Mycobacterium abscessus Meningitis Associated with Stem Cell Treatment During Medical Tourism.

Mycobacterium abscessus infections have been reported as adverse events related to medical tourism. We report M. abscessus meningitis in a patient who traveled from Colorado, USA, to Mexico to receive intrathecal stem cell injections as treatment for multiple sclerosis. We also review the management of this challenging central nervous system infection.

A Multicenter, Prospective, Observational, Cohort-Controlled Study of Clinical Outcomes Following Coronavirus Disease 2019 (COVID-19) Convalescent Plasma Therapy in Hospitalized Patients With COVID-19.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused high inpatient mortality and morbidity throughout the world. COVID-19 convalescent plasma (CCP) has been utilized as a potential therapy for patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia. This study evaluated the outcomes of hospitalized patients with COVID-19 treated with CCP in a prospective, observational, multicenter trial. METHODS: From April through August 2020, hospitalized patients with COVID-19 at 16 participating hospitals in Colorado were enrolled and treated with CCP and compared with hospitalized patients with COVID-19 who were not treated with convalescent plasma. Plasma antibody levels were determined following the trial, given that antibody tests were not approved at the initiation of the trial. CCP-treated and untreated hospitalized patients with COVID-19 were matched using propensity scores followed by analysis for length of hospitalization and inpatient mortality. RESULTS: A total of 542 hospitalized patients with COVID-19 were enrolled at 16 hospitals across the region. A total of 468 hospitalized patients with COVID-19 were entered into propensity score matching with 188 patients matched for analysis in the CCP-treatment and control arms. Fine-Gray models revealed increased length of hospital stay in CCP-treated patients and no change in inpatient mortality compared with controls. In subgroup analysis of CCP-treated patients within 7 days of admission, there was no difference in length of hospitalization and inpatient mortality. CONCLUSIONS: These data show that treatment of hospitalized patients with COVID-19 treated with CCP did not significantly improve patient hospitalization length of stay or inpatient mortality.

Two Cases of Monkeypox-Associated Encephalomyelitis - Colorado and the District of Columbia, July-August 2022.

Monkeypox virus (MPXV) is an orthopoxvirus in the Poxviridae family. The current multinational monkeypox outbreak has now spread to 96 countries that have not historically reported monkeypox, with most cases occurring among gay, bisexual, and other men who have sex with men (1,2). The first monkeypox case in the United States associated with this outbreak was identified in May 2022 in Massachusetts (1); monkeypox has now been reported in all 50 states, the District of Columbia (DC), and one U.S. territory. MPXV is transmitted by close contact with infected persons or animals; infection results in a febrile illness followed by a diffuse vesiculopustular rash and lymphadenopathy. However, illness in the MPXV current Clade II outbreak has differed: the febrile prodrome is frequently absent or mild, and the rash often involves genital, anal, or oral regions (3,4). Although neuroinvasive disease has been previously reported with MPXV infection (5,6), it appears to be rare. This report describes two cases of encephalomyelitis in patients with monkeypox disease that occurred during the current U.S. outbreak. Although neurologic complications of acute MPXV infections are rare, suspected cases should be reported to state, tribal, local, or territorial health departments to improve understanding of the range of clinical manifestations of and treatment options for MPXV infections during the current outbreak.

Severely ill and high-risk COVID-19 patients exhibit increased peripheral circulation of CD62L+ and perforin+ T cells.

Introduction: The emergence of SARS-CoV-2, which causes COVID-19, has led to over 400 million reported cases worldwide. COVID-19 disease ranges from asymptomatic infection to severe disease and may be impacted by individual immune differences. Methods: We used multiparameter flow cytometry to compare CD4+ and CD8+ T cell responses in severe (ICU admitted) and non-severe (admitted to observational unit) hospitalized COVID-19 patients. Results: We found that patients with severe COVID- 19 had greater frequencies of CD4+ T cells expressing CD62L compared to non-severe patients and greater frequencies of perforin+ CD8+ T cells compared to recovered patients. Furthermore, greater frequencies of CD62L+ CD4+ and CD8+ T cells were seen in severely ill diabetic patients compared to non-severe and non-diabetic patients, and increased CD62L+ CD4+ T cells were also seen in severely ill patients with hypertension. Discussion: This is the first report to show that CD62L+ T cells and perforin+ T cells are associated with severe COVID-19 illness and are significantly increased in patients with high-risk pre-existing conditions including older age and diabetes. These data provide a potential biological marker for severe COVID-19.

Herpesvirus-Associated Encephalitis: an Update.

