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Accurate methods of identifying patients with COVID-19 who are at high risk of poor outcomes has become especially important with the advent of limited-availability therapies such as monoclonal antibodies. Here we describe development and validation of a simple but accurate scoring tool to classify risk of hospitalization and mortality. All consecutive patients testing positive for SARS-CoV-2 from March 25-October 1, 2020 within the Intermountain Healthcare system were included. The cohort was randomly divided into 70% derivation and 30% validation cohorts. A multivariable logistic regression model was fitted for 14-day hospitalization. The optimal model was then adapted to a simple, probabilistic score and applied to the validation cohort and evaluated for prediction of hospitalization and 28-day mortality. 22,816 patients were included; mean age was 40 years, 50.1% were female and 44% identified as non-white race or Hispanic/Latinx ethnicity. 6.2% required hospitalization and 0.4% died. Criteria in the simple model included: age (0.5 points per decade); high-risk comorbidities (2 points each): diabetes mellitus, severe immunocompromised status and obesity (body mass index≥30); non-white race/Hispanic or Latinx ethnicity (2 points), and 1 point each for: male sex, dyspnea, hypertension, coronary artery disease, cardiac arrythmia, congestive heart failure, chronic kidney disease, chronic pulmonary disease, chronic liver disease, cerebrovascular disease, and chronic neurologic disease. In the derivation cohort (n = 16,030) area under the receiver-operator characteristic curve (AUROC) was 0.82 (95% CI 0.81-0.84) for hospitalization and 0.91 (0.83-0.94) for 28-day mortality; in the validation cohort (n = 6,786) AUROC for hospitalization was 0.8 (CI 0.78-0.82) and for mortality 0.8 (CI 0.69-0.9). A prediction score based on widely available patient attributes accurately risk stratifies patients with COVID-19 at the time of testing. Applications include patient selection for therapies targeted at preventing disease progression in non-hospitalized patients, including monoclonal antibodies. External validation in independent healthcare environments is needed.

Transesophageal echocardiography (TEE) is becoming increasingly utilized by emergency medicine providers during cardiac arrest. Intra-arrest, TEE confers several benefits including shorter pauses in chest compressions and direct visualization of cardiac compressions. Many ultrasound probe manufacturers recommend against performing defibrillation with the TEE probe in the mid-esophagus for fear of causing esophageal injury or damage to the probe, however no literature exists that has investigated this concern. To assess this, we performed cardiopulmonary resuscitation (CPR) and multiple defibrillations in 8 swine with a TEE probe in place. We performed TEE on 8 adult swine during CPR and performed multiple 200 J defibrillations with the TEE probe in the mid-esophagus. Post-mortem, esophagi were dissected and inspected for evidence of injury. On macroscopic inspection of 8 esophagi, no evidence of hematoma, thermal injury, or perforation was noted. Our study suggests that performing defibrillation during CPR with a TEE probe in place in the mid-esophagus is likely safe and low risk for significant esophageal injury. This further bolsters the use of TEE in CPR and would enable continuous visualization of cardiac activity without the need to remove the TEE probe for defibrillation.

For patients on extracorporeal membrane oxygenation (ECMO) who require renal replacement therapy (RRT), dialysis can be achieved through a dedicated hemodialysis (HD) catheter or direct connection to the ECMO circuit. The relative effect of each on filtration efficacy is not known. We conducted a retrospective single-center analysis of patients on ECMO who required CRRT. We examined the outcomes of blood biomarkers and transmembrane filter pressures, comparing sessions by attachment approach. All analyses were clustered by patient. Of the 33 patients (7 ECMO access and 23 HD catheter access) that met the inclusion criteria, there were a total of 493 CRRT sessions (93 ECMO access and 400 HD catheter access). At the end of the first 12 h of CRRT therapy, the ECMO group had a greater rate of decline in serum BUN than the HD catheter access group (2.5 mg/dl (SD 11) vs. 2 mg/dl (SD 6), p = 0.035). Additionally, the platelet level was significantly higher in the ECMO group compared to the HD catheter access group after 72 h (94.5 k/uL (SD 41) vs. 71 k/uL (SD 29), p = 0.008). Utilizing the ECMO circuit as direct venous access for CRRT was associated with some improved filtration proximal outcomes.

