Tag: nevin manimala

J Pharmacokinet Pharmacodyn. 2026 Feb 16;53(2):11. doi: 10.1007/s10928-026-10019-w.

ABSTRACT

The pharmacokinetic literature is rich in aggregated concentration data that contain valuable information, yet tools to extract this information remain limited. This work introduces distributional physics-informed neural networks (D-PINNs), a novel algorithm designed to enable statistical modelling within the PINN framework, allowing recovery of pharmacokinetic parameter distributions at the population level from published concentration means and variances. Unlike traditional PINNs, which often focus on point estimates, D-PINNs incorporate distributional assumptions directly into the optimisation process. The framework utilises neural networks for predicting the mean and variance of the concentration over time. These predictions are then incorporated into a sampling-based procedure within the residual network, which uses the governing ordinary differential equation (ODE) system to compute the physics-informed loss term. The methodology accounts for both interindividual variability through the parameter distribution and measurement noise through a residual error model. The capability of D-PINNs to infer population-level parameter distributions from concentration summary statistics was demonstrated through a simple proof-of-concept using simulated data from a one-compartment pharmacokinetic model of intravenous drug administration. The model achieved high accuracy in estimating both the parameter distribution and the residual error. Hyperparameter tuning highlighted important aspects of model development. The modelling framework was then applied to real-world data to demonstrate its ability to recover information on the distribution of kinetic parameters in the studied population. Specifically, a minimal physiologically-based pharmacokinetic (mPBPK) model for monoclonal antibodies (mAbs) was fitted to aggregated plasma concentration data reported in the literature using D-PINNs. The same aggregated data were also analysed using a Markov chain Monte Carlo (MCMC) analogue to benchmark the proposed methodology.

PMID:41699348 | DOI:10.1007/s10928-026-10019-w

Ann Biomed Eng. 2026 Feb 16. doi: 10.1007/s10439-026-04014-y. Online ahead of print.

ABSTRACT

PURPOSE: Deep vein thrombosis (DVT) poses significant health risks, including potentially fatal pulmonary embolism. Current clinical practice relies heavily on ultrasonography, requiring a skilled specialist. Alternative methods, such as light reflection rheography (LRR) and venous occlusion plethysmography (VOP), are non-invasive and simple; however, studies report limited consistency and standardization. The development of biosignal-based diagnostic tools is constrained by the inherent risks of DVT, including embolization, and challenges in patient recruitment. The ability to simulate DVT-like conditions would aid in developing and testing alternative screening methods. This study aims to present a simulation method of venous hemodynamic alterations resembling deep vein thrombosis using controlled external thigh compression with ultrasonic visualization.

METHODS: Data collection with thirty healthy volunteers was conducted in a laboratory using a commercially available system VasoScreen 5000-4000 to record LRR and VOP signals. Vein stenosis at varying levels was induced through controlled external thigh compression under ultrasonic guidance.

RESULTS: The experimental simulation showed statistically significant but small changes in LRR parameters across different stenosis levels. In comparison, VOP results showed greater differences across stenosis levels, with 70% and 100% performing the best. In these cases, 47% and 70% of the measurements, respectively, were below the normal reference limit, with a notably increased outflow time constant, compared to the baseline measurements, where it remained low despite varying venous capacity.

CONCLUSION: Presented hemodynamic alterations demonstrated to be a feasible option for simulating DVT-like conditions via controlled external pressure on the thigh.

PMID:41699339 | DOI:10.1007/s10439-026-04014-y

Eur J Pediatr. 2026 Feb 16;185(3):134. doi: 10.1007/s00431-026-06795-9.

ABSTRACT

This study aimed to describe the implementation and functioning of a regional hub-and-spoke model (“Gaslini Diffuso”) for managing pediatric bronchiolitis in Liguria, Italy, during the 2023-2024 season, focusing on severity stratification, resource allocation, and outcomes. A retrospective observational study was conducted across one tertiary hub (IRCCS Istituto Giannina Gaslini, Genoa) and four affiliated spoke hospitals. Medical records of all patients aged 0-2 years hospitalized with bronchiolitis (ICD-9-CM 466.19) between October 2023 and March 2024 were reviewed. Demographic, clinical, microbiological, and treatment data were analyzed. Predictors of centralization to the hub were identified through multivariable logistic regression. A total of 562 patients were included (median age 95 days; 40.4% female). Most cases were mild to moderate, with 56.6% requiring respiratory support-mainly low-flow oxygen or HFNC-and only 2% requiring mechanical ventilation. Thirteen patients (2.3%) were admitted to the PICU, and no deaths occurred. Centralized patients (n = 10) were significantly younger (median 43.5 days) and had higher severity indicators, including elevated CO₂ and CRP levels, and longer respiratory support (median 5 vs. 3-4 days, p < 0.001). Independent risk factors for centralization were age < 60 days (OR 23.1, p = 0.004) and HFNC use (OR 20.5, p = 0.006). Spoke centers showed homogeneous adherence to referral criteria, though some variability in ancillary treatments persisted.

