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Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within the ACC and explore potential associations between the bacterial community structure, patient clinical characteristics, and tumor molecular features obtained through RNA sequencing. The bacterial composition in the ACC was significantly different from that in adjacent normal salivary tissue, and the ACC exhibited diverse levels of species richness. We identified two main microbial subtypes within the ACC: oral-like and gut-like. Oral-like microbiomes, characterized by increased diversity and abundance of Neisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, and Veillonella (commonly found in healthy oral cavities), were associated with a less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with a more diverse microbiome, less aggressive tumor phenotype, and better survival that reveal the genera as potential pancancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. Conversely, gut-like intratumoral microbiomes, which feature low diversity and colonization by gut mucus layer-degrading species, such as Bacteroides, Akkermansia, Blautia, Bifidobacterium, and Enterococcus, were associated with poorer outcomes. Elevated levels of Bacteroides thetaiotaomicron were independently associated with significantly worse survival and positively correlated with tumor cell biosynthesis of glycan-based cell membrane components.
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Carcinoma Adenoide Cístico , Neoplasias de Cabeça e Pescoço , Microbiota , RNA Ribossômico 16S , Humanos , Carcinoma Adenoide Cístico/microbiologia , Carcinoma Adenoide Cístico/patologia , Neoplasias de Cabeça e Pescoço/microbiologia , Neoplasias de Cabeça e Pescoço/patologia , Feminino , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Idoso , Adulto , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificaçãoRESUMO
Tools for genome-wide rapid identification of peptide-major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APC) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell-APC aggregates were detected by dual-reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq). When applied to a previously characterized TCR specific for the E7 antigen derived from human papillomavirus type 16 (HPV16), Tsyn-seq successfully enriched the correct cognate antigen from a cDNA library derived from an HPV16-positive cervical cancer cell line. Tsyn-seq provides a method for rapidly identifying antigens recognized by TCRs of interest from a tumor cDNA library. See related Spotlight by Makani and Joglekar, p. 515.
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Sinapses Imunológicas , Receptores de Antígenos de Linfócitos T , Linfócitos T , Humanos , Células Apresentadoras de Antígenos/imunologia , Linhagem Celular Tumoral , Biblioteca Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 16/genética , Sinapses Imunológicas/imunologia , Fatores de Transcrição NFATC/metabolismo , Fatores de Transcrição NFATC/imunologia , Proteínas E7 de Papillomavirus/imunologia , Proteínas E7 de Papillomavirus/genética , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Linfócitos T/imunologiaRESUMO
PHENOMENON: Despite the nearly universal presence of chief residents within U.S. and Canadian residency programs and their critical importance in graduate medical education, to our knowledge, a comprehensive synthesis of publications about chief residency does not exist. An understanding of the current state of the literature can be helpful to program leadership to make evidence-based improvements to the chief residency and for medical education researchers to recognize and fill gaps in the literature. APPROACH: We performed a scoping review of the literature about chief residency. We searched OVID Medline, PsycINFO, ERIC, and Web of Science databases through January 2023 for publications about chief residency. We included publications addressing chief residency in ACGME specialties in the U.S. and Canada and only those using the term "chief resident" to refer to additional responsibilities beyond the typical residency training. We excluded publications using chief residents as a convenience sample. We performed a topic analysis to identify common topics among studies. FINDINGS: We identified 2,064 publications. We performed title and abstract screening on 1,306 and full text review on 208, resulting in 146 included studies. Roughly half of the publications represented the specialties of Internal Medicine (n = 37, 25.3%) and Psychiatry (n = 30, 20.5%). Topic analysis revealed six major topics: (1) selection of chief residents (2) qualities of chief residents (3) training of chief residents (4) roles of chief residents (5) benefits/challenges of chief residency (6) outcomes after chief residency. INSIGHTS: After reviewing our topic analysis, we identified three key areas warranting increased attention with opportunity for future study: (1) addressing equity and bias in chief resident selection (2) establishment of structured expectations, mentorship, and training of chief residents and (3) increased attention to chief resident experience and career development, including potential downsides of the role.
