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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.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.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.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.

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.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.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 of2 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%).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 Score2 (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.

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.

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

Introduction: Although emergency department (ED) discharge presents patient-safety challenges and opportunities, the ways in which EDs address discharge risk in the general ED population remains disparate and largely uncharacterized. In this study our goal was to conduct a review of how EDs identify and target patients at increased risk at time of discharge. Methods: We conducted a literature search to explore how EDs assess patient risk upon discharge, including a review of PubMed and gray literature. After independently screening articles for inclusion, we recorded study characteristics including outcome measures, patient risk factors, and tool descriptions. Based on this review and discussion among collaborators, major themes were identified. Results: PubMed search yielded 384 potentially eligible articles. After title and abstract review, we screened 235 for potential inclusion. After full text and reference review, supplemented by Google Scholar and gray literature reviews, we included 30 articles for full review. Three major themes were elucidated: 1) Multiple studies include retrospective risk assessment, whereas the use of point-of-care risk assessment tools appears limited; 2) of the point-of-care tools that exist, inputs and outcome measures varied, and few were applicable to the general ED population; and 3) while many studies describe initiatives to improve the discharge process, few describe assessment of post-discharge resource needs. Conclusion: Numerous studies describe factors associated with an increased risk of readmission and adverse events after ED discharge, but few describe point-of-care tools used by physicians for the general ED population. Future work is needed to investigate standardized tools that assess ED discharge risk and patients’ needs upon ED discharge.

Identifying the extent of 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 4411 US employees in four 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 adjusted odds ratio of 0.09 (95% CI: 0.005 – 0.48) for reinfection, implying that the presence of SARS-CoV-2 antibodies at baseline is associated with around 91% reduced odds of a subsequent PCR positive test. This suggests that primary infection with SARS-CoV-2 provides protection against reinfection in the majority of individuals, at least over a sixth month time period. We also highlight two major sources of bias and uncertainty to be considered when estimating reinfection risk, confounders and the choice of baseline time point, and show how to account for both in our analysis.

Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response remain poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups, we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection, and remarkably homogenous immune activity across BMI categories suggests immune protection across these groups may be similar.

Introduction Point-of-care ultrasound (POCUS) is an essential tool in the timely evaluation of an undifferentiated patient in the emergency department (ED). Our primary objective in this study was to determine the perceived impact of POCUS in high-risk cases presented at emergency medicine (EM) morbidity and mortality (M&M) conferences. Additionally, we sought to identify in which types of patients POCUS might be most useful, and which POCUS applications were considered to be highest yield. Methods This was a retrospective survey of cases submitted to M&M at an EM residency program that spans two academic EDs, over one academic year. Postgraduate year 4 (PGY) residents who presented M&M cases at departmental sessions were surveyed on perceived impacts of POCUS on individual patient outcomes. We evaluated POCUS use and indications while the POCUS was used. Results Over the 12-month period, we reviewed 667 cases from 18 M&M sessions by 15 PGY-4 residents and a supervising EM attending physician who chairs the M&M committee. Of these cases, 75 were selected by the M&M committee for review and presentation. POCUS was used in 27% (20/75) of the cases and not used in 73% (55/75). In cases where POCUS was not used, retrospective review determined that if POCUS had been used it would have "likely prevented the M&M" in 45% (25/55). Of these 25 cases, the majority of POCUS applications that could have helped were cardiac (32%, 8/25) and lung (32%, 8/25) ultrasound. POCUS was felt to have greatest potential in identifying missed diagnoses (92%, 23/25), and decreasing the time to diagnosis (92%, 23/25). Patients with cardiopulmonary chief complaints and abnormal vital signs were most likely to benefit. There were seven cases (35%, 7/20, 95% CI 15-59%) in which POCUS was performed and thought to have possibly adversely affected the outcome of the M&M. Conclusion POCUS was felt to have the potential to reduce or prevent M&M in 45% of cases in which it was not used. Cardiac and lung POCUS were among the most useful applications, especially in patients with cardiopulmonary complaints and in those with abnormal vital signs.

