Nevin Manimala

Crit Care. 2025 Aug 29;29(1):390. doi: 10.1186/s13054-025-05628-9.

ABSTRACT

BACKGROUND: Glucocorticoid (GC) signaling plays a crucial role in immune regulation during critical illness, but cell-specific responses remain poorly understood. While previous studies have predominantly examined glucocorticoid receptor (GCR)-α and GCR-β, the roles of alternative isoforms (GCR-γ, GCR-P) and the downstream effectors GC-induced leucine zipper (GILZ) and dual-specific phosphatase 1 (DUSP1) across different immune cell populations in critical illness remain unexplored.

METHODS: In this prospective, observational study, we enrolled 43 critically ill patients and 25 healthy controls. Longitudinal blood samples were collected at ICU admission (24-48 h) and days 4 (4d), 8 (8d), and 14 (14d). We quantified the mRNA expression of four GCR variants (GCR-α, GCR-β, GCR-γ, and GCR-P) and GC downstream targets (GILZ and DUSP1) in isolated polymorphonuclear cells (PMNs) and peripheral blood mononuclear cells (PBMCs) via RT‒PCR. Serum cortisol, adrenocorticotropic hormone (ACTH), and cytokines (interleukin (IL)-6 and IL-10) were measured concurrently. Statistical analyses included mixed-effects modeling to assess temporal and cell-specific patterns.

RESULTS: PMNs exhibited sustained downregulation of GCR-α, GCR-β, and GCR-γ, with preserved GILZ expression, while GCR-P remained stable. In PBMCs, GCR-α, GCR-β, GCR-γ, and GILZ levels showed no significant changes compared to controls, yet GCR-P was upregulated. DUSP1 was downregulated in PMNs and elevated in PBMCs. Negative correlations emerged between IL-6 and both GILZ and DUSP1. All expression patterns remained stable across time points in the subset of patients who completed the 2-week study despite dynamic ACTH changes and persistently elevated cortisol.

CONCLUSIONS: PMNs show reduced GCR-α/β/γ with preserved GILZ, while PBMCs maintain GCR-α/β/γ but upregulate GCR-P and DUSP1. These findings highlight divergent GC responsiveness between innate and adaptive immune cells, with implications for cortisol’s role in immune regulation during critical illness and may reflect cell-specific effects driven by changes in glucocorticoid receptor signaling.

PMID:40883751 | DOI:10.1186/s13054-025-05628-9

Biomed Eng Online. 2025 Aug 29;24(1):104. doi: 10.1186/s12938-025-01436-y.

ABSTRACT

BACKGROUND: Coronary artery calcification (CAC) represents a major cardiovascular risk in patients with end-stage renal disease (ESRD) undergoing hemodialysis. Given that radial artery pulse waveforms can reflect vascular status, this study aimed to evaluate their utility in the non-invasive assessment of CAC severity.

METHODS: 58 patients with ESRD undergoing hemodialysis were enrolled. CAC severity was assessed using low-dose computed tomography (LDCT) and classified into four groups based on Agatston scores: no calcification (0), mild (1-100), moderate (101-400), and severe (> 400). Radial artery pulse waveforms were recorded before, hourly during, and after hemodialysis. Key features were extracted based on morphological differences among groups. Statistical inter-group comparisons and intra-group trend analyses were performed. A gradient boosting decision tree (GBDT) model was trained to classify CAC severity using waveform features.

RESULTS: Clear morphological differences were observed among the four CAC groups. The non-calcified group showed a distinct main wave followed by identifiable tidal waves. With increasing CAC severity, the tidal waves became progressively attenuated and less distinguishable, resulting in a smoother overall waveform, particularly in the severe calcification group. Pulse waveform features exhibited significant variation across CAC groups and over the hemodialysis process, including parameters related to waveform morphology, descending limb, complexity and distribution, mean value, and full-process stereoscopic pulse wave features. The GBDT model demonstrated robust and consistent performance, with an average accuracy of 84.1% and a macro-AUC of 0.962 in fivefold cross-validation, and comparable results (83.9% accuracy, 0.961 macro-AUC) on the independent test set. Notably, the model performed particularly well in identifying Severe Calcification cases.

CONCLUSIONS: Radial artery pulse wave analysis may serve as a non-invasive adjunct for assessing CAC severity in patients with ESRD undergoing hemodialysis.

PMID:40883745 | DOI:10.1186/s12938-025-01436-y

BMC Surg. 2025 Aug 30;25(1):400. doi: 10.1186/s12893-025-03150-x.

ABSTRACT

BACKGROUND: Accurately predicting cavoatrial junction (CAJ) position is important for totally implantable venous-access port (TIVAP) application, which could reduce complications.

