BackgroundSome clinical features of severe COVID-19 represent blood vessel damage induced by activation of host immune responses initiated by the coronavirus SARS-CoV-2. We hypothesized ...autoantibodies against angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 receptor expressed on vascular endothelium, are generated during COVID-19 and are of mechanistic importance.MethodsIn an opportunity sample of 118 COVID-19 inpatients, autoantibodies recognizing ACE2 were detected by ELISA. Binding properties of anti-ACE2 IgM were analyzed via biolayer interferometry. Effects of anti-ACE2 IgM on complement activation and endothelial function were demonstrated in a tissue-engineered pulmonary microvessel model.ResultsAnti-ACE2 IgM (not IgG) autoantibodies were associated with severe COVID-19 and found in 18/66 (27.2%) patients with severe disease compared with 2/52 (3.8%) of patients with moderate disease (OR 9.38, 95% CI 2.38-42.0; P = 0.0009). Anti-ACE2 IgM autoantibodies were rare (2/50) in non-COVID-19 ventilated patients with acute respiratory distress syndrome. Unexpectedly, ACE2-reactive IgM autoantibodies in COVID-19 did not undergo class-switching to IgG and had apparent KD values of 5.6-21.7 nM, indicating they are T cell independent. Anti-ACE2 IgMs activated complement and initiated complement-binding and functional changes in endothelial cells in microvessels, suggesting they contribute to the angiocentric pathology of COVID-19.ConclusionWe identify anti-ACE2 IgM as a mechanism-based biomarker strongly associated with severe clinical outcomes in SARS-CoV-2 infection, which has therapeutic implications.FUNDINGBill & Melinda Gates Foundation, Gates Philanthropy Partners, Donald B. and Dorothy L. Stabler Foundation, and Jerome L. Greene Foundation; NIH R01 AR073208, R01 AR069569, Institutional Research and Academic Career Development Award (5K12GM123914-03), National Heart, Lung, and Blood Institute R21HL145216, and Division of Intramural Research, National Institute of Allergy and Infectious Diseases; National Science Foundation Graduate Research Fellowship (DGE1746891).
Background The reported mortality rate of peripartum cardiomyopathy (PPCM) is high, although the potential for spontaneous recovery of ventricular function is well established. The prevalence of ...myocarditis in PPCM has varied widely between studies. The purposes of this study were to define the long-term prognosis in a referral population of patients with PPCM, to determine the prevalence of myocarditis on endomyocardial biopsy in this population, and to identify clinical variables associated with poor outcome. Methods We analyzed clinical, echocardiographic, hemodynamic, and histologic features of 42 women with PPCM evaluated at our institution over a 15-year period. Each patient underwent an extensive evaluation, including echocardiography, endomyocardial biopsy, and right heart catheterization. Data were analyzed to identify features at initial examination associated with the combined end point of death or cardiac transplantation by the use of Kaplan-Meier survival curves and a Cox proportional hazards model. Results Three (7%) patients died and 3 (7%) patients underwent heart transplantation during a median follow-up of 8.6 years. Endomyocardial biopsy demonstrated a high prevalence of myocarditis (62%), but the presence or absence of myocarditis was not associated with survival. Of the prespecified variables assessed, only decreased left ventricular stroke work index was associated with worsened outcome. Conclusions In patients with PPCM, (1) long-term survival is better than has been historically reported, (2) the prevalence of myocarditis is high, and (3) decreased left ventricular stroke work index is associated with worse clinical outcomes. (Am Heart J 2000;140:785-91.)
Few instruments are available to measure the performance of intensive care unit (ICU) clinical information systems. Our objectives were: 1) to develop a survey-based metric that assesses the ...automation and usability of an ICU’s clinical information system; 2) to determine whether higher scores on this instrument correlate with improved outcomes in a multi-institution quality improvement collaborative.
This is a cross-sectional study of the medical directors of 19 Michigan ICUs participating in a state-wide quality improvement collaborative designed to reduce the rate of catheter-related blood stream infections (CRBSI). Respondents completed a survey assessing their ICU’s information systems.
The mean of 54 summed items on this instrument yields the clinical information technology (CIT) index, a global measure of the ICU’s information system performance on a 100 point scale. The dependent variable in this study was the rate of CRBSI after the implementation of several evidence-based recommendations. A multivariable linear regression analysis was used to examine the relationship between the CIT score and the post-intervention CRBSI rates after adjustment for the pre-intervention rate.
In this cross-sectional analysis, we found that a 10 point increase in the CIT score is associated with 4.6 fewer catheter related infections per 1,000 central line days for ICUs who participate in the quality improvement intervention for 1 year (95% CI: 1.0 to 8.0).
This study presents a new instrument to examine ICU information system effectiveness. The results suggest that the presence of more sophisticated information systems was associated with greater reductions in the bloodstream infection rate.
The authors describe a success rate of 90% (37 patients, 41 attempted angioplasties); a less optimistic intention-to-treat reckoning might also include some or all of the following: one patient who ...died prior to angiography; two patients referred for bypass surgery after angiography; and two patients managed conservatively after angiography. ...the actual angioplasty success rate was between 80% (37 successful angioplasties among 46 patients randomized) and 90%. The next priority involves a paradigm shift from drugs and devices within the current fragmented system of care to health system integration, beginning with the emergency medical system. Since a minority of chest pain patients actually have an AMI, derivation and validation of field triage criteria to identify high-risk patients are urgently needed, along with quantitative assessment of any risks from longer transport time.
