Nevin Manimala

J Med Internet Res. 2025 Aug 12;27:e70414. doi: 10.2196/70414.

ABSTRACT

BACKGROUND: Virtual care interventions have the potential to improve access to care and serial medication intensification for patients with chronic heart failure with reduced ejection fraction (HFrEF). However, concerns remain that these interventions might unintentionally create or widen existing disparities in care delivery and patient outcomes.

OBJECTIVE: This study aimed to characterize the health care use patterns of patients who have HFrEF, including specialty type and frequency of in-person and virtual visits.

METHODS: We conducted a retrospective cohort study of patients with HFrEF within a large health system. Inclusion criteria were patients alive with an ejection fraction ≤40% as of September 1, 2021, and at least one virtual or in-person outpatient visit to a primary care or cardiology clinician in the prior year. Descriptive statistics were used to evaluate baseline patient demographics and clinical use data and outcomes. Univariate analyses were performed both with virtual visits as a variable (received or did not receive) using the chi-square test for association and as a discrete outcome using the Wilcoxon rank-sum test to capture potentially important predictor variables that could influence use or frequency of using virtual visits. The primary outcome of interest was the odds of at least one virtual visit during the 1-year evaluation period from 2021 to 2022. Descriptive statistics were used to evaluate baseline patient demographics and care use. A logistic regression model was used to model at least one primary care or cardiology virtual visit.

RESULTS: A total of 8481 patients were included in the analysis. The mean age was 65.9 years (SD 15.1), 5672 (66.9%) patients were male and 6608 (77.9%) patients were non-Hispanic White. The majority of patients had no cardiology (7938/8481, 93.6%) or primary care (7955/8481, 93.8%) virtual visits during the evaluation period. Multivariable logistic regression showed significantly higher odds of having at least one virtual visit for patients with certain digital access-for example, email on file (odds ratio [OR] 9.3, P≤.001), cell phone on file (OR 2.9, P≤.001), and active electronic health record patient portal (OR 2.8, P≤.001)-than those without. Age, race, ethnicity, rurality, and Social Vulnerability Index were not associated with virtual visits.

CONCLUSIONS: Only a minority of patients with HFrEF were seen via virtual visits. Patients who regularly used digital technology were more likely to have virtual visits. Patients were more likely to be seen in a cardiology clinic than by a primary care provider. Although there was no evidence of an association between social determinants of health factors like race, ethnicity, or rurality with digital divide indicators, these findings should be interpreted with caution given the limitations of these data. Future studies should aim to replicate the findings of this study and explore ways to enhance the effective and equitable use of virtual visits.

PMID:40795329 | DOI:10.2196/70414

J Bone Miner Res. 2025 Aug 8:zjaf091. doi: 10.1093/jbmr/zjaf091. Online ahead of print.

ABSTRACT

The aim of this international meta-analysis was to quantify the predictive value of body mass index (BMI) for incident fracture and relationship of this risk with age, sex, follow-up time and bone mineral density (BMD). 1 667 922 men and women from 32 countries (63 cohorts), followed for a total of 16.0 million person-years were studied. 293 325 had femoral neck BMD measured (2.2 million person-years follow-up). An extended Poisson model in each cohort was used to investigate relationships between WHO-defined BMI categories (Underweight:<18.5 kg/m2; Normal:18.5-24.9 kg/m2; Overweight:25.0-29.9 kg/m2; Obese I:30.0-34.9 kg/m2; Obese II:≥35.0 kg/m2) and risk of incident osteoporotic, major osteoporotic and hip fracture (HF). Inverse-variance weighted β-coefficients were used to merge the cohort-specific results. For the subset with BMD available, in models adjusted for age and follow-up time, the hazard ratio (95%CI) for HF comparing underweight with normal weight was 2.35 (2.10-2.60) in women and for men was 2.45 (1.90-3.17). HF risk was lower in overweight and obese categories compared to normal weight [obese II vs normal: women 0.66 (0.55-0.80); men 0.91 (0.66-1.26). Further adjustment for femoral neck BMD T-score attenuated the increased risk associated with underweight [underweight vs normal: women 1.69 (1.47-1.96); men 1.46 (1.00-2.13)]. In these models, the protective effects of overweight and obesity were attenuated, and in both sexes the direction of association reversed to higher fracture risk in Obese II category [Obese II vs Normal: women 1.24 (0.97-1.58); men 1.70 (1.06-2.75)]. Results were similar for other fracture outcomes. Underweight is a risk factor for fracture in both men and women regardless of adjustment for BMD. However, whilst overweight/obesity appeared protective base models, they became risk factors after additional adjustment for femoral neck BMD, particularly in the Obese II category. This effect in the highest BMI categories was of greater magnitude in men than women. These results will inform the second iteration of FRAX.

