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Introduction Treatment with dexamethasone reduces mortality in patients with coronavirus disease 2019 (COVID-19) pneumonia requiring supplemental oxygen, but the optimal dose has not been determined. Objective To determine whether weight-based dexamethasone of 0.2 mg/kg is superior to 6 mg daily in reducing 28-day mortality in patients with COVID-19 and hypoxemia. Materials and methods A multicenter, open-label, randomized clinical trial was conducted between March 2021 and December 2021 at seven hospitals within Northwell Health. A total of 142 patients with confirmed COVID-19 and hypoxemia were included. Participants were randomized in a 1:1 ratio to dexamethasone 0.2 mg/kg intravenously daily (n = 70) or 6 mg daily (n = 72) for up to 10 days. Results There was no statistically significant difference in the primary outcome of 28-day all-cause mortality with deaths in 12 of 70 patients (17.14%) in the intervention group and 15 of 72 patients (20.83%) in the control group (p = 0.58). There were no statistically significant differences among the secondary outcomes. Conclusion In patients with COVID-19 and hypoxemia, the use of weight-based dexamethasone dosing was not superior to dexamethasone 6 mg in reducing all-cause mortality at 28 days. Clinical trial registration This study was registered under ClinicalTrials.gov (identifier: NCT04834375).

BACKGROUND: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) continues to be a global challenge due to the lack of definitive treatment strategies. We sought to determine the efficacy of early administration of anti-interleukin 6 therapy in reducing hospital mortality and progression to mechanical ventilation. METHODS: This was a retrospective chart review of 11,512 patients infected with SARS-CoV-2 who were admitted to a New York health system from March to May 2020. Tocilizumab was administered to subjects at the nasal cannula level of oxygen support to maintain an oxygen saturation of >88%. The Charlson comorbidity index was used as an objective assessment of the burden of comorbidities to predict 10-year mortality. The primary outcome of interest was hospital mortality. Secondary outcomes were progression to mechanical ventilation; the prevalence of venous thromboembolism and renal failure; and the change in C-reactive protein, D-dimer, and ferritin levels after tocilizumab administration. Propensity score matching by using a 1:2 protocol was used to match the tocilizumab and non-tocilizumab groups to minimize selection bias. The groups were matched on baseline demographic characteristics, including age, sex, and body mass index; Charlson comorbidity index score; laboratory markers, including ferritin, D-dimer, lactate dehydrogenase, and C-reactive protein values; and the maximum oxygen requirement at the time of tocilizumab administration. Mortality outcomes were evaluated based on the level of oxygen requirement and the day of hospitalization at the time of tocilizumab administration. RESULTS: The overall hospital mortality was significantly reduced in the tocilizumab group when tocilizumab was administered at the nasal cannula level (10.4% vs 22.0%; P = .002). In subjects who received tocilizumab at the nasal cannula level, the progression to mechanical ventilation was reduced versus subjects who were initially on higher levels of oxygen support (6.3% vs 18.7%; P < .001). There was no improvement in mortality when tocilizumab was given at the time of requiring non-rebreather, high-flow nasal cannula, noninvasive ventilator, or invasive ventilator. CONCLUSIONS: Early use of anti-interleukin 6 therapy may be associated with improved hospital mortality and reduction in progression to more severe coronavirus disease 2019.

Central sleep apnea (CSA) is characterized by intermittent repetitive cessation and/or decreased breathing without effort caused by an abnormal ventilatory drive. Although less prevalent than obstructive sleep apnea, it is frequently encountered. CSA can be primary (idiopathic) or secondary in association with Cheyne-Stokes respiration, drug-induced, medical conditions such as chronic renal failure, or high-altitude periodic breathing. Risk factors have been proposed, including gender, age, heart failure, opioid use, stroke, and other chronic medical conditions. This article discusses the prevalence of CSA in the general population and within each of these at-risk populations, and clinical presentation, diagnostic methods, and treatment.

Insomnia afflicts many geriatric patients worldwide and results in both clinical and economic consequences. Prescribing hypnotics to the elderly is particularly challenging due to multitudes of adverse effects and drug interactions. Although benzodiazepines and "Z" drugs such as zolpidem have been popular in the past, they carry a high risk of adverse effects in the elderly, such as devastating falls and injuries as well as potentially an increase in mortality. Newer classes of hypnotics such as dual orexin receptor antagonists are much better tolerated and can be explored as a potential treatment for insomnia in the elderly.

