Category: Nevin Manimala

Ann Med. 2025 Dec;57(1):2451762. doi: 10.1080/07853890.2025.2451762. Epub 2025 Jan 23.

ABSTRACT

BACKGROUND: This study was aimed to explore the global burden and trends of Clostridioides difficile infections (CDI) associated diseases.

METHODS: Data for this study were obtained from the Global Burden of Disease Study 2021. The burden of CDI was assessed using the age-standardized rates of disability-adjusted life years (ASR-DALYs) and deaths (ASDRs). Trends in the burden of CDI were presented using average annual percentage changes (AAPCs).

RESULTS: The ASR-DALYs for CDI increased from 1.83 (95% UI: 1.53-2.18) per 100,000 in 1990 to 3.46 (95% UI: 3.04-3.96) per 100,000 in 2021, with an AAPC of 2.03% (95% CI: 1.67-2.4%). The ASDRs for CDI rose from 0.10 (95% UI: 0.08-0.11) per 100,000 in 1990 to 0.19 (95% UI: 0.16-0.23) per 100,000 in 2021, with an AAPC of 2.26% (95% CI: 1.74-2.79%). In 2021, higher burdens of ASR-DALYs (10.7 per 100,000) and ASDRs (0.53 per 100,000) were observed in high socio-demographic index (SDI) areas, and among age group over 70 years (31.62/100,000 for ASR-DALYs and 2.45/100,000 for ASDRs). During the COVID-19 pandemic, the global ASR-DALYs and ASDRs slightly decreased. However, in regions with low SDI, low-middle and middle SDI, those rates slightly increased.

CONCLUSION: The global burden of CDI has significantly increased, particularly in regions with high SDI and among individuals aged 70 years and above. During the COVID-19 pandemic period from 2020 to 2021, the burden of CDI further increased in regions with low, low-middle, and middle SDI. These findings underscore the need for increased attention and intervention, especially in specific countries and populations.

PMID:39847395 | DOI:10.1080/07853890.2025.2451762

Transl Vis Sci Technol. 2025 Jan 2;14(1):21. doi: 10.1167/tvst.14.1.21.

ABSTRACT

PURPOSE: Regulating intraocular pressure (IOP), mainly via the trabecular meshwork (TM), is critical in developing glaucoma. Whereas current treatments aim to lower IOP, directly targeting the dysfunctional TM tissue for therapeutic intervention has proven challenging. In our study, we utilized Dexamethasone (Dex)-treated TM cells as a model to investigate how extracellular vesicles (EVs) from immortalized corneal stromal stem cells (imCSSCs) could influence ANGPTL7 and MYOC genes expression within TM cells.

METHODS: Human TM cell lines were isolated and cultured from donor corneoscleral rims. EVs were purified from imCSSC conditioned media (CM) using size exclusion chromatography and characterized by nanoparticle tracking analysis, transmission electron microscopy (TEM), and ExoView technology. TM cells were treated with either Dex alone or with EVs for 5 days. Quantitative polymerase chain reaction (PCR) was carried out to quantify the mRNA level of MYOC and ANGPTL7.

RESULTS: A notable increase in the expression levels of MYOC and ANGPTL7 genes was observed compared with untreated TM cells (control). Furthermore, upon comparing Dex-treated TM cells with those receiving both Dex and EV treatments, a statistically significant reduction in ANGPTL7 expression (P < 0.05) was detected.

CONCLUSIONS: The present study demonstrates that imCSSCs-derived EVs can effectively decrease the expression of ANGPLT7, a gene associated with fibrosis and implicated in the abnormal elevation of IOP in patients with glaucoma.

TRANSLATIONAL RELEVANCE: Our study shows that imCSSC-derived EVs can specifically target ANGPTL7 expression, making them a promising preclinical therapy for glaucoma.

PMID:39847376 | DOI:10.1167/tvst.14.1.21

Transl Vis Sci Technol. 2025 Jan 2;14(1):23. doi: 10.1167/tvst.14.1.23.

