Frontiers in Medicine
○ Frontiers Media SA
Preprints posted in the last 90 days, ranked by how well they match Frontiers in Medicine's content profile, based on 120 papers previously published here. The average preprint has a 0.13% match score for this journal, so anything above that is already an above-average fit.
Tian, L.; Yang, S.; Zhou, Q.; Song, Y.; Kan, Y.; Zhao, M.; Jiang, Y.
Show abstract
Abstract: Objective To explore how a novel set of occluding glasses compare with handheld spoon shaped occluders in young children in terms of visual acuity test results, and how children felt about the two tools . Setting Outpatient clinic of the ophthalmology department in a university teaching hospital in Wuhan, China. Participants 210 children aged 3-9 yeas visiting the clinic for VAT from June 1 through July 30,2024 were conveniently selected as participants, among whom, 10 were excluded as their parents did not sign the informed consent paper. Study design This diagnostic agreement study compared two types of eye occluders using a cross-over design. The 200 children were divided into two equal batches: the first batch (case no.1-100) received VAT using handheld spoon-shaped eye occluders followed by occluding glasses, while the second batch (case no.101-200) received the interventions in the reverse order. Outcome measures Paired VAT scores generated from the study were compared with the Bland-Altman analysis. All children were asked of their acceptance regarding the two eye-covering tools upon completion of the 2nd VAT. Results The VAT score measured with occluding glasses were closely comparable with those measured with the handheld spoon-shaped eye occluders, with interclass correlation coefficient ( ICC ) of 0.989 and 0.989 for left eyes and right eyes, respectively(P<0.001). The mean difference of VAT score measured by the 2 tools was 0.007 for right eyes versus 0.005 for left eyes, and the 95% limits of agreement (LoA) ranged from -0.07 to 0.08 for right eyes versus 0.07 to 0.08 for left eyes ,with 0.5 % versus 1 % of the measurements outside the 95% LoA. 61%(122/200) of the children preferred the appearance of the occluding glasses and considered it "more attractive than the handheld one". However, respectively 90.0% and 93.0% of the children favored the hand-held occluder in terms of convenience and comfort. Conclusions The VAT measurements obtained with the two types of eye occluders showed excellent agreement, justifying the use of the occluding glasses as a promising tool for VAT in young children. Yet, refinement of the novel product is needed to enhance convenience and comfort. Key words myopia, visual acuity test, eye occluders, young children
Wang, Y.; Guo, Y.
Show abstract
Background: In 2026, the US Food and Drug Administration (FDA) identified uveitis as a potential signal of serious risk for the B-cell maturation antigen (BCMA) x CD3 bispecific antibodies teclistamab and elranatamab. Uveitis in this setting may reflect opportunistic infection or immune-mediated inflammation, which require opposite management. Methods: We analyzed FDA Adverse Event Reporting System (FAERS) reports from July 2020 to June 2026 (8,690,601 reports after deduplication) using a case-non-case design, calculating reporting odds ratios (RORs) and the information component for primary-suspect reports. Comparators were belantamab mafodotin, talquetamab and CD3 bispecific antibodies used outside myeloma. Every primary-suspect uveitis report (n = 76) was classified as infectious, probable immune-mediated (hereafter immune-mediated) or indeterminate by a physician blinded to a rule-based algorithm. Results: Uveitis was reported in 18 of 2,995 teclistamab and 29 of 1,691 elranatamab reports (ROR 4.10 [95% CI 2.58-6.52] and 11.85 [8.21-17.12]). Of these 47 cases, 20 were infectious (18 cytomegalovirus chorioretinitis; median onset 92 days), and infection-specified uveitis was disproportionately reported for both agents and for CD3 bispecific antibodies used outside myeloma. Thirteen were immune-mediated, arose early (median onset 4 days) and were co-reported with cytokine release syndrome in six; immune-mediated uveitis showed a signal only for elranatamab (8 cases; ROR 3.59, 1.79-7.18), not for teclistamab or any comparator. Six of the eight elranatamab cases originated from Japan. Agreement between physician and algorithm was 98.7%. Conclusions: The FDA uveitis signal appears to comprise a late infectious uveitis shared by most T-cell-redirecting bispecific antibodies examined and an early immune-mediated uveitis that showed a signal only with elranatamab. These hypothesis-generating findings support prompt ophthalmological assessment of new visual symptoms and exclusion of cytomegalovirus retinitis before corticosteroids are started.
Oyarzun, R.; Hernandez, P.
