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Nevin Manimala Statistics

The impact of white matter lesions on seizure recurrence after first epileptic seizures in the elderly: a prospective study

Neurol Res Pract. 2025 May 20;7(1):36. doi: 10.1186/s42466-025-00391-2.

ABSTRACT

BACKGROUND: Despite considerable previous research, to what degree white matter lesions (WML) may be epileptogenic remains unclear. Therefore, the decision of initiating treatment with antiseizure medication (ASM) can be challenging in patients with only WML on neuroimaging. In this prospective study we assessed whether the prevalence, localization or severity of WML impact the risk of seizure recurrence in patients aged 60 years or older after first-time seizures.

METHODS: Data was analyzed from 168 patients, aged ≥ 60 years-old who had experienced a previous unprovoked seizure and had either a potentially epileptogenic lesion or WML on neuroimaging. The frequency of seizure recurrence was documented after 6, 12, and 24 months. Pearson´s chi-square test of independence (categorical variables) and the independent Student´s t-test (continuous variables) were used to analyze intergroup differences. Binary logistic regressions were calculated to examine the influence of WML locations as a predictor of seizure recurrence. Kaplan-Meier survival analyses and log-rank statistics were performed to determine the cumulative recurrence rates between the groups.

RESULTS: Fifteen patients had only potentially epileptogenic lesions on neuroimaging (EPI) and 93 showed WML only (OWML). Sixty patients showed both of them on neuroimaging (EWML). Frontal and parieto-occipital were the predominant WML locations. Neither severity nor location of WML had a significant impact on recurrence rates. The two-year cumulative probability of becoming seizure-free was significantly lower in the EPI group compared to the EWML (χ2 [1] = 4.425, p = 0.035) and the OWML group (χ2 [1] = 13.094, p < 0.001). A significant association between interictal epileptiform discharges in EEG and seizure recurrence was found in OWML patients (p = 0.004).

CONCLUSION: We could not find any association between prevalence, severity or location of WML and seizure recurrence after first seizures in the elderly. Therefore, treatment with ASM should be started with caution in those patients. Our results show a trend of WML not having epileptogenic potential, but further studies are needed to get better evidence.

TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration and Results, NCT06836687, AZ 199/17, release: 03/19/2024 retrospectively registered. https://register.

CLINICALTRIALS: gov/prs/beta/studies/S000EBC700000025/recordSummary.

PMID:40394715 | DOI:10.1186/s42466-025-00391-2

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Nevin Manimala Statistics

Impact of ventilatory and laboratory parameter trajectories on short-term survival in acute respiratory distress syndrome patients: a retrospective study using joint models

Eur J Med Res. 2025 May 20;30(1):406. doi: 10.1186/s40001-025-02650-z.

ABSTRACT

BACKGROUND: Clinical research is based on the parameters at defined time points, such as admission, diagnosis or discharge, for the purpose of risk factor analysis in relation to outcome. However, these parameters are collected with greater frequency in clinical practice. The objective of this study was to demonstrate a correlation between the time course of closely monitored parameters, such as blood gases, ventilatory parameters or routine laboratory values, and the survival of patients with acute respiratory distress syndrome (ARDS) caused by pneumonia.

METHODS: This single-center, retrospective study included 274 ARDS patients with primary pneumonia requiring invasive mechanical ventilation. Patients were treated at a German university hospital between January 2014 and April 2021. Ethical approval was obtained from the local ethics committee (BO-EK-374072021). Longitudinal data on ventilatory and inflammatory parameters were collected during ICU stays. The analysis was conducted using descriptive statistics, cox regression and joint models. Joint modelling was used to integrate the progression of these parameters with survival outcomes, with the modelling of longitudinal data performed using quadratic B-splines.

RESULTS: The cohort included 274 patients, with an ICU mortality rate of 49.6%. Non-survivors were older (67 vs. 62 years, p < 0.001) and had higher SOFA scores at admission (10 vs. 8, p < 0.001). Differences in ventilatory parameters, including driving pressure and the PaO₂/FIO₂ ratio, as well as inflammatory markers such as procalcitonin, were observed between survivors and non-survivors during the ICU stay. The joint model analysis revealed a significant effect of the time course of parameters, such as positive end-expiratory pressure (PEEP), peak airway pressure (Ppeak), driving pressure, minute ventilation, tidal volume, C-reactive protein (CRP) and procalcitonin on mortality. The increase over time (slope-dependent association) for these parameters was strongly associated with mortality. For example, driving pressure was associated with mortality both by its current value (HR 1.16) and by its increase over time (HR 7.10). Similarly, tidal volume (HR 0.72 and 0.07), minute ventilation (HR 0.91 and 0.36), PEEP (HR 1.32 and 13.52), Ppeak (HR 1.20 and 3.28) and CRP (HR 1.14 and 4.25) showed a current value association and a strong slope-dependent association with mortality.

