Category: Nevin Manimala

Isr Med Assoc J. 2025 Aug;27(8):504-509.

ABSTRACT

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin tumor with an increasing incidence in Western countries. Predominantly affecting older individuals, MCC represents less than 1% of malignant skin tumors.

OBJECTIVES: To characterize the clinical presentation, therapeutic interventions, and follow-up outcomes of MCC patients. To promote heightened clinical awareness regarding the early recognition and diagnosis of MCC.

METHODS: We conducted a retrospective cohort study analyzing medical records of MCC patients at the Shaare Zedek Medical Center between 2015-2022. From 19 initially identified patients, 17 met the inclusion criteria. Data collection included demographic, epidemiological, clinical, and pathological characteristics.

RESULTS: The study included 17 patients, predominantly of Jewish origin, with a mean age of 70.06 years; 58.8% female. Medical co-morbidities included 64.7% hypertension and 35.3% diabetes. MCC tumors were predominantly left-sided (58.8%), with varied locations including limbs, trunk, and face. Surgical treatment consisted of excision and primary closure (64.7%) or skin grafting (23.5%). The average tumor diameter was 3.41 cm clinically and 3.83 cm pathologically. Lymph node involvement occurred in 29.4% of cases; 23.5% showed metastatic disease at diagnosis, with metastases diffused in different body areas. Kaplan-Meier survival analysis showed no statistically significant differences across most variables, except for a significantly lower survival rate in patients with ischemic heart disease (P = 0.009).

CONCLUSIONS: Our study reveals unique characteristics of MCC, predominance of female patients, and a slightly younger average diagnosis age compared to existing literature. The 2-year survival rate in our cohort was 82%. The study underscores the importance of early detection and diagnosis of MCC, thereby enhancing clinical awareness and improving patient outcomes.

PMID:40819201

Sci Rep. 2025 Aug 16;15(1):30011. doi: 10.1038/s41598-025-15185-4.

ABSTRACT

Despite advancements in treatment strategies, glioblastoma, also known as GBM, remains an exceptionally aggressive primary brain tumor with a grim prognosis. Despite innovations in treatment strategies, GBM continues to pose significant challenges. The assessment of GBM mainly depends on neuroimaging methods, with contrast-enhanced magnetic resonance imaging (MRI) being the widely accepted standard. In recent years, positron emission tomography (PET) has emerged as a supplementary imaging modality offering insights into the biological behavior and aggressiveness of GBM tumors. PET, often referred to as PET, complements MRI in the diagnostic process of GBM. The objective of this study was to explore the potential advantages of combining PET and MRI in diagnosing GBM. Twenty-two patients diagnosed with GBM underwent four 18 F-fluorothymidine (FLT)-PET/MRI examinations before and during treatment. Advanced image analysis methods, including MATLAB and the imlook4d analysis platform, were employed. These methods encompassed adaptive threshold algorithms, batch processing pipelines, and image attribute extraction algorithms. MRI evaluations revealed significant variations in tumor response to radiation therapy among patients with long-term and short-term survival rates, as determined by the study findings (p < 0.04). Furthermore, PET measurements, including maximum standardized uptake value (SUVmax), PET tumor volume, and total lesion activity (TLA), showed trends toward statistical significance; however, the differences did not reach conventional significance thresholds. These results underscore the need for further research into the therapeutic efficacy of PET parameters in managing this aggressive brain tumor. The findings of this study highlight the potential of fusion imaging using PET and MRI as an effective diagnostic technique for glioblastoma multiforme (GBM) and emphasize the importance of ongoing research in this area to improve patient outcomes.

PMID:40819176 | DOI:10.1038/s41598-025-15185-4

Sci Data. 2025 Aug 16;12(1):1437. doi: 10.1038/s41597-025-05757-4.

ABSTRACT

Accurate diagnosis of thyroid nodules using ultrasonography is a highly valuable, but challenging task. With the emergence of artificial intelligence, deep learning based methods can provide assistance to radiologists, whose performance heavily depends on the quantity and quality of training data, but current ultrasound image datasets for thyroid nodule either directly utilize the TI-RADS assessments as labels or are not publicly available. Faced with these issues, an open-access ultrasound image dataset for thyroid nodule detection and classification is proposed, i.e. the TN5000, which comprises 5,000 B-mode ultrasound images of thyroid nodule, as well as complete annotations and biopsy confirmations by expert radiologists. Additionally, the statistical characteristics of this proposed dataset have been analyzed clearly, some baseline methods for the detection and classification of thyroid nodules are recommended as the benchmark, along with their evaluation results. To our best knowledge, TN5000 is the largest open-access ultrasound image dataset of thyroid nodule with professional labeling, and is the first ultrasound image dataset designed both for the thyroid nodule detection and classification. These kinds of images with annotations can contribute to analyze the intrinsic properties of thyroid nodules and to determine the necessity of FNA biopsy, which are crucial in ultrasound diagnosis.

