Tag: nevin manimala

J Neurooncol. 2025 Apr 28. doi: 10.1007/s11060-025-05031-y. Online ahead of print.

ABSTRACT

PURPOSE: High-Mobility Group A1 (HMGA1) is a chromatin-associated protein involved in regulating key cellular processes, including DNA transcription, replication, recombination, and repair. It is highly expressed during embryogenesis and reactivated in various cancers, where it contributes to tumor progression and metastasis. We investigated the prognostic significance of HMGA1 gene expression in gliomas by comparing its expression in normal brain tissue and different glioma grades.

METHODS: Real-time quantitative PCR (qPCR) was performed on 75 glioma samples obtained from Aga Khan University Hospital (Pakistan), along with 10 Normal Adjacent Tissue (NAT) samples. The correlation between HMGA1 expression and prognosis was evaluated using Kaplan-Meier (KM) plotter in glioma patients. Statistical analyses were conducted using the R platform and further validated through the online database Chinese Glioma Genome Atlas (CGGA) using online tools.

RESULTS: HMGA1 expression was significantly upregulated in gliomas compared to NAT (p < 0.001) and increased with tumor grade (p = 0.015). High HMGA1 expression correlated with Ki-67 levels and was associated with worse survival (p = 0.0014). Patients with elevated HMGA1 had a 3.5-fold higher mortality risk (95% CI: 1.5-7.9, p = 0.003). ROC analysis yielded an AUC of 0.752, indicating its potential prognostic value.

CONCLUSION: HMGA1 overexpression is associated with poor prognosis in gliomas, suggesting its potential as a prognostic marker. However, further validation is needed to confirm its clinical utility.

PMID:40293672 | DOI:10.1007/s11060-025-05031-y

Int J Clin Pharm. 2025 Apr 28. doi: 10.1007/s11096-025-01924-0. Online ahead of print.

ABSTRACT

BACKGROUND: The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer incidence compared to other hypoglycemic drugs remains unclear.

AIM: This systematic review and meta-analysis was designed to investigate the association of SGLT2 inhibitors with cancer compared to active comparators.

METHOD: A systematic search was conducted up to March 11, 2024 across Web of Science, PubMed, and ClinicalTrials.gov, and included trials with a follow-up period of at least 52 weeks. The Mantel-Haenszel statistical method was utilized, applying risk ratio (RR) and 95% confidence intervals (CI) for binary variables.

RESULTS: Twenty trials covering 16,399 type 2 diabetes mellitus patients were included. Median follow-up duration was 1.0 (1.0) years. The effect of SGLT2 inhibitors on the overall risk of cancer was neutral compared to active comparators (RR 1.00; 95%CI 0.71-1.40; p = 0.99; moderate certainty of evidence). SGLT2 inhibitors did not have a significant impact on breast cancer, endometrial/uterine cancer, gastrointestinal cancer, prostate cancer, renal cancer, or respiratory cancer. Subgroup analysis indicated a significant reduction in the risk of gastrointestinal cancer with SGLT2 inhibitors compared to metformin (RR 0.23; 95%CI 0.06-0.95; p = 0.04). SGLT2 inhibitors potentially increased gastrointestinal cancer risk relative to sulfonylureas (RR 3.52; 95%CI 0.91-13.64; p = 0.07).

CONCLUSION: SGLT2 inhibitors showed neutral cancer risk in T2DM patients but may reduce gastrointestinal cancer versus metformin, guiding tailored therapy based on patient risk profiles.

PMID:40293640 | DOI:10.1007/s11096-025-01924-0

Biochem Genet. 2025 Apr 28. doi: 10.1007/s10528-025-11119-x. Online ahead of print.