Background: Extracorporeal membrane oxygenation (ECMO) has expanding indications for cardiopulmonary resuscitation including severe acute respiratory distress syndrome (ARDS). Despite the adjunct of ECMO for patients with severe ARDS, they often have prolonged mechanical ventilation and are subject to many of its inherent complications. Here, we describe patients who were cannulated for venovenous (VV) ECMO and were taken off positive pressure ventilation. Methods: This is a primary analysis of patients admitted at a tertiary medical center between the dates of August 2014 to January 2020 who were cannulated to ECMO for refractory respiratory failure. We included all patients ≥18 years old. Patients who were extubated or had a tracheostomy and taken off positive pressure while on ECMO were classified as “off positive pressure ventilation (PPV)” and were compared to patients who remained “on PPV” while on ECMO. Primary outcome was survival to hospital discharge. Secondary outcomes were ventilator free days at 30 days and 60 days after ECMO cannulation, time from cannulation to date of first out-of-bed (OOB), and hospital length of stay (LOS). Patient characteristics were derived from routine clinical information in the electronic health record (EHR). Categorical characteristics were compared using chi-square test or Fisher exact test. Continuous characteristics were compared using independent samples t-test or Wilcoxon–Mann–Whitney test. p-values were reported from all analysis. Results: Sixty-five patients were included in this retrospective analysis. Forty-eight were managed on ECMO with PPV and 17 patients were removed from PPV. Patients removed from PPV had significantly higher lung injury scores prior to cannulation (2.5 ± 0.6 vs. 1.04 ± 0.3; p = 0.031) and non-significantly longer duration of ventilation prior to ECMO (6.1 days ± 2.1 vs. 5.0 days ± 01.1; p = 0.634). One hundred percent (100%) of patients removed from PPV survived to hospital discharge compared to 45% who received PPV throughout their duration of ECMO management (p < 0.001). The mean ventilator free days at day 60 was 15 with PPV and 36 without PPV (p = 0.003). The average duration from cannulation to mobilization (i.e., out-of-bed) was 18 days with PPV and 7 days without PPV (p = 0.015). Conclusions: Patients taken off PPV while on ECMO had a very high likelihood of survival to discharge and were mobilized in half as many days. While this likely reflects patient selection, the benefit of early mobilization is well documented and the approach of extubating while on ECMO warrants further investigation.

Trials comparing balanced crystalloids with normal saline have yielded mixed results regarding reductions in kidney complications and mortality for hospitalized patients receiving intravenous fluids. To evaluate the association of a multifaceted implementation program encouraging the preferential use of lactated Ringer solution with patient outcomes and intravenous fluid-prescribing practices in a large, multilevel health care system. This type 2 hybrid implementation and comparative effectiveness study enrolled all patients 18 years or older who received 1 L or more of intravenous fluids while admitted to an emergency department and/or inpatient unit at 1 of 22 hospitals in Idaho and Utah between November 1, 2018, and February 29, 2020. An interrupted time series analysis was used to assess study outcomes before and after interventions to encourage use of lactated Ringer solution. Implementation program combining order set modification, electronic order entry alerts, and sequential clinician-targeted education to encourage prescribing of lactated Ringer solution instead of normal saline. The primary implementation outcome was the patient-level proportion of intravenous fluids that was balanced crystalloids. The primary effectiveness outcome was the incidence of major adverse kidney events (MAKE30)-a composite of new persistent kidney dysfunction, new initiation of dialysis, and death-at 30 days. Among 148 423 patients (median [IQR] age, 47 [30-67] years; 91 302 women [61%]), the proportion of total fluids received that was lactated Ringer solution increased from 28% to 75% in the first week vs the last week of the study (immediate implementation effect odds ratio [OR], 3.44; 95% CI, 2.79-4.24). The estimated MAKE30 absolute risk reduction was 2.2% (95% CI, 1.3%-3.3%) based on interrupted time series analysis showing a decrease in the week-on-week trend for MAKE30 (OR difference, 0.03; 95% CI, 0.03-0.03, P < .001). The immediate postimplementation OR for MAKE30 was 0.88 (95% CI, 0.76-1.01), with a decrease in persistent kidney dysfunction (OR, 0.80; 95% CI, 0.69-0.93) and mortality (OR, 0.78; 95% CI, 0.65-0.93) but not dialysis (OR, 1.00; 95% CI, 0.76-1.32). In this comparative effectiveness study, an implementation program was associated with an increase in the proportion of fluids administered as lactated Ringer solution compared with normal saline and was associated with a reduction in MAKE30 events among patients treated in a large integrated health care system.