PMID:40819171 | DOI:10.1038/s41597-025-05757-4

BMC Musculoskelet Disord. 2025 Aug 16;26(1):791. doi: 10.1186/s12891-025-08998-x.

ABSTRACT

OBJECTIVE: To identify the risk factors for subsequent vertebral fractures after percutaneous vertebral augmentation through the meta-analysis.

METHODS: Articles from 2019 to 2024 were retrieved from PubMed, Cochrane Library, Embase, and Web of Science. The quality of included studies was assessed using the Newcastle-Ottawa Scale (NOS), while data analysis was performed with R (The R Project for Statistical Computing).

RESULTS: Fourteen articles comprising data from 5,673 patients were included in the analysis. Statistically significant differences were identified for age, gender, T-score (measured by dual-energy X-ray absorptiometry), body mass index (BMI), Computed tomography Hounsfield unit (CT HU) value, intravertebral cleft (IVC), multi-segment vertebral fractures, and bone cement leakage. In contrast, no statistically significant differences were observed for hypertension history, diabetes history, thoracolumbar vertebral fracture, postoperative Cobb angle, surgical method（percutaneous vertebroplasty/percutaneous kyphoplasty）, puncture method (unilateral/bilateral puncture), or bone cement volume.

CONCLUSION: In Asian populations, advanced age, female, low T-score, low BMI, low CT HU values, presence of IVC, multi-segment vertebral fractures, and bone cement leakage are identified as significant risk factors for subsequent vertebral fractures following PVA. Conversely, a history of anti-osteoporosis treatment is identified as a protective factor, whereas hypertension history, diabetes history, thoracolumbar vertebral fracture, postoperative Cobb angle, surgical method, puncture method, and bone cement volume demonstrate no significant correlation with subsequent vertebral fractures after PVA.

PMID:40819163 | DOI:10.1186/s12891-025-08998-x

Eur Radiol. 2025 Aug 16. doi: 10.1007/s00330-025-11844-2. Online ahead of print.

ABSTRACT

OBJECTIVES: This systematic review and meta-analysis aimed to assess the diagnostic accuracy of CT in differentiating high-risk from low-risk colon cancer, with a focus on staging parameters and the impact of CT slice thickness.

MATERIALS AND METHODS: A systematic search of Ovid MEDLINE and Embase.com was conducted from January 1, 2015, to September 24, 2024, to identify studies evaluating CT-based staging accuracy using histopathology as the reference standard. The QUADAS-2 tool assessed the risk of bias. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a bivariate random-effects model. Subgroup analyses explored the influence of CT techniques, slice thickness, and study design on diagnostic performance.

RESULTS: The meta-analysis included forty-four studies. CT demonstrated 83% sensitivity (95% CI, 79-86%) and 70% specificity (95% CI, 66-74%) for detecting pT3-T4 tumors (DOR: 10.0). For pT3cd-T4 (> 5 mm muscularis propria invasion), sensitivity was 67% (61-73%), specificity 88% (83-92%) and DOR 13.7 (9.0-21.0). Detection of pN+ yielded 64% sensitivity (60-68%), 67% specificity (62-72%) and DOR of 3.5 (3.0-4.2). Sensitivity for extramural venous invasion (EMVI+) was 49% (41-56%), with 77% specificity (67-84%) and DOR 3.0 (2.0-4.4). Studies with < 5 mm slice thickness showed higher sensitivity but lower specificity. High I² values indicated substantial heterogeneity across studies.

CONCLUSION: CT demonstrates high sensitivity for detecting T3-T4 colon cancer but moderate sensitivity for nodal involvement and EMVI+. Diagnostic performance varies with technical factors, emphasizing the need for standardized imaging protocols and supplementary diagnostic tools to improve colon cancer staging.

REGISTRATION: PROSPERO (International Prospective Register of Systematic Reviews) CRD42022374615.

