Journal of Clinical Pathology

Background: Early access to pregnancy assessment units now detects many tubal ectopic pregnancies (TEP) at a stage when they could resolve spontaneously, creating a management dilemma. Methods: We performed a hypothesis-generating exploratory analysis in a retrospective study to assess whether serum progesterone (P4) levels in women with TEP are associated with management outcome. Results: Ninety-one cases of TEP managed in a single centre over three years were analysed. Receiver operating characteristic (ROC) curve analysis was used to explore serum levels of progesterone (P4), first human chorionic gonadotropin (hCG) and peak hCG (alone and in combination) in relation with successful completion of expectant management. Decision-tree analysis using first hCG and P4 was additionally performed to explore clinical sequential risk stratification. 23% (n=21) successfully completed expectant management. P4 concentrations in the expectant management group (median 3 nmol/L, IQR 2.00 to 8.50) were significantly lower than in those requiring surgical or medical management (median 17 nmol/L, IQR 5.75 to 29.25; p=0.0002). Area under the ROC curve (AUC) values for P4, log10 first hCG, log10 peak hCG and P4 with log10 first hCG were 0.766, 0.814, 0.811 and 0.835, respectively, for predicting successful expectant management. However, hCG was not significantly outperformed. Nonetheless, Youden optimised thresholds for hCG and P4 are reported, alongside decision-tree analysis that identified sequential first hCG and P4 thresholds associated with successful expectant management. Conclusion: Lower P4 levels are associated with successful expectant management of TEP but they do not outperform hCG either alone or as an adjunctive marker.

Background: Pregnancies complicated by fetal growth restriction are at increased risk of fetal demise and adverse neonatal outcomes. Distinguishing growth-restricted fetuses from constitutionally small ones remains challenging. Given the variability in current diagnostic criteria and the importance of identifying at-risk fetuses, fetal growth velocity has emerged as a predictor of adverse neonatal outcomes. Objective: To evaluate whether percentile-based fetal growth velocity, defined as change in estimated fetal weight percentile per week, predicts adverse neonatal outcomes in pregnancies affected by fetal growth restriction or small-for-gestational-age neonates. The primary aim was to determine the relationship between growth velocity and a composite of adverse neonatal outcomes. Study Design: This was a retrospective cohort study of pregnant patients 18 - 45 years old who delivered between August 2017 to December 2022 in a single healthcare system. Patients were excluded who had fewer than 2 ultrasounds after 16 weeks gestation, genetic or anatomic abnormalities, or a multiple gestation. Results: 300 patients met all inclusion criteria, and most patients (n=199) delivered at the tertiary care center. Three had an intrauterine fetal demise at a mean gestational age of 35w3d. 74 neonates were admitted to the NICU with a mean length of stay of 8.5 days; 29 required respiratory support. No neonatal deaths occurred. In fetuses with initial estimated fetal weight <3rd percentile (n=33), the probability of composite outcome was increased (50%, 95% CI 44.8-55.2) compared to those >50th percentile (5%, 95% CI 3.7-6.6). In the 3-10th and 10 - 50th percentile subgroups with decelerated growth, composite outcome rates were also increased (56.2% and 44.1%) compared to those with neutral or increased growth velocity. Conclusion: Percentile-based fetal growth velocity is a simple calculation that correlates with adverse neonatal outcomes regardless of initial estimated fetal weight. As fetal growth velocity decreased, our cohort saw increased rates of adverse outcomes. Change in EFW percentile normalizes for gestational age and allows ease of clinical interpretation. Decelerated growth identified fetuses at highest risk, suggesting growth velocity as a useful metric in routine surveillance.

Background: Lung cancer is leading cause of cancer related death globally. It is second most prevalent cancer among women worldwide and ranks third among females in Nepal. Contributing factors are smoking, tobacco use, air pollution, and delayed diagnosis. Image-guided fine needle aspiration cytology (FNAC) is rapid diagnostic technique for evaluating lung lesions. It is minimally invasive procedure with less complications. This study examine histocytologic makeup of lung lesions and link the results. Materials and Methods: This cross-sectional observational study included 65 patients irrespective of age and sex presenting with lung masses at Chitwan Medical College and Teaching Hospital from April 2023 to September 2024. After clinical and radiologic evaluation, all cases underwent image-guided FNAC and biopsy. Only specimens with unequivocal malignant features were classified positive. Histopathology served as diagnostic reference standard. Results: FNAC diagnosed 90.8% as malignant and 9.2% as benign. Biopsy confirmed malignancy in 92.3% of cases. FNAC demonstrated a sensitivity of 98.33%, specificity of 100%, positive predictive value(PPV) of 100%, and negative predictive value (NPV) of 83.33%. Concordance between FNAC and histopathological subtyping was 98.46%. Adenocarcinoma was most common subtype, followed by Squamous cell carcinoma(SCC) and small cell carcinoma. Smoking was most common contributing factor associated with malignancy. Conclusion and implications: Image-guided FNAC is an excellent diagnostic accuracy tool which possess higher level of concordance with biopsy in evaluating lung masses. It should be considered as frontline diagnostic tool, especially in resource limited settings. Keywords: FNAC, Lung cancer, Biopsy, SCC, Adenocarcinoma, Small cell carcinoma, Nepal

