Early Outpatient Treatment for Covid-19 with Convalescent Plasma.

BACKGROUND: Polyclonal convalescent plasma may be obtained from donors who have recovered from coronavirus disease 2019 (Covid-19). The efficacy of this plasma in preventing serious complications in outpatients with recent-onset Covid-19 is uncertain. METHODS: In this multicenter, double-blind, randomized, controlled trial, we evaluated the efficacy and safety of Covid-19 convalescent plasma, as compared with control plasma, in symptomatic adults (≥18 years of age) who had tested positive for severe acute respiratory syndrome coronavirus 2, regardless of their risk factors for disease progression or vaccination status. Participants were enrolled within 8 days after symptom onset and received a transfusion within 1 day after randomization. The primary outcome was Covid-19-related hospitalization within 28 days after transfusion. RESULTS: Participants were enrolled from June 3, 2020, through October 1, 2021. A total of 1225 participants underwent randomization, and 1181 received a transfusion. In the prespecified modified intention-to-treat analysis that included only participants who received a transfusion, the primary outcome occurred in 17 of 592 participants (2.9%) who received convalescent plasma and 37 of 589 participants (6.3%) who received control plasma (absolute risk reduction, 3.4 percentage points; 95% confidence interval, 1.0 to 5.8; P = 0.005), which corresponded to a relative risk reduction of 54%. Evidence of efficacy in vaccinated participants cannot be inferred from these data because 53 of the 54 participants with Covid-19 who were hospitalized were unvaccinated and 1 participant was partially vaccinated. A total of 16 grade 3 or 4 adverse events (7 in the convalescent-plasma group and 9 in the control-plasma group) occurred in participants who were not hospitalized. CONCLUSIONS: In participants with Covid-19, most of whom were unvaccinated, the administration of convalescent plasma within 9 days after the onset of symptoms reduced the risk of disease progression leading to hospitalization. (Funded by the Department of Defense and others; CSSC-004 ClinicalTrials.gov number, NCT04373460.).

Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial.

BACKGROUND: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. RESULTS: In total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups. CONCLUSIONS: Administration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection. CLINICAL TRIALS REGISTRATION: NCT04323800.

Transfusion reactions associated with COVID-19 convalescent plasma in outpatient clinical trials.

BACKGROUND: COVID-19 convalescent plasma (CCP) is an important therapeutic option for outpatients at high risk of hospitalization from SARS-CoV-2 infection. We assessed the safety of outpatient CCP transfusions administered during clinical trials. STUDY DESIGN AND METHODS: We analyzed data pertaining to transfusion-related reactions from two randomized controlled trials in the U.S. that evaluated the efficacy of CCP versus control plasma in various ambulatory settings. Multivariable logistic regression was used to assess whether CCP was associated with transfusion reactions, after adjusting for potential confounders. RESULTS: The combined study reported 79/1351 (5.9%) adverse events during the transfusion visit, with the majority 62/1351 (4.6%) characterized by mild, allergic-type findings of urticaria, and/or pruritus consistent with minor allergic transfusion reactions; the other reported events were attributed to the patients' underlying disease, COVID-19, or vasovagal in nature. We found no difference in the likelihood of allergic transfusion reactions between those receiving CCP versus control plasma (adjusted odds ratio [AOR], 0.75; 95% CI, 0.43-1.31). Risk of urticaria and/or pruritus increased with a pre-existing diagnosis of asthma (AOR, 2.33; 95% CI, 1.16-4.67). We did not observe any CCP-attributed antibody disease enhancement in participants with COVID-19 or increased risk of infection. There were no life-threatening severe transfusion reactions and no patients required hospitalization related to transfusion-associated complications. DISCUSSION: Outpatient plasma administration was safely performed for nearly 1400 participants. CCP is a safe therapeutic option for outpatients at risk of hospitalization from COVID-19.

Improving Outpatient Antibiotic Prescribing for Respiratory Tract Infections in Primary Care: A Stepped-Wedge Cluster Randomized Trial.

