Nilima Rajpal Kundnani

Background: An age of 45 years is often used to guide endometrial assessment in abnormal uterine bleeding (AUB), but age is only one component of clinical risk. We described the relationship between age and histopathological yield among premenopausal women who had undergone endometrial sampling. Methods: This single-centre retrospective cross-sectional study analysed the index sampling episodes of 824 women with AUB documented as premenopausal or perimenopausal (January 2022–May 2026). The clinically more consequential endpoint was endometrial intraepithelial neoplasia (EIN)/atypical hyperplasia or carcinoma; the primary statistical outcome was a broader composite that also included hyperplasia without atypia. Modified Poisson regression estimated the adjusted association between age ≥45 years and the primary outcome. Discrimination of age alone and of an exploratory model using variables available before biopsy was compared in 776 complete cases with bootstrap internal validation. Results: EIN/carcinoma occurred in 4/361 (1.1%) women aged p = 0.047). Results were similar across sensitivity analyses (adjusted RRs 1.52–1.68). With age coded as ≥45 years in both models, the optimism-corrected AUC was 0.686 for the exploratory pre-biopsy model and 0.575 for age alone (difference 0.111, 95% CI 0.060–0.196). Conclusions: Among premenopausal women selected for endometrial sampling, histopathological yield increased with age, and most EIN/carcinoma cases occurred at age ≥45 years, but the adjusted association for the broad outcome was imprecise, and age alone had limited discrimination. Model performance was assessed only internally and only in sampled women; this study cannot establish a biopsy rule for all women with AUB because women not sampled were not observed.

Introduction: Acute liver failure (ALF) is a life-threatening condition associated with hepatic encephalopathy (HE), characterised by neurological impairments, hyperammonemia, oxidative stress, and inflammation. Diindolylmethane (DIM), a bioactive compound derived from cruciferous vegetables, has shown potential hepatoprotective and neuroprotective effects via its antioxidant and anti-inflammatory properties. Despite beneficial effects, its protective effects have not been investigated against HE. The present study evaluated the hepatoprotective and neuroprotective effects of DIM in a rat model of thioacetamide (TAA)- induced ALF and HE. Methods: ALF was induced using thioacetamide (TAA; 300 mg/kg, i.p.). DIM at doses of 12.5, 25, and 50 mg/kg, p.o., was administered for 7 days prior to TAA injection. Behavioral assessments, including the open field test and Y-maze, were performed to evaluate motor and cognitive functions. Biochemical parameters (AST, ALT, ALP, and LDH), ammonia levels, oxidative stress markers (MDA, NRF2, SOD, GSH, and catalase), inflammatory cytokines (IL-6, TNF-α, and IL-10), and apoptotic markers (cytochrome c, caspase 9, and caspase 3) were analysed. Histopathological examinations of the liver, cortex, and hippocampus were conducted using hematoxylin and eosin staining. Results: DIM pretreatment significantly reduced liver enzyme levels (AST, ALT, ALP, and LDH), normalised organ weight ratios, and decreased ammonia levels in blood, liver, and brain. DIM attenuated oxidative stress by reducing MDA levels and enhancing NRF2, SOD, GSH, and catalase activity, suggesting its antioxidant potential. Further, DIM reduced IL-6 and TNF-α levels and increased IL-10 levels, indicating its antiinflammatory effects. Furthermore, DIM reduced the apoptotic markers, including cytochrome c, caspase 9, and caspase 3, suggesting attenuation of apoptosis. Additionally, DIM improved motor activity and spatial memory and exhibited an anxiolytic effect. DIM mitigated the TAA-induced liver, hippocampal, and cortical tissue abnormalities. Discussion: The findings suggest that DIM exerts protective effects against ALF-induced HE by modulating key pathological mechanisms, including oxidative stress, neuroinflammation, and apoptosis. The reduction in hyperammonemia and restoration of biochemical and behavioral parameters indicate its potential role in preserving liver and brain function. Conclusion: DIM demonstrates significant hepatoprotective and neuroprotective effects in TAA-induced ALF and HE. These effects are mediated through multiple mechanisms, suggesting DIM as a potential therapeutic candidate for managing ALF-associated neurological complications. Future studies require investigating the in-depth mechanism of DIM against HE.