Show abstract
Background. Whether predictors of intraoperative hypotension (IOH) add information beyond the mean arterial pressure (MAP) already displayed on the monitor is contested: selection bias in common evaluation designs inflates apparent performance, and the field has called for comparisons against simple MAP-based references under bias-resistant protocols. Existing predictors also depend on proprietary waveform analysis or pulse-contour monitors, restricting both deployment and external validation. Methods. Using 807 non-cardiac surgery patients from the open VitalDB database, we derived an additive gradient boosting model (one split per tree: a learned shape function per variable, no interactions) from three variables computable from an arterial line alone: current MAP, its drift from the patient's own 20-minute baseline, and the growth of its rolling variance (critical slowing down). Evaluation used patient-level 5-fold cross-validation under a strict protocol - exclusion of the 65-75 mmHg grey zone and of all samples already hypotensive at prediction time - with MAP alone (same learner class) as comparator. The frozen model was then validated, without any refitting, on an independent cohort from another continent (MOVER, University of California Irvine) following a pre-registered plan sealed before external data access. Results. In development the pressure-only model reached AUROC 0.907 vs. 0.884 for MAP alone (Delta AUROC +0.023, 95% CI +0.017 to +0.029) at 5 min, with +0.031 and +0.032 at 10 and 15 min, and good calibration (Brier skill +0.418 vs. prevalence). In external validation on 3,069 patients (442,194 samples, 1-minute charting, event prevalence 5.8%), the advantage not only transferred but was larger than in development: AUROC 0.696 vs. 0.638, Delta AUROC +0.058 (95% CI +0.051 to +0.064), meeting both pre-registered gates. Discrimination transferred; calibration did not (external Brier skill -0.014), requiring local recalibration. In the unrestricted scenario, where samples already at threshold are retained, the advantage collapsed (+0.007), reproducing the selection effect this paper documents. A secondary model adding pulse-contour cardiac output and stroke volume variation improved development discrimination further (Delta AUROC +0.035) but could be externally validated in only 39 patients, because those signals are rarely recorded. Conclusions. The dynamics of arterial pressure itself - drift from a patient-specific baseline and variance growth - carry predictive information beyond its current value, in a fully interpretable additive model that requires only an arterial line, no waveform access and no proprietary hardware. The advantage is confirmed in a pre-registered frozen-model external validation of over three thousand patients, and is largest at coarse recording cadence, where instantaneous pressure is least informative.
Motchoffo Simo, G.; Rizzo, A.; Muy, K.; Quintanilla, N.; Scotland, K.
Show abstract
Objective: To determine whether the most cited and the most publicly discussed benign prostatic hyperplasia (BPH) literature describe the same body of work, and whether clinicians and patients read different evidence. Methods: Four Boolean Web of Science searches and four matched Altmetric Explorer searches were run in February 2024, restricted to literature indexed with urologic terminology, and screened in duplicate. Two arms were assembled: the 50 most-cited articles (citation census May 2024) and the 50 with the highest Altmetric Attention Scores. Funding source and intervention focus were hand-coded from the full text of all 100 articles; open-access status came from Unpaywall. Arms were compared with Mann-Whitney U and Fisher exact tests Results: Eight of 50 articles (16%) appeared in both arms. Citation selected articles were older (median 2008 versus 2018, p<0.001), more often randomized trials (58% versus 22%, p<0.001), and more often published in urology-specific journals (96% versus 66%, p<0.001). Industry funded 50% versus 18% of articles (p=0.001) and non-industry sources 8% versus 36% (p=0.001). Only 10% of citation-selected articles were open access versus 56% (p<0.001). Attention data were recoverable for only 13 citation-selected articles (median score 9 versus 17). The two arms were cited in the 2026 AUA BPH Guideline at indistinguishable rates (22% versus 20%, p=1.00). Conclusions: These are largely distinct bodies of work, separated most decisively by whether they can be read without a subscription, yet both inform guideline development equally. Patients arrive with evidence systematically different from, and no less guideline-relevant than, that underpinning their urologist's training.
Koller, C. N.; Maglione, J.; Blanchard, M.; Dumusc, A.; Dan, D.; Brulhart, L.; Nissen, M.; Andor, M.; Micheroli, R.; Scherer, A.; Polysopoulos, C.; Rubbert-Roth, A.; Iking-Konert, C.; Manigold, T.; Moeller, B.; Manolarki, C.; Geurts, J.; Huegle, T.