RationaleOxidative stress, resulting from an imbalance between the production of reactive oxygen species (ROS) and antioxidant defence mechanisms, disrupts cellular redox homeostasis and contributes to damage of biomolecules, including nucleic acids, proteins and lipids. Such disturbances can impair intracellular signalling pathways and have been implicated in the pathophysiology of female reproductive disorders. Nitroblue Tetrazolium (NBT) is a distinctive dye that assesses cellular redox activity in neutrophils through the detection of superoxide anion (O2-). However, the relationship between neutrophil-derived oxidative stress and women infertility remains to be fully elucidated. Aim of the study: We aimed to investigate the role of neutrophil oxidative stress in women infertility using a novel Nitroblue Tetrazolium (NBT) method developed in our laboratory. Materials and methodsBlood and serum specimens were obtained from a total of 100 Libyan women, comprising healthy fertile women (n = 21; controls) and infertile women (n = 79). Superoxide anion (O2-) generation in neutrophils was assessed using the novel NBT method, while malondialdehyde (MDA), a marker of lipid peroxidation, was determined using the thiobarbituric acid reactive substances (TBARS) assay. ResultsA significant increase in both NBT-reactivity levels and the percentage of NBT-positive neutrophils was observed in infertile women compared with healthy fertile controls (P < 0.0001). In addition, MDA levels were significantly higher in infertile women than in the control group, indicating enhanced lipid peroxidation. MDA levels were positively correlated with NBT-reactivity levels (r = 0.410, P = 0.0001) and the percentage of NBT-positive neutrophils (r = 0.21, P = 0.047). A significant positive correlation was also observed between NBT-reactivity levels and the percentage of NBT-positive neutrophils (r = 0.510, P = 0.0001), demonstrating a close association between neutrophil oxidative activity and lipid peroxidation in women infertility. ConclusionThe present study demonstrates the utility of a novel NBT method for detecting reactive oxygen species (ROS), a marker of oxidative stress, in neutrophils from both blood and serum specimens. The findings demonstrate increased neutrophil-derived oxidative stress in infertile women and suggest that this method may have potential as a diagnostic tool for the assessment of women infertility. ImpactThis study provides evidence that neutrophil-derived oxidative stress is significantly increased in women infertility and demonstrates the application of a novel Nitroblue Tetrazolium (NBT) assay for assessing oxidative stress in both blood and serum specimens. The significant associations between NBT-reactivity, NBT-positive neutrophils and malondialdehyde levels provide further insight into the contribution of oxidative stress to female reproductive pathophysiology. These findings support the potential utility of the novel NBT method as a simple and reliable diagnostic approach for evaluating oxidative stress in women infertility and provide a foundation for future studies investigating oxidative stress biomarkers in reproductive medicine.

Background. In Europe, first-trimester combined screening with the Fetal Medicine Foundation (FMF) algorithm identifies women at increased risk of preeclampsia who may benefit from personalized aspirin prophylaxis. However, a substantial proportion of early-onset preeclampsia (EOPE) remains undetected at clinically acceptable specificity. Objective. To evaluate the first-trimester performance of MaiRa for early-onset preeclampsia (EOPE) risk stratification by benchmarking it against FMF screening in the same women, characterizing discordant patient-level classification profiles and exploring potential implementation strategies. Study Design. This secondary case-control analysis was nested within the prospective, multicentre PREMOM cohort [NCT04990141], which enrolled women with singleton pregnancies across 14 tertiary hospitals in Spain. First-trimester MaiRa and FMF risk estimates were evaluated in the same 126 pregnant women, comprising 99 uncomplicated controls and 27 EOPE cases, defined by disease onset before 34 weeks. Discrimination was compared using a stratified paired bootstrap analysis of the areas under the receiver-operating-characteristic curves. Performance was assessed at prespecified clinical thresholds, and detection rates were evaluated at fixed false-positive rates. Universal and contingent MaiRa implementation strategies were also evaluated. Results. MaiRa showed greater first-trimester discrimination for EOPE than FMF combined screening (AUC, 0.974 vs 0.900; P=.040) and consistently achieved higher detection rates across fixed false-positive rates. At false-positive rates of 5% and 10%, MaiRa detected 85.2% and 92.6% of EOPE cases, compared with 44.4% and 70.4% for FMF, respectively. Patient-level analysis demonstrated that MaiRa identified 12 of 27 EOPE cases (44.4%) classified as low risk by FMF; these pregnancies generally exhibited less abnormal conventional first-trimester profiles, including fewer maternal risk factors, lower mean arterial pressure and lower uterine artery pulsatility index, yet 8 of 12 (66.7%) subsequently developed severe EOPE. Exploratory implementation analyses showed that universal MaiRa screening achieved the highest EOPE detection, whereas a contingent strategy using FMF for triage and reflex MaiRa testing reduced molecular testing to 35.7% of pregnancies while maintaining 77.8% sensitivity and 97.0% specificity. Conclusion. MaiRa provided greater first-trimester discrimination for EOPE than conventional combined screening and detected additional pregnancies that later developed severe disease despite less abnormal conventional screening profiles. The findings suggest that maternal plasma cfRNA profiling captures biological alterations not fully reflected by combined first-trimester screening and support further prospective evaluation in an independent, unselected obstetric population. Key words: early-onset preeclampsia; first-trimester screening; cell-free RNA; liquid biopsy; Fetal Medicine Foundation algorithm; combined screening; risk stratification; aspirin prophylaxis.