METHODS: Clinical information of 117 breast cancer (BRCA) patients who underwent TIVAP implantation was collected. The length of the implanted catheter was determined by a chest radiograph method in the test group, as follows: total catheter insertion length was L, and the distance from the pre-puncture point to the right sternoclavicular joint was measured as L1; the distance from the right sternoclavicular joint to 1.5 vertebral bodies under the trachea carina in the chest radiograph was measured as L2; the preset catheter length was L = L1 + L2. The length of the implanted catheter was determined by a surface measurement method in the control group, as follows: total length of catheter insertion was L; the distance from the pre-puncture point to the right sternoclavicular joint was measured as L1; the distance from the third anterior intercostal space of the right sternoclavicular joint was measured on the body surface as L2; the preset catheter length was L = L1 + L2. CAJ positioning rate and complication rate were compared between the two method groups. Logistic regression analysis, receiver operating characteristic, and decision curve analysis were performed to evaluate the predictive value of the chest radiograph.

RESULTS: For BRCA patients, the chest radiograph was exhibited more accurately in predicting CAJ position. Subgroup analysis indicated a remarkably higher CAJ position rate in the chest radiograph method group regardless of age, while no significant difference between the two measurement groups for patients with BMI > 24.9 kg/m² was observed.

CONCLUSION: The chest radiograph method could more effectively predict the CAJ position than the surface measurement in the overall cohort. However, subgroup analysis revealed that this advantage was not statistically significant in patients with BMI > 24.9 kg/m², suggesting reduced efficacy in high-BMI populations.

PMID:40883736 | DOI:10.1186/s12893-025-03150-x

BMC Med. 2025 Aug 29;23(1):508. doi: 10.1186/s12916-025-04229-1.

ABSTRACT

BACKGROUND: Each year, over 700,000 pregnancies occur in the UK, with up to 10% affected by complications such as hypertensive disorders of pregnancy and gestational diabetes mellitus. Pregnancy-related complications and reproductive factors are associated with an increased risk of cardiovascular disease (CVD) later in life. Our aim was to determine whether adding pregnancy factors to a prediction model with established CVD risk factors improves 10-year risk prediction of CVD in postpartum women, using QRISK®-3 as a benchmark model.

METHODS: We used a population-based retrospective cohort of women aged 15 to 49 who had been pregnant from the Clinical Practice Research Datalink (CPRD) primary care database. Women who were CVD-free were followed from 6 months postpartum. We evaluated the performance of QRISK®-3 and updated the risk prediction model using established risk factors for CVD from QRISK®-3 and additional risk factors specific to pregnancy. Models were developed using Cox-proportional hazards regression for CVD within 10 years. Models were evaluated and compared using measures of overall model fit, calibration, discrimination and clinical utility.

RESULTS: Among 567,667 eligible women, 2175 (0.38%) experienced a CVD event within 10 years. The median follow-up was 4 years. Of the additional pregnancy factors, gestational hypertension, preeclampsia, miscarriage, stillbirth, postnatal depression, gravidity, endometriosis and polycystic ovary syndrome remained associated with CVD after adjusting for other established risk factors of CVD. Adding pregnancy factors to those from QRISK®-3 led to marginal improvements in model performance (QRISK®-3 C-statistic: 0.703 (95% CI 0.687 to 0.718), updated model C-statistic: 0.726 (95% CI 0.711 to 0.740) Although calibration did not improve overall, subgroup analysis showed better calibration in women with a history of pre-eclampsia, postnatal depression and preterm birth using the updated model. The clinical utility was improved for updated models.

CONCLUSIONS: The updated risk prediction models resulted in marginal improvement in discrimination and calibration compared to QRISK®-3 in postpartum women. This could be due to the known association of pregnancy-related complications with established risk factors of CVD. Although the overall predictive performance and calibration of the updated models was similar, the updated model resulted in better clinical utility.

PMID:40883735 | DOI:10.1186/s12916-025-04229-1

Endocr Connect. 2025 Aug 29:EC-25-0350. doi: 10.1530/EC-25-0350. Online ahead of print.

ABSTRACT

BACKGROUND: Neuroendocrine tumours (NETs) are a heterogeneous group of rare neoplasms arising from neuroendocrine cells, most commonly found in the gastrointestinal tract and pancreas. Despite novel diagnostic techniques, identifying reliable biomarkers for NETs still remains a challenge.

OBJECTIVES: Our study explores the diagnostic, monitoring and prognostic value of alpha-fetoprotein (AFP) in pancreatic NETs.

MATERIALS AND METHODS: We recruited 41 adult patients diagnosed with liver metastatic non-functioning pancreatic NETs. Serum AFP levels were assessed at three-month intervals over a span of four years. For comparative purposes, we analysed data in relation to sex, age, liver tumour burden (LTB; <10%, 10-25%), tumour grade based on the WHO 2022 classification (G1, G2), and treatment response on baseline as defined by RECIST 1.1 criteria (SD – stable disease, PD – progressive disease). Every patient underwent treatment with somatostatin analogues during the study period.