ABSTRACT

PURPOSE: To clarify the clinical and imaging characteristics of Candida keratitis using in vivo confocal microscopy (IVCM) for improved early diagnosis and management.

METHODS: A retrospective study of 40 patients with Candida keratitis at Beijing Tongren Hospital from January 2015 to December 2023 was conducted. Data included demographics, risk factors, clinical assessments, lab tests, and IVCM images. Ex vivo confocal microscopy and methylene blue staining of Candida colonies were also analyzed to complement the findings.

RESULTS: Key risk factors identified were topical steroid use, intraocular surgery history, and systemic diseases. Common clinical signs included multifocal infiltration, cream-colored infiltration, and blurred boundary lesions. IVCM on 37 eyes (92.5%) consistently showed round, highly reflective Candida spores, and short rod-shaped spores in some cases. Spores exhibited two patterns: caviar-like clusters (51.4%) and sand-like dispersion (89.2%). Multifocal infiltration was significantly associated with a greater prevalence of clustered spores (75.0% vs. 33.3%; P < 0.05). Candida pseudo-hyphae appeared as beaded (91.7%) or lotus root-shaped (41.7%), highly reflective structures. These IVCM findings closely matched colony ex vivo confocal microscopy and light microscopy observations. After treatment, 45% of patients required surgery owing to minimal improvement in best-corrected visual acuity. Poor outcomes were linked to cream-colored infiltration, blurred lesions boundaries, hypopyon, high inflammatory cell density, and deep Candida infiltration (P < 0.05). Clustered spores suggested better outcomes, but lacked statistical significance (P > 0.05).

CONCLUSIONS: IVCM effectively identifies characteristic spores and pseudo-hyphae in Candida keratitis, facilitating early detection and timely management, particularly in cases with multifocal infiltration and blurred boundary lesions.

TRANSLATIONAL RELEVANCE: IVCM works well for the early diagnosis of Candida keratitis, especially in cases of deep corneal stromal infiltration or corneal interface infection after corneal transplantation.

PMID:39847374 | DOI:10.1167/tvst.14.1.23

JAMA Oncol. 2025 Jan 23. doi: 10.1001/jamaoncol.2024.5917. Online ahead of print.

ABSTRACT

IMPORTANCE: The effect of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX (combination leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin in full or modified dosing) chemotherapy on overall survival (OS) is unclear because current studies do not account for the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

OBJECTIVE: To investigate the association of adjuvant chemotherapy following resection of pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX with OS, taking into account the number of cycles of preoperative chemotherapy and adjuvant chemotherapy regimen.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study included patients with localized pancreatic adenocarcinoma treated with 2 to 11 cycles of preoperative (m)FOLFIRINOX followed by resection across 48 centers in 20 countries from 2010 to 2018. Patients who died within 3 months after surgery were excluded (landmark). Data were analyzed from February 1 to December 31, 2023.

EXPOSURES: Preoperative (m)FOLFIRINOX chemotherapy followed by resection and eventually followed by adjuvant chemotherapy.

MAIN OUTCOMES AND MEASURES: The primary outcome was OS, calculated from the 3-month landmark. Cox regression analysis, including interaction analyses, was performed to investigate the association of adjuvant chemotherapy with OS.

RESULTS: Overall, 767 patients were included after resection of pancreatic adenocarcinoma (median [IQR] age, 62 [55-67] years; 404 [52.7%] male). Adjuvant chemotherapy was independently associated with prolonged OS (hazard ratio [HR], 0.66; 95% CI, 0.49-0.87), confirmed by adjusted OS curves. The interaction analysis to assess estimated treatment effect across subgroups was not statistically significant. The forest plot and interaction test suggest that the association of adjuvant chemotherapy was lower among patients receiving 8 or more cycles of preoperative (m)FOLFIRINOX, those who had radiological response, and those with ypN0 disease. Compared to no adjuvant chemotherapy, both adjuvant (m)FOLFIRINOX (HR, 0.57; 95% CI, 0.40-0.80) and other multiagent adjuvant regimens (HR, 0.61; 95% CI, 0.41-0.92) were associated with prolonged OS, whereas single-agent adjuvant chemotherapy was not (HR, 0.75; 95% CI, 0.55-1.03).