Show abstract
Background: Smartphone enabled remote patient monitoring has the potential to complement conventional follow-up in inflammatory arthritis. We previously presented the finger fold index (FFI) derived from hand photographs as ratio of automated detected proximal interphalangeal (PIP) joint diameter and surface of dorsal finger folds as a digital biomarker for clinical joint swelling and disease activity in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Objective: To evaluate the feasibility, image quality, patient engagement, and clinical utility of both HCP- and patient-collected hand photographs integrated into a national rheumatology registry, and to assess the performance of the FFI as an image-derived digital biomarker for clinical joint swelling of the proximal interphalangeal joints in a real-world arthritis cohort. Methods: In this longitudinal multicenter study, a photo function with written instructions were integrated into the Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) registry and their mySCQM mobile application, respectively. Patients with RA or PsA contributed longitudinal smartphone photographs together with patient-reported outcomes (PROs) via the mySCQM mobile application while health care professionals (HCPs) acquired images during routine visits. After manual quality assessment, images were processed using an automated computer vision pipeline to derive the FFI, a digital biomarker based on dorsal finger-fold morphology. Image quality was evaluated for both HCP- and participant-collected photographs, and patient engagement was assessed. Associations between FFI, clinical proximal interphalangeal (PIP) joint swelling, RADAI-5, DAS28-CRP and longitudinal changes were assessed. A generalized linear mixed model was used to estimate the association between FFI and joint swelling while accounting for repeated measures and within-subject correlations. Results: Between 2023 and 2025, 374 RA and PsA patients were included. HCPs captured 977 hand images while 174 patients collected 1228 hand images via the mySCQM app. Patients demonstrated sustained engagement after instruction, contributing a mean of seven images during data collection. Following quality control, 1729 hand images comprising 4048 PIP joints were included for analysis. Image quality was comparable between patient-acquired and HCP-acquired photographs; 78.3% of the patient-acquired vs. 73.5% of the HCP-acquired hand images were suitable to run the ML-model. 23.1% of the cropped joints had to be removed after the running of the FFI algorithm due to false diameter or finger fold detection e.g. due to wrong hand positioning. In images taken by HCPs, mean FFI and DAS28-CRP were weakly but significantly correlated (Spearmans {rho} = 0.164; 95% CI [0.004 to 0.317]; p = 0.039). Conversely, RADAI-5 scores did not correlate with the mean FFI in RA patients (r = 0.007, p = 0.932, 95% CI [-0.169-0.183]). At follow-up visits, clinical swelling resolved in 40 joints, of which in 68.0% the direction of the delta FFI was concordant with the clinical change. In contrast, 13 joints developed incident clinical swelling, of which 87.5% had a direction of the delta FFI that was concordant with the clinical change. However, the GLMM showed no significant associations between swelling and joint location or time-varying FFI, and no evidence of interaction between FFI and PIP joint. Conclusion: Integration of patient self-imaging into a remote monitoring application for inflammatory arthritis is feasible and achieves image quality comparable to clinician acquired photographs. The FFI derived from collected images shows association with clinical joint swelling and disease activity scores, but not PROs. In a substantial proportion of images, the FFI algorithm could not be applied because of insufficient image quality. More standardized image acquisition and further refinement of the FFI algorithm are warranted.
Umbarkar, S.; Patne, H.; Patil, M.; Dixit, P.
Show abstract
Background and aims- Patients for interventional pulmonary procedures (IPP) are inherently high risk due to various comorbidities as well as the procedure being variable in duration and adverse events. Incomplete muscle reversal can delay rapid recovery and lead to adverse events in the postoperative period. Sugammadex as a reversal agent, may offer distinct advantages when residual neuromuscular blockade is poorly tolerated. Limited data is available on use of suggamadex in high risk IPP regaurding extubation times and adverse events. Studies on pulmonary complications and anaphylaxis in this subset of pulmonary patients is controvertial. Moreover in the Indian setup optimizing the turnaround time to justify the cost of suggamadex for IPP is yet to be determined. In this retrospective study we will compare the advantages of using Sugammadex over the conventional reversal agent Neostigmine for time to extubation and time to shifting the patient to PACU in patients undergoing IPP. The hemodynamic parameters and adverse events will also be noted. Materials and methods-After ethics approval from institute (EC/OA- 48/2025) we conducted a retrospective cohort study of 70 adults (18-60yrs) for a duration of 6 months in our institute who underwent IPP under general anaesthesia ( tracheal dilation, tracheal biopsy, EBUS TBNA,BAL etc) . They were categorized into two groups: Group A- suggamadex vs. Group B- neostigmine. TOF monitoring was recorded and time to extubation and shift to PACU was noted along with hemodynamics and adverse effects. The statistical software SPSS version 16 was used for the analysis. Results-A total of 70 patients were included. Patients in Group sugammadex showed less time to extubate (5.80+/-0.96 vs 13.26+/-1.88 ,P value 0.0001) and discharge from PACU (10.49+/-1.44 vs 28.57+/-3.34 min, P = 0.000003) than in Group neostigmine. The difference between heart rate , blood pressure and respiratory rate and adverse events were not statistically significant. Conclusion-Sugammadex shortens the time to extubate and discharge from PACU in patients undergoing IPP, accelerating recovery and turnaround time. No additional adverse events or hemodynamic instability were noted with suggamadex in this subset of patients. No coughing irritable airway.
Chang, T.-M.; Wu, C.-C.; Huang, H.-C.; Lu, J.-Y.; Chen, Y.-S.; Kao, P.-L.; Tang, W.-H.; Hsieh, W.-J.; Liu, L. T.-C.; Percec, I.; Chen, C.; Kuo, T.-Y.
