Blunt Thoracolumbar-Spine Trauma Evaluation in the Emergency Department: A Meta-Analysis of Diagnostic Accuracy for History, Physical Examination, and Imaging.

BACKGROUND: Delayed diagnoses of unstable thoracolumbar spine (TL-spine) fractures can result in neurologic deficits and avoidable pain, so it is important for clinicians to reach prompt diagnostic decisions. There are no validated decision aids for determining which trauma patients warrant TL-spine imaging. OBJECTIVE: Our aim was to quantify the diagnostic accuracy of the injury mechanism, physical examination, associated injuries, clinical decision aids, and imaging for evaluating blunt TL-spine trauma patients. METHODS: A search strategy for studies including adult blunt TL-spine trauma using PubMed, Embase, Scopus, CENTRAL, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov was performed. Excluded studies lacked data to construct 2 × 2 tables, were duplicates, were not primary research, did not focus on blunt trauma, examined associated injuries without any utility in identifying TL-spine injuries, only studied cervical-spine fractures, were non-English, had a pediatric setting, or were cadaver/autopsy reports. Risk of bias was assessed using the Quality Assessment Tool for Diagnostic Accuracy Studies. Diagnostic predictors were analyzed with a meta-analysis of sensitivity, specificity, and likelihood ratios. RESULTS: In blunt trauma patients in the emergency department, the weighted pretest probability of a TL-spine fracture was 15%. The estimates for detection of TL-spine fractures with plain film were: positive likelihood ratio (+LR) = 25.0 (95% confidence interval [CI] 4.1-152.2; I2 = 94%; p < 0.001) and negative likelihood ratio (-LR) = 0.43 (95% CI 0.32-0.59; I2 = 84%; p < 0.001), and for computed tomography (CT) were: +LR = 81.1 (95% CI 14.1-467.9; I2 = 87%; p < 0.001) and -LR = 0.04 (95% CI 0.02-0.08; I2 = 23%; p = 0.26). CONCLUSIONS: CT is more accurate than plain films for detecting TL-spine fractures. Injury mechanism, physical examination, and associated injuries alone are not accurate to rule-in or rule-out TL-spine fractures.

Clinical Decision Rules in the Evaluation and Management of Adult Gastrointestinal Emergencies.

Although abdominal pain is a common chief complaint in the emergency department, only 1 in 6 patients with abdominal pain are diagnosed with a gastrointestinal (GI) emergency. These patients often undergo extensive testing as well as hospitalizations to rule out an acute GI emergency and there is evidence that not all patients benefit from such management. Several clinical decision rules (CDRs) have been developed for the diagnosis and management of patients with suspected acute appendicitis and upper GI bleeding to identify those patients who may safely forgo further testing or hospital admission. Further validation studies demonstrating the superiority of these CDRs over contemporary practice are needed.

Cardiac arrest survivors lost to follow-up after 3-Months, 6-Months and 1-Year.

BACKGROUND: Long-term assessment of global functional outcomes in cardiac arrest (CA) survivors allows for evaluation of acute care practices and referral to rehabilitation services. Given that many post-CA patients are lost to follow-up (LTFU), we explored whether these patients are systematically different from those who complete follow-up based on demographic, resuscitation and outcome characteristics. METHODS: We conducted a prospective cohort study of 168 English-speaking CA survivors between 9/25/2016 and 5/31/2018. We measured demographic data and global functional outcomes using Modified Rankin Scale (mRS), and Cerebral Performance Category (CPC) in-person at hospital discharge, and via telephone at 3-, 6-months, and 1-year. We compared patients LTFU (e.g., failure to contact or refused to follow-up) with those contacted. Patients who were hospitalized, in a rehabilitation facility, missed by the research team, or dead were considered not eligible for follow-up. RESULTS: Of the 116 patients eligible for follow-up at 3-months, the majority completed follow-up (n = 69; 59.5%) and 47 (40.5%) were LTFU. Conversely, at 6-months and 1-year, fewer subjects were assessed (42% and 47%) compared to those who were LTFU (58% and 53%), respectively. At 3-months, LTFU patients were younger, unmarried, and had longer ICU stay. At 6-months and 1-year, LTFU patients were primarily male, had a non-shockable primary rhythm, and non-cardiac arrest etiologies. CONCLUSIONS: Over one-third of patients are LTFU during the first year after CA, and differences emerged for demographics and characteristics of the event. Future research should account for the informative, non-random distribution of patients LTFU.