PMID:40795319 | DOI:10.1093/jbmr/zjaf091

J Immunol. 2025 Aug 7:vkaf155. doi: 10.1093/jimmun/vkaf155. Online ahead of print.

ABSTRACT

Tumor clearance by T cells is impaired by insufficient tumor antigen recognition, insufficient tumor infiltration, and the immunosuppressive tumor microenvironment. Although targeted T cell therapy circumvents failures in tumor antigen recognition, suppression by the tumor microenvironment and failure to infiltrate the tumor can hinder tumor clearance. Checkpoint inhibitors (CPIs) promise to reverse T cell suppression and can be combined with bispecific antibody armed T cell (BAT) therapy to improve clinical outcomes. We hypothesize that adoptively transferred T cell function may be improved by the addition of CPIs if the inhibitory pathway is functionally active. This study develops a kinetic-dynamic model of killing of hormone receptor-positive breast cancer cells mediated by BATs using single-cell transcriptomic and temporal protein data to identify T cell phenotypes and quantify inhibitory receptor expression. LAG3, PD-1, and TIGIT were identified as inhibitory receptors expressed by cytotoxic effector CD8 BATs upon exposure to hormone receptor-positive breast cancer cell lines. These data were combined with real-time tumor cytotoxicity data in a multivariate statistical analysis framework to predict the relevant contributions of T cells expressing each receptor to tumor reduction. A mechanistic kinetic-dynamic mathematical model was developed and parametrized using protein expression and cytotoxicity data for in silico validation of the findings of the multivariate statistical analysis. The model corroborated the predictions of the multivariate statistical analysis which identified LAG3+ BATs as the primary effectors, while TIGIT expression dampened cytotoxic function. These results inform CPI selection for BATs combination therapy and provide a framework to maximize BATs antitumor function.

PMID:40795300 | DOI:10.1093/jimmun/vkaf155

J Proteome Res. 2025 Aug 12. doi: 10.1021/acs.jproteome.5c00297. Online ahead of print.

ABSTRACT

Over the past 30 years, software for searching tandem mass spectrometry data against a protein database has improved dramatically in speed and statistical power. However, existing tools can still struggle to analyze truly massive data sets when either the number of spectra or the number of proteins being analyzed grows too large. Here, we describe enhancements to the Tide search engine that allow it to handle data sets containing >10 million spectra and databases containing >7 billion peptides on commodity hardware. We demonstrate that the new Tide architecture is around 2-7 times faster than the previous version and is now comparable to MSFragger and Sage in speed while requiring much less memory. Tide is open source and is publicly available as precompiled binaries for Windows, Linux, and Mac.

PMID:40795295 | DOI:10.1021/acs.jproteome.5c00297

J Crohns Colitis. 2025 Aug 8:jjaf132. doi: 10.1093/ecco-jcc/jjaf132. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: We investigated the correlations between patient-reported outcome measures (PROMs) and other measures of inflammatory bowel disease (IBD) activity.

METHODS: A systematic literature review was performed up to June 2022. Searches were conducted in PubMed, Scopus and Web of Science. A descriptive analysis was performed. The search protocol was registered in PROSPERO (CRD42022383899).

RESULTS: Nineteen studies assessed correlations between PROMs and clinical, endoscopic, and laboratory measures of disease activity in IBD. In Crohn’s disease (CD), weak positive correlations were reported for PROMs (e.g. the two-item patient reported outcome [PRO-2], mobile Health Index [mHI] for CD) and endoscopic scores, more often the Simple Endoscopic Score for CD (SES-CD). In ulcerative colitis (UC), PROMs like PRO-2, the Monitor IBD at Home rectal bleeding item and the mHI, showed weak-to-moderate correlations with the Mayo endoscopic subscore (MES). PROMs also demonstrated limited concordance with laboratory measures such as faecal calprotectin (FCP) and C-reactive protein (CRP) in both CD and UC. The substantial heterogeneity in study designs precluded a structured analysis.