CONCLUSION: This study underscores the importance of analyzing the dynamics of clinical parameters rather than static values for ARDS management. The findings suggest that changes in routine clinical parameters over time provide valuable prognostic information and should be prioritized in risk assessment and therapeutic decision making.

PMID:40394713 | DOI:10.1186/s40001-025-02650-z

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Nevin Manimala Statistics

Developing and validating a predictive model for all-cause mortality in patients with metabolic dysfunction-associated steatotic liver disease

Diabetol Metab Syndr. 2025 May 20;17(1):161. doi: 10.1186/s13098-025-01724-6.

ABSTRACT

OBJECTIVE: This study aimed to construct a scientific, accurate, and readily applicable clinical all-cause mortality prediction model for patients with metabolic dysfunction-associated steatotic liver disease (MASLD) to enhance the efficiency of disease management and improve patient prognosis.

METHODS: This study was a retrospective cohort study based on the National Health and Nutrition Examination Survey database. The 17,861 participants diagnosed with MASLD were randomly assigned to either a training cohort (n = 12,503) or a validation cohort (n = 5358). Potential predictors were subjected to LASSO regression analysis, and independent risk factors were subsequently identified through multivariate Cox regression analysis. An all-cause mortality prediction model was constructed based on the significant predictors, and a nomogram was generated to illustrate the survival probability of patients at various time points. The model’s performance was evaluated using receiver operating characteristic (ROC), calibration, and decision curve analysis (DCA) curves.

RESULTS: A multiple Cox regression analysis identified several independent predictors significantly influencing all-cause mortality in patients with MASLD. These included gender, age, smoking status, hypertension, red blood cell count, albumin, glutamyl transpeptidase, glycosylated hemoglobin, and creatinine. The constructed predictive model demonstrated high accuracy in the training and validation cohorts, with AUC values approaching 0.85 at 3, 5, and 10 years, respectively. Calibration and DCA curves were employed to verify the stability and generalizability of the model.

CONCLUSIONS: We successfully constructed and validated an all-cause mortality prediction model for MASLD patients. This model provides a powerful tool for clinical risk assessment and treatment decision-making.

PMID:40394710 | DOI:10.1186/s13098-025-01724-6

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mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED): statistical analysis plan

Trials. 2025 May 20;26(1):166. doi: 10.1186/s13063-025-08865-z.

ABSTRACT

BACKGROUND: Type 2 diabetes and prediabetes represent significant global health challenges, with physical activity (PA) being essential for disease management and prevention. Despite the well-documented benefits, many individuals with (pre)diabetes remain insufficiently active. General practitioners (GP) provide an accessible platform for delivering interventions; however, integrating PA interventions into routine care is hindered by resource constraints.

OBJECTIVES: The ENERGISED trial aims to address these barriers through an innovative GP-initiated mHealth intervention combining wearable technology and just-in-time adaptive interventions.

METHODS: The ENERGISED trial is a pragmatic, 12-month, multicentre, randomised controlled trial, assessing a GP-initiated mHealth intervention to increase PA and reduce sedentary behaviour in patients with type 2 diabetes and prediabetes. The primary outcome is daily step count, assessed via wrist-worn accelerometry. The primary analysis follows the intention-to-treat principle, using mixed models for repeated measures. Missing data will be handled under the missing-at-random assumption, with sensitivity analyses exploring robustness through reference-based multiple imputation. The trial incorporates the estimand framework to provide transparent and structured treatment effect estimation.

DISCUSSION: This statistical analysis plan outlines a robust approach to addressing participant non-adherence, protocol violations, and missing data. By adopting the estimand framework and pre-specified sensitivity analyses, the plan ensures methodological rigour while enhancing the interpretability and applicability of results.

CONCLUSIONS: The ENERGISED trial leverages innovative mHealth strategies within primary care to promote PA in individuals with (pre)diabetes. The pre-specified statistical framework provides a comprehensive guide for analysing trial data and contributes to advancing best practices in behavioural intervention trials for public health.

TRIAL REGISTRATION: ClinicalTrials.gov NCT05351359 . Registered on April 28, 2022.

