RESUMEN
OBJECTIVE: The study aimed to assess the diagnostic accuracy of point-of-care ultrasound (POCUS) in identifying small bowel obstruction (SBO) and to investigate the impact of clinician experience level and body mass index (BMI) on POCUS performance for diagnosing SBO in the Emergency Department. METHODS: We systematically searched PubMed and Cochrane databases from January 2011-2022. We performed a meta-analysis using individual patient-level data from prospective diagnostic accuracy studies from which we obtained data from the corresponding authors. Overall test characteristics and subgroup analysis across clinician experience levels and a range of BMI were calculated. The primary outcome was SBO as the final diagnosis during hospitalization. RESULTS: We included Individual patient data from 433 patients from 5 prospective studies. Overall, 33% of patients had a final diagnosis of SBO. POCUS had 83.0% (95%CI 71.7%-90.4%) sensitivity and 93.0% (95%CI 55.3%-99.3%) specificity; LR+ was 11.9 (95%CI 1.2-114.9) and LR- was 0.2 (95%CI 0.1-0.3). Residents had exhibited a sensitivity of 73.0% (95%CI 56.6%-84.9%) and specificity of 88.2% (95%CI 58.8%-97.5%), whereas attendings had demonstrated a sensitivity of 87.7% (95%CI 71.1%-95.4%) and specificity of 91.4% (95%CI 57.4%-98.8%). Among those patients with BMI<30 kg/m2, POCUS showed a sensitivity of 88.6% (95%CI 79.5%-94.7%) and a specificity of 84.0% (95%CI 75.3%-90.6%), while patients with BMI ≥ 30 kg/m2 exhibited a sensitivity of 72.0% (95%CI 50.6%-87.9%) and specificity of 89.5% (95%CI 75.2%-97.1%). CONCLUSIONS: POCUS correctly identified those patients with SBO with high sensitivity and specificity. Diagnostic accuracy was slightly reduced when performed by resident physicians and among patients with a BMI ≥ 30 kg/m2. REGISTRATION: PROSPERO registration number: CRD42022303598.
Asunto(s)
Obstrucción Intestinal , Sistemas de Atención de Punto , Humanos , Estudios Prospectivos , Ultrasonografía , Pruebas en el Punto de Atención , Obstrucción Intestinal/diagnóstico por imagen , Servicio de Urgencia en Hospital , Sensibilidad y Especificidad , Estudios Multicéntricos como AsuntoRESUMEN
BACKGROUND: Point-of-care ultrasound (US) has been suggested as the primary imaging in evaluating patients with suspected diverticulitis. Discrimination between simple and complicated diverticulitis may help to expedite emergent surgical consults and determine the risk of complications. This study aimed to: (1) determine the accuracy of an US protocol (TICS) for diagnosing diverticulitis in the emergency department (ED) setting and (2) assess the ability of TICS to distinguish between simple and complicated diverticulitis. METHODS: Patients with clinically suspected diverticulitis who underwent a diagnostic computed tomography (CT) scan were identified prospectively in the ED. Emergency US faculty and fellows blinded to the CT results performed and interpreted US scans. The presence of simple or complicated diverticulitis was recorded after each US evaluation. The diagnostic ability of the US was compared to CT as the criterion standard. Modified Hinchey classification was used to distinguish between simple and complicated diverticulitis. RESULTS: A total of 149 patients (55% female, mean ± SD age 58 ± 16 years) were enrolled and included in the final analyses. Diverticulitis was the final diagnosis in 75 of 149 patients (50.3%), of whom 53 had simple diverticulitis and 22 had perforated diverticulitis (29.4%). TICS protocol's test characteristics for simple diverticulitis include a sensitivity of 95% (95% confidence interval [CI] 87%-99%), specificity of 76% (95% CI 65%-86%), positive predictive value of 80% (95% CI 71%-88%), and negative predictive value of 93% (95% CI 84%-98%). TICS protocol correctly identified 12 of 22 patients with complicated diverticulitis (sensitivity 55% [95% CI 32%-76%]) and specificity was 96% (95% CI 91%-99%). Eight of 10 missed diagnoses of complicated diverticulitis were identified as simple diverticulitis, and two were recorded as negative. CONCLUSIONS: In ED patients with suspected diverticulitis, US demonstrated high accuracy in ruling out or diagnosing diverticulitis, but its reliability in differentiating complicated from simple diverticulitis is unsatisfactory.
