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AbstractBackgroundRecently the US Food and Drug Administration has granted variances to select blood centers to supply cold‐stored platelet components (CSP). In hemorrhage resuscitation warming of blood components with approved fluid warming devices is common.Study Design and MethodsPathogen‐reduced apheresis platelet units were collected and stored in one of two ways: (1) CSP‐I, (2) CSP‐D. CSP‐I were collected and immediately stored at 1–6°C until used. CSP‐D were collected and stored at 20–24°C for 5 days and transferred to storage at 1–6°C until use. Aggregometry using arachidonic acid (AA), adenosine diphosphate (ADP) and collagen as agonists was performed on the unit samples before and after the units were infused through a Ranger blood‐warming device.ResultsCSP‐I, 23 units, had very high aggregation responses to all agonists (all ≥47.6 ± 20.7). There was a statistically significant reduction in ADP‐induced aggregometry results from 55.1 ± 23.2 before compared to 33.5 ± 14.6 following infusion of the PLT through the blood warmer (p < .001). There were no differences in AA and collagen aggregometry results before and after the infusion of the platelets through the blood warmer. CSP‐D had 5 of the 15 units with visible clotting in the bag. The 10 CSP‐Ds studied had lower aggregation than all agonists before and after infusion through the blood‐warming device (all ≤49.9 ± 35.9).ConclusionWe detected a statistically significant reduction in ADP‐induced aggregometry in CSP‐I run through a Ranger blood‐warming device with no change with AA or collagen agonist aggregometry.

Background Although corticosteroids have become the standard of care for patients with coronavirus disease-2019 (COVID-19) on supplemental oxygen, there is growing evidence of differential treatment response. This study aimed to evaluate if there was an association between biomarker-concordant corticosteroid treatment and COVID-19 outcomes. Methods This registry-based cohort study included adult COVID-19 hospitalized patients between January 2020 and December 2021 from 109 institutions. Patients with available C-reactive protein (CRP) levels within 48 h of admission were evaluated. Those on steroids before admission, stayed in the hospital for <48 h, or were not on oxygen support were excluded. Corticosteroid treatment was biomarker-concordant if given with high baseline CRP ≥150 mg/L or withheld with low CRP (<150 mg/L) and vice-versa was considered discordant (low CRP with steroids, high CRP without steroids). Hospital mortality was the primary outcome. Sensitivity analyses were conducted using varying CRP level thresholds. The model interaction was tested to determine steroid effectiveness with increasing CRP levels. Results Corticosteroid treatment was biomarker-concordant in 1778 (49%) patients and discordant in 1835 (51%). The concordant group consisted of higher-risk patients than the discordant group. After adjusting for covariates, the odds of in-hospital mortality were significantly lower in the concordant group than the discordant (odds ratio [95% confidence interval (C.I.)] = 0.71 [0.51, 0.98]). Similarly, adjusted mortality difference was significant at the CRP thresholds of 100 and 200 mg/L (odds ratio [95% C.I.] = 0.70 [0.52, 0.95] and 0.57 [0.38, 0.85], respectively), and concordant steroid use was associated with lower need for invasive ventilation for 200 mg/L threshold (odds ratio [95% C.I.] = 0.52 [0.30, 0.91]). In contrast, no outcome benefit was observed at CRP threshold of 50. When the model interaction was tested, steroids were more effective at reducing mortality as CRP levels increased. Conclusion Biomarker-concordant corticosteroid treatment was associated with lower odds of in-hospital mortality in severe COVID-19.

Background This study aims to assess the association of postoperative stroke with intraoperative hemodynamic variability and transfusion management. Methods In this case-control study, adult patients (≥ 18 years) who had a stroke within 72 hours of a surgical procedure were matched to 2 control patients according to age, sex, and procedure type. Primary risk factors assessed were intraoperative fluid administration, blood product transfusion, vasopressor use, and measures of variability in systolic and diastolic blood pressure and heart rate: maximum, minimum, range, SD, and average real variability. The variables were analyzed with conditional logistic regression, which accounted for the 1:2 matched case-control study design. Results Among 687 581 procedures, we identified 64 postoperative strokes (incidence, 9.3 [95% CI, 7.2-11.9] strokes per 100 000 procedures). These cases were matched with 128 controls. Stroke cases had higher Charlson cmorbidity index scores than did controls (P = .046). Blood pressure and heart rate variability measures were not associated with stroke. The risk of stroke was increased with red blood cell (RBC) transfusion (odds ratio [OR], 14.82; 95% CI, 3.40-64.66; P < .001), vasopressor use (OR, 3.91; 95% CI, 1.59-9.60; P = .003), and longer procedure duration (OR, 1.23/h; 95% CI, 1.01-1.51; P = .04). Multivariable analysis of procedure duration, RBC transfusion, and vasopressor use showed that only RBC transfusion was independently associated with an increased risk of stroke (OR, 10.10; 95% CI, 2.14-47.72; P = .004). Conclusions Blood pressure variability was not associated with an increased risk of postoperative stroke; however, RBC transfusion was an independent risk factor.