CONCLUSIONS: The Ligurian hub-and-spoke model demonstrated internal consistency between referral criteria and observed patient severity, supporting appropriate case stratification within the regional network. This integrated framework enhanced regional coordination and represents a scalable, sustainable model for pediatric respiratory disease management.

WHAT IS KNOWN: • Bronchiolitis is the leading cause of hospitalization in infants under two, with seasonal surges that may overwhelm pediatric services; management remains largely supportive. • Hub-and-spoke models have been proposed to optimize care and resource allocation, but real-world data on their clinical and organizational impact, especially post-COVID, is limited.

WHAT IS NEW: • This study evaluates, for the first time in Italy, the real-world implementation of a regional hub-and-spoke model (Gaslini Diffuso) for bronchiolitis management. • The model enabled effective stratification of disease severity, with high specificity in centralizing only the most critical cases, ensuring efficient use of pediatric intensive care resources.

PMID:41699321 | DOI:10.1007/s00431-026-06795-9

Int Orthop. 2026 Feb 17. doi: 10.1007/s00264-026-06756-9. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aims to determine whether distal femoral morphology (DFM) constitutes a risk factor for periprosthetic femoral fractures (PPFs) in a cohort of patients who underwent posterior-stabilized total knee arthroplasty (PS-TKA).

MATERIALS AND METHODS: Retrospective study of patients who had undergone primary PS-TKA, with a follow-up of minimum two years. Citak’s ratio was calculated, and patients were classified according to DFM. Univariate and multivariate statistical analysis was performed to identify PPFs risk factors. ROC analysis was performed to evaluate the ability of DFM to distinguish patients at risk for PPFs.

RESULTS: A total of 2452 patients 1644 female, 808 male were included in the analysis. The mean age of the participants was 70.2 years (SD = 6.4). PPFs were detected in 33 patients (1.35%). According to the Citak classification, patients were categorized as Group A (4/33, 12.1%), Group B (8/33, 24.2%), and Group C (21/33, 63.7%). DFM was significantly related to the PPFs rate (p = 0.001). The ROC curve analysis yielded an Area Under the Curve (AUC) of 0.669 (CI 95% 0.580-0.758) for the DFM.

CONCLUSIONS: Preoperative evaluation of distal femoral morphology and management of osteoporosis may reduce the risk of fractures after PS-TKA.

PMID:41699317 | DOI:10.1007/s00264-026-06756-9

Arch Toxicol. 2026 Feb 17. doi: 10.1007/s00204-025-04277-9. Online ahead of print.

ABSTRACT

This review comprehensively examines the variability and uncertainty associated with test guideline (TG)-conform genotoxicity data and explores the respective implications for the integration of non-animal-methods (NAMs) into regulatory frameworks. Historical amendments to OECD TGs are mapped to reveal the method’s evolution that improves the scientific quality of the data but also explains data heterogeneity within available databases. An analysis of the major genotoxicity databases ECVAM, ISSMIC, and OASIS demonstrates substantial variability in genotoxicity calls. Using the EFSA genotoxicity database, which currently harbours the best-curated (meta-) data, we estimate that 22-77% of compounds exhibit similarity of replicate results below 85%, depending on the assay. The potentially most important variables statistically explaining variability and sensitivity were analysed. The practical limitations to identify them with high reliability and to define their optimum needs to be accepted as a qualitative baseline uncertainty. These findings underscore the necessity of contextualizing NAM performance evaluations within the intrinsic variability and uncertainty of animal and in vitro reference data. We propose that this variability is explicitly considered in the development and validation of NAM-based Integrated Approaches for Testing and Assessment. This review provides a critical foundation for regulators and scientists aiming to enhance the acceptance and utility of NAMs in genotoxicity assessment.

PMID:41699308 | DOI:10.1007/s00204-025-04277-9

Hypertens Res. 2026 Feb 17. doi: 10.1038/s41440-026-02571-2. Online ahead of print.

ABSTRACT

Emerging evidence links maternal immune dysregulation to hypertensive disorders of pregnancy (HDP), yet gestational immune alterations preceding symptom onset remain unclear. This study aimed to evaluate the associations between first-trimester immune biomarkers and incident HDP risk across clinical subtypes. This retrospective cohort study enrolled pregnant women aged ≥18 years undergoing first-trimester antenatal screening at a tertiary hospital from March to November 2023. First-trimester peripheral immune markers-neutrophils, monocytes, lymphocytes, and platelets-were measured, with derived indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), and aggregate index of systemic inflammation (AISI). Outcomes included HDP, gestational hypertension (GHTN), and preeclampsia confirmed via electronic medical records. Multivariable logistic regression models were performed to evaluate the relationship between peripheral immune markers and outcomes. Among the 2739 pregnant women who met inclusion criteria, 195 developed HDP, including 96 GHTN and 99 preeclampsia. Multivariable logistic regression demonstrated that first-trimester neutrophils, monocytes, platelets, lymphocytes, SII, and AISI were independently and positively associated with HDP risk in a linear dose-response manner (all FDR P < 0.05), with platelets exhibiting the strongest association (OR _{T3 vs. T1}: 2.20; per log-SD: OR = 1.55). Distinct biomarker profiles were identified between GHTN and preeclampsia: GHTN exhibited associations with neutrophils, platelets, SII, and AISI, while preeclampsia correlated with monocytes, platelets, lymphocytes, SII, and AISI (all FDR P < 0.05). Elevated first-trimester immune markers correlate with HDP, particularly platelet-related indices. Divergent immune signatures between GHTN and preeclampsia suggest subtype-specific pathophysiological mechanisms.

