An Exploratory Analysis of Physical Examination Subtypes in Pediatric Athletes With Concussion.

OBJECTIVE: Pediatric athletes with concussion present with a variety of impairments on clinical assessment and require individualized treatment. The Buffalo Concussion Physical Examination is a brief, pertinent clinical assessment for individuals with concussion. The purpose of this study was to identify physical examination subtypes in pediatric athletes with concussion within 2 weeks of injury that are relevant to diagnosis and treatment. DESIGN: Secondary analysis of a published cohort study and clinician consensus. SETTING: Three university-affiliated sports medicine centers. PARTICIPANTS: Two hundred seventy children (14.9 ± 1.9 years). INDEPENDENT VARIABLES: Orthostatic intolerance, horizontal and vertical saccades, smooth pursuits, vestibulo-ocular reflex, near-point convergence, complex tandem gait, neck range of motion, neck tenderness, and neck spasm. MAIN OUTCOME MEASURES: Correlations between independent variables were calculated, and network graphs were made. k-means and hierarchical clustering were used to identify clusters of impairments. Optimal number of clusters was assessed. Results were reviewed by experienced clinicians and consensus was reached on proposed subtypes. RESULTS: Physical examination clusters overlapped with each other, and no optimal number of clusters was identified. Clinician consensus suggested 3 possible subtypes: (1) visio-vestibular (horizontal and vertical saccades, smooth pursuits, and vestibulo-ocular reflex), (2) cervicogenic (neck range of motion and spasm), and (3) autonomic/balance (orthostatic intolerance and complex tandem gait). CONCLUSIONS: Although we identified 3 physical examination subtypes, it seemed that physical examination findings alone are not enough to define subtypes that are both statistically supported and clinically relevant, likely because they do not include symptoms, assessment of mood or cognitive problems, or graded exertion testing.

Vps18 contributes to phagosome membrane integrity in Mycobacterium tuberculosis-infected macrophages.

Mycobacterium tuberculosis (Mtb) has evolved to be exquisitely adapted to survive within host macrophages. The capacity to damage the phagosomal membrane has emerged as central to Mtb virulence. While Mtb factors driving membrane damage have been described, host factors that repair that damage to contain the pathogen remain largely unknown. We used a genome-wide CRISPR screen to identify novel host factors required to repair Mtb-damaged phagosomal membranes. Vacuolar protein sorting-associated protein 18 (Vps18), a member of the HOPS and CORVET trafficking complexes, was among the top hits. Vps18 colocalized with Mtb in macrophages beginning shortly after infection, and Vps18-knockout macrophages demonstrated increased damage of Mtb-containing phagosomes without impaired autophagy. Mtb grew more robustly in Vps18-knockout cells, and the first-line anti-tuberculosis antibiotic pyrazinamide was less effective. Our results identify Vps18 as required for phagosomal membrane integrity in Mtb-infected cells and suggest that modulating phagosome integrity may hold promise for improving the efficacy of antibiotic treatment for TB.

Nationwide Analysis of Hospital Admissions Prior to Hartmann's Procedure for Acute Diverticulitis.

INTRODUCTION: Diverticular disease is one of the most common gastrointestinal diseases that require hospital admission. This study aims to identify trends in prior hospital admissions for patients that ultimately require a Hartmann's procedure for complicated diverticulitis. METHODS: The Nationwide Readmissions Database for 2010-2014 was queried for all patients aged 18 years or older admitted with an ICD-9 code for colonic diverticulitis and end colostomy creation. Patients with prior hospital admissions were identified. The primary outcome was mortality after Hartmann's procedure. Secondary outcomes were prior hospital admission and previous percutaneous drain placement. Multivariable logistic regression was performed to control for confounding factors for each outcome and results were weighted for national estimates. RESULTS: There were 90,162 patients admitted with complicated diverticulitis requiring end colostomy creation. Prior hospital admissions were found in 28.1% (n = 25,307) and 14.4% (n = 12,947) had a previous percutaneous drain placed during a prior admission. The overall mortality rate was 5.9% (n = 5314) after Hartman's procedure. The mortality rate for patients with prior hospital admissions was 8.7% (P < .001), and the mortality rate for patients with previous percutaneous drain placement was 4.3% (P < .001). After controlling for confounding factors including comorbidities, patients with prior admission had an increased risk of mortality (OR 1.48 [1.40-1.58], P < .001) and patients with previous percutaneous drain placement had a decreased risk of mortality (OR .66 [.60-.72], P < .001). CONCLUSIONS: Hospitalizations for complications of diverticulitis are a costly burden to our healthcare system. By identifying those patients at high risk for readmission and emergency surgery, perioperative outcomes may be improved.

