Categories
Nevin Manimala Statistics

Mitochondrial DNA variation and intervertebral disc degeneration: a genotypic analysis in a South African cohort

Mol Biol Rep. 2025 Mar 7;52(1):288. doi: 10.1007/s11033-025-10394-6.

ABSTRACT

BACKGROUND: Non-communicable diseases are multifactorial in that they can be caused by genetic factors, age, sex and poor lifestyle choices. They are estimated to account for 71% of deaths globally with 80% of these deaths occurring in low- and middle-income countries. This is particularly true for Intervertebral Disc Degeneration associated with mitochondrial dysfunction. Interestingly, mitochondrial dysfunction can arise from mutations in both the nuclear and the mitochondrial genomes. The present study, therefore, aimed to determine if there is an association between mitochondrial DNA mutations associated with mitochondrial dysfunction and disc degeneration in a South African cohort, and in addition, generate genetic data for understudied mutations in African populations.

METHODS AND RESULTS: Mutations were selected using a systematic literature review. DNA was collected using buccal swabs and extracted using a standard salt-lysis protocol. Mass-array genotyping was done for previously reported as well as novel mutations. GenAlEx (version 6.5), RStudio and SHEsis were used for statistical analyses. Although no significant associations were found, the identified polymorphic mutations C16223T, A10398G and A8536G were found to have higher mutant allele frequencies in case individuals indicating that had a larger cohort been used, significance may have been observed.

CONCLUSIONS: This study was able to generate genotypic information for a South African cohort for both reported and understudied mutations. Furthermore, the identification of higher mutant allele frequencies for C16223T, A10398G and A8536G highlights the importance of considering these mutations in future studies using a larger cohort.

PMID:40053230 | DOI:10.1007/s11033-025-10394-6

Categories
Nevin Manimala Statistics

Unraveling the causal relationship and underlying mechanisms between cathepsins on liver cancer: findings from mendelian randomization and bioinformatics analysis

Discov Oncol. 2025 Mar 7;16(1):277. doi: 10.1007/s12672-025-02030-3.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are two major types of primary liver cancer (PLC). Earlier research has indicated a potential link between cathepsins and liver cancer. Nonetheless, there have been limited clinical trials examining the connection between cathepsins and PLC. Therefore, we conducted a two-sample Mendelian randomization (MR) study to evaluate the causal relationship between cathepsins and PLC.

METHODS: Data from genome-wide association studies (GWAS) focusing on cathepsins was collected. Additionally, summary data for GCST90018803 (Hepatic bile duct cancer, HBDC), and GCST90018858 (related to hepatic cancer, HC), were employed in the discovery and validation phases of the study, respectively. The inverse variance weighted (IVW) method was served as the primary analytical method in our Mendelian randomization (MR) study, supplemented by the MR-Egger, weighted median, simple mode, and weighted mode methods. To assess heterogeneity and pleiotropy, we conducted the MR-Egger intercept test, Cochran’s Q test, as well as the MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analysis, along with the leave-one-out analysis. After that, bioinformatic analysis based on the Gene Expression Omnibus (GEO) databases were utilized, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were utilized for exploring the underlying mechanisms. Additionally, protein-protein docking was employed to confirm the interaction between related proteins.

RESULTS: The results showed that cathepsin F (CTSF), was causally associated with HBDC. CTSF decrease the risk of HBDC (OR = 0.826, 95% CI 0.711-0.959, P = 0.012). CTSF may play protective roles in patients with HBDC. No heterogeneity or pleiotropy was observed. Additionally, the expression of CTSF genes is lower in patients with HBDC, GO and KEGG functional enrichment analysis revealed CTSF were mainly related to cell cycle, and P53 pathway in HBDC. Docking results showed that CTSF had good binding ability with MDM2, the most well-established negative regulator of p53.

CONCLUSION: This study provided new evidence of the relationship between CTSF and HBDC, suggesting that CTSF plays an inhibition role in HBDC progression. CTSF could be a novel and effective way to for HDBC treatment.

