Psychosocial Aspects of Sport-Related Concussion in Youth.

Participation in youth sport is not without the potential for risk including exposure to injury and sport-related concussion (SRC). SRC is an injury that disproportionately affects active youths and carries with it numerous psychological, social, and biological implications. This article aims to (1) examine the scope of the problem that SRC poses for the athletic community, (2) explore the social impact that SRC and media portrayal of this injury has, (3) discuss how this may affect an athlete who has experience SRC and efforts to return to activity, (4) and evaluate a meaningful way to navigate all of these factors with athletes who experience SRC.

KRD (carfilzomib and lenalidomide plus dexamethasone) for the treatment of relapsed or refractory multiple myeloma in the real-life: a retrospective survey in 123 patients.

From April 2016, carfilzomib, in combination with lenalidomide and dexamethasone (KRD), became available for use in the daily practice in Italy for patients with relapsed or refractory multiple myeloma (RRMM). We performed a retrospective survey at 14 different institutions from Southern Italy in order to evaluate patient characteristics and treatment results from an unselected series of patients treated accordingly so far. One hundred and twenty-three consecutive patients were included, with a median of 2 previous lines of therapy (range 1-9) and a median age of 63 years (range 39-82). At the time of analysis, median number of courses administered is 11 (range 1-34), and all patients are evaluable for response. Overall response rate including complete remission, very good partial remission, and partial remission is 85%. After a median follow-up of 27 months, median overall and progression-free survival are 33 and 23 months, respectively. Sixty-three patients are alive and between them, 45 (37%) are in continuous remission. Sixty patients have died (49%), mainly from progressive disease. There were 6 treatment-related deaths (5% of the whole patient population). Overall, hematological and non-hematological toxicity were manageable, mostly on outpatient basis. Arterial hypertension has been observed in 43 cases (35%) but did not lead to treatment interruption. Our data demonstrate that in real life, KRD is highly effective and well tolerated in the majority of patients with RRMM.

Trends in Estimated Thyroid, Salivary Gland, Brain, and Eye Lens Doses From Intraoral Dental Radiography Over Seven Decades (1940 TO 2009).

The purpose of this study is to support retrospective dose estimation for epidemiological studies by providing estimates of historical absorbed organ doses to the brain, lens of the eye, salivary glands, and thyroid from intraoral dental radiographic examinations performed from 1940 to 2009. We simulated organ doses to an adult over 10 y time periods from 1940 to 2009, based on commonly used sets of x-ray machine settings collected from the literature. Simulations to estimate organ dose were performed using personal computer x-ray Monte Carlo software. Overall, organ doses were less than 1 mGy for a single intraoral radiograph for all decades. From 1940 to 2009, doses to the brain, eye lens, salivary glands, and thyroid decreased by 86, 96, 95, and 89%, respectively. Of these four organs, the salivary glands received the highest doses, with values decreasing from about 0.23 mGy in the 1940s to 0.025 mGy in the 2000s for a single intraoral radiograph. Based on simulations using collected historical data on x-ray technical parameters, improvements in technology and optimization of the technical settings used to perform intraoral dental radiography have resulted in a decrease in absorbed dose to the brain, eye lens, salivary glands, and thyroid over the period from 1940 to 2009.

A proposal for a new PhD level curriculum on quantitative methods for drug development.

This paper provides an overview of "Improving Design, Evaluation and Analysis of early drug development Studies" (IDEAS), a European Commission-funded network bringing together leading academic institutions and small- to large-sized pharmaceutical companies to train a cohort of graduate-level medical statisticians. The network is composed of a diverse mix of public and private sector partners spread across Europe, which will host 14 early-stage researchers for 36 months. IDEAS training activities are composed of a well-rounded mixture of specialist methodological components and generic transferable skills. Particular attention is paid to fostering collaborations between researchers and supervisors, which span academia and the private sector. Within this paper, we review existing medical statistics programmes (MSc and PhD) and highlight the training they provide on skills relevant to drug development. Motivated by this review and our experiences with the IDEAS project, we propose a concept for a joint, harmonised European PhD programme to train statisticians in quantitative methods for drug development.

Effects of aging and depression on mnemonic discrimination ability.

Aging and depression have been found to be associated with poorer performance in mnemonic discrimination. In the current study, a two-response format mnemonic similarity test, Cognitive Drug Research MST, was used to compare these effects. Seventy-six participants were tested; with 52 participants in the young group, aged 18-35 years, and 24 participants in the elderly group, aged 55 