Nevin Manimala

Front Endocrinol (Lausanne). 2025 Nov 19;16:1689238. doi: 10.3389/fendo.2025.1689238. eCollection 2025.

ABSTRACT

INTRODUCTION: Acute decompensated heart failure (ADHF), a critical cardiovascular emergency, is driven by a metabolic and inflammatory imbalance that serves as the central mechanism of disease progression. This study aims to analyze the heterogeneity of mortality risk in patients with comorbid diabetes mellitus (DM) and HF using the C-reactive protein-triglyceride-glucose index (CTI).

METHODS: This study evaluated 1,051 ADHF patients from the Jiangxi-ADHF II cohort. The Boruta algorithm, a fully automated feature selection method, was applied to identify key predictive variables and rank their importance. Cox proportional hazard models were constructed to assess the association between the CTI and 30-day mortality risk in ADHF patients, stratified by DM status. To further elucidate the nonlinear characteristics of risk associations, restricted cubic splines were employed to construct dose-response relationship curves. Additionally, heatmaps were used to assess the joint association of CTI components with mortality risk.

RESULTS: The 30-day follow-up revealed a mortality rate of 8.3%. Through the Boruta algorithm and multivariate Cox regression analysis, we identified CTI as a key prognostic factor for short-term mortality risk in ADHF patients, especially in those with comorbid DM. The restricted cubic splines model further confirmed the linear and non-linear associations between CTI and mortality in ADHF patients with and without DM. Additionally, heatmaps visualized the association between CTI components and mortality: to summarize, the mortality risk is relatively low when the triglyceride-glucose index remains within specific ranges (8.25-9.0 for patients with DM; 7.0-9.0 for non-DM patients) and the C-reactive protein level is maintained below 50 mg/L. Further subgroup analyses highlighted distinct risk modulation patterns: non-DM ADHF patients exhibited mortality risk heterogeneity across gender, hypertension, and stroke subgroups; however, the DM comorbid group demonstrated uniform risk profiles with no statistically significant differences.

DISCUSSION: This study demonstrates the clinical utility of the novel inflammatory-metabolic index CTI in mortality risk assessment for ADHF patients, with superior risk stratification efficacy observed in those with DM comorbidity.

PMID:41347140 | PMC:PMC12672285 | DOI:10.3389/fendo.2025.1689238

Depress Anxiety. 2025 Nov 26;2025:4470169. doi: 10.1155/da/4470169. eCollection 2025.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) is common and associated with high social and economic burden. Knowledge of characteristics of hospitalized adults with MDD can help identify clinical treatment and prevention targets.

METHODS: The multicenter “Patient Characteristics, Validity of Clinical Diagnoses and Outcomes Associated with Suicidality in Inpatients with Symptoms of Depression” (OASIS-D) study assessed characteristics of patients aged 18-75 years hospitalized between October 2020 and December 2024, who were admitted to a psychiatric inpatient unit for MDD at eight German centers. Baseline illness-, treatment-, and suicidality-related characteristics of the overall sample are reported.

RESULTS: Among 3795 patients (median age = 42.0, interquartile range [IQR] = 27.5-57.0 years; females = 53.9%) with MDD (severe episode = 75.3%, psychotic features = 7.9%; first episode = 34.9%; treatment-resistant depression [TRD] = 18.2%). Psychiatric comorbidities of MDD were present in 46.2% and included substance use disorder (18.9%), personality disorders (8.4%), stress/adjustment disorders (7.6%), and phobic/other anxiety disorders (6.6%). In 42.5%, the admission was prompted by a psychiatric emergency, primarily due to suicidality (35.0%), followed by stupor/refusal/intoxication/acute agitation (0.9%-1.5%), or danger to others/delirium (0.1%-0.3%). Overall, 72.0% of patients had active or passive suicidal thoughts, and 11.5% had attempted suicide within 2 weeks prior to admission. Furthermore, 83.9% had lifetime suicidal thoughts, and 36.0% had lifetime suicide attempts. Altogether, 76.8% had received outpatient psychiatric care within their lifetime (62.3% within 6 months), and 57.8% of patients had lifetime inpatient treatment for MDD. At admission, 71.6% of patients were prescribed psychiatric medications: antidepressants = 59.8%; antipsychotic = 25.1%, anxiolytics/hypnotics = 11.8%, and mood stabilizers = 8.6%. Additionally, 4.0% had previously received electroconvulsive therapy (ECT). The median hospitalization duration was 31.0 (IQR = 13.0, 57.0) days.