Show abstract
Beyond their cosmetic significance, eyelashes are critical for retaining ocular moisture and protection against mechanical debris, environmental stressors, and excessive light. While recombinant growth factors support hair growth through activating key follicular signaling pathways, plant-derived EVs modulate local inflammatory and oxidative stress pathways to optimize the follicular microenvironment. Here we conducted a randomized, double-blind, placebo-controlled pilot study to investigate the synergistic effects of a serum containing recombinant Fc-fusion growth factors (rIGF-1, rFGF-7) and extracellular vesicles (EVs) derived from Zingiber officinale (ginger) and Curcuma longa (turmeric). Thirty healthy female participants were recruited and allocated to Group A (active serum) or Group B (placebo) at a ratio of 1:1. Participants applied the intervention twice daily for 8 weeks. The VISIA Skin Analysis System was used during clinical visits to objectively measure eyelash density and average length at baseline, Week 4, and Week 8. Group A exhibited a mean density increase of 3.3% at Week 4 and 4.4% at Week 8 relative to baseline. Eyelash length in Group A exhibited significant increases, reaching 8.1% at Week 4 and 11.0% by Week 8. In contrast, Group B showed slight reductions in length (-1.7% and -3.7% at Weeks 4 and 8, respectively) and a negligible change in density (+0.8% and -1.0% at Week 4 and 8, respectively). Notably, no periocular skin hyperpigmentation, a frequent adverse event associated with pharmacologic agents such as bimatoprost, was observed. These findings demonstrated the potential of combining long-acting recombinant growth factors with plant-derived EVs as an effective, highly tolerable, non-pharmaceutical cosmetic strategy for eyelash enhancement.
Mafumhe, T.; Charamba, V.; Mugauri, H. D.; Azu, O. O.
Show abstract
Healthcare workers are occupationally exposed to blood and body fluids and require effective protection against hepatitis B virus infection. Evidence on hepatitis B surface antibody (anti-HBs) seroprotection among healthcare workers in Namibia remains limited. We estimated the prevalence of anti-HBs seroprotection and examined associated factors among healthcare workers tested at Eastgate Clinic in Windhoek, Namibia. We conducted a cross-sectional analysis of routinely collected anti-HBs test records from 1 January to 31 December 2025. The first chronological test per individual was included. Anti-HBs concentrations [≥]10 mIU/mL were classified as seroprotective. Results outside the assay reporting range were treated as censored but remained classifiable for the binary outcome. Prevalence estimates were reported with Wilson 95% confidence intervals (CIs). Modified Poisson regression with robust standard errors was used to estimate adjusted prevalence ratios (aPRs). The register contained 304 test records representing 299 unique individuals. After excluding three individuals with missing anti-HBs results, 296 were analysed; 163 (55.1%) were female. Overall, 148 individuals were seroprotected, corresponding to a prevalence of 50.0% (95% CI 44.3-55.7%). Seroprotection was lowest among participants aged 18-29 years (35.3%) and highest among those aged 50-59 years (71.1%). Each 10-year increase in age was associated with a higher prevalence of seroprotection after adjustment for sex (aPR 1.14, 95% CI 1.06-1.24; p=0.001), whereas sex was not independently associated with seroprotection (aPR 0.97, 95% CI 0.78-1.22; p=0.797). The age association remained consistent across sensitivity analyses. Half of the healthcare workers tested had anti-HBs concentrations below the operational seroprotection threshold. These findings support systematic vaccination verification, appropriately timed post-vaccination testing, and documented follow-up of non-protective results. The absence of vaccination history, occupational characteristics, testing indications, and additional hepatitis B serological markers limited causal and clinical interpretation.
Samela, T.; Priori, R.; Colonna, L.; Zozi, L.; Gallo, V.; Assorgi, C.; Garcovich, S.; Paganelli, A.
Show abstract
Introduction: Lichen sclerosus (LS) is a chronic inflammatory dermatosis predominantly affecting the anogenital region of both women and men. Sexual dysfunction remains among the most debilitating and overlooked consequences of the disease, as available patient-reported outcome measures are either restricted to one sex or capture sexual health only partially. The aim of the present work is to validate the Qualisex questionnaire (in its the Italian version) in patients with LS and to evaluate its psychometric properties, factor structure, convergent, discriminant validity, and sex symmetry. Methods: A cross-sectional study was conducted on 211 patients (167 women, 44 men; mean age 52.9 years) with a confirmed diagnosis of LS. Participants completed the Italian Qualisex, Skindex-29, DASS-21, and sexual-health-specific scales, the Female Sexual Function Index (FSFI) for women, and the International Index of Erectile Function (IIEF) for men. Construct validity was assessed via Principal Component Analysis (PCA), and reliability via Cronbach's alpha. Convergent and discriminant validities were evaluated against standard psychometric batteries. Results: Item 2 was removed due to low communality (0.167). PCA on the remaining 9 items revealed a two-factor structure accounting for 72.5% of total variance: Component 1 (Sexual Functioning and Satisfaction, 59.89%) and Component 2 (Partner Devaluation, 12.66%). Internal consistency was high (alpha= 0.911 overall; alpha= 0.841 in women; alpha= 0.899 in men). Qualisex scores correlated strongly with Skindex-29 Social Functioning (r = 0.582) and Emotions (r = 0.531) subscales, as well as FSFI (r = -0.391) and IIEF (alpha= -0.566). Discriminant validity was supported by low-to-moderate correlations with DASS-21 domains (r < 0.38). While FSFI and IIEF showed significant negative correlations with age (p = 0.002), Qualisex remained age-independent across sexes (p > 0.05). Conclusion. The 9-item Italian Qualisex is a reliable, sex-symmetrical, and age-independent patient-reported outcome measure for assessing sexual health impairment in LS, successfully isolating disease-specific distress from physiological aging and general distress.
