Nevin Manimala

AIDS Behav. 2025 Jan 30. doi: 10.1007/s10461-025-04616-y. Online ahead of print.

ABSTRACT

Pre-exposure prophylaxis (PrEP) has proven to be a powerful tool in preventing HIV infection. There is limited information about the factors associated with willingness to use different PrEP modalities among adolescent girls and young women (AGYW) in Africa. We assessed willingness to use long-acting injectable PrEP (LAI-PrEP) among 14-24-year-old AGYW at high risk of HIV in Uganda, and associated factors determined using multivariable complementary log-log regression. Of the 285 participants, 69.8% of participants showed willingness to use LAI-PrEP despite only 3.9% having knowledge about it before enrolment. Report of recent transactional sex was high (92.6%). Participants that were divorced/separated (aOR = 1.74, 95% CI 1.03-2.92) and those with multiple sexual partners (aOR = 2.11, 95% CI 1.46-3.06) compared to those with one partner were more likely to be willing to use LAI-PrEP while those that were screened as heavy episodic drinkers (consuming 6 or more drinks on an occasion as per the AUDIT tool) were less likely to be willing to use LAI-PrEP (aOR = 0.61, 95% CI 0.42-0.87). LAI PrEP has shown efficacy in clinical trials; the product is approved for use by the Government of Uganda (MoH) and should be expedited for use by AGYW engaged in paid sex and those with multiple sexual partnerships. As it becomes available, we recommend PrEP education and counseling to increase awareness of LAI PrEP as an alternative HIV prevention method.

PMID:39883369 | DOI:10.1007/s10461-025-04616-y

J Nephrol. 2025 Jan 30. doi: 10.1007/s40620-025-02211-x. Online ahead of print.

ABSTRACT

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is caused primarily by pathogenic variants in the PKD1 and PKD2 genes. Although the type of ADPKD variant can influence disease severity, rare, hypomorphic PKD1 variants have also been reported to modify disease severity or cause biallelic ADPKD. This study examines whether rare, additional, potentially protein-altering, non-pathogenic PKD1 variants contribute to ADPKD phenotypic outcomes.

METHODS: We investigated the prevalence of rare, additional, potentially protein-altering PKD1 variants in patients with PKD1-associated ADPKD. The association between rare, additional, potentially protein-altering variants and phenotypic outcomes, including progression to kidney failure, age at onset of hypertension and urological events, height-adjusted total kidney volume, and predicting renal outcomes in PKD (PROPKD) score, were examined.

RESULTS: Rare, additional, potentially protein-altering variants were detected in 6% of the 932 ADPKD patients in the study. The presence of rare, additional, potentially protein-altering variants was associated with 4 years earlier progression to kidney failure (hazard ratio (HR): 1.66; 95% confidence interval (CI): 1.18-2.34; P = 0.003), with in-trans rare, additional, potentially protein-altering variants (n = 13/894) showing a greater risk of kidney failure (HR: 1.83; 95% CI 1.00-3.33; P = 0.049). We did not detect statistically significant differences between rare, additional, potentially protein-altering variants and other phenotypic outcomes compared to those without rare, additional, potentially protein-altering variants.

CONCLUSIONS: In patients with PKD1-associated ADPKD, our findings suggest that rare, additional, potentially protein-altering variants in PKD1 may influence disease severity. These findings have potential clinical implications in counselling and treating patients with rare, additional, potentially protein-altering variants, but further investigation of such variants in larger, longitudinal cohorts with detailed, standardised phenotype data is required.

PMID:39883360 | DOI:10.1007/s40620-025-02211-x

Neurol Sci. 2025 Jan 30. doi: 10.1007/s10072-025-08020-1. Online ahead of print.

ABSTRACT

BACKGROUND: Non-motor symptoms, including depression, anxiety, sleep disturbances, pain and cognitive dysfunction, are a much more important predictor of quality of life than the severity of dystonia.

OBJECTIVES: To assess the effect of Botulinum toxin on non-motor symptoms and quality of life in patients with adult-onset idiopathic focal dystonia.

METHODS: Patients aged > 18 years diagnosed with idiopathic focal dystonia were recruited in this longitudinal cohort study. The severity of dystonia, non-motor symptoms, and quality of life were evaluated using the BFMDRS, DNMSQuest, and EQ-5D at baseline and 1 and 3 months after botulinum toxin.

RESULTS: 65 patients were recruited with a median age of 59 years. Blepharospasm was the most common phenomenology. 49.2% of patients had depression at baseline assessed using the Beck Depression Inventory (BDI). There was a significant negative correlation between baseline BFMDRS, DNMSQuest, BDI, and HAM-A scores and quality of life, but there was no relation with the type of focal dystonia. The mean percentage improvement in the BFMDRS-M, BFMDRS-D, DNMSQuest, BDI, HAM-A and EQ-5D was 25%, 52%, 16%,20%,23% and 23%, respectively, at one month. There was no statistically significant correlation between percentage change in motor scores compared to depression and quality of life scores at one month.

