A Comparison of Methylprednisolone and Dexamethasone in Intensive Care Patients With COVID-19.

OBJECTIVES: This study retrospectively compares the effectiveness of methylprednisolone to dexamethasone in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) requiring intensive care. DESIGN: This is an institutional review board approved cohort study in patients with COVID-19 requiring intensive care unit (ICU) admission. Patients admitted and requiring oxygen supplementation were treated with no steroids, methylprednisolone, or dexamethasone. SETTING: This study takes place in the ICU's at a large, tertiary, public teaching hospital serving a primarily low-income community in urban Los Angeles. PATIENTS: All eligible patients admitted to the ICU for COVID-19 respiratory failure from March 1 to July 31, 2020 were included in this study. INTERVENTIONS: A total of 262 patients were grouped as receiving usual care (n = 75), methylprednisolone dosed at least at 1mg/kg/day for ≥ 3 days (n = 104), or dexamethasone dosed at least at 6 mg for ≥7 days (n = 83). MEASUREMENTS AND MAIN RESULTS: All-cause mortality within 50 days of initial corticosteroid treatment as compared to usual care was calculated. The mortality effect was then stratified based on levels of respiratory support received by the patient. In this cohort of 262 patients with severe COVID-19, all-cause mortalities in the usual care, methylprednisolone, and dexamethasone groups were 41.3%, 16.4% and 26.5% at 50 days (P < 0.01) respectively. In patients requiring mechanical ventilation, mortality was 42% lower in the methylprednisolone group than in the dexamethasone group (hazard ratio 0.48, 95% CI: 0.235-0.956, P = 0.0385). CONCLUSIONS: In COVID-19 patients requiring mechanical ventilation, sufficiently dosed methylprednisolone can lead to a further decreased mortality as compared to dexamethasone.

Medical management of COVID-19 clinic.

The start of the global pandemic secondary to the novel SARS-CoV-2 virus was a time of uncertainty and fear as it claimed the lives of many across the world. Since then, there has been a plethora of research designs and trials in order to understand what we can do to stop the spread of the disease. Scientists and health care providers have utilized old medications and revamped them for current use such a convalescent plasma and steroids, as well as creating novel therapeutics, some with promising results. In this article, we review the major therapeutic options currently available and look into what the future still holds in order to further our understanding of this mysterious disease.

Quantification of critical care medicine: An ICU survey.

BACKGROUND: The shortage in intensivist workforce has been long recognized but no solution has been identified. Meanwhile, fellowships in pulmonary and critical care medicine (PCCM) are expanding, other critical care medicine (CCM) programs are contracting. No explanation exists for this contradictory trend, although understanding contributory factors may lead to a solution for the shortage. The fundamental difference between PCCM and other CCM programs lies in the residency training of trainees. We tested the hypothesis that the nature of CCM practice determines its attractiveness to potential candidates. METHODS: A questionnaire-based survey was administered recording all daily activities in four different kinds of ICUs at two teaching hospitals one was public, and one was private. Activities were categorized into conventional CCM, respiratory, medical, and surgical interventions. RESULTS: The average daily census was 17.6 ± 6.6. Across two MICU, one trauma/surgical and one cardiothoracic ICU the average daily activity ranged from 152 to 203 of these CCM formed 27%-36%, respiratory 10%-13%, medical 43%-59%, and surgical 1%-15%. The combination of medical and respiratory interventions represented >50% of daily activities among all the ICUs. CONCLUSIONS: Quantitative description of ICU activities indicates that the majority of the ICU daily practice relies on medical and respiratory interventions, which may explain why PCCM remains popular.

A 47-year-old woman with hypercapnia and altered mental status.

Permissive hypercapnia is a commonly used ventilator strategy in attempt to improve refractory hypoxemia. The rationale of such practice is based on the assumption that hypercapnia, although associated with altered mental status, is well tolerated. Here, we report a case in which the altered mental status caused by hypercapnia is underlined by a life-threatening mechanism. The case indicates the severity of hypercapnia may have been mistakenly overlooked in the past.

Establishing Pulmonary and Critical Care Medicine in China: 2016 Report on Implementation and Government Recognition: Joint Statement of the Chinese Association of Chest Physicians and the American College of Chest Physicians.

This article provides an update on progress toward establishing pulmonary and critical care medicine (PCCM) fellowship training as one of the first four subspecialties to be recognized and supported by the Chinese government. Designed and implemented throughout 2013 and 2014 by a collaborative effort of the Chinese Thoracic Society (CTS) and the American College of Chest Physicians (CHEST), 12 leading Chinese hospitals enrolled a total of 64 fellows into standardized PCCM training programs with common curricula, educational activities, and assessment measures. Supplemental educational materials, online assessment tools, and institutional site visits designed to evaluate and provide feedback on the programs' progress are being provided by CHEST. As a result of this initial progress, the Chinese government, through the Chinese Medical Doctor's Association, endorsed the concept of subspecialty fellowship training in China, with PCCM as one of the four pilot subspecialties to be operationalized nationwide in 2016, followed by implementation across other subspecialties by 2020. This article also reflects on the achievements of the training sites and the challenges they face and outlines plans to enhance and expand PCCM training and practice in China.