Background: Atrial fibrillation (AF) is associated with atrial remodelling, hemodynamic stress, and complex cardiopulmonary interactions. While natriuretic peptides and echocardiographic abnormalities are established markers of AF-related substrate, the contribution of spirometry changes, as a landmark of pulmonary impairment, remains less clearly defined. This study evaluated whether AF is associated with an integrated cardiopulmonary profile characterized by altered spirometry, increased NT-proBNP, and conventional echocardiographic markers of left atrial structure and function. Methods: We performed a retrospective, single-center observational study based on an existing clinical database of adult patients referred for 24 h 12-lead Holter ECG monitoring because of palpitations and/or chest pain. None of the included patients had a previously documented diagnosis of atrial fibrillation before Holter monitoring. Because a single 24 h Holter recording cannot establish spontaneous termination or long-term temporal pattern with certainty, AF documented for the first time during this recording is referred to throughout as “newly detected AF” rather than “paroxysmal AF”. During Holter monitoring, no ECG changes suggestive of myocardial ischemia were detected. From 536 records of patients without previously known AF who underwent 24 h 12-lead Holter ECG monitoring for palpitations and/or chest pain, 164 patients were retained for the main comparison, including 48 with newly detected paroxysmal AF and 116 without AF. Demographic, biochemical, spirometric, and echocardiographic variables were analyzed. The main respiratory parameters were forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and peak expiratory flow (PEF). NT-proBNP was the primary biomarker, while conventional left atrial structural and functional variables were used for echocardiographic assessment. Results: NT-proBNP was markedly higher in the AF group (684.5 vs. 62.3 pg/mL, p = 0.001), even when accounting for confounders like age, CKD, or CPD, showing by far the largest between-group difference among the biomarkers assessed (formal discrimination statistics such as ROC/AUC were not computed). The exploratory inflammatory markers assessed (hs-CRP, neutrophil/lymphocyte ratio, homocysteine) showed only modest, non-significant differences. Conventional echocardiographic parameters did not differ significantly between groups. In the strict complete-case comparison, spirometric indices did not reach statistical significance; however, preliminary project-level analysis showed lower FVC, FEV1, and PEF in AF patients, but without supporting the COPD diagnosis, and exploratory correlations suggested a relationship between spirometric performance and left atrial function. Conclusions: In this cohort, AF was most strongly associated with NT-proBNP, while the respiratory signal was weaker but directionally consistent with a broader cardiopulmonary phenotype. These findings do not support spirometry or NT-proBNP as stand-alone diagnostic tools for AF. However, when interpreted alongside traditional AF risk factors and symptoms, elevated NT-proBNP with concordant spirometric impairment may represent a hypothesis-generating additive signal supporting longer or repeated rhythm monitoring beyond 24 h in selected patients with suspected AF; this additive value was not formally tested against clinical models alone and requires prospective confirmation.

Background: Many patients with heart failure with reduced ejection fraction (HFrEF) remain undertreated in routine practice. Delayed treatment intensification, poor adherence, and fragmented follow-up are common barriers. Low-cost digital support may help reduce this implementation gap. Objective: This study evaluated whether a simple digital support pathway was associated with better 6-month treatment adherence and guideline-directed medical therapy (GDMT) optimization in ambulatory patients with stable HFrEF. Methods: This single-center matched cohort study compared a prospective digital-support cohort with a historical usual-care cohort. The intervention combined smartphone-based telemanagement, home blood pressure and heart-rate reporting, daily weight surveillance, and scheduled video consultations. The co-primary endpoints were treatment adherence at 6 months and GDMT optimization, assessed by change in foundational HFrEF drug classes and by a prespecified exploratory GDMT optimization score. Results: After 1:1 propensity-score matching, 200 patients were included, with 100 patients in each cohort. Treatment adherence at 6 months was higher in the digital-support cohort than in usual care (82.0% vs. 64.0%, p = 0.004). The intervention cohort also had more frequent class addition, more dose escalation, a greater increase in foundational drug classes, and a larger improvement in GDMT optimization score (all p < 0.001). Heart failure hospitalization and the composite of heart failure hospitalization or all-cause death were less frequent in the digital-support cohort, but these clinical outcomes were exploratory. Conclusions: A pragmatic low-cost digital support pathway was associated with better adherence and more complete GDMT optimization in ambulatory patients with HFrEF. The findings support further prospective multicenter evaluation.