CONCLUSION: Almost half of admissions in adults with MDD were considered emergencies, with 90% being related to suicidality, and only <60% received antidepressants at admission. These data underscore the need for early identification and treatment of adults with MDD, especially those with suicidality. Outcomes of this population required further study. Trial Registration: ClinicalTrials.gov identifier: NCT04404309.

PMID:41347111 | PMC:PMC12674865 | DOI:10.1155/da/4470169

BMC Urol. 2025 Dec 4. doi: 10.1186/s12894-025-02011-2. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate the ability of the systemic immune-inflammation index (SII), which is tested before transrectal ultrasound-guided systematic prostate biopsy, to predict the histopathology of non-malignant and malignant prostate tissue.

METHODS: Data from 1040 patients who underwent transrectal ultrasound-guided prostate biopsy between June 2019 and January 2023 due to high prostate-specific antigen levels or palpation of suspicious prostate cancer nodules via digital rectal examination were analyzed retrospectively. The patients were divided into two groups as biopsy negative and prostate cancer. The SII, platelet/lymphocyte ratio (PLR), and neutrophil/lymphocyte ratio (NLR) were compared between the two groups. Statistical analyses were performed using Student’s t, Mann-Whitney U, and one-way ANOVA tests, along with ROC curve analysis and DeLong’s test to assess diagnostic performance.

RESULTS: There was no difference between the groups in terms of the SII, PLR, or NLR (p > 0.05). When evaluated according to the European Urology Association risk groups for biochemical recurrence of localized and locally advanced prostate cancer based on systematic biopsy, a significant difference was observed in the SII and PLR markers between the groups with biopsy negative and those with high-risk prostate cancer (p = 0.009, and p < 0.001, respectively). In the ROC analysis, the AUC for the SII was 0.568 (95% CI 0.523-0.628). The best limit value was determined to be 591.4, and for values ≥ 591.4, the sensitivity was determined to be 0.5, and the specificity was 0.571. For the PLR, the AUC was 0.618 (95% CI 0.559-0.676). The best limit value was 139.6, and for values ≥ 139.6, the sensitivity was 0.52, and the specificity was 0.72.

CONCLUSIONS: Hematological inflammatory parameters before prostate biopsy are not effective markers for distinguishing between biopsy negative and malignant pathologies. The inflammatory markers SII and PLR can be used as diagnostic tools in high-risk prostate cancer patients but cannot be used as markers for the detection of pathologies in low- and intermediate-risk patients.

PMID:41345845 | DOI:10.1186/s12894-025-02011-2

Med Phys. 2025 Dec;52(12):e70183. doi: 10.1002/mp.70183.

ABSTRACT

BACKGROUND: Compared to photon therapy (XT), proton therapy (PT) can often reduce normal tissue toxicity for head and neck (HN) cancer patients, despite being a limited resource. On the other hand, clinical decision-making process to select between PT and XT (e.g., treatment planning and then plan evaluation for comparing normal tissue complication probabilities (NTCP) between XT and PT) is time-consuming and resource demanding.

PURPOSE: This study aims to develop and validate the feasibility of an artificial intelligence (AI)-based automated method for efficient patient selection between PT and XT.

METHODS: A heterogeneous cohort of 104 bilateral HN patients with auto-planned PT and XT plans was analyzed, covering diverse tumor subsites and prescription dose levels. To ensure accurate dose and NTCP prediction, a joint-modality prediction framework was developed, incorporating a 3D attention-gated U-net with a multi-constrained loss function. A stratified 10-fold cross-validation strategy was employed to evaluate and compare model performance. The NTCP differences between XT and PT for grade II/III xerostomia/dysphagia exceeding certain thresholds are used to select patients for PT according to the Landelijk Indicatie Protocol Protonentherapie (versie 2.2) (LIPPv2.2).

