Performance of the APACHE II and SOFA Scores in Diabetic Ketoacidosis.

Accurate prediction of severity and mortality in diabetic ketoacidosis (DKA) is important for allocation of resources. The APACHE II and SOFA scores are used to predict mortality in critically ill patients, however neither has been tested exclusively in DKA. We sought to determine if these scoring systems can accurately predict mortality in patients with DKA. This was an observational study of patients presenting to an urban tertiary care center with a diagnosis of DKA. Adult patients (age ≥ 18 years) with glucose > 250 mg/dL, bicarbonate ≤ 20 mEg/L, an anion gap ≥ 16 mEg/L, pH ≤ 7.30, and urine ketones were included. Predicted mortality based upon APACHE II and SOFA scores were compared to observed mortality. A total of 50 patients were included. There was no observed mortality in our population. The median APACHE II score was 10 (IQR: 6, 15) which predicted a mortality of 15% and the median SOFA score was 1 (IQR: 0, 2) which predicted a mortality of 0%. In summary, we found the APACHE II illness severity score does not accurately predict mortality in a population of patients with DKA, while the SOFA score appears to predict mortality in the same population.

Variation in SOFA (Sequential Organ Failure Assessment) Score Performance in Different Infectious States.

INTRODUCTION: In this study, we investigated whether the Sequential Organ Failure Assessment (SOFA) score performance differs based on the type of infection among patients admitted to the intensive care unit (ICU) with infection. MATERIALS AND METHODS: Single-center, retrospective study of adult ICU patients admitted with infection between January 2008 and April 2018 at an urban tertiary care center. Patients were uniquely classified into different infection types based on International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes. Infection types included were pneumonia, meningitis, bacteremia, cellulitis, cholangitis/cholecystitis, intestinal and diarrheal disease, endocarditis, urinary tract infection (UTI), and peritonitis. The SOFA score performance and mortality in relation to SOFA score were compared across infection types. RESULTS: A total of 12 283 patients were included. Of these, 50.6% were female and the median age was 70 years (interquartile range: 57-82). The most common infection types were pneumonia (32.2%) and UTI (31.0%). Overall, 1703 (13.9%) patients died prior to hospital discharge. The median baseline SOFA score (within 24 hours of ICU admission) for the cohort was 5 (3-8). Patients with peritonitis had the highest median SOFA score, 7 (4-9), and patients with cellulitis and UTI had the lowest median SOFA score, 4 (2-7). The SOFA score discrimination to predict mortality was highest among patients with endocarditis (area under the receiver operating characteristic [AUC]: 0.79, 95% CI: 0.69-0.90) and lowest for patients with isolated bacteremia (AUC: 0.59, 95% CI: 0.49-0.70). Observed mortality by quartile of SOFA score differed substantially across infection types. CONCLUSIONS: Type of infection is an important consideration when interpreting the SOFA score. This is relevant as SOFA emerges as an important tool in the definition and prognostication of sepsis.

Characteristics and outcomes of patients receiving high flow nasal cannula therapy prior to mechanical ventilation in COVID-19 respiratory failure: A prospective observational study.

BACKGROUND: Treatment strategies for acute hypoxic respiratory failure secondary to coronavirus 2019 disease (COVID-19) had significant variation early in the pandemic. We sought to determine if patients treated with high flow nasal cannula (HFNC) prior to mechanical ventilation had differing outcomes compared to those treated only with conventional oxygen. METHODS: This was a prospective, observational study of patients with COVID-19 admitted to a tertiary care medical center with a diagnosis of acute hypoxic respiratory failure. Adult patients with a positive polymerase chain reaction test for COVID-19 who required mechanical ventilation were included. RESULTS: A total of 91 patients met the inclusion criteria for our study. The mean age was 68.4 years (standard deviation [SD] ± 12) and 58% were male. The mean initial partial pressure of arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio was 152 (SD ± 65) and was not significantly different between the HFNC group and the conventional oxygen strategy group (P = 0.95). The observed mortality rate was 30% in the HFNC group versus 52% in the conventional oxygen strategy group (P = 0.05). The multivariate odds ratio of mortality for patients on HFNC was 0.375 compared to a conventional oxygen strategy (95% confidence interval 0.122-1.151, P = 0.09). CONCLUSIONS: While HFNC appears to be safe as the initial treatment strategy for COVID-19 associated respiratory failure, HFNC did not result in a statistically significant difference in mortality compared to a conventional oxygen strategy. Further studies are needed to confirm these findings.

