Air Medical Blood Transfusion as a Trigger of Massive Transfusion Protocol.

Air medical services can improve access to blood products at the point of injury. Studies have shown that early activation of mass transfusion protocols (MTPs) can improve the survival of trauma patients by up to 25%. There are several scoring systems to guide early activation, but the use of a single criterion has been elusive. Our study sought to determine if air medical administration of blood products was a risk factor for massive transfusion activation and utilization of prehospital vital signs for calculation of the shock index. In our retrospective study, we evaluated adult trauma patients transfused by helicopter emergency medical services (HEMS) and as a control all patients in our institution receiving the MTP. Our study found HEMS blood transfusion was not a reliable trigger for MTP, although the sample size may have limited our findings. We found that HEMS care resulted in an overall reduction in the volume of transfusion and an improvement in hemodynamic parameters upon trauma center arrival. HEMS transfusion and a higher rate of tranexamic acid administration may have contributed to these findings. Of note, the assessment of blood consumption score and shock index were nonspecific in the study populations.

Trends in Drug Tests among Children: A 22-Year Retrospective Analysis.

There are several pathophysiological outcomes associated with substance abuse including metabolic disbalance, neurodegeneration, and disordered redox. Drug use in pregnant women is a topic of great concern due to developmental harm which may occur during gestation and the associated complications in the neonate after delivery. We sought to determine what the trajectory of drug use is like in children aged 0-4 years and mothers of neonates. Urine drug screen (UDS) results were obtained of our target demographic during 1998-2011 and 2012-2019 from LSU Health Sciences Center in Shreveport (LSUHSC-S). Statistical analysis was performed using R software. We observed an increase in cannabinoid-positive UDS results in both Caucasian (CC) and African American (AA) groups between 1998-2011 and 2012-2019 periods. Cocaine-positive UDS results decreased in both cohorts. CC children had higher UDS positive results for opiates, benzodiazepines, and amphetamines, while AA children had a higher percentage for illicit drugs such as cannabinoids and cocaine. Neonate's mothers had similar UDS trends to that in children during 2012-2019. Overall, while percentage of positive UDS results for both AA and CC 0-4 year old children started to decline for opiate, benzodiazepine, and cocaine during 2012-2019, cannabinoid- and amphetamine (CC)-positive UDS steadily increased. These results suggest a shift in the type of drug use by mothers from opiates, benzodiazepines, and cocaine to cannabinoids and/or amphetamines. We also observed that 18-year-old females who tested positive for opiates, benzodiazepine, or cocaine had higher than average chances of testing positive for cannabinoids later in life.

Improved Healthcare Access Reduces Requirements for Surgery in Indigent IBD Patients Using Biologic Therapy: A 'Safety-Net' Hospital Experience.

Low socioeconomic status (SES) is associated with greater morbidity and increased healthcare resource utilization (HRU) in IBD. We examined whether a financial assistance program (FAP) to improve healthcare access affected outcomes and HRU in a cohort of indigent IBD patients requiring biologics. IBD patients (>18 years) receiving care at a 'safety-net' hospital who initiated biologics as outpatients between 1 January 2010 and 1 January 2019 were included. Patients were divided by FAP status. Patients without FAP had Medicare, Medicaid, or commercial insurance. Primary outcomes were steroid-free clinical remission at 6 and 12 months. Secondary outcomes were surgery, hospitalization, and ED utilization. Multivariate logistic regression was used to calculate odds ratio (OR) and 95% confidence interval (CI). Decision tree analysis (DTA) was also performed. We included 204 patients with 258 new biologic prescriptions. FAP patients had less complex Crohn's disease (50.7% vs. 70%, p = 0.033) than non-FAP patients. FAP records indicated fewer prior surgeries (19.6% vs. 38.4% p = 0.003). There were no statistically significant differences in remission rates, disease duration, or days between prescription and receipt of biologics. In multivariable logistic regression, adjusting for baseline demographics and disease severity variables, FAP patients were less likely to undergo surgery (OR: 0.28, 95% CI [0.08−0.91], p = 0.034). DTA suggests that imaging utilization may shed light on surgical differences. We found FAP enrollment was associated with fewer surgeries in a cohort of indigent IBD patients requiring biologics. Further studies are needed to identify interventions to address healthcare disparities in IBD.

A retrospective analysis of calcium levels in pediatric trauma patients.