The COVID-19 pandemic has had devastating medical and economic consequences globally. The severity of COVID-19 is related, in a large measure, to the extent of pulmonary involvement. The role of chest CT imaging in the management of patients with COVID-19 has evolved since the onset of the pandemic. Specifically, the description of CT scan findings, use of chest CT imaging in various acute and subacute settings, and its usefulness in predicting chronic disease have been defined better. We performed a review of published data on CT scans in patients with COVID-19. A summary of the range of imaging findings, from typical to less common abnormalities, is provided. Familiarity with these findings may facilitate the diagnosis and management of this disease. A comparison of sensitivity and specificity of chest CT imaging with reverse-transcriptase polymerase chain reaction testing highlights the potential role of CT imaging in difficult-to-diagnose cases of COVID-19. The usefulness of CT imaging to assess prognosis, to guide management, and to identify acute pulmonary complications associated with SARS-CoV-2 infection is highlighted. Beyond the acute stage, it is important for clinicians to recognize pulmonary parenchymal abnormalities, progressive fibrotic lung disease, and vascular changes that may be responsible for persistent respiratory symptoms. A large collection of multi-institutional images were included to elucidate the CT scan findings described.

Areas of diminished lung density are frequently identified both on routine chest radiographs and chest CT examinations. Colloquially referred to as hyperlucent foci of lung, a broad range of underlying pathophysiologic mechanisms and differential diagnoses account for these changes. Despite this, the spectrum of etiologies can be categorized into underlying parenchymal, airway, and vascular-related entities. The purpose of this review is to provide a practical diagnostic algorithmic approach to pulmonary hyperlucencies incorporating clinical history and characteristic imaging patterns to narrow the differential.

Insomnia afflicts many geriatric patients worldwide and results in both clinical and economic consequences. Prescribing hypnotics to the elderly is particularly challenging due to multitudes of adverse effects and drug interactions. Although benzodiazepines and "Z" drugs such as zolpidem have been popular in the past, they carry a high risk of adverse effects in the elderly, such as devastating falls and injuries as well as potentially an increase in mortality. Newer classes of hypnotics such as dual orexin receptor antagonists are much better tolerated and can be explored as a potential treatment for insomnia in the elderly.

Noninvasive ventilation has been used as a preventative and therapeutic modality in cardiac, thoracoabdominal, and abdominal surgical patients. In both scenarios, noninvasive ventilation reduces intubation rates and postoperative pulmonary complications. There is inconclusive evidence on mortality reduction with noninvasive ventilation use in the postoperative period. The present chapter examines the recent literature concerning the use of noninvasive ventilation for management of postoperative patients.

Hypersomnolence is one of the more common symptoms reported after mild traumatic brain injury (TBI) and often one of the most difficult to treat. This case series presents a cohort of patients with TBI related hypersomnolence associated with a de novo autoimmune process that successfully resolved with pulse dose corticosteroid treatment. When associated with an autoimmune inflammatory process, corticosteroids may serve to stabilize the blood brain barrier leading to the successful and sustained resolution of TBI induced sleepiness. CITATION: Oks M, Kothare SV. Steroids: a wake-up call in TBI induced hypersomnolence. J Clin Sleep Med. 2019;15(7):1063–1065.

Areas of diminished lung density are frequently identified both on routine chest radiographs and chest CT examinations. Colloquially referred to as hyperlucent foci of lung, a broad range of underlying pathophysiologic mechanisms and differential diagnoses account for these changes. Despite this, the spectrum of etiologies can be categorized into underlying parenchymal, airway, and vascular-related entities. The purpose of this review is to provide a practical diagnostic algorithmic approach to pulmonary hyperlucencies incorporating clinical history and characteristic imaging patterns to narrow the differential.

Background: Alcohol withdrawal syndrome (AWS) is a common reason for admission to a medical intensive care unit (MICU) and requires significant hospital resource utilization. Benzodiazepines are first-line therapy for AWS in many intensive care units. We propose the use of symptom-triggered phenobarbital for the treatment of AWS as a safe alternative to benzodiazepines. Methods: This was a retrospective observational study of a 4-year period, 2011 to 2015, of all patients with AWS admitted to the MICU of 1 tertiary care hospital and treated with phenobarbital. A symptom-triggered protocol was used. Resolution of AWS was assessed with the Richmond Agitation Sedation Scale to goal score of 0 to −1. The Charlson Comorbidity Index was used as an index of patient illness severity. Complications associated with phenobarbital use and/or the AWS admission were analyzed. Results: Data of 86 AWS patient encounters were analyzed. The mean Clinical Institute Withdrawal Assessment for Alcohol–Revised score of patients admitted to the MICU with AWS was 19 ± 9. The mean phenobarbital dose administered during the MICU stay was 1977.5 ± 1531.5 mg. There were a total of 17 (20%) intubations. The most frequent cause of mechanical ventilation in patients with AWS was loss of airway clearance, followed by hemodynamic instability secondary to upper gastrointestinal bleeding and the corresponding need for endoscopy. Conclusions: Sole use of phenobarbital use for control of AWS may be a safe alternative to benzodiazepines. Further study is needed to correlate phenobarbital serum levels with clinical control of AWS.