PMID:40053224 | DOI:10.1007/s12672-025-02030-3

Categories
Nevin Manimala Statistics

Complications associated with postoperative stiffness following rotator cuff repair

Eur J Orthop Surg Traumatol. 2025 Mar 7;35(1):101. doi: 10.1007/s00590-025-04212-9.

ABSTRACT

PURPOSE: Shoulder stiffness is a common complication following rotator cuff repair (RCR) surgery. However, there is a paucity of literature on the short-term effects of postoperative stiffness on outcomes following RCR. The purpose of this study is to analyze the effect of postoperative shoulder stiffness on short-term outcomes following RCR.

METHODS: The Nationwide Readmissions Database (NRD) was queried from 2015 to 2020 for primary RCR patients. Stiffness was defined using International Classification of Disease Clinical Modification and Procedure Coding System codes for arthrofibrosis, adhesive capsulitis, stiffness, synovitis, or contracture of the shoulder. Patients were separated into stiff and non-stiff cohorts and a case-control match was performed based upon age, sex, and Charlson Comorbidity Index (CCI) for a total number in the control group of 358 and a total subject count of 489. Postoperative complications, reoperations, readmissions, mortality, and hospital cost metrics were compared between cohorts using t-test and fisher’s exact test.

RESULTS: Rates of complications, reoperation, readmission, and death were similar between the stiff and non-stiff cohorts and there were likely no clinically significant differences. Stiff patients were more likely to be discharged to home and less likely to be discharged to another type of facility (p = 0.007).

CONCLUSION: Postoperative stiffness was not predictive of increased complications, readmissions, or healthcare costs following RCR. These findings suggest that stiffness may not represent a significant clinical or economic burden, helping to guide patient expectations and management strategies. However, stiff patients were more likely to be discharged home and less likely to require facility-based care, suggesting potential differences in postoperative recovery or support needs.

PMID:40053210 | DOI:10.1007/s00590-025-04212-9

Categories
Nevin Manimala Statistics

Clinical Impact of Continuous Dasatinib Administration on the Prognosis of Patients With BCR::ABL1 Acute Lymphoblastic Leukemia: Result of the Prospective MRD2014 Study Conducted by Fukuoka Blood and Marrow Transplantation Group (FBMTG)

Eur J Haematol. 2025 Mar 7. doi: 10.1111/ejh.14407. Online ahead of print.

ABSTRACT

AIM: To assess the efficacy of continuous dasatinib in improving outcomes for adult patients with BCR::ABL1 ALL.

METHODS: The prospective, multicenter ALL/MRD2014 trial introduced a modified protocol compared to the MRD2008 trial, incorporating continuous dasatinib use and reduced chemotherapy intensity.

RESULTS: Among the 164 adult ALL patients enrolled (2014-2019), 61 were Philadelphia-positive (Ph+) (median age 50 years; 38 males, 23 females). Post-induction, 96.7% achieved complete remission (CR). The 3-year event-free survival (EFS) and overall survival (OS) were 51% and 76%, respectively. Patients undergoing allo-HSCT in CR1 had improved outcomes, with a 3-year EFS of 64% and OS of 87%. MRD-negative patients before transplantation exhibited superior survival (EFS: 71% vs. 29%; OS: 94% vs. 57%). Comparison with the MRD2008 trial revealed similar outcomes, with the MRD2014 trial achieving a 3-year EFS of 51% and OS of 76% vs. 52% and 84% in MRD2008. Although not statistically significant, the MRD2014 trial showed trends of increased relapse (CIR: 39% vs. 26%, p = 0.305) and reduced non-relapse mortality (NRM: 10% vs. 21%, p = 0.181).

CONCLUSION: The ALL/MRD2014 trial underscores the importance of MRD status and allo-HSCT in Ph+ ALL. Continuous dasatinib-based regimens offer favorable outcomes in MRD-negative patients.

TRIAL REGISTRATION: This study was registered with the UMIN Clinical Trials Registry (UMIN-CTR), number UMIN000012382.