Asunto(s)
Diverticulitis , Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Masculino , Estudios Prospectivos , Reproducibilidad de los Resultados , Diverticulitis/complicaciones , Diverticulitis/diagnóstico por imagen , Valor Predictivo de las Pruebas , Ultrasonografía , Sensibilidad y EspecificidadRESUMEN
Identifying the potential for SARS-CoV-2 reinfection is crucial for understanding possible long-term epidemic dynamics. We analysed longitudinal PCR and serological testing data from a prospective cohort of 4,411 United States employees in 4 states between April 2020 and February 2021. We conducted a multivariable logistic regression investigating the association between baseline serological status and subsequent PCR test result in order to calculate an odds ratio for reinfection. We estimated an odds ratio for reinfection ranging from 0.14 (95% CI: 0.019 to 0.63) to 0.28 (95% CI: 0.05 to 1.1), implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 72% to 86% reduced odds of a subsequent PCR positive test based on our point estimates. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a 6-month time period. We also highlight 2 major sources of bias and uncertainty to be considered when estimating the relative risk of reinfection, confounders and the choice of baseline time point, and show how to account for both in reinfection analysis.
Asunto(s)
Anticuerpos Antivirales/sangre , COVID-19/inmunología , Reinfección/inmunología , Adolescente , Adulto , Anciano , COVID-19/epidemiología , COVID-19/prevención & control , Prueba de Ácido Nucleico para COVID-19 , Prueba Serológica para COVID-19 , Humanos , Modelos Logísticos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Estudios Prospectivos , Reinfección/prevención & control , SARS-CoV-2/inmunología , Estudios Seroepidemiológicos , Factores de Tiempo , Estados Unidos/epidemiología , Lugar de Trabajo/estadística & datos numéricos , Adulto JovenRESUMEN
STUDY OBJECTIVE: We sought to determine the ability of lung point-of-care ultrasound (POCUS) to predict mechanical ventilation and in-hospital mortality in patients with coronavirus disease 2019 (COVID-19). METHODS: This was a prospective observational study of a convenience sample of patients with confirmed COVID-19 presenting to 2 tertiary hospital emergency departments (EDs) in Iran between March and April 2020. An emergency physician attending sonographer performed a 12-zone bilateral lung ultrasound in all patients. Research associates followed the patients on their clinical course. We determined the frequency of positive POCUS findings, the geographic distribution of lung involvement, and lung severity scores. We used multivariable logistic regression to associate lung POCUS findings with clinical outcomes. RESULTS: A total of 125 patients with COVID-like symptoms were included, including 109 with confirmed COVID-19. Among the included patients, 33 (30.3%) patients were intubated, and in-hospital mortality was reported in 19 (17.4%). Lung POCUS findings included pleural thickening 95.4%, B-lines 90.8%, subpleural consolidation 86.2%, consolidation 46.8%, effusions 19.3%, and atelectasis 18.3%. Multivariable logistic regression incorporating binary and scored POCUS findings were able to identify those at highest risk for need of mechanical ventilation (area under the curve 0.80) and in-hospital mortality (area under the curve 0.87). In the binary model ultrasound (US) findings in the anterior lung fields were significantly associated with a need for intubation and mechanical ventilation (odds ratio [OR] 3.67; 0.62-21.6). There was an inverse relationship between mortality and posterior lung field involvement (OR 0.05; 0.01-0.23; and scored OR of 0.57; 0.40-0.82). Anterior lung field involvement was not associated with mortality. CONCLUSIONS: In patients with COVID-19, the anatomic distribution of findings on lung ultrasound is associated with outcomes. Lung POCUS-based models may help clinicians to identify those patients with COVID-19 at risk for clinical deterioration.Key Words: COVID-19; Lung Ultrasound; Mechanical ventilation; Prediction; ICU admission; Mortality; Clinical outcome; Risk stratification; Diagnostic accuracy.