ABSTRACT

Mitochondrial sirtuin 3 (SIRT3) is a gene involved in key functions like acetylation, DNA repair, stress response, and tumorigenesis. Several studies have been published that showed the role of SIRT3 in various cancers. Still, few studies have been reported on the genetic and expression variation of the SIRT3 gene in gastric carcinogenesis. This study was designed to explore the involvement of the SIRT3 gene in gastric cancer. In this study, we used two study cohorts, cohort 1 contained 510 gastric cancer (GC) patients and an equal number of age and gender-matched controls. Cohort 2 included 220 GC tissue samples along with adjacent control tissues. Tetra Arms PCR was used to measure the frequency of three selected SNPs of the SIRT3 gene (rs28365927, rs11246029, and rs3817629) in cohort 1. Quantitative PCR and immunohistochemistry were performed to analyze the SIRT3 expression variation in cohort 2 GC patients. The superoxide dismutase (SOD), and 8-hydroxydeoxyguanosine (8-OHdG) levels were measured using ELISA, and DNA damage was measured using the LORD-Q assay. Statistical analysis showed the significant increased frequency of mutant allele of selected SNPs (rs28365927 (p < 0.0001); rs11246029 (p < 0.0001); and rs3817629 (p < 0.0001) in GC patients compared to controls. Expression analysis results showed significant downregulation of the SIRT3 gene at mRNA level (P < 0.001) and protein level (P < 0.001) in gastric tumor section vs control tissues. Multivariant Cox regression analysis showed that downregulated SIRT3 expression (p < 0.000001), H. pylori status (p < 0.0001), T-stage (p < 0.008), and N-stage (p < 0.001) act as prognostic markers in GC patients. ROC curve analysis showed the 90% and 100% specificity of the SIRT3 gene as a diagnostic marker in GC at the mRNA level and protein level, respectively. Significant increased oxidative stress (antioxidant enzyme level p < 0.0001; 8-OHdG level p < 0.0001) and lesion frequency/10 kb (p < 0.03) were indicated in the gastric tumor tissue sections vs controls. The result showed the tumor suppressor role of the SIRT3 gene in GC and was found linked with the surge in oxidative stress and damage in GC patients.

PMID:40293630 | DOI:10.1007/s10528-025-11119-x

Environ Sci Process Impacts. 2025 Apr 28. doi: 10.1039/d4em00804a. Online ahead of print.

ABSTRACT

Volatile chemical products (VCPs) in urban environments account for a significant portion of the volatile organic compounds (VOCs), enhancing the production of tropospheric ozone and secondary organic aerosols. Residential areas are an important source of VCPs in the urban environment, though few studies have examined the emission of VCPs in metropolitan areas from subtropical regions. To bridge the knowledge gap, this study aims to analyze the concentration and emission of D5-siloxane, a compound typically served as a tracer to characterize VCP emission from residential areas. The Texas A&M mobile laboratory, equipped with a Vocus 2R Chemical Ionization Mass Spectrometer (CIMS), and other gas and particle analyzers, continuously sampled the ambient gas phase concentration of D5-siloxane during a field deployment in a residential neighborhood near Houston, TX. A 0-D box model combining Planetary Boundary Layer Height (PBL) height, hourly D5-siloxane concentration, gas deposition velocities, and D5-siloxane reaction rate with hydroxyl radicals was constructed to represent emissions during our sampling period to derive the emission intensities of D5-siloxane. Monte Carlo statistical analysis was performed to gain insights into the emission profile of D5-siloxane, showing higher emission rates compared with other cities in North America but comparable to emissions of European cities. This study presents time-series concentrations and emissions of D5-siloxane in a subtropical residential area during the wintertime. The findings illustrate the temporal profile of D5-siloxane in a typical residential neighborhood in the Southeast United States and provide valuable data to enhance model parameterizations.

PMID:40289910 | DOI:10.1039/d4em00804a

Arthritis Care Res (Hoboken). 2025 Apr 28. doi: 10.1002/acr.25562. Online ahead of print.

ABSTRACT

OBJECTIVES: This study aimed to improve contraception and reproductive planning documentation within rheumatology providers’ notes at a single academic center.

METHODS: Female patients aged 18-45 years old with autoimmune inflammatory rheumatic diseases were identified and chart review was performed for documentation of contraception and pregnancy planning. Baseline data were collected from 148 charts between May 2022 and March 2023. In June 2023, a reproductive health assessment questionnaire was integrated into the electronic health record and sent to patients for completion prior to their visits. Post intervention data was collected from 176 charts between July 2023 and December 2023. Demographics of patients (race, ethnicity, gender) and provider gender were collected. Telehealth and face to face visits were assessed separately.

RESULTS: A statistically significant increase (p<0.0001) was seen in provider documentation of both contraception (44.6% to 70.5%) and pregnancy planning (15.5% to 60.2%) after implementation of the pre-visit questionnaire. When patients prescribed teratogenic medications were analyzed separately, there was statistically significant (p<0.0001) better documentation of pregnancy planning after the intervention. Secondary analyses found that patient age, race/ethnicity, encounter type, or provider gender had no significant impact on documentation rates.