Under the Microscope: The Evolution of Surgical Loupes.

Fine motor movements of the surgeon's hands are limited by the resolution of the eye. Surgical loupes have allowed the profession of surgery to surpass this threshold. This is a review of the historical milestones that lead up to the development of the modern-day loupes. We explore the Greco-Roman history of the magnifying lens, its subsequent application to corrective eyewear centuries later, and the multiple ground-breaking advancements of the compound lens microscope. Moreover, we review the development of pre-modern loupes as each iteration improved through time. The aim of this historical review is to kindle an appreciation for the millennia of development that led to such instrumental modern-day technology.

The Evolution of Bariatric Surgery-From Sewing Lips to Constructing the Sleeve.

Bariatric surgery remains the most durable weight loss option to address morbid obesity, providing lasting reduction of debilitating chronic comorbidities. This is a review of the historical milestones that led up to the development of this surgical practice. We explore perceptions and interventions for obesity as early as the 10th century, as well as pre-modern surgical perceptions and advancements in foregut and obesity surgery. Additionally, we recount select social and surgical landmarks in the modern bariatric era. The aim of this review is to reflect on and appreciate the centuries of progress that have led to such an instrumental branch of risk reductive surgery.

Student Perspectives on Implementing Stop the Bleed Training into Medical School Curriculum.

BACKGROUND: Following the Hartford Consensus guidelines and recommendations, third-year medical students from a single institution were offered an optional Stop the Bleed (STB) training course in August 2018. The aim of this study was to assess medical students' confidence in performing bleeding control techniques and teaching others after completing the STB course. The secondary goal was to assess student perception on integrating mandatory STB training into the medical school curriculum. MATERIALS AND METHODS: A 24-question survey using a 4-point Likert scale was administered to all medical students who completed STB training. Students were anonymously asked to self-report their confidence in performing bleeding control techniques, training others after STB training, and their perception on integrating STB training into medical school curriculum. RESULTS: After completing the STB course, 95% of students were comfortable applying a tourniquet, 92% of students were confident in packing wounds, and 99% of students could apply direct pressure to wounds to stop bleeding. Overall, 94% of students reported that STB training would be helpful for their clinical rotations. CONCLUSION: These results demonstrate that medical students are positively impacted by Stop the Bleed courses and validate that the implementation of mandatory STB courses into medical school curriculum will improve medical students' knowledge and skills for hemorrhage control.

Bile Leak following Laparoscopic Cholecystectomy due to Perforated Duodenal Ulcer in Patient with Roux-en-Y Gastric Bypass.

Perforated ulcers of the excluded stomach or duodenum are exceedingly rare in patients who have undergone Roux-en-Y gastric bypass surgery. The diagnosis of perforated ulcer after Roux-en-Y gastric bypass remains challenging as there is often absence of free air or contrast extravasation from the biliopancreatic limb. We present a patient with signs and symptoms of acute cholecystitis. Laparoscopic cholecystectomy was complicated by postoperative bile leak. EDGE procedure was performed to access the remnant stomach and endoscopic evaluation revealed a perforated ulcer in the posterior duodenal bulb. Although unusual, in patients with bariatric surgery and upper abdominal pain, differential diagnosis including perforated ulcer of the biliopancreatic limb must be considered and early surgical exploration is essential.