RESUMEN
BACKGROUND: The impact of alcohol or opioid use disorders on medication dosing for procedural sedation in the emergency department (ED) is unclear, as most of the literature is from gastrointestinal endoscopy. Exploring how these patient factors affect sedative and analgesic medications may inform more nuanced sedation strategies in the emergency department. METHODS: This was a retrospective chart-review cohort study across five EDs from 2015 to 2020. Included were adult patients who underwent procedural sedation in the ED, categorized into three a priori groups: alcohol use disorder (AUD), opioid use disorder (OUD), and individuals with neither (non-SUD). Wilcoxon test was used to compare the time-averaged dose of agents between groups. Logistic regression was used to model multi-agent sedations. The propofol time-averaged dose was the primary outcome. Secondary outcomes included other agents, sedation duration, and switching to other agents. RESULTS: 2725 sedations were included in the analysis. 59 patients had a history of AUD, and 40 had a history of OUD. Time-averaged doses of medications did not differ significantly between AUD and non-SUD patients. Likewise, patients with OUD did not receive different doses of medications compared to non-SUD. The propofol doses for non-SUD, AUD, and OUD were 0.033 IQR 0.04; 0.042 IQR 0.05; and 0.058 IQR 0.04 mg/kg*min, respectively. Sedation duration was not different across groups. Having AUD or OUD is not associated with increased odds of requiring multiple sedative agents. CONCLUSION: Although sedation in patients with AUD or OUD may be associated with significant case bias, these patient factors did not significantly alter outcomes compared to the general population. This study suggests there is no evidence to proactively adjust medication strategy in ED patients with AUD or OUD.
Asunto(s)
Relación Dosis-Respuesta a Droga , Hipnóticos y Sedantes/administración & dosificación , Trastornos Relacionados con Sustancias/complicaciones , Adulto , Anciano , Estudios de Cohortes , Minería de Datos , Servicio de Urgencia en Hospital/organización & administración , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Hipnóticos y Sedantes/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trastornos Relacionados con Sustancias/fisiopatología , Resultado del TratamientoRESUMEN
BACKGROUND: Acute cholecystitis can be difficult to diagnose in the emergency department (ED); no single finding can rule in or rule out the disease. A prediction score for the diagnosis of acute cholecystitis for use at the bedside would be of great value to expedite the management of patients presenting with possible acute cholecystitis. The 2013 Tokyo Guidelines is a validated method for the diagnosis of acute cholecystitis but its prognostic capability is limited. The purpose of this study was to prospectively validate the Bedside Sonographic Acute Cholecystitis (SAC) Score utilizing a combination of only historical symptoms, physical exam signs, and point-of-care ultrasound (POCUS) findings for the prediction of the diagnosis of acute cholecystitis in ED patients. METHOD: This was a prospective observational validation study of the Bedside SAC Score. The study was conducted at two tertiary referral academic centers in Boston, Massachusetts. From April 2016 to March 2019, adult patients (≥18 years old) with suspected acute cholecystitis were enrolled via convenience sampling and underwent a physical exam and a focused biliary POCUS in the ED. Three symptoms and signs (post-prandial symptoms, RUQ tenderness, and Murphy's sign) and two sonographic findings (gallbladder wall thickening and the presence of gallstones) were combined to calculate the Bedside Sonographic Acute Cholecystitis (SAC) Score. The final diagnosis of acute cholecystitis was determined from chart review or patient follow-up up to 30 days after the initial assessment. In patients who underwent operative intervention, surgical pathology was used to confirm the diagnosis of acute cholecystitis. Sensitivity, specificity, PPV and NPV of the Bedside SAC Score were calculated for various cut off points. RESULTS: 153 patients were included in the analysis. Using a previously defined cutoff of ≥ 4, the Bedside SAC Score had a sensitivity of 88.9% (95% CI 73.9%-96.9%), and a specificity of 67.5% (95% CI 58.2%-75.9%). A Bedside SAC Score of < 2 had a sensitivity of 100% (95% CI 90.3%-100%) and specificity of 35% (95% CI 26.5%-44.4%). A Bedside SAC Score of ≥ 7 had a sensitivity of 44.4% (95% CI 27.9%-61.9%) and specificity of 95.7% (95% CI 90.3%-98.6%). CONCLUSION: A bedside prediction score for the diagnosis of acute cholecystitis would have great utility in the ED. The Bedside SAC Score would be most helpful as a rule out for patients with a low Bedside SAC Score < 2 (sensitivity of 100%) or as a rule in for patients with a high Bedside SAC Score ≥ 7 (specificity of 95.7%). Prospective validation with a larger study is required.