A National Study of Emergency Thoracotomy for Trauma.

INTRODUCTION: The role of resuscitative thoracotomy in the emergency department (ED) for patients that have suffered severe thoracoabdominal trauma has been the subject of much debate. Most studies that characterize emergency thoracotomy are from urban, academic, and trauma centers. We sought to describe patient and hospital characteristics of a nationally representative sample of ED thoracotomy (EDT). METHODS: The health-care cost and utilization project 2013 National ED Sample (NEDS) and the 2013 National Inpatient Sample (NIS) maintained by the agency for health-care research and quality were used to generate a nationally representative estimate of resuscitative thoracotomies performed in the ED. We obtained patient demographics and clinical characteristics and compared the descriptive statistics of the two datasets. RESULTS: The NEDS dataset identified 124 unsuccessful EDTs, whereas the NIS dataset identified 77 admissions for thoracotomy. When weighted to create a national estimate, these represent 952 emergency thoracotomies performed in the US in 2013. Most were male (82.5% and 88.2% in NEDS and NIS, respectively). In addition, 32.9% and 36.4% in NEDS and NIS, respectively, were between the ages of 20 and 29. The majority of thoracotomies were performed at metropolitan teaching hospitals (64.2% and 75.3%, NEDS and NIS, respectively). The mean total ED charges for patients who had an unsuccessful thoracotomy were $32,664 and the mean total inpatient charges were $141,215. CONCLUSION: Nearly 1000 thoracotomies are performed annually on the day of presentation to U. S. hospitals. Although emergency thoracotomy for trauma is an infrequently performed procedure, it almost always occurs at an urban, high volume, and level I or level II trauma centers.

Akt/protein kinase b and glycogen synthase kinase-3beta signaling pathway regulates cell migration through the NFAT1 transcription factor.

The phosphoinositide 3-kinase (PI3K) pathway regulates a multitude of cellular processes. Deregulation of PI3K signaling is often observed in human cancers. A major effector of PI3K is Akt/protein kinase B (PKB). Recent studies have pointed to distinct roles of Akt/PKB isoforms in cancer cell signaling. Studies have shown that Akt1 (PKBalpha) can attenuate breast cancer cell motility, whereas Akt2 (PKBbeta) enhances this phenotype. Here, we have evaluated the mechanism by which Akt1 blocks the migration of breast cancer cells through the transcription factor NFAT. A major effector of Akt/PKB is glycogen synthase kinase-3beta (GSK-3beta), also a NFAT kinase. Inhibition of GSK-3beta using short hairpin RNA or a selective inhibitor potently blocks breast cancer cell migration concomitant with a reduction in NFAT activity. GSK-3beta-mediated inhibition of NFAT activity is due to proteasomal degradation. Experiments using GSK-3beta mutants, which are unresponsive to Akt/PKB, reveal that inhibition of cell migration by Akt/PKB is mediated by GSK-3beta. These effects are recapitulated at the levels of NFAT degradation by the proteasome. Our studies show that activation of Akt/PKB leads to inactivation of the effector GSK-3beta and the outcome of this signaling event is degradation of NFAT by the proteasome and subsequent inhibition of cell migration.

Vasopressors during adult cardiac arrest: A systematic review and meta-analysis.

AIM: To systematically review the literature on the use of vasopressors during adult cardiac arrest to inform an update of international guidelines. METHODS: PRISMA guidelines were followed. We searched Medline, Embase, Web of Science, CINAHL, and the Cochrane Library for controlled trials and observational studies. The population included adults with cardiac arrest in any setting. Pairs of investigators reviewed studies for relevance, extracted data, and assessed the risk of bias for individual studies. Certainty of evidence was evaluated using GRADE for controlled trials and meta-analyses were performed when at least two studies could be pooled. RESULTS: We included 15 controlled trials and 67 observational studies. The majority of studies included out-of-hospital cardiac arrest only. Meta-analyses were performed for two controlled trials comparing epinephrine to placebo, three comparing vasopressin to epinephrine, and three comparing epinephrine plus vasopressin to epinephrine only. All controlled trials ranged between low to some concern in risk of bias. The certainty of evidence ranged from very low to high. Risk of bias for observational studies was generally critical or serious, largely due to confounding and selection bias. CONCLUSIONS: Controlled trial data suggest that epinephrine improves return of spontaneous circulation, survival to hospital discharge, and 3-month survival in out-of-hospital cardiac arrest. The improvement in short-term outcomes appeared more pronounced for non-shockable rhythms. Differences in long-term neurological outcome did not reach statistical significance, although there was a signal toward improved outcomes. Controlled trial data indicated no benefit from vasopressin with or without epinephrine compared to epinephrine only.