CONCLUSIONS: By integrating an electronic, pre-visit questionnaire into the patient portal, documentation was significantly improved for contraception and pregnancy planning. The results were sustained for 6 months. Further studies are needed to see if improved documentation translates into more effective reproductive health care discussions, referrals to gynecology, and subsequent improvement in reproductive health outcomes.

PMID:40289896 | DOI:10.1002/acr.25562

Arthritis Rheumatol. 2025 Apr 28. doi: 10.1002/art.43199. Online ahead of print.

ABSTRACT

OBJECTIVES: Tapering of tumor necrosis factor inhibitor (TNFi) treatment in rheumatoid arthritis (RA) remission is debated. We assessed the effect of tapering TNFi to withdrawal versus continued stable TNFi on flare-free survival and joint damage progression over three years.

METHODS: ARCTIC REWIND was a multicenter, open-label, non-inferiority trial including patients with RA in remission for ≥12 months on stable TNFi therapy. Patients were randomized 1:1 to taper TNFi to withdrawal or continue stable treatment. The primary endpoints of the current study were flare-free survival and radiographic progression over three years. Flare-free survival was analyzed by Kaplan-Meier methods, flare rates by Cox regression, and radiographic progression by logistic mixed effects models.

RESULTS: Of 99 randomized patients, 92 received the allocated therapy, 80 completed 3-year follow-up. Mean baseline DAS based on 44 joint count was 0.8, csDMARD co-medication was used by 90%. After 3 years, 25% (95%CI: 13-38%) remained flare-free in the tapering TNFi group compared to 85% (70-93%) in the stable group, corresponding hazard ratio for flare 9.4 (3.9-22.8), p<0.0001. In the tapering group 6/41 (15%) experienced radiographic progression, compared with 3/38 (8%) in the stable group, risk difference 6.7% (-7.1%-20.5%, p=0.3). Adverse events occurred in 81% of the patients in the tapering group, and 89% of the patients in the stable group.

CONCLUSION: In contrast to those receiving stable TNFi treatment, a minority of RA patients in remission tapering TNFi to withdrawal remained flare-free over three years. There was no statistically significant difference in radiographic progression between the groups.

PMID:40289847 | DOI:10.1002/art.43199

Pediatr Transplant. 2025 Jun;29(4):e70095. doi: 10.1111/petr.70095.

ABSTRACT

BACKGROUND: Waitlist mortality remains a critical issue for pediatric heart transplant (HTx) candidates, particularly for candidates with congenital heart disease. Listing center organ offer acceptance practices have been identified as a factor influencing waitlist outcomes. We utilized machine learning (ML) to identify factors associated with waitlist mortality, combining variables associated with institutional offer acceptance practices as well as candidate-specific risk factors.

METHODS: We analyzed the Organ Procurement and Transplantation Network database for pediatric HTx candidates listed between 2010 and 2020. Various statistical and ML models were employed to identify predictors of waitlist mortality or clinical deterioration leading to waitlist removal. The dataset was split into training (82%) and testing (18%), and the final model was selected based on predictive performance. SHAP values were used to assess variable importance.

RESULTS: Among 5523 pediatric candidates, overall waitlist mortality was 9.8%. The CatBoost model achieved the highest predictive performance with an AUC-ROC score of 0.74 and a recall score of 0.75. Key predictors included candidate diagnosis, age/size, ventilator use, eGFR, serum albumin, ECMO, and institutional factors such as high offer refusal rates and low transplant volume.

CONCLUSIONS: Institutional organ offer acceptance practices influence waitlist outcomes for pediatric HTx candidates. Centers with higher organ refusal rates are associated with worse outcomes, independent of candidate-specific risk factors, underscoring the need for standardizing organ acceptance criteria across institutions to reduce variability in decision-making and improve waitlist survival. Additionally, addressing modifiable risk factors such as malnutrition and renal dysfunction could further optimize patient outcomes.

PMID:40289835 | DOI:10.1111/petr.70095

Circ Cardiovasc Qual Outcomes. 2025 Apr 28:e011719. doi: 10.1161/CIRCOUTCOMES.124.011719. Online ahead of print.