PMID:41699290 | DOI:10.1038/s41440-026-02571-2

Eur J Nucl Med Mol Imaging. 2026 Feb 17. doi: 10.1007/s00259-025-07741-x. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the feasibility and diagnostic performance of ⁶⁸Ga-CBP8 PET/MR enterography for noninvasive detection of bowel collagen deposition and differentiation of inflammatory from fibrotic or mixed strictures in Crohn’s disease.

MATERIALS AND METHODS: Patients with stricturing Crohn’s disease scheduled for bowel resection or endoscopic biopsy were prospectively enrolled. PET/MR enterography was performed after intravenous administration of ⁶⁸Ga-collagen binding probe 8 (⁶⁸Ga-CBP8). Focal radiotracer uptake was defined as activity exceeding local background and anatomically corresponding to an MR-identified bowel stricture. Surgical and biopsy specimens underwent blinded pathologic evaluation for fibrosis. Descriptive statistics, sensitivity and specificity were calculated to assess diagnostic performance. Differences in SUVmax and SUVmax stricture-to-uninvolved bowel ratio between fibrotic and non-fibrotic segments were evaluated using the Mann-Whitney U test, with p < 0.05 considered statistically significant.

RESULTS: Five patients (4 M, 1 F; median age: 50; IQR: 11) with seven strictured bowel segments (median length: 24 mm; IQR: 14) were included. Five segments (71.4%) demonstrated focal ⁶⁸Ga-CBP8 uptake and were pathologically confirmed as mixed inflammatory-fibrotic strictures. Two segments (28.6%) showed no significant uptake and were confirmed as strictures devoid of fibrosis. ⁶⁸Ga-CBP8 PET/MR enterography achieved 100% sensitivity for mixed inflammatory-fibrotic strictures and 100% specificity for non-fibrotic strictures. SUVmax and SUVmax stricture-to-uninvolved bowel ratio were higher in fibrotic than non-fibrotic segments (median SUVmax: 2.29 vs. 1.01; median ratio: 2.36 vs. 0.88), although without statistically significant differences (both p = 0.095).

CONCLUSION: ⁶⁸Ga-CBP8 PET/MR enterography is a feasible noninvasive technique to assess bowel strictures in Crohn’s disease and may enable differentiation of inflammatory and fibrotic components.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT06252493. Date of first enrollment: 19 December 2023. Registered: 2 February 2024 (retrospectively registered).

PMID:41699282 | DOI:10.1007/s00259-025-07741-x

Nat Rev Clin Oncol. 2026 Feb 16. doi: 10.1038/s41571-026-01132-3. Online ahead of print.

NO ABSTRACT

PMID:41699272 | DOI:10.1038/s41571-026-01132-3

Eur J Hum Genet. 2026 Feb 16. doi: 10.1038/s41431-026-02031-y. Online ahead of print.

ABSTRACT

In the context of limited resources and growing demand, patients access genetic testing for hereditary breast and ovarian cancer (HBOC) through various service models, some of which include genetic counseling sessions. This study assessed the impact of these service models and participation in genetic counseling on patients’ experiences and satisfaction with the genetic testing process. A total of 501 patients undergoing genetic testing for HBOC completed a 35-item survey, which included the Genetic Counseling Satisfaction Scale, the Decision Regret Scale, and a modified Royal Marsden Satisfaction Questionnaire. Additional information was gathered from the medical records. Descriptive statistics and Fisher’s exact tests were employed for the analysis. Four aspects of the genetic testing experience differed between service models and attendance to genetic counseling: i) receipt of informational materials prior to testing, ii) information that additional discussions with the genetic team were possible, iii) clarity regarding the timeline for receiving results, and iv) explanation of how the results would be delivered. The service model and participation in genetic counseling seem to influence patients’ experiences with genetic testing for HBOC. However, satisfaction was generally high and decision regret was low across all service models, highlighting the promise of care models designed to enhance accessibility.

PMID:41699267 | DOI:10.1038/s41431-026-02031-y

Eur Arch Otorhinolaryngol. 2026 Feb 16. doi: 10.1007/s00405-026-10069-3. Online ahead of print.

NO ABSTRACT

PMID:41699250 | DOI:10.1007/s00405-026-10069-3