Combined Myocardial Bridge and Coronary Vessel Disease Requiring Coronary Artery Bypass Grafting and Myotomy of the Myocardial Bridge.

Myocardial bridging (MB) describes a band of myocardium that covers the epicardial surface of the coronary artery. This band can vary both in thickness and distance to which it covers the artery. It is broadly classified as superficial or deep, depending on the thickness of the covering muscle layer. It can be asymptomatic, or it could present with different complications. Reported complications have included ischemia and acute coronary syndromes, coronary spasm, ventricular septal rupture, and arrhythmias. MB is most commonly found in the middle segment of the left anterior descending (LAD) coronary artery. There is controversy with regard to therapy for symptomatic patients who are refractory to medical management. Percutaneous coronary intervention and surgical myotomy (unroofing) have been proposed; yet, each one has its pros and cons. MB can be associated with the development of atherosclerosis proximal to the MB segment in the involved coronary artery, and patients can present having both pathologies. We present a case series of six patients with atherosclerotic coronary lesions requiring coronary artery bypass grafting (CABG) with an accidental perioperative finding of MB, which required myotomy.

Clinical use of high mobility group box 1 and the receptor for advanced glycation end products in the prognosis and risk stratification of heart failure: a literature review.

Heart failure (HF) is a clinical syndrome that represents the end stage of heart disease and remains the leading cause of morbidity and mortality worldwide. As heart failure mortality rates remain elevated, additional biomarkers that facilitate early detection or risk stratification in HF is of particularly great interest. High mobility group box 1 (HMGB1) and receptor for advanced glycation end products (RAGE) cause the activation of intracellular signaling, gene expression, and production of inflammatory cytokines and have been linked to many inflammatory disease states such as diabetes mellitus and atherosclerosis. Few studies have investigated their role in the pathophysiology of HF and any significant correlation remains uncertain. Review of the available literature discussing HMGB1 and RAGE clinical values as independent prognostic variables in HF resulted in the inclusion of 11 studies, which enrolled a total of 2025 heart failure patients. Overall, the data suggests a statistically significant positive correlation between RAGE and HF, with increasing RAGE levels associated with increasing New York Heart Association (NYHA) functional class of heart failure. HMGB1 correlations were not as extensively studied, but there is evidence that both HMGB1 and RAGE have a definite potential as biomarkers for the prognosis and risk stratification of HF patients.

Metal oxide based multisensor array and portable database for field analysis of antioxidants.

We report a novel chemical sensing array based on metal oxide nanoparticles as a portable and inexpensive paper-based colorimetric method for polyphenol detection and field characterization of antioxidant containing samples. Multiple metal oxide nanoparticles with various polyphenol binding properties were used as active sensing materials to develop the sensor array and establish a database of polyphenol standards that include epigallocatechin gallate, gallic acid, resveratrol, and Trolox among others. Unique charge-transfer complexes are formed between each polyphenol and each metal oxide on the surface of individual sensors in the array, creating distinct optically detectable signals which have been quantified and logged into a reference database for polyphenol identification. The field-portable Pantone/X-Rite© CapSure® color reader was used to create this database and to facilitate rapid colorimetric analysis. The use of multiple metal-oxide sensors allows for cross-validation of results and increases accuracy of analysis. The database has enabled successful identification and quantification of antioxidant constituents within real botanical extractions including green tea. Formation of charge-transfer complexes is also correlated with antioxidant activity exhibiting electron transfer capabilities of each polyphenol. The antioxidant activity of each sample was calculated and validated against the oxygen radical absorbance capacity (ORAC) assay showing good comparability. The results indicate that this method can be successfully used for a more comprehensive analysis of antioxidant containing samples as compared to conventional methods. This technology can greatly simplify investigations into plant phenolics and make possible the on-site determination of antioxidant composition and activity in remote locations.