Traumatic injury is a major cause of morbidity and mortality in pediatric patients. Hemorrhage is a known but treatable component of these outcomes. Evidence exists that major trauma patients are at high risk for hypocalcemia but the rate of pediatric occurrence is not documented. The purpose of this study was to determine the incidence of hypocalcemia in pediatric trauma patients, as well as to investigate any correlation between hypocalcemia and the need for transfusion and operative intervention. After IRB approval a retrospective analysis was conducted of all pediatric trauma patients seen in our Adult Level One, Pediatric Level Two trauma center. Significance testing for mortality was performed using Pearson's χ2 test. For the remaining numeric variables, association was determined one-way analysis of variance (when comparing all classes) or Welch's two-sample t-test (when comparing subsets based on calcium or mortality). In any event, significance was determined using α=0.05. A total of 2,928 patients were identified, 1623 were excluded, primarily due to incomplete data. Patients were predominantly male following blunt trauma. Initial calcium levels were 8.73 mg/dL, 95% CI [4-10.9] and 8.97 mg/dL, 95% CI [6.42-13.1] when correcting for albumin levels. Acute declines were noted when comparing initial and corrected serum calcium levels in patients requiring transfusion (7.99 mg/dL and 8.72 mg/dL) and operative intervention (8.54 mg/dL and 8.91 mg/dL). 456 (34.9%) patients required operative intervention, 138 (10.6%) required transfusion and 29 (2.2%) required massive transfusion. Patients in our cohort arrived with calcium values on the low end of normal, with a trend towards hypocalcemia if operative intervention or blood transfusion was required. This has been previously associated with increased mortality. Patients requiring operative intervention and transfusion are at increased risk for hypocalcemia and recognition of this potential is key for improved outcomes.

Plasma hydrogen sulfide: A biomarker of Alzheimer's disease and related dementias.

While heart disease remains a common cause of mortality, cerebrovascular disease also increases with age, and has been implicated in Alzheimer's disease and related dementias (ADRD). We have described hydrogen sulfide (H2 S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. We hypothesize that plasma H2 S and its metabolites also relate to vascular and cognitive dysfunction in ADRD. We used analytical biochemical methods to measure plasma H2 S metabolites and MRI to evaluate indicators of microvascular disease in ADRD. Levels of total H2 S and specific metabolites were increased in ADRD versus controls. Cognition and microvascular disease indices were correlated with H2 S levels. Total plasma sulfide was the strongest indicator of ADRD, and partially drove the relationship between cognitive dysfunction and white matter lesion volume, an indicator of microvascular disease. Our findings show that H2 S is dysregulated in dementia, providing a potential biomarker for diagnosis and intervention.

Experimental Evaluation of the Elson Test Efficiency Following Central Slip Injury.

Purpose: The purpose of this article is to explore the amount of work, quantitated by flexion and extension cycles, that is needed to obtain a positive Elson test following a central slip injury. Methods: Thirteen frozen cadaveric fingers from individuals with an average age of 79.6 years were used. Testing was performed by imposing sinusoidal displacement of the 2 tendons, with loads ranging from 30 N to 2 N at 1 Hz. Following transection to the central slip, each finger was cycled 1,000 times using the same protocol adopted for the control. Following 100, 200, 300, and 1,000 cycles, we measured the extension angles of the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints from the flexed position and the distance between landmarks of the extensor apparatus and simulated an Elson test. Results: In both the fingers, the range of motion of the metacarpophalangeal and distal interphalangeal joints measured in the controls remained unchanged, whereas the range of motion of the proximal interphalangeal joint was significantly reduced immediately after central slip transection. Combining both ring and middle fingers, for a displacement of 5 mm, the force measured in the control (1.05 ± 0.69 N) increased to the value of 2.36 ± 0.97 N at the 1,000th cycle. Although the middle finger has shown a significant difference in force at 100 cycles following central slip transection, 200 cycles were needed to observe a difference on the ring finger. Conclusions: In controlled conditions, there is a variation in resistance to flexion of the distal interphalangeal joint. However, the amplitude of the forces is so small that they are likely imperceptible clinically. Delayed testing should be considered to increase the sensitivity of the test or in patients experiencing pain. Type of study/level of evidence: Diagnostic V.

Risk Stratification in Post-ERCP Pancreatitis: How Do Procedures, Patient Characteristics and Clinical Indicators Influence Outcomes?

