RESUMEN
BACKGROUND: Lumenal obstruction has typically been regarded as the cause of acute appendicitis (AA). Recent evidence including data from "antibiotics first" trials suggests that this disease may result from invasion of the appendix by specific pathogens. Small studies have identified an abundance of bacteria from the genus Fusobacterium in appendixes from patients with AA. We aimed to validate these findings in a larger cohort of children with appendicitis in addition to profiling the appendiceal microbiota in a population of children without appendicitis. METHODS: Appendix swabs were collected from children undergoing appendectomy for AA (n = 60), incidental appendectomy for reasons other than appendicitis (n = 18), or ileocecectomy for inflammatory bowel disease (n = 7), in addition to samples from other sites. Bacterial 16S ribosomal RNA gene sequences from each sample were amplified, sequenced, and analyzed with the UPARSE and QIIME programs. RESULTS: We found that the normal human appendix harbors populations of Fusobacteria that are generally absent in fecal samples from healthy adults and children. In patients with AA, Fusobacteria populations proliferate and often persist despite several weeks of broad-spectrum antibiotics prior to surgery. Relative to non-AA samples, AA samples were depleted of sequences from the genus Bacteroides Phylogenetic analysis of sequence data indicates that F. nucleatum, F. necrophorum, and F. varium are the species of Fusobacterium observed in AA samples. CONCLUSIONS: These results indicate that the appendiceal niche harbors distinct microbial populations that likely contribute to the pathogenesis of appendicitis, which may one day be leveraged to improve the diagnosis and/or treatment of patients with AA.
Asunto(s)
Apendicitis/microbiología , Apéndice/microbiología , Fusobacterias/genética , Infecciones por Bacterias Gramnegativas/microbiología , Enfermedad Aguda , Adolescente , Adulto , Apendicitis/epidemiología , Niño , Preescolar , Estudios de Cohortes , Heces/microbiología , Fusobacterias/aislamiento & purificación , Microbioma Gastrointestinal/genética , Infecciones por Bacterias Gramnegativas/epidemiología , HumanosAsunto(s)
Vacunas contra la COVID-19/inmunología , COVID-19/inmunología , Inmunoglobulina G/sangre , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto , COVID-19/diagnóstico , Prueba de Ácido Nucleico para COVID-19 , Vacunas contra la COVID-19/administración & dosificación , Intervalos de Confianza , Femenino , Personal de Salud , Humanos , Inmunización Secundaria , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
Arthropod-borne viruses represent a crucial public health threat. Current arboviral serology assays are either labor intensive or incapable of distinguishing closely related viruses, and many zoonotic arboviruses that may transition to humans lack any serologic assays. In this study, we present a programmable phage display platform, ArboScan, that evaluates antibody binding to overlapping peptides that represent the proteomes of 691 human and zoonotic arboviruses. We confirm that ArboScan provides detailed antibody binding information from animal sera, human sera, and an arthropod blood meal. ArboScan identifies distinguishing features of antibody responses based on exposure history in a Colombian cohort of Zika patients. Finally, ArboScan details epitope level information that rapidly identifies candidate epitopes with potential protective significance. ArboScan thus represents a resource for characterizing human and animal arbovirus antibody responses at cohort scale.
Asunto(s)
Anticuerpos Antivirales , Arbovirus , Humanos , Arbovirus/inmunología , Arbovirus/aislamiento & purificación , Animales , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Péptidos/inmunología , Péptidos/química , Infección por el Virus Zika/virología , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/sangre , Virus Zika/inmunología , Epítopos/inmunología , Pruebas Serológicas/métodos , Infecciones por Arbovirus/virología , Infecciones por Arbovirus/inmunología , Proteoma , Colombia , Femenino , Biblioteca de Péptidos , Técnicas de Visualización de Superficie Celular , MasculinoRESUMEN
OBJECTIVE: The risk of COVID-19 infection is increased in patients with systemic lupus erythematosus (SLE) versus those without SLE. Some immunosuppressive medications increase COVID-19 infection and decrease the efficacy of vaccination. Consensus documents have suggested management strategies for handling immunosuppressive medications to increase vaccine efficacy, but the benefit of such strategies has not been proven. The current study was undertaken to determine the effect of immunosuppressive drugs on vaccine response in SLE. METHODS: We collected information on COVID-19 infection, vaccination history, and COVID-19 antibodies in the Hopkins Lupus Cohort. A cohort of health care workers was used for comparison. Outcome measures included SARS-CoV-2 antibody IgG levels after vaccination over time in both cohorts and effect of immunosuppressive medications on postvaccination IgG levels in SLE patients. RESULTS: The analysis was based on 365 observations from 334 different patients in the SLE cohort, and 2,235 observations from 1,887 different health care workers. SLE patients taking immunosuppressive medications had lower vaccine IgG levels than SLE patients who were not; but both groups had lower levels than health care workers. Holding mycophenolate for 1 week after vaccination increased postvaccine IgG levels significantly without leading to clinical flares. In multiple variable models, mycophenolate mofetil, tacrolimus, and belimumab all significantly reduced antibody response to vaccination. CONCLUSION: SLE patients, regardless of background immunosuppressive therapy, had lower vaccine IgG levels than health care workers. Mycophenolate, tacrolimus, and belimumab significantly reduced IgG response to vaccination. Holding mycophenolate for 1 week improved vaccine efficacy, providing clinical benefit on vaccine response without leading to clinical flares.