Purpose of Review: Herpesviruses are a leading cause of encephalitis worldwide. The article reviews the eight human herpesviruses with a focus on recent advances as they pertain to encephalitis. Recent Findings: Notable recent updates include the development of multiplex polymerase chain reaction (PCR)-based panels, which have improved access to PCR tests, especially in rural and resource-limited areas. Despite unchanged treatment recommendations, research is ongoing into novel therapies. There have been recent advances in vaccines, particularly for varicella zoster virus (VZV) which may impact neurologic complications. Finally, the recent discovery of an association between herpes encephalitis and post-infectious autoimmune encephalitis has had a critical impact on the fields of infectious and autoimmune neurology, though there remains much to learn. Summary: Most herpesviruses are neurotropic and must be considered on the differential diagnosis for infectious encephalitis. This article describes recent advances in the diagnosis, treatment, complications, and management of these infections.

The Predictive Potential of Elevated Serum Inflammatory Markers in Determining the Need for Intubation in CoVID-19 Patients.

Introduction: The predictive potential of demographics, clinical characteristics, and inflammatory markers at admission to determine future intubation needs of hospitalised CoVID-19 patients is unknown. The study aimed to determine the predictive potential of elevated serum inflammatory markers in determining the need for intubation in CoVID-19 Patients. Methods: In a retrospective cohort study of hospitalised SARS-CoV2 positive patients, single and multivariable regression analyses were used to determine covariate effects on intubation odds, and a minimax concave penalty regularised logistic regression was used to build a predictive model. A second prospective independent cohort tested the model. Results: Systemic inflammatory markers obtained at admission were higher in patients that required subsequent intubation, and adjusted odds of intubation increased for every standard deviation above the mean for c-reactive protein (CRP) OR:2.8 (95% CI 1.8-4.5, p<0.001) and lactate dehydrogenase OR:2.1 (95% CI 1.33.3, p=0.002). A predictive model incorporating C-reactive protein, lactate dehydrogenase, and diabetes status at the time of admission predicted intubation status with an area under the curve (AUC) of 0.78 with corresponding sensitivity of 86%, specificity of 63%. This predictive model achieved an AUC of 0.83, 91% sensitivity, and 41% specificity on the validation cohort. Conclusion: In patients hospitalised with CoVID-19, elevated serum inflammatory markers measured within the first twenty-four hours of admission are associated with an increased need for intubation. Additionally, a model of C-reactive protein, lactate dehydrogenase, and the presence of diabetes may play a predictive role in determining the future need for intubation.

Neurology of Acute Viral Infections.

As specialists in acute neurology, neurohospitalists are often called upon to diagnose and manage acute viral infections affecting the nervous system. In this broad review covering the neurology of several acute viral infections, our aim is to provide key diagnostic and therapeutic pearls of practical use to the busy neurohospitalist. We will review acute presentations, diagnosis, and treatment of human herpesviruses, arboviruses, enteroviruses, and some vaccine-preventable viruses. The neurological effects of coronaviruses, including COVID-19, are not covered in this review.

Impact of a pilot multimodal intervention to decrease antibiotic use for respiratory infections in a geriatric clinic.

Background: More than 80% of antibiotics are prescribed in the outpatient setting, of which 30% are inappropriate. The National Action Plan for Combating Antimicrobial Resistance called for a 50% decrease in outpatient antibiotic use by 2020. Inappropriate antibiotics are associated with adverse reactions and Clostridioides difficile infection, especially among older adults. Study design: Before and after study. Methods: We performed a quality improvement initiative at the University of Colorado Seniors Clinic. Providers received education on antibiotic guidelines, electronic antibiotic order sets were introduced with standardized stop dates. Antibiotic use data were collected for 6 months before and 6 months after the intervention, from December to May to avoid seasonal variation. Descriptive statistics and linear mixed-effects regression models were used for this comparison. Results: Total antibiotic prescriptions for acute respiratory conditions decreased from 137 prescriptions before the intervention (December 1, 2017, to May 31, 2018) to 112 prescriptions after the intervention (December 1, 2018, to May 31, 2019), driven primarily by decreases in antibiotic prescriptions for pneumonia, sinusitis, and bronchitis. Prescriptions for broad-spectrum antibiotics declined following the intervention including decreases in levofloxacin from 12 (9%) to 3 (3%) and amoxicillin-clavulanate from 15 (12%) to 7 (7%). We detected significant reductions in prescribed antibiotic durations (days) after the intervention for sinusitis (estimate, -2.0; 95% CI, -3.1 to -1.0; P = .0003), pharyngitis (estimate, -2.5; 95% CI, -4.6 to -0.5; P = .018), and otitis (-3.2; 95% CI, -5.2 to -1.3; P = .008). Conclusions: Low-cost interventions were initially successful in changing patterns of antibiotic use and decreasing overall antibiotic prescribing among older patients in the outpatient setting. Long-term follow-up studies are needed to determine the sustainability and clinical impact of these interventions.

Nervous System Manifestations of Arboviral Infections.