Sun, C.; Michel, P.-O.; rigouzzo, A.; Loh, J.; longrois, d.; Constant, I.; holcman, D.
Show abstract
Background: Depth of anesthesia is routinely monitored using electroencephalographic (EEG) indices such as the Bispectral Index (BIS), which reduce cortical activity to a single numerical real-time series. However, these scalar descriptors fail to capture inter-individual variability, drug-specific EEG signatures, and transitions between brain states. Methods: We analyzed transient EEG patterns during general anesthesia induced by propofol and sevoflurane in 89 patients. Iso-electric suppressions (IES), $\alpha$-suppressions, and spectral power in the $\alpha$ and $\delta$ bands were quantified across controlled concentration plateaus. We compared conventional BIS monitoring with a novel State-Chart representation mapping EEG activity into discrete depth states. Results: Increasing hypnotic concentration produced a consistent shift from $\alpha$-dominant to $\delta$-dominant activity and a reduction in maximal $\alpha$ frequency. IES occurred predominantly at high propofol concentrations and remained infrequent under sevoflurane. Compared with BIS, the State-Chart showed a marked reduction in temporal variability (0.5 $\pm$ 0.6 vs 4.0 $\pm$ 2.9; $p<10^{-90}$). Importantly, our State-Chart separates stable from transition regimes and discriminates identical concentration levels. Statistics computed over prior dosing (ascending vs descending), reveals refined clustering not captured by BIS. Conclusions: Anesthesia depth drugs concentrations vs EEG effects is more accurately described by structured EEG state transitions than by a single numerical index. The State-Chart provides a stable, physiologically interpretable representation of brain activity and reveals transition states preceding deep cortical suppression, supporting individualized and predictive monitoring of anesthesia.
Zumba, M. A.; S., M.; A., J.; E., L.; H., M.; A., O.; F, R.; M., E.
Show abstract
Sepsis is a global health problem. Patients in the Intensive Care Unit (ICU) are at risk of having sepsis because of their vulnerability and use of invasive medical devices. Emerging antimicrobial-resistance complicates treatment. Understanding bacterial profiles and antibiotic sensitivity patterns in the ICU plays an important role in managing sepsis, optimizing antimicrobial use, and improving patient outcomes. The aim of this study was to show bacterial profiles and antibiotic sensitivity patterns among patients who were admitted to the ICU at Mbeya Zonal Referral Hospital for 12 months. This was a prospective cross-sectional study among 187 sepsis-suspected patients. Data analysis was performed using SPSS Version 27. Categorical data were summarized by frequency and percentage. Fishers exact test, chi-square test, and modified Poisson regression were used to show the association between patients clinical variables and culture positivity at a 95% CI. Statistical significance was set at a p-value < 0.05. Out of 187 samples, 41.7% were culture positive. Gram-negative bacteria were commonly isolated (65.4%, with Klebsiella pneumoniae and Escherichia coli being commonly isolated. Commonly isolated Gram-positive bacteria were Coagulase-negative Staphylococcus species (19%). 100% of gram-positive bacteria and 96% of gram-negative bacteria were Multi-Drug Resistant (MDR), respectively. In multivariable analysis, patients who were intubated and mechanically ventilated (aPR = 2.208, 95% CI: 1.133-4.305, p = 0.020) and post-laparotomy patients (aPR = 3.241,95% CI: 1.320-7.958, p = 0.010) independently had a higher proportion of Gram-negative bacteria. The study reveals a high level of resistance to commonly used antimicrobials in our setting, necessitating strengthening of the antimicrobial stewardship program and routine surveillance of antimicrobial resistance patterns.
Davis, A. J.; Hochberg, C. H.; Aziz, K. B.; Yan, L.; Sahetya, S.; Hager, D. N.; Iwashyna, T. J.
Show abstract
Objective: To test the hypothesis that selected SIRS and SOFA criteria measured at ICU admission have divergent associations with (1) the development of new culture-confirmed infections and (2) early empiric broad-spectrum antibiotic receipt in critically ill patients with cirrhosis. Design: Retrospective, observational study using electronic health record (EHR) data. Setting: Both community and academic ICUs within a five-hospital health system between July 2017 and December 2025. Subjects: Adult patients >18 years of age diagnosed with cirrhosis admitted to the ICU within 96 hours of hospital admission. Patients transferred from outside facilities and those with positive cultures collected >24 hours before ICU admission were excluded. Interventions: None. Measurements: Multivariable logistic regression tested the association of the most aberrant values in nine SIRS/SOFA vital sign and laboratory parameters measured during the 24 hours prior to ICU admission with (1) the development a newly positive culture collected during the 24 hours before through the 96 hours after ICU admission and (2) receipt of broad-spectrum antibiotics during the 24 hours before through the 24 hours after ICU admission. Main Results: The presence of hyperthermia, hypothermia, hypoxia, or hypotension at ICU admission was associated with both culture positivity and antibiotic receipt. The presence of leukocytosis was associated with antibiotic receipt but not culture positivity. Among patients in the 21.6% of encounters with newly positive cultures, normothermia and normal WBC were common (respectively present in 97.2% and 77.5% of encounters) and associated with antibiotic omission at ICU admission despite the subsequent development culture positivity. Conclusions: Traditional physiologic markers of infection are often absent in critically ill patients with cirrhosis who develop new culture-confirmed infections at ICU admission, possibly contributing to delayed antibiotics. There may be opportunities to improve antibiotic delivery and stewardship at ICU admission in this high-risk population.