CONCLUSIONS AND RELEVANCE: In this cohort study, adjuvant (m)FOLFIRINOX and other multiagent chemotherapy regimens were associated with improved OS following resection of localized pancreatic adenocarcinoma after preoperative (m)FOLFIRINOX, whereas single-agent adjuvant chemotherapy was not. The impact of adjuvant chemotherapy on OS may be lower in subgroups such as patients with 8 or more preoperative cycles of (m)FOLFIRINOX, those having radiological response, and those with ypN0.

PMID:39847363 | DOI:10.1001/jamaoncol.2024.5917

JAMA. 2025 Jan 23. doi: 10.1001/jama.2024.24276. Online ahead of print.

ABSTRACT

IMPORTANCE: Previous studies have demonstrated the advantages of short-term histopathological outcomes and complications associated with transanal total mesorectal excision (TME) compared with laparoscopic TME. However, the long-term oncological outcomes of transanal TME remain ambiguous. This study aims to compare 3-year disease-free survival of transanal TME with laparoscopic TME.

OBJECTIVE: To evaluate 3-year disease-free survival between transanal TME and laparoscopic TME in patients with rectal cancer.

DESIGN, SETTING, AND PARTICIPANTS: This randomized, open-label, noninferiority, phase 3 clinical trial was performed in 16 different centers in China. Between April 2016 and June 2021, a total of 1115 patients with clinical stage I to III mid-low rectal cancer were enrolled. The last date of participant follow-up was in June 2024.

INTERVENTIONS: Participants were randomly assigned in a 1:1 ratio before their surgical procedure to undergo either transanal TME (n = 558) or laparoscopic TME (n = 557).

MAIN OUTCOMES AND MEASURES: The primary end point was 3-year disease-free survival, with a noninferiority margin of -10% for the comparison between transanal TME and laparoscopic TME. Secondary outcomes included 3-year overall survival and 3-year local recurrence.

RESULTS: In the primary analysis set, the median patient age was 60 years. A total of 692 male and 397 female patients were included in the analysis. Three-year disease-free survival was 82.1% (97.5% CI, 78.4%-85.8%) for the transanal TME group and 79.4% (97.5% CI, 75.6%-83.4%) for the laparoscopic TME group, with a difference of 2.7% (97.5% CI, -3.0% to 8.1%). The lower tail of a 2-tailed 97.5% CI for the group difference in 3-year disease-free survival was above the noninferiority margin of -10 percentage points. Furthermore, the 3-year local recurrence was 3.6% (95% CI, 2.0%-5.1%) for transanal TME and 4.4% (95% CI, 2.6%-6.1%) for laparoscopic TME. Three-year overall survival was 92.6% (95% CI, 90.4%-94.8%) for transanal TME and 90.7% (95% CI, 88.3%-93.2%) for laparoscopic TME.

CONCLUSIONS AND RELEVANCE: In patients with mid-low rectal cancer, 3-year disease-free survival for transanal TME was noninferior to that of laparoscopic TME.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02966483.

PMID:39847361 | DOI:10.1001/jama.2024.24276

JAMA Netw Open. 2025 Jan 2;8(1):e2455955. doi: 10.1001/jamanetworkopen.2024.55955.

ABSTRACT

IMPORTANCE: Food insecurity is a growing public health concern, but its association with perinatal complications remains unclear.

OBJECTIVE: To examine whether food insecurity in pregnancy was associated with the risk of perinatal complications and determine whether these potential associations differed by receipt of food assistance.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from a pregnancy survey conducted between June 22, 2020, and September 9, 2022, at Kaiser Permanente Northern California, an integrated health care system serving a diverse population of 4.6 million. Participants included individuals who delivered singletons. Data were analyzed from December 2023 to June 2024.

EXPOSURE: Food insecurity in pregnancy assessed using the validated 2-item Hunger Vital Sign screener.

