Diagnosis and management of elevated intracranial pressure in the emergency department.

BACKGROUND: Elevated intracranial pressure is a devastating complication of catastrophic brain injury. Intracranial hypertension is commonly seen in neurologic injury secondary to traumatic brain injuries. Uncontrolled pressures can lead to permanent neurologic damage, but acute medical management is often overlooked when pursuing surgical management options that may not always be indicated. DISCUSSION: Traumatic brain injury is the leading cause of death in patients with severe neurologic injury. Diagnosing elevated intracranial pressures is imperative in initiating prompt treatment to reduce secondary central nervous system injury, morbidity, and mortality. Although the initial injury to the brain is typically irreversible, intracranial pressure control can assist in salvaging the remaining brain tissue from additional damage. We will discuss the initial medical and surgical management of traumatic brain injury to prevent further neurologic deterioration and reduce mortality. CONCLUSION: Recent literature has reported several methods to detect elevated intracranial pressure easily and studies describing multiple treatment modalities. These investigations suggest that early detection and timely treatment of intracranial hypertension are beneficial in reducing mortality.

Extracellular vesicle proteomics and phosphoproteomics identify pathways for increased risk in patients hospitalized with COVID-19 and type 2 diabetes mellitus.

Recent studies suggest that extracellular vesicles (EVs) play a role in the pathogenesis of SARS-CoV-2 infection and the severity of COVID-19. However, their role in the interaction between COVID-19 and type 2 diabetes (T2D) has not been addressed. Here, we characterized the circulating EV proteomic and phosphoproteomic landscape in patients with and without T2D hospitalized with COVID-19 or non-COVID-19 acute respiratory illness (RSP). We detected differentially expressed protein and phosphoprotein signatures that effectively characterized the study groups. The trio of immunomodulatory and coagulation proteins C1QA, C1QB, and C1QC appeared to be a central cluster in both the COVID-19 and T2D functional networks. PKCß appeared to be retained in cells by being diverted from EV pathways and contribute to the COVID-19 and T2D interaction via a PKC/BTK/TEC axis. EV-shuttled CASP3 and ROCK1 appeared to be coregulated and likely contribute to disease interactions in patients with COVID-19 and T2D. Predicted activation of AMPK, MAPK, and SYK appeared to also play important roles driving disease interaction. These results suggest that activated cellular kinases (i.e., PKC, AMPK, MAPK, and SYK) and multiple EV-shuttled kinases (i.e., PKCß, BTK, TEC, MAP2K2, and ROCK1) may play key roles in severe COVID-19, particularly in patients with comorbid diabetes.

A Case of Transient Gestational Hyperthyroidism Complicated With Acute Liver Injury Successfully Treated With Plasma Exchange.

Therapeutic Plasma Exchange (TPE) in pregnancy is rare due to the uncertainty of efficiency and safety in clinical practice. It is experience-based on extrapolation of efficacy and safety in non-pregnant populations than evidence-based. We reported a case of severe refractory hyperemesis gravidarum secondary to transient gestational hyperthyroidism in a first-trimester pregnancy, which was complicated by acute hepatic injury during the clinical course and successfully managed with TPE. Both the clinical picture and objective index were improved dramatically after plasma exchanges. Three sessions of plasma exchange provided a 61% decrease in serum FT4 (free thyroxine) concentration (4.34 ng/dL to 1.71 ng/dL) and 89% decrease in alanine aminotransferase (ALT) (647 units/L to 69 units/L). The patient's symptoms improved significantly after TPE. In two weeks follow-up visit, her thyroid function was in the recommended range of 1st-trimester pregnancy (1.06 ng/dL) and her liver function was normalized (ALT 15 units/L, aspartate aminotransferase {AST} 11 units/L). In conclusion, plasma exchange may be used as an alternative therapeutic option in pregnancy to manage transient hyperthyroidism who failed or was unable to tolerate or have contradictions to antithyroid medications and thyroidectomy. Our case provides evidence of TPE in the treatment of thyrotoxicosis in pregnancy.

Hypothesis-Agnostic Network-Based Analysis of Real-World Data Suggests Ondansetron is Associated with Lower COVID-19 Any Cause Mortality.