Objective: The purpose of this study was to estimate the negative predictive value (NPV) of screening for group B streptococcus (GBS) colonization in pregnant patients undergoing antepartum hospitalization for GBS colonization status at the time of preterm delivery. Study Design: This prospective, observational cohort study compared GBS colonization status upon initial hospital admission to that at the time of delivery. Pregnant patients at 22 to 35 weeks gestation admitted to the antepartum unit at a tertiary care hospital underwent standard screening for GBS colonization. When preterm labor progressed or iatrogenic preterm delivery was indicated, the GBS colonization test was repeated. Comparison of the sequential test results was performed to determine the NPV of the antepartum screening test for the intrapartum status. Results: 159 eligible patients were enrolled in the study, and 100 completed the study and were included in the analysis. The average gestational age at admission was 30 weeks 1 day (95% confidence interval [CI] 29w4d to 30w6d) and the average duration of pregnancy latency in the study group was 17.5 days (95% CI 15.1 to 19.8). GBS colonization rate at the time of admission was 18% and at the time of delivery was 20%. The NPV of GBS screening at admission was 91.5% (95% CI 83.2 to 96.5%) and the positive predictive value (PPV) was 72.2% (95% CI 46.4 to 90.3%). Conclusion: In a cohort of pregnant patients with preterm pregnancy complications, GBS screening at the time of antepartum hospital admission has an NPV of 91.5% (95% CI 83.2 to 96.5%) for GBS colonization at the time of preterm delivery. This is comparable to the published NPV of routine GBS screening for colonization status at term delivery.

Background: Gastric carcinoma remains a major cause of cancer related mortality worldwide, with tumor progression increasingly recognized as a consequence of complex interactions within the tumor microenvironment. Hypoxia induced signaling, cancer associated fibroblast (CAF) heterogeneity, and immune checkpoint activation play critical roles in tumor progression and immune evasion. However, their integrated relationship in gastric carcinoma remains insufficiently characterized. Objectives: To evaluate the expression of Hypoxia inducible factor 1 alpha and its association with cancer-associated fibroblast subtypes and Programmed death-ligand 1 expression in gastric carcinoma. Methods: This cross sectional analytical study included 100 histologically confirmed gastric carcinoma cases from Satkhira Medical College. Immunohistochemistry was performed for HIF 1 alpha, smooth muscle actin (SMA), fibroblast activation protein (FAP), and PD L1. CAFs were subclassified into myofibroblastic CAFs (myCAFs) and inflammatory CAFs (iCAFs). Associations between biomarkers and clinicopathological variables were analyzed using chi square test, Spearman correlation, and multivariate logistic regression. Receiver operating characteristic (ROC) curve analysis was used to assess model performance. Result: High HIF 1 alpha expression was observed in 55% of cases and demonstrated significant association with poor differentiation (p = 0.001), advanced tumor stage (p = 0.002), and lymph node metastasis (p = 0.001). iCAF predominance was significantly associated with poor differentiation (p = 0.003), advanced stage (p = 0.004), and nodal metastasis (p = 0.004). High PD L1 expression was significantly associated with poor differentiation (p = 0.03), advanced stage (p = 0.001), and lymph node metastasis (p = 0.002). Multivariate logistic regression identified high HIF 1 alpha expression (OR = 3.8, p = 0.001), iCAF dominance (OR = 4.5, p < 0.001), and advanced tumor stage (OR = 2.9, p = 0.004) as independent predictors of high PD L1 expression. Combined high HIF 1 alpha expression and CAF activation demonstrated the highest rate of PD L1 positivity (76.7%, p < 0.001). ROC curve analysis demonstrated good predictive performance of the model with an area under the curve of 0.81. Conclusion: The present study demonstrates a significant interaction between hypoxia, stromal remodeling, and immune checkpoint activation in gastric carcinoma. High HIF 1 alpha expression and inflammatory CAF predominance are strongly associated with aggressive clinicopathological features and increased PD L1 expression, supporting the existence of a coordinated hypoxia stroma immune axis in gastric carcinoma progression. These findings may have potential implications for prognostic stratification and combined targeted therapeutic strategies.