BACKGROUND: Inappropriate antibiotic prescribing is common in primary care (PC), particularly for respiratory tract diagnoses (RTDs). However, the optimal approach for improving prescribing remains unknown. METHODS: We conducted a stepped-wedge study in PC practices within a health system to assess the impact of a provider-targeted intervention on antibiotic prescribing for RTDs. RTDs were grouped into tiers based on appropriateness of antibiotic prescribing: tier 1 (almost always indicated), tier 2 (may be indicated), and tier 3 (rarely indicated). Providers received education on appropriate RTD prescribing followed by monthly peer comparison feedback on antibiotic prescribing for (1) all tiers and (2) tier 3 RTDs. A χ 2 test was used to compare the proportion of visits with antibiotic prescriptions before and during the intervention. Mixed-effects multivariable logistic regression analysis was performed to assess the association between the intervention and antibiotic prescribing. RESULTS: Across 30 PC practices and 185 755 total visits, overall antibiotic prescribing was reduced with the intervention, from 35.2% to 23.0% of visits (P < .001). In multivariable analysis, the intervention was associated with a reduced odds of antibiotic prescription for tiers 2 (odds ratio [OR] 0.57; 95% confidence interval [CI] .52-.62) and 3 (OR 0.57; 95% CI .53-.61) but not for tier 1 (OR 0.98; 95% CI .83-1.16). CONCLUSIONS: A provider-focused intervention reduced overall antibiotic prescribing for RTDs without affecting prescribing for infections that likely require antibiotics. Future research should examine the sustainability of such interventions, potential unintended adverse effects on patient health or satisfaction, and provider perceptions and acceptability.

The Impact of Reported Beta-Lactam Allergy in Hospitalized Patients With Hematologic Malignancies Requiring Antibiotics.

Background: Patients hospitalized with hematologic malignancy are particularly vulnerable to infection. The impact of reported beta-lactam (BL) allergy in this population remains unknown. Methods: This was a retrospective cohort study of adult inpatients with hematologic malignancy admitted at 2 tertiary care hospitals from 2010 through 2015. The primary outcome was hospital length of stay (LOS) after administration of the first antibiotic. Secondary outcomes included readmission, mortality, complications, hospital charges, and antibiotic usage. Our goal was to define the impact of BL-only allergy (BLOA) label on clinical outcomes compared to those with no BL allergy (NBLA) in hematologic malignancy inpatients who required systemic antibiotics. Results: In our cohort (n = 4671), 38.3% had leukemia, 4.9% had Hodgkin lymphoma, 36.1% had non-Hodgkin lymphoma, and 20.7% had multiple myeloma. Among patients, 35.1% reported antibiotic allergy, and 14.1% (n = 660) had BLOA (including 9.3% with penicillin-only allergy and 3.3% cephalosporin-only allergy). Patients with BLOA had longer median LOS compared to patients with NBLA (11.3 vs 7.6 days, P < .001), which remained significant after multivariable adjustment. Patients with BLOA also had significantly worse outcomes in terms of mortality rate at 30 days (7.6% vs 5.3%, P = .017) and 180 days (15.8% vs 12.2%, P = .013), 30-day readmission rate, Clostridium difficile rate, hospital charges ($223 046 vs $173 256, P < .001), antibiotic classes used, and antibiotic duration. Conclusions: In hospitalized patients with hematologic malignancy, patients with reported BL allergy had worse clinical outcomes and higher healthcare cost than those without BL allergy label.

Comparison of Culture-Based Methods for Identification of Colonization with Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus in the Context of Cocolonization.

Two screening methods to detect staphylococcal colonization in humans were compared. Direct plating to CHROMagar (BD Diagnostics) was compared to a broth preenrichment followed by plating to Baird-Parker agar. The broth-enrichment method was comparable to CHROMagar for methicillin-resistant Staphylococcus aureas (MRSA) detection, but the enrichment method was optimum for recovery of coagulase-positive Staphylococcus spp.