ABSTRACT

BACKGROUND: The ability of the American Heart Association Predicting Risk of Cardiovascular Disease Events (PREVENT) calculator to accurately assign 10-year atherosclerotic cardiovascular disease (ASCVD) risk in older individuals, including those aged ≥80 years, is unknown. This study compares PREVENT with the 2013 Pooled Cohort Equation (PCE) calculator for predicting 10-year ASCVD risk in a large cohort of older adults.

METHODS: This was a prospective cohort study of adults without CVD from Australia and the United States aged ≥70 years (≥65 years, if US minorities). They were enrolled from 2010 to 2014 in the ASPREE trial (Aspirin in Reducing Events in the Elderly), a 5-year randomized trial of low-dose aspirin in community-dwelling older adults with posttrial observational follow-up extending to 2022. ASCVD events were adjudicated by expert panels. The discriminative ability of the 2 risk calculators was assessed by Harell C statistic following Cox regression in the 65- to 79-year age group and >80-year age group, separately. For calibration, predicted event numbers were calculated using PREVENT and PCE, scaled for the actual length of follow-up, and compared with the number of observed events in-trial and during extended follow-up.

RESULTS: Among the 15 510 participants aged 65 to 79 years (median age, 73.2 years; 56.1% women), 1084 ASCVD events occurred (median follow-up, 8.3 years); PCE predicted 3102 events while PREVENT predicted 1290 events. For the 2787 participants ≥80 years (median age, 82.6 years; 59.2% women), 355 ASCVD events occurred (median follow-up, 7.4 years); PCE predicted 1067 events while PREVENT predicted 350 events. PREVENT showed superior discriminative performance compared with PCE (PREVENT versus PCE, C statistic, 0.793 versus 0.740; P<0.001 in participants aged 65 -79 years; 0.854 versus 0.799; P<0.001 in those aged ≥80 years).

CONCLUSIONS: The PREVENT risk calculator is superior to the PCE calculator in predicting ASCVD events in older adults from the United States and Australia, including those aged ≥80 years.

REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583. URL: https://www.isrctn.com; Unique identifier: ISRCTN83772183.

PMID:40289804 | DOI:10.1161/CIRCOUTCOMES.124.011719

Zhonghua Yi Xue Za Zhi. 2025 Apr 29;105(17):1362-1368. doi: 10.3760/cma.j.cn112137-20240829-01991.

ABSTRACT

Objective: To explore the correlation between fat and iron accumulation in the liver and pancreas of obese patients with glycemic metabolic indicators, and to analyze the risk factors for glycemic abnormalities in obese patients. Methods: A prospective study enrolled 160 obese patients who visited Xiangya Third Hospital of Central South University from October 2022 to October 2023. The age [M (Q₁, Q₃)] was 40.8 (29.5, 43.9) years, with 74 males and 86 females. According to the results of the oral glucose tolerance test (OGTT), they were divided into the normal glucose metabolism (NGT) group(n=68), the impaired glucose tolerance (IGR) group(n=37), and the type 2 diabetes mellitus (T2DM) group(n=55). The proton density fat fraction (PDFF) measured by the MRI-based Dixon technique was used to quantitatively assess the fat content in the liver and pancreas, and the R2^* value was used to quantify the iron content in the liver and pancreas. Correlation analysis was used to analyze the correlation between fat and iron deposition in the liver and pancreas of obese patients and glucose metabolism indicators. The multivariate logistic regression model was used to analyze the influencing factors of abnormal glucose metabolism in obese patients. Results: The differences in liver PDFF, liver R2^*, pancreatic PDFF, and pancreatic R2^* among the three groups were all statistically significant (all P<0.05). The pancreatic PDFF in the T2DM group [12.8% (6.9%, 18.5%)] was higher than that in both the NGT group [7.6% (4.7%, 10.3%)] and the IGR group [7.0% (4.1%, 12.0%)] (all P<0.05). The pancreatic R2^* in the T2DM group [33.7 (28.3, 39.0)/s] was higher than that in the NGT group [28.6 (26.3, 33.3)/s] and the IGR group [28.5 (25.9, 32.9)/s] (all P<0.05). Significant differences were also observed among the three groups in terms of the homeostatic model assessment of insulin resistance (HOMA-IR), the homeostatic model assessment of β-cell function (HOMA-β), the insulin sensitivity index (ISI), and blood glucose levels at 0, 0.5, and 2.0 h during the oral glucose tolerance test (OGTT) (all P<0.05). The T2DM group had the lowest HOMA-β, while the NGT group had the highest (all P<0.05). Liver PDFF was positively correlated with HOMA-IR and blood glucose levels at 0, 0.5, and 2.0 h during OGTT (all r>0.25) and negatively correlated with ISI (r=-0.54) (all P<0.05). Pancreatic PDFF was negatively correlated with HOMA-β (r=-0.27) and positively correlated with blood glucose levels at 0, 0.5, and 2.0 h during OGTT (all r>0.24) (all P<0.05). Liver R2^* was positively correlated with HOMA-IR and blood glucose levels at 0, 0.5, and 2.0 h during OGTT (all r>0.24) and negatively correlated with ISI (r=-0.29) (all P<0.05). Pancreatic R2^* was negatively correlated with HOMA-β (r=-0.26) and positively correlated with blood glucose levels at 0, 0.5, and 2.0 h during OGTT (all r>0.21) (all P<0.05). Multivariate logistic regression analysis revealed that liver PDFF≥9.4% (OR=0.044, 95%CI: 1.03-5.76) was a risk factor for abnormal glucose metabolism in obese patients. Conclusions: Fat and iron accumulation in the liver and pancreas of obese patients is closely related to the occurrence of abnormal glucose metabolism. Fat deposition in the liver is a risk factor for abnormal glucose metabolism in obese patients.