MAIN OUTCOMES AND MEASURES: Maternal (gestational diabetes, gestational hypertension, preeclampsia, cesarean delivery) and neonatal (preterm birth, neonatal intensive care unit [NICU] admission, small-for-gestational age [SGA], and large-for-gestational age [LGA]) complications extracted from the electronic health records, and a composite adverse perinatal outcome (APO) of maternal and neonatal complications. Modified Poisson regression models were adjusted for covariates and stratified by receipt of food assistance in pregnancy.

RESULTS: Among 19 338 individuals, 2707 (14.0%) reported food insecurity in pregnancy. Individuals with food insecurity in pregnancy had a higher risk of gestational diabetes (adjusted relative risk [aRR], 1.13 [95% CI, 1.01-1.29]), preeclampsia (aRR, 1.28 [95% CI, 1.11-1.49]), preterm birth (aRR, 1.19 [95% CI, 1.02-1.38]), NICU admission (aRR, 1.23 [95% CI, 1.07-1.42]), and APO (aRR, 1.07 [95% CI, 1.02-1.13]) compared with individuals without food insecurity. Among 1471 individuals (7.6%) who received food assistance in pregnancy, associations of food insecurity in pregnancy with perinatal complications were attenuated to the null, except for preeclampsia (aRR, 1.64 [95% CI, 1.06-2.53]). On the contrary, the associations persisted among individuals who did not receive food assistance: gestational diabetes (aRR, 1.20 [95% CI, 1.04-1.37]), preeclampsia (aRR, 1.24 [95% CI, 1.06-1.46]), preterm birth (aRR, 1.23 [95% CI, 1.05-1.46]), NICU admission (aRR, 1.31 [95% CI, 1.12-1.52]), and APO (aRR, 1.12 [95% CI, 1.06-1.18]).

CONCLUSIONS AND RELEVANCE: In this cohort study, food insecurity in pregnancy was associated with a higher risk of perinatal complications, and these associations were overall attenuated to the null among individuals who received food assistance in pregnancy. These findings support clinical guidelines of screening for food insecurity in pregnancy and provide evidence to expand food assistance programs that may help improve maternal and neonatal outcomes.

PMID:39847356 | DOI:10.1001/jamanetworkopen.2024.55955

JAMA Netw Open. 2025 Jan 2;8(1):e2455963. doi: 10.1001/jamanetworkopen.2024.55963.

ABSTRACT

IMPORTANCE: The degree that in-home cannabis smoking can be detected in the urine of resident children is unclear.

OBJECTIVE: Test association of in-home cannabis smoking with urinary cannabinoids in children living at home.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used baseline data from Project Fresh Air, a 2012-2016 randomized clinical trial to reduce fine particulate matter levels. Eligible participants were recruited from households in San Diego County, California, with children under age 14 years and an adult tobacco smoker in residence. Children’s urine samples were analyzed in 2022.

EXPOSURES: In-home cannabis smoking, measured by: parent or guardian report of in-home cannabis smoking; number of daily nonspecific smoking events computed via an air particle count algorithm; and number of daily cannabis smoking events ascertained by residualization, adjusting for air nicotine, tobacco smoking, and other air particle generating or ventilating activities.

MAIN OUTCOMES AND MEASURES: Levels of the cannabis biomarker Δ9-tetrahydrocannabinol (THC) and its major metabolites, 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol. Biomarker molar equivalents were summed to represent total THC equivalents (TTE) in urine. Logistic regression assessed whether in-home smoking was associated with cannabis biomarker detection. For children with detectable urinary cannabinoids, linear regression assessed in-home smoking association with quantity of urinary TTE.