We tested whether acute hormone therapy reduces ambulatory electrocardiographic ischemia in postmenopausal (PMP) women with unstable angina (UA).
Endothelial dysfunction contributes to the ...pathophysiology of UA. Acute estrogen administration improves endothelial function in PMP women with coronary artery disease and increases coronary artery blood flow.
Two hundred ninety-three PMP women with UA (mean age 69.7 years), treated with standard anti-ischemic therapy, were enrolled within 24 h of symptom onset. In a double-blind fashion, subjects were randomized to receive intravenous followed by oral conjugated estrogen for 21 days, intravenous estrogen followed by oral conjugated estrogen plus medroxyprogesterone for 21 days or placebo. The primary end point was the number of ambulatory electrocardiographic ischemic events over the first 48 h. Clinical events were also determined over six months of follow-up.
Electrocardiographic ischemia did not differ among the three randomized groups. The mean number of ischemic events per patient over 48 h was 0.74 for estrogen, 0.86 for estrogen plus progesterone and 0.74 for the placebo groups (p = 0.87). The percentage of patients with ischemic events and the mean duration of ischemia did not differ between hormone- and placebo-treated patients. In-hospital and six-month rates of adverse clinical events were also similar among the three randomized groups.
Acute hormone therapy does not reduce ischemia in PMP women with UA when added to standard anti-ischemic therapy.
Coxsackievirus infection causes myocarditis and pancreatitis in humans. In certain strains of mice, Coxsackievirus causes a severe pancreatitis. We explored the role of NO in the host immune response ...to viral pancreatitis. Coxsackievirus replicates to higher titers in mice lacking NO synthase 2 (NOS2) than in wild-type mice, with particularly high viral titers and viral RNA levels in the pancreas. Mice lacking NOS have a severe, necrotizing pancreatitis, with elevated pancreatic enzymes in the blood and necrotic acinar cells. Lack of NOS2 leads to a rapid increase in the mortality of infected mice. Thus, NOS2 is a critical component in the immune response to Coxsackievirus infection.
In-hospital antimicrobial approval policies are designed to curb the indiscriminant use of antimicrobials. These policies usually require written forms and/or direct requests to an Infectious Disease ...specialist (or surrogate) prior to release of the antimicrobial. We hypothesized that the approval processes at our institution results in delayed antimicrobial administration.
We performed a retrospective cohort study examining the time from order to administration for 25 different antimicrobials ordered "stat." Antimicrobials were classified as restricted (required approval) or unrestricted. We compared these 2 classes to each other both during the daytime (8 AM to 10 PM), when approval is required for restricted antimicrobials, and at night when the first dose of all antimicrobials is exempted. We defined a delay in administration when the medication was given >1 hour from time of order. We separately examined delays of >2 hours.
A higher percentage of >1-hour delays occurred when the antimicrobial was restricted (odds ratio OR = 1.49; 95% confidence interval CI = 1.23-1.82). Similar results were seen for >2-hour delays (OR = 1.78; 95% CI = 1.39-2.21). During the exempt-from-restriction time period (10 PM to 8 AM), there was no difference between these 2 classes of antimicrobials. Results were unchanged by adjustment for service (medicine vs. surgery vs. other), patient characteristics (age, sex, race), or by weekday vs. weekend.
Statistically significant delays in stat antimicrobial administration occur in our institution when antimicrobials require preapproval. These findings illustrate the importance of considering clinical efficiency when restrictions are put in place for time-sensitive therapies such as antimicrobials.
Measurements provided by the Magnetometer and the Extreme Ultraviolet Monitor (EUVM) on board the Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft together with atomic H exospheric densities ...derived from numerical simulations are studied for the time interval from October 2014 up to March 2016. We determine the proton cyclotron waves (PCWs) occurrence rate observed upstream from Mars at different times. We also study the relationship with temporal variabilities of the high‐altitude Martian hydrogen exosphere and the solar EUV flux reaching the Martian environment. We find that the abundance of PCWs is higher when Mars is close to perihelion and decreases to lower and approximately constant values after the Martian Northern Spring Equinox. We also conclude that these variabilities cannot be associated with biases in MAVEN's spatial coverage or changes in the background magnetic field orientation. Higher H exospheric densities on the Martian dayside are also found when Mars is closer to perihelion, as a result of changes in the thermospheric response to variability in the ultraviolet flux reaching Mars at different orbital distances. A consistent behavior is also observed in the analyzed daily irradiances measured by the MAVEN EUVM. The latter trends point toward an increase in the planetary proton densities upstream from the Martian bow shock near perihelion. These results then suggest a method to indirectly monitor the variability of the H exosphere up to very high altitudes during large time intervals (compared to direct measurements of neutral particles), based on the observed abundance of PCWs.
Key Points
First confirmation that PCWs abundance upstream from the Martian bow shock varies with time, with higher values near perihelion
At higher altitudes, temporal variabilities in the dayside exospheric H density display a similar long‐term trend
Exospheric variability partly caused by solar UV forcing on the thermosphere; water vapor might also contribute
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