesion-versus-normal AUC compared with the best segmentation baseline (0.974 [95% CI: 0.964, 0.984] vs 0.956; P = .006) and increased small-lesion sensitivity at 95% specificity (0.727 [95% CI: 0.653, 0.801] vs 0.600; P = .012). Performance gains were observed across lesion classes, with significant improvements for PDAC and PanNET detection. On the external dataset, SCOPE improved PDAC-versus-non-PDAC AUC (0.978 vs 0.861, P < .001) and achieved higher sensitivity at 90% and 95% specificity without retraining. For the small-lesion reader study, SCOPE achieved lesion-versus-normal AUC of 0.922 and performed within the range of subspecialty abdominal radiologists; SCOPE provided the correct diagnosis in 14.5% (29/200) of cases in which two or more readers were incorrect. ConclusionSCOPE improves early detection of small, potentially curable, pancreatic lesions on CT by combining local segmentation and global pancreatic context. Its consistent performance across internal, external, and reader datasets supports potential use as a concurrent reader for earlier and more accurate pancreatic lesion detection.

Background and ObjectivesDecision-making about resuscitating a critically ill child is complex yet common. We aimed to study the survival thresholds at which physicians, compared to parents, decide to treat or withhold resuscitating a child. Moreover, we aimed to compare physicians survival estimates with those from a nationwide registry. MethodsWe conducted a cross-sectional survey-based study in the United States. Clinical vignettes based on hypothetical survival probabilities were used to study and compare the decision thresholds for parents and physicians. Vignettes developed using the Get-With-The-Guidelines-Resuscitation registry were used to explore physicians decision thresholds and compare their survival estimates with those from the data. Thresholds were determined using mixed-effect logistic regression models. ResultsWe had decisions for 501 and 257 vignettes from 167 parents and 43 physicians, respectively. The decision threshold for survival to discharge was 5.3% (95% CI: 3.7 to 7.0) for physicians and 1.2% (95% CI: -0.8 to 3.0) for parents. Whereas the decision threshold for survival to discharge with PCPC 1 or 2 was 3.5% (95% CI: 1.1 to 7.1) for physicians and 0.6% (95% CI: -1.2 to 1.8) for parents. About 58% of the physicians overestimated the likelihood of survival. ConclusionsThe study found that the decision threshold for the physicians was higher than that for the parents (5.3% vs. 1.2%). This illustrates that parents still want to attempt resuscitation at a survival probability where physicians would recommend withholding resuscitation. These findings have implications for clinical practice and counseling the parents of critically ill hospitalized children.