BACKGROUND: The COVID-19 pandemic generated a massive amount of clinical data, which potentially hold yet undiscovered answers related to COVID-19 morbidity, mortality, long-term effects, and therapeutic solutions. OBJECTIVES: The objectives of this study were (1) to identify novel predictors of COVID-19 any cause mortality by employing artificial intelligence analytics on real-world data through a hypothesis-agnostic approach and (2) to determine if these effects are maintained after adjusting for potential confounders and to what degree they are moderated by other variables. METHODS: A Bayesian statistics-based artificial intelligence data analytics tool (bAIcis®) within the Interrogative Biology® platform was used for Bayesian network learning and hypothesis generation to analyze 16,277 PCR+ patients from a database of 279,281 inpatients and outpatients tested for SARS-CoV-2 infection by antigen, antibody, or PCR methods during the first pandemic year in Central Florida. This approach generated Bayesian networks that enabled unbiased identification of significant predictors of any cause mortality for specific COVID-19 patient populations. These findings were further analyzed by logistic regression, regression by least absolute shrinkage and selection operator, and bootstrapping. RESULTS: We found that in the COVID-19 PCR+ patient cohort, early use of the antiemetic agent ondansetron was associated with decreased any cause mortality 30 days post-PCR+ testing in mechanically ventilated patients. CONCLUSIONS: The results demonstrate how a real-world COVID-19-focused data analysis using artificial intelligence can generate unexpected yet valid insights that could possibly support clinical decision making and minimize the future loss of lives and resources.

A Multicenter Evaluation of the Seraph 100 Microbind Affinity Blood Filter for the Treatment of Severe COVID-19.

The Seraph100 Microbind Affinity Blood Filter (Seraph 100) (ExThera Medical, Martinez, CA) is an extracorporeal therapy that can remove pathogens from blood, including severe acute respiratory syndrome coronavirus 2. The aim of this study was to evaluate safety and efficacy of Seraph 100 treatment for COVID-19. DESIGN: Retrospective cohort study. SETTING: Nine participating ICUs. PATIENTS: COVID-19 patients treated with Seraph 100 (n = 53) and control patients matched by study site (n = 53). INTERVENTION: Treatment with Seraph 100. MEASUREMENTS AND MAIN RESULTS: At baseline, there were no differences between the groups in terms of sex, race/ethnicity, body mass index, and need for mechanical ventilation. However, patients in the Seraph 100 group were younger (median age, 54 yr; interquartile range [IQR], 41-65) compared with controls (median age, 64 yr; IQR, 56-69; p = 0.009). Charlson comorbidity index scores were lower in the Seraph 100 group (2; IQR, 0-3) compared with the control group (3; IQR, 2-4; p = 0.006). Acute Physiology and Chronic Health Evaluation II scores were also lower in Seraph 100 subjects (12; IQR, 9-17) compared with controls (16; IQR, 12-21; p = 0.011). The Seraph 100 group had higher vasopressor-free days with an incidence rate ratio of 1.30 on univariate analysis. This difference was not significant after adjustment. Seraph 100-treated subjects were less likely to die compared with controls (32.1% vs 64.2%; p = 0.001), a difference that remained significant after adjustment. However, no difference in mortality was observed in a post hoc analysis utilizing an external control group. In the full cohort of 86 treated patients, there were 177 total treatments, in which only three serious adverse events were recorded. CONCLUSIONS: Although this study did not demonstrate consistently significant clinical benefit across all endpoints and comparisons, the findings suggest that broad spectrum, pathogen agnostic, blood purification can be safely deployed to meet new pathogen threats while awaiting targeted therapies and vaccines.

Subarachnoid hemorrhage in the emergency department.

BACKGROUND: Subarachnoid hemorrhage accounts for more than 30,000 cases of stroke annually in North America and encompasses a 4.4% mortality rate. Since a vast number of subarachnoid hemorrhage cases present in a younger population and can range from benign to severe, an accurate diagnosis is imperative to avoid premature morbidity and mortality. Here, we present a straightforward approach to evaluating, risk stratifying, and managing subarachnoid hemorrhages in the emergency department for the emergency medicine physician. DISCUSSION: The diversities of symptom presentation should be considered before proceeding with diagnostic modalities for subarachnoid hemorrhage. Once a subarachnoid hemorrhage is suspected, a computed tomography of the head with the assistance of the Ottawa subarachnoid hemorrhage rule should be utilized as an initial diagnostic measure. If further investigation is needed, a CT angiography of the head or a lumbar puncture can be considered keeping risks and limitations in mind. Initiating timely treatment is essential following diagnosis to help mitigate future complications. Risk tools can be used to assess the complications for which the patient is at greatest. CONCLUSION: Subarachnoid hemorrhages are frequently misdiagnosed; therefore, we believe it is imperative to address the diagnosis and initiation of early management in the emergency medicine department to minimize poor outcomes in the future.

ICU outcomes and survival in patients with severe COVID-19 in the largest health care system in central Florida.