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Introduction: Despite its importance in illness recovery, the sleep of hospitalized children is frequently interrupted. This quality improvement intervention aimed to reduce overnight room entries by minimizing unnecessary interventions. Methods: This study occurred at a university-affiliated children's hospital on the hospital medicine services from March 26, 2021, to April 14, 2022. The intervention included order set changes and the implementation of a rounding checklist designed to address factors most closely associated with sleep disruption and overnight room entries. The outcome measure was overnight (10 pm to 6 am) room entries, counted using room entry sensors. Process measures reflected the intervention targets (overnight vital sign orders, medication administration, and intravenous fluid use). The method of analysis was statistical process control charting. Results: After identifying special cause variation, the average number of overnight room entries decreased from 8.1 to 6.8, a 16% decrease. This decrease corresponded with the implementation of a rounding checklist. However, there continued to be variability in average room entries, suggesting a process lacking ongoing stability. During this period, avoidance of overnight medications and intravenous fluid increased by 28% and 17%, respectively. Conclusions: Implementing a rounding checklist to a broad patient population decreased overnight room entries. However, future work is needed to better understand the factors associated with sustaining such an improvement.
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BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is active against most Staphylococcus aureus isolates but is not widely used for the treatment of pediatric osteoarticular infections. METHODS: This was a comparative effectiveness study of hospitalized patients ≤18 years treated with TMP-SMX vs. other antibiotic regimens for acute osteoarticular infections between 2016 and 2021 at 3 hospitals using inverse probability of treatment weighted propensity score analysis. The primary outcome was treatment failure, a composite of unanticipated emergency department (ED) or outpatient visits, hospital readmissions, extension, or change of antibiotic therapy due to inadequate clinical response, or death, all within 6 months after completing antibiotics. The secondary outcome was antibiotic-associated adverse events (AEs) within 6 months. The exposed group for the treatment failure analysis included children who received ≥7 days of TMP-SMX and did not experience treatment failure while on another antibiotic. Children receiving at least 1 dose of TMP-SMX were the exposed group for the AE analysis. RESULTS: One-hundred and sixteen patients met eligibility criteria; 26 (22.4%) patients were classified into the TMP-SMX cohort and 90 (77.6%) into the other antibiotics cohort (most commonly clindamycin, vancomycin, and cefazolin). There was no significant difference in treatment failure between TMP-SMX and other antibiotics (43% vs. 19%; 95% CI .9-10.4). More patients in the TMP-SMX cohort experienced an unplanned ED or outpatient visit (OR 4.8, 95% CI 1.3-17.8). There was no difference in hospital readmission, antibiotic change, or duration extension. Exposure to TMP-SMX was associated with more AEs (41% vs. 19%, Pâ =â .012). CONCLUSIONS: Treatment with TMP-SMX was not associated with greater clinical failure but was associated with more AEs compared to alternative agents for the treatment of pediatric acute osteoarticular infections.
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Infecções Estafilocócicas , Combinação Trimetoprima e Sulfametoxazol , Humanos , Criança , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Estudos Retrospectivos , Antibacterianos/efeitos adversos , Clindamicina/efeitos adversos , Infecções Estafilocócicas/tratamento farmacológicoRESUMO
Immune checkpoint inhibitors (ICIs) target advanced malignancies with high efficacy but also predispose patients to immune-related adverse events like immune-mediated colitis (IMC). Given the association between gut bacteria with response to ICI therapy and subsequent IMC, fecal microbiota transplantation (FMT) represents a feasible way to manipulate microbial composition in patients, with a potential benefit for IMC. Here, we present a large case series of 12 patients with refractory IMC who underwent FMT from healthy donors as salvage therapy. All 12 patients had grade 3 or 4 ICI-related diarrhea or colitis that failed to respond to standard first-line (corticosteroids) and second-line immunosuppression (infliximab or vedolizumab). Ten patients (83%) achieved symptom improvement after FMT, and three patients (25%) required repeat FMT, two of whom had no subsequent response. At the end of the study, 92% achieved IMC clinical remission. 16S rRNA sequencing of patient stool samples revealed that compositional differences between FMT donors and patients with IMC before FMT were associated with a complete response after FMT. Comparison of pre- and post-FMT stool samples in patients with complete responses showed significant increases in alpha diversity and increases in the abundances of Collinsella and Bifidobacterium, which were depleted in FMT responders before FMT. Histologically evaluable complete response patients also had decreases in select immune cells , including CD8+ T cells, in the colon after FMT when compared with non-complete response patients (n = 4). This study validates FMT as an effective treatment strategy for IMC and gives insights into the microbial signatures that may play a critical role in FMT response.