RESULTS: A total of 275 children were included in analysis (mean [SD] age, 3.6 [3.6] years; 144 male [52.4%]; 38 Black [13.8%], 132 Hispanic [48.0%], and 52 White [18.9%]). Twenty-nine households (10.6%) reported in-home cannabis smoking in the past 7 days; 75 children [27.3%] had detectable urinary cannabinoids. Odds of detectable TTE in children’s urine were significantly higher in households with reported in-home cannabis smoking than households without (odds ratio [OR], 5.0; 95% CI, 2.4-10.4) and with each additional ascertained daily cannabis smoking event (OR, 2.5; 95% CI, 1.6-3.9). Although the point estimate for TTE levels was higher among children with detectable urinary cannabinoids and exposure to more daily cannabis smoking events (increase per event, 35.68%; 95% CI, -7.12% to 98.21%), the difference was not statistically significant.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, in-home cannabis smoking was associated with significantly increased odds of child exposure to cannabis smoke, as assessed by urinary cannabinoid biomarkers. As young children spend most of their time at home, reducing in-home cannabis smoking could substantially reduce their exposure to the toxic and carcinogenic chemicals found in cannabis smoke.

PMID:39847355 | DOI:10.1001/jamanetworkopen.2024.55963

JAMA Netw Open. 2025 Jan 2;8(1):e2456050. doi: 10.1001/jamanetworkopen.2024.56050.

ABSTRACT

IMPORTANCE: Associations between child maltreatment (CM) and health have been studied broadly, but most studies focus on multiplicity (number of experienced subtypes of CM). Studies assessing multiple CM characteristics are scarce, partly due to methodological challenges, and were mostly conducted in patient samples.

OBJECTIVE: To determine the importance of CM characteristics in association with physical multimorbidity in adulthood for women and men in a German representative sample.

DESIGN, SETTING, AND PARTICIPANTS: This survey study used data from a representative sample of the German population between July and October 2021. Households were randomly selected within regional areas by a German demographic consultation company, and the Kish-Grid method was applied to ensure random participation. Reasons for nonparticipation were refusal of the selected household or target person to participate and failure to contact a household after 4 visits. Analyses took place between June 2023 and July 2024.

EXPOSURE: Characteristics of CM, including subtypes of CM, multiplicity, age at time of maltreatment (timing), number of years of experienced maltreatment (duration), frequency, and subjective severity (measured with the ISPCAN Child Abuse Screening Tools Retrospective version questionnaire).

MAIN OUTCOMES AND MEASURES: The main outcome was physical multimorbidity, defined as the sum score of lifetime leading morbidity and mortality causes in Western countries (obesity, diabetes, cancer, hypertension, myocardial infarction, chronic obstructive pulmonary disease, and incident stroke). Conditioned random forest regression analyses (a machine learning regression technique) were conducted to examine what characteristics of CM were most importantly associated with physical multimorbidity in adulthood while considering all other variables in the model.

RESULTS: Of 5908 individuals invited, the study sample included 2514 participants (response rate, 42.6%), with 1297 (51.6%) women (mean [SD] age, 50.6 [17.9] years) and 1217 (48.4%) men (mean [SD] age, 49.5 [18.2] years). Duration of CM was the most important factor for physical multimorbidity in adulthood for both women (importance = 0.595; 95% CI, 0.599-0.601) and men (importance = 1.389; 95% CI, 1.386-1.394). Duration and timing variables were more importantly associated with outcomes than multiplicity in women and men. For women, severity and experiencing CM at age 4 years was significantly associated with physical multimorbidity in adulthood. For men, experiencing CM at age 11 years was most importantly associated with physical multimorbidity in adulthood.

CONCLUSIONS AND RELEVANCE: In this survey study, conditioned random forest regression analyses were applied to provide insights in the importance of duration and timing of CM for physical health in addition to the frequently studied multiplicity. These findings suggest that CM assessments should be considered in diagnostics of individuals with physical health conditions and may also inform strategies to mitigate the risk.

PMID:39847353 | DOI:10.1001/jamanetworkopen.2024.56050

JAMA Netw Open. 2025 Jan 2;8(1):e2456074. doi: 10.1001/jamanetworkopen.2024.56074.

ABSTRACT

IMPORTANCE: Many physician groups are in 2-sided risk payment arrangements with Medicare Advantage plans (at-risk MA). Analysis of quality and health resource use under such arrangements may inform ongoing Medicare policy concerning payment and service delivery.