BACKGROUND: Observational studies have consistently described poor clinical outcomes and increased ICU mortality in patients with severe coronavirus disease 2019 (COVID-19) who require mechanical ventilation (MV). Our study describes the clinical characteristics and outcomes of patients with severe COVID-19 admitted to ICU in the largest health care system in the state of Florida, United States. METHODS: Retrospective cohort study of patients admitted to ICU due to severe COVID-19 in AdventHealth health system in Orlando, Florida from March 11th until May 18th, 2020. Patients were characterized based on demographics, baseline comorbidities, severity of illness, medical management including experimental therapies, laboratory markers and ventilator parameters. Major clinical outcomes analyzed at the end of the study period were: hospital and ICU length of stay, MV-related mortality and overall hospital mortality of ICU patients. RESULTS: Out of total of 1283 patients with COVID-19, 131 (10.2%) met criteria for ICU admission (median age: 61 years [interquartile range (IQR), 49.5-71.5]; 35.1% female). Common comorbidities were hypertension (84; 64.1%), and diabetes (54; 41.2%). Of the 131 ICU patients, 109 (83.2%) required MV and 9 (6.9%) received ECMO. Lower positive end expiratory pressure (PEEP) were observed in survivors [9.2 (7.7-10.4)] vs non-survivors [10 (9.1-12.9] p = 0.004]. Compared to non-survivors, survivors had a longer MV length of stay (LOS) [14 (IQR 8-22) vs 8.5 (IQR 5-10.8) p< 0.001], Hospital LOS [21 (IQR 13-31) vs 10 (7-1) p< 0.001] and ICU LOS [14 (IQR 7-24) vs 9.5 (IQR 6-11), p < 0.001]. The overall hospital mortality and MV-related mortality were 19.8% and 23.8% respectively. After exclusion of hospitalized patients, the hospital and MV-related mortality rates were 21.6% and 26.5% respectively. CONCLUSIONS: Our study demonstrates an important improvement in mortality of patients with severe COVID-19 who required ICU admission and MV in comparison to previous observational reports and emphasizes the importance of standard of care measures in the management of COVID-19.

A Case of Pulmonary Cement Embolism Managed through Symptomatic Treatment.

OBJECTIVE: This case describes symptomatic pulmonary cement embolism as a rare postvertebroplasty complication and highlights its critical yet ill-defined management. BACKGROUND: Pulmonary cement embolism (PCE) is a feared complication of vertebroplasty in the treatment of vertebral fractures. While the majority of PCEs are asymptomatic, symptomatic PCEs often present with chest pain, tachycardia, signs of severe respiratory distress, and death. Computer tomography angiogram (CTA) allows visualization of cement within the pulmonary vasculature. Despite the well-established risk of PCE, clinical management is unclear with limited research on treatment options. Reported treatments include anticoagulation, embolectomy, CPR, and supportive care and observation. Report. We report the case of a 75-year-old woman who experienced shortness of breath, tachypnea, tachycardia, hypertension, and hypoxemia five days following a corrective surgery for a compression fracture of L3 with pedicle screw fixation, fusion of L2 through L4, and L2 vertebral body cement augmentation with polymethyl methacrylate. RESULTS: Breath sounds were diminished bilaterally with respiratory alkalosis and hypoxemia evident on arterial blood gas. CTA revealed intravasated cement throughout the right lung, including the pulmonary artery and upper and middle lobar arteries. The proposed mechanism is embolization of cement particles from the lumbar veins, which also showed intravasation. Due to the inorganic nature of the occluding material, the use of a thrombolytic agent was ruled against. Treatment included bronchodilators, 3 L of oxygen via nasal cannula, and prophylactic antibiotics, pulmonary toilet, and incentive spirometry. Symptomatic management was continued until she was discharged from the hospital in a stable condition. CONCLUSIONS: Postvertebroplasty pulmonary cement embolisms can be managed conservatively, without the use of anticoagulant or thrombolytic agents. This case illustrates a variation of care for this rare presentation and adds to the sparse literature on the management of PCEs.

A Case of Reverse Takotsubo Cardiomyopathy Incited by a Spinal Subdural Hematoma.

