Characterization of Altered Gene Expression and Histone Methylation in Peripheral Blood Mononuclear Cells Regulating Inflammation in COVID-19 Patients.

The pandemic of COVID-19 has caused >5 million deaths in the world. One of the leading causes of the severe form of COVID-19 is the production of massive amounts of proinflammatory cytokines. Epigenetic mechanisms, such as histone/DNA methylation, miRNA, and long noncoding RNA, are known to play important roles in the regulation of inflammation. In this study, we investigated if hospitalized COVID-19 patients exhibit alterations in epigenetic pathways in their PBMCs. We also compared gene expression profiles between healthy controls and COVID-19 patients. Despite individual variations, the expressions of many inflammation-related genes, such as arginase 1 and IL-1 receptor 2, were significantly upregulated in COVID-19 patients. We also found the expressions of coagulation-related genes Von Willebrand factor and protein S were altered in COVID-19 patients. The expression patterns of some genes, such as IL-1 receptor 2, correlated with their histone methylation marks. Pathway analysis indicated that most of those dysregulated genes were in the TGF-ß, IL-1b, IL-6, and IL-17 pathways. A targeting pathway revealed that the majority of those altered genes were targets of dexamethasone, which is an approved drug for COVID-19 treatment. We also found that the expression of bone marrow kinase on chromosome X, a member of TEC family kinases, was increased in the PBMCs of COVID-19 patients. Interestingly, some inhibitors of TEC family kinases have been used to treat COVID-19. Overall, this study provides important information toward identifying potential biomarkers and therapeutic targets for COVID-19 disease.

Derivation of a quick Pitt bacteremia score to predict mortality in patients with Gram-negative bloodstream infection.

PURPOSE: This retrospective cohort study derived a "quick" version of the Pitt bacteremia score (qPitt) using binary variables in patients with Gram-negative bloodstream infections (BSI). The qPitt discrimination was then compared to quick sepsis-related organ failure assessment (qSOFA) and systemic inflammatory response syndrome (SIRS). METHODS: Hospitalized adults with Gram-negative BSI at Palmetto Health hospitals in Columbia, SC, USA from 2010 to 2013 were identified. Multivariate Cox proportional hazards regression was used to determine variables associated with 14-day mortality. RESULTS: Among 832 patients with Gram-negative BSI, median age was 65 years and 449 (54%) were women. After adjustments for age and Charleston comorbidity score, all five components of qPitt were independently associated with mortality: temperature < 36 °C [hazard ratio (HR) 3.02, 95% confidence interval (CI) 1.95-4.62], systolic blood pressure < 90 mmHg or vasopressor use (HR 2.40, 95% CI 1.37-4.13), respiratory rate ≥ 25/min or mechanical ventilation (HR 3.01, 95% CI 1.81-5.14), cardiac arrest (HR 5.35, 95% CI 2.81-9.43), and altered mental status (HR 3.99, 95% CI 2.44-6.80). The qPitt had higher discrimination to predict mortality [area under receiver operating characteristic curve (AUROC) 0.85] than both qSOFA (AUROC 0.77, p < 0.001) and SIRS (AUROC 0.63, p < 0.001). There was a significant difference in mortality between appropriate and inappropriate empirical antimicrobial therapy in patients with qPitt ≥ 2 (24% vs. 49%, p < 0.001), but not in those with qPitt < 2 (3% vs. 5%, p = 0.36). CONCLUSIONS: The qPitt had good discrimination in predicting mortality following Gram-negative BSI and identifying opportunities for improved survival with appropriate empirical antimicrobial therapy.

The evolution of an integrated ultrasound curriculum (iUSC) for medical students: 9-year experience.