RESULTS: AI-assisted patient selection process took about 10.1 s per patient. Our method achieved an accuracy of 85.58% and a weighted accuracy of 81.11% in patient selection. For dysphagia grades ≥ 2 and ≥ 3, the predicted results exhibited consistent selection with the ground truth in 86.54% and 89.42% of cases, respectively. Compared to previous models, the average ΔNTCP prediction error (ΔNTCP ground truth-ΔNTCP predicted, mean ± SD) of the proposed method was 1.47 ± 1.80%, statistically lower than U-net (1.67 ± 2.20%) and hierarchically densely connected U-net (2.34 ± 3.25%). Moreover, the joint-modality prediction of PT and XT dose distributions using Attention U-net achieved comparable performance to separate single-modality predictions.

CONCLUSION: This study highlights the potential of a novel AI-assisted framework with joint-modality prediction to enhance efficiency and precision for proton-photon patient selection in the heterogeneous dataset, demonstrating the generalizability and robustness of the proposed approach.

PMID:41345820 | DOI:10.1002/mp.70183

Neurogastroenterol Motil. 2025 Dec 4:e70216. doi: 10.1111/nmo.70216. Online ahead of print.

ABSTRACT

BACKGROUND: The reference standard for the assessment of esophageal motility and sphincter function is high-resolution esophageal manometry (HRM). Diagnostic values for HRM are determined by the Chicago Classification (CC v4.0), which is based almost entirely on distal esophageal function without measures to address the proximal esophageal segment. Therefore, we sought to determine normal HRM values for proximal esophageal function when obtained in the standard HRM positions (supine and upright).

METHODS: Healthy, asymptomatic adults (≥ 18 years) were recruited. All participants completed a standard protocol. CC v4.0 measurements, along with a proximal contractile integral (PCI) (millimeters mercury-seconds-centimeters[mmHg-s-cm]), temporal measures of proximal and distal contractility (seconds), and lengths of proximal and distal esophagus (centimeters), were performed. Summary statistics, tests of normality, and paired two-sided t-tests were performed.

RESULTS: HRM data from 30 participants were included. Mean supine PCI was 423.9 mmHg-s-cm with a mean contraction time of 3.2 s and a mean length of 5.5 cm. The mean upright PCI was 183.9 mmHg-s-cm with a mean contraction time of 2.2 s, and a mean length of 4.5 cm. All proximal values were significantly different comparing the two positions (PCI p < 0.0001; time p < 0.0001; length p < 0.0001). All distal measurements fell within the ranges of normal, and all measures for contractile integral, contraction time, and contraction length were statistically significantly different (p < 0.0001 for all) comparing proximal versus distal measurements.

CONCLUSIONS: These preliminary data represent our first attempt to quantify normal proximal esophageal function using HRM measurements of contractile vigor, contraction length, and time.

PMID:41345798 | DOI:10.1111/nmo.70216

Magn Reson Med. 2025 Dec 4. doi: 10.1002/mrm.70212. Online ahead of print.

ABSTRACT

PURPOSE: Magnetic resonance elastography (MRE) of the heart has predominantly utilized breath-held acquisitions with limited anatomic coverage. This work investigates the feasibility of 3D, free-breathing cardiac MRE.

METHODS: A 3D hybrid radial and EPI acquisition is utilized and combined with retrospective binning of k-space via physiologic monitoring, iterative reconstruction, MRE processing and inversions, and post-processing specialized for cardiac imaging.