PMID:40394706 | DOI:10.1186/s13063-025-08865-z

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HHLA2 activates c-Met and identifies patients for targeted therapy in hepatocellular carcinoma

J Exp Clin Cancer Res. 2025 May 20;44(1):153. doi: 10.1186/s13046-025-03407-6.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is a highly aggressive malignancy with limited treatment options in advanced stages. While c-Met is a promising therapeutic target in HCC, identifying patients who will benefit from c-Met inhibitors remains a significant challenge. This study aimed to investigate the role of HHLA2, a B7 family member, in HCC and its potential as a liquid biopsy marker for c-Met inhibitor therapy.

METHODS: HHLA2 expression was analyzed in clinical HCC samples and public databases. In vitro studies using HCC cell lines assessed HHLA2’s impact on proliferation, migration, invasion, and angiogenesis. In vivo studies using mouse models (orthotopic xenografts and hydrodynamic tail vein injection) evaluated HHLA2’s role in tumor growth and metastasis. Mass spectrometry, co-immunoprecipitation, split-luciferase, and ELISA assays were used to investigate HHLA2-c-Met interactions. Patient-derived organoids (PDOs) were used to assess drug response. Statistical analyses included Student’s t-tests, ANOVA, and Cox regression.

RESULTS: HHLA2 was found to be upregulated in HCC and associated with advanced disease, aggressive clinicopathological features, and poor prognosis. HHLA2 interacted with and constitutively activated c-Met, leading to increased expression of MMP9 and VEGFA, enhancing HCC cell proliferation, invasion, and angiogenesis. HHLA2 also suppressed hepatic natural killer cell infiltration in vivo. Inhibition of c-Met with PHA665752 effectively reversed HHLA2-mediated tumor-promoting effects in vitro and in vivo. HHLA2 expression in HCC tissues correlated with c-Met phosphorylation, and HHLA2 could be detected in the serum of patients with high tumor HHLA2 levels. PDOs with high HHLA2 expression exhibited increased sensitivity to c-Met inhibition.

CONCLUSIONS: HHLA2 acts as an oncogene in HCC by activating c-Met, promoting tumor progression and metastasis. HHLA2 expression correlates with c-Met activation and predicts poor prognosis in HCC patients. Importantly, HHLA2 can serve as a stratification marker for c-Met inhibitor therapy, potentially enabling a personalized approach to improve therapeutic outcomes in this challenging disease.

PMID:40394703 | DOI:10.1186/s13046-025-03407-6

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Nevin Manimala Statistics

Green, white and simple polymeric-coated graphite sensor for rapid in situ determination of acrylamide in food products

BMC Chem. 2025 May 20;19(1):134. doi: 10.1186/s13065-025-01501-6.

ABSTRACT

Acrylamide (ACM) is a food processing contaminant classified as a probable genotoxic and carcinogenic substance for humans. The rapid and economical determination of ACM in food products poses a major challenge for food safety. This research intended to fabricate a simple, selective, and cost-effective polymeric-coated graphite sensor. This potentiometric sensor is suitable for direct and in situ ACM analysis in food products without tedious sample pretreatment procedures. The sensor was successfully developed based on the ion association complex of the ACM cation with sodium tetraphenylborate (TPB) anion as an ion exchange site, using dibutyl phthalate (DBP) as a plasticizer. The sensor demonstrated a fast, stable, selective, and linear Nernstian response (57.45 mV/decade) over a wide concentration range from 1 × 10-7 to 1 × 10-1 M of ACM, with a detection limit of 1 × 10-8 M. The sensor’s selectivity behavior, response time, lifetime, pH working range, and fundamental validation parameters were assessed. Compared to a published chromatographic method, the developed sensor operated effectively to determine the ACM content in several food products. Greenness and whiteness were also assessed for the developed sensor, confirming that it is an excellent green and cost-effective option. Furthermore, the developed sensor was compared statistically with recently published ACM sensors to ensure optimal performance.

PMID:40394682 | DOI:10.1186/s13065-025-01501-6

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Analysis of clinical audiological characteristics in children with Williams syndrome in China

Orphanet J Rare Dis. 2025 May 20;20(1):240. doi: 10.1186/s13023-025-03650-2.

ABSTRACT

BACKGROUND: Williams Syndrome (WS) is a neurodevelopmental disorder caused by microdeletion on chromosome 7. Hearing loss (HL) is common in this population but is rarely taken seriously. Previous studies had small sample sizes and mixed conclusions, and few studies have investigated HL in children with WS.