Background: Socio-cognitive deficits constitute a core and persistent feature of adolescent-onset schizophrenia, significantly impairing functional outcomes. However, the interplay between genetic metabolic markers such as CYP2D6 and specific socio-cognitive phenotypes remains poorly understood. Methods: This cross-sectional study included 73 adolescents with schizophrenia and 58 matched healthy controls. Theory of Mind (ToM) was evaluated using the Reading the Mind in the Eyes Test (RMET), while empathy was assessed with the Cambridge Empathy Quotient. Symptom severity was measured via the Positive and Negative Syndrome Scale (PANSS). CYP2D6 polymorphisms were genotyped using RT-PCR, classifying participants as Normal or Reduced (Intermediate) metabolizers. Hierarchical multiple regression analyses were performed, controlling for sex, IQ, and psychosocial factors. Results: Patients demonstrated significantly lower RMET and empathy scores compared to controls. Reduced CYP2D6 metabolizers exhibited poorer ToM performance and more severe negative symptoms. The final RMET model accounted for 88.8% of variance (p < 0.001), with CYP2D6 status emerging as a significant independent predictor (β = 0.178, p = 0.005), alongside IQ and negative symptoms. In contrast, the empathy model explained 49.0% of variance, with CYP2D6 effects fully mediated by negative symptom severity. Conclusion: Adolescents with reduced CYP2D6 metabolic activity exhibit greater negative symptom burden and impaired social-cognitive functioning. Our findings reveal a double dissociation: ToM functions as a stable, biologically anchored trait, while empathy serves as a state-dependent construct primarily driven by the negative syndrome. These insights advocate for the integration of pharmacogenetic stratification in the treatment of early-onset schizophrenia.

Background and Objectives: Schizophrenia in adolescence severely impairs quality of life (QoL) and disrupts critical social, academic, and neurodevelopmental periods. Beyond symptom remission, functional recovery and subjective well-being have become central therapeutic goals; however, the specific contributions of pharmacogenetic, social–cognitive, and residual clinical factors to QoL in early-onset schizophrenia remain largely unexplored. This study investigated the contribution of CYP2D6 metabolizer status, social cognition (theory of mind and empathy), residual psychopathology, and family factors to subjective QoL in adolescents with schizophrenia. Materials and Methods: A cross-sectional study of 52 adolescents with DSM-5 schizophrenia (PAT-SCZ) and 51 matched healthy controls. QoL was measured with the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q). Social cognition was assessed using the revised Reading the Mind in the Eyes Test (RMET). Residual symptoms were rated with the Positive and Negative Syndrome Scale (PANSS). CYP2D6 genotyping classified patients as normal metabolizers (NMs) or reduced-function metabolizers (RM: intermediate/poor). Two multivariable OLS regression models examined predictors of QoL. Results: Patients showed markedly lower QoL, impaired theory of mind, lower empathy, and higher residual symptoms than controls (all p < 0.0001). Within patients, reduced-function metabolizer (RM) status was associated with poorer QoL, weaker social cognition, higher negative/general psychopathology, and lower IQ. Two multivariable regression models explained 84.2–84.3% of the variance in QoL (adjusted R²). Social cognition (RMET scores) and CYP2D6 reduced-function metabolizer status emerged as the strongest predictors (β = 0.363 and β = −0.362, respectively, both p < 0.0001), followed by negative symptom severity and dysfunctional family relationships (all p < 0.05). Conclusions: Pharmacogenetic (CYP2D6), social–cognitive, and clinical factors strongly determine QoL in adolescent schizophrenia. Routine CYP2D6 genotyping, social-cognition remediation, and family interventions should be integrated into early treatment to improve long-term well-being.