Kasugai, D.; Onizuka, H.; Numaguchi, A.; Yamamoto, T.; Kato, N.; Sumiyoshi, R.; Fukui, S.; Koga, T.; Kawakami, A.; Fujii, W.; Kawahito, Y.; Maruyama, S.; Shimamura, T.
Show abstract
Sepsis mimics resemble sepsis clinically but may require different treatments. We evaluated whether inflammatory protein profiles could distinguish these conditions in a retrospective case-control study using 4 prospective Japanese cohorts. The study included 34 adults with sepsis and 46 with sepsis mimics. We measured 92 proteins using Olink, assessed between-group differences with false discovery rate (FDR) adjustment, and evaluated 3 prediction models using repeated nested cross-validation. No protein met the FDR threshold; the lowest FDR-adjusted P value was 0.345. The primary elastic-net model had an area under the receiver operating characteristic curve of 0.442 (95% confidence interval, 0.315-0.574), based on cross-validation predictions averaged for each participant. Random forest and gradient boosting also showed no clear evidence of discrimination above chance. Confidence intervals included chance performance in both the all-serum and quality-control-Pass sensitivity analyses. In this cohort, a single measurement of an inflammation-focused protein panel showed limited discrimination between sepsis and sepsis mimics. Integration with clinical information and longitudinal measurements warrants further investigation.
Chen, Y.; Cai, Y.; Bian, H.; Fu, M.
Show abstract
Abstract Background: In patients with sepsis and pre-existing hypertension, admission findings may not adequately describe the subsequent course of circulatory support and organ dysfunction. We developed and externally validated a model to reassess in-hospital mortality risk after the first 72 hours of intensive care. Methods: This retrospective study used MIMIC-IV for development and eICU-CRD for external validation. Patients had received vasoactive agents and remained in the ICU for at least 72 hours. Static variables were combined with features from six consecutive 12-hour windows. Imputation, feature selection, model fitting, and calibration were performed within training folds during five-fold cross-validation. The final XGBoost model was applied externally without refitting. Evaluation included discrimination, calibration, decision curves, and risk stratification, with an exploratory comparison of static-only and static-plus-dynamic feature sets. Results: The development and external cohorts included 1019 and 1747 patients, with 338 (33.2%) and 516 (29.5%) deaths, respectively. Internal area under the receiver operating characteristic curve (AUC) was 0.752 (95% CI 0.720-0.784). External AUC was 0.713 (95% CI 0.687-0.739), average precision was 0.536, the Brier score was 0.185, and the calibration slope was 0.744. Mortality increased across external risk tertiles from 13.7% to 47.3%. In an exploratory feature-set comparison, the static-plus-dynamic feature set showed a 0.071 higher internal AUC than the static feature set (95% CI 0.042-0.109). Conclusions: Information accumulated during the first 72 hours supported subsequent mortality risk stratification in this selected population. The model retained moderate discrimination externally, supporting further evaluation as an adjunct to clinical reassessment. Local calibration and the clinical consequences of acting on model predictions require evaluation before routine use.
Kwarshak, Y. K.; Dakum, N. K.; ofoha, C. O.; akpayak, I. C.; Ramyil, V. M.; Shuaibu, S. I.; Galam, Z. Z.
Show abstract
BACKGROUND: Zinc inhibits energy production, growth, and proliferation in normal prostate cells while suppressing the malignant potential and angiogenesis that are essential to prostate cancer aggressiveness. The study aimed to determine the correlation of serum zinc with Gleason score as a marker for prostate cancer aggressiveness METHODOLOGY: We conducted a hospital-based cross-sectional analytical study carried out on forty-two (42) eligible participants with newly diagnosed histologically confirmed prostate adenocarcinoma over one year. Spearman's rank correlation was used to assess the relationship between serum zinc and prostate cancer aggressiveness as measured by the Gleason score. The impact of serum zinc level on the aggressiveness of severe prostate cancer was assessed using a binary regression model, adjusting for age as a confounder in the logistic regression model. A statistically significant P value was set at 0.05. RESULTS: The mean age of participants was 67.12 years, with a range of 45- 90 years. High-grade disease (Gleason 8) was the most common, representing 57.1% of patients. The median serum zinc concentration was 71.5 microgram/dL (IQ: 47.6 to 88.5 microgram/dL). Serum zinc and Gleason score showed a statistically significant inverse correlation (Spearman r = -0.514, p < 0.001). Reduced zinc levels were significantly associated with higher Gleason scores (MannWhitney; 140.0, p = 0.002). Low serum zinc independently predicted high-grade disease after adjusting for age. CONCLUSION: This study found a statistically significant inverse correlation between serum zinc concentrations and Gleason score in men with prostate cancer. This finding indicates that reduced serum zinc levels are associated with higher Gleason scores
Jahan, S. T.; Akter, A.; Hossain, S.; Reza, M. S.; Rahman, M. M.; Alam, M. M.; Huq, M. M.