OBJECTIVES: To investigate audiological characteristics of children with WS, analyze the influence factors, and to provide scientific basis for further improvement of ear and hearing care in children with WS.

METHODS: Children with WS aged 0-18yrs, followed up in the Department of Pediatric Healthcare of the Children’s Hospital of Zhejiang University School of Medicine from June 2020 to June 2024 were enrolled in this study. Children aged 0-18yrs who came in the same period for health examination were matched as the control group. Both groups underwent a series of audiological examinations such as tympanogram, distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR) and pure-tone audiometry (PTA), to analyze the audiological characteristics of WS at different ages, and their difference with control group. Tympanogram and DPOAE were suggested to retest 1 year later and the results of first and second test were also compared.

RESULTS: Tympanogram and DPOAE were completed in 130 WS and control subjects, ranging in age from 1.0 to 12.4 years in the WS group and 0.8-13.1 years in the control group. The passing rate of tympanogram and DPOAE in WS was significantly decreased when compared with control group (p < 0.05), and these differences were found in all age groups. The lower DPOAE passing rate still remain after the tympanogram abnormal data were excluded. The SNR of 2000-5000 Hz were statistically lower in children with WS after tympanogram, DPOAE abnormal data were excluded. Tympanogram and DPOAE were rested in 25 WS 1 year later, and no significant difference was found in the passing rate of these test. ABR tests were completed in 28 WS and 44 control subjects, ranging in age from 0.7 to 5.2 years in the WS group and 0.4-5.2 years in the control group. Threshold of ABR in WS was higher than control group. The latency of wave I, III and the interpeak latency I-III in WS were significantly longer (p < 0.05), and the interpeak latency III-V was significantly shorter than that in control group (p < 0.05). PTA were completed in 20 WS and 28 control subjects, ranging in age from 5.9 to 13.7 years in the WS group and 5.9-12.5 years in the control group. 50% of WS was assessed as HL by PTA, with conductive hearing loss (CHL) in 60%, sensorineural hearing loss (SNHL) in 20% and mixed hearing loss (MHL) in 20%, most were mildly. The threshold of 250-8000 Hz in WS group were significantly higher than that in control group (p < 0.05), either in air or bone conduction.

CONCLUSIONS: This study revealed that children with WS frequently exhibit middle and inner ear dysfunction, often accompanied by HL or subclinical cochlear impairment, which can emerge before age 3. Prolonged ABR latency indicates delayed auditory nerve myelination, while shortened interpeak latency III-V may serve as an electrophysiological marker in this population. Long-term, regular hearing follow-up is recommended to enable early HL detection and timely treatment of contributing conditions.

PMID:40394675 | DOI:10.1186/s13023-025-03650-2

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Nevin Manimala Statistics

Knee morphology and patella malalignment in neglected developmental dysplasia of the hip: a systematic review and meta-analysis

J Orthop Surg Res. 2025 May 20;20(1):489. doi: 10.1186/s13018-025-05877-y.

ABSTRACT

PURPOSE: To quantitatively analyze the structural changes of the knee in patients with neglected developmental dysplasia of the hip (DDH).

METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were searched to identify studies comparing the morphological parameters of the knee between DDH patients and healthy individuals. Data on rotational and mechanical parameters of the lower limb, rate of occasional anterior knee pain (AKP), and knee morphological parameters, were extracted. Review Manager and R statistic software were used to perform the statistical analysis.

RESULTS: Nine studies with a total of 790 legs in 521 neglected DDH patients and 431 legs in 303 health subjects were included. Patients were predominantly female (88.3%). The Crowe classification is most commonly used to assess the severity of DDH. The total incidence of occasional AKP ranged from 8.6 to 20.6%, with an overall pooled rate of 14.4% (95%CI = 9.8-19.8%). In patients with neglected DDH, significant increases (P < 0.0001) were observed in femoral anteversion (weighted mean: 39.1° vs. 17.7°), knee torsion (weighted mean: 9.0° vs. 1.6°), and the vertical dimension of the medial femoral condyle (weighted mean: 13.8 mm vs. 11.6 mm), along with a significant decrease in the lateral distal femoral angle (weighted mean: 82.1° vs. 84.8°), which can lead to torsion deformity of the lower limb and valgus inclination of the distal femoral articular surface. Compared with the intact subjects, DDH knees demonstrated an increased sulcus angle (weighted mean: 144.9° vs. 137.5°; P < 0.0001), decreased trochlear depth (weighted mean: 3.1 mm vs. 4.5 mm; P < 0.0001), increased lateral shift of the patella (5.1 mm vs. 3.8 mm, P = 0.06), and increased patellar tilt angle (weighted mean: 18.2° vs. 13.2°; P < 0.0001). These findings were associated with developmental dysplasia of femoral trochlear and patellar instability.