PMID:40289778 | DOI:10.3760/cma.j.cn112137-20240829-01991

Zhonghua Yi Xue Za Zhi. 2025 Apr 29;105(17):1355-1361. doi: 10.3760/cma.j.cn112137-20241217-02867.

ABSTRACT

Objective: To compare the differences in perioperative blood loss and the coagulation-fibrinolysis system between patients undergoing robot-assisted or traditional total knee arthroplasty (TKA). Methods: A retrospective cohort study was conducted to analyze the clinical data of 232 patients who underwent TKA at the Department of Orthopedics, the First Affiliated Hospital of Chongqing Medical University, from March 2021 to September 2023. The cohort included 25 men and 207 women with a mean age of (69.1±7.5) years. The patients were further divided into two groups based on whether robot-assisted surgery was performed: the conventional group (168 patients, including 15 men and 153 women) and the robot-assisted group (64 patients, including 10 men and 54 women). Data on perioperative laboratory tests and postoperative complications were collected. The differences in perioperative blood loss, coagulation index (CI), fibrinolysis index, fibrinogen degradation products (FDP), D-dimer (D-D), and postoperative complications such as ecchymosis and venous thromboembolism (VTE) were compared between the two groups. Results: There was no statistically significant differences in the baseline characteristics between the two groups (all P>0.05). The incidence of bleeding-related complications, specifically ecchymosis, was significantly lower in the robot-assisted group compared to the conventional group [20.3% (13/64) vs 33.9% (57/168), P=0.043]. In terms of blood loss, the robot-assisted group exhibited significantly lower total blood loss and occult blood loss on the first postoperative day compared to the conventional group [total blood loss: (263±167) ml vs (382±173) ml, P<0.001; occult blood loss: (222±163) ml vs (342±173) ml, P<0.001]. Similarly, on the third postoperative day, the robot-assisted group had lower total blood loss and occult blood loss [total blood loss: (504±240) ml vs (680±222) ml, P<0.001; occult blood loss: (468±238) ml vs (640±222) ml, P<0.001]. Regarding coagulation function, the robot-assisted group had a lower CI on thromboelastography postoperatively (0.33±1.34 vs 0.93±1.59, P=0.008) and fewer patients with a hypercoagulable state (CI>3) [0 vs 7.1%(12/168), P=0.028]. In terms of fibrinolysis function, the robot-assisted group had lower levels of FDP and D-D on the first postoperative day [FDP: (6.24±4.49) mg/L vs (9.24±6.47) mg/L, P<0.001; D-D: (3.23±2.96) mg/L vs (4.23±2.97) mg/L, P=0.023]. Conclusion: Compared with manual TKA, robot-assisted TKA not only effectively reduces perioperative blood loss but also offers advantages in controlling postoperative hypercoagulability and hyperfibrinolysis.

PMID:40289777 | DOI:10.3760/cma.j.cn112137-20241217-02867