PMID:40052397 | DOI:10.1111/ejh.14407

Categories
Nevin Manimala Statistics

Mid-regional pro-adrenomedullin: A rapid sepsis biomarker for diagnosing spontaneous bacterial peritonitis in cirrhosis

Eur J Clin Invest. 2025 Mar 7:e70021. doi: 10.1111/eci.70021. Online ahead of print.

ABSTRACT

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a frequent and life-threatening complication of cirrhosis, contributing to considerable morbidity and mortality.

METHODS: A cross-sectional derivation study was conducted to assess the diagnostic accuracy of two sepsis-related calcitonin peptide family biomarkers, mid-regional pro-adrenomedullin (MR-pro-ADM) and procalcitonin, in ascitic fluid for identifying bacteriologically confirmed SBP (BC-SBP). In a subsequent validation study, the diagnostic performance of the ‘SBP score’ was evaluated in an independent patient cohort using an absolute polymorphonuclear (PMN) leukocyte count threshold of ≥250 cells/mm3 as the diagnostic benchmark for diagnosing SBP.

RESULTS: In the derivation study, the concentration of MR-pro-ADM in ascitic fluid was significantly higher in patients with BC-SBP compared to those without BC-SBP (3.14 nmol/L [IQR, 2.39-6.74] vs. 1.91 nmol/L [IQR, 1.33-2.80]; p = .0002). Bayesian ANOVA indicated that MR-pro-ADM was highly discriminative for diagnosing BC-SBP, with a substantial Bayes factor (BFM = 2505), whereas procalcitonin exhibited poor discriminatory performance. Receiver-operating characteristic (ROC) analysis identified an optimal MR-pro-ADM cut-off of ≥2.50 nmol/L for diagnosing BC-SBP, with an area under the ROC curve (AUROC) of 0.746 (95% CI, 0.685-0.801; p < .0001). Multivariable logistic regression identified three independent predictors of BC-SBP, which were subsequently incorporated into the ‘SBP score’ (MR-pro-ADM ≥2.5 nmol/L, absolute PMN count ≥250 cells/mm3 and Child-Pugh score). In the validation study, the ‘SBP score’ demonstrated an AUROC of 0.993 (95% CI, 0.929-1.000; p < .0001) for diagnosing SBP.

CONCLUSION: MR-pro-ADM in ascitic fluid emerges as a promising biomarker for SBP diagnosis. Combining MR-pro-ADM with absolute PMN count and Child-Pugh score in the ‘SBP score’ greatly improves the diagnostic accuracy of SBP.

PMID:40052388 | DOI:10.1111/eci.70021

Categories
Nevin Manimala Statistics

Mediators of Racial Inequities in Non-Small Cell Lung Cancer Care

Cancer Med. 2025 Mar;14(5):e70757. doi: 10.1002/cam4.70757.

ABSTRACT

BACKGROUND: Black patients with non-small cell lung cancer (NSCLC) are more often diagnosed at a later stage and receive inadequate evaluation and treatment compared to White patients. We aimed to identify factors representing exposure to structural racism that mediate the association between race and NSCLC care.

METHODS: We queried Surveillance, Epidemiology, and End Results-Medicare for non-Hispanic Black and White patients ≥ 67 years diagnosed with NSCLC from 2013 to 2019. Our outcomes were localized diagnosis stage, receipt of stage-appropriate evaluation, receipt of stage-appropriate treatment, two-year survival, and receipt of “optimal” care, an aggregate metric comprising the first three listed outcomes. We estimated indirect effects of mediators on the association between race and outcomes.

RESULTS: Of 69,130 patients, 8.2% were Black. Medicare-Medicaid dual eligibility, a marker of individual-level socioeconomic status (SES), accounted for the largest proportion of mediating effects for most outcomes, ranging from 13.6% (p < 0.001) for localized diagnosis stage to 25.0% (p < 0.001) for two-year survival. Receipt of an influenza vaccine, a marker of health care access, had the second largest mediating effects on the associations between race and diagnosis stage (9.5%, p < 0.001), treatment (15.3%, p < 0.001), and optimal care (11.4%, p < 0.001). Neighborhood-level SES accounted for the third largest proportion of the effects of race on each outcome, explaining between 9% and 16% of the racial inequities at each phase (all p < 0.001).

