Nevin Manimala

Int J Gynaecol Obstet. 2026 Jan 22. doi: 10.1002/ijgo.70831. Online ahead of print.

ABSTRACT

OBJECTIVE: Cervical cancer remains a major public health concern globally. It is the fourth leading cause of cancer deaths among women worldwide. In 2020, the global incidence of cervical cancer was estimated to be 604 000 with a standardized mortality rate of 341 000. In Tanzania, cervical cancer is the most common female cancer and a leading cause of cancer-related deaths. The majority of data demonstrating the survival rate of cervical cancer originates from high- and middle-income countries with contributions from low-income countries such as Tanzania being relatively scarce. Determining the factors associated with survival is critical in an attempt to inform strategies to improve outcome of women with cervical cancer. The aim of the present study was to determine the 3-year overall survival rate and associated factors among women with invasive cervical cancer attended at Ocean Road Cancer Institute (ORCI) from 2018 to 2020.

METHODS: A retrospective cohort study was conducted at ORCI by using their cancer registry database. The study included 256 women diagnosed with cervical cancer from 2018 to 2020. Survival analysis was estimated by using Kaplan-Meir analysis, Cox regression hazard proportion and log-rank test and a P value of less than 0.05 was considered statistically significant. Stata version 17 was used for analysis.

RESULTS: Among 256 women with cervical cancer, the survival rate across one-, two- and 3-years, respectively were 83.6%, 77.0%, and 72.7%. Survival rate was significantly associated with both FIGO stage during diagnosis and hemoglobin level. Those who received concurrent chemoradiotherapy had a higher survival rate compared to those who received radiotherapy or chemotherapy only, and it was statistically significant with P < 0.001.

CONCLUSION: The study found an overall survival rate of 72.7% over 3 years. Factors associated with survival rate were early FIGO stage at diagnosis, normal hemoglobin level at diagnosis, and the use of concurrent chemoradiotherapy. Proper staging, good patient preparation and good choice of treatment improves survival. With availability of advance treatment options in the country the survival rate of women is promising.

PMID:41568557 | DOI:10.1002/ijgo.70831

J Am Heart Assoc. 2026 Jan 22:e044241. doi: 10.1161/JAHA.125.044241. Online ahead of print.

ABSTRACT

BACKGROUND: The role of colchicine, an anti-inflammatory agent, in improving cardiovascular outcomes in patients with recent myocardial infarction remains unclear. We sought to evaluate the efficacy and safety of colchicine compared with placebo in patients with recent myocardial infarction (within 1 month of symptom onset) at a follow-up of at least 1 year.

METHODS: We systematically searched MEDLINE, Embase, and the Cochrane Library until January 2025 for randomized controlled trials comparing colchicine to placebo in recent myocardial infarction. The primary outcome was major adverse cardiovascular events (MACE; as defined by the included studies) at maximum follow-up. Secondary outcomes included individual MACE components and safety (serious adverse events [AEs], any AEs, and gastrointestinal AEs). Count data were pooled using random-effects models with inverse variance weighting to estimate risk ratios (RRs) and 95% CIs.

RESULTS: A total of 5 randomized controlled trials were included with 6620 patients randomized to colchicine and 6625 to placebo. Most participants (79%) were male, with mean ages ranging from 59 to 61 years. Follow-up durations ranged from 1 to 3 years. At maximum follow-up, there was no statistically significant difference in MACE between colchicine and placebo (8.2% versus 9.3%; RR, 0.83 [95% CI, 0.66-1.04]). Analyses of individual MACE components were also inconclusive. Randomization to colchicine did not increase the overall incidence of AEs or serious AEs compared with placebo.

CONCLUSIONS: In patients with recent myocardial infarction, the available evidence assessing the effect of colchicine, in addition to standard therapy, on MACE remains inconclusive over a median follow-up duration of 1 year.

PMID:41568554 | DOI:10.1161/JAHA.125.044241

J Am Geriatr Soc. 2026 Jan 22. doi: 10.1111/jgs.70301. Online ahead of print.

ABSTRACT

BACKGROUND: In 2015, the Netherlands implemented long-term care (LTC) reforms to promote aging-in-place, potentially impacting nursing home (NH) access for older individuals with dementia. This study examines how the reform affected NH admission rates and waiting list prevalence for this population.

METHODS: We performed interrupted time series analyses to evaluate trends in NH admissions (2011-2019, Statistics Netherlands) and waiting list prevalence (2013-2018, National Healthcare Institute) before and after the 2015 LTC reform. Incidence rate ratios (IRR) were calculated for monthly NH admission rates and waiting list prevalence.