ImportanceThere is limited evidence for therapeutic options for pediatric COVID-19 outside of multisystem inflammatory syndrome in children (MIS-C).ObjectiveTo determine whether the use of steroids within 2 days of admission for non–MIS-C COVID-19 in children is associated with hospital length of stay (LOS). The secondary objective was to determine their association with intensive care unit (ICU) LOS, inflammation, and fever defervescence.Design, Setting, and ParticipantsThis cohort study analyzed data retrospectively for children (&amp;lt;18 years) who required hospitalization for non–MIS-C COVID-19. Data from March 2020 through September 2021 were provided by 58 hospitals in 7 countries who participate in the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS) COVID-19 registry.ExposureAdministration of steroids within 2 days of admission.Main Outcomes and MeasuresLength of stay in the hospital and ICU. Adjustment for confounders was done by mixed linear regression and propensity score matching.ResultsA total of 1163 patients met inclusion criteria and had a median (IQR) age of 7 years (0.9-14.3). Almost half of all patients (601/1163, 51.7%) were male, 33.8% (392/1163) were non-Hispanic White, and 27.9% (324/1163) were Hispanic. Of the study population, 184 patients (15.8%) received steroids within 2 days of admission, and 979 (84.2%) did not receive steroids within the first 2 days. Among 1163 patients, 658 (56.5%) required respiratory support during hospitalization. Overall, patients in the steroids group were older and had greater severity of illness, and a larger proportion required respiratory and vasoactive support. On multivariable linear regression, after controlling for treatment with remdesivir within 2 days, country, race and ethnicity, obesity and comorbidity, number of abnormal inflammatory mediators, age, bacterial or viral coinfection, and disease severity according to ICU admission within first 2 days or World Health Organization ordinal scale of 4 or higher on admission, with a random intercept for the site, early steroid treatment was not significantly associated with hospital LOS (exponentiated coefficient, 0.94; 95% CI, 0.81-1.09; P = .42). Separate analyses for patients with an LOS of 2 days or longer (n = 729), those receiving respiratory support at admission (n = 286), and propensity score–matched patients also showed no significant association between steroids and LOS. Early steroid treatment was not associated with ICU LOS, fever defervescence by day 3, or normalization of inflammatory mediators.Conclusions and RelevanceSteroid treatment within 2 days of hospital admission in a heterogeneous cohort of pediatric patients hospitalized for COVID-19 without MIS-C did not have a statistically significant association with hospital LOS.

AbstractBackgroundHospitalization in older age is associated with accelerated cognitive decline, typically preceded by neuropathologic changes. We assess the association between indication for hospitalization and brain neurodegeneration.MethodsIncluded were participants from the Mayo Clinic Study of Aging, a population-based longitudinal study, with ≥1 brain imaging available in those older than 60 years of age between 2004 and 2017. Primary analyses used linear mixed-effects models to assess association of hospitalization with changes in longitudinal trajectory of cortical thinning, amyloid accumulation, and white matter hyperintensities (WMH). Additional analyses were performed with imaging outcomes dichotomized (normal vs abnormal) using Cox proportional hazards regression.ResultsOf 2 480 participants, 1 966 had no hospitalization and 514 had ≥1 admission. Hospitalization was associated with accelerated cortical thinning (annual slope change −0.003 mm [95% confidence interval (CI) −0.005 to −0.001], p = .002), but not amyloid accumulation (0.003 [95% CI −0.001 to 0.006], p = .107), or WMH increase (0.011 cm3 [95% CI −0.001 to 0.023], p = .062). Interaction analyses assessing whether trajectory changes are dependent on admission type (medical vs surgical) found interactions for all outcomes. While surgical hospitalizations were not, medical hospitalizations were associated with accelerated cortical thinning (−0.004 mm [95% CI −0.008 to −0.001, p = .014); amyloid accumulation (0.010, [95% CI 0.002 to 0.017, p = .011), and WMH increase (0.035 cm3 [95% CI 0.012 to 0.058, p = .006). Hospitalization was not associated with developing abnormal cortical thinning (p = .407), amyloid accumulation (p = .596), or WMH/infarctions score (p = .565).ConclusionsMedical hospitalizations were associated with accelerated cortical thinning, amyloid accumulation, and WMH increases. These changes were modest and did not translate to increased risk for crossing the abnormality threshold.