BACKGROUND: Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains common, and severe complications are associated with ERCP. There is no previous study detailing the effect of race and gender in a US-based population on risk of PEP. METHODS: Data were collected on 269 "first-performed" consecutive ERCPs followed by division by race (White vs. African-American) and sex (Female vs. Male). A total of 53 probable risk factors were evaluated by uni- and multivariate analysis followed by outcomes expressed as an odds ratio (OR) (with a 95% confidence interval, 95% CI). Finally, a principal component analysis was performed to construct a risk prediction model for PEP, which can be used by clinicians at bedside. RESULTS: After analyzing the risk factors based on race and gender-based groups, Caucasian males with PEP are more likely to have prior history of pancreatitis (p = 0.009), lower hemoglobin (p = 0.02)/blood urea nitrogen (BUN) (p = 0.01)/creatinine before ERCP (p = 0.07) and lower BUN (p = 0.01)/creatinine after ERCP (p = 0.07), while Caucasian females with PEP are more likely to have higher white blood cell (WBC) count before ERCP (p = 0.08) and lower amylase (p = 0.10)/bilirubin (p = 0.09)/aspartate aminotransferase (AST) after ERCP (p = 0.08). African-American males with PEP are more likely to have lower weight (p = 0.001)/smaller height (p = 0.0005)/lower alkaline phosphatase (p = 0.002)/AST (p = 0.04)/alanine transaminase (ALT) (p = 0.03) before ERCP and lower alkaline phosphatase (p = 0.002)/AST (p = 0.01)/ALT (p = 0.004) after ERCP, while African-American females with PEP are more likely to have prior history of pancreatitis (p = 0.004)/higher lipase before (p = 0.0001) and after (p = 0.05) ERCP along with increased risk with pancreatic duct cannulation (p = 0.0001) and injection (p = 0.0001)/biliary sphincterotomy (p = 0.0001). Importantly, prior history of ERCP, elevated AST after ERCP, and BUN prior to ERCP were found to be important clinical features predicting post-ERCP pancreatitis. To our knowledge, this is a first known attempt at developing a risk scoring system for PEP in a US population with decision tree learning. CONCLUSIONS: It is very evident that both patient and procedure-related risk factors vary by race and gender in the US population, leading to the development of a new risk assessment tool for PEP that can be used in clinical practice. We need to follow up with a larger prospective study to validate this novel race and gender-based risk scoring system for PEP.

Incidence of Hypocalcemia and Role of Calcium Replacement in Major Trauma Patients Requiring Operative Intervention.

Traumatic injury is a major cause of morbidity and mortality, and hemorrhage is a primary factor. Evidence exists that major trauma patients are at high risk of hypocalcemia. The purpose of this study was to determine the incidence and rate of calcium replacement in major trauma patients requiring operative intervention, and to investigate the impact of hypocalcemia on rate of transfusion and mortality. A retrospective analysis was conducted of all top-tier trauma activations presenting to our institution during a 12-month period. A total of 638 activations were identified; 441 were excluded, primarily because of lack of operative intervention. Patients were predominantly male following blunt trauma. The mean initial calcium level was 8.11 mg/dL and 8.64 mg/dL, correcting for albumin levels. An acute decline was noted when initial serum calcium levels and intraoperative calcium levels were compared (7.51 mg/dL). Intraoperative ionized calcium levels were on the low end of the normal range, and 28.42% received supplemental calcium. Patients in our cohort arrived hypocalcemic, which has been previously associated with increased mortality. Patients requiring operative intervention are at increased risk of hypocalcemia. Recognition of this potential is key for improved outcomes.

(-)-Oleocanthal as a Dual c-MET-COX2 Inhibitor for the Control of Lung Cancer.

Lung cancer (LC) represents the topmost mortality-causing cancer in the U.S. LC patients have overall poor survival rate with limited available treatment options. Dysregulation of the mesenchymal epithelial transition factor (c-MET) and cyclooxygenase 2 (COX2) initiates aggressive LC profile in a subset of patients. The Mediterranean extra-virgin olive oil (EVOO)-rich diet already documented to reduce multiple malignancies incidence. (-)-Oleocanthal (OC) is a naturally occurring phenolic secoiridoid exclusively occurring in EVOO and showed documented anti-breast and other cancer activities via targeting c-MET. This study shows the novel ability of OC to suppress LC progression and metastasis through dual targeting of c-MET and COX-2. Western blot analysis and COX enzymatic assay showed significant reduction in the total and activated c-MET levels and inhibition of COX1/2 activity in the lung adenocarcinoma cells A549 and NCI-H322M, in vitro. In addition, OC treatment caused a dose-dependent inhibition of the HGF-induced LC cells migration. Daily oral treatment with 10 mg/kg OC for 8 weeks significantly suppressed the LC A549-Luc progression and prevented metastasis to brain and other organs in a nude mouse tail vein injection model. Further, microarray data of OC-treated lung tumors showed a distinct gene signature that confirmed the dual targeting of c-MET and COX2. Thus, the EVOO-based OC is an effective lead with translational potential for use as a prospective nutraceutical to control LC progression and metastasis.