RESULTS: Feasibility of free-breathing stiffness mapping of the left ventricular myocardium was demonstrated in 11 participants. Myocardial stiffness estimates were obtained throughout the left ventricle for seven temporal states of the cardiac cycle. Stiffness estimates were presented in participant-specific images, 17-segment bullseye plots, and stiffness plots throughout the cardiac cycle. Results indicate increased stiffness in systolic states, with localized stiffness heterogeneity observed between participants, illustrating a key benefit of 3D cardiac MRE acquisition. Mean stiffness estimates obtained through 11 subjects were 4.44 ± 0.68 kPa (begin-systole), 5.74 ± 0.94, 5.42 ± 0.87 (end-systole), 3.84 ± 0.71 (begin-diastole), 3.51 ± 0.74, 3.54 ± 0.52, and 3.55 ± 0.59 kPa (end-diastole). Statistical testing indicated significant differences in stiffness across cardiac states with one-way, repeated-measures ANOVA (p < 0.001) and Friedman’s test (p < 0.001). Experiments in scanning three participants with and without applied motion indicated that stiffness changes were more robustly detected in systole than in diastole, although patterns were subject-specific. Comparison of free-breathing stiffness measurements against reference breath-held measurements yielded similar systolic stiffness estimates.

CONCLUSIONS: This study establishes the feasibility of free-breathing, 3D cardiac MRE in healthy volunteers. With the current framework, stiffness estimation appears more robust in systole, and the reliability of diastolic estimates is limited and subject-specific.

PMID:41345797 | DOI:10.1002/mrm.70212

Nat Methods. 2025 Dec 4. doi: 10.1038/s41592-025-02893-y. Online ahead of print.

ABSTRACT

Pose estimation methods and motion capture systems have opened doors to quantitative measurements of animal kinematics. While animal behavior experiments are expensive and complex, tracking errors sometimes make large portions of the experimental data unusable. Here our deep learning method, Deep Imputation for Skeleton data (DISK), uncovers dependencies between keypoints and their dynamics to impute missing tracking data without the help of any manual annotations. We demonstrate the utility and performance of DISK on seven animal skeletons including multi-animal setups. The imputed recordings allow us to detect more episodes of motion, such as steps, and obtain more statistically robust results when comparing these episodes between experimental conditions. In addition, by learning to impute the missing content, DISK learns meaningful representations of the data capturing, for example, underlying actions. This stand-alone imputation package, available at https://github.com/bozeklab/DISK.git/ , is applicable to outputs of tracking methods (marker-based or markerless) and allows for varied types of downstream analysis.

PMID:41345771 | DOI:10.1038/s41592-025-02893-y

Nat Methods. 2025 Dec 4. doi: 10.1038/s41592-025-02896-9. Online ahead of print.

ABSTRACT

We propose a latent space-based statistical network analysis (LatentSNA) method that implements network science in a generative Bayesian framework, preserves neurologically meaningful brain topology and improves statistical power for imaging biomarker detection. LatentSNA (1) addresses the lack of power and inflated type II errors in current analytic approaches when detecting imaging biomarkers, (2) allows unbiased estimation of the influence of biomarkers on behavioral variants, (3) quantifies uncertainty and evaluates the likelihood of estimated biomarker effects against chance and (4) improves brain-behavior prediction in new samples as well as the clinical utility of neuroimaging findings. LatentSNA is broadly applicable across multiple imaging modalities and outcome measures in developing, aging and transdiagnostic cohorts, totaling 8,003 to 11,861 participants. LatentSNA achieves substantial accuracy gains (averaging 110-150%) and replicability improvements (averaging 153%) over existing approaches in moderate to large datasets. As a result, LatentSNA elucidates how network topology is implicated in brain-behavior relationships.

PMID:41345770 | DOI:10.1038/s41592-025-02896-9

Pharmacoeconomics. 2025 Dec 4. doi: 10.1007/s40273-025-01566-0. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Chimeric antigen receptor T-cell therapies have changed the treatment paradigm of relapsed or refractory large B-cell lymphoma but are among the most expensive treatments. Moreover, their comparative economic value remains uncertain in adults with relapsed or refractory large B-cell lymphoma. The objective of this study was to understand the comparative value of these therapies in this population and the main factors that influenced conclusions on which intervention was considered more cost effective than others.