Duration of Colonization and Determinants of Earlier Clearance of Colonization With Methicillin-Resistant Staphylococcus aureus.

BACKGROUND: The duration of colonization and factors associated with clearance of methicillin-resistant Staphylococcus aureus (MRSA) after community-onset MRSA skin and soft-tissue infection (SSTI) remain unclear. METHODS: We conducted a prospective cohort study of patients with acute MRSA SSTI presenting to 5 adult and pediatric academic hospitals from 1 January 2010 through 31 December 2012. Index patients and household members performed self-sampling for MRSA colonization every 2 weeks for 6 months. Clearance of colonization was defined as negative MRSA surveillance cultures during 2 consecutive sampling periods. A Cox proportional hazards regression model was developed to identify determinants of clearance of colonization. RESULTS: Two hundred forty-three index patients were included. The median duration of MRSA colonization after SSTI diagnosis was 21 days (95% confidence interval [CI], 19-24), and 19.8% never cleared colonization. Treatment of the SSTI with clindamycin was associated with earlier clearance (hazard ratio [HR], 1.72; 95% CI, 1.28-2.30; P < .001). Older age (HR, 0.99; 95% CI, .98-1.00; P = .01) was associated with longer duration of colonization. There was a borderline significant association between increased number of household members colonized with MRSA and later clearance of colonization in the index patient (HR, 0.85; 95% CI, .71-1.01; P = .06). CONCLUSIONS: With a systematic, regular sampling protocol, duration of MRSA colonization was noted to be shorter than previously reported, although 19.8% of patients remained colonized at 6 months. The association between clindamycin and shorter duration of colonization after MRSA SSTI suggests a possible role for the antibiotic selected for treatment of MRSA infection.

Pulmonary Renal Syndrome in ANCA-Negative Vasculitis.

Below we highlight a rare case of anti-neutrophil cytoplasmic antibody (ANCA)-negative vasculitis, unique in its own right, as the diagnosis was hard to make and the respiratory decline rapid, with the patient going from a 23% fraction of inspired oxygen (FiO2) on admission to 100% FiO2 within four days for what was initially presumed to be community-acquired pneumonia. Precise data on the incidence or prevalence of ANCA-associated vasculitis are lacking. However, a 20-year population-based study in the United States found that, of 58 incident cases, 9% were ANCA-negative. We present the case of a 69-year-old Egyptian male with worsening shortness of breath who was found to have elevated inflammatory markers and an ANCA-negative panel and was later diagnosed with ANCA-negative vasculitis. By highlighting this case, we aim to increase awareness and point out the need to keep the disease high on the list of differential diagnoses in order to allow for timely intervention. Though there isn't a lot of data available on definitive treatment or the disease itself, there are studies that point to rituximab, cyclophosphamide, plasmapheresis, and hemodialysis as useful interventions for treatment.

A Case of Cryoglobulinemia With Central Nervous System Involvement.

Cryoglobulinemia may result in small-to-medium vessel vasculitis. Central nervous system (CNS) involvement is rare, and presentation may range from stroke/transient ischemic attack, reversible ischemic neurological deficits, to encephalopathic syndromes. This is a rare case discussing cryoglobulinemia with CNS involvement. A 56-year-old female with a history of cryoglobulinemia was found unresponsive to verbal and physical stimuli. She was admitted to the intensive care unit. CT head without contrast showed diffuse cerebral edema and mass effect in the right cerebral hemisphere causing right to left midline shift, brainstem infarct, hemorrhage in the right lateral ventricle, and obstruction of the fourth ventricle. The patient was managed with hypertonic saline, external ventricular drain (EVD) placement, and high-dose steroids, which led to an improvement in her condition. In conclusion, testing for cryoglobulins and serologic tests for hepatitis C should be considered in syndromes of cerebral ischemia or infarction without an obvious cause, especially in young individuals since encephalopathy may be reversible. Cryoglobulinemia with CNS manifestations may be associated with purpura, high RF, and low C4. The treatment can be a combination of steroids, immunosuppressants, plasmapheresis, and rituximab. Cyclophosphamide may also be considered as adjunctive therapy to corticosteroids in rapidly progressive severe neurological complications. Further research for treatment standards in nonviral cryoglobulinemia is needed.