Introduction Accurate measurement of blood loss after caesarean birth is important for early identification of postpartum haemorrhage. Commonly used visual estimation underestimates blood loss. We compared two methods for objectively assessing blood loss. Methods Measured blood loss was obtained by weighing swabs and pads combined with blood from suction and drapes. Calculated blood loss was derived from maternal weight and peripartum haemoglobin change. Data were from the I'M WOMAN trial investigating tranexamic acid for postpartum haemorrhage prevention. This was a secondary analysis of prospectively collected trial data. We reported median (IQR) blood loss, assessed agreement using Bland-Altman analysis and compared the percentages of women exceeding 500 ml, 1000 ml and 1500 ml. We graphed proportional haemoglobin drop by categories of measured blood loss, stratified by anaemia status. We compared AUCs for measured and calculated blood loss predicting haemodynamic compromise (shock index above 1.0) and death or near-miss. Results A total of 10,393 women were included in this study. Median measured and calculated blood loss were 545 ml (IQR 430-700) and 505 ml (IQR 180-908) respectively, with weak correlation (Spearmans rho=0.28). The IQR was wider for calculated blood loss than for measured blood loss, indicating greater variability. Bland-Altman analysis showed a small mean bias of -39 ml but wide limits of agreement (lower -1196 ml, upper 1118 ml). Measured versus calculated blood loss exceeded 500 ml in 60% versus 51% of women, 1000 ml in 7% versus 21%, and 1500 ml in 2% versus 8%. Women without anaemia had a greater proportional haemoglobin drop than women with anaemia for blood losses below 1000 ml. Measured blood loss had better predictive ability for death or near-miss (AUC 0.87 vs 0.76, p<0.001) and haemodynamic compromise (AUC 0.66 vs 0.62, p=0.001). Conclusion While median measured and calculated blood losses were similar, they were only weakly correlated. Calculated blood loss classified more women as having blood loss above higher thresholds. Women without anaemia had a greater proportional haemoglobin drop than women with anaemia for blood loss below 1000 ml. Measured blood loss had a modest advantage in predicting death or near-miss and haemodynamic compromise, but calculated blood loss remains an objective measure suitable as a trial outcome when direct measurement is not feasible.

Background: Prospective pregnancy registries and biobanking infrastructures are essential for future translational studies investigating maternal, placental and offspring health. However, circulating nucleic acid analyses are highly sensitive to preanalytical variability, particularly regarding blood-collection tube type and sample processing conditions. We established a prospective pregnancy registry and biobanking workflow at Cruces University Hospital and evaluated the impact of preanalytical variables on circulating cell-free DNA (cfDNA) and cell-free RNA (cfRNA) preservation in maternal plasma collected at delivery. Methods: The Registry of Pregnant Women at Cruces University Hospital was designed as a prospective infrastructure integrating placental sampling, maternal blood collection and ethically controlled future access to maternal and offspring clinical data. Within this framework, peripheral blood samples from 50 women at delivery were simultaneously collected into EDTA, Norgen and Roche tubes. Plasma samples processed within or after 24 hours following collection underwent cfDNA/cfRNA extraction, electrophoretic profiling, fluorometric quantification and RT-qPCR analyses targeting different stress-related genes. Results: By the end of June 2026, 1,127 women had been prospectively recruited into the registry, with 661 plasma samples, 637 serum samples and 858 sets of four placental biopsies collected, processed and stored in the Basque Biobank. In the preanalytical substudy, EDTA tubes yielded higher cfDNA concentrations, likely reflecting reduced cellular preservation and genomic DNA contamination. In contrast, Roche tubes showed superior cfRNA preservation, with higher cfRNA concentrations and more consistent detection of the characteristic 5S rRNA peak compared with EDTA and Norgen tubes. Processing delays beyond 24 hours reduced cfRNA concentration, while associations between circulating transcripts and gestational age were more consistently detectable in preservative-containing tubes. Conclusions: Prospective infrastructures like ours offer strong foundation for large scale, long-term studies in the framework of the Developmental Origins of Health and Disease hypothesis. Technically, Roche tubes provided superior cfRNA preservation and enhanced sensitivity for detecting subtle biological associations, supporting the importance of standardized preanalytical workflows within prospective pregnancy biobanking resource.

Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, and the great majority of these deaths are caused by metastatic disease. Whether the immunohistochemical (IHC) phenotype of breast cancer is associated with the anatomical site of metastasis has been characterized mainly in high-income, registry-based populations, while data from ecologically stressed and medically under-served regions such as the Lower Aral Sea basin are lacking. Methods: We retrospectively reviewed 652 women diagnosed with breast cancer at the Khorezm Branch of the Republican Specialized Scientific-Practical Medical Center of Oncology and Radiology (Uzbekistan) between 2020 and 2024, of whom 213 had metastatic disease (306 metastatic foci). Histological type was assessed on hematoxylin-eosin and van Gieson-stained sections; quantitative morphometry was performed in Fiji/ImageJ; and HER2, estrogen receptor (ER), progesterone receptor (PR) and Ki-67 were assessed by IHC. The association between marker expression and metastatic site (liver, lung, lymph node) was tested in 187 foci with adequate tissue using the chi-square test, with significance at p < 0.05. Results: Invasive ductal carcinoma predominated. Metastatic site was significantly associated with the IHC phenotype. Liver metastases showed the highest frequency of HER2 3+ (45.7%), ER-negativity (65.2%), PR-negativity (69.6%) and high proliferation (Ki-67 [&ge;] 60%; 47.8%), whereas lymph-node metastases were more often hormone-receptor-positive (ER+ 58.7%; PR+ 52.4%) with lower HER2 3+ (22.2%); lung metastases were intermediate (all p < 0.05). The combination of HER2 3+ and Ki-67 [&ge;] 60% was associated with multi-organ spread. Morphometry corroborated these patterns: liver lesions had larger atypical cells (up to 132.8 m), a higher nuclear-to-cytoplasmic ratio (0.76 vs 0.51) and more extensive necrosis and microvascularity than lymph-node lesions. A pragmatic 5-criterion morphological score (histological type, Ki-67, HER2, ER/PR status, atypical-cell size) stratified metastatic risk into three tiers. Conclusions: In this regional cohort, the IHC phenotype of breast cancer tracked the anatomical site of metastasis, with an aggressive HER2-driven, hormone-receptor-negative profile concentrated in liver metastases and a hormone-receptor-positive profile in lymph-node metastases. These findings reproduce established organotropism patterns in a previously uncharacterized population and support phenotype-aware, site-specific surveillance together with a low-cost morphological risk score for resource-limited settings.

Background: Pregnancy in women with sickle cell disease (SCD) is associated with substantial maternal and perinatal risk, but prospective data from Uganda remain limited. We described the clinical profile, maternal complications, and fetal and neonatal outcomes among pregnant women with confirmed SCD receiving tertiary-level care in Uganda. Methods: We conducted a hospital-based prospective cohort study of 159 pregnant women with confirmed HbSS at Kawempe National Referral Hospital and Mbale Regional Referral Hospital, Uganda, between October 2024 and March 2026. Participants were recruited consecutively during antenatal care or at admission for delivery and followed until maternal discharge. Outcomes were summarized descriptively using explicit denominators. Maternal complications were reported at woman level, while fetal and neonatal outcomes were reported at fetus/newborn level to account for multiple gestations. Secondary regression analyses were treated as exploratory. Results: The mean maternal age was 24.3 years (SD 4.7), and 82/159 women (51.6%) were referred in labor or on admission rather than being known from the study-site antenatal clinics. At baseline, median hemoglobin was 7.5 g/dL (IQR 6.4-8.75), and 118/132 women (89.4%) had hemoglobin below 10 g/dL. The most frequent maternal complications were anemia (93/159, 58.5%), vaso-occlusive crisis (87/159, 54.7%), acute chest syndrome (31/159, 19.5%), recurrent infections (27/159, 17.0%), postpartum hemorrhage (21/159, 13.2%), and preeclampsia (17/159, 10.7%). Maternal death occurred in 15/159 women (9.4%). Among women with recorded mode of delivery, 107/137 (78.1%) delivered by caesarean section. The 159 women contributed 166 fetal outcomes, including seven twin pregnancies. Of these, 22/166 (13.3%) were abortions. Among 144 fetal/newborn outcomes after exclusion of abortions, 119/144 (82.6%) were live births and 25/144 (17.4%) were stillbirths. Early neonatal death occurred in 12/119 live births (10.1%). Low birthweight occurred in 76/117 newborns with recorded birthweight (65.0%), and NICU admission was recorded in 83/118 newborns with recorded admission status (70.3%). Conclusion: Pregnancy among women with SCD receiving tertiary referral care in Uganda was characterized by high maternal morbidity, substantial maternal mortality, and poor fetal and neonatal outcomes. The findings support early identification and referral, structured multidisciplinary antenatal care, reliable transfusion readiness, rapid escalation for acute chest syndrome, preeclampsia and infection, and close coordination between obstetric and neonatal services.

Cell-free DNA (cfDNA), released from apoptotic and necrotic cells into body fluids, represents a non-invasive source of genetic information for disease prediction, diagnosis, and monitoring. However, its low physiological abundance makes cfDNA highly susceptible to pre-analytical influences. In particular, genomic DNA (gDNA) released from lysed white blood cells (WBCs) can contaminate plasma and compromise downstream cfDNA analyses. This study evaluated the impact of different blood collection tubes and isolation methods on cfDNA stability and yield. Blood samples from 13 healthy donors were collected using cfDNA-stabilizing tubes (Cell-Free DNA BCT, Streck; S-Monovette cfDNA Exact, Sarstedt) and stored at room temperature for 1, 5, or 10 days before plasma isolation. CfDNA was extracted using either a magnetic bead-based method or a silica column-based approach. DNA quantity and quality were assessed by fluorometric quantification, automated fragment analysis, and gene-specific quantitative PCR. Streck-based workflows maintained stable cfDNA yields and characteristic mononucleosomal fragmentation profiles across all storage times. In contrast, Sarstedt tubes showed reduced cfDNA concentrations after 5 days and a pronounced increase at 10 Days, accompanied by high-molecular weight DNA patterns consistent with WBC lysis. These trends were largely independent of the extraction method. Overall, the results demonstrate that blood collection tube chemistry critically influences cfDNA integrity during delayed processing. Streck tubes, particularly when combined with QIAamp, provided the most robust and reproducible workflow for routine molecular diagnostics, whereas Sarstedt tubes produced physiologically implausible results after extended storage.

