Dengue: A focused review for the emergency clinician.

Dengue is an arbovirus transmitted by the Aedes spp. mosquito. Approximately 390 million infections occur annually per World Health Organization estimates, with significant increases in infections throughout the last decade. The disease is endemic in warmer climates throughout the world, though cases may also be imported to non-endemic regions by returning travelers. Patients experience a wide variety of symptoms ranging from asymptomatic infection to severe disease requiring critical care. Emergency clinicians should consider the diagnosis of dengue in patients from endemic areas presenting with a flu-like illness, rash, and evidence of bleeding.

Predicting severe disease in patients diagnosed with seasonal influenza in the emergency department.

Objectives: We sought to develop an evidence-based tool to risk stratify patients diagnosed with seasonal influenza in the emergency department (ED). Methods: We performed a single-center retrospective cohort study of all adult patients diagnosed with influenza in a large tertiary care ED between 2008 and 2018. We evaluated demographics, triage vital signs, chest x-ray and laboratory results obtained in the ED. We used univariate and multivariate statistics to examine the composite primary outcome of death or need for intubation. We validated our findings in patients diagnosed between 2018 and 2020. Results: We collected data from 3128 subjects; 2196 in the derivation cohort and 932 in the validation cohort. Medical comorbidities, multifocal opacities or pleural effusion on chest radiography, older age, elevated respiratory rate, hypoxia, elevated blood urea nitrogen, blood glucose, blood lactate, and red blood cell distribution width were factors associated with intubation or death. We developed the Predicting Intubation in seasonal Influenza Patients diagnosed in the ED (PIIPED) risk-stratification tool from these factors. The PIIPED tool predicted intubation or death with an area under the receiver operating characteristic curve (AUC) of 0.899 in the derivation cohort and 0.895 in the validation cohort. A version of the tool including only factors available at ED triage, before laboratory or radiographic evaluation, exhibited AUC of 0.852 in the derivation cohort and 0.823 in the validation cohort. Conclusion: Clinical findings during an ED visit predict severe outcomes in patients with seasonal influenza. The PIIPED risk stratification tool shows promise but requires prospective validation.

Evolving Stroke Systems of Care: Stroke Diagnosis and Treatment in the Post-Thrombectomy Era.

Thrombectomy became the gold-standard treatment of acute ischemic stroke caused by large-vessel occlusions (LVO) in 2015 after five clinical trials published that year demonstrated significantly improved patient outcomes. In subsequent years, advances in stroke systems of care have centered around improving access to and expanding patient eligibility for thrombectomy. The prehospital and acute stroke treatment settings have had the greatest emphasis. Numerous prehospital stroke scales now provide emergency medical services with focused physical exams to identify LVOs, and many devices to non-invasively detect LVO are undergoing clinical testing. Mobile stroke units deployed throughout Western Europe and the USA also show promising results by bringing elements of acute stroke care directly to the patient. Numerous clinical trials since 2015 have aimed to increase candidates for thrombectomy by expanding indications and the eligibility time window. Further optimizations of thrombectomy treatment have focused on the role of thrombolytics and other adjunctive therapies that may promote neuroprotection and neurorecovery. While many of these approaches require further clinical investigation, the next decade shows significant potential for further advances in stroke care.

High risk and low prevalence diseases: Adult bacterial meningitis.

INTRODUCTION: Acute bacterial meningitis in adults is a rare but serious condition that carries a high rate of morbidity. OBJECTIVE: This review highlights pearls and pitfalls of acute bacterial meningitis in adults, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Meningitis encompasses a broad spectrum of disease involving inflammation of the meninges and subarachnoid space. It classically presents with fever, nuchal rigidity, and altered mental status, but this triad is not present in all cases. Up to 95% of patients will have at least two of the following four cardinal symptoms: fever, nuchal rigidity, altered mental status, and headache. The most common bacterial etiologies are S. pneumoniae and N. meningitidis. Cerebrospinal fluid testing obtained by lumbar puncture remains the gold standard in diagnosis. Head computed tomography prior to lumbar puncture may not be necessary in most patients. Empiric treatment consists of vancomycin, ceftriaxone, and dexamethasone. Elevated intracranial pressure should be managed using established neurocritical care strategies. CONCLUSION: A better understanding of the pearls and pitfalls of acute bacterial meningitis can assist emergency clinicians in pursuing its timely diagnosis and management.

A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study.

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over 6 months (March-August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of - 3 to - 5 or Riker Sedation-Agitation Scale of 1-3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. RESULTS: 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65-7.17; p < 0.01). These results were stable in the subgroup of patients with COVID-19. CONCLUSIONS: The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach.

A Dual-Center Cohort Study on The Association Between Early Deep Sedation and Clinical Outcomes in Mechanically Ventilated Patients During the COVID-19 Pandemic: the COVID-SED Study.

Background : Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. Study Design and Methods : Dual-center, retrospective cohort study conducted over six months (March - August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 hours were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Riker Sedation-Agitation Scale of 1 - 3. To examine impact of early sedation depth on hospital mortality (primary outcome) we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. Results : 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation ( p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65 - 7.17; p <0.01). These results were stable in the subgroup of patients with COVID-19. Conclusions : The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach. Clinical Trial Registration : Not applicable.

Elucidating immunometabolic targets in glioblastoma.

Immunometabolism has recently emerged on the forefront of cancer research as a new avenue to potentially develop more effective and targeted treatment options. Several pathologically altered metabolic targets across various cancer types have been identified, including lactate in aerobic glycolysis; tryptophan in amino acid metabolism; and arginine in the urea cycle. Numerous advancements have improved our understanding of the dual function of these targets in influencing immune functions as an auxiliary function to their well-established metabolic role. This paper provides a comprehensive overview of immunometabolism research and attempts to provide insight into potential immunometabolic targets in glioblastoma for the purpose of future development and study of targeted therapies.