The Caenorhabditis elegans ekl (enhancer of ksr-1 lethality) genes include putative components of a germline small RNA pathway.

A canonical Ras-ERK signaling pathway specifies the fate of the excretory duct cell during Caenorhabditis elegans embryogenesis. The paralogs ksr-1 and ksr-2 encode scaffolding proteins that facilitate signaling through this pathway and that act redundantly to promote the excretory duct fate. In a genomewide RNAi screen for genes that, like ksr-2, are required in combination with ksr-1 for the excretory duct cell fate, we identified 16 "ekl" (enhancer of ksr-1 lethality) genes that are largely maternally required and that have molecular identities suggesting roles in transcriptional or post-transcriptional gene regulation. These include the Argonaute gene csr-1 and a specific subset of other genes implicated in endogenous small RNA processes, orthologs of multiple components of the NuA4/Tip60 histone acetyltransferase and CCR4/NOT deadenylase complexes, and conserved enzymes involved in ubiquitination and deubiquitination. The identification of four small RNA regulators (csr-1, drh-3, ego-1, and ekl-1) that share the Ekl phenotype suggests that these genes define a functional pathway required for the production and/or function of particular germline small RNA(s). These small RNAs and the other ekl genes likely control the expression of one or more regulators of Ras-ERK signaling that function at or near the level of kinase suppressor of Ras (KSR).

A novel gain-of-function mutant of the cyclic GMP-dependent protein kinase egl-4 affects multiple physiological processes in Caenorhabditis elegans.

cGMP-dependent protein kinases are key intracellular transducers of cell signaling. We identified a novel dominant mutation in the C. elegans egl-4 cGMP-dependent protein kinase (PKG) and show that this mutation causes increased normal gene activity although it is associated with a reduced EGL-4 protein level. Prior phenotypic analyses of this gain-of-function mutant demonstrated a reduced longevity and a reduced feeding behavior when the animals were left unperturbed. We characterize several additional phenotypes caused by increased gene activity of egl-4. These phenotypes include a small body size, reduced locomotion in the presence of food, a pale intestine, increased intestinal fat storage, and a decreased propensity to form dauer larvae. The multiple phenotypes of egl-4 dominant mutants are consistent with an instructive signaling role of PKG to control many aspects of animal physiology. This is among the first reported gain-of-function mutations in this enzyme of central physiological importance. In a genetic screen we have identified extragenic suppressors of this gain-of-function mutant. Thus, this mutant promises to be a useful tool for identifying downstream targets of PKG.

The impact of cardiac dysfunction on acute respiratory distress syndrome and mortality in mechanically ventilated patients with severe sepsis and septic shock: an observational study.

PURPOSE: Acute respiratory distress syndrome (ARDS) is associated with significant mortality and morbidity in survivors. Treatment is only supportive, therefore elucidating modifiable factors that could prevent ARDS could have a profound impact on outcome. The impact that sepsis-associated cardiac dysfunction has on ARDS is not known. MATERIALS AND METHODS: In this retrospective observational cohort study of mechanically ventilated patients with severe sepsis and septic shock, 122 patients were assessed for the impact of sepsis-associated cardiac dysfunction on incidence of ARDS (primary outcome) and mortality. RESULTS: Sepsis-associated cardiac dysfunction occurred in 44 patients (36.1%). There was no association of sepsis-associated cardiac dysfunction with ARDS incidence (p= 0.59) or mortality, and no association with outcomes in patients that did progress to ARDS after admission. Multivariable logistic regression demonstrated that higher BMI was associated with progression to ARDS (adjusted OR 11.84, 95% CI 1.24 to 113.0, p= 0.02). CONCLUSIONS: Cardiac dysfunction in mechanically ventilated patients with sepsis did not impact ARDS incidence, clinical outcome in ARDS patients, or mortality. This contrasts against previous investigations demonstrating an influence of nonpulmonary organ dysfunction on outcome in ARDS. Given the frequency of ARDS as a sequela of sepsis, the impact of cardiac dysfunction on outcome should be further studied.

Restoration of Glucose Counterregulation by Islet Transplantation in Long-standing Type 1 Diabetes.