Background: While critical care pharmacists (CCPs) are broadly associated with improvements in outcomes for critically ill patients, operationalizing staffing in the intensive care unit (ICU) requires further study. The purpose of this evaluation was to determine the relationship of a CCP on interprofessional rounds for weekday admissions of ICU patients on patient-centered outcomes. Methods: This post-hoc analysis of the Optimizing Pharmacist-Team Integration for ICU Patient Management (OPTIM) study included adults admitted to an ICU on a weekday in the multicenter observational study. The primary outcome was in-hospital mortality. The primary exposure was level of comprehensive medication management (CMM) during the first 24 hours of ICU stay. A secondary exposure was pharmacist-to-patient ratio. Multivariable generalized estimating equations (GEE) were used to estimate associations between mortality and patient, ICU, and institution variables. Fine-Gray sub-distribution hazards regression estimated hazard of discharge alive (HDA) from the ICU and hospital and hazard of extubation alive. Results: 21,835 patients met inclusion criteria, and 76.1% of patients had CMM delivered on interprofessional rounds. Patients who had no CMM on the first ICU day had an increased risk of mortality of 23% (Odds Ratio (OR) 1.23, 95% Confidence Interval (CI) 1.04-1.46, p=0.02) compared to those who received CMM on interprofessional rounds. Patients with no CMM also had decreased HDA from the ICU and hospital and decreased hazard of extubation alive. No difference was seen in any outcomes when comparing other levels of CMM (CMM delivered outside of interprofessional rounds or abbreviated CMM) compared to CMM delivered on rounds. Conclusions: Absence of pharmacist CMM on the first day of ICU stay for patients with weekday admission was associated with an increased risk of in-hospital mortality, but no difference was seen in other levels of CMM: this signal supports further investigation in prospective analysis.

Objective: To perform internal and external validation of a gradient-boosted decision tree (GBDT) fusion model that integrates zygote morphokinetic parameters with conventional embryo assessment features for blastocyst prediction, and to compare its discriminative performance against senior embryologists. Methods: This retrospective cohort study included 631 normally fertilized zygotes from 218 treatment cycles. A GBDT fusion model integrating 84 zygote morphokinetic parameters and 8 conventional assessment features was evaluated internally (5-fold cross-validation) and externally on a public dataset of 523 embryos with blastocyst outcomes. Model performance was assessed using area under the ROC curve (AUC), area under the precision-recall curve (AUPRC), F1 score, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Discrimination was compared with embryologist consensus using the DeLong test; agreement was assessed with Cohen's kappa. Results: The model achieved an internal AUC of 0.78 (95% CI 0.74-0.82), AUPRC 0.72, F1 0.73, sensitivity 0.74, specificity 0.77, PPV 0.72, and NPV 0.79. External validation on the public dataset demonstrated acceptable generalizability (AUC 0.76, 95% CI 0.71-0.81). The model significantly outperformed embryologist consensus (AUC 0.70, P<0.001) with moderate agreement (kappa=0.56). Decision curve analysis confirmed clinical net benefit at threshold probabilities of 0.15-0.55. Conclusions: The GBDT fusion model integrating zygote morphokinetics with conventional assessment demonstrates good discrimination and external generalizability for blastocyst prediction, providing an interpretable decision-support tool for embryo selection in IVF practice.

P2Y12 receptor (P2RY12), mainly expressed on platelets, is known for its central role in hemostasis. P2RY12 activation is also involved in cancer development through platelet adhesion to cancer cells supporting immune-evasion, promoting tumor angiogenesis and metastasis, among others. P2RY12 is known as an actionable target, and P2RY12 antagonists are in clinical use for cardiovascular diseases. However, very little data are available regarding the protein expression of P2RY12 in lung carcinomas. We performed immunohistochemical staining for P2RY12 in a cohort of non-small cell lung cancer (NSCLC) samples comprising 320 adenocarcinomas (LUAD) and 158 squamous cell carcinomas (LUSC). Results were evaluated using a dual approach combining microscopic assessment and digital image analysis (QuPath). Results were correlated with clinical-pathological data. We found significantly higher P2RY12 protein expression in LUSC compared to LUAD (p<0.001) via eyeballing (absent/low expression in 21.7% (34/158) and moderate/high expression in 78.3% (124/158) of LUSC cases versus absent/low expression in 98.4% (315/320) and moderate/high expression in 1.6% (5/320) of LUAD cases). Digital analysis yielded similar results. High P2RY12 expression was associated with a significantly better 5-year overall survival rate for the entire cohort (p=0.0048) as well as for the LUAD (p=0.015) and LUSC (p=0.05) subgroups. Furthermore, P2RY12 showed excellent discriminatory performance for classifying carcinomas as LUAD or LUSC, with an AUC of 0.916 in ROC-analysis. High P2RY12 expression is linked to a better prognosis and might serve as a promising novel prognostic biomarker for NSCLC. Its assessment could be implemented in future routine diagnostic workup. At the same time, the data suggest that P2RY12 could also serve as a diagnostic marker for LUSC.

