Emergency medicine (EM) can safely manage geriatric trauma patients sustaining ground level falls: Fostering EM autonomy while safely offloading a busy trauma service.

OBJECTIVE: Limited data exists regarding different specialties care of geriatric (>74 years-old) trauma patients (GTPs). We created a "Tier-III" designation for ground-level fall (GLF) GTPs to be managed by EM, with a trauma consult as needed. MATERIALS AND METHODS: A single-center comparison of PRE (1/1/2013-4/30/2016) versus POST (5/1/2016-11/30/2019) Tier-III GTP GLFs. The primary outcome was mortality. Secondary outcomes included admissions, trauma bay procedures and length of stay (LOS). RESULTS: 1,652 patients (314-PRE vs. 1,338-POST) were included. The admission rate was lower in the POST (56.9% vs. 88.9%, p < 0.001) cohort. There were no differences in LOS or trauma bay procedures between cohorts (p > 0.05). On multivariable analysis there was similar associated risk of mortality between groups (p = 0.68). CONCLUSION: The associated risk of mortality was similar between GLF GTP cohorts managed initially by EM and trauma surgeons, however the admission rate was lower in the POST group suggesting EM management may improve hospital bed utilization.

Comparing Point-of-care-ultrasound (POCUS) to MRI for the Diagnosis of Medial Compartment Knee Injuries.

BACKGROUND: Ultrasound has become an increasingly utilized tool for the imaging of the musculoskeletal system, especially for imaging the components of the knee. Even though MRI is touted as being the golden standard for identifying knee pathologies, the use of ultrasound has gained popularity in this field given its ability for rapid diagnosis. This study aims to investigate the efficacy of point-of-care ultrasound (POCUS) to diagnose injuries to the medial knee compartment when compared to magnetic resonance imaging (MRI). METHODS: This was a prospective, observational study conducted at an orthopedic outpatient clinic. Prospective patients with medial knee pain scheduled for an MRI of the knee were evaluated by POCUS prior to the MRI. Sonographic findings were then compared to MRI results to assess correlation. RESULTS: Nine patients were enrolled in the study. Median age was 53 years and eight were male (89%). POCUS demonstrated 100% sensitivity and 50% specificity for medial meniscus tear and 67% sensitivity and 83% specificity for medial collateral ligament (MCL) tear. CONCLUSION: Ultrasound may have a role as the initial rapid imaging modality in patients with suspected medial meniscus or MCL tears as it is highly sensitive, and it may serve as an effective screening tool for patients with both acute and chronic knee pain.

The total synthesis of K-252c (staurosporinone) via a sequential C-H functionalisation strategy.

A synthesis of the bioactive indolocarbazole alkaloid K-252c (staurosporinone) via a sequential C-H functionalisation strategy is reported. The route exploits direct functionalisation reactions around a simple arene core and comprises of two highly-selective copper-catalysed C-H arylations, a copper-catalysed C-H amination and a palladium-catalysed C-H carbonylation, which build up the structural complexity of the natural product framework.

Ultrasound in medical education: listening to the echoes of the past to shape a vision for the future.

PURPOSE: Ultrasound in medical education has seen a tremendous growth over the last 10-20 years but ultrasound technology has been around for hundreds of years and sound has an even longer scientific history. The development of using sound and ultrasound to understand our body and our surroundings has been a rich part of human history. From the development of materials to produce piezoelectric conductors, ultrasound has been used and improved in many industries and medical specialties. METHODS: As diagnostic medical ultrasound has improved its resolution and become more portable, various specialties from radiology, cardiology, obstetrics and more recently emergency, critical care and proceduralists have found the added benefits of using ultrasound to safely help patients. The past advancements in technology have established the scaffold for the possibilities of diagnostic ultrasound's use in the present and future. RESULTS: A few medical educators have integrated ultrasound into medical school while a wealth of content exists online for learning ultrasound. Twenty-first century learners prefer blended learning where material can be reviewed online and personalize the education on their own time frame. This material combined with hands-on experience and mentorship can be used to develop learners' aptitude in ultrasound. CONCLUSIONS: As educators embrace this ultrasound technology and integrate it throughout the medical education journey, collaboration across specialties will synthesize a clear path forward when needs and resources are paired with vision and a strategic plan.

Immunotherapy trial as diagnostic test in evaluating patients with presumed autoimmune gastrointestinal dysmotility.