Study Objectives: Chest CT scan (CT) is often considered the gold-standard imaging modality to evaluate pulmonary pathology, and thus is used to assess patients with COVID-19 While CT offers higher resolution images, Point-of-care ultrasound (POCUS) has the advantages of being rapid, low cost, low radiation exposure, and offers the ability for monitoring real-time disease progression As such, POCUS has also been used to assess patients with COVID-19, and characteristic POCUS findings of COVID-19 are described In the present study, we compare chest CT to lung ultrasound findings in patients with COVID-19 and examine consistency in pathological findings between the two imaging modalities Methods: 125 patients presenting to an urban emergency department in Tehran, Iran with symptoms concerning for COVID-19 were prospectively enrolled Participants underwent lung POCUS following a 12-zone protocol assessing each zone for pleural line irregularities, alveolar interstitial syndrome (eg, B-lines), and presence of consolidations including subpleural consolidations (SCs) Patients also received chest CT read by a radiologist evaluating for ground glass opacity, crazy paving patterns, or consolidations For POCUS and CT, each zone was scored using a 4-point measure, then aggregated total lung involvement scores were calculated for each patient and imaging modality Descriptive statistics were performed to asses consistently between POCUS and CT findings Results: POCUS findings overall corresponded well with abnormalities seen on CT, without a significant difference in lung involvement scores between the modalities On CT, COVID-19 patients showed greater incidence of crazy paving in the AI, PS, PI, AX, PLAPS, CS, and CI distributions (p adj= 00293, 0, 000600, 000533, 00272, 0004) and effusion in CI (p adj= 0216), and on POCUS patients had increased B-lines in the AS, AX, and PLAPS distributions (p adj= 0086, 0012, 0024 respectively), increased pleural thickening in all lung regions (AS, AI, PS, PI, AX, PLAPS;p adj= 0182, 0014, 0375, 0328, 0003, 0), and SCs in AS, AX, and PLAPS (p adj= 0312, 0398, 0324) Both CT and POCUS demonstrated more right-sided findings as a whole, though sidedness of findings was not statistically significant Both CT and POCUS demonstrated differences in finding densities between lung regions (for CT- ARDS: p adj= 1 00e+ 0;consolidation: p adj= 1 04e- 1;Crazy Paving: p adj= 1 92e-16;effusion: p adj= 8 4 94e- 8;GGO: p adj= 8 73e- 2;interstitial: p ajd= 68e- 6;POCUS- atelectasis: p adj= 1 92e- 7;B-lines: p adj= 6 77e -7;consolidation: p adj= 0 00119;effusion: p adj= 7 20e- 9;pleural thickening: p adj= 7 20e -9;SCs: p adj= 4 39e -5) with the highest concentration of positive findings in the PLAPS region on both modalities Conclusion: Given comparable findings in the presence and distribution of abnormalities between POCUS and chest CT, POCUS may be a viable alternative to chest CT for diagnosis and risk stratification in patients with suspected COVID-19 [Formula presented]

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 value = 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.

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.

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.

Study Objectives: Point-of-care ultrasound (POCUS) may be used as a valuable tool for risk stratification of patients with COVID-19 as its characteristic POCUS findings have recently been described In the present study, we aim to define the prognostic value of cardiopulmonary POCUS in patients with COVID-19 Here, we correlate POCUS findings with patient-centered outcomes such as need for intubation, intensive care unit (ICU) admission, and mortality Methods: 125 patients presenting to an urban ED in Tehran, Iran with symptoms concerning for COVID-19 were prospectively enrolled between March 8 and April 4, 2020 Participants underwent pulmonary POCUS following a 12-zone PLUS-Co protocol, and cardiac POCUS using a standardized 4-view protocol ED physicians performed scans and provided real-time scan interpretations, images were reassessed by a second, blinded reviewer for quality control and inter-rater reliability For pulmonary POCUS, each lung zone was individually assessed for pleural line irregularities, alveolar interstitial syndrome (eg, B-lines), and subpleural consolidations (SCs), then scored using a 4-point measure Zone scores were aggregated to generate a cumulative lung involvement score per patient Cardiac POCUS was assessed for ejection fraction, right ventricular function, pericardial effusion and inferior vena cava collapsibility Clinical course and outcome variables were collected via retrospective chart review Descriptive statistics were performed to evaluate the distribution and frequency of positive POCUS findings and their correlation with patient outcomes including ICU admission, mechanical ventilation, inpatient length of stay, and mortality Results: COVID-19-positive patients demonstrated higher bilateral lung involvement scores than COVID-19-negative patients overall (p< 001, r2= 667), with significantly increased B-lines (p adj= 000000804), pulmonary consolidations (p adj= 0304), pleural thickening (p adj= 000000742), and SCs (p adj= 000000500) Increased B-lines were most pronounced in the AS, AX, and PLAPS distributions (p adj= 0086, 0012, 0024 respectively), whereas pleural thickening was noted in all lung regions (AS, AI, PS, PI, AX, PLAPS;p adj= 0182, 0014, 0375, 0328, 0003, 0), and subpleural consolidation were most prominent in AS, AX, and PLAPS (p adj= 0312, 0398, 0324) In performing regression analysis no single positive POCUS finding was significantly correlated with patient outcomes inducing mortality, and need for intubation, nor was lung involvement score as a whole Conclusion: In patients with COVID-19, regionalized POCUS findings and aggregate lung involvement scores were not predictive of patient outcomes including mortality Despite this, cardiopulmonary POCUS may still provide valuable diagnostic and risk stratification data in patients with suspected COVID-19 Further investigation of the clinical applications of a cardiopulmonary POCUS disease profile in COVID-19 is needed [Formula presented]

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.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.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).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.

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.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.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.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.