RESULTS: Elevated AFP concentrations showed a continuous upward trend across all participants and were significantly associated with indicators of more aggressive disease: greater liver tumour burden (10-25%, p < 0.001), higher tumour grade (G2, p < 0.001), and progression of disease (PD, p < 0.001). No statistically significant differences in AFP levels were observed in relation to age or sex.

CONCLUSION: AFP consistently increases in patients with progressive pancreatic NETs compared to patients with stable disease on baseline. Potential utility of AFP measurements requires further follow-up studies, especially as a prognostic biomarker.

PMID:40880168 | DOI:10.1530/EC-25-0350

Indian J Ophthalmol. 2025 Sep 1;73(9):1383-1388. doi: 10.4103/IJO.IJO_242_25. Epub 2025 Aug 29.

ABSTRACT

This study aimed to assess the interchangeability of pachymetry measurements obtained by anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) in children with congenital corneal opacity (CCO). In this single-centre, comparative case series, children with unilateral or bilateral CCO who underwent examination under anesthesia (EUA) were evaluated using both AS-OCT and UBM. Pachymetry values from both modalities were compared using Bland-Altman analysis, and topography maps from AS-OCT were examined. A total of 54 eyes from 34 children (16 males, 18 females) were included. The mean age at first EUA was 263.93 ± 348.98 days (range: 11 days to 4 years). Mean pachymetry was 785.83 ± 23 μm with UBM and 719.80 ± 247 μm with AS-OCT, showing a statistically significant mean difference of 66.04 ± 133.55 μm (P = 0.0006). UBM consistently yielded higher measurements, and Bland-Altman analysis indicated poor agreement between the two devices. The findings suggest that AS-OCT and UBM are not interchangeable for pachymetry assessment in CCO. However, AS-OCT, being non-contact and usable without sedation, provides practical advantages for longitudinal follow-up and also offers topographic imaging, making it a useful tool in pediatric corneal evaluation.

PMID:40880157 | DOI:10.4103/IJO.IJO_242_25

Indian J Ophthalmol. 2025 Sep 1;73(9):1364-1370. doi: 10.4103/IJO.IJO_2271_24. Epub 2025 Aug 29.

ABSTRACT

PURPOSE: Access to eye surgical care in low- and middle-income countries (LMICs) remains limited due to geographical and financial barriers. This survey evaluated the travel and financial burden on patients and caregivers attending perioperative cataract care at an urban base hospital (UBH) versus community clinics (vision centers [VC]) at the Aravind Eye Care System in South India.

METHODS: This cross-sectional study surveyed 105 cataract surgery patients divided into three groups based on perioperative appointment location: UBH-only (appointments at UBH), VC-only (appointments at VCs), and UBH/VC (Day 1 postoperative appointment at VCs, others at UBH). Descriptive statistics and linear regression assessed associations between subgroups and travel and financial burden. The UBH/VC group reported their preferred location and the reasons.

RESULTS: Over the entire appointment period, transport time for VC-only (353 ± 118 min) was over 3 h lower than UBH-only (589 ± 418 min) and UBH/VC (568 ± 230 min; P < 0.001). Total appointment time was lowest for VC-only (562 ± 177; 1069 ± 439 in UBH-only; 1021 ± 383 min in UBH/VC; P < 0.001). Compared to UBH-only, the VC-only group had the lowest transport time (-236 min, 95% CI: -371 to -102, P = 0.001) and total appointment time (-507 min, 95% CI: -673 to -340, P < 0.001). Transport costs and missed wages were lower for VC-only participants for preoperative and postoperative Day 1 appointments (P < 0.001). Among UBH/VC, 63% (n = 22) preferred VC, while 37% (n = 13) preferred UBH.

CONCLUSIONS: Decentralized perioperative follow-up care is associated with reduced travel and financial burdens for cataract surgery patients in rural, low-resource settings. Further research is needed to evaluate the clinical effectiveness and operational feasibility of decentralized postoperative care in LMICs.

PMID:40880154 | DOI:10.4103/IJO.IJO_2271_24

Indian J Ophthalmol. 2025 Sep 1;73(9):1355-1363. doi: 10.4103/IJO.IJO_2323_24. Epub 2025 Aug 29.

ABSTRACT

PURPOSE: We aimed to estimate prevalence of vision impairment (VI) due to cataract and its associated factors and barriers for accessing cataract surgical services in India in persons aged ≥50 years.

METHODS: Analysis of data collected in National Blindness and Visual Impairment Survey, India (2015-2018), was performed (n = 85135). Prevalence of cataract-associated VI was defined as cataract in at least one eye, pinhole visual acuity (PinVA) worse than threshold (6/12, 3/60) in the cataract-affected eye, and not having a more avoidable cause of VI (presenting visual acuity PVA < 6/12 in better eye) in the person.