CONCLUSIONS: Individual- and neighborhood-level structural factors partly explain inequities in NSCLC care, and their effects vary based on the phase of care. Interventions should be adapted to the phase of care.

PMID:40052387 | DOI:10.1002/cam4.70757

Categories
Nevin Manimala Statistics

Exploring the Nexus of Professional Commitment, Emotional Labor, and Self-Efficacy Among Community Pharmacists: Implications for Healthcare Delivery

Turk J Pharm Sci. 2025 Mar 7;22(1):38-45. doi: 10.4274/tjps.galenos.2024.19947.

ABSTRACT

OBJECTIVES: This study aimed to explore the relationship between emotional labor, professional commitment, and self-efficacy among community pharmacists. Specifically, this study examined how self-efficacy influences professional commitment and the mediating role of emotional labor strategies in this relationship.

MATERIALS AND METHODS: A cross-sectional survey design was used to collect data from 396 community pharmacists. The study used a convenience sampling method and included standardized measures of emotional labor, professional commitment, and self-efficacy. Descriptive statistics were used to examine the levels of these variables among the participants. Multiple regression analyses were conducted to assess the interdependencies and mediating effects of emotional labor strategies.

RESULTS: General self-efficacy was positively correlated with emotional commitment (β=0.275, p<0.05) and continuance commitment (β=0.364, p<0.05), explaining 5% and 8% of their variances, respectively. A normative commitment was influenced by self-efficacy (β=0.464, p<0.05) and deep emotional labor (β=0.134, p<0.05), explaining 11% of its variance. Self-efficacy and deep emotional labor positively affected overall professional commitment (β=0.368, p<0.05), accounting for 15% of the variance.

CONCLUSION: The results highlight the crucial role of self-efficacy in managing the emotional demands of the pharmacy profession and in fostering stronger professional commitment. Enhancing pharmacists’ self-efficacy and emotional management skills can improve their job satisfaction and commitment to the profession. These findings have clinical implications for the development of training interventions aimed at supporting pharmacists in coping with the emotional aspects of their work and improving their overall professional well-being.

PMID:40052379 | DOI:10.4274/tjps.galenos.2024.19947

Categories
Nevin Manimala Statistics

Trends in Complications of Pediatric Rhinosinusitis Before and During the COVID-19 Era

Otolaryngol Head Neck Surg. 2025 Mar 7. doi: 10.1002/ohn.1196. Online ahead of print.

ABSTRACT

OBJECTIVE: To examine changes in trends of the incidence and characteristics of pediatric complicated rhinosinusitis with respect to the coronavirus disease 2019 (COVID-19) pandemic.

STUDY DESIGN: Retrospective cohort.

SETTING: Single tertiary-care center.

METHODS: A review of patients who presented to St. Louis Children’s Hospital (SLCH) with complicated rhinosinusitis from 2017 to 2022 was performed. Clinical and follow-up data were analyzed in association with COVID-19.

RESULTS: Eighty-three patients with complicated rhinosinusitis were identified and analyzed according to hospitalization before or after March 2020. No differences in demographic variables were found between the two groups. More patients had developmental comorbidities in the COVID-19 group (7 vs 1, P = .049). More patients with intracranial complications (55% vs 45%, P = .48) and Pott’s puffy tumor (78% vs 22%, P = .13) were observed in the COVID-19 era group; however, this difference was not statistically significant. In the COVID-19 group, more patients were found to have Streptococcus anginosus growth in their surgical cultures (67% vs 33%, P = .03). The incidence of complicated sinusitis correlated with the incidence of all viral cases at SLCH, particularly in 2021 and 2022, and increased following COVID-19.

CONCLUSION: Trends in complicated sinusitis vary before and after the onset of the COVID-19 pandemic. There was an increase in complications of sinusitis due to S. anginosus species in the COVID-19 era and trends towards increased intracranial complications and Pott’s puffy tumor. After an initial decrease, the incidence of complicated sinusitis per year increased following COVID-19.