A 46-year-old woman with left shoulder pain and worsening dyspnea.

A 46-year-old woman presented with worsening dyspnea and palpitations for 3 days following an episode of left shoulder pain. The patient had received a diagnosis of patent ductus arteriosus with Eisenmenger syndrome in childhood but had been inconsistently taking digoxin and diuretics since then. She was married but had never been pregnant. Over the previous 2 to 3 years, her exercise capacity had decreased significantly, with frequent episodes of near syncope and chest pain. She had developed bilateral leg edema. Three days prior to admission, she noticed an episode of severe, sharp pain in her left shoulder that was nonradiating but associated with palpitations and sweating and that lasted for about 20 min. The shoulder pain subsided spontaneously but her dyspnea worsened significantly, which prompted her to present to the ED.

Establishing pulmonary and critical care medicine as a subspecialty in China: joint statement of the Chinese thoracic society and the American college of chest physicians.

This commentary heralds the recognition in China of a new subspecialty, Pulmonary and Critical Care Medicine, and the first national fellowship training pathway in any medical specialty. Because of striking environmental health-care similarities that existed in the United States, the Chinese medical community decided to model the specialty after that in the United States. Because of its expertise in educating pulmonary and critical care physicians in the United States, the American College of Chest Physicians was chosen by the Chinese Thoracic Society, with the approval of the Chinese government, to help with the transformation of this new specialty. A work group representing the two societies is collaborating to reorganize ICUs within a select group of large teaching hospitals in China and to introduce standardized and rigorous training in pulmonary and critical care medicine as a national program.

Respiratory medicine in China: progress, challenges, and opportunities.

The past century witnessed a rapid development of respiratory medicine in China. The major burden of respiratory disease has shifted from infectious diseases to chronic noninfectious diseases. Great achievements have been made in improving the national standard of clinical management of various respiratory diseases and in smoking control. The specialty of respiratory medicine is expanding into pulmonary and critical care medicine. Nevertheless, respiratory diseases remain a major public health problem, with new challenges such as air pollution and nosocomial infections. This review describes the history, accomplishments, new challenges, and opportunities in respiratory medicine in China.

Use of SPECT to detect changes in diastolic and coronary reserve in patients with obstructive sleep apnea.

PURPOSE: To assess diastolic function and coronary artery reserve in patients with obstructive sleep apnea (OSA) using single-photon emission computer tomography (SPECT). METHODS: Patients with OSA who had normal echocardiograph/electrocardiogram findings were divided into three groups based on OSA severity: mild (n = 15), moderate (n = 13), or severe (n = 18). A control group of participants without OSA (n = 17) was included. SPECT (with technetium-99 m-labeled red blood cells) was performed after the induction of cardiac stress by injection of dobutamine. The following ventricular parameters were determined: left ventricular ejection fraction, peak filling rate (PFR), peak ejection rate, 1/3 filling fraction (1/3FF), and regional ejection fractions (rEF). RESULTS: The median ages of OSA and control participants were 45.0 and 51.0 years, respectively. Median apnea-hypopnea index scores were 3.3, 9.1, 38.5, and 65.2 for the control, mild OSA, moderate OSA, and severe OSA groups, respectively. Post-stress, 1/3FF was significantly lower in the overall OSA group compared with the control group (P < 0.05). PFR was significantly lower in the overall OSA group compared with the control group (P < 0.05) and was significantly lower in the severe OSA group compared with the mild OSA group. Regional ejection fractions rEF3 (cardiac apex and a small part of the inferior wall) and rEF4 (anteroseptal wall) were significantly lower in the overall OSA group compared with the control group, suggesting decreased coronary artery reserve. CONCLUSION: Our findings suggest that SPECT can be used to detect abnormalities in diastolic function and coronary reserve in patients with OSA who have normal electrocardiogram or echocardiograph findings. SPECT may be useful for the early detection of cardiovascular disease in patients with OSA.

Pulmonary actinomycosis presenting as a mass-like consolidation.

Pulmonary actinomycosis presented as a mass-like consolidation. The diagnosis was not established until clinical suspicion prompted special staining of the pathology material. Response to antibiotics was facilitated by a removal of the airway plug through bronchoscopy. Airway obstruction may contribute to the prolonged medical treatment of pulmonary actinomycosis.

Systematic comparison of the human saliva and plasma proteomes.