AbstractIntroductionCoronavirus disease 2019 (COVID‐19) is associated with high rates of morbidity and mortality. Primary hypothyroidism is a common comorbid condition, but little is known about its association with COVID‐19 severity and outcomes. This study aims to identify the frequency of hypothyroidism in hospitalized patients with COVID‐19 as well as describe the differences in outcomes between patients with and without pre‐existing hypothyroidism using an observational, multinational registry.MethodsIn an observational cohort study we enrolled patients 18 years or older, with laboratory‐confirmed severe acute respiratory syndrome coronavirus‐2 infection between March 2020 and February 2021. The primary outcomes were (1) the disease severity defined as per the World Health Organization Scale for Clinical Improvement, which is an ordinal outcome corresponding with the highest severity level recorded during a patient's index COVID‐19 hospitalization, (2) in‐hospital mortality and (3) hospital‐free days. Secondary outcomes were the rate of intensive care unit (ICU) admission and ICU mortality.ResultsAmong the 20,366 adult patients included in the study, pre‐existing hypothyroidism was identified in 1616 (7.9%). The median age for the Hypothyroidism group was 70 (interquartile range: 59–80) years, and 65% were female and 67% were White. The most common comorbidities were hypertension (68%), diabetes (42%), dyslipidemia (37%) and obesity (28%). After adjusting for age, body mass index, sex, admission date in the quarter year since March 2020, race, smoking history and other comorbid conditions (coronary artery disease, hypertension, diabetes and dyslipidemia), pre‐existing hypothyroidism was not associated with higher odds of severe disease using the World Health Organization disease severity index (odds ratio [OR]: 1.02; 95% confidence interval [CI]: 0.92, 1.13; p = .69), in‐hospital mortality (OR: 1.03; 95% CI: 0.92, 1.15; p = .58) or differences in hospital‐free days (estimated difference 0.01 days; 95% CI: −0.45, 0.47; p = .97). Pre‐existing hypothyroidism was not associated with ICU admission or ICU mortality in unadjusted as well as in adjusted analysis.ConclusionsIn an international registry, hypothyroidism was identified in around 1 of every 12 adult hospitalized patients with COVID‐19. Pre‐existing hypothyroidism in hospitalized patients with COVID‐19 was not associated with higher disease severity or increased risk of mortality or ICU admissions. However, more research on the possible effects of COVID‐19 on the thyroid gland and its function is needed in the future.

Abstract Background We describe the clinical course of medical and surgical patients who received naloxone on general hospital wards for suspected opioid-induced respiratory depression (OIRD). Methods From May 2018 through October 2020, patients who received naloxone on hospital wards were identified and their records reviewed for incidence and clinical course. Results There were 86,030 medical and 106,807 surgical admissions. Naloxone was administered to 99 (incidence 11.5 [95% confidence interval 9.4–14.0] per 10,000 admissions) medical and 63 (5.9 [95% confidence interval 4.5–7.5]) surgical patients (P &lt; 0.001). Median oral morphine equivalents administered within 24 hours before naloxone were 32 [15, 64] and 60 [32, 88] mg for medical and surgical patients, respectively (P = 0.002). The rapid response team was activated in 69 (69.7%) vs 42 (66.7%) and critical care transfers in 51 (51.5%) vs 30 (47.6%) medical and surgical patients respectively. The number of in-hospital deaths was 21 (21.2%) vs two (3.2%) and the number of discharges to hospice 12 (12.1%) vs one (1.6%) for medical and surgical patients, respectively (P = 0.001). Naloxone did not reverse OIRD in 38 (23%) patients, and these patients had more transfers to the intensive care unit and a higher 30-day mortality rate. Conclusion Medical inpatients are more likely to suffer OIRD than are surgical inpatients despite lower opioid doses. Definitive OIRD was confirmed in 77% of patients because of immediate naloxone response, whereas 23% of patients did not respond, and this subset was more likely to need a higher level of care and had a higher 30-day mortality rate. Careful monitoring of mental and respiratory variables is necessary when opiates are used in hospital.