Purpose of Review: Complex environmental factors and human intervention influence the spread of arthropod vectors and the cycle of transmission of arboviruses. The spectrum of clinical manifestations is diverse, ranging from serious presentations like viral hemorrhagic fever (e.g., dengue, yellow fever, rift valley fever) or shock syndromes (e.g., dengue virus) to organ-specific illness like meningoencephalitis. Recent Findings: A spectrum of clinical neurologic syndromes with potential acute devastating consequences or long-term sequelae may result from some arboviral infections. Summary: In this review, we describe some of the most frequent and emerging neuro-invasive arboviral infections, spectrum of neurologic disorders including encephalitis, meningitis, myelitis or poliomyelitis, acute demyelinating encephalomyelitis, Guillain-Barré syndrome, and ocular syndromes.

Neutralizing COVID-19 Convalescent Plasma in Adults Hospitalized With COVID-19: A Blinded, Randomized, Placebo-Controlled Trial.

BACKGROUND: Convalescent plasma has been one of the most common treatments for COVID-19, but most clinical trial data to date have not supported its efficacy. RESEARCH QUESTION: Is rigorously selected COVID-19 convalescent plasma with neutralizing anti-SARS-CoV-2 antibodies an efficacious treatment for adults hospitalized with COVID-19? STUDY DESIGN AND METHODS: This was a multicenter, blinded, placebo-controlled randomized clinical trial among adults hospitalized with SARS-CoV-2 infection and acute respiratory symptoms for < 14 days. Enrolled patients were randomly assigned to receive one unit of COVID-19 convalescent plasma (n = 487) or placebo (n = 473). The primary outcome was clinical status (disease severity) 14 days following study infusion measured with a seven-category ordinal scale ranging from discharged from the hospital with resumption of normal activities (lowest score) to death (highest score). The primary outcome was analyzed with a multivariable ordinal regression model, with an adjusted odds ratio (aOR) < 1.0 indicating more favorable outcomes with convalescent plasma than with placebo. In secondary analyses, trial participants were stratified according to the presence of endogenous anti-SARS-CoV-2 antibodies ("serostatus") at randomization. The trial included 13 secondary efficacy outcomes, including 28-day mortality. RESULTS: Among 974 randomized patients, 960 were included in the primary analysis. Clinical status on the ordinal outcome scale at 14 days did not differ between the convalescent plasma and placebo groups in the overall population (aOR, 1.04; one-seventh support interval [1/7 SI], 0.82-1.33), in patients without endogenous antibodies (aOR, 1.15; 1/7 SI, 0.74-1.80), or in patients with endogenous antibodies (aOR, 0.96; 1/7 SI, 0.72-1.30). None of the 13 secondary efficacy outcomes were different between groups. At 28 days, 89 of 482 (18.5%) patients in the convalescent plasma group and 80 of 465 (17.2%) patients in the placebo group had died (aOR, 1.04; 1/7 SI, 0.69-1.58). INTERPRETATION: Among adults hospitalized with COVID-19, including those seronegative for anti-SARS-CoV-2 antibodies, treatment with convalescent plasma did not improve clinical outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04362176; URL: www. CLINICALTRIALS: gov.

Prevention of yellow fever in travellers: an update.

For centuries, yellow fever virus infection generated substantial fear among explorers, tourist travellers, workers, military personnel, and others entering areas of transmission. Currently, there is transmission only in some areas of tropical South America and sub-Saharan Africa. When symptomatic, yellow fever infection causes severe liver dysfunction and coagulopathy with elevated mortality rates. Since there is no effective treatment, vaccination against yellow fever, available since 1937, represents an important preventive intervention in endemic areas. Every year, an increasing number of individuals are travelling to yellow fever endemic areas, many of whom have complex medical conditions. Travel health practitioners should do individualised assessments of the risks and benefits of yellow fever vaccination to identify potential contraindications. The most relevant contraindications include a history of thymoma or thymus dysfunction, AIDS, and individuals receiving immunosuppressive drugs including biological therapies or chemotherapy. We briefly review strategies to prevent yellow fever infection in travellers with the use of yellow fever vaccination and the use of personal protection measures to avoid mosquito bites.

Appropriateness of antibiotic prescriptions for acute sinusitis and pharyngitis in an integrated healthcare system.

We evaluated the appropriateness of antibiotic prescriptions for acute sinusitis and pharyngitis. Overall, 81% of antibiotic prescriptions for acute sinusitis were inappropriate and 48% of antibiotic prescriptions for pharyngitis were inappropriate. Types of prescribing errors differed between the 2 infections, including lack of an indication for antibiotics and excessive duration in ~50% of sinusitis cases and incorrect antibiotic dose in ~33% of pharyngitis cases.Infect Control Hosp Epidemiol 2018; 0, 1-3.