A prospective evaluation of indications for neurological consultation in the emergency department.

BACKGROUND: Recognizing the diverse presentation of neurological conditions that emergency physicians encounter can be challenging, and management of these patients often requires consultation with a neurologist. Accurate diagnosis is critical in neurological emergencies because patient outcomes are often dependent on timely treatment. Our primary objective was to ascertain whether consultant neurologists understood the reason for consultation in the emergency department. METHODS: The authors conducted a prospective study of a non-consecutive sample of 94 patients seen in an academic tertiary care emergency department (ED) who underwent consultation by neurologist over 4 consecutive months. At the time a consult was requested, we independently surveyed the treating ED physician for their differential diagnosis. Neurologists were also queried as to whether there was a clear indication for consultation. We then followed the patients to determine their final diagnosis and outcome. RESULTS: The median age was 57 years (interquartile range 45-78). 45.7 % were male. The clinical reasons for all the consults were 61 % focal symptom, 12 % concern about a specific diagnosis, 9 % radiological finding, 9 % diagnostic ambiguity, and 11 % other. There was no significant difference in the rate of a final neurological diagnosis based on the clinical reason for consult (p = 0.13). In the 17 % of patients for whom the treating neurologist reported a lack of a clear indication for the consultation, 25 % were later admitted to a neurological service, and 69 % ultimately had a neurological diagnosis. CONCLUSIONS: Although patients with neurological emergencies can have diverse presentations, emergency physicians appear to utilize neurologic consultation appropriately. Additionally, nearly 70 % of patients for whom the consultant did not precisely understand the need for the consultation had neurological diagnoses. Time and resource constraints in the ED create challenges in making correct diagnosis.

Collagen I provides a survival advantage to MD-1483 head and neck squamous cell carcinoma cells through phosphoinositol 3-kinase signaling.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has a 50% relapse rate. The tumor microenvironment has been linked to resistance of cancer cells to chemotherapy. We hypothesized that the tumor matrix proteins collagen and fibronectin play protective roles in HNSCC. MATERIALS AND METHODS: We investigated the effects of collagen I, collagen IV and fibronectin on growth, 2-D and 3-D clonogenic potential, resistance to paclitaxel, apoptosis and activation of phosphoinositol-3 kinase (PI3K) in MD-1483 HNSCC cells. RESULTS: Collagen I, collagen IV and fibronectin specifically increased the efficiency of 2-D colony formation through binding integrins α2ß1 and α5ß1, respectively, and provided resistance to paclitaxel-induced colony elimination and apoptosis. Collagen I, but not fibronectin, increased the efficiency of 3-D colony formation and induced resistance to paclitaxel. Activation of protein kinase-B by collagen I was necessary for the protective effect. CONCLUSION: These data support the potential contribution of fibronectin and collagen to chemotherapy resistance in HNSCC, with effects of collagen mediated by PI3K.

Analysis and validation of putative substances involved in fatal poisonings.

Each year, poison control centers throughout the United States respond to over 4 million calls for help in treating individuals exposed to toxic substances. Although most cases develop no or minimal clinical effects, a small proportion of patients who receive medical care for overdoses with poison center consultation expire. When such cases are investigated by a medical examiner, the postmortem toxicology results may show substances other than those considered in the consultation with the poison center. We sought to determine the characteristics of discordance in fatal cases between the toxic substances reported to a regional poison control center and postmortem toxicology results. We conducted a retrospective study of the New Jersey regional poison control center records of all fatal cases between the years 1986 and 2006. Substances reported as putative agents to the poison center were compared to the postmortem toxicology results obtained by the medical examiner. The frequencies and characteristics surrounding discordance were examined. Of the 708 fatal cases reported to our poison center within the study period, complete postmortem toxicological evaluations were available for 206 (29.0%). Comparison of putative agents between information obtained by history and at postmortem evaluation showed discordance in 41 (19.9%). In a substantial number of fatal cases receiving poison center consultation, substances were found at the time of postmortem examination that were not considered in the poison center consultation. The reasons for this discordance may include a lack of thorough history-taking or a cognitive bias to the substances initially reported.