BACKGROUND: Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under-recognized etiology. We evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility (AGID). METHODS: Twenty-three subjects evaluated at the Mayo Clinic for suspected AGID (August 2006-February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy-manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6-12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies). KEY RESULTS: Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra-intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re-evaluated had scintigraphic evidence of improvement. The majority of responders who were re-evaluated had improvement in autonomic testing (six of seven) or manometry (two of two). CONCLUSIONS & INFERENCES: This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy.

Comparison of the novel quantitative ARMS assay and an enriched PCR-ASO assay for K-ras mutations with conventional cytology on endobiliary brush cytology from 312 consecutive extrahepatic biliary stenoses.

BACKGROUND: Extrahepatic biliary stenosis (EBS) has malignant and benign causes. Patients with EBS are at risk of having or developing malignancy. Accurate diagnostic tests for early detection and surveillance are needed. The sensitivity of biliary cytology for malignancy is low. K-ras mutation analysis on brush cytology is a valuable adjunct, but specificity is low. A quantitative test for K-ras mutations has been developed: the amplification refractory mutation system (ARMS). AIM: To assess the test characteristics and additional value of ARMS in diagnosing the cause of EBS. METHODS: Brush samples from endoscopic retrograde cholangiopancreatography were collected from 312 patients with EBS. K-ras mutation analysis was performed using ARMS-allele specific amplification was coupled with real time fluorescent detection of PCR products. Results were compared with conventional cytology and K-ras mutation analysis using allele specific oligonucleotide (ASO) hybridisation, and evaluated in view of the final diagnosis. RESULTS: The test characteristics of ARMS and ASO largely agreed. Sensitivity for detecting malignancy was 49% and 42%, specificity 93% and 88%, and positive predictive value (PPV) 96% and 91%, respectively. The sensitivity of ARMS and cytology combined was 71%, and PPV was 93%. The specificity of ARMS could be increased to 100% by setting limits for the false positives, but reduced sensitivity from 49% to 43%. CONCLUSIONS: ARMS can be considered supplementary to conventional cytology, and comparable to ASO in diagnosing malignant EBS. A specificity of 100% can be achieved with ARMS, which should be considered in the surveillance of patients at risk for pancreatic cancer.

Day-to-day reproducibility of anorectal sensorimotor assessments in healthy subjects.

The reproducibility of tests widely utilized to assess anorectal sensorimotor functions is not well established. Our aims were to assess the intra-individual day-to-day reproducibility of these parameters in healthy subjects. Anal sphincter pressures were assessed by perfusion manometry on two separate days in 19 healthy subjects. Rectal pressure-volume (p-v) curves and sensory thresholds were assessed in 12/19 subjects by inflating a highly compliant polyethylene balloon from 0 to 32 mmHg in 4 mmHg steps. Subjects also rated intensity of perception by visual analogue scale (VAS) during phasic distentions 8, 16 and 24 mmHg above operating pressure, in randomized sequence. Resting and squeeze anal pressures and rectal compliance were highly reproducible (r(s) > or = 0.7) in the same subject on separate days. Pressure thresholds for urgency appeared less reproducible than thresholds for initial perception and the desire to defecate. VAS scores were highly reproducible only during the 24-mmHg distention. Thus, anal pressures and rectal compliance are highly reproducible within healthy subjects on separate days, while sensory thresholds are reproducible to a variable degree, dependent on the intensity of stimulation and the perception being assessed.

Further evidence to support the melanocytic origin of MDA-MB-435.

BACKGROUND/AIMS: Until recently, the cell line MDA-MB-435 was widely accepted as originating from a breast cancer. However, microarray derived data have suggested that this cell line may in fact originate from an occult melanoma. This study was designed to investigate this hypothesis further. METHODS: Quantitative reverse transcription polymerase chain reaction and immunohistochemistry were used to investigate the tissue of origin of two sublines of MDA-MB-435 (MDA-MB-435 S and MDA-MB-435 HGF). The expression of a panel of genes typical of breast cells or melanocytes was analysed. RESULTS: The MDA-MD-435 cell lines expressed none of the genes characteristic of breast cancer cells but did express several genes commonly expressed by melanocytes. CONCLUSIONS: These results strongly suggest that MDA-MB-435 is indeed of melanoma origin.

Decision rule and utility of routine urine toxicology screening of trauma patients.