Objective: To develop and externally validate a simple antepartum cumulative risk score that stratifies both vaginal birth after cesarean (VBAC) success and neonatal morbidity among patients undergoing trial of labor after cesarean (TOLAC). Methods: This retrospective cohort study was conducted in 2 stages: model development in a single tertiary care center in California (2019 to 2025) and external validation in the National Vital Statistics System natality files (2020 to 2024). The derivation cohort included 1,418 TOLAC attempts; the national validation cohort included 477,693 TOLAC attempts. A point-based score was constructed from routinely available antepartum characteristics associated with VBAC. VBAC success and neonatal intensive care unit (NICU) admission were evaluated across score levels in both cohorts, and model discrimination was assessed using area under the receiver operating characteristic curve (AUC). Results: In the derivation cohort, 1,087 of 1,418 patients (76.7%) achieved VBAC. The logistic regression model showed reasonable discrimination (AUC 0.70, 95% CI 0.67-0.73). VBAC success declined from 89.1% at a score of -1 to 37.8% at scores of 4 or higher, whereas NICU admission increased from 31.7 to 200.0 per 1,000. Uterine rupture occurred in 28 of 1,418 TOLAC attempts (1.97%) and was not predicted by antepartum characteristics. In the national cohort, VBAC success similarly declined from 90.5% to 44.8%, whereas NICU admission increased from 43.8 to 111.1 per 1,000 across the same score range. Conclusion: A simple antepartum risk score stratified both VBAC success and neonatal morbidity in single-center and national TOLAC cohorts, supporting its potential use in patient-centered counseling.

Abstract Introduction Intrauterine fetal death (IUFD) beyond 24 weeks of gestation, particularly when accompanied by an unfavourable cervix, poses a distinct obstetric challenge in achieving safe and timely vaginal delivery while minimising maternal distress. Mifepristone priming followed by misoprostol and intracervical Foley's catheter combined with misoprostol are both established approaches for cervical ripening and induction of labour in this setting, but direct comparative data especially from Indian tertiary care populations remain limited. Methods This prospective comparative study was conducted in the Department of Obstetrics and Gynaecology, Kamla Raja Hospital, Gajra Raja Medical College (GRMC), Gwalior, Madhya Pradesh, India, over a two-year period (November 2020 - October 2022). One hundred and fourteen women with ultrasonography-confirmed IUFD beyond 24 weeks of gestation were alternately allocated to Group A (n=57; oral mifepristone 200 mg followed by gestational-age-adjusted vaginal misoprostol) or Group B (n=57; intracervical 16F Foley's catheter followed by gestational-age-adjusted vaginal misoprostol). Outcomes assessed included pre- and post-induction Bishop score, induction-to-delivery interval, misoprostol dose requirement, need for oxytocin augmentation, mode of delivery, blood loss, maternal complications, pain (visual analogue scale, VAS), and patient satisfaction. Results Baseline age, parity, gestational age, and pre-induction Bishop score were comparable between groups (p>0.05). The mean post-induction (24-hour) Bishop score was significantly higher in Group A (7.39+/- 2.07) than Group B (6.37+/-1.89; p=0.007). The mean induction-to-delivery interval was significantly shorter in Group A (25.43+/- 6.84 hours) than Group B (29.26+/- 5.54 hours; p=0.0014), and the median misoprostol dose requirement was significantly lower in Group A (50 mcg) than Group B (100 mcg; p<0.01). Mode of delivery, blood loss, oxytocin augmentation requirement, and overall maternal complication rates did not differ significantly between groups (all p>0.05). Pain scores were significantly lower in Group A (VAS 2.83+/- 1.16) than Group B (VAS 6.18+/- 1.69; p<0.0001), while patient satisfaction was comparable between groups (96.5% vs. 91.23%; p=0.244). Conclusions Both mifepristone-misoprostol and Foley's catheter-misoprostol regimens are safe and effective methods for induction of labour following IUFD beyond 24 weeks of gestation with an unfavourable cervix. Mifepristone priming achieved a shorter induction-to-delivery interval, lower total misoprostol requirement, and substantially less procedural pain, making it an attractive first-line option where available, while Foley's catheter remains a safe, low-cost, and widely accessible alternative, notwithstanding lower patient comfort.