RESULTS: The prevalence of cataract-associated VI at PinVA < 6/12 was 12.9% (95% CI: 11.8, 14.0) and 3.0% (95% CI: 2.6, 3.5) at PinVA < 3/60. The highest prevalences at PinVA < 6/12 were noted in Janjgir-Champa (19.0%), Nalbari (17.9%), and Warangal (17.9%). Females had higher prevalence at PinVA < 6/12 (univariate odds ratio [OR] 1.2) and PinVA <3/60 (univariate OR 1.5). Statistically significant gender differences (females worse off) were noted in Sikar, Ambedkar Nagar, Guna, Banda, and Thrissur at PinVA < 6/12. Prevalence increased with increasing age and decreasing literacy and varied across administrative zones on multivariate analysis. Need not felt was the major reason for not availing cataract surgical services in persons with visual impairment at PinVA < 6/12 (48.1%) and PinVA < 3/60 (27.8%) thresholds.

CONCLUSIONS: The burden of cataract-associated VI at PinVA < 6/12 in India is significant. Interventions to overcome social determinants and enhance awareness about surgery are required.

PMID:40880153 | DOI:10.4103/IJO.IJO_2323_24

Indian J Ophthalmol. 2025 Sep 1;73(9):1344-1349. doi: 10.4103/IJO.IJO_450_25. Epub 2025 Aug 29.

ABSTRACT

PURPOSE: The aim of the study was to evaluate optical coherence tomography (OCT) and indocyanine green angiography (ICGA) biomarkers in patients with chronic central serous chorioretinopathy (cCSC) as potential indicators of response to treatment with subthreshold nanosecond laser (NSL).

METHODS: In this retrospective study, we examined 36 eyes of 32 cCSC patients after NSL. High response (HR) was defined as complete resolution of subretinal fluid (SRF) 3 months after first NSL treatment, full response (FR) as complete resolution of SRF, 3 months after the last NSL, with all NSL sessions occurring within 1 year from the first NSL. Biomarkers included central macular thickness (CMT), subfoveal choroidal thickness (SFCT), and intervortex venous anastomosis (IVA).

RESULTS: Patients were 54 ± 12 years old on average; 86% were male. OCT at baseline showed a mean CMT of 364 ± 130 µm and SFCT of 292 ± 45 µm; 64% showed IVA in ICGA. HR was seen in 50% and FR in 78%. Higher IVA rates (83% vs. 44%, P = 0.03) predicted poor response after the first NSL. Patients with IVA presence at baseline showed a statistically significant higher likelihood of requiring more than one NSL session compared to those without IVA presence (57% vs. 15%, P = 0.02).

CONCLUSION: OCT and ICGA biomarkers may play a role as indicators of anatomical responses to NSL. Patients with IVA at baseline showed a poor first response and may need repetitive laser treatments.

PMID:40880151 | DOI:10.4103/IJO.IJO_450_25

Indian J Ophthalmol. 2025 Sep 1;73(9):1307-1313. doi: 10.4103/IJO.IJO_14_25. Epub 2025 Aug 29.

ABSTRACT

PURPOSE: This study aimed to assess BioRing’s (Biotech, India) clinical and topographic efficacy in treating moderate-to-advanced keratoconus and compare its visual, refractive, and keratometric results to Keraring (Mediphacos, Brazil) at different stages of the disease.

METHODS: This retrospective study evaluated the results of 74 eyes (58 patients) that received femtosecond laser-assisted intrastromal corneal ring segment implantation from March 2019 to March 2024. The Amsler-Krumeich classification classified the patients as having either moderate or advanced keratoconus. Group 1 comprised 39 eyes with BioRing implants, whereas group 2 consisted of 35 eyes with Keraring implants. We classified each group into moderate and advanced keratoconus categories. Preoperative and 6-month postoperative assessments encompassed uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), refractive errors, and corneal tomography metrics.

RESULTS: Both BioRing and Keraring showed statistically significant increases in visual acuity, refractive errors, and topographic parameters between preoperative and postoperative examinations. However, when postoperative results were compared between groups, no significant difference in UCVA was found (P = 0.097). In contrast, the Keraring group had considerably superior BCVA than the BioRing group (P = 0.042). In terms of topographic metrics, Keraring considerably improved keratometric flattening, including Kmax (P = 0.040), K1 (P = 0.012), and K2 (P = 0.024). Subgroup analysis revealed comparable improvements in moderate keratoconus, while Keraring showed superior outcomes in advanced cases.

CONCLUSION: BioRing and Keraring effectively improved visual acuity, refractive errors, and topographic parameters in moderate-to-advanced keratoconus. Keraring showed superior outcomes, particularly in advanced keratoconus.

PMID:40880150 | DOI:10.4103/IJO.IJO_14_25