medRxiv (Cold Spring Harbor Laboratory)最新文献

{"title":"Automated quantitative evaluation of thymic involution and hyperplasia on plain chest CT","authors":"Yuki T. Okamura, Katsuhiro Endo, Akira Toriihara, Issei Fukuda, Jun Isogai, Yasunori Sato, Kenji Yasuoka, Shin-Ichiro Kagami","doi":"10.1101/2023.11.13.23298440","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298440","url":null,"abstract":"Objective: To establish an automatic method to quantify thymic involution and hyperplasia based on plain chest computed tomography (CT). Methods: We defined the thymic region for quantification (TRQ) as the target region. We manually segmented the TRQ in 135 CT studies, followed by construction of segmentation neural network (NN) models based on the data. We developed the estimator of thymic volume (ETV), a measure of the thymic tissue volume in the segmented TRQ. The Hounsfield unit (HU) value and volume of the TRQ were measured, and the ETV was calculated in each CT study from 853 healthy subjects. We investigated how these measures were related to the age and sex using quantile additive regression models. We defined the ETV z-score, an age- and sex-adjusted version of ETV, to distinguish between subjects with thymic hyperplasia (18 cases) and healthy subjects. A receiver operating characteristic (ROC) curve analysis was conducted. Results: A significant correlation between the NN-segmented and manually segmented TRQ was seen for both the HU value and volume of the TRQ (r = 0.996 and r = 0.986 respectively). The ETV could detect age-related decline in the thymic tissue volume (p < 0.001). No statistically significant difference was detected between male and female subjects (p = 0.19). The ETV was significantly higher in the thymic hyperplasia group as compared with that in the healthy control group (p < 0.001). The ETV z-score could distinguish between subjects with thymic hyperplasia and healthy subjects, with the ROC curve analysis revealing an area under the curve (AUC) of 0.88 (95% CI: 0.75-1.0). Conclusion: Our method enabled robust quantification of thymic involution and hyperplasia. The results were consistent with the trends found in previous studies.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"7 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134956672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atrial Fibrillation Catheter Ablation among Cancer Patients: Utilization Trends and In-Hospital Outcomes","authors":"Gilad Margolis, Ofir Goldhaber, Mark Kazatsker, Ofer Kobo, Ariel Roguin, Eran Leshem","doi":"10.1101/2023.11.13.23298490","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298490","url":null,"abstract":"BACKGROUND: Atrial fibrillation (AF) catheter ablation in cancer patients was evaluated in very few studies. We aimed to investigate trends of utilizations as well as in-hospital outcomes of AF catheter ablation procedures among cancer patients, in a large inpatient US registry. METHODS AND RESULTS: Using the National Inpatient Sample (NIS) database, patients who underwent AF catheter ablations in the US between 2012 and 2019 were identified using ICD-9/10 codes. Sociodemographic, clinical data, in-hospital procedures and outcomes as well as in-hospital mortality and length-of-stay (LOS) were collected. Baseline characteristics and in-hospital outcomes were compared between patients with and without cancer. An estimated total of 67915 patients underwent AF catheter ablation between 2012-2019 in the US. Of them, 950 (1.4%) had cancer diagnosis. Compared with non-cancer patients, patients with cancer were older, had higher Charlson Comorbidity Index, as well as CHA2DS2-VASc and ATRIA bleeding indices scores. Higher rate of total complications was observed in cancer patients (10.5% vs 7.9, p<0.001) driven mainly by more bleeding and infectious complications. LOS was also significantly longer in cancer patients (4.9 ± 5.8 vs. 2.7 ± 3.0 days, p<0.001). However, no significant differences in cardiac or neurological complications as well as in-hospital mortality rates were observed and were relatively low in both groups. CONCLUSIONS: AF catheter ablation in cancer patients is associated with higher bleeding and infectious complication rates, but not with increased cardiac complications or in-hospital mortality rates in a nationwide, all-comer registry.