RESULTS: Among 270,706 older people with dementia, the reform was negatively associated with NH admission rates (IRR 0.610 [0.547-0.681]), halting the pre-reform decline and stabilizing the post-reform trend (IRR 1.001 [0.999-1.002]). The reform was positively associated with NH waiting list prevalence (IRR 1.159 [1.048-1.282]).

CONCLUSION: Among older Dutch people with dementia, the 2015 Dutch LTC reform was associated with fewer NH admissions and longer waiting lists. While stabilization of the NH admissions may reflect prioritization of persons with dementia within stricter eligibility criteria, the concurrent rise in waiting list prevalence suggests that institutional capacity did not keep pace with persistent need. As a result, many older people with dementia remain longer in the community, raising concerns regarding their health and safety as well as the burden on their informal caregivers.

PMID:41568552 | DOI:10.1111/jgs.70301

Gynecol Endocrinol. 2026 Dec 31;42(1):2618881. doi: 10.1080/09513590.2026.2618881. Epub 2026 Jan 22.

ABSTRACT

BACKGROUND: Astrocytes, once regarded as passive support cells, are recognized as active regulators of synaptic organization and neuronal integration. Through extension or retraction of their processes, astrocytes influence synapse formation and elimination. Astrocytes express estrogen receptors, and animal studies have shown that estradiol modifies astrocytic morphology in relation to synaptic density.

OBJECTIVE: To examine the effects of estradiol and two clinically available selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene on astrocyte processes in human brain tissue.

METHODS: Human temporal lobe cortical slices were incubated for 60 min with estradiol (10 nM), tamoxifen (1.0 µM), or raloxifene (1.0 µM), and the results were compared with untreated control slices. Astrocytes were visualized by immunostaining for the glial cytoskeletal marker glial fibrillary acidic protein (GFAP). Light microscopy image analysis was used to quantify astrocytic process thickness and branching, using Neurolucida® software.

RESULTS: Control slices exhibited astrocytic branch extension and thinning during the incubation period. Similar morphological changes were observed in the tamoxifen-treated slices. In contrast, raloxifene treatment was associated with a significant reduction in astrocyte branching and thinning compared with controls (p = 0.01 for primary processes). Estradiol treatment resulted in intermediate reductions in astroglial process measures that did not reach statistical significance.

CONCLUSIONS: Estradiol, tamoxifen, and raloxifene – widely used hormonal agents – were associated with distinct effects on astrocyte morphology in human cortical tissue. These findings support a role for estrogen receptor modulation in astroglial structural regulation and suggest a potential cellular mechanism contributing to central nervous system symptoms reported in clinical settings.

PMID:41568550 | DOI:10.1080/09513590.2026.2618881

Haematologica. 2026 Jan 22. doi: 10.3324/haematol.2025.288956. Online ahead of print.

ABSTRACT

Red blood cell (RBC) transfusions for anemia associated with lower-risk myelodysplastic syndromes/neoplasms (LR-MDS) often contribute to reduced quality of life (QOL). Thus, reduction in RBC transfusion dependency (TD) is a primary therapeutic goal. Imetelstat is a firstin-class, competitive telomerase inhibitor approved to treat certain adult patients with LR-MDS with RBC-TD anemia who have not responded to, have lost response to, or are ineligible for erythropoiesis-stimulating agents. In the phase III IMerge study (NCT02598661), treatment with imetelstat resulted in clinically meaningful, statistically significant increases in the primary endpoint of ≥8-week RBC transfusion independence (TI) versus placebo. Because patients with LR-MDS experience detrimental effects on numerous facets of QOL (physical, emotional, social, and functional), these exploratory analyses assessed patient-reported outcomes using the Functional Assessment of Chronic Illness Therapy-Fatigue, Quality of Life in Myelodysplasia Scale, and Functional Assessment of Cancer Therapy-Anemia questionnaires as part of the phase III IMerge study. Nominal P values were reported. Fewer imetelstat-treated patients experienced deterioration in fatigue and more imetelstat-treated patients experienced sustained improvement in fatigue and QOL versus placebo. In the imetelstat group, 8-week, 24-week, and 1-year RBC-TI responders had sustained improvements in predefined significance thresholds versus nonresponders for fatigue (70%, 73%, and 88%, respectively, vs. 37%, 41%, and 44%, respectively; P.

PMID:41568521 | DOI:10.3324/haematol.2025.288956

Curr Drug Targets. 2026 Jan 9. doi: 10.2174/0113894501406097251015114440. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aimed to investigate the expression of the epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) tissues and its association with the frequency of legume food intake.