OBJECTIVE: To compare quality and efficiency measures under 2 payment models: at-risk MA and fee-for-service (FFS) MA.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used Medicare encounter and enrollment data from 2016 to 2019 covering 17 physician groups, 15 488 physicians, and 35 health insurers to compare quality and health resource use for Medicare beneficiaries within the same physician groups. The data were analyzed between August 4 and October 30, 2024.

EXPOSURES: Care delivered under at-risk MA and FFS MA payment arrangements by the same physicians and medical groups.

MAIN OUTCOMES AND MEASURES: Twenty quality and efficiency measures across 4 domains of patient care (hospital care, avoidance of the emergency department [ED], avoidance of disease-specific admissions, and outpatient care) were examined using logistic regression analysis.

RESULTS: The overall sample comprised 5 278 717 person-years (37.7% at-risk MA and 62.3% FFS MA). The mean (SD) age of beneficiaries was 73.6 (9.2) years in the at-risk MA group (56.8% women) and 71.8 (10.4) years in the FFS MA group (57.4% women). For at-risk MA compared with FFS MA, inpatient admissions and 30-day readmissions per 1000 were 10.03 (95% CI, -10.61 to -9.44) and 1.95 (95% CI, -2.18 to -1.73) lower. ED use measures per 1000 ranged from 2.95 (95% CI, -3.28 to -2.63) lower for avoidable ED visits to 26.02 (95% CI, -26.92 to -25.12) lower for overall ED visits. Avoidance of disease-specific admissions per 1000 ranged from 0.24 (95% CI, -0.35 to -0.13) lower for composite diabetes-related admissions to 2.18 (95% CI, -2.43 to -1.94) lower for the composite of chronic disease-related admissions. High-risk drug use per 1000 was 14.26 (95% CI, -14.85 to -13.67) lower. Overall, compared with FFS MA, at-risk MA was associated with higher quality and efficiency in 18 of 20 measures after adjusting for differences in demographics, Hierarchical Condition Categories Risk Adjustment Factor scores, and other health characteristics.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, at-risk MA payment arrangements managed by physician groups were associated with higher quality and efficiency compared with FFS MA managed by the same groups. The population and methods used provide robust evidence that at-risk payment arrangements in MA may improve health care delivery for the MA population.

PMID:39847351 | DOI:10.1001/jamanetworkopen.2024.56074

Proc Natl Acad Sci U S A. 2025 Jan 28;122(4):e2306025121. doi: 10.1073/pnas.2306025121. Epub 2025 Jan 23.

ABSTRACT

Looking at the world often involves not just seeing things, but feeling things. Modern feedforward machine vision systems that learn to perceive the world in the absence of active physiology, deliberative thought, or any form of feedback that resembles human affective experience offer tools to demystify the relationship between seeing and feeling, and to assess how much of visually evoked affective experiences may be a straightforward function of representation learning over natural image statistics. In this work, we deploy a diverse sample of 180 state-of-the-art deep neural network models trained only on canonical computer vision tasks to predict human ratings of arousal, valence, and beauty for images from multiple categories (objects, faces, landscapes, art) across two datasets. Importantly, we use the features of these models without additional learning, linearly decoding human affective responses from network activity in much the same way neuroscientists decode information from neural recordings. Aggregate analysis across our survey, demonstrates that predictions from purely perceptual models explain a majority of the explainable variance in average ratings of arousal, valence, and beauty alike. Finer-grained analysis within our survey (e.g. comparisons between shallower and deeper layers, or between randomly initialized, category-supervised, and self-supervised models) point to rich, preconceptual abstraction (learned from diversity of visual experience) as a key driver of these predictions. Taken together, these results provide further computational evidence for an information-processing account of visually evoked affect linked directly to efficient representation learning over natural image statistics, and hint at a computational locus of affective and aesthetic valuation immediately proximate to perception.

PMID:39847334 | DOI:10.1073/pnas.2306025121