KEY POINTS: Question Accurate CT staging is crucial for guiding neoadjuvant therapy in colon cancer, but its ability to distinguish high-risk from low-risk cases remains uncertain. Findings CT showed high sensitivity for distinguishing pT3-T4 tumors but only moderate sensitivity for pT3cd-T4, nodal involvement, and extramural venous invasion. Clinical relevance This systematic review critically evaluates CT diagnostic accuracy in colon cancer staging, revealing its strengths and limitations. The findings highlight the need for optimized imaging protocols and complementary tools to enhance risk stratification and guide clinical decisions.

PMID:40819156 | DOI:10.1007/s00330-025-11844-2

Ther Innov Regul Sci. 2025 Aug 16. doi: 10.1007/s43441-025-00861-4. Online ahead of print.

ABSTRACT

BACKGROUND: Cardiovascular and oncology trials increasingly require large sample sizes and long follow-up periods. Several approaches have been developed to optimize sample size including sample size re-estimation based on the promising zone approach. With time-to-event endpoints, methods traditionally used to test for treatment effects are based on proportional hazards assumptions, which may not always hold. We propose an adaptive design wherein using interim data, Bayesian computation of Predictive Power (PP) guides the increase in sample size and/or the minimum follow-up duration.

METHODS: PROTECT IV is designed to evaluate mechanical circulatory support device vs. standard of care during high-risk percutaneous coronary intervention with the initial enrolment of 1252 patients and initial minimum follow-up of 12 months. The primary endpoint is the composite rate of all-cause death, stroke, durable left ventricular assist device implant or heart transplant, myocardial infarction or hospitalization for cardiovascular causes. The study will employ an adaptive increase in sample size and/or minimum follow-up at the Interim analysis. The adaptations utilize simulations to choose a new sample size up to 2500 and new minimal follow-up time up to 36 months that provides PP of at least 90%.

RESULTS: Via extensive simulations, we have examined the utility of the proposed design for situations like delayed treatment effect, early benefit only and in general crossing of survival curves. Separate Piece-wise Constant Hazard Models with non-influential (weakly-informative) Gamma-priors are fitted to the interim data for the two treatment arms, free from the proportional hazards assumptions, thus yielding more robust interim decision making. The Bayesian modeling facilitates sampling of future observations from the posterior predictive distributions with the predictive probability of trial success is computed via Monte-Carlo simulations. Simulation results show that the fitting Bayesian Piecewise Exponential models to the interim data along with the use of the posterior predictive distributions lead to more “specific” adaptation rules compared to the frequentist Conditional Power while the overall operating characteristics, type-I error and power, are similar.

CONCLUSION: For clinical trials with time-to-event endpoints and where crossing of survival curves might be anticipated at the planning stage, flexible modeling along with wholesome use of patient-level data such as the calculation of predictive power as proposed here, may be more robust and efficient in making interim decisions such as sample size increase than the traditional use of the conditional power based on summary statistics and proportional hazards assumption.

PMID:40819155 | DOI:10.1007/s43441-025-00861-4

Sci Rep. 2025 Aug 16;15(1):29995. doi: 10.1038/s41598-025-15761-8.

ABSTRACT

Acute block of hERG channels is the most common mechanism underlying drug-induced QT_C prolongation and potentially fatal Torsade de Pointes arrhythmia. Updates to ICH E14 Q&As now allow for using negative nonclinical data, including hERG, to support QT_C risk assessment in late-stage clinical development. To interpret the hERG results, understanding hERG assay reproducibility or hERG data variability is pivotal. Protocol and best practice recommendations have been provided with the goal of minimizing lab-to-lab data differences, but the impact remains unclear. To fill this knowledge gap, hERG data from a HESI-coordinated multi-laboratory study were leveraged. Using standardized protocol and following best practices for patch clamp studies, five laboratories tested 28 drugs using the manual patch clamp technique. Systematic differences in block potencies were observed for data generated by one laboratory for the first 21 drugs, and these differences disappeared for the last seven drugs. Exposure, pharmacological sensitivity of the cell lines, and cell/data qualities were ruled out as the factors underlying systematic differences. All laboratories retested two drugs and obtained results within 1.6X of the initial testings, except for another laboratory that obtained data for one drug that differed from its initial testing by 7.6X. Descriptive statistics and meta-analysis were applied to the dataset to estimate what the distribution in hERG block potencies would be if a laboratory were to test the same drug repeatedly. This measure, or hERG data variability, was ~ 5X. Based on these results, hERG block potency values within 5X of each other should not be considered different, since these values are within the natural data distribution of the hERG assay; laboratory-specific safety margin threshold may be required to account for systematic data differences.

PMID:40819150 | DOI:10.1038/s41598-025-15761-8

Ann Surg Oncol. 2025 Aug 16. doi: 10.1245/s10434-025-18037-7. Online ahead of print.