METHODS: Clinical data from 93 NSCLC patients at Jiujiang University-affiliated Hospital (2018-2023) were collected. Postoperative recurrence status and legume intake were obtained via telephone follow-up. Fourteen patients with recurrence or metastasis were assigned to the first progression (FP) group. Propensity score matching (1:3) was used to select 42 non-progression (NP) matched patients, totaling 56 for analysis. Patients were divided into low- and high-legume intake groups. EGFR expression was assessed by immunohistochemistry and statistical analysis.

RESULTS: EGFR positivity was higher in the FP group (78.6%, 11/14) than in the NP group (47.6%, 20/42) (P < 0.05). The NP group had a greater proportion of patients with high-frequency legume consumption compared to the FP group (71.4% vs. 35.7%, P < 0.05). Furthermore, patients with high-frequency legume intake (42.9%, 15/35) showed significantly lower EGFR positivity than those in the low-frequency intake group (76.2%, 16/21) (P < 0.05). These results indicate that higher legume intake correlates with both reduced EGFR expression and a decreased postoperative recurrence risk.

DISCUSSION: These findings suggest that higher legume intake is associated with reduced EGFR expression and better postoperative outcomes in NSCLC patients. Legume consumption may modulate disease progression through EGFR regulation.

CONCLUSION: High legume intake correlates with improved prognosis and lower EGFR expression in NSCLC. Further large-scale prospective studies are needed to validate these associations and explore their clinical implications.

PMID:41568509 | DOI:10.2174/0113894501406097251015114440

Curr Top Med Chem. 2026 Jan 9. doi: 10.2174/0115680266377273251010093254. Online ahead of print.

ABSTRACT

INTRODUCTION: The objective of this study was to synthesize and characterize the Formononetin- Celecoxib Conjugate, evaluate its efficacy both in vitro and in vivo, and ascertain its potential as a medicinal agent for osteoarthritis (OA).

METHODS: Phytoconstituents from Glycine max and FDA-approved drugs were meticulously curated and subjected to computational analyses for target identification and molecular docking. The Formononetin-Celecoxib Conjugate was subsequently synthesized and characterized using spectroscopic techniques. In vitro assessments included MTT viability assays and ELISA analyses. In vivo efficacy was evaluated using an MIA-induced OA mouse model.

RESULTS: Molecular Formononetin-Celecoxib Conjugate has high binding affinity towards MMP-9. In vitro, the conjugate was non-toxic and significantly reduced MMP-9 expression. In vivo, it attenuated paw volume (p < 0.05) and prevented body weight loss in OA-induced mice, especially at 200 mg/kg. Statistical analysis (Mean ± SD; two-way ANOVA with Tukey’s test) confirmed significant therapeutic benefits.

DISCUSSION: The study validates the conjugate’s anti-inflammatory and disease-modifying potential through both computational and experimental approaches. Its effects on MMP-9 inhibition suggest translational relevance for human OA. However, small sample size and lack of blinding remain limitations requiring further investigation.

CONCLUSION: Our study demonstrates the promising potential of the Formononetin-Celecoxib Conjugate as a novel therapeutic intervention for OA. By integrating computational predictions with experimental validations, this approach represents a step toward precision medicine in managing OA.

PMID:41568487 | DOI:10.2174/0115680266377273251010093254

Arterioscler Thromb Vasc Biol. 2026 Jan 22. doi: 10.1161/ATVBAHA.125.324017. Online ahead of print.

ABSTRACT

BACKGROUND: Obesity predisposes individuals to multiple pathologies, including metabolic dysfunction-associated steatotic liver disease and diabetes. Although it is known that accumulation of proinflammatory macrophages within adipose tissues drives adiposity and provokes obesity-linked sequelae, the molecular mechanisms that provoke macrophage dysfunction in obesity remain elusive. Macrophages express high levels of uPA (urokinase plasminogen activator), and uPA has been implicated in leukocyte migration.

METHODS: Human adipose tissues from patients receiving bariatric surgery were collected and analyzed for uPA protein levels. To determine the impact of uPA in adipose tissue and subsequent high-fat diet (HFD)-induced weight gain and metabolic diseases, a novel mouse model with a conditional knockout of uPA (Plau^fl/fl) was generated. Plau^WT/WT, Plau^KO/KO (global uPA deficiency), and Plau^fl/fl/LysM Cre+ (conditional uPA deficiency in macrophages) mice were fed low-fat diet or HFD for up to 20 weeks.