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Vacunas contra la COVID-19 , COVID-19 , Lupus Eritematoso Sistémico , Humanos , Anticuerpos Antivirales/uso terapéutico , Formación de Anticuerpos , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , Inmunoglobulina G/uso terapéutico , Inmunosupresores/efectos adversos , Lupus Eritematoso Sistémico/tratamiento farmacológico , SARS-CoV-2 , Tacrolimus/uso terapéutico , VacunaciónRESUMEN
In a large healthcare worker cohort, we quantified the association between behaviors and risk of coronavirus disease 2019 (COVID-19) during different pandemic phases, adjusting for prior infection and vaccination. Individual characteristics, including personal concerns, were associated with these behaviors. Public health messaging should target high-risk populations and behaviors as the pandemic evolves.
RESUMEN
Introduction: Clinical Coaching Cards is a serious game for faculty development in which players take turns as Teacher and Coach to apply teaching techniques on game cards to identify new approaches to teaching in the clinical environment. The game employs active learning theory and coaching frameworks. Methods: Based on a literature search and local faculty practices, we identified 14 techniques for clinical teaching and created a deck of cards summarizing each. We adapted rules from social judgment games so that participants proposed and selected techniques for applicability to their own teaching. The game was presented as a subsession of larger faculty development workshops hosted by the University of Washington, and players included faculty, residents, and medical students. Evaluations focused on the applicability of techniques to participants' clinical practice and preferred new techniques. Results: Seventy-four players provided evaluations out of over 150 participants across six workshops. Participants rated the session as mostly or very organized in 70 of 74 evaluations (95%), the introductory material as mostly or very relevant in 67 evaluations (91%), and the teaching techniques as most or several being useful in 69 evaluations (93%). Although some techniques were more popular than others, every technique was selected as a Top 3 technique for future practice. Discussion: Clinical Coaching Cards is a card game that applies active learning within a framework of peer coaching to teach bedside and clinical teaching techniques.
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Tutoría , Estudiantes de Medicina , Docentes , Humanos , Grupo Paritario , Aprendizaje Basado en ProblemasRESUMEN
The emergency department (ED) is an increasingly important site of care for patients who have undergone solid organ transplantation or hematopoietic cell transplantation. It is paramount for emergency physicians to recognize infections early on, obtain appropriate diagnostic testing, initiate empirical antimicrobial therapy, and consider specialty consultation and inpatient admission when caring for these patients. This review provides emergency physicians with an approach to the assessment of transplant patients' underlying risk for infection, formulation of a broad differential diagnosis, and initial management of transplant infectious disease emergencies in the ED.
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Infecciones Bacterianas/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Trasplante de Órganos , Complicaciones Posoperatorias/epidemiología , Trasplantes/estadística & datos numéricos , Humanos , Huésped Inmunocomprometido , Incidencia , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Although luminal obstruction has traditionally been viewed as the underlying cause of appendicitis, recent evidence has suggested that the disease may result directly from invasion by specific pathogens, e.g. Fusobacterium nucleatum. The purpose of this study was to survey microbial communities within pediatric appendectomy specimens using a culture-independent approach. METHODS: We performed 16S ribosomal gene sequence analysis to profile the microbiota present within luminal fluid obtained from 22 pediatric appendectomy specimens. These included 10 simple appendicitis cases, 5 perforated appendicitis cases, 2 interval appendectomies, and 5 incidental appendectomies. RESULTS: Samples could be divided into 2 distinct clusters based upon the composition of the appendiceal bacterial communities. Appendicitis samples contained an increased abundance of Fusobacterium spp. and a reduced abundance of Bacteroides spp. relative to non-appendicitis cases. Appendicitis samples also contained variable amounts of other oral taxa such as Porphyromonas, Parvimonas, and Gemella, whereas these taxa were generally absent from non-appendicitis samples. CONCLUSIONS: Acute appendicitis is associated with an abundance of Fusobacterium spp. and other pathogens commonly found in the oral cavity. Further research is needed to determine whether these organisms directly cause appendicitis or rather proliferate in the appendix as a secondary consequence of inflammation.
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Apendicitis/microbiología , Fusobacterium/aislamiento & purificación , Microbiota , Adolescente , Apendicectomía , Apendicitis/etiología , Apendicitis/cirugía , Apéndice/microbiología , Bacteroides/aislamiento & purificación , Líquidos Corporales/microbiología , Niño , Preescolar , ADN Bacteriano/análisis , ADN Bacteriano/genética , ADN Ribosómico/análisis , ADN Ribosómico/genética , Fusobacterium/genética , Humanos , Lactante , Boca/microbiología , Proyectos Piloto , Porphyromonas/aislamiento & purificación , Proteobacteria/aislamiento & purificación , ARN Bacteriano/genética , ARN Ribosómico 16S/genética , Ribotipificación , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Previous studies of infant fecal samples have failed to clarify the role of gut bacteria in the pathogenesis of NEC. We sought to characterize bacterial communities within intestinal tissue resected from infants with and without NEC. METHODS: 26 intestinal samples were resected from 19 infants, including 16 NEC samples and 10 non-NEC samples. Bacterial 16S rRNA gene sequences were amplified and sequenced. Analysis allowed for taxonomic identification, and quantitative PCR was used to quantify the bacterial load within samples. RESULTS: NEC samples generally contained an increased total burden of bacteria. NEC and non-NEC sample sets were both marked by high inter-individual variability and an abundance of opportunistic pathogens. There was no statistically significant distinction between the composition of NEC and non-NEC microbial communities. K-means clustering enabled us to identify several stable clusters, including clusters of NEC and midgut volvulus samples enriched with Clostridium and Bacteroides. Another cluster containing both NEC and non-NEC samples was marked by an abundance of Enterobacteriaceae and decreased diversity among NEC samples. CONCLUSIONS: The results indicate that NEC is a disease without a uniform pattern of microbial colonization, but that NEC is associated with an abundance of strict anaerobes and a decrease in community diversity.