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Colite , Transplante de Microbiota Fecal , Inibidores de Checkpoint Imunológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Colite/induzido quimicamente , Colite/terapia , Transplante de Microbiota Fecal/métodos , RNA Ribossômico 16S/genética , Fezes/microbiologia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , IdosoRESUMO
OBJECTIVES: Autonomy is necessary for resident professional development and well-being. A recent focus on patient safety has increased supervision and decreased trainee autonomy. Few validated interventions exist to improve resident autonomy. We aimed to use quality improvement methods to increase our autonomy metric, the Resident Autonomy Score (RAS), by 25% within 1 year and sustain for 6 months. METHODS: We developed a bundled-intervention approach to improve senior resident (SR) perception of autonomy on Pediatric Hospital Medicine (PHM) services at 5 academic children's hospitals. We surveyed SR and PHM faculty perceptions of autonomy and targeted interventions toward areas with the highest discordance. Interventions included SR and faculty development, expectation-setting huddles, and SR independent rounding. We developed a Resident Autonomy Score (RAS) index to track SR perceptions over time. RESULTS: Forty-six percent of SRs and 59% of PHM faculty completed the needs assessment survey querying how often SRs were afforded opportunities to provide autonomous medical care. Faculty and SR ratings were discordant in these domains: SR input in medical decisions, SR autonomous decision-making in straightforward cases, follow-through on SR plans, faculty feedback, SR as team leader, and level of attending oversight. The RAS increased by 19% (3.67 to 4.36) 1 month after SR and faculty professional development and before expectation-setting and independent rounding. This increase was sustained throughout the 18-month study period. CONCLUSIONS: SRs and faculty perceive discordant levels of SR autonomy. We created an adaptable autonomy toolbox that led to sustained improvement in perception of SR autonomy.
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Cirurgia Geral , Internato e Residência , Criança , Humanos , Autonomia Profissional , Inquéritos e Questionários , Docentes de Medicina , Competência ClínicaRESUMO
Importance: The prevalence of urinary tract infection (UTI), bacteremia, and bacterial meningitis in febrile infants with SARS-CoV-2 is largely unknown. Knowledge of the prevalence of these bacterial infections among febrile infants with SARS-CoV-2 can inform clinical decision-making. Objective: To describe the prevalence of UTI, bacteremia, and bacterial meningitis among febrile infants aged 8 to 60 days with SARS-CoV-2 vs without SARS-CoV-2. Design, Setting, and Participants: This multicenter cross-sectional study was conducted as part of a quality improvement initiative at 106 hospitals in the US and Canada. Participants included full-term, previously healthy, well-appearing infants aged 8 to 60 days without bronchiolitis and with a temperature of at least 38 °C who underwent SARS-CoV-2 testing in the emergency department or hospital between November 1, 2020, and October 31, 2022. Statistical analysis was performed from September 2022 to March 2023. Exposures: SARS-CoV-2 positivity and, for SARS-CoV-2-positive infants, the presence of normal vs abnormal inflammatory marker (IM) levels. Main Outcomes and Measures: Outcomes were ascertained by medical record review and included the prevalence of UTI, bacteremia without meningitis, and bacterial meningitis. The proportion of infants who were SARS-CoV-2 positive vs negative was calculated for each infection type, and stratified by age group and normal vs abnormal IMs. Results: Among 14â¯402 febrile infants with SARS-CoV-2 testing, 8413 (58.4%) were aged 29 to 60 days; 8143 (56.5%) were male; and 3753 (26.1%) tested positive. Compared with infants who tested negative, a lower proportion of infants who tested positive for SARS-CoV-2 had UTI (0.8% [95% CI, 0.5%-1.1%]) vs 7.6% [95% CI, 7.1%-8.1%]), bacteremia without meningitis (0.2% [95% CI, 0.1%-0.3%] vs 2.1% [95% CI, 1.8%-2.4%]), and bacterial meningitis (<0.1% [95% CI, 0%-0.2%] vs 0.5% [95% CI, 0.4%-0.6%]). Among infants aged 29 to 60 days who tested positive for SARS-CoV-2, 0.4% (95% CI, 0.2%-0.7%) had UTI, less than 0.1% (95% CI, 0%-0.2%) had bacteremia, and less than 0.1% (95% CI, 0%-0.1%) had meningitis. Among SARS-CoV-2-positive infants, a lower proportion of those with normal IMs had bacteremia and/or bacterial meningitis compared with those with abnormal IMs (<0.1% [0%-0.2%] vs 1.8% [0.6%-3.1%]). Conclusions and Relevance: The prevalence of UTI, bacteremia, and bacterial meningitis was lower for febrile infants who tested positive for SARS-CoV-2, particularly infants aged 29 to 60 days and those with normal IMs. These findings may help inform management of certain febrile infants who test positive for SARS-CoV-2.