In this letter we report the findings of a voluntary program for SARS-CoV-2 antibody testing for faculty and staff at the University of Utah Hospital Emergency Department (ED), an urban, academic emergency department in Salt Lake City, Utah. Positive and indeterminate results were accompanied by a statement that the results did not indicate immunity to COVID-19 and employees should continue to wear full personal protective equipment when caring for patients with respiratory complaints. Testing occurred at a hospital that has admitted 48 patients with laboratory-confirmed COVID-19 and in a state with good access to RT-PCR testing for SARS-CoV-2.

Modified Early Warning Systems (MEWS) scores offer proxies for morbidity and mortality that are easily acquired, but there are limited data on what changing MEWS scores within the ED indicate. We examined the correlation of changing MEWS scores during resuscitation in the ED and in-hospital morbidity and mortality. We conducted a retrospective analysis on medical ED patients with simplified MEWS scores (without urine output or mental status) admitted to a single academic tertiary care center over one year. Triage-to-Last delta MEWS score and Triage-to-Max delta MEWS scores were calculated and correlated to in-hospital mortality, ICU admission, length of stay (LOS) and diagnosis of sepsis. Our analysis included 8322 ED patients with an ICU admission rate of 17% and a mortality rate of 2%. Every point of worsened MEWS after triage was more strongly associated with all-cause mortality (OR 2.41, 95% CI 1.96–2.97) than triage MEWS alone (OR 1.33, 95% CI 1.23–1.44; p < 0.001). Likewise, each point of worsened MEWS was associated with increased odds of ICU admission (Triage-to-Last: OR 2.12, 95% CI 1.92–2.33 and Triage-to-Max: OR 1.52, 95% CI 1.45–1.60, respectively). Among patients with suspected infection, similar associations are found. Dynamic vital signs in the emergency department, as categorized by delta MEWS, and failure to normalize abnormalities, were associated with increased mortality, ICU admission, LOS, and the diagnosis of sepsis. Our results suggest that MEWS scores that do not normalize, from triage onward, are more strongly associated with outcome than any single score.

BackgroundAccurate methods of identifying patients with COVID-19 who are at high risk of poor outcomes has become especially important with the advent of limited-availability therapies such as monoclonal antibodies. Here we describe development and validation of a simple but accurate scoring tool to classify risk of hospitalization and mortality.MethodsAll consecutive patients testing positive for SARS-CoV-2 from March 25-October 1, 2020 within the Intermountain Healthcare system were included. The cohort was randomly divided into 70% derivation and 30% validation cohorts. A multivariable logistic regression model was fitted for 14-day hospitalization. The optimal model was then adapted to a simple, probabilistic score and applied to the validation cohort and evaluated for prediction of hospitalization and 28-day mortality.Results22,816 patients were included; mean age was 40 years, 50.1% were female and 44% identified as non-white race or Hispanic/Latinx ethnicity. 6.2% required hospitalization and 0.4% died. Criteria in the simple model included: age (0.5 points per decade); high-risk comorbidities (2 points each): diabetes mellitus, severe immunocompromised status and obesity (body mass index≥30); non-white race/Hispanic or Latinx ethnicity (2 points), and 1 point each for: male sex, dyspnea, hypertension, coronary artery disease, cardiac arrythmia, congestive heart failure, chronic kidney disease, chronic pulmonary disease, chronic liver disease, cerebrovascular disease, and chronic neurologic disease. In the derivation cohort (n = 16,030) area under the receiver-operator characteristic curve (AUROC) was 0.82 (95% CI 0.81-0.84) for hospitalization and 0.91 (0.83-0.94) for 28-day mortality; in the validation cohort (n = 6,786) AUROC for hospitalization was 0.8 (CI 0.78-0.82) and for mortality 0.8 (CI 0.69-0.9).ConclusionA prediction score based on widely available patient attributes accurately risk stratifies patients with COVID-19 at the time of testing. Applications include patient selection for therapies targeted at preventing disease progression in non-hospitalized patients, including monoclonal antibodies. External validation in independent healthcare environments is needed.