The objective of this study was to determine the impact of urine drug screening of major trauma victims on patient care and derive a decision rule for selective screening. Retrospective chart review of 170 trauma patients at a Level I Trauma Center, certified by the American College of Surgeons, was undertaken. The decision rule was developed by Classification and Regression Tree (CART) analysis to maximize sensitivity, with secondary attention to specificity. Eighty-nine percent of trauma patients were screened, while 26.0% had positive tests for illicit drugs. Serum ethanol was positive in 31.2%, over the legal limit of 0.08 g/dl. Both a legally intoxicated ethanol level and positive illicit drug screen were found in 11.0%. Additionally, 42.5% of patients with a positive illicit drug screen were also intoxicated (blood alcohol level above legal limit). Conversely, 35.4% of legally intoxicated patients also had positive illicit screens. Drug treatment referral occurred in 17.5% of positive drug screens. For urgent surgery, median time to drug screen result was 117 min, while median time to operation was 110 min. Of operative patients, 57% had the drug screen result recorded on the chart at any time, but only 14.3% of illicit screens were noted in the anaesthesia record. For all patients with and without operations, 71.1% had the result noted on the chart. We derived a 'low risk rule' to identify most patients with positive illicit drug screens (95% sensitivity, 55% specificity, 66% positive and 93% negative predictive values; accuracy 74%), while limiting the number of unnecessary tests. The rule avoids screening 48% of patients, missing only 5% of true positives. It is concluded that urine screening for illicit drugs in trauma patients can be performed selectively according to a decision rule based on demographics, mechanism of injury and time of presentation. This rule, which captures most positive screens while eliminating screening in low risk patients, could result in significant cost savings. Only prospective validation of these rules in patient populations of other trauma centres will offer confidence that the decision points are valid. Urine drug screening infrequently affected patient management or resulted in drug treatment referral in our sample. We call for increased vigilance in recording results and referring patients for treatment.

Vitreous-induced modulation of integrins in retinal pigment epithelial cells: effects of fibroblast growth factor-2.

Growth in the presence of vitreous results in transformation of human RPE cells from an epithelioid to a fibroblast-like appearance and leads to an elevation of the expression of alpha(5) and alpha(2) integrins, while the level of alpha(3) integrin is reduced. These changes are inhibited by the presence of FGF-2. Vitreous treatment increases mobility, as does antibody neutralization of FGF-2 or antibody blockade of FGF receptors. The vitreous-induced rise in mobility depends on an increase in alpha(5) integrin expression since it is inhibited by anti-alpha(5) integrin antibodies. Expression of alpha(5) integrin as a result of infection of RPE cells with an alpha(5) integrin-encoding adenovirus induced morphological transformation and an increase in mobility similar to that seen with vitreous. It is concluded that a decrease in FGF-2 plays an important role in vitreous-induced alterations of RPE cell morphology, integrin expression and mobility. High FGF-2 levels prevent at least some of the increased mobility of RPE cells induced by vitreous. This is mediated via extracellular FGF-2 binding to FGF receptor(s) since antibodies to FGF-2 or to its receptor(s) mimic the effects of vitreous. Changes in mobility and morphology involve altered alpha(5) integrin expression since mobility is blocked by antibodies against these proteins while elevated alpha(5) integrin expression increases mobility and leads to morphological changes.

A prospective evaluation of lipoprotein-associated phospholipase A(2) levels and the risk of future cardiovascular events in women.

OBJECTIVES: We sought to determine prospectively whether lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) was a predictor of future cardiovascular risk in women. BACKGROUND: Inflammatory markers may help predict cardiovascular risk. Lp-PLA(2) levels have recently been hypothesized to be an independent predictor of cardiovascular risk in hypercholesterolemic men. METHODS: We conducted a prospective, nested case-control study among 28,263 apparently healthy middle-aged women to assess the risk of death from coronary heart disease, non-fatal myocardial infarction, and stroke associated with baseline levels of Lp-PLA(2) over a mean follow-up of three years. RESULTS: In univariate analysis, mean levels of Lp-PLA(2) correlated strongly with low-density lipoprotein cholesterol (r = 0.51; p = 0.0001), were lower among women currently using hormone replacement therapy (mean 0.98 mg/l vs. 1.23 mg/l; p = 0.0001) and were significantly higher at baseline among cases (n = 123) than controls (n = 123) (mean 1.20 mg/l vs. 1.05 mg/l; p = 0.016). However, the predictive value of Lp-PLA(2) was markedly attenuated after adjustment for these and other cardiovascular risk factors. Specifically, the multivariate relative risks of future cardiovascular events for women in the lowest (referent) to highest quartiles of Lp-PLA(2) were 1.00, 0.75, 0.64 and 1.17, respectively (all p values non-significant). In contrast, the adjusted relative risks of future cardiovascular events for each increasing quartile of C-reactive protein (another marker of low-grade inflammation) were 1.00, 1.78, 2.02 and 4.66, respectively (p-value for trend = 0.002). Inclusion of Lp-PLA(2) levels did not significantly attenuate this latter observation. CONCLUSIONS: In contrast to prior data among hyperlipidemic men, the current data suggest that Lp-PLA(2) is not a strong predictor of future cardiovascular risk among unselected women.