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Bacteriemia , COVID-19 , Meningites Bacterianas , Infecções Urinárias , Lactente , Humanos , Masculino , Feminino , SARS-CoV-2 , Prevalência , Estudos Transversais , Teste para COVID-19 , COVID-19/epidemiologia , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Meningites Bacterianas/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologiaRESUMO
PURPOSE: To determine whether a formal note-writing session and note template for medical students (MS) during the Core Clerkship in Pediatrics (CCP) increase note quality, shortens note length, and decreases time of documentation. METHODS: In this single site, prospective study, MS participating in an 8-week CCP received a didactic session on note-writing in the electronic health record (EHR) and utilized EHR template developed for the study. We assessed note quality (measured by Physician Documentation Quality Instrument-9 [PDQI-9]), note length and note documentation time in this group compared to MS notes on the CCP in the prior academic year. We used descriptive statistics and Kruskal-Wallis tests for analysis. RESULTS: We analyzed 121 notes written by 40 students in the control group and 92 notes writing by 41 students in the intervention group. Notes from the intervention group were more "up to date," "accurate," "organized," and "comprehensible" compared to the control group (P = 0.02, P = 0.04, P = 0.01, and P = 0.02, respectively). Intervention group notes received higher cumulative PDQI-9 scores compared to the control group (median score 38 (IQR 34-42) versus 36 (IQR 32-40) out of 45 total, P = 0.04). Intervention group notes were approximately 35% shorter than the control group notes (median 68.5 lines vs 105 lines, P < 0.0001) and were signed earlier than control group notes (median file time 316 minute vs 352 minute, P = 0.02). CONCLUSIONS: The intervention successfully decreased note length, improved note quality based on standardized metrics, and reduced time to completion of note documentation.
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Estudantes de Medicina , Humanos , Criança , Estudos Prospectivos , Registros Eletrônicos de Saúde , Documentação , RedaçãoRESUMO
Increasing evidence suggests that the gut microbiome may modulate the efficacy of cancer immunotherapy. In a B cell lymphoma patient cohort from five centers in Germany and the United States (Germany, n = 66; United States, n = 106; total, n = 172), we demonstrate that wide-spectrum antibiotics treatment ('high-risk antibiotics') prior to CD19-targeted chimeric antigen receptor (CAR)-T cell therapy is associated with adverse outcomes, but this effect is likely to be confounded by an increased pretreatment tumor burden and systemic inflammation in patients pretreated with high-risk antibiotics. To resolve this confounding effect and gain insights into antibiotics-masked microbiome signals impacting CAR-T efficacy, we focused on the high-risk antibiotics non-exposed patient population. Indeed, in these patients, significant correlations were noted between pre-CAR-T infusion Bifidobacterium longum and microbiome-encoded peptidoglycan biosynthesis, and CAR-T treatment-associated 6-month survival or lymphoma progression. Furthermore, predictive pre-CAR-T treatment microbiome-based machine learning algorithms trained on the high-risk antibiotics non-exposed German cohort and validated by the respective US cohort robustly segregated long-term responders from non-responders. Bacteroides, Ruminococcus, Eubacterium and Akkermansia were most important in determining CAR-T responsiveness, with Akkermansia also being associated with pre-infusion peripheral T cell levels in these patients. Collectively, we identify conserved microbiome features across clinical and geographical variations, which may enable cross-cohort microbiome-based predictions of outcomes in CAR-T cell immunotherapy.