Background/Objectives: The angiosome concept is widely used to guide infrapopliteal revascularization in patients with chronic limb-threatening ischemia (CLTI). However, clinical outcomes are not always fully explained by anatomical target-artery alignment alone. The present study aimed to revisit a previously published angiosome-based cohort through a wound-oriented conceptual perspective and to explore whether perfusion heterogeneity may help contextualize variability in clinical outcomes. Methods: This retrospective secondary analysis included 51 patients with CLTI who underwent infrapopliteal endovascular revascularization. Patients were originally classified as direct, indirect, or mixed revascularization according to angiosome-based criteria. The present study represents an exploratory conceptual reinterpretation of the original dataset. No new variables were introduced, and the woundosome concept was not operationalized as a measurable patient-level variable. Statistical analyses were exploratory and descriptive in nature. Results: High rates of wound healing and limb salvage were observed across all revascularization patterns at 12 months. Within the limitations of this small exploratory cohort, no consistent detectable differences in clinical outcomes were observed across anatomical revascularization patterns. Stratification according to the number of affected angiosomes did not reveal clear outcome differences. The findings suggest that factors beyond anatomical target-artery alignment may contribute to wound healing variability in CLTI. Conclusions: The present study does not establish a validated wound-oriented perfusion model but highlights the limitations of relying exclusively on anatomical angiosome classification when interpreting clinical outcomes in CLTI. In this context, the woundosome may serve as a descriptive and hypothesis-generating conceptual framework for discussing perfusion heterogeneity and wound-level perfusion complexity. Prospective studies integrating objective perfusion assessment and standardized wound evaluation are required.

Background: Antenatal depression has been associated with systemic inflammation, autonomic imbalance, and vascular dysfunction, yet its relationship with clinically relevant cardiovascular complications during pregnancy remains insufficiently defined. Objective: To evaluate whether antenatal depression diagnosed before cardiologic assessment is associated with gestational hypertension, preeclampsia, and clinically significant Holter-confirmed arrhythmias in a tertiary-care population of pregnant women referred for cardiology assessment. Methods: We conducted a retrospective secondary matched cohort analysis nested within a prospectively approved doctoral research protocol (approval no. 76/02.10.2023; approved study interval: 2 October 2023–10 February 2025), including deliveries from October 2023 to February 2025. During this 16-month interval, 12,436 deliveries were recorded. The index point was the first cardiology specialist evaluation performed between 22 + 0 and 36 + 6 weeks’ gestation. Pregnancies with a depressive disorder diagnosed by structured psychiatric interview (SCID-5) before cardiology evaluation were classified as exposed. Depression severity was categorized as mild (n = 44), moderate (n = 62), or severe (n = 24), and psychotropic medication class at index was recorded. Each depressed case was matched 1:3 with non-depressed controls by gestational age at index, calendar year, maternal age, BMI category, smoking status, and parity; adjusted models included BMI and psychotropic medication class. Results: The final referral-enriched cohort included 130 depressed pregnancies and 390 matched controls (n = 520), all of whom underwent cardiology evaluation. Between 22 + 0 and 36 + 6 weeks’ gestation, gestational hypertension occurred in 18.5% vs. 10.0% (p = 0.010), preeclampsia in 8.5% vs. 4.9% (p = 0.12), and clinically significant Holter-confirmed arrhythmias in 15.4% vs. 6.9% (p = 0.003) in depressed versus control groups, respectively. After adjustment, depression remained independently associated with gestational hypertension (aOR 1.85, 95% CI 1.12–3.05; p = 0.016) and arrhythmia (aOR 2.05, 95% CI 1.18–3.57; p = 0.011). A numerical, exploratory severity-response gradient was observed across mild, moderate, and severe depression strata, most clearly for Holter-confirmed arrhythmias; however, the severe-depression stratum was small (n = 24). Conclusions: Antenatal depression was associated with a modest but significant increase in gestational hypertension and clinically significant Holter-confirmed arrhythmias during late pregnancy among women referred for cardiology assessment. The higher preeclampsia rate in depressed pregnancies was not statistically significant. These findings support antenatal depression as a cardiovascular risk marker in gestation rather than proof of causality.