PMID:40052376 | DOI:10.1002/ohn.1196

Categories
Nevin Manimala Statistics

Nonpharmacological Pain Management for People With Dementia: A Scoping Review Mapping Research Gaps From a Pragmatic Lens

J Am Geriatr Soc. 2025 Mar 7. doi: 10.1111/jgs.19418. Online ahead of print.

ABSTRACT

BACKGROUND: Nonpharmacological pain interventions are effective but underutilized in people living with dementia (PLWD). Leveraging an implementation lens (i.e., the Readiness Assessment for Pragmatic Trials [RAPT] model) to scope the literature may reveal research gaps contributing to this underutilization. The purpose of this scoping review is to summarize the literature, map the studies to the RAPT model, and identify research gaps.

METHODS: Following Arksey and O’Malley’s framework and Preferred Reporting Items for Systematic Review and Meta-Analyses Extension for Scoping Reviews (PRISMA- ScR) guidelines, two reviewers screened, collated, extracted, and mapped data from eligible studies to the 9 RAPT domains (implementation, evidence, risk, feasibility, measurement, cost, acceptability, alignment, and impact). We used descriptive statistics to summarize the studies and the extent to which interventions were mapped to RAPT domains.

RESULTS: Of 81 studies covering 24 interventions, 64% were in long-term care facilities (LTCFs), 66% reported unspecified pain, and 32% reported unspecified dementia. Of the interventions, the Tailored Activities Program had literature informing the most domains (6 domains), followed by exercise, pain education, and stepwise approaches (5 domains each). Most studies were mapped to the evidence domain (33 studies), few studies to feasibility (7 studies), acceptability (5 studies), and implementation (10 studies) domains, one study to cost, and no studies to risk or impact.

CONCLUSION: Despite the variety of nonpharmacological pain interventions studied, there is a notable lack of literature that aligns with the RAPT model. Furthermore, there is limited consideration of the specific pain and dementia conditions, as well as the diverse environments where PLWD reside and receive care. These gaps underscore the need for robust and holistic research to ensure pain interventions are effectively tailored and implemented for PLWD. Starting with acceptability and feasibility studies can establish a foundation for building robust evidence, ensuring practical and well-received interventions before larger-scale clinical trials.

PMID:40052350 | DOI:10.1111/jgs.19418

Categories
Nevin Manimala Statistics

The perioperative outcomes of papillary versus non-papillary access in percutaneous nephrolithotomy

BJU Int. 2025 Mar 7. doi: 10.1111/bju.16694. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare the perioperative outcomes of papillary versus non-papillary access in percutaneous nephrolithotomy (PCNL), which is the ‘gold standard’ for managing large renal calculi.

PATIENTS AND METHODS: In this prospective, randomised trial, 70 patients with de novo renal stones amenable to PCNL were allocated to undergo either papillary (n = 35) or non-papillary (n = 35) access. Primary outcomes included haemoglobin drop and the need for blood transfusion. Secondary outcomes assessed were: operative time, stone-free rates (SFRs; initial and final), the need for auxiliary procedures, incidence and grading of complication rates.

RESULTS: There were no statistically significant differences between the papillary and non-papillary groups in terms of perioperative haemoglobin drop (P = 0.971) or transfusion rates (P = 0.69). Although the non-papillary group had a shorter mean operative time (83 vs 92 min, P = 0.103) and a marginally higher initial SFR (88.6% vs 82.9%, P = 0.495), these differences were not statistically significant. Final SFRs were similar (94.3% vs 97.1%, P = 0.555). Both groups experienced low and comparable complication rates, including fever, sepsis, and prolonged urinary leakage, with no significant difference between them.

CONCLUSION: Both papillary and non-papillary access approaches in PCNL show comparable safety and efficacy. While non-papillary access was associated with a slight reduction in operative time and a higher SFR, these findings were not statistically significant.

PMID:40052346 | DOI:10.1111/bju.16694