Takotsubo cardiomyopathy is a rare syndrome of transient, reversible left ventricular systolic dysfunction. It mimics myocardial infarction clinically and includes elevated cardiac enzymes, but echocardiography reveals apical ballooning and basal hyperkinesis. Infrequently, midventricular or even reverse Takotsubo patterns have been described, involving ballooning of the basal heart without the characteristic 'Takotsubo' appearance. There are cases in the literature that support a connection between reverse Takotsubo cardiomyopathy (r-TTC) and neurological insults as inciting factors. We report a case of r-TTC in an otherwise healthy 23-year-old man presenting with back pain, urinary retention, bradycardia, and hypertension. Troponin levels and brain natriuretic peptide (BNP) were elevated, and echocardiogram revealed an ejection fraction (EF) of less than 20%. In addition, MRI demonstrated a spinal subdural hematoma from T1-S1 with no cord compression. Repeated echocardiogram demonstrated an EF of 20-25% with a reverse Takotsubo pattern of cardiomyopathy. With supportive care, his clinical picture improved with normalization of cardiac enzyme and BNP values. This case represents a r-TTC presenting as heart failure in a young, apparently healthy male likely incited by a spinal subdural hematoma. To our knowledge, it is the first of its kind reported.

Insurance Coverage Predicts Mortality in Patients Transferred Between Hospitals: a Cross-Sectional Study.

BACKGROUND: Patients transferred between hospitals are at high risk of adverse events and mortality. The relationship between insurance status, transfer practices, and outcomes has not been definitively characterized. OBJECTIVE: To identify the association between insurance coverage and mortality of patients transferred between hospitals. DESIGN: We conducted a single-institution observational study, and validated results using a national administrative database of inter-hospital transfers. SETTING: Three ICUs at an academic tertiary care center validated by a nationally representative sample of inter-hospital transfers. PATIENTS: The single-institution analysis included 652 consecutive patients transferred from 57 hospitals between 2011 and 2012. The administrative database included 353,018 patients transferred between 437 hospitals. MEASUREMENTS: Adjusted inpatient mortality and 24-h mortality, stratified by insurance status. RESULTS: Of 652 consecutive transfers to three ICUs, we observed that uninsured patients had higher adjusted inpatient mortality (OR 2.67, p = 0.021) when controlling for age, race, gender, Apache-II, and whether the patient was transferred from an ED. Uninsured were more likely to be transferred from ED (OR 2.3, p = 0.026), and earlier in their hospital course (3.9 vs 2.0 days, p = 0.002). Using an administrative dataset, we validated these observations, finding that the uninsured had higher adjusted inpatient mortality (OR 1.24, 95% CI 1.13-1.36, p < 0.001) and higher mortality within 24 h (OR 1.33 95% CI 1.11-1.60, p < 0.002). The increase in mortality was independent of patient demographics, referral patterns, or diagnoses. LIMITATIONS: This is an observational study where transfer appropriateness cannot be directly assessed. CONCLUSIONS: Uninsured patients are more likely to be transferred from an ED and have higher mortality. These data suggest factors that drive inter-hospital transfer of uninsured patients have the potential to exacerbate outcome disparities.

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD.

Correction: Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis.

[This corrects the article DOI: 10.1371/journal.pone.0178091.].

Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis.

INTRODUCTION: Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a sensitive and specific diagnostic test for acute kidney injury (AKI) in the Emergency Department (ED), but its economic impact has not been investigated. We hypothesized that uNGAL used in combination with serum creatinine (sCr) would reduce costs in the management of AKI in patients presenting to the ED in comparison to using sCr alone. MATERIALS AND METHODS: A cost simulation model was developed for clinical algorithms to diagnose AKI based on sCr alone vs. uNGAL plus sCr (uNGAL+sCr). A cost minimization analysis was performed to determine total expected costs for patients with AKI. uNGAL test characteristics were validated with eight-hundred forty-nine patients with sCr ≥1.5 from a completed study of 1635 patients recruited from EDs at two U.S. hospitals from 2007-8. Biomarker test, AKI work-up, and diagnostic imaging costs were incorporated. RESULTS: For a hypothetical cohort of 10,000 patients, the model predicted that the expected costs were $900 per patient (pp) in the sCr arm and $950 in the uNGAL+sCr arm. uNGAL+sCr resulted in 1,578 fewer patients with delayed diagnosis and treatment than sCr alone (2,013 vs. 436 pts) at center 1 and 1,973 fewer patients with delayed diagnosis and treatment than sCr alone at center 2 (2,227 vs. 254 patients). Although initial evaluation costs at each center were $50 pp higher in with uNGAL+sCr, total costs declined by $408 pp at Center 1 and by $522 pp at Center 2 due to expected reduced delays in diagnosis and treatment. Sensitivity analyses confirmed savings with uNGAL + sCr for a range of cost inputs. DISCUSSION: Using uNGAL with sCr as a clinical diagnostic test for AKI may improve patient management and reduce expected costs. Any cost savings would likely result from avoiding delays in diagnosis and treatment and from avoidance of unnecessary testing in patients given a false positive AKI diagnosis by use of sCr alone.