CONCLUSION: Botulinum toxin improved motor and non-motor scores and quality of life at 1 and 3 months after botulinum toxin therapy. The motor scores did not correlate with depression and DNMSQUEST scores but showed a weak positive correlation with anxiety scores.

PMID:39883352 | DOI:10.1007/s10072-025-08020-1

Bull Math Biol. 2025 Jan 30;87(3):37. doi: 10.1007/s11538-025-01414-4.

ABSTRACT

Compared to our closest primate relatives, human life history involves greater longevity, which includes a distinctive postmenopausal life stage. Given mammalian reproductive physiology in which females build a finite stock of cells that can become oocytes early in life, which then continuously deplete mostly through cell death while males produce new sperm throughout adulthood, the postmenopausal stage makes the sex ratio in the fertile pool, called the adult sex ratio (ASR), male biased. Additionally, this affects a more fine-grained ratio, the operational sex ratio (OSR), defined as the ratio of males to females currently able to conceive. Here, we construct an ODE model in which males compete for paternities using either a multiple-mating or mate-guarding strategy. Our focus is on investigating the differences of strategy choice between populations with varying life histories, which include a distinct post-fertile stage for adult females. By simulating the system, we determine the dominant strategy and its dependence on various parameter combinations. Our results show that an increase in OSR and ASR correlates well with a change in the dominant strategy from multiple mating to guarding.

PMID:39883339 | DOI:10.1007/s11538-025-01414-4

Updates Surg. 2025 Jan 30. doi: 10.1007/s13304-025-02086-4. Online ahead of print.

ABSTRACT

BACKGROUND: Primary hyperparathyroidism (PHPT) due to a parathyroid adenoma stands as one of the most prevalent endocrinological disorders, with focused parathyroidectomy being the established therapeutic strategy.

AIM: This study aims to investigate whether the volume of the pathological gland influences perioperative outcomes and postoperative morbidity.

METHODS: A retrospective analysis was conducted on data from 141 patients who underwent focused parathyroidectomy for PHPT at the University Hospital of Basel between 2007 and 2022.

RESULTS: A total of 141 patients underwent surgery, with a mean age of 57.2 years and prevalence of women (64.5%).The volume of the lesion was divided into three groups (low < 1 ml, middle 1-1.99 ml, large > 2 ml) based on pathological specimen analysis. Preoperative calcium and parathyroid hormone (PTH) values were significantly higher in the large volume group compared to the low volume group (p < 0.05), while phosphate and vitamin D values were significantly lower (p < 0.05). A comparison of adenoma volume in symptomatic patients with asymptomatic patients revealed no statistically significant difference (p = 0.845) and the volume of the gland of any group did not influence the length of the operation (p = 0.173) and the perioperative morbidity (p = 0.108).

CONCLUSION: Compared to a volume of less than 1 ml, a parathyroid gland volume greater than 2 ml was associated with higher preoperative PTH and calcium levels and lower phosphate and vitamin D levels. The volume of the parathyroid gland does not seem to impact the clinical manifestations, or the incidence of perioperative complications.

PMID:39883321 | DOI:10.1007/s13304-025-02086-4

Adv Ther. 2025 Jan 30. doi: 10.1007/s12325-024-03099-y. Online ahead of print.

ABSTRACT

INTRODUCTION: Atrial fibrillation (AF), a common heart rhythm abnormality, is linked to a higher risk of stroke. Traditionally, warfarin has been the primary anticoagulation treatment for reducing the stroke risk. The new standard of treatment by direct oral anticoagulants (DOACs) offers greater benefits including improved efficacy and fewer adverse effects with reduced monitoring. This study aims to evaluate the risk of stroke/systemic embolism (SE) and major bleeding (MB) among patients with AF who switched from warfarin to DOACs.

METHODS: This study utilized Medicare data to conduct a retrospective analysis of patients with non-valvular atrial fibrillation (NVAF) who switched from warfarin to DOACs between January 1, 2012, and December 31, 2019. Patients with NVAF aged 65 and older who switched from warfarin and had continuous health plan enrollment were included. Descriptive statistics, propensity score matching (PSM), and Cox proportional hazard (PH) models were utilized to compare the outcomes and assess risks of SE and MB across the DOAC cohorts.