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"16 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134955336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An agent-based model to simulate the transmission dynamics of bloodborne pathogens within hospitals","authors":"Paul Henriot, Mohamed El Kassas, Wagida Anwar, Samia Girgis, Kevin Jean, Laura Temime","doi":"10.1101/2023.11.14.23298506","DOIUrl":"https://doi.org/10.1101/2023.11.14.23298506","url":null,"abstract":"Bloodborne pathogens are a major public health concern as they can lead to a variety of medical conditions, including cirrhosis and cancers with significant mortality and morbidity. Three viruses are of major concern: HCV, HBV and HIV. Their transmission is mostly community-associated but the iatrogenic risk of infection is not negligible, even today. Mathematical models are widely used to describe and assess pathogens transmission, within communities and hospitals. Nevertheless, few are focusing on the transmission of pathogens through blood and even fewer on their transmission within hospital as they usually study the risk of community-associated infection in vulnerable populations such as MSM or drug users. Herein, we propose an agent- based SEI (Susceptible-Exposed-Infected) model to explore the transmission dynamics of bloodborne pathogens within hospitals. This model simulates the dynamics of patients between hospital wards, from their admission to discharge, as well as the dynamics of the devices used during at-risk invasive procedures, considering that patient contamination occurs after exposure to a contaminated device. Multiple parameters of the model, such as HCV prevalence, transition probabilities between wards or ward-specific probabilities of undergoing different invasive procedures, were informed with data collected in the University Hospital of Ain Shams in Cairo, Egypt in 2017. We explored the effect of device shortage as well as the effect of random and systematic screening with associated modification in disinfection practices on the risk of infection for patients. By modifying some parameters of the model, we then explored the case of HBV in Ethiopia. In the future, this model could be used to assess the risk of transmission of other bloodborne pathogens in other contexts.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134957712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise intervention for the management of chemotherapy-induced peripheral neuropathy: A systematic review and network meta-analysis","authors":"Natsuki Nakagawa, Sena Yamamoto, Akiko Hanai, Ayano Oiwa, Harue Arao","doi":"10.1101/2023.11.13.23298326","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298326","url":null,"abstract":"Purpose: Although exercise is recommended for cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN), the effective types of exercise for preventing and treating CIPN remain unclear. This systematic review and network meta-analysis (NMA) aimed to evaluate the comparative effects of exercise on CIPN. Methods: We included relevant randomized controlled trials (RCTs) identified in a 2019 systematic review that evaluated the effects of exercise on CIPN and conducted an additional search for RCTs published until 2023. We evaluated the risk of bias for each RCT; the comparative effectiveness of exercise on patient-reported quality of life (QOL) through an NMA; and the effectiveness of exercise on QOL scores, patient-reported CIPN symptoms, and pain through additional meta-analyses. Results: Twelve studies (exercise, n=540; control, n=527) comparing 8 exercise interventions were included in the analysis. All studies were determined to have a high risk of bias. The meta-analyses showed significantly improved QOL (standard mean differences [SMD] 0.45; 95% confidence interval [CI] = 0.12 to 0.78) and CIPN symptoms (SMD 0.46; 95% CI = 0.11 to 0.82). No severe adverse events were reported. Pain tended to improve with exercise (SMD 0.84; 95% CI = -0.11 to 1.80). An NMA suggested that the interventions of combination of balance and strength training showed the significant improvement in QOL scores compared to the control. Conclusion: Exercise interventions are safe and effective in improving QOL. For exercise categories, the combination of balance and strength training would be the promising program. Patients with CIPN will benefit from frequent exercise focusing on the declined symptoms.