METHODS: To assess the comparative cost effectiveness of chimeric antigen receptor T-cell therapies and the drivers of cost-effectiveness results, a systematic literature search of Embase, Scopus, and PubMed was conducted from inception to December 2024 and updated in October 2025. Studies were selected if they were full economic evaluations of head-to-head comparisons of chimeric antigen receptor T-cell therapies for relapsed or refractory large B-cell lymphoma. Two reviewers independently extracted data on key information such as population characteristics and model structure. Results were reported in their original format, and conclusions on cost effectiveness were evaluated based on country-specific willingness-to-pay thresholds. The reporting quality of the included studies was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist and the Drummond 10-Item Checklist.

RESULTS: Eight full economic evaluations across the USA, Spain, France, and Japan were included in this systematic review. All studies modeled an adult population or patients with relapsed or refractory large B-cell lymphoma who had failed two or more lines of prior therapy, were conducted over a lifetime horizon, and mostly used the payer perspective (n = 6). All studies utilized three-state partitioned survival models but relied heavily on indirect comparison methods such as matching-adjusted indirect comparison. Three chimeric antigen receptor T-cell therapies were evaluated: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabtagene maraleucel (liso-cel). Axi-cel was the most frequently reported cost-effective option (n = 7) with two studies concluding it was the dominant strategy. There was substantial uncertainty in the model results given the lack of individual patient-level data for each arm and reliance on indirect comparisons.

CONCLUSIONS: In this systematic review of economic evaluations of head-to-head comparisons of chimeric antigen receptor T-cell therapies for relapsed or refractory large B-cell lymphoma, current evidence suggests that axi-cel may be the most cost-effective option. However, given the studies’ reliance on indirect comparisons and the absence of any study conducted in low- to middle-income countries, these results must be carefully interpreted until additional evaluations or clinical trials are conducted.

PMID:41345759 | DOI:10.1007/s40273-025-01566-0

Eur J Pediatr. 2025 Dec 4;184(12):819. doi: 10.1007/s00431-025-06584-w.

ABSTRACT

Research on the infection-related etiologies of neonatal acute respiratory distress syndrome (NARDS) remains limited. This study aimed to investigate mortality risk differences in NARDS attributed to distinct infection origins (sepsis of extrapulmonary origin or pulmonary infection origin). Subjects were derived from a multicenter retrospective study organized by the Jiangsu Provincial Neonatal Respiratory Failure Collaboration Network. It included neonates with NARDS who initiated invasive mechanical ventilation (IMV) within 72 h of birth. A total of 268 from 1275 NARDS cases with infectious etiologies were enrolled. Multivariate Cox regression found a significant difference in the survival prognosis (sepsis of extrapulmonary origin, adjusted hazard ratio (HR): 3.93, 95% CI 1.79-8.62, log-rank test: P < 0.001]. Further multi-model and sensitivity analysis confirmed the robustness. Between early-onset and late-onset NARDS, the subgroup analysis showed no significant differences in the mortality risk, whether it was pulmonary infection origin (HR 1.69, 95% CI 0.61-4.64) or sepsis of extrapulmonary origin (HR 0.50, 95% CI 0.17-1.51). Restricted cubic spline also exhibited that the onset time of NARDS was not related to the mortality risk.

CONCLUSION: This study suggests that for sepsis of extrapulmonary origin, we should be more vigilant about the mortality risk it brings and deal with the risk factors more actively and prudently.

WHAT IS KNOWN: • Limited research has systematically investigated the association between infection origin and mortality risk in neonatal acute respiratory distress syndrome (NARDS).

WHAT IS NEW: • Our study found that sepsis of extrapulmonary origin was associated with an increased mortality risk in neonates with gestational age > 34 weeks, with robust results from multivariate Cox modeling and sensitivity analyses. • It highlights the need for heightened vigilance and proactive management of extrapulmonary sepsis-related NARDS to mitigate mortality risk in neonates.

PMID:41345740 | DOI:10.1007/s00431-025-06584-w