CONCLUSIONS: Although current PROMs offer valuable complementary insights into IBD control from the patient’s perspective, they cannot replace objective measures of IBD activity. Future research should focus on refining PROMs and generating composite indices to improve their accuracy and usefulness.

PMID:40795293 | DOI:10.1093/ecco-jcc/jjaf132

J Trop Pediatr. 2025 Aug 8;71(5):fmaf034. doi: 10.1093/tropej/fmaf034.

ABSTRACT

The World Health Organization (WHO) recommends Xpert® MTB/RIF (Xpert) and its advanced version, Xpert® MTB/RIF Ultra (Xpert Ultra), as first-line diagnostic tests for detecting pulmonary tuberculosis (PTB) and rifampicin resistance in children suspected of having the disease. Respiratory specimens (gastric lavage/bronchoalveolar lavage/sputum/endotracheal aspirate) obtained from 116 children with presumptive PTB were simultaneously processed using liquid medium culture, Xpert assay, and Xpert Ultra assay. Among the specimens from 116 children, six were excluded due to culture contamination (n = 5) or error in Xpert Ultra results (n = 1). Among the remaining 110 specimens, 20 were positive by liquid culture. The former and latter, of the two comparator tests gave a sensitivity of 90% and 95%, respectively. The respective specificity was 93.3% and 88.9%. Xpert Ultra showed a statistically significant slightly higher sensitivity than Xpert. Xpert Ultra showed slightly higher sensitivity than Xpert, with a minimal loss in specificity, partly due to the inclusion of trace results, which help detect paucibacillary cases.

PMID:40795255 | DOI:10.1093/tropej/fmaf034

Genetics. 2025 Aug 7:iyaf158. doi: 10.1093/genetics/iyaf158. Online ahead of print.

ABSTRACT

Testing inferred haplotype genealogies for association with phenotypes has been a longstanding goal in human genetics given their potential to detect association signals driven by allelic heterogeneity – when multiple causal variants modulate a phenotype – in both coding and noncoding regions. Recent scalable methods for inferring locus-specific genealogical trees along the genome, or representations thereof, have made substantial progress towards this goal; however, the problem of testing these trees for association with phenotypes has remained unsolved due to the growth in the number of clades with increasing sample size. To address this issue, we introduce several practical improvements to the kalis ancestry inference engine, including a general optimal checkpointing algorithm for decoding hidden Markov models, thereby enabling efficient genome-wide analyses. We then propose LOCATER, a powerful new procedure based on the recently proposed Stable Distillation framework, to test local tree representations for trait association. Although LOCATER is demonstrated here in conjunction with kalis, it may be used for testing output from any ancestry inference engine, regardless of whether such engines return discrete tree structures, relatedness matrices, or some combination of the two at each locus. Using simulated quantitative phenotypes, our results indicate that LOCATER achieves substantial power gains over traditional single marker testing, ARG-Needle, and window-based testing in cases of allelic heterogeneity, while also improving causal region localization. These findings suggest that genealogy-based association testing will be a fruitful approach for gene discovery, especially for signals driven by multiple ultra-rare variants.

PMID:40795253 | DOI:10.1093/genetics/iyaf158

J Gerontol B Psychol Sci Soc Sci. 2025 Aug 7:gbaf151. doi: 10.1093/geronb/gbaf151. Online ahead of print.

ABSTRACT

OBJECTIVES: Recent studies suggest that the association between social participation and mental health may change with age, although the direction of this relationship is unclear. While some suggest that the mental health benefits of social participation decline with age, others argue they become more important in later life. In this paper, we suggest a context-dependent divergence in aging trajectories: whereas urban older adults continue to gain mental health benefits from social participation, their rural counterparts gradually stop deriving such benefits over time.

METHODS: We drew on four waves of the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018; N = 16,233; 53,056 person-years) to examine how social participation shapes depressive symptoms among adults aged 45 and older. Growth curve models were employed to assess the age-related trajectories of the effects of social participation on depressive symptoms, and interaction terms were introduced to analyze urban-rural differences.