Show abstract
Abstract Cardiovascular disease (CVD) is a major cause of morbidity and premature mortality in people with rheumatoid arthritis (RA). Whether multidimensional cardiometabolic, inflammatory, renal, behavioral, and psychosocial factors define distinct cardiovascular risk phenotypes in RA remains unclear. This study aimed to identify data-driven phenotypes and evaluate their associations with prevalent CVD. We analyzed 3,252 adults aged over 20 years with self-reported RA from the 2005-2018 National Health and Nutrition Examination Survey (NHANES). Unsupervised partitioning around medoids (PAM) clustering using Gower distance identified distinct data-driven cardiovascular-risk profiles. Cluster validity was assessed using silhouette analysis and internal train test validation. Survey-weighted binary logistic regression evaluated associations between phenotype membership and prevalent CVD. Six clinically interpretable data-driven phenotypes were identified with varying CVD prevalence: Severe Metabolic Diabetic (40.3%), Aging Diabetic Hypertensive (34.9%), Non-Diabetic Intermediate (20.2%), Mild Metabolic (14.8%), Cardiometabolic (10.4%), and Smoking-Predominant (19.4%). Compared with the Cardiometabolic phenotype, the Severe Metabolic Diabetic phenotype exhibited the highest odds of prevalent CVD (aOR 4.11, 95%CI:2.56-6.59), followed by the Aging Diabetic-Hypertensive phenotype (aOR 3.38, 95%CI:2.22-5.15). Higher odds of prevalent CVD were also observed in the Smoking-Predominant (aOR 1.99, 95% CI: 1.26-3.13) and Non-Diabetic Intermediate (aOR 1.77, 95% CI: 1.10-2.84) phenotypes. The six-cluster solution demonstrated moderate separation and strong internal correspondence across training and testing sets, while the phenotype-informed model showed moderate discrimination for prevalent CVD (AUC = 0.72). Among adults with rheumatoid arthritis (RA), distinct data-driven phenotypes were identified based on combined patterns of metabolic, inflammatory, renal, behavioral, and psychosocial factors, with differing burdens of prevalent cardiovascular disease (CVD). Phenotype-based approaches may provide a comprehensive framework for characterizing multidimensional cardiovascular risk in RA.
Bhujel, A.; K.C, P.; Thapa, D.
Show abstract
Background: Abortion is safe when carried out using a method recommended by the World Health Organization (WHO), appropriate to the pregnancy duration, and by someone with the necessary skills. lobally, around 73 million induced abortions take place each year. Around 95% of maternal deaths occur in developing countries due to childbirth and pregnancy-related complications. Methodology: A descriptive cross-sectional study was used for the study among the married reproductive (20-45 years) age women using a non-probability purposive sampling technique. A self-developed semi-structured questionnaire was used via face-to-face interview for data collection. The collected data were analyzed using SPSS 16.0 version descriptive and inferential statistics were used to find the association between variables. Results: The findings of the study show that among 118 respondents, nearly two-thirds (57.6%) of the respondents had adequate knowledge and less than half (42.4%) of the respondents had inadequate knowledge regarding safe abortion. The study further shows that there was a significant association between the level of knowledge regarding safe abortion and education status and education level with p-value <0.05. Conclusion: The study concludes that nearly two third of the respondents have adequate knowledge regarding safe abortion. Educational status significantly influenced their level of knowledge. Thus, we could provide correct knowledge, education, and enhance awareness to married women in the reproductive age group.
Escarraman Martinez, D.; Sanchez Diaz, S.; Pedraza Yanez, K. I.; Escorza Molina, C. A.; Guerrero Alberto, M. A.; Noriega Salas, L.; Solis Perez, G. A.; Antolinez-Motta, J. M.; Flores Rodriguez, A. d. J.
Show abstract
Background: Acute kidney injury (AKI) is a common complication after liver transplantation (LT). Alactic base excess (ABE) reflects the metabolic component of acid base disturbances not attributable to lactate and has been associated with kidney dysfunction in other clinical settings. We evaluated the association between intraoperative ABE and postoperative AKI after LT. Methods: We conducted a retrospective cohort study of adult patients undergoing LT. ABE was calculated from standard base excess and lactate obtained from the last intraoperative arterial blood gas analysis. The primary outcome was creatinine based AKI occurring within the first 7 postoperative days according to Kidney Disease: Improving Global Outcomes criteria. The association between ABE and AKI was estimated using modified Poisson regression with robust variance, adjusted for age, sex, body mass index, MELD score, cold ischemia time, and anhepatic phase duration. A post hoc exploratory analysis evaluated severe AKI, defined as KDIGO stages 2,3. Results: Seventy patients were included, of whom 32 (45.7%) developed AKI. ABE values were lower among patients who developed AKI than among those who did not (median, -1.15 vs 0.75 mmol/L; Hodges Lehmann location shift, -1.60 mmol/L; 95%CI, -2.80 to -0.20). After multivariable adjustment, ABE was not independently associated with AKI (aRR, 0.91; 95%CI, 0.82-1.01; p=0.07). Severe AKI occurred in 14 patients (20.0%), and ABE was not independently associated with severe AKI (aRR, 0.98; 95%CI, 0.78-1.23; p=0.87). Sensitivity analyses yielded consistent findings. Conclusions: A single intraoperative ABE measurement was not independently associated with postoperative AKI or severe AKI after LT. Serial measurements across different phases of transplantation may better characterize the potential relationship between ABE dynamics and postoperative kidney injury.