CONCLUSION: Developmental dysplasia of the hip leads to patellar malalignment and developmental changes in the bony anatomy of the knee joint, including the development of a valgus deformity of the lower extremity and trochlear dysplasia. These findings may be associated with patellar instability.

LEVEL OF EVIDENCE: III, systematic review.

REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42025640292).

PMID:40394669 | DOI:10.1186/s13018-025-05877-y

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Risk factors for severity of breast cancer-related lymphedema

Radiat Oncol. 2025 May 20;20(1):81. doi: 10.1186/s13014-025-02663-2.

ABSTRACT

INTRODUCTION: Breast cancer-related lymphedema (BCRL) is a debilitating condition that affects a significant proportion of breast cancer survivors, profoundly impacting their quality of life. While many studies have investigated the risk factors for BCRL occurrence, the determinants of its severity remain underexplored.

METHODS: This retrospective observational study evaluated the risk factors associated with BCRL severity among patients treated at the Motamed Cancer Institute, Tehran, Iran. Female patients with unilateral BCRL aged 25-75 years were included. Data were collected over a 10-year period and analyzed for demographic, clinical, and pathological variables. Lymphedema severity was assessed using established clinical staging criteria and categorized into early-stage (stages 1 and 2a) and advanced-stage (stages 2b and 3) groups. Also, presence of fibrosis and non-pitting edema were other indicators of BCRL severity. Statistical analyses included univariate and multivariate logistic regression to identify predictors of advanced-stage BCRL.

RESULTS: A total of 500 participants were analyzed, with a mean age of 41.16 ± 10.20 years and BMI of 28.72 ± 4.78 kg/m². Advanced-stage BCRL was significantly associated with older age (p = 0.00), higher number of excised lymph nodes (p = 0.04), and radiotherapy (p = 0.00). Multivariate analysis identified radiotherapy as the strongest independent predictor of advanced-stage BCRL (OR: 2.12, 95% CI: 1.22-3.67, p = 0.007). Other variables, including tumor grade, molecular subtypes, and type of surgery, did not independently predict BCRL severity.

CONCLUSION: Advanced-stage BCRL is influenced by multiple factors, particularly radiotherapy and the extent of lymph node dissection. These findings underscore the importance of strategies to mitigate risk among breast cancer survivors, especially those undergoing radiotherapy. Further research is warranted to explore targeted interventions for reducing BCRL severity.

PMID:40394662 | DOI:10.1186/s13014-025-02663-2

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Lifestyle factors and health outcomes associated with infertility in women: A case-control study using National Health Insurance Database

Reprod Health. 2025 May 21;22(1):88. doi: 10.1186/s12978-025-02030-0.

ABSTRACT

BACKGROUND: Approximately one in six people is experiencing infertility at some point in their lives. In response, health insurance coverage for infertility treatments has been strengthened. However, studies examining lifestyle factors that affect infertility remain lacking, highlighting the need to generate objective evidence to address infertility issues using national-level datasets.

METHODS: The General Healthcare Screening Program dataset from National Health Insurance Service database was employed in this study to examine infertility and childbirth among women aged 22-49 years. In 2020, 25,333 women with infertility and 73,759 women who had given birth were initially identified. After applying propensity score matching for age, Charlson Comorbidity Index score, and income level, the final study population included 24,325 women with infertility and 24,325 women who with childbirth. Employing a case-control study design, lifestyle factors (drinking, smoking, and physical activity) and health checkup outcomes (underweight, overweight, hypertension, diabetes, kidney function, anemia, and menstrual disorders) were assessed in this study. Statistical analyses included chi-squared tests, t-tests, and logistic regression.

RESULTS: This study revealed significant risk factors for infertility: two high-risk lifestyle factors, including heavy drinking and smoking, and five health conditions, comprising underweight, hypertension, diabetes, kidney function loss, and menstrual disorders. Conversely, being overweight, not engaging in vigorous physical activity, and anemia were negatively associated with infertility.

CONCLUSIONS: These findings underscore the need for lifestyle modifications and personalized preconception care to improve fertility outcomes.

TRIAL REGISTRATION: Not available.

PMID:40394661 | DOI:10.1186/s12978-025-02030-0