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Microbioma Gastrointestinal , Linfoma de Células B , Receptores de Antígenos Quiméricos , Humanos , Microbioma Gastrointestinal/genética , Imunoterapia , Imunoterapia Adotiva/efeitos adversos , Linfócitos T , Antígenos CD19RESUMO
Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of Bacteroides ovatus from the microbiome. In a mouse model of carbapenem-aggravated GVHD, introducing Bacteroides ovatus reduced severity of GVHD and improved survival. Bacteroides ovatus reduced degradation of colonic mucus by another intestinal commensal, Bacteroides thetaiotaomicron, via its ability to metabolize dietary polysaccharides into monosaccharides, which then inhibit mucus degradation by Bacteroides thetaiotaomicron and reduce GVHD-related mortality.
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The Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey measures patient perceptions of hospital experience to determine the annual Center for Medicare and Medicaid Services (CMS) reimbursement. This study focuses on the "Quiet at Night" variable and identifies institutions with the highest scores to determine characteristics that facilitate patient sleep. The key findings were as follows: CMS Top Rated Hospitals have a mean score of 5 on the "Quiet at Night" variable.US News Honor Roll Hospitals have a mean score of 2.67, with a statistically significant difference of P < .001 between the groups.The key characteristics of the CMS Hospitals are that they are predominantly privately owned, specialized, surgical facilities with few total hospital beds.Knowing that HCAHPS scores directly impact and reflect patient experience, the objective of this study was to better understand the hospital practices that facilitate a high score on the "Quiet at Night" question to empower low scoring hospitals to improve their sleep practices at night and to score higher on the HCAHPS survey.
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INTRODUCTION: This study aimed to evaluate the clinical and economic outcomes of implementing a Clostridiodes difficile infection (CDI) Treatment Optimization and Access Pathway (treatment pathway) directing first-line use of fidaxomicin for CDI. METHODS: This was a retrospective, quasi-experimental study of adult patients with CDI using Electronic Health Record data from a single center. The primary intervention was implementation of a treatment pathway directing first-line use of fidaxomicin for patients with first/second CDI episode and at high risk of recurrence. The primary clinical outcome was CDI recurrence within 30 days of completing therapy in patients achieving clinical cure. Secondary clinical outcomes included clinical cure and sustained response evaluated at 90 days after completion of CDI treatment. Economic outcomes included costs associated with hospital stay at index admission and 30- and 90-day readmission. Differences between the pre- and post-implementation cohorts were assessed for baseline characteristics, CDI treatment utilization, clinical outcomes, and economic outcomes. The budget impact was calculated for the pre- vs. post-implementation cohorts, each normalized to 100 patients. RESULTS: Post- vs. pre-implementation, 30-day recurrence (6.4% vs. 18.0%., p = 0.001), 90-day recurrence (14.9% vs. 27.1%, p = 0.009), and 30-day (4.6% vs. 12.7%, p = 0.007) and 90-day CDI-related readmissions (8.5% vs. 18.9%, p = 0.007) were lower. The clinical cure (94.1% vs. 84.4%, p = 0.002) and 90-day sustained response rates were higher (73.3% vs. 55.9%, p < 0.001). Median total costs were also lower in the post- vs. pre-implementation cohorts at index admission ($11,934.64 vs. $14,523.27, p = 0.048), and 30-day ($7685.82 vs. $12,424.44, p = 0.102) and 90-day CDI-related readmission episodes ($8246.69 vs. $12,729.57, p = 0.042). The budget impact analyses of 100 patients post- vs. pre-implementation found saving of $222,895 overall and $9432 per CDI-readmission avoided. CONCLUSIONS: Implementation of the CDI treatment pathway was associated with better clinical outcomes and hospital cost savings. The findings help validate real-world value of fidaxomicin for CDI disease management.