ABSTRACT

BACKGROUND: Stricture is a major adverse event following esophageal endoscopic submucosal dissection (ESD). Although postoperative esophageal stenosis after ESD is clearly associated with large mucosal defects, there are no quantitative criteria for the degree of the defect. We aimed to examine the predictive factors associated with the development of esophageal stenosis after ESD, and to explore quantitative indicators for predicting postoperative stenosis.

PATIENTS AND METHODS: A retrospective analysis of endoscopic data from patients with esophageal ESD was conducted. The area and perimeter of the resected mucosa defect were measured by Image Pro Plus 6.0. Logistic regression, receiver operating characteristic (ROC) curve, and nomogram model were adopted for analysis.

RESULTS: The median area of resected mucosal defect was 527.74 mm² (IQR 322.80-823.48), the median perimeter was 91.75 mm (IQR 71.69-118.32), and the median circumferential ratio was 33% (IQR 20-40). Owing to collinearity between the perimeter and area of the resected mucosal defect, these variables were analyzed individually in the multivariate analysis (r = 0.958, P < 0.001). All three factors mentioned above were identified as independent risk factors for postoperative esophageal stenosis (P < 0.05), while intraoperative muscularis propria injury was not (P > 0.05). On the basis of the above results, prediction models were constructed and validated internally. The concordance statistics (C-statistics) of the training and validation sets including perimeter or area were 0.875 and 0.830 and 0.747 and 0.835, respectively. The Hosmer-Lemeshow goodness-of-fit test results were not significant (P > 0.05).

CONCLUSIONS: Accurate quantification of the area and perimeter of resected mucosa by image analysis technology can accurately predict esophageal stenosis after ESD.

PMID:40819145 | DOI:10.1245/s10434-025-18037-7

Sci Rep. 2025 Aug 16;15(1):30030. doi: 10.1038/s41598-025-14973-2.

ABSTRACT

There is a knowledge gap about the quantitative aspects of mycorrhizal fungi’s influence on ecological succession on tailings. Here, we demonstrate that inoculating mine tailings with 2% fungi yields significantly better results in terms of plant biomass and lower lipid peroxidation compared to 1% and 0%, both when growing Agrostis capillaris alone and in combination with Melilotus albus. Lipid peroxidation in the A. capillaris is positively predicted by Cu, and negatively predicted by the total Kjeldahl nitrogen in plants. The biomass of M. albus is positively predicted by the N/P ratio, and negatively by Cu concentration in the plant. This improvement was related to differences between the Technosols properties at the end of the experiment (pH, EC, N-NH₄⁺, N-NO₃^–), which modulated the changes of the tailing material properties from the wet to the dry state, and to differences in the accumulation factors of Cu and Pb from substrate to plant roots, and of the transfer factors from roots to aboveground parts. This is the first time that the effects of such a slight increase in fungal inoculum percentage have been reported. Fine-tuning the fungi treatment can lead to cost-effective techniques for tailings remediation. Block diagrams of an eco-technology are proposed.

PMID:40819128 | DOI:10.1038/s41598-025-14973-2

Sci Rep. 2025 Aug 16;15(1):29991. doi: 10.1038/s41598-025-15815-x.

ABSTRACT

Mineral elements in colostrum play crucial roles in neonatal growth and development. This study assessed the concentrations of ten essential mineral elements in the colostrum of moderately preterm and full-term mothers in Ghana, and examined their associations with maternal characteristics. A total of 47 mothers provided single 12 mL colostrum samples collected between postpartum days 1 to 4 using standardized, aseptic manual expression procedures. The samples were digested and analyzed using ICP-OES. Statistical analyses included tests for normality, Spearman correlation, and group comparisons using Kruskal-Wallis and Mann-Whitney U tests. The concentrations ranged from 0.1 ± 0.0 mg/L (Se) to 602.6 ± 77.6 mg/L (K). Significant positive correlations were observed among several mineral pairs. Notably, potassium levels were significantly associated with maternal employment status (p = 0.047), and zinc levels were significantly related to maternal parity (p = 0.028). Although differences between preterm and full-term samples were not statistically significant, preterm colostrum showed trends of higher zinc and potassium concentrations. Compared to global data, the Ghanaian samples exhibited relatively elevated levels of phosphorus, sodium, and selenium. These findings provide foundational data on early breast milk composition in Ghana and highlight maternal and gestational factors that may influence neonatal mineral intake.

PMID:40819102 | DOI:10.1038/s41598-025-15815-x