Asunto(s)
Colecistitis Aguda/diagnóstico por imagen , Reglas de Decisión Clínica , Servicio de Urgencia en Hospital , Pruebas en el Punto de Atención , Adulto , Femenino , Humanos , Masculino , Anamnesis , Examen Físico , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , UltrasonografíaRESUMEN
INTRODUCTION: The importance of this study is to devise an efficient tool for assessing frailty in the ED. The goals of this study are 1) to correlate ultrasonographic (US) measurements of muscle thickness in older ED patients with frailty and 2) to correlate US-measured sarcopenia with falls, subsequent hospitalizations and ED revisits. METHODS: Participants were conveniently sampled from a single ED in this prospective cohort pilot study of patients aged 65 or older. Participants completed a Fatigue, Resistance, Ambulation, Illness and Loss of Weight (FRAIL) scale assessment and US measurements of their upper arm muscles, quadricep muscles, and abdominal wall muscles thickness. We conducted one-month follow-up phone calls to assess for falls, ED revisits, and subsequent hospital visits. RESULTS: We enrolled 43 patients (mean age of 78.5). Ultrasound measurements of the three muscle groups were not significantly different between frail and non-frail groups. Frail participants had greater bicep asymmetry (a difference of 0.47 cm vs 0.24 cm, p < .01). A predictive logistic regression model using average quadriceps thickness and biceps asymmetry was found to identify frail patients (AUC of 0.816). Participants with subsequent falls had smaller quadriceps (1.18 cm smaller, p < .01). Subsequently hospitalized patients were found to have smaller quadriceps muscles (0.54 cm smaller, p = .03) and abdominal wall muscles (0.25 cm smaller, p = .01). CONCLUSION: US measurements of sarcopenia in older patients had mild to moderate associations with frailty, falls and subsequent hospitalizations. Further investigation is needed to confirm these findings.
Asunto(s)
Accidentes por Caídas , Anciano Frágil , Sarcopenia/diagnóstico por imagen , Ultrasonografía/métodos , Anciano , Anciano de 80 o más Años , Servicio de Urgencia en Hospital , Femenino , Evaluación Geriátrica , Humanos , Masculino , Proyectos Piloto , Estudios Prospectivos , Medición de RiesgoRESUMEN
Confirmation of endotracheal tube (ETT) placement during intubation is a critical skill for emergency medicine (EM) residents; airway ultrasonography has been suggested as an accessible and accurate method of ETT confirmation. Here, we investigated the accuracy with which EM residents could identify ETT location in cadavers using different ultrasound modes. EM attendings intubated either the trachea or the esophagus of a cadaver, and blinded residents identified ETT position using either B-mode or B-mode plus color Doppler. Residents correctly identified ETT location in 1075 of 1203 trials (89.4%); performance improved with post-graduate year (residents in post-graduate year 3 had 97.8% accurate identifications). There were 556 (91.7%) correct identifications made with B-mode and 519 (86.9%) with B-mode plus color Doppler (p valueâ¯=â¯0.007); thus, accuracy did not improve with addition of color Doppler to B-mode. Further research is needed on the efficacy of different ultrasound modes in confirming ETT placement in live intubations.