Takeuchi, T.; Nomiya, A.
Show abstract
Background: A 2019 report from our institution described a multilayer artificial neural network (ANN) for predicting prostate cancer at biopsy in 334 patients, trained with TensorFlow 1.x and evaluated at three fixed step counts without separating hyperparameter selection from test evaluation. We re-analyzed an expanded cohort from the same institution using contemporary machine-learning practice. Methods: We pooled all available biopsy episodes from the same institutional database (n = 526; 524 after excluding one non-binary outcome code and one record with missing digital rectal examination [DRE] data), retaining the same seven predictors used in the original report (age, prior biopsy history, PSA, prostate volume, DRE, and MRI diffusion-weighted imaging findings in the peripheral and transition zones). Because 27 patients contributed more than one biopsy episode, we used patient-ID-grouped, stratified k-fold cross-validation (StratifiedGroupKFold; scikit-learn 1.8.0) with 3 and 5 folds, repeated over 10 random partitions, to avoid leakage between folds. Four classifiers were compared: L2-regularized logistic regression, gradient boosting, random forest, and a shallow (single hidden layer) multilayer perceptron. Two outcomes were modeled: detection of any prostate cancer, and detection of clinically significant prostate cancer (Gleason score [≥] 7). Results: Any-cancer prevalence was 55.7% (292/524) and Gleason score [≥] 7 prevalence was 39.7% (208/524). With repeated 5-fold cross-validation, gradient boosting gave the highest discrimination for any prostate cancer (mean AUC 0.826, 95% CI 0.823-0.830) and for Gleason score [≥] 7 (mean AUC 0.855, 95% CI 0.852-0.859), closely followed by random forest and logistic regression (AUC 0.81-0.85). The shallow multilayer perceptron performed worse and less consistently than the other three models (any-cancer AUC 0.671; Gleason score [≥] 7 AUC 0.742) and than the deeper five-hidden-layer ANN reported in 2019. Results with 3-fold cross-validation were essentially unchanged. Conclusions: In an expanded cohort, regularized logistic regression, gradient boosting, and random forest all discriminated prostate cancer at biopsy at least as well as the previously reported multilayer ANN, using far simpler models and a methodology that separates hyperparameter tuning from performance estimation. A shallow neural network offered no advantage over these simpler alternatives in this sample size. This is a preprint; the study has not undergone external peer review.
Guin, A.; Misra, S.; Bhattacharjee, D.; Chatterjee, S.; Ghosh, A.
Show abstract
Background: Chronic lowgrade inflammation in long standing rheumatoid arthritis (RA) contributes not only to joint damage but also to metabolic dysregulation, endothelial dysfunction, and elevated cardiovascular (CV) risk. Although combination disease modifying anti rheumatic drugs (DMARDs) remain the mainstay of therapy, their long term efficacy in controlling systemic inflammation and preventing metabolic complications appears limited. Phytochemicals such as resveratrol, a polyphenolic compound widely used in traditional and complementary medicine, possess anti inflammatory and immunomodulatory properties. Objectives: To investigate whether resveratrol can complement the immunomodulatory effects of combination DMARDs in long duration RA patients by modulating inflammatory cytokines and the JNK-IRS-Akt insulin signaling axis. Methods: This study enrolled early and late rheumatoid arthritis patients to assess disease activity, vascular markers, and ex vivo PBMC responses. PBMCs were isolated for cytotoxicity testing and resveratrol treatment, followed by ELISA and Western blot analysis. Statistical comparisons evaluated immunomodulatory effects and alterations in inflammatory signaling. Results: Longitudinal follow up of RA patients showed significant first year improvement in disease activity and atherosclerotic markers, correlated with MTX dose. An early versus late RA comparison revealed elevated cytokines and enhanced JNK mediated stress signaling in longstanding disease. Resveratrol maintained PBMC viability, reduced LPS induced TNF&alpha and adipokine levels, and downregulated pJNK and GSK&beta, indicating targeted anti inflammatory modulation independent of Akt activation. Conclusion: Chronic RA showed persistent inflammatory and metabolic dysregulation driven by JNK-NF&kappaB activation. Resveratrol reduced cytokines, corrected adipokine imbalance, and selectively inhibited JNK, suggesting adjunct therapeutic value alongside DMARDs for improving immunometabolic disturbances in long-standing RA.