Chronic, non-healing wounds are a major complication of diabetes associated with high morbidity and health care expenditures estimated at $9-13 billion annually in the US. Though microbial infection and critical colonization is hypothesized to impair healing and contribute to severe outcomes such as amputation, antimicrobial therapy is inefficacious and the role of microbes in tissue repair, regeneration, and healing remains unclear. Here, in a longitudinal prospective cohort study of 100 subjects with non-infected neuropathic diabetic foot ulcer (DFU), we performed metagenomic shotgun sequencing to elucidate microbial temporal dynamics at strain-level resolution, to investigate pathogenicity and virulence of the DFU microbiome with respect to outcomes, and to determine the influence of therapeutic intervention on the DFU microbiota. Slow healing DFUs were associated with signatures of biofilm formation, host invasion, and virulence. Though antibiotic resistance was widespread at the genetic level, debridement, rather than antibiotic treatment, significantly shifted the DFU microbiome in patients with more favorable outcomes. Primary clinical isolates ofS. aureus, C. striatum, andA. faecalisinduced differential biological responses in keratinocytes and in a murine model of diabetic wound healing, with theS. aureusstrain associated with non-healing wounds eliciting the most severe phenotype. Together these findings implicate strain-level diversification of the wound pathogenS. aureusin chronic wound outcomes, while revealing potential contributions from skin commensals and other previously underappreciated constituents of the wound microbiota.

Summary 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.

Summary 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.

Chronic nonhealing wounds have been heralded as a silent epidemic, causing significant morbidity and mortality especially in elderly, diabetic, and obese populations. Polymicrobial biofilms in the wound bed are hypothesized to disrupt the highly coordinated and sequential events of cutaneous healing. Both culture-dependent and -independent studies of the chronic-wound microbiome have almost exclusively focused on bacteria, omitting what we hypothesize are important fungal contributions to impaired healing and the development of complications. Here we show for the first time that fungal communities (the mycobiome) in chronic wounds are predictive of healing time, associated with poor outcomes, and form mixed fungal-bacterial biofilms. We longitudinally profiled 100, nonhealing diabetic-foot ulcers with high-throughput sequencing of the pan-fungal internal transcribed spacer 1 (ITS1) locus, estimating that up to 80% of wounds contain fungi, whereas cultures performed in parallel captured only 5% of colonized wounds. The “mycobiome” was highly heterogeneous over time and between subjects. Fungal diversity increased with antibiotic administration and onset of a clinical complication. The proportions of the phylum Ascomycota were significantly greater ( P = 0.015) at the beginning of the study in wounds that took >8 weeks to heal. Wound necrosis was distinctly associated with pathogenic fungal species, while taxa identified as allergenic filamentous fungi were associated with low levels of systemic inflammation. Directed culturing of wounds stably colonized by pathogens revealed that interkingdom biofilms formed between yeasts and coisolated bacteria. Combined, our analyses provide enhanced resolution of the mycobiome during impaired wound healing, its role in chronic disease, and impact on clinical outcomes. IMPORTANCE Wounds are an underappreciated but serious complication for a diverse spectrum of diseases. High-risk groups, such as persons with diabetes, have a 25% lifetime risk of developing a wound that can become chronic. The majority of microbiome research related to chronic wounds is focused on bacteria, but the association of fungi with clinical outcomes remains to be elucidated. Here we describe the dynamic fungal communities in 100 diabetic patients with foot ulcers. We found that communities are unstable over time, but at the first clinical presentation, the relative proportions of different phyla predict healing times. Pathogenic fungi not identified by culture reside in necrotic wounds and are associated with a poor prognosis. In wounds stably colonized by fungi, we identified yeasts capable of forming biofilms in concert with bacteria. Our findings illuminate the associations of the fungal mycobiome with wound prognosis and healing.

Microbial burden of chronic wounds is believed to play an important role in impaired healing and development of infection-related complications. However, clinical cultures have little predictive value of wound outcomes, and culture-independent studies have been limited by cross-sectional design and small cohort size. We systematically evaluated the temporal dynamics of the microbiota colonizing diabetic foot ulcers (DFU), a common and costly complication of diabetes, and its association with healing and clinical complications. Dirichlet multinomial mixture modeling, Markov chain analysis, and mixed-effect models were used to investigate shifts in the microbiota over time and its associations with healing. Here we show to our knowledge previously unreported temporal dynamics of the chronic wound microbiome. Microbiota community instability was associated with faster healing and improved outcomes. DFU microbiota were found to exist in one of four community types that experienced frequent and non-random transitions. Transition patterns and frequencies associated with healing time. Exposure to systemic antibiotics destabilized the wound microbiota, rather than altering overall diversity or relative abundance of specific taxa. This study provides to our knowledge previously unreported evidence that the dynamic wound microbiome is indicative of clinical outcomes and may be a valuable guide for personalized management and treatment of chronic wounds.

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.