A Retrospective Study of Transfusion Requirements in Trauma Patients Receiving Tranexamic Acid.

The Military Application of Tranexamic Acid in Trauma Emergency Resuscitation Study (MATTERs) and Clinical Randomisation of an Antifibrinolytic in Significant Haemorrhage-2 (CRASH-2) studies demonstrate that tranexamic acid (TXA) reduces mortality in patients with traumatic hemorrhage. However, their results, conducted in foreign countries and U.S. military soldiers, provoke concerns over generalizability to civilian trauma patients in the United States. We report the evaluation of patient outcomes and transfusion requirements following treatment with TXA by a civilian air medical program. We conducted a retrospective chart review of trauma patients transported by air service to a Level 1 trauma center. For the purposes of intervention evaluation, patients meeting this criterion for the 2 years (2012-2014) prior to therapy implementation were compared with patients treated during the 2-year study period (2014-2016). Goals were to evaluate morbidity, mortality, transfusion requirements, and length of stay. During the review, 52 control (non-TXA) and 43 study (TXA) patients were identified as meeting inclusion criteria. Patients in the control group were found to be less acute, which correlated with shorter hospitals stays. There was reduced mortality for patients receiving TXA in spite of their increased acuity and decreased likelihood of survival. Trauma patients from this cohort study receiving TXA demonstrate decreased mortality in spite of increased acuity. This increased acuity is associated with increased transfusion requirements. Future research should evaluate patient selection with concern for fibrinolysis and provider bias. Randomized controlled trial is needed to evaluate the role of TXA administration in the United States.

GatewayNet: a form of sequential rule mining.

BACKGROUND: The gateway hypothesis (and particularly the prediction of developmental stages in drug abuse) has been a subject of protracted debate since the 1970s. Extensive research has gone into this subject, but has yielded contradictory findings. We propose an algorithm for detecting both association and causation relationships given a discrete sequence of events, which we believe will be useful in addressing the validity of the gateway hypothesis. To assess the gateway hypothesis, we developed the GatewayNet algorithm, a refinement of sequential rule mining called initiation rule mining. After a brief mathematical definition, we describe how to perform initiation rule mining and how to infer causal relationships from its rules ("gateway rules"). We tested GatewayNet against data for which relationships were known. After constructing a transaction database using a first-order Markov chain, we mined it to produce a gateway network. We then discuss various incarnations of the gateway network. We then evaluated the performance of GatewayNet on urine drug screening data collected from the emergency department at LSU Health Sciences Center in Shreveport. A de-identified database of urine drug screenings ordered by the department between August 1998 and June 2011 was collected and then restricted to patients having at least one screening succeeding their first positive drug screening result. RESULTS: In the synthetic data, a chain of gateway rules was found in the network which demonstrated causation. We did not find any evidence of gateway rules in the empirical data, but we were able to isolate two documented transitions into benzodiazepine use. CONCLUSIONS: We conclude that GatewayNet may show promise not only for substance use data, but other data involving sequences of events. We also express future goals for GatewayNet, including optimizing it for speed.

Urine Drug Screen Trends from 1998 through 2011 Among Emergency Department Patients Treated in a University Teaching Hospital.

The emergency department (ED) at Louisiana State University-Health Science Center in Shreveport (LSUHSC-S) serves an urban population with a large rural catchment area. This study focuses on demographic variables in substance abuse trends in this region based on urine drug screen (UDS) results. A database of de-identified UDSs ordered in the ED at LSUHSC-S between 1998 and 2011 was analyzed. Samples were tested for the presence of amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, 3,4-methylenedioxymethamphetamine (MDMA), methadone, methamphetamine, opiates, phencyclidine, and propoxyphene. The patient population was categorized by age group, gender, and race. The majority of tests were performed on African-American and Caucasian patients ages 18 to 54 followed by the 0 to 11-year-old group. Of the drugs tested, cannabinoids represented the highest percentage of positive results in both the African-American and Caucasian populations. Opiates returned the highest percent of positive results among all prescription drugs. The Caucasian population predominated in positive tests for prescription drugs (opiates and benzodiazepines), while the African-American population predominated in results positive for illicit drugs (cannabinoids and cocaine). The increasing presence of opiates and cannabinoids, particularly in very young patients, should prompt policy makers and healthcare providers to develop intervention strategies to protect the most vulnerable populations.