Asunto(s)
Medicina de Emergencia/educación , Internado y Residencia , Intubación Intratraqueal , Ultrasonografía/métodos , Cadáver , Esófago/diagnóstico por imagen , Humanos , Intubación Intratraqueal/normas , Tráquea/diagnóstico por imagen , Ultrasonografía Doppler en ColorRESUMEN
BACKGROUND AND PURPOSE: Ultrasound (US) measurement of the optic nerve sheath diameter (ONSD) and optic nerve diameter (OND) is a method frequently used to screen for an increased intracranial pressure. The aim of this study was to assess the accuracy of US measurements of ONSD and OND, when compared to magnetic resonance imaging (MRI) measurements as the criterion standard. METHODS: In this prospective, single-institution study, orbital US was performed for those patients requiring an emergent brain MRI. ONSD and OND of both eyes were measured in the axial and coronal planes in straight gaze by US. ONSD and OND from brain and orbital MRI were measured by two neuroradiologists. Correlation and agreement between readings were assessed using Pearson's correlations. RESULTS: Eighty-two patients met inclusion criteria. The mean axial and coronal ONSD in the MRI examinations was 5.6 and 5.7 mm at 3-5.9 mm behind the globe, respectively. The mean ONSD from the US measurements was 6.22 and 5.52 mm in the axial and coronal planes, respectively. The mean OND in US examinations was 4.31 mm (axial) and 3.68 mm (coronal). Axial versus coronal measurements of ONSD had a modest correlation in US assessment with an r2 of .385 (P < .001) but there were no correlations between any of the US and MRI measurements. CONCLUSIONS: In measuring ONSD and OND, US measurements showed a modest correlation between axial and coronal measurements, but no concordance was found between US and MRI in our setting.
Asunto(s)
Hipertensión Intracraneal/diagnóstico por imagen , Imagen por Resonancia Magnética , Nervio Óptico/diagnóstico por imagen , Ultrasonografía , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuroimagen , Sistemas de Atención de Punto , Estudios ProspectivosRESUMEN
OBJECTIVES: Difficult intravenous access (DIVA) is common in the emergency department (ED). We investigated the extent to which DIVA is associated with care delay outcomes including time to first laboratory draw, therapies, imaging, and ED disposition. METHODS: An observational retrospective cohort analysis of patients with DIVA treated between 2018 and 2020 at 2 urban academic EDs was performed. DIVA was defined as patients requiring ultrasound-guided intravenous access placed by physicians or advanced practice providers (APPs) as opposed to landmark-based intravenous placement by nurses. ED throughput variables and disposition time were compared. We correlated DIVA with time to administration of intravenous pain medications, fluids, imaging contrast, laboratory results, and ED disposition. RESULTS: A total of 108,256 subjects with 161,122 total encounters were included. DIVA occurred in 4961 (3.1%) of ED visits. Patients with DIVA were more likely to be female (3.5% vs 2.6% for males, odds ratio [OR] 1.34, 95% confidence interval [CI]: 1.27-1.42), self-identify as black (OR 1.78, 95% CI: 1.66-1.91), and have higher acuity of illness (P < 0.001). Among pediatric patients, DIVA occurred most often in the first year of life at a rate of 3.25%. In adults, DIVA occurred in 2 age peaks; at 35 years (4.02%), and at 63 years (3.44%). In all workflow metrics, the presence of DIVA was associated with significant delays in median time to completion: 50 minutes for pain medication administration, 36 minutes for intravenous fluid administration, 29 minutes for laboratory results, 57 minutes for intravenous contrast administration, and 87 minutes for discharge orders. CONCLUSION: DIVA was associated with increased time to therapies, diagnostic studies, imaging completion, and ED disposition. A more expeditious approach to achieving intravenous access in patients with predicted DIVA could improve ED throughput and patient care overall.