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"5 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134954396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Brucellosis in Iraq: what does a spatiotemporal data analysis from 2007-2018 reveal?","authors":"Ali Hazim Mustafa, Hanan Abdulghafoor Khaleel, Faris Lami","doi":"10.1101/2023.11.13.23298496","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298496","url":null,"abstract":"Abstract Background: Brucellosis is both endemic and enzootic in Iraq, resulting in long-term morbidity for humans as well as economic loss. No previous study of the spatial and temporal patterns of brucellosis in Iraq was done to identify potential clustering of cases. Objectives: This study aims to detect the spatial and temporal distribution of human brucellosis in Iraq and identify any changes that occurred from 2007 to 2018. Methods: A descriptive cross-sectional study using secondary data from the Communicable Diseases Control Center / Ministry of Health surveillance section. We used Moran's I, local Getis-Ord's Gi*, and the local indicators of spatial association (LISA) to detect the spatial distribution of the data. The data was analyzed using Excel software and the Quantum GIS (QGIS) version 2.18.20 (Steiniger and Hunter, 2013). Results: 50,621 human brucellosis cases were reported during the 12-year study period. Human brucellosis persisted annually in Iraq across the study period with no specific temporal clustering of cases. In contrast, spatial clustering was predominant in the Northern region of Iraq. Conclusion: There were significant differences in the geographic distribution of brucellosis. The number of cases is highest in the north and northeast of the country, which has borders with nearby countries. In addition, people in these areas depend more on locally made dairy products, which can be inadequately pasteurized. Despite the lack of significant temporal clustering of cases, the highest number of cases were reported during Summer and Spring.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"8 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134956857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide association study analysis of disease severity in acne reveals novel biological insights.","authors":"Zhaohui Du, Tejaswi Iyyanki, Samuel Lessard, Michael Chao, FinnGen FinnGen, Christian Asbrand, Dany Nassar, Katherine Klinger, Emanuele de Rinaldis, Shameer Khader, Clement Chatelain","doi":"10.1101/2023.11.13.23298473","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298473","url":null,"abstract":"Acne vulgaris is a common skin disease that affects &gt;85% of teenage young adults among which &gt;8% develop severe lesions that leaves permanent scars. Genetic heritability studies of acne in twin cohorts have estimated that the heritability for acne is 80%. Previous genome-wide association studies (GWAS) have identified 50 genetic loci associated with increased risk of developing acne when compared to healthy individuals. However only a few studies have investigated genetic association with disease severity. GWAS of disease progression may provide a more effective approach to unveil potential disease modifying therapeutic targets. Here, we performed a multi-ethnic GWAS analysis to capture disease severity in acne patients by using individuals with normal acne as a control. Our cohort consists of a total of 2,956 participants, including 290 severe acne cases and 930 normal acne controls from FinnGen, and 522 cases and 1,214 controls from BioVU. We also performed mendelian randomization (MR), colocalization analyses and transcriptome-wide association study (TWAS) to identify putative causal genes. Lastly, we performed gene-set enrichment analysis using MAGMA to implicate biological pathways that drive disease severity in Acne. We identified two new loci associated with acne severity at the genome-wide significance level, six novel associated genes by MR, colocalization and TWAS analyses, including genes CDC7, SLC7A1, ADAM23, TTLL10, CDK20 and DNAJA4, and 5 novel pathways by MAGMA analyses. Our study suggests that the etiologies of acne susceptibility and severity have limited overlap, with only 26% of known acne risk loci presenting nominal association with acne severity and none of the novel severity associated genes reported as associated with acne risk in previous GWAS.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"24 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134954034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ability of calculated right adrenal vein aldosterone levels to identify the aldosterone-overproducing side in patients with primary aldosteronism undergoing adrenal venous sampling","authors":"Supamai Soonthornpun, Lalita Tuandam","doi":"10.1101/2023.11.13.23298491","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298491","url":null,"abstract":"Backgroud: Adrenal venous sampling (AVS) is a gold standard procedure to determine the dominant side of aldosterone secretion in patients with primary aldosteronism. Unsuccessful cannulation of right adrenal vein (RAV) is a common problem in performing AVS. Objective: To use calculated aldosterone concentration in the RAV (cAldoRAV) for identifying the dominant side of