Cardiogenic Shock in a Patient With 4G/4G PAI Polymorphism and MTHFR A1298C Mutation.

Myocardial infarction (MI) remains a common cause of morbidity and mortality. Although many well-known risk factors exist, the association between inherited thrombophilia disorders and acute MI is not well described. Here, we present a case of a 75-year-old male with known 4G/4G PAI-1 polymorphism, methylenetetrahydrofolate reductase (MTHFR) mutation, and peripheral artery disease (PAD) post stent placement who presented with cardiogenic shock in the setting of acute MI with no prior significant cardiac history.

Post-COVID-19 Vaccine Thromboembolic Complication in the Setting of Newly Diagnosed May-Thurner Syndrome.

May-Thurner syndrome (MTS) can lead to deep venous thrombosis (DVT) in the left lower extremity, and it is often triggered by factors such as surgery or pregnancy. We present a rare case where the risk factor for thromboembolism in MTS is a complication from COVID-19 vaccination. A 44-year-old female who presented with fatigue, fever, and myalgia had developed thromboembolism as a complication of the Johnson & Johnson COVID-19 vaccine. Diagnostic criteria for vaccine-induced immune thrombotic thrombocytopenia (VITT) should be considered in such cases that include symptoms within 5-30 days post vaccination, elevated D-dimer, and thrombosis. Treatment involved anticoagulants and intervention for MTS included thrombectomy and stent placement. Recognition of post-COVID-19 vaccination complications such as VITT is crucial for early intervention and patient awareness during vaccination decisions.

COVID-19 convalescent plasma therapy decreases inflammatory cytokines: a randomized controlled trial.

IMPORTANCE: This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUNDCOVID-19 convalescent plasma (CCP) virus-specific antibody levels that translate into recipient posttransfusion antibody levels sufficient to prevent disease progression are not defined.METHODSThis secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double-blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low posttransfusion antibody levels was established by 2 methods: (i) analyzing virus neutralization-equivalent anti-Spike receptor-binding domain immunoglobulin G (anti-S-RBD IgG) responses in donors or (ii) receiver operating characteristic (ROC) curve analysis.RESULTSSARS-CoV-2 anti-S-RBD IgG antibody was volume diluted 21.3-fold into posttransfusion seronegative recipients from matched donor units. Virus-specific antibody delivered was approximately 1.2 mg. The high-antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP-recipient analysis for antibody thresholds correlated to reduced hospitalizations found a statistical significant association between early transfusion and high antibodies versus all other CCP recipients (or control plasma), with antibody cutoffs established by both methods-donor-based virus neutralization cutoffs in posttransfusion recipients (0/85 [0%] versus 15/276 [5.6%]; P = 0.03) or ROC-based cutoff (0/94 [0%] versus 15/267 [5.4%]; P = 0.01).CONCLUSIONIn unvaccinated, seronegative CCP recipients, early transfusion of plasma units in the upper 30% of study donors' antibody levels reduced outpatient hospitalizations. High antibody level plasma units, given early, should be reserved for therapeutic use.TRIAL REGISTRATIONClinicalTrials.gov NCT04373460.FUNDINGDepartment of Defense (W911QY2090012); Defense Health Agency; Bloomberg Philanthropies; the State of Maryland; NIH (3R01AI152078-01S1, U24TR001609-S3, 1K23HL151826NIH); the Mental Wellness Foundation; the Moriah Fund; Octapharma; the Healthnetwork Foundation; the Shear Family Foundation; the NorthShore Research Institute; and the Rice Foundation.