RESULTS: Protein levels of visceral adipose tissue uPA positively correlated with body mass index in patients with obesity, and uPA levels decreased in adipose tissue 2 years after bariatric surgery. The expression and activity of uPA also increased in the adipose tissue of HFD-fed control mice. Plau^KO/KO mice displayed reduced weight gain and metabolic sequelae through 14 weeks on a HFD compared with Plau^WT/WT mice, but not with prolonged HFD feeding. Interestingly, Plau^fl/fl/LysM Cre+ mice developed HFD-induced metabolic pathologies equivalently to Plau^WT/WT mice.

CONCLUSIONS: Our findings suggest that global uPA deletion, but not selective deletion of uPA in LysM+ myeloid cells, attenuates the development of early-stage HFD-driven obesity and pathologies consistent with metabolic syndrome.

PMID:41568458 | DOI:10.1161/ATVBAHA.125.324017

Circ Cardiovasc Imaging. 2026 Jan 22:e018677. doi: 10.1161/CIRCIMAGING.125.018677. Online ahead of print.

ABSTRACT

BACKGROUND: Computed tomography based planimetric assessment of the anatomic aortic valve area (aAVA^CTA) in aortic stenosis is routinely performed. Unlike transthoracic echocardiography-based effective AVA by transthoracic echocardiography, it lacks clearly defined severity cutoff values, limiting clinical utility.

METHODS: In this retrospective single-center analysis with computed tomography angiography data from 2013 to 2025, cutoffs were determined from 1294 transthoracic echocardiography-based conclusive severe or nonsevere patients by congruence of maximum velocity, mean pressure gradient, and effective AVA by transthoracic echocardiography. In separate receiver operator curves analyses for tricuspid and bicuspid valves, the severe stenosis likely cutoff was defined by Youden index and the unlikely cutoff by a negative likelihood ratio <0.1. Cutoffs were internally validated in 480 patients, compared with the Agatston score by net reclassification index, and tested in 190 separate normal flow-low gradient-aortic stenosis cases.

RESULTS: Correlation between aAVA^CTA and effective AVA by transthoracic echocardiography was moderate and strong in tricuspid and bicuspid valves, respectively (Pearson r 0.67 and 0.78; P<0.001). Severe stenosis was likely in tricuspid valves at aAVA^CTA ≤0.95 cm² (sensitivity 87%, specificity 78.9%) and unlikely at ≥1.10 cm² (negative likelihood ratio, 0.092). In bicuspid valves severe stenosis was likely at aAVA^CTA ≤1.08 cm² (sensitivity 88.3%, specificity 77.3%) and unlikely at ≥1.20cm² (negative likelihood ratio, 0.091). Validation showed comparable results. Net reclassification index compared with the Agatston score was 0.16 for likely and 0.17 for unlikely cutoffs (P<0.001). Cutoffs were applied to 190 suspected severe low-gradient cases. Adding aAVA^CTA as an additional severity marker led to reclassification to nonsevere in 5.8% of cases.

CONCLUSIONS: Direct planimetry of AVA is feasible and shows utility in low gradient-aortic stenosis. However, as the hemodynamic effect is impacted by valve shape, cutoff values should differentiate between tricuspid and bicuspid valves.

PMID:41568440 | DOI:10.1161/CIRCIMAGING.125.018677

J Interprof Care. 2026 Jan 22:1-13. doi: 10.1080/13561820.2025.2609088. Online ahead of print.

ABSTRACT

Validating an interprofessional education and collaborative practice (IPECP) curriculum prior to implementation is uncommon. A sound empirical investigation involving external and internal participants considered four criteria: relevance, consistency, practicality, and effectiveness, as part of an educational design research process to assess whether the proposed curriculum content was valid for the South African healthcare higher education context. Participants provided quantitative input on the four criteria on a visual analog scale (0-100) and qualitative comments to suggest improvements to the proposed curriculum. Descriptive statistics and deductive thematic analysis were used for data analysis. The participants lauded the proposed curriculum. Relevance generated strong agreement and consensus (m = 99, IQR = 6.75), with a lower, but still adequate, rating and consensus for practicality (m = 85.5, IQR = 25.75). The consistency and effectiveness, rated across years of study and streams, indicated in ratings and consensus with an increase across years of study from the first to the last year. Of the streams, the proposed Research and Ethics stream appeared to be the most problematic with moderate consensus (m = 90, IQR = 19.75). Curriculum validation before implementation illuminated concerns requiring refinement and strengthening responsive strategies to ensure a tailored implementation of the proposed curriculum.

PMID:41568431 | DOI:10.1080/13561820.2025.2609088