RESUMEN
OBJECTIVE: Early diagnostic prediction in patients with small bowel obstruction (SBO) can improve time to definitive management and disposition in the emergency department. We sought to develop a nomogram to leverage point-of-care ultrasound (POCUS) and maximize accuracy of prediction of SBO diagnosis. METHODS: Using data from a prospective cohort of 125 patients with suspected SBO who were evaluated with POCUS in the ED, we developed a nomogram integrating age, gender, comorbidities, prior abdominal surgery, physician's pre-test probability, and POCUS findings to determine post-test risk of SBO. The primary outcome was to develop a nomogram to allow calculating output probabilities for predictive models using POCUS findings. The discriminative ability of the nomogram was tested using a C-statistics, calibration plots, and receiver operating characteristic curves. RESULTS: The derivation cohort included 125 patients with a median age of 54 years who underwent POCUS for a suspected SBO. One-fourth of the patients (25.6% [32/125]) had SBO. Using a retrospective stepwise selection of clinically important variables with the POCUS results, the final nomogram incorporated four relevant factors for the prediction of SBO: small bowel diameter (odds ratio [OR] per 1 mm increase, 1.10; 95% CI, 1.03-1.17; P = 0.001), positive free intraperitoneal fluid between bowel loops (OR, 8.19; 95% CI, 2.62-25.62; P < 0.001), clinician's moderate (OR, 5.94; 95% CI, 0.83-42.57; P = 0.08) or high pretest probability (OR, 11.26; 95% CI, 1.44-88.25; P = 0.02), and patient age (OR per 1 year increase, 1.03; 95% CI, 1.00 to1.07; P = 0.08).The discriminative ability and calibration of the nomogram revealed good predictive ability as indicated by the C-statistic of 0.89 for the SBO diagnosis. CONCLUSION: A unique nomogram incorporating patient age, physician pretest probability of SBO, and POCUS measurements of small bowel diameter and the presence of free intraperitoneal fluid between bowel loops was developed to accurately predict the diagnosis of SBO in the emergency department. The nomogram should be externally validated in a novel cohort of patients at risk for SBO to better assess predictability and generalizability.
Asunto(s)
Obstrucción Intestinal/diagnóstico , Intestino Delgado/diagnóstico por imagen , Nomogramas , Servicio de Urgencia en Hospital , Femenino , Humanos , Intestino Delgado/patología , Masculino , Persona de Mediana Edad , Sistemas de Atención de Punto , Estudios Prospectivos , UltrasonografíaRESUMEN
Chronic wounds are a major complication of diabetes associated with high morbidity and health care expenditures. To investigate the role of colonizing microbiota in diabetic wound healing, clinical outcomes, and response to interventions, we conducted a longitudinal, prospective study of patients with neuropathic diabetic foot ulcers (DFU). Metagenomic shotgun sequencing revealed that strain-level variation of Staphylococcus aureus and genetic signatures of biofilm formation were associated with poor outcomes. Cultured wound isolates of S. aureus elicited differential phenotypes in mouse models that corresponded with patient outcomes, while wound "bystanders" such as Corynebacterium striatum and Alcaligenes faecalis, typically considered commensals or contaminants, also significantly impacted wound severity and healing. Antibiotic resistance genes were widespread, and debridement, rather than antibiotic treatment, significantly shifted the DFU microbiota in patients with more favorable outcomes. These findings suggest that the DFU microbiota may be a marker for clinical outcomes and response to therapeutic interventions.