aldosterone secretion. Design: Retrospective study, 2011-2023. Methods: Based on the assumption that cortisol production from both adrenal glands is equal, aldosterone concentration in the RAV was calculated by using the data from left adrenal vein (LAV) and inferior vena cava. The aldosterone concentration in the LAV (AldoLAV) compared to the cAldoRAV (AldoLAV:cAldoRAV ratio) was then used to determine the dominant side of aldosterone secretion in patients with primary aldosteronism. Results: Of 117 patients with successful AVS, 95 (81.2%) had concordant results between adrenal imaging and AVS study and were used as the gold standard for studying diagnostic performance. The AldoLAV:cAldoRAV ratio with the cutoff values of ?3 and ?0.33 could identify unilateral diseases (left-sided and right-sided disease, respectively) with 93.8% sensitivity and 100% specificity. In 22 patients who had discordant results between adrenal imaging and standard AVS interpretation, 11 had concordant results when using the AldoLAV:cAldoRAV ratio. Conclusions: The AldoLAV:cAldoRAV ratio can determine the dominant side of aldosterone secretion with high sensitivity and specificity. It can not only be used for patients with unsuccessful cannulation of RAV but also increase the concordance rate in those who have discordance between adrenal imaging and standard AVS interpretation.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"11 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134956988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Right ventricular pressure-strain relationship-derived myocardial work reflects contractility: validation with invasive pressure-volume analysis","authors":"Balint Karoly Lakatos, Zvonimir Rako, Adam Szijarto, Bruno R. Brito da Rocha, Manuel J. Richter, Alexandra Fabian, Henning Gall, Hossein A. Ghofrani, Nils Kremer, Werner Seeger, Daniel Zedler, Selin Yildiz, Athiththan Yogeswaran, Bela Merkely, Khodr Tello, Attila Kovacs","doi":"10.1101/2023.11.14.23298344","DOIUrl":"https://doi.org/10.1101/2023.11.14.23298344","url":null,"abstract":"Background Three-dimensional (3D) echocardiography-derived right ventricular (RV) ejection fraction (EF) and global longitudinal strain (GLS) are valuable RV functional markers; nevertheless, they are substantially load-dependent. Global myocardial work index (GMWI) adjusts myocardial deformation to instantaneous pressure; therefore, it may better reflect contractility. Accordingly, we aimed to calculate RV GMWI using 3D echocardiography and examine its relationship with RV contractility's gold standard invasive measurement. Methods Sixty patients (65±14 years, 65% female) with suspected or established pulmonary hypertension were enrolled. Detailed 3D echocardiography was performed to quantify RV EF and GLS using the ReVISION software. Patients underwent RV pressure-conductance catheterization to obtain the RV pressure curve and to assess contractility (end-systolic elastance - Ees) and ventriculo-arterial coupling (Ees/arterial elastance - Ees/Ea). RV GMWI was calculated using the RV GLS and the RV pressure trace curve. Results While neither RV EF (r=-0.143, p=0.275) nor GLS (r=-0.067, p=0.611) correlated with Ees, GMWI showed a strong correlation with it (r=0.669, p<0.001). In contrast, RV EF and GLS showed a relationship with Ees/Ea (RVEF: r=0.552; GLS: r=0.460, both p<0.001). By dividing the population based on the Reveal Lite 2 risk classification, EF and GLS showed a significant decrease only in the high-risk group (low vs. intermediate vs. high risk; EF: 48.8±6.6 vs. 44.0±9.4 vs. 35.0±7.8%, ANOVA p<0.001; GLS: 18.6±3.6 vs. 17.0±4.5 vs. 13.3±3.9%, ANOVA p<0.001), whereas GMWI already showed an increase in the intermediate group (550±267 vs. 831±361 vs. 797±265 mmHg%, ANOVA p<0.01). Conclusions RV EF and GLS reflect ventriculo-arterial coupling, while GMWI strongly correlates with contractility. RV GMWI may emerge as a useful clinical tool for risk stratification and follow-up in patients with pulmonary hypertension.