Background: In resource-limited settings, a critical bottleneck in cervical cancer prevention is the lack of practical strategies to triage high-risk human papillomavirus (HR-HPV)- positive women. Therefore, this study aimed to develop and internally validate a genotype-specific risk stratification model. Methods: A cross-sectional study enrolled 555 women in Cameroon. Data collection integrated cervical cytology and HPV genotyping using Abbott m2000rt and Sacace multiplex systems. An iterative modeling approach with bootstrap validation was used to develop the model and address model instability. HR-HPV genotypes were transformed into a hierarchical risk variable due to sparsity and integrated with significant predictors. The final model was translated into a scoring system, and the risk gradients and performances were evaluated at two thresholds. Data was analyzed using SPSS 27.0. Results: The mean age was 44.8 years, and the prevalence of HR-HPV was 26.5% (147/555). The final model, incorporating HPV categories, age, and tobacco, demonstrated moderate discriminative ability (AUC=0.702, 0.642-0.762) with a good calibration (Hosmer-Lemeshow {chi}{superscript 2}=4.05, p=0.399). The scoring system assigned women to risk groups based on their total scores which produced a clear monotonic risk gradient; the observed probability of high-grade lesions/cancer ranged from 15% (score 0) to >65% (score [&ge;]4). At a conservative threshold ([&ge;]4 points), 4.7% (26/555) of women were classified as high-risk, concentrating 46% (6/13) of cancers (positive predictive value[PPV]=58%) while a sensitive threshold ([&ge;]3 points) had 16.8% (93/555) high-risk, concentrating 77% (10/13) cancers (PPV=38%). Both thresholds maintained a high negative predictive value (>95%). Conclusion: This bootstrap-validated, risk-stratification tool is a proof-of-concept in resource limited settings that assigns HR-HPV-positive women to distinct management pathways using three variables. After refining through a longitudinal study and external validation, this scoring system can improve the efficiency of cervical cancer screening programs in low-resource settings.

Background: Mortality prediction models often combine early electronic health record data, but the relative prognostic value of baseline vulnerability, physiological severity, treatment exposure, and procedure burden remains unclear. Objective: To compare routinely available first-24-hour clinical domains for visit-level 30-day mortality prediction and assess whether domain-level patterns replicated in MIMIC-IV. Methods: We used CHoRUS, an OMOP-formatted acute-care dataset, with independent domain-level replication in MIMIC-IV. CHoRUS included 22,098 visits among 5,892 unique patients, with 1,004 30-day mortality events and 4.5% mortality prevalence. MIMIC-IV included 23,000 acute-care visits among 10,006 unique patients, with 819 events and 3.6% prevalence. Across both datasets, 45,098 visits and 15,898 unique patients were analyzed. Predictors were restricted to the first 24 hours after visit start. Performance was evaluated using AUPRC, AUROC, Brier score, calibration, sensitivity at 90% specificity, highest-risk 10% analyses, decision-curve analysis, and SHAP summaries. Because 30-day mortality was infrequent, the classification task was class-imbalanced. Accordingly, AUPRC was interpreted relative to the prevalence-based no-skill baseline, rather than as an absolute measure alone. Results and Conclusion: Physiological severity produced the largest improvement beyond baseline in CHoRUS, with median AUPRC 0.38 and median AUROC 0.86, and showed the same primary domain-level pattern in MIMIC-IV. Treatment exposure and procedure burden provided smaller gains. In CHoRUS, the best pairwise model combined baseline, physiological severity, and procedure burden features, with median AUPRC 0.41; the all-domain model was slightly lower, with median AUPRC 0.40 and median AUROC 0.86. In MIMIC-IV, the all-domain model had the highest median AUPRC, 0.25, only modestly above the best pairwise model. First-24-hour physiological severity features therefore provided the most consistent prognostic information across datasets, supporting parsimonious, clinically interpretable acute-care risk models centered on high-quality early physiological data.

Purpose To determine the frequency of echocardiographic abnormalities in women with preeclampsia with severe features. To describe the spectrum and types of echocardiographic abnormalities associated with preeclampsia with severe features. Method This is a Prospective observational study conducted in Vani Vilas hospital attached to Bangalore Medical College and Research Institute, Bangalore from January 2023 to December 2025. 560 pregnant women diagnosed with severe preeclampsia(SPE) were included in the study. Chronic hypertension without superimposed preeclampsia, underlying cardiac diseases and previous history of peripartum cardiomyopathy were excluded from the study. Transthoracic echocardiography-TTE (2D ECHO) was done to evaluate cardiac structure and function. Echocardiographic abnormalities identified during the study were documented and analysed using descriptive statistical methods. Results Abnormalities in ECHO was noted in 23.03%. A unique finding was the documentation of elevated pulmonary artery systolic pressures (PASP) suggestive of Pulmonary Hypertension (PH) (PASP >35 mm HG) among 20.25% of the participants. It was also the commonest abnormality on ECHO. Mild PH was the commonest (15.71%), moderate PH was seen in 3.92% and severe PH in 0.71% of cases. Next most frequent abnormality was moderate to severe valvular regurgitation (10%), followed by left ventricular hypertrophy (5.53%). Diastolic dysfunction (DD) was seen in 3.92%, systolic dysfunction(SD) in 3.57%, chamber dilatation in 3.57% and LV global hypokinesia in 3.03% cases of SPE Conclusion Preeclampsia with severe features (SPE) is associated with 23.03% abnormalities on echocardiography. SPE is associated with systolic dysfunction, diastolic dysfunction, chamber dilatation, valvular regurgitation, left ventricular hypertrophy and pulmonary hypertension.