Plasmapheresis vs Conventional Insulin Therapy in Hypertriglyceridemia-Induced Acute Pancreatitis.

Hypertriglyceridemia is a rare yet firm etiology of pancreatitis, with an incidence of 2-4% in the general population. The etiology of hypertriglyceridemia itself consists of both primary and secondary causes. We discuss the case of a 37-year-old female with a strong family history of hypertriglyceridemia (primary cause) along with daily alcohol consumption (secondary cause) who initially presented to the emergency department with tingling and numbness of her bilateral upper extremities, bilateral lower extremity cramping and spasm and pins, and needles sensation in all extremities. She was found to have acute pancreatitis (AP) as a cause of hypocalcemia with elevated triglycerides of 5,823 mg/dl responsive to plasmapheresis combined with insulin drip. We explore the pathophysiology of hypertriglyceridemia-induced acute pancreatitis and the different modalities used to treat it which are still largely debated. The choice of therapy has been influenced by the cost, perceived effectiveness, and availability.

Analysis of seasonal variation of antibiotic prescribing for respiratory tract diagnoses in primary care practices.

Objective: To determine antibiotic prescribing appropriateness for respiratory tract diagnoses (RTD) by season. Design: Retrospective cohort study. Setting: Primary care practices in a university health system. Patients: Patients who were seen at an office visit with diagnostic code for RTD. Methods: Office visits for the entire cohort were categorized based on ICD-10 codes by the likelihood that an antibiotic was indicated (tier 1: always indicated; tier 2: sometimes indicated; tier 3: rarely indicated). Medical records were reviewed for 1,200 randomly selected office visits to determine appropriateness. Based on this reference standard, metrics and prescriber characteristics associated with inappropriate antibiotic prescribing were determined. Characteristics of antibiotic prescribing were compared between winter and summer months. Results: A significantly greater proportion of RTD visits had an antibiotic prescribed in winter [20,558/51,090 (40.2%)] compared to summer months [11,728/38,537 (30.4%)][standardized difference (SD) = 0.21]. A significantly greater proportion of winter compared to summer visits was associated with tier 2 RTDs (29.4% vs 23.4%, SD = 0.14), but less tier 3 RTDs (68.4% vs 74.4%, SD = 0.13). A greater proportion of visits in winter compared to summer months had an antibiotic prescribed for tier 2 RTDs (80.2% vs 74.2%, SD = 0.14) and tier 3 RTDs (22.9% vs 16.2%, SD = 0.17). The proportion of inappropriate antibiotic prescribing was higher in winter compared to summer months (72.4% vs 62.0%, P < .01). Conclusions: Increases in antibiotic prescribing for RTD visits from summer to winter were likely driven by shifts in diagnoses as well as increases in prescribing for certain diagnoses. At least some of this increased prescribing was inappropriate.

Dynamics of inflammatory responses after SARS-CoV-2 infection by vaccination status in the USA: a prospective cohort study.