Differences in the composition of the gut microbiota of infants associate with relative risk of atopy in childhood, and metabolites linked with these distinct microbial states alter T cell differentiation ex vivo . Gut microbiota bacterial depletions and altered metabolic activity at 3 months are implicated in childhood atopy and asthma 1 . We hypothesized that compositionally distinct human neonatal gut microbiota (NGM) exist, and are differentially related to relative risk (RR) of childhood atopy and asthma. Using stool samples ( n = 298; aged 1–11 months) from a US birth cohort and 16S rRNA sequencing, neonates (median age, 35 d) were divisible into three microbiota composition states (NGM1–3). Each incurred a substantially different RR for multisensitized atopy at age 2 years and doctor-diagnosed asthma at age 4 years. The highest risk group, labeled NGM3, showed lower relative abundance of certain bacteria (for example, Bifidobacterium, Akkermansia and Faecalibacterium) , higher relative abundance of particular fungi ( Candida and Rhodotorula ) and a distinct fecal metabolome enriched for pro-inflammatory metabolites. Ex vivo culture of human adult peripheral T cells with sterile fecal water from NGM3 subjects increased the proportion of CD4 + cells producing interleukin (IL)-4 and reduced the relative abundance of CD4 + CD25 + FOXP3 + cells. 12,13-DiHOME, enriched in NGM3 versus lower-risk NGM states, recapitulated the effect of NGM3 fecal water on relative CD4 + CD25 + FOXP3 + cell abundance. These findings suggest that neonatal gut microbiome dysbiosis might promote CD4 + T cell dysfunction associated with childhood atopy.

Background Individuals with certain chronic inflammatory lung diseases have a higher risk of developing lung cancer (LC). However, the underlying mechanisms remain largely unknown. Here, we hypothesized that chronic exposure to house dust mites (HDM), a common indoor aeroallergen associated with the development of asthma, accelerates LC development through the induction of chronic lung inflammation (CLI).  Methods The effects of HDM and heat-inactivated HDM (HI-HDM) extracts were evaluated in two preclinical mouse models of LC (a chemically-induced model using the carcinogen urethane and a genetically-driven model with oncogenic Kras G12D activation in lung epithelial cells) and on murine macrophages in vitro . Pharmacological blockade or genetic deletion of the Nod-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome, caspase-1, interleukin-1β (IL-1β), and C–C motif chemokine ligand 2 (CCL2) or treatment with an inhaled corticosteroid (ICS) was used to uncover the pro-tumorigenic effect of HDM.  Results Chronic intranasal (i.n) instillation of HDM accelerated LC development in the two mouse models. Mechanistically, HDM caused a particular subtype of CLI, in which the NLRP3/IL-1β signaling pathway is chronically activated in macrophages, and made the lung microenvironment conducive to tumor development. The tumor-promoting effect of HDM was significantly decreased by heat treatment of the HDM extract and was inhibited by NLRP3, IL-1β, and CCL2 neutralization, or ICS treatment. Conclusions Collectively, these data indicate that long-term exposure to HDM can accelerate lung tumorigenesis in susceptible hosts (e.g., mice and potentially humans exposed to lung carcinogens or genetically predisposed to develop LC).