RESULTS: Among 1,843,495 patients with NVAF on warfarin, 171,700 switched to DOACs within 90 days of discontinuation (apixaban: 90,850; rivaroxaban: 67,698; dabigatran: 12,900). The mean follow-up period across DOAC cohorts ranged from 552 to 628 days. After PSM, apixaban showed significantly lower rates of stroke/SE compared to dabigatran (2.99% vs. 3.98%, p < 0.0001) and rivaroxaban (3.08% vs. 3.80%, p < 0.0001). MB rates were also lower with apixaban versus dabigatran (4.29% vs. 5.57%, p < 0.0001) and rivaroxaban (4.07% vs. 6.35%, p < 0.0001). Cox PH models confirmed these findings, with apixaban demonstrating lower risks of stroke/SE [hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.72-0.96 vs. dabigatran; HR 0.91, 95% CI 0.85-0.96 vs. rivaroxaban] and MB (HR 0.79, 95% CI 0.71-0.89 vs. dabigatran; HR 0.68, 95% CI 0.65-0.72 vs. rivaroxaban).

CONCLUSION: The risk of stroke/SE and MB varies significantly among patients with NVAF switching from warfarin to different DOACs, with apixaban presenting the lowest risk compared to dabigatran and rivaroxaban.

PMID:39883308 | DOI:10.1007/s12325-024-03099-y

J Assist Reprod Genet. 2025 Jan 30. doi: 10.1007/s10815-024-03374-5. Online ahead of print.

ABSTRACT

The objective of this study is to explore the impact of the use of granulocyte-macrophage colony-stimulating factor (GM-CSF) in female undergoing assisted reproductive technology (ART) on reproductive outcomes. A literature search was performed using electronic databases (PubMed, EMBASE, Web of Science, CNKI, Wanfang data, Geen Medical, and Cochrane Library). Risk ratio (RR), odds ratio (OR), and mean difference (MD) with 95% confidence intervals (CI) for various outcomes were presented. The publication bias and heterogeneity were determined using funnel plot symmetry and I² test separately. The combined results of the RCT studies did not reveal statistical differences between the GM-CSF group and the control group for any outcome indicators. However, our pooling of results showed that after meta-analysis of non-RCT studies, GM-CSF had a positive effect on implantation rate (OR 1.90; 95% CI 1.11-3.24), clinical pregnancy rate (OR 1.54; 95% CI 1.21-1.95), live birth rate (OR 1.43; 95% CI 1.04-1.98), and available embryo rate (OR 1.27; 95% CI 1.10-1.46). In conclusion, these results suggest that for a subset of women undergoing ART, GM-CSF may favorably affect CPR, LBR, IR, and available embryo rate (AER). TRIAL REGISTRATION: PROSPERO registration number CRD42022322778.

PMID:39883302 | DOI:10.1007/s10815-024-03374-5

Diabetes Ther. 2025 Jan 30. doi: 10.1007/s13300-025-01696-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Scientific publications have shown sodium-glucose co-transporter-2 (SGLT2) inhibitors to have several beneficial effects in patients with complex type 2 diabetes mellitus (T2DM). However, sodium-glucose co-transporter-1 (SGLT-1) inhibitor is still under investigation in clinical trials. Recently, a dual inhibitor of sodium-glucose co-transporter (SGLT1/2), sotagliflozin, has been approved for use in patients with T2DM. In this analysis, we aimed to systematically compare the cardiovascular outcomes in patients with complex T2DM who were treated with the newly approved dual (SGLT 1 and 2) inhibitor sotagliflozin.

METHODS: Electronic databases, including Embase, MEDLINE, http://www.

CLINICALTRIALS: gov , Web of Science, Google Scholar, the Cochrane database, and reference lists of relevant publications, were searched for publications comparing the novel SGLT1/2 inhibitor versus placebo for the treatment of patients with complex T2DM. The primary endpoint, including total number of deaths from cardiovascular causes, hospitalization for heart failure, and urgent visits for heart failure, death from cardiovascular causes, cardiac mortality, hospitalization for heart failure, non-fatal myocardial infarction, and total number of cardiac events, were considered as the endpoints in this analysis. The RevMan software version 5.4 was used to carry out the statistical analysis. Risk ratios (RR) with 95% confidence intervals (CI) were used to represent the data following analysis.

RESULTS: A total of 13,054 participants enrolled between 2017 and 2020 were included in this analysis, with 6734 participants assigned to sotagliflozin and 6320 assigned to placebo. The results of this analysis showed that the primary endpoint was significantly in favor of sotagliflozin with (RR: 0.73, 95% CI 0.67-0.80; P = 0.00001). Hospitalization for heart failure (RR: 0.67, 95% CI 0.60-0.75; P = 0.00001) and the total number of cardiac events (RR: 0.73, 95% CI 0.67-0.79; P = 0.00001) were also significantly lower with sotagliflozin when compared to placebo in these patients with complex T2DM. However, the risk for cardiovascular mortality and non-fatal myocardial infarction were not significantly different with (RR: 0.91, 95% CI 0.76-1.09; P = 0.31) and (RR: 0.92, 95% CI 0.27-3.12; P = 0.89), respectively.