BACKGROUND: Cytokines and chemokines play a critical role in the response to infection and vaccination. We aimed to assess the longitudinal association of COVID-19 vaccination with cytokine and chemokine concentrations and trajectories among people with SARS-CoV-2 infection. METHODS: In this longitudinal, prospective cohort study, blood samples were used from participants enrolled in a multi-centre randomised trial assessing the efficacy of convalescent plasma therapy for ambulatory COVID-19. The trial was conducted in 23 outpatient sites in the USA. In this study, participants (aged ≥18 years) were restricted to those with COVID-19 before vaccination or with breakthrough infections who had blood samples and symptom data collected at screening (pre-transfusion), day 14, and day 90 visits. Associations between COVID-19 vaccination status and concentrations of 21 cytokines and chemokines (measured using multiplexed sandwich immunoassays) were examined using multivariate linear mixed-effects regression models, adjusted for age, sex, BMI, hypertension, diabetes, trial group, and COVID-19 waves (pre-alpha or alpha and delta). FINDINGS: Between June 29, 2020, and Sept 30, 2021, 882 participants recently infected with SARS-CoV-2 were enrolled, of whom 506 (57%) were female and 376 (43%) were male. 688 (78%) of 882 participants were unvaccinated, 55 (6%) were partly vaccinated, and 139 (16%) were fully vaccinated at baseline. After adjusting for confounders, geometric mean concentrations of interleukin (IL)-2RA, IL-7, IL-8, IL-15, IL-29 (interferon-λ), inducible protein-10, monocyte chemoattractant protein-1, and tumour necrosis factor-α were significantly lower among the fully vaccinated group than in the unvaccinated group at screening. On day 90, fully vaccinated participants had approximately 20% lower geometric mean concentrations of IL-7, IL-8, and vascular endothelial growth factor-A than unvaccinated participants. Cytokine and chemokine concentrations decreased over time in the fully and partly vaccinated groups and unvaccinated group. Log10 cytokine and chemokine concentrations decreased faster among participants in the unvaccinated group than in other groups, but their geometric mean concentrations were generally higher than fully vaccinated participants at 90 days. Days since full vaccination and type of vaccine received were not correlated with cytokine and chemokine concentrations. INTERPRETATION: Initially and during recovery from symptomatic COVID-19, fully vaccinated participants had lower concentrations of inflammatory markers than unvaccinated participants suggesting vaccination is associated with short-term and long-term reduction in inflammation, which could in part explain the reduced disease severity and mortality in vaccinated individuals. FUNDING: US Department of Defense, National Institutes of Health, Bloomberg Philanthropies, State of Maryland, Mental Wellness Foundation, Moriah Fund, Octapharma, HealthNetwork Foundation, and the Shear Family Foundation.

Outpatient COVID-19 convalescent plasma recipient antibody thresholds correlated to reduced hospitalizations within a randomized trial.

BACKGROUND: The COVID-19 convalescent plasma (CCP) viral specific antibody levels that translate into recipient post-transfusion antibody levels sufficient to prevent disease progression is not defined. METHODS: This secondary analysis correlated donor and recipient antibody levels to hospitalization risk among unvaccinated, seronegative CCP recipients within the outpatient, double blind, randomized clinical trial that compared CCP to control plasma. The majority of COVID-19 CCP arm hospitalizations (15/17, 88%) occurred in this unvaccinated, seronegative subgroup. A functional cutoff to delineate recipient high versus low post-transfusion antibody levels was established by two methods: 1) analyzing virus neutralization-equivalent anti-S-RBD IgG responses in donors or 2) receiver operating characteristic (ROC) analysis. RESULTS: SARS-CoV-2 anti-S-RBD IgG antibody was diluted by a factor of 21.3 into post-transfusion seronegative recipients from matched donor units. Viral specific antibody delivered approximated 1.2 mg. The high antibody recipients transfused early (symptom onset within 5 days) had no hospitalizations. A CCP recipient analysis for antibody thresholds correlated to reduced hospitalizations found a significant association with Fisher's exact test between early and high antibodies versus all other CCP recipients (or control plasma) with antibody cutoffs established by both methods-donor virus neutralization-based cutoff: (0/85; 0% versus 15/276; 5.6%) p=0.03 or ROC based cutoff: (0/94; 0% versus 15/267; 5.4%) p=0.01. CONCLUSION: In unvaccinated, seronegative CCP recipients, early transfusion of plasma units corresponding to the upper 30% of all study donors reduced outpatient hospitalizations. These high antibody level plasma units, given early, should be reserved for therapeutic use.Trial registration: NCT04373460. FUNDING: Defense Health Agency and others.

Emphysematous Cystitis Complicated by Pneumorrhachis.

Emphysematous cystitis (EC) is a potentially life-threatening urinary tract infection (UTI) characterized by the presence of gas within the bladder wall and lumen. The extension of gas beyond the bladder wall is rare and indicative of severe disease. We present a case of septic shock secondary to EC with the extension of air through the paraspinal and psoas muscles and into the epidural space of the lumbar spinal canal. This finding of intraspinal air is a rare radiographic phenomenon known as pneumorrhachis (PR).