Inhibition of protein phosphatase 2A radiosensitizes pancreatic cancers by modulating CDC25C/CDK1 and homologous recombination repair.

PURPOSE: To identify targets whose inhibition may enhance the efficacy of chemoradiation in pancreatic cancer and thus improve survival, we conducted an siRNA library screen in pancreatic cancer cells. We investigated PPP2R1A, a scaffolding subunit of protein phosphatase 2A (PP2A) as a lead radiosensitizing target. EXPERIMENTAL DESIGN: We determined the effect of PP2A inhibition by genetic (PPP2R1A siRNA) and pharmacologic (LB100, a small molecule entering phase I clinical trials) approaches on radiosensitization of Panc-1 and MiaPaCa-2 pancreatic cancer cells both in vitro and in vivo. RESULTS: PPP2R1A depletion by siRNA radiosensitized Panc-1 and MiaPaCa-2 cells, with radiation enhancement ratios of 1.4 (P < 0.05). Likewise, LB100 produced similar radiosensitization in pancreatic cancer cells, but minimal radiosensitization in normal small intestinal cells. Mechanistically, PPP2R1A siRNA or LB100 caused aberrant CDK1 activation, likely resulting from accumulation of the active forms of PLK1 (pPLK1 T210) and CDC25C (pCDC25C T130). Furthermore, LB100 inhibited radiation-induced Rad51 focus formation and homologous recombination repair (HRR), ultimately leading to persistent radiation-induced DNA damage, as reflected by γ-H2AX expression. Finally, we identified CDC25C as a key PP2A substrate involved in LB100-mediated radiosensitization as depletion of CDC25C partially reversed LB100-mediated radiosensitization. In a mouse xenograft model of human pancreatic cancer, LB100 produced significant radiosensitization with minimal weight loss. CONCLUSIONS: Collectively, our data show that PP2A inhibition radiosensitizes pancreatic cancer both in vitro and in vivo via activation of CDC25C/CDK1 and inhibition of HRR, and provide proof-of-concept evidence that PP2A is a promising target for the improvement of local therapy in pancreatic cancer.

Renal, cardiovascular and endocrine responses of fetal sheep at 0.8 of gestation to an infusion of amino acids.

Amino acid infusions increase renal blood flow (RBF) and glomerular filtration rate (GFR) and stimulate tubular reabsorption in adults. To characterize the effects of amino acids on fetal renal haemodynamics, tubular sodium reabsorption, acid-base homeostasis and plasma renin levels, 11 chronically catheterized fetal sheep aged 121 +/- 1 days (term ~150 days) were infused I.V. for 4 h with alanine, glycine, proline and serine (0.1, 0.1, 0.06 and 0.06 mmol min(-1), respectively) in 0.15 M saline at 0.165 ml min(-1). Eight control fetuses were given saline. During amino acid infusion, plasma amino acid levels increased up to 20-fold (P < 0.005). GFR increased by 50 +/- 8 % (P < 0.001); there was only a small transient increase in RBF. Proximal fractional sodium reabsorption fell from 74.6 +/- 2.9 to 55.5 +/- 5.4 % (P < 0.005). Distal sodium delivery increased, but a smaller percentage of this distal sodium load was reabsorbed (P < 0.005). Thus fractional sodium reabsorption fell from 95.5 +/- 0.9 to 81.4 +/- 2.0 % (P < 0.005). There was a large diuresis, natriuresis, kaliuresis and increase in osmolar excretion (P < 0.005). Plasma sodium and chloride concentrations fell (P < 0.005). Plasma osmolality did not change. Plasma renin levels fell (P < 0.05), cortisol levels increased (P < 0.05), and there was a compensated metabolic acidosis. Thus the fetal sheep kidney demonstrated a remarkable functional capacity to respond to amino acid infusion. The increase in filtration fraction and the lack of an increase in RBF suggest that efferent arteriolar vasoconstriction occurred, a very different response from the renal vasodilatation seen in adult animals.