BACKGROUND:Point-of-care ultrasonography performed by frontline intensivists offers the possibility of reducing the use of traditional imaging in the medical ICU (MICU). We compared the use of traditional radiographic studies between two MICUs: one where point-of-care ultrasonography is used as a primary imaging modality, the other where it is used only for procedure guidance. METHODS:This study was a retrospective 3-month chart review comparing the use of chest radiographs, CT scans (chest and abdomen/pelvis), transthoracic echocardiography performed by the cardiology service, and DVT ultrasonography studies performed by the radiology service between two MICUs of similar size and acuity and staffing levels. RESULTS:Total number of admissions, patient demographics, and disease acuity were similar between MICUs. Comparing the non-point-of-care ultrasonography MICU with the point-of-care ultrasonography MICU, there were 3.75 ± 4.6 vs 0.82 ± 1.85 (P< .0001) chest radiographs per patient, 0.10 ± 0.31 vs 0.04 ± 0.20 (P= .0007) chest CT scans per patient, 0.17 ± 0.44 vs 0.05 ± 0.24 (P< .0001) abdomen/pelvis CT scans per patient, 0.20 ± 0.47 vs 0.02 ± 0.14 (P< .0001) radiology service-performed DVT studies per patient, and 0.18 ± 0.40 vs 0.07 ± 0.26 (P< .0001) cardiology service-performed transthoracic echocardiography studies per patient, respectively. CONCLUSIONS:The use of point-of-care ultrasonography in an MICU is associated with a significant reduction in the number of imaging studies performed by the radiology and cardiology services.

To determine whether strong CD4+ T cell immunity could be induced to a nonmutated self protein that is important for tumorigenesis, we selectively targeted the xenogeneic form of survivin, a survival protein overexpressed in tumors, to maturing dendritic cells in lymphoid tissues. Dendritic cell targeting via the DEC205 receptor in the presence of anti-CD40 and poly(I:C) as maturation stimuli, induced strong human and mouse survivin-specific CD4+ T cell responses, as determined by IFN-γ, TNF-α, and IL-2 production, as well as the development of lytic MHC class II-restricted T cells and memory. Immunity was enhanced further by depletion of CD25+foxp3+ cells before vaccination. anti-DEC205-human survivin was superior in inducing CD4+ T cell responses relative to other approaches involving survivin plasmid DNA or survivin peptides with adjuvants. However, we were unable to induce CD8+ T cell immunity to survivin by two doses of DEC205-targeted survivin or the other strategies. Therefore, significant CD4+ T cell immunity to a self protein that is overexpressed in most human cancers can be induced by DEC205 targeting of the Ag in its xenogeneic form to maturing DCs.

DNA vaccines promote an immune response by providing antigen-encoding DNA to the recipient, but the efficacy of such vaccines needs improving. Many approaches have considerable potential but currently induce relatively weak immune responses despite multiple high doses of DNA vaccine. Here, we asked whether targeting vaccine antigens to DCs would increase the immunity and protection that result from DNA vaccines. To determine this, we generated a DNA vaccine encoding a fusion protein comprised of the vaccine antigen and a single-chain Fv antibody (scFv) specific for the DC-restricted antigen-uptake receptor DEC205. Following vaccination of mice, the vaccine antigen was expressed selectively by DCs, which were required for the increased efficacy of MHC class I and MHC class II antigen presentation relative to a control scFv DNA vaccine. In addition, a DNA vaccine encoding an HIV gag p41-scFv DEC205 fusion protein induced 10-fold higher antibody levels and increased numbers of IFN-gamma-producing CD4+ and CD8+ T cells. After a single i.m. injection of the DNA vaccine encoding an HIV gag p41-scFv DEC205 fusion protein, mice were protected from an airway challenge with a recombinant vaccinia virus expressing the HIV gag p41, even with 1% of the dose of nontargeted DNA vaccine. The efficacy of DNA vaccines therefore may be enhanced by inclusion of sequences such as single-chain antibodies to target the antigen to DCs.