Takotsubo Cardiomyopathy as a Cardiovascular Manifestation of COVID-19: A Case Report and Literature Review.

Coronavirus disease 2019 (COVID-19) has a wide range of clinical manifestations, affecting multiple organ systems. Cardiovascular manifestations of COVID-19 that have been reported include arrhythmias, myocarditis, and an increased predisposition to acute myocardial infarction. Takotsubo cardiomyopathy (TCM), which is characterized by apical ballooning of the heart leading to acute left ventricular dysfunction, is scarcely seen in COVID-19 patients. We present a case of COVID-19-associated TCM in a 68-year-old man.  A 68-year-old man with no significant past medical history presented with sudden-onset midsternal pressure-like chest pain at rest, associated with diaphoresis and shortness of breath. This occurred ten days after diagnosis of COVID-19 with mild symptoms, with no other recent physical or emotional stressors. At presentation, he was afebrile (98.5 °F), hypertensive (177/108 mmHg), tachycardic (HR 118 bpm), and saturating 100% on room air. Labs were significant for leukocytosis with 15.1 × 103 WBCs/mcL, elevated creatinine (1.46 g/dL), brain natriuretic peptide (BNP) of 156, troponin of 4 ng/mL that peaked at 16.28 ng/mL. The rapid COVID-19 test was positive. EKG showed anterolateral ST elevation and QTc interval of 446 ms. Echo showed severe hypokinesis of mid and apical segments and severely decreased left ventricular ejection fraction (LVEF)of <30%. Emergent left heart catheterization showed 75% mid left anterior descending coronary artery (LAD) stenosis and moderate right coronary artery (RCA) disease, while the ventriculogram showed a left ventricular ejection fraction of 35% with anteroapical and inferoapical akinesia suggestive of Takotsubo cardiomyopathy. The patient was placed on aspirin, ticagrelor, and atorvastatin, carvedilol, and lisinopril. EKG the next day showed a prolonged QTc of 526 ms with T-wave inversion and no ST elevations. The patient had no findings consistent with myocarditis or pheochromocytoma. He was discharged two days later. Within the next few weeks, his symptoms improved, and a follow-up echo confirmed normalization of left ventricular function.  There has been an increased incidence of Takotsubo cardiomyopathy during the COVID-19 pandemic compared to the pre-pandemic period. There is only a slight female preponderance in COVID-19-induced TCM, possibly because males are predominantly affected by COVID-19. Our patient satisfied all four Mayo Clinic criteria required for the diagnosis of TCM. Pathophysiology of TCM in COVID-19 is linked with cytokine storm and consequent catecholamine surge. Most patients improve within succeeding weeks or months. Nonetheless, the case fatality rate is high 36.5%, which is significantly higher compared to TCM patients without COVID-19. COVID-19 has a multisystem involvement with various clinical presentations. New cardiomyopathy in COVID-19 patients should raise suspicion among clinicians regarding stress-induced cardiomyopathy.

An Unusual Presentation of Clostridioides Difficile Colitis in a Patient on Opioids.

Clostridioides difficile colitis is an inflammation of the colon due to toxins produced by a gram-positive bacterium called Clostridioides difficile (also known as Clostridium difficile). Clostridioides difficile colitis is associated with an increased risk of morbidity and mortality in elderly patients. The infection develops because of the disruption of the microbiome that usually suppresses the overgrowth of Clostridioides difficile. Testing for Clostridium difficile infection is routinely recommended in patients with at least three loose bowel movements in a day. We present an unusual case of a 74-year-old woman on chronic opioids who presented with a three-day history of lower abdominal pain, constipation, hematochezia, with no diarrhea. Radiologic imaging showed evidence of colitis, and the patient was found to have Clostridium difficile colitis.