CONCLUSIONS: Cardiovascular outcomes, including the total number of adverse cardiac events and hospitalization for heart failure, were significantly reduced with the newly approved SGLT1/2 inhibitor sotagliflozin apparently showing its cardiovascular efficacy in patients with complex T2DM. Future trials with larger sample sizes and a longer follow-up time could possibly confirm this hypothesis.

PMID:39883288 | DOI:10.1007/s13300-025-01696-w

Invest New Drugs. 2025 Jan 30. doi: 10.1007/s10637-025-01506-x. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) combined with anti-vascular endothelial growth factor (VEGF) have been the standard first-line treatment of hepatocellular carcinoma (HCC). However, the efficacy of this combination in post-line treatment is still unknown. This study aimed to evaluate the efficacy and safety of the combination of anti-PD-L1 envafolimab and novel humanized anti-VEGF suvemcitug as second-line treatment for patients with HCC.

METHODS: This open-label, prospective phase II clinical study (NCT05148195) comprised safety run-in stage and dose expansion stage of HCC cohort. Eligible patients were aged ≥ 18 years and had undergone at least a prior line of treatment. Patients received fixed-dose envafolimab and suvemcitug until termination of disease progression, unacceptable toxicities, or withdrawal. The primary endpoint of safety run-in stage was recommended dose (RD), and dose expansion stage was objective response rate (ORR).

RESULTS: As of August 10, 2023, no dose-limiting toxicity was observed in six patients in the safety-run-in stage, and 2 mg/kg dose every 3 weeks was declared the RD of suvemcitug. Among 20 patients with HCC, the median age was 54.5 (range, 42-70) years. Of these patients, 20 (100.0%) received ≥ one prior line treatment, with 20 (100%) received tyrosine kinase inhibitor (TKI) treatment and 8 (40.0%) received prior ICI treatment. The ORR was 10.0% (95% confidence interval (CI), 1.2-31.7), DCR was 65.0% (95% CI, 40.8-84.6), and DoR was not reached (NR). With a median follow-up of 13.9 months, the median progression-free survival (PFS) and median overall survival (OS) were 4.3 months (95% CI, 1.4-8.1) and 10.7 months (95% CI, 6.0-not evaluable [NE]), respectively. Treatment-related adverse events (TRAEs) of grade ≥ 3 occurred in 40% patients, with proteinuria (20.0%, 4/20) being the most frequent. The ORR of no lung metastasis, prior first-line treatment and IO naïve treatment subgroup was 16.7%.

CONCLUSIONS: The combination of envafolimab and suvemcitug showed a tolerable safety profile and promising antitumor activity in HCC patients who failed later-line treatment.

PMID:39883265 | DOI:10.1007/s10637-025-01506-x

Lasers Med Sci. 2025 Jan 30;40(1):54. doi: 10.1007/s10103-025-04296-z.

ABSTRACT

To investigate the efficacy and safety of picosecond (PS) and nanosecond (NS) 1064-nm neodymium-doped yttrium aluminum garnet (Nd: YAG) laser in treating Café-au-lait macules (CALMs). We retrospectively analyzed the medical records of patients with CALMs, who were treated with PS or NS 1064-nm lasers from January 2020 to January 2022. The efficacy was determined based on the before and after pictures by two independent investigators. The incidence of adverse events and recurrence were explored after treatments. A total of 116 patients (83 in the PS group and 33 in the NS group) were recruited. For subjects in the PS group, after 1-9 sessions, the lesion clearance was poor in 15 patients (18.1%), fair in 29 (34.9%), good in 14 (16.9%), and excellent in 25 (30.1%). In the NS group, after 1-7 sessions, the lesion clearance was poor, fair, good, and excellent in 7 (21.2%), 8 (24.2%), 13 (39.4%), and 5 (15.2%) patients, respectively. There was no statistically significant difference in efficacy between the two lasers (p > 0.05). The incidence of complications (hyperpigmentation, hypopigmentation) in the PS group (16.9%) was numerically lower than in the NS group (24.2%) (p = 0.136). Among patients who responded well to the treatment, 10.3% of patients in the PS group experienced relapse, compared with 22.2% in the NS group (p = 0.926). The PS 1064-nm laser provided comparable efficacy and potentially fewer complications compared with the NS laser in treating CALMs.

PMID:39883241 | DOI:10.1007/s10103-025-04296-z