Asunto(s)
Antiinfecciosos/uso terapéutico , Coinfección/microbiología , Desbridamiento , Pie Diabético/microbiología , Microbiota , Infección de Heridas/microbiología , Animales , Coinfección/terapia , Pie Diabético/terapia , Modelos Animales de Enfermedad , Estudios Longitudinales , Ratones , Estudios Prospectivos , Resultado del Tratamiento , Cicatrización de Heridas , Infección de Heridas/terapiaRESUMEN
Plaque psoriasis, a chronic inflammatory disease primarily affecting the skin, is thought to have a multifactorial etiology, including innate immune system dysregulation, environmental triggers, and genetic susceptibility. We sought to further understand the role of skin microbiota in psoriasis pathogenesis, as well as their response to therapy. We systematically analyzed dynamic microbiota colonizing psoriasis lesions and adjacent nonlesional skin in 114 patients prior to and during ustekinumab treatment in a phase 3b clinical trial. By sequencing the bacterial 16S ribosomal RNA gene from skin swab samples obtained at six anatomical sites, we identified minor, site-specific differences in microbial diversity and composition between pretreatment lesional and nonlesional skin. During therapy, microbial communities within lesional and nonlesional skin diverged, and body-site dispersion increased, reflecting microbial skin site-specificity. Microbiota demonstrated greater pretreatment heterogeneity in psoriatic lesions than in nonlesional skin, and variance increased as treatment progressed. Microbiota colonizing recurrent lesions did not overlap with pretreatment lesional microbiota, suggesting colonization patterns varied between initial and recurrent psoriatic lesions. While plaque psoriasis does not appear to be associated with specific microbes and/or microbial diversity, this large dataset provides insight into microbial variation associated with (i) disease in different body locations, (ii) initial versus recurrent lesions, and (iii) anti-IL12/23 therapy.
Asunto(s)
Bacterias/genética , Microbiota/efectos de los fármacos , Psoriasis/tratamiento farmacológico , Piel/microbiología , Ustekinumab/administración & dosificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/aislamiento & purificación , Estudios Transversales , Fármacos Dermatológicos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Psoriasis/metabolismo , Psoriasis/microbiología , ARN Bacteriano/análisis , Estudios Retrospectivos , Piel/patología , Adulto JovenRESUMEN
Skin microbiota can impact allergic and autoimmune responses, wound healing, and anti-microbial defense. We investigated the role of skin microbiota in cutaneous leishmaniasis and found that human patients infected with Leishmania braziliensis develop dysbiotic skin microbiota, characterized by increases in the abundance of Staphylococcus and/or Streptococcus. Mice infected with L. major exhibit similar changes depending upon disease severity. Importantly, this dysbiosis is not limited to the lesion site, but is transmissible to normal skin distant from the infection site and to skin from co-housed naive mice. This observation allowed us to test whether a pre-existing dysbiotic skin microbiota influences disease, and we found that challenging dysbiotic naive mice with L. major or testing for contact hypersensitivity results in exacerbated skin inflammatory responses. These findings demonstrate that a dysbiotic skin microbiota is not only a consequence of tissue stress, but also enhances inflammation, which has implications for many inflammatory cutaneous diseases.
Asunto(s)
Disbiosis/etiología , Disbiosis/inmunología , Inflamación , Leishmania braziliensis/patogenicidad , Leishmaniasis Cutánea/complicaciones , Leishmaniasis Cutánea/microbiología , Microbiota/fisiología , Piel/inmunología , Animales , Modelos Animales de Enfermedad , Humanos , Hipersensibilidad , Inflamación/inmunología , Inflamación/microbiología , Leishmania major/inmunología , Leishmania major/patogenicidad , Ratones , Ratones Endogámicos C57BL , Microbiota/inmunología , Piel/microbiología , Piel/parasitología , Staphylococcus/inmunología , Staphylococcus/patogenicidad , Streptococcus/inmunología , Streptococcus/patogenicidadRESUMEN
Cutaneous leishmaniasis is a disease characterized by ulcerating skin lesions, the resolution of which requires an effective, but regulated, immune response that limits parasite growth without causing permanent tissue damage. While mechanisms that control the parasites have been well studied, the factors regulating immunopathologic responses are less well understood. IL-22, a member of the IL-10 family of cytokines, can contribute to wound healing, but in other instances promotes pathology. Here we investigated the role of IL-22 during leishmania infection, and found that IL-22 limits leishmania-induced pathology when a certain threshold of damage is induced by a high dose of parasites. Il22-/- mice developed more severe disease than wild-type mice, with significantly more pathology at the site of infection, and in some cases permanent loss of tissue. The increased inflammation was not due to an increased parasite burden, but rather was associated with the loss of a wound healing phenotype in keratinocytes. Taken together, these studies demonstrate that during cutaneous leishmaniasis, IL-22 can play a previously unappreciated role in controlling leishmania-induced immunopathology.