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"7 8","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134956861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of Antipsychotics in Primary Care: Insights from Healthcare Professionals and Policy Makers in the UK","authors":"Alan A Woodall, A S Abuzour, S A Wilson, Frances S Mair, Iain Buchan, Sally B Sheard, Paul Atkinson, Dan W Joyce, Pyers Symon, Lauren E Walker","doi":"10.1101/2023.11.13.23298487","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298487","url":null,"abstract":"Introduction: Antipsychotic medication is increasingly prescribed to patients with serious mental illness. Patients with serious mental illness often have cardiovascular and metabolic comorbidities, and antipsychotics independently increase the risk of cardiometabolic disease. Despite this, many patients prescribed antipsychotics are discharged to primary care without planned psychiatric review. We explore perceptions of healthcare professionals and managers/planners of policy regarding management of antipsychotics in primary care. Methods: Qualitative study using semi-structured interviews with 11 general practitioners (GPs), 8 psychiatrists, and 11 managers/planners of policy in the United Kingdom. Interviews were studied using inductive thematic analysis. Results: Respondents reported competency gaps that impaired ability to manage patients prescribed antipsychotic medications holistically, arising from inadequate postgraduate training and professional development. GPs lacked confidence to manage antipsychotic medications alone; psychiatrists lacked skills to address cardiometabolic risks and did not perceive this as their role. Communication barriers, lack of integrated care records, limited psychology provision, lowered expectation of patients with serious mental illness by professionals, and pressure to discharge from hospital resulted in patients in primary care becoming ‘trapped’ on antipsychotics, inhibiting opportunities to deprescribe. Organisational and contractual barriers between organisations exacerbate this risk, with socioeconomic deprivation and lack of access to non-pharmacological alternatives driving overprescribing. GPs and psychiatrists voiced professional fears of being blamed if an event causing harm occurred after stopping an antipsychotic, which inhibited deprescribing. A range of actions to overcome these barriers were suggested. Conclusions: People prescribed antipsychotics experience a fragmented health system and suboptimal care. Many simple steps could be taken to improve quality of care for this population but inadequate availability of non-pharmacological alternatives and socioeconomic factors increasing mental distress need key policy changes to improve the current situation.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"11 11","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134956982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delivery mode impacts gut bacteriophage colonization during infancy","authors":"Poorani Subramanian, Hector N Romero-Soto, David B Stern, George L Maxwell, Shira Levy, Suchitra K Hourigan","doi":"10.1101/2023.11.13.23298307","DOIUrl":"https://doi.org/10.1101/2023.11.13.23298307","url":null,"abstract":"Background: Cesarean section delivery is associated with altered early-life bacterial colonization and later adverse inflammatory and immune health outcomes. Although gut bacteriophages can alter gut microbiome composition and impact host immune responses, little is known about how delivery mode impacts bacteriophage colonization over time. To begin to address this we examined how delivery mode affected bacteriophage colonization over the first two years of life. Results: Shotgun metagenomic sequencing was conducted on 272 serial stool samples from 55 infants, collected at 1-2 days of life and 2, 6, 12 and 24 months. 33/55 (60%) infants were born by vaginal delivery. DNA viruses were identified, and by host inference, 94% of the viral sequences were found to be bacteriophages. Alpha diversity of the virome was increased in vaginally delivered infants compared to cesarean section delivered infants at 2 months (Shannon index, p=0.022). Beta diversity significantly differed by delivery mode at 2, 6, and 12 months when stratified by peripartum antibiotic use (Bray Curtis dissimilarity, all p<0.05). Significant differentially abundant predicted bacteriophage hosts by delivery mode were seen at all time points. Moreover, there were differences in predicted bacteriophage functional gene abundances up to 24 months by delivery mode. Many of the functions considered to play a role in host response were increased in vaginal delivery. Conclusions: Clear differences in bacteriophage composition and function were seen by delivery mode over the first two years of life. Given that phages are known to affect host immune response, our results suggest that future investigation into how delivery mode may lead to adverse inflammatory outcomes should not only include bacterial microbial colonization but also the potential role of bacteriophages and transkingdom interactions.","PeriodicalId":478577,"journal":{"name":"medRxiv (Cold Spring Harbor Laboratory)","volume":"49 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136281495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}