Patients with long-standing type 1 diabetes (T1D) may exhibit defective glucose counterregulation and impaired hypoglycemia symptom recognition that substantially increase their risk for experiencing severe hypoglycemia. The purpose of this study was to determine whether intrahepatic islet transplantation improves endogenous glucose production (EGP) in response to hypoglycemia in T1D patients experiencing severe hypoglycemia. We studied longitudinally subjects (n = 12) with ∼30 years, disease duration before and 6 months after intrahepatic islet transplantation using stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-(2)H2-glucose and compared the results with those from a nondiabetic control group (n = 8). After islet transplantation, HbA1c was normalized, and time spent while hypoglycemic (<70 mg/dL) was nearly abolished as indicated by continuous glucose monitoring. In response to insulin-induced hypoglycemia, C-peptide (absent before transplant) was appropriately suppressed, glucagon secretion was recovered, and epinephrine secretion was improved after transplantation. Corresponding to these hormonal changes, the EGP response to insulin-induced hypoglycemia, which was previously absent, was normalized after transplantation, with a similar effect seen for autonomic symptoms. Because the ability to increase EGP is ultimately required to circumvent the development of hypoglycemia, these results provide evidence that intrahepatic islet transplantation can restore glucose counterregulation in long-standing T1D and support its consideration as treatment for patients with hypoglycemia unawareness experiencing severe hypoglycemia.

Comparative Effectiveness Research: Alternatives to "Traditional" Computed Tomography Use in the Acute Care Setting.

Computed tomography (CT) scanning is an essential diagnostic tool and has revolutionized care of patients in the acute care setting. However, there is widespread agreement that overutilization of CT, where benefits do not exceed possible costs or harms, is occurring. The goal was to seek consensus in identifying and prioritizing research questions and themes that involve the comparative effectiveness of "traditional" CT use versus alternative diagnostic strategies in the acute care setting. A modified Delphi technique was used that included input from emergency physicians, emergency radiologists, medical physicists, and an industry expert to achieve this.

Mechanical ventilation and acute lung injury in emergency department patients with severe sepsis and septic shock: an observational study.

OBJECTIVES: The objectives were to characterize the use of mechanical ventilation in the emergency department (ED), with respect to ventilator settings, monitoring, and titration and to determine the incidence of progression to acute lung injury (ALI) after admission, examining the influence of factors present in the ED on ALI progression. METHODS: This was a retrospective, observational cohort study of mechanically ventilated patients with severe sepsis and septic shock (June 2005 to May 2010), presenting to an academic ED with an annual census of >95,000 patients. All patients in the study (n = 251) were analyzed for characterization of mechanical ventilation use in the ED. The primary outcome variable of interest was the incidence of ALI progression after intensive care unit (ICU) admission from the ED and risk factors present in the ED associated with this outcome. Secondary analyses included ALI present in the ED and clinical outcomes comparing all patients progressing to ALI versus no ALI. To assess predictors of progression to ALI, significant variables in univariable analyses at a p ≤ 0.10 level were candidates for inclusion in a bidirectional, stepwise, multivariable logistic regression analysis. RESULTS: Lung-protective ventilation was used in 68 patients (27.1%) and did not differ based on ALI status. Delivered tidal volume was highly variable, with a median tidal volume delivered of 8.8 mL/kg ideal body weight (IBW; interquartile range [IQR] = 7.8 to 10.0) and a range of 5.2 to 14.6 mL/kg IBW. Sixty-nine patients (27.5%) in the entire cohort progressed to ALI after admission to the hospital, with a mean (±SD) onset of 2.1 (±1) days. Multivariable logistic regression analysis demonstrated that a higher body mass index (BMI), higher Sequential Organ Failure Assessment (SOFA) score, and ED vasopressor use were associated with progression to ALI. There was no association between ED ventilator settings and progression to ALI. Compared to patients who did not progress to ALI, patients progressing to ALI after admission from the ED had an increase in mechanical ventilator duration, vasopressor dependence, and hospital length of stay (LOS). CONCLUSIONS: Lung-protective ventilation is uncommon in the ED, regardless of ALI status. Given the frequency of ALI in the ED, the progression shortly after ICU admission, and the clinical consequences of this syndrome, the effect of ED-based interventions aimed at reducing the sequelae of ALI should be investigated further.