Information handoff and outcomes of critically ill patients transferred between hospitals.

PURPOSE: Patients transferred between hospitals are at high risk of adverse events and mortality. This study aims to identify which components of the transfer handoff process are important predictors of adverse events and mortality. MATERIALS AND METHODS: We conducted a retrospective, observational study of 335 consecutive patient transfers to 3 intensive care units at an academic tertiary referral center. We assessed the relationship between handoff documentation completeness and patient outcomes. The primary outcome was in-hospital mortality. Secondary outcomes included adverse events, duplication of labor, disposition error, and length of stay. RESULTS: Transfer documentation was frequently absent with overall completeness of 58.3%. Adverse events occurred in 42% of patients within 24 hours of arrival, with an overall in-hospital mortality of 17.3%. Higher documentation completeness was associated with reduced in-hospital mortality (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.02 to 0.38; P = .002), reduced adverse events (coefficient, -2.08; 95% CI, -2.76 to -1.390; P < .001), and reduced duplication of labor (OR, 0.19; 95% CI, 0.04 to 0.88; P = .033) when controlling for severity of illness. CONCLUSIONS: Documentation completeness is associated with improved outcomes and resource utilization in patients transferred between hospitals.

Interhospital transfer handoff practices among US tertiary care centers: A descriptive survey.

BACKGROUND: Interhospital transfer is an understudied area within transitions of care. The process by which hospitals accept and transfer patients is not well described. National trends and best practices are unclear. OBJECTIVE: To describe the demographics of large transfer centers, to identify common handoff practices, and to describe challenges and notable innovations involving the interhospital transfer handoff process. DESIGN AND PARTICIPANTS: A convenience sample of 32 tertiary care centers in the United States was studied. Respondents were typically transfer center directors surveyed by phone. MAIN MEASURES: Data regarding transfer center demographics, handoff communication practices, electronic infrastructure, and data sharing were obtained. RESULTS: The median number of patients transferred each month per receiving institution was 700 (range, 250-2500); on average, 28% of these patients were transferred to an intensive care unit. Transfer protocols and practices varied by institution. Transfer center coordinators typically had a medical background (78%), and critical care-trained registered nurse was the most prevalent (38%). Common practices included: mandatory recorded 3-way physician-to-physician conversation (84%) and mandatory clinical status updates prior to patient arrival (81%). However, the timeline of clinical status updates was variable. Less frequent transfer practices included: electronic medical record (EMR) cross-talk availability and utilization (23%), real-time transfer center documentation accessibility in the EMR (32%), and referring center clinical documentation available prior to transport (29%). A number of innovative strategies to address challenges involving interhospital handoffs are reported. CONCLUSIONS: Interhospital transfer practices vary widely amongst tertiary care centers. Practices that lead to improved patient handoffs and reduced medical errors need additional prospective evaluation. Journal of Hospital Medicine 2016;11:413-417. © 2016 Society of Hospital Medicine.

Acute exacerbations of chronic obstructive pulmonary disease: diagnosis, management, and prevention in critically ill patients.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is a substantial source of disability in the United States. Moderate-to-severe acute exacerbations of COPD (AECOPD) can progress to respiratory failure, necessitating ventilator assistance in patients in the intensive care unit (ICU). Patients in the ICU with AECOPD requiring ventilator support have higher morbidity and mortality rates as well as costs compared with hospitalized patients not in the ICU. The mainstay of management for patients with AECOPD in the ICU includes ventilator support (noninvasive or invasive), rapid-acting inhaled bronchodilators, systemic corticosteroids, and antibiotics. However, evidence supporting these interventions for the treatment of AECOPD in critically ill patients admitted to the ICU is scant. Corticosteroids have gained widespread acceptance in the management of patients with AECOPD necessitating ventilator assistance, despite their lack of evaluation in clinical trials as well as controversies surrounding optimal dosage regimens and duration of treatment. Recent studies evaluating the safety and efficacy of corticosteroids have found that higher doses are associated with increased adverse effects, which therefore support lower dosing strategies, particularly for patients admitted to the ICU for COPD exacerbations. This review highlights recent findings from the current body of evidence on nonpharmacologic and pharmacologic treatment and prevention of AECOPD in critically ill patients. In addition, the administration of bronchodilators using novel delivery devices in the ventilated patient and the conflicting evidence surrounding antibiotic use in AECOPD in the critically ill is explored. Further clinical trials, however, are warranted to clarify the optimal pharmacotherapy management for AECOPD, particularly in critically ill patients admitted to the ICU.