What and how are EM residents being taught to respond to the next disaster?

OBJECTIVE: Disasters, both natural and man-made, have become commonplace and emergency physicians serve on the front line. Residency may be the only time that emergency physicians are exposed to a disaster, through training, until one happens in their department; therefore, it is critical to provide residents with appropriate and timely disaster education. The goal of this study was to assess the current status of disaster education in emergency medicine (EM) residencies in the United States. METHODS: A list of disaster topics was generated by reviewing disaster literature and validated by subject matter experts. Between May and December 2016, the authors conducted a national computerized survey of the 229 US EM residencies listed by the American Osteopathic Association and the American Medical Association. It focused on the methods of instruction and amount of time devoted to each topic. RESULTS: Of the 229 eligible residency programs, 183 (79.9 percent) completed the survey. Of those, 98.9 percent report teaching disaster management topics. Nine of 18 disaster medicine topics were taught at >60 percent of responding programs. The most common topics were emergency management principles and mass casualty triage, while the least common was hazard vulnerability analysis. The most common method of instruction was lecture (68.5 percent) and the least common methods were journal club and field exercises. CONCLUSIONS: Broad education in disaster medicine is provided in most US EM residencies. Standardization of topics is still lacking and would be beneficial to encourage comprehensive education. Addressing the educational gaps and curriculum methodology changes identified in this survey would increase curriculum standardization.

Genome-wide DNA methylation as an epigenetic consequence of Epstein-Barr virus infection of immortalized keratinocytes.

UNLABELLED: The oral cavity is a persistent reservoir for Epstein-Barr virus (EBV) with lifelong infection of resident epithelial and B cells. Infection of these cell types results in distinct EBV gene expression patterns regulated by epigenetic modifications involving DNA methylation and chromatin structure. Regulation of EBV gene expression relies on viral manipulation of the host epigenetic machinery that may result in long-lasting host epigenetic reprogramming. To identify epigenetic events following EBV infection, a transient infection model was established to map epigenetic changes in telomerase-immortalized oral keratinocytes. EBV-infected oral keratinocytes exhibited a predominantly latent viral gene expression program with some lytic or abortive replication. Calcium and methylcellulose-induced differentiation was delayed in EBV-positive clones and in clones that lost EBV compared to uninfected controls, indicating a functional consequence of EBV epigenetic modifications. Analysis of global cellular DNA methylation identified over 13,000 differentially methylated CpG residues in cells exposed to EBV compared to uninfected controls, with CpG island hypermethylation observed at several cellular genes. Although the vast majority of the DNA methylation changes were silent, 65 cellular genes that acquired CpG methylation showed altered transcript levels. Genes with increased transcript levels frequently acquired DNA methylation within the gene body while those with decreased transcript levels acquired DNA methylation near the transcription start site. Treatment with the DNA methyltransferase inhibitor, decitabine, restored expression of some hypermethylated genes in EBV-infected and EBV-negative transiently infected clones. Overall, these observations suggested that EBV infection of keratinocytes leaves a lasting epigenetic imprint that can enhance the tumorigenic phenotype of infected cells. IMPORTANCE: Here, we show that EBV infection of oral keratinocytes led to CpG island hypermethylation as an epigenetic scar of prior EBV infection that was retained after loss of the virus. Such EBV-induced epigenetic modification recapitulated the hypermethylated CpG island methylator phenotype (CIMP) observed in EBV-associated carcinomas. These epigenetic alterations not only impacted gene expression but also resulted in delayed calcium and methylcellulose-induced keratinocyte differentiation. Importantly, these epigenetic changes occurred in cells that were not as genetically unstable as carcinoma cells, indicating that EBV infection induced an epigenetic mutator phenotype. The impact of this work is that we have provided a mechanistic framework for how a tumor virus using the epigenetic machinery can act in a "hit-and-run" fashion, with retention of epigenetic alterations after loss of the virus. Unlike genetic alterations, these virally induced epigenetic changes can be reversed pharmacologically, providing therapeutic interventions to EBV-associated malignancies.