Background/Objectives: Chronic limb-threatening ischemia (CLTI) is the most advanced stage of peripheral arterial disease and is associated with high rates of major amputation and mortality. The angiosome concept has become an important tool for planning targeted revascularization. However, its clinical value may be limited in patients with complex arterial disease, impaired collateral circulation, and microvascular dysfunction. This review explores the relationship between angiosome-guided revascularization and the emerging woundosome concept, which focuses on functional wound perfusion. Methods: A narrative review with a structured literature search was performed using PubMed/MEDLINE, Scopus, and Web of Science. Studies evaluating angiosome-guided revascularization, direct versus indirect revascularization, collateral circulation, pedal arch integrity, and perfusion-related outcomes in CLTI and diabetic foot disease were included. Results: Most observational studies and meta-analyses suggest that direct angiosome-targeted revascularization may improve wound healing and limb salvage in selected patients. However, clinical outcomes are also influenced by collateral circulation, anatomical variability, infra-malleolar perfusion, pedal arch integrity, and microvascular function. The woundosome concept expands the traditional angiosome model by emphasizing effective perfusion of the wound bed through direct arterial inflow, collateral pathways, and functional perfusion assessment. Conclusions: Combining the angiosome and woundosome concepts may provide a more practical and individualized approach to revascularization planning in CLTI by integrating anatomical vascular mapping with functional wound perfusion assessment.

Background: Schizophrenia in adolescence disrupts neurodevelopment and long-term functioning. While symptom reduction remains a primary treatment goal, quality of life (QoL) represents a critical, patient-centered outcome. Pharmacogenetic variability, particularly in CYP2D6 metabolism of second-generation antipsychotics, may influence tolerability and subjective well-being beyond symptom control. Materials and Methods: Forty-seven adolescents (aged 14–18 years) diagnosed with schizophrenia (DSM-5) were followed in routine clinical care. CYP2D6 genotyping classified patients as normal metabolizers (NM, n = 27) or reduced-function metabolizers (RFM, including intermediate/poor, n = 20). Symptom severity was assessed with PANSS, QoL was assessed with the Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q), and adverse effects (hyperprolactinemia, extrapyramidal symptoms, sedation, metabolic changes) were monitored. Non-parametric tests and multiple linear regression were applied. Results: At 12 months, RFM patients showed significantly higher PANSS scores, markedly more adverse reactions (95% vs. 48.1%), and lower PQ-LES-Q total and domain scores (all p < 0.0001) compared to NM patients. A regression analysis identified the metabolizer status (β = −0.410, p = 0.001), extrapyramidal symptoms (β = −0.248, p = 0.003), sedation (β = −0.193, p = 0.029), and hyperprolactinemia (β = −0.190, p = 0.012) as independent predictors of a reduced QoL, explaining 84% of the variance. The residual symptom severity was not independently associated. Conclusions: In adolescent schizophrenia, the CYP2D6-reduced metabolizer status is the strongest independent predictor of long-term QoL impairment, associated primarily through a substantially higher burden of treatment-related adverse effects (metabolic, endocrine, neurological, and sedative) rather than through persistence of psychotic symptoms alone. These findings support early pharmacogenetic testing to guide individualized dosing and improve tolerability and patient-reported outcomes.