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BACKGROUND AND OBJECTIVES: Sleep is vital to recovery from illness, yet it is frequently interrupted in the hospital setting. Existing literature relying on survey data identifies vitals, medications, and pulse oximetry as major disruptors to sleep. This study was designed to assess the degree to which these candidate sleep disruptors are associated with objective room entries. METHODS: Room entry sensors were placed on doors to 18 rooms on acute medical-surgical units at a tertiary academic center. The number of entries into rooms between 10 Pm and 6 Am were logged on patients admitted to hospital medicine services from March 2021 through February 2022. Medical records were reviewed to extract orders for vital sign frequency, medication timing, continuous pulse oximetry, and intravenous fluid use overnight. Negative binomial regression was used to evaluate associations. RESULTS: Room entry data were collected for 112 admissions and 192 patient-nights. There was an average of 7.8 room entries per patient-night. After adjustments for the other variables and for patients represented in multiple nights, vitals ordered every 4 hours were associated with a 1.3-fold increase in room entries (95% confidence interval 1.0-1.5; P = .013), as were medications scheduled during overnight hours (1.3; 95% confidence interval 1.0-1.5; P = .016). There was no association between room entries and continuous pulse oximetry use. After adjustment, there was also no association with administration of intravenous fluids. CONCLUSIONS: Vitals ordered every 4 hours and medications scheduled during sleep hours are independently associated with increased room entries and may be reasonable initial targets for quality improvement interventions designed to minimize nighttime disruptions.
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Hospitais , Sono , Humanos , Oximetria , Hospitalização , Fatores de TempoRESUMO
Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant (n = 119), the fecal microbiome was characterized at onset of severe neutropenia. A total of 63 patients (53%) developed a subsequent fever, and their fecal microbiome displayed increased relative abundances of Akkermansia muciniphila, a species of mucin-degrading bacteria (P = 0.006, corrected for multiple comparisons). Two therapies that induce neutropenia, irradiation and melphalan, similarly expanded A. muciniphila and additionally thinned the colonic mucus layer in mice. Caloric restriction of unirradiated mice also expanded A. muciniphila and thinned the colonic mucus layer. Antibiotic treatment to eradicate A. muciniphila before caloric restriction preserved colonic mucus, whereas A. muciniphila reintroduction restored mucus thinning. Caloric restriction of unirradiated mice raised colonic luminal pH and reduced acetate, propionate, and butyrate. Culturing A. muciniphila in vitro with propionate reduced utilization of mucin as well as of fucose. Treating irradiated mice with an antibiotic targeting A. muciniphila or propionate preserved the mucus layer, suppressed translocation of flagellin, reduced inflammatory cytokines in the colon, and improved thermoregulation. These results suggest that diet, metabolites, and colonic mucus link the microbiome to neutropenic fever and may guide future microbiome-based preventive strategies.
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Microbioma Gastrointestinal , Transplante de Células-Tronco Hematopoéticas , Neoplasias , Neutropenia , Camundongos , Animais , Propionatos , Verrucomicrobia , Muco/metabolismo , Mucinas/metabolismo , Dieta , Neutropenia/metabolismo , Neoplasias/metabolismoRESUMO
The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteroides , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Meropeném , Camundongos , Mucinas/metabolismo , Muco/metabolismo , Polissacarídeos/metabolismo , XiloseRESUMO
We report the complete genome sequence of a clinical isolate of Providencia stuartii strain CMC-4104, isolated from a splenic abscess. Oxford Nanopore Technologies (ONT) and Illumina sequencing reads were assembled using Geneious to generate a 4,504,925-bp circular chromosome containing multiple copies of the NDM-1 and PER-1 genes in a genomic resistance island.
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The objective of this study was to understand the existing practices and attitudes regarding inpatient sleep at the 2020 US News and World Report (USNWR) Honor Roll pediatric (n = 10) and adult (n = 20) hospitals. Section chiefs of Hospital Medicine from these institutions were surveyed and interviewed between June and August 2021. Among 23 of 30 surveyed physician leaders (response rate = 77%), 96% (n = 22) rated patient sleep as important, but only 43% (n = 10) were satisfied with their institutions' efforts. A total of 96% (n = 22) of institutions lack sleep equity practices. Fewer than half (48%) of top hospitals have sleep-friendly practices, with the most common practices including reducing overnight vital sign monitoring (43%), decreasing ambient light in the wards (43%), adjusting lab and medication schedules (35%), and implementing quiet hours (30%). Major themes from qualitative interviews included: importance of universal sleep-friendly cultures, environmental changes, and external incentives to improve patient sleep.