The proteome of human salivary fluid has the potential to open new doors for disease biomarker discovery. A recent study to comprehensively identify and catalog the human ductal salivary proteome led to the compilation of 1166 proteins. The protein complexity of both saliva and plasma is large, suggesting that a comparison of these two proteomes will provide valuable insight into their physiological significance and an understanding of the unique and overlapping disease diagnostic potential that each fluid provides. To create a more comprehensive catalog of human salivary proteins, we have first compiled an extensive list of proteins from whole saliva (WS) identified through MS experiments. The WS list is thereafter combined with the proteins identified from the ductal parotid, and submandibular and sublingual (parotid/SMSL) salivas. In parallel, a core dataset of the human plasma proteome with 3020 protein identifications was recently released. A total of 1939 nonredundant salivary proteins were compiled from a total of 19 474 unique peptide sequences identified from whole and ductal salivas; 740 out of the total 1939 salivary proteins were identified in both whole and ductal saliva. A total of 597 of the salivary proteins have been observed in plasma. Gene ontology (GO) analysis showed similarities in the distributions of the saliva and plasma proteomes with regard to cellular localization, biological processes, and molecular function, but revealed differences which may be related to the different physiological functions of saliva and plasma. The comprehensive catalog of the salivary proteome and its comparison to the plasma proteome provides insights useful for future study, such as exploration of potential biomarkers for disease diagnostics.

Effects of KGF on alveolar epithelial cell transdifferentiation are mediated by JNK signaling.

Rat alveolar epithelial cells (AEC) in primary culture transdifferentiate from a type II (AT2) toward a type I (AT1) cell-like phenotype, a process that can be both prevented and reversed by keratinocyte growth factor (KGF). Microarray analysis revealed that these effects of KGF are associated with up-regulation of key molecules in the mitogen-activated protein kinase (MAPK) pathway. To further explore the role of three key MAPK (i.e., extracellular signal-related kinase [ERK] 1/2, c-Jun N-terminal kinase [JNK] and p38) in mediating effects of KGF on AEC phenotype, primary rat AEC cultivated in minimal defined serum-free medium (MDSF) were treated with KGF (10 ng/ml) from Day 4 for intervals up to 48 hours. Exposure to KGF activated all three MAPK, JNK, ERK1/2, and p38. Inhibition of JNK, but not of ERK1/2 or p38, abrogated the ability of KGF to maintain the AT2 cell phenotype, as evidenced by loss of expression of lamellar membrane protein (p180) and increased reactivity with the AT1 cell-specific monoclonal antibody VIIIB2 by Day 6 in culture. Overexpression of JNKK2, upstream kinase of JNK, increased activation of endogenous c-Jun in association with increased expression of p180 and abrogation of AQP5, suggesting that activation of c-Jun promotes retention of the AT2 cell phenotype. These results indicate that retention of the AT2 cell phenotype by KGF involves c-Jun and suggest that activation of c-Jun kinase may be an important determinant of maintenance of AT2 cell phenotype.

Subunit-specific coordinate upregulation of sodium pump activity in alveolar epithelial cells by lentivirus-mediated gene transfer.

Resolution of alveolar edema depends on active ion transport by sodium pumps located on the basolateral surface of alveolar epithelial cells (AECs), suggesting that upregulation of sodium pump activity may facilitate clearance of edema fluid. We have investigated the use of lentiviral vectors to augment sodium pump activity via gene transfer of sodium pump subunits to AECs. Full-length cDNA for the alpha(1) or beta(1) subunit of rat Na(+),K(+)-ATPase was cloned into the lentiviral vector pRRLsin.hCMV.IRES.EGFP. Rat AECs in primary culture were transduced on day 4 with lentiviral vectors pseudotyped with vesicular stomatitis virus glycoprotein G. Transduction with lentiviral vectors encoding either alpha(1) subunit (Lenti-alpha(1)-EGFP) or beta(1) subunit (Lenti-beta(1)-EGFP) led to dose-dependent increases in mRNA and protein for the corresponding subunit. Transduction with Lenti-beta(1)-EGFP was accompanied by coordinate upregulation of endogenous alpha(1) expression, whereas endogenous beta(1) expression was unchanged after transduction with Lenti-alpha(1)-EGFP. Consistent with these findings, transduction with Lenti-beta(1)-EGFP, but not Lenti-alpha(1)-EGFP, led to augmentation of sodium pump activity as a result of increases in Na(+),K(+)-ATPase holoenzyme. Sodium pump alpha(2) subunit and sodium channel protein did not change after Lenti-beta(1)-EGFP transduction. These results demonstrate that overall sodium pump activity can be efficiently upregulated in AECs specifically via gene transfer of the sodium pump beta(1) subunit and support the feasibility of lentivirus-mediated gene transfer to augment alveolar fluid clearance.