Trabecular eccentricity and bone adaptation.

It is well established that bones functionally adapt by mechanisms that control tissue density, whole bone geometry, and trabecular orientation. In this study, we propose the existence of another such powerful mechanism, namely, trabecular eccentricity, i.e. non-central placement of trabecular bone within a cortical envelope. In the human femoral neck, trabecular eccentricity results in a thicker cortical shell on the inferior than superior aspect. In an overall context of expanding understanding of bone adaptation, the goal of this study was to demonstrate the biomechanical significance of, and provide a mechanistic explanation for, the relationship between trabecular eccentricity and stresses in the human femoral neck. Using composite beam theory, we showed that the biomechanical effects of eccentricity during a habitual loading situation were to increase the stress at the superior aspect of the neck and decrease the stress at the inferior aspect, resulting in an overall protective effect. Further, increasing eccentricity had a stress-reducing effect equivalent to that of increasing cortical thickness or increasing trabecular modulus. We conclude that an asymmetric placement of trabecular bone within a cortical bone envelope represents yet another mechanism by which whole bones can adapt to mechanical demands.

Barriers to help seeking for mental disorders in a rural impoverished population.

This study examined barriers to seeking mental health care reported by individuals in a rural impoverished population, by screening 646 randomly selected adults for depression, anxiety, and alcohol abuse. Respondents who screened positive were randomly assigned to one of three groups: (1) no intervention, (2) an educational intervention alone, or (3) the educational intervention in the presence of a significant other. Those who screened positive for disorders cited barriers to care at significantly higher rates than respondents who screened negative. Respondents who received the educational intervention endorsed several barriers at significantly lower rates in the follow-up telephone call (subsequent to the intervention) than in the original interview (prior to the intervention). Virtually all respondents in a subsample of 142 subjects (99.3%) said they would seek mental health care if they thought mental health services would help them.

Outcome in cardiac arrest patients found to have cardiac standstill on the bedside emergency department echocardiogram.

UNLABELLED: Patients presenting in cardiac arrest frequently have poor outcomes despite heroic resuscitative measures in the field. Many emergency medical systems have protocols in place to stop resuscitative measures in the field; however, further predictors need to be developed for cardiac arrest patients brought to the emergency department (ED). OBJECTIVE: To examine the predictive value of cardiac standstill visualized on bedside ED echocardiograms during the initial presentations of patients receiving cardiopulmonary resuscitation (CPR). METHODS: The study took place in a large urban community hospital with an emergency medicine residency program and a high volume of cardiac arrest patients. As part of routine care, all patients arriving with CPR in progress were subject to immediate and brief subxiphoid or parasternal cardiac ultrasound examination. This was followed by brief repeat ultrasound examination during the resuscitation when pulses were checked. A 2.5-MHz phased-array probe was used for imaging. Investigators filled out standardized data sheets. Examinations were taped for review. Statistical analysis included descriptive statistics, positive and negative predictive values, and likelihood ratios. RESULTS: One hundred sixty-nine patients were enrolled in the study. One hundred thirty-six patients had cardiac standstill on the initial echocardiogram. Of these, 71 patients had an identifiable rhythm on monitor. No patient with sonographically identified cardiac standstill survived to leave the ED regardless of his or her initial electrical rhythm. Cardiac standstill on echocardiogram resulted in a positive predictive value of 100% for death in the ED, with a negative predictive value of 58%. CONCLUSIONS: Patients presenting with cardiac standstill on bedside echocardiogram do not survive to leave the ED regardless of their electrical rhythms. This finding was uniform regardless of downtime. Although larger studies are needed, this may be an additional marker for cessation of resuscitative efforts.

K-ras point mutation detection in lung cancer: comparison of two approaches to somatic mutation detection using ARMS allele-specific amplification.