RESULTS: A significant three-way interaction (Informal Social Participation × Rural × Age) revealed that the mental health benefits of informal social participation increased with age among urban older adults but gradually declined among their rural counterparts. This divergence became statistically significant at around age 60 and continued to widen thereafter, indicating a growing urban advantage in the protective effects of informal engagement over time.

DISCUSSION: These findings suggest that the mental health benefits of social participation change with age in ways shaped by residential context, highlighting the need to consider how urban and rural environments differently influence aging trajectories.

PMID:40795235 | DOI:10.1093/geronb/gbaf151

Blood Adv. 2025 Aug 12:bloodadvances.2025017004. doi: 10.1182/bloodadvances.2025017004. Online ahead of print.

ABSTRACT

Atypical hemolytic uremic syndrome (aHUS), a life-threatening complement-mediated disorder, is now treatable with terminal complement inhibitors like eculizumab. Although effective, these therapies are costly and increase susceptibility to infections, notably meningococcal disease, raising concerns about long-term use. The optimal duration of complement inhibition remains unclear, prompting efforts to explore the possibility of treatment discontinuation. We conducted a systematic review and meta-analysis to evaluate the benefits and risks of stopping terminal complement inhibitor therapy in aHUS. We searched PubMed, Scopus, and CINAHL for studies of continuing vs. stopping anti-complement treatment in aHUS. Of 3303 identified studies, 13 observational studies (3 case-control, 10 cohort) comprising 584 patients were included. Overall, continuing treatment was associated with an approximately 76% reduction in the odds of relapse (odds ratio [OR] 0.24, 95% CI: 0.09 to 0.62; p= 0.01.) Study design influenced results: cohort studies showed a more modest effect (OR=0.40 (95% CI: 0.15 to 1.09), while case-control studies reported inflated estimates (OR=0.04 (95%CI: 0.02 to 0.08); subgroup interaction p=0.03). Patients with various genetic variants [CFH, CFHdel, MCP] had decreased relapse with continued therapy when case-control studies were included in the analysis. When the analysis was restricted to cohort studies, the effects became uncertain [statistically non-significant with large confidence intervals]. While current evidence is insufficient to provide personalized guidance on which patients with aHUS can safely discontinue anti-complement therapy, findings from higher-quality studies-which show no statistical difference between continued and discontinued treatment-suggest that discontinuation may be possible for at least some patients.

PMID:40795230 | DOI:10.1182/bloodadvances.2025017004

J Antimicrob Chemother. 2025 Aug 7:dkaf295. doi: 10.1093/jac/dkaf295. Online ahead of print.

ABSTRACT

OBJECTIVES: The spread of carbapenem-resistant Gram-negative bacteria (CR-GNB) related to nosocomial infections is an important public health challenge, and polymyxins have become the last line of defence against CR-GNB. In this study, we aimed to compare the efficacy and safety of different polymyxins.

METHODS: This retrospective cohort study included neurocritical care patients with CR-GNB pneumonia. The efficacy and safety were compared in original and inverse probability of treatment weighting cohorts. A subgroup analysis was further conducted to explore the impact of augmented renal clearance status at baseline on treatment efficacy.

RESULTS: Of the 331 patients included, 90 received colistin sulphate, 187 received polymyxin B, and 54 received colistin methanesulfonate sodium. Compared with colistin sulphate, colistin methanesulfonate sodium significantly reduced the clinical failure rate on Day 7 (20.8% versus 37.2%, P = 0.034) and 28-day mortality rate (6.2% versus 16.9%, P = 0.013) and improved the microbiological eradication rate on Day 28 (94.8% versus 84.2%, P = 0.013). The colistin methanesulfonate sodium group also had a lower mortality rate (6.2% versus 15.7%, P = 0.005) and clinical failure rate on Day 28 (17.1% versus 27.4%, P = 0.020) than the polymyxin B group. However, colistin methanesulfonate sodium was more nephrotoxic than colistin sulphate and polymyxin B (P = 0.001 and P = 0.004, respectively). Subgroup analysis revealed no statistical difference in clinical failure rate and mortality risk between the three groups.

CONCLUSIONS: For CR-GNB pneumonia in neurocritical care patients, intravenous colistin methanesulfonate sodium may provide a useful treatment option, but vigilance is warranted for nephrotoxicity.

PMID:40795180 | DOI:10.1093/jac/dkaf295