Interest in ultrasound education in medical schools has increased dramatically in recent years as reflected in a marked increase in publications on the topic and growing attendance at international meetings on ultrasound education. In 2006, the University of South Carolina School of Medicine introduced an integrated ultrasound curriculum (iUSC) across all years of medical school. That curriculum has evolved significantly over the 9 years. A review of the curriculum is presented, including curricular content, methods of delivery of the content, student assessment, and program assessment. Lessons learned in implementing and expanding an integrated ultrasound curriculum are also presented as are thoughts on future directions of undergraduate ultrasound education. Ultrasound has proven to be a valuable active learning tool that can serve as a platform for integrating the medical student curriculum across many disciplines and clinical settings. It is also well-suited for a competency-based model of medical education. Students learn ultrasound well and have embraced it as an important component of their education and future practice of medicine. An international consensus conference on ultrasound education is recommended to help define the essential elements of ultrasound education globally to ensure ultrasound is taught and ultimately practiced to its full potential. Ultrasound has the potential to fundamentally change how we teach and practice medicine to the benefit of learners and patients across the globe.

Dysregulation in microRNA expression in peripheral blood mononuclear cells of sepsis patients is associated with immunopathology.

Sepsis is a major cause of death worldwide. It triggers systemic inflammation, the role of which remains unclear. In the current study, we investigated the induction of microRNA (miRNA) during sepsis and their role in the regulation of inflammation. Patients, on days 1 and 5 following sepsis diagnosis, had reduced T cells but elevated monocytes. Plasma levels of IL-6, IL-8, IL-10 and MCP-1 dramatically increased in sepsis patients on day 1. T cells from sepsis patients differentiated primarily into Th2 cells, whereas regulatory T cells decreased. Analysis of 1163 miRNAs from PBMCs revealed that miR-182, miR-143, miR-145, miR-146a, miR-150, and miR-155 were dysregulated in sepsis patients. miR-146a downregulation correlated with increased IL-6 expression and monocyte proliferation. Bioinformatics analysis uncovered the immunological associations of dysregulated miRNAs with clinical disease. The current study demonstrates that miRNA dysregulation correlates with clinical manifestations and inflammation, and therefore remains a potential therapeutic target against sepsis.

Effect of bedside ultrasonography on the certainty of physician clinical decisionmaking for septic patients in the emergency department.

STUDY OBJECTIVE: Sepsis protocols promote aggressive patient management, including invasive procedures. After the provision of point-of-care ultrasonographic markers of volume status and cardiac function, we seek to evaluate changes in emergency physician clinical decisionmaking and physician assessments about the clinical utility of the point-of-care ultrasonographic data when caring for adult sepsis patients. METHODS: For this prospective before-and-after study, patients with suspected sepsis received point-of-care ultrasonography to determine cardiac contractility, inferior vena cava diameter, and inferior vena cava collapsibility. Physician reports of treatment plans, presumed causes of observed vital sign abnormalities, and degree of certainty were compared before and after knowledge of point-of-care ultrasonographic findings. The clinical utility of point-of-care ultrasonographic data was also evaluated. RESULTS: Seventy-four adult sepsis patients were enrolled: 27 (37%) sepsis, 30 (40%) severe sepsis, 16 (22%) septic shock, and 1 (1%) systemic inflammatory response syndrome. After receipt of point-of-care ultrasonographic data, physicians altered the presumed primary cause of vital sign abnormalities in 12 cases (17% [95% confidence interval {CI} 8% to 25%]) and procedural intervention plans in 20 cases (27% [95% CI 17% to 37%]). Overall treatment plans were changed in 39 cases (53% [95% CI 41% to 64%]). Certainty increased in 47 (71%) cases and decreased in 19 (29%). Measured on a 100-mm visual analog scale, the mean clinical utility score was 65 mm (SD 29; 95% CI 58 to 72), with usefulness reported in all cases. CONCLUSION: Emergency physicians found point-of-care ultrasonographic data about cardiac contractility, inferior vena cava diameter, and inferior vena cava collapsibility to be clinically useful in treating adult patients with sepsis. Increased certainty followed acquisition of point-of-care ultrasonographic data in most instances. Point-of-care ultrasonography appears to be a useful modality in evaluating and treating adult sepsis patients.

Implementation of transvaginal ultrasound in an emergency department residency program: an analysis of resident interpretation.

BACKGROUND: Emergency physicians are increasingly performing transvaginal ultrasound (TVUS) to rule out ectopic pregnancy. However, little is known about appropriate educational pathways to train emergency medicine residents in TVUS. STUDY OBJECTIVES: To evaluate the ability of Emergency Medicine (EM) residents who underwent a training program in TVUS to detect the presence or absence of an intrauterine pregnancy (IUP) in patients of < 13 weeks gestation with vaginal bleeding or abdominal pain, as compared to the final interpretation of each study as determined by the Emergency Department (ED) Director of Ultrasound. METHODS: This was a prospective, observational study in a single residency program. Training included a lecture, competency examination, and 10 supervised TVUSs. The EM residents then performed TVUSs with the goal of determining the presence or absence of an IUP without input from an attending physician. Correlation with the ED Director of Ultrasound was assessed for the cohort, and stratified by year of training. RESULTS: There were 22 residents who performed 75 TVUSs over 17 months. Correlation with the ED Director of Ultrasound was 93.3%. Differences in correlation with the ED Director of Ultrasound were noted when compared by year of training: post-graduate year (PGY)-3 (93.3%), PGY-2 (92.1%), and PGY-1 (100%); p < 0.001. CONCLUSION: Residents were able to perform TVUSs to determine the presence or absence of an IUP in patients in whom the diagnosis of ectopic pregnancy was being considered with a high degree of correlation with the ED Director of Ultrasound after a brief training program. Correlation with the ED director of ultrasound was influenced by year of training.

An integrated ultrasound curriculum (iUSC) for medical students: 4-year experience.

A review of the development and implementation of a 4-year medical student integrated ultrasound curriculum is presented. Multiple teaching and assessment modalities are discussed as well as results from testing and student surveys. Lessons learned while establishing the curriculum are summarized. It is concluded that ultrasound is a well received, valuable teaching tool across all 4 years of medical school, and students learn ultrasound well, and they feel their ultrasound experience enhances their medical education.

Blood pressure control in acute cerebrovascular disease.

Acute cerebrovascular diseases (ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage) affect 780,000 Americans each year. Physicians who care for patients with these conditions must be able to recognize when acute hypertension requires treatment and should understand the principles of cerebral autoregulation and perfusion. Physicians should also be familiar with the various pharmacologic agents used in the treatment of cerebrovascular emergencies. Acute ischemic stroke frequently presents with hypertension, but the systemic blood pressure should not be treated unless the systolic pressure exceeds 220 mm Hg or the diastolic pressure exceeds 120 mm Hg. Overly aggressive treatment of hypertension can compromise collateral perfusion of the ischemic penumbra. Hypertension associated with intracerebral hemorrhage can be treated more aggressively to minimize hematoma expansion during the first 3 to 6 hours of illness. Subarachnoid hemorrhage is usually due to aneurysmal rupture; systolic blood pressure should be kept <150 mm Hg to prevent re-rupture of the aneurysm. Nicardipine and labetalol are recommended for rapidly treating hypertension during cerebrovascular emergencies. Sodium nitroprusside is not recommended due to its adverse effects on cerebral autoregulation and intracranial pressure. Hypoperfusion of the injured brain should be avoided at all costs.

Bedside ultrasound for verification of shoulder reduction.

Shoulder dislocations are a common complaint in the emergency department. The management of these injuries is well described and often involves procedural sedation. Unfortunately, patients often recover from this sedation before radiographs can verify successful reduction. We describe 2 patients with glenohumeral dislocations and subsequent reduction immediately verified by bedside ultrasound before the patients' recovery from procedural sedation. Our experience suggests that ultrasound may reduce the need for repeated sedation, expedite care, and reduce costs.