BACKGROUND: The use of sensitive molecular techniques to detect rare cells in a population is of increasing interest to the molecular pathologist, but detection limits often are poorly defined in any given molecular assay. We combined the approaches of real-time quantitative PCR with ARMS(TM) allele-specific amplification in a novel assay for detecting mutant K-ras sequences in clinical samples. METHODS: ARMS reactions were used to detect seven commonly occurring mutations in the K-ras oncogene. These mutations produce amino acid changes in codon 12 (Gly to Ala, Arg, Asp, Cys, Ser, or Val) and codon 13 (Gly to Asp). A control reaction was used to measure the total amount of amplifiable K-ras sequence in a sample so that the ratio of mutant to wild-type sequence could be measured. Quantitative data were confirmed for a selection of samples by an independent cloning and sequencing method. The assay was used to analyze 82 lung tumor DNA samples. RESULTS: The assay detected K-ras mutations in 44% of adenocarcinomas, which is equivalent to frequencies reported in the literature using ultrasensitive techniques. Forty-six percent of squamous carcinomas were also positive. The ratio of mutant sequence in the tumor DNA samples was 0.04-100%. CONCLUSIONS: The assay is homogeneous, with addition of tumor DNA sample being the only step before results are generated. The quantitative nature of the assay can potentially be used to define the analytical sensitivity necessary for any specified diagnostic application of K-ras (or other) point mutation detection.

Physician versus computer knowledge of potential drug interactions in the emergency department.

INTRODUCTION: Proliferation of Food and Drug Administration-approved drugs makes it impossible for emergency medicine (EM) faculty to stay current on potential interactions between drugs, and with diseases, laboratory tests, and ethanol. A computer database may augment physician knowledge. OBJECTIVES: To compare the performance of EM faculty and an "expert" emergency physician (EP) with that of a criterion standard computer database in identifying potential drug interactions, and to report the incidence of drug-ethanol and drug-laboratory test interactions. METHODS: This was a retrospective review of 276 emergency department charts for drug, ethanol, lab, and medical history. Evaluation by both EM faculty and an "expert" EP of patient history was done to identify potential interactions, and comparison with the Micromedex Drug-Reax database for potential interactions (graded minor, moderate, or major) was made. Clinical significance of potential interactions was judged by a second EM faculty member. RESULTS: Seventeen percent of the patients had potential drug-drug interactions, and 25% of these were judged to be clinically significant. Up to 52% of the patients had potential drug-ethanol interactions, while 38% of the patients could have potential drug-lab interactions. Sensitivity, specificity, and positive and negative predictive values of the EM faculty for potential drug-drug interactions compared with the computer were poor, at 14%, 58%, 6%, and 23%, respectively. The corresponding values for the "expert" EP were 25%, 86%, 26%, and 85%. The "expert" EP was statistically better than the EM faculty, but still less sensitive and predictive than the computer. CONCLUSIONS: A computer can aid the physician in avoiding potential drug interactions. Prospective validation of these findings should be done.

Efficacy of a modified polymerase chain reaction assay for detection of Ehrlichia canis infection.

Detection of Ehrlichia canis in acutely infected and convalescent dogs is important for effective treatment and control. However, accurate detection has been difficult to achieve, in part because dogs that have been treated therapeutically often remain seropositive for extended periods. A new method, polymerase chain reaction (PCR) assay using biotinylated E. canis-specific primers (PCR-BP), was developed for detection of E. canis. Four dogs experimentally infected with E. canis by intravenous inoculation of whole blood from carrier dogs and 2 naturally infected convalescent carriers were used to compare the specificity and sensitivity of the new method with that of microscopy/blood smear evaluation, serologic test, and conventional PCR assay using E. canis-specific primers. In experimentally infected animals, infection was detected as early as 7 days post-exposure using PCR-BP. Although the 2 naturally infected dogs were positive by serologic test and PCR-BP, both were negative by conventional PCR. Results suggest that the new method is a sensitive assay for detection of E. canis infection. In addition, results were obtained more rapidly than with other PCR-based assays.

Coordinate regulation of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 expression in human vascular smooth muscle cells.

The expression of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) by human vascular smooth muscle cells (SMC) was monitored as a function of the phenotypic modulation in vitro. Cell phenotype was manipulated by varying serum concentration and cell density. Synthetic phenotype was characterized by a minimum expression of the contractile proteins and a maximal proliferation rate. Contractile phenotype was quiescent and expressed a maximal level of contractile proteins. Synthetic cells expressed the highest levels of both MMP-1 and TIMP-1 and displayed maximal collagenolytic activity. No significant change was detected in MMP-2 expression or catalytic activity. Enzyme immunoassays revealed that MMP-1 expression fell by 77+/-2.4-95+/-0.5%, and that of TIMP-1 by 34+/-0.5-59+/-1.9%, as the cells acquired a contractile phenotype. The level of the MMP-1/TIMP-1 complex was similarly reduced by 78+/-2.9-85+/-1.6%. These data demonstrate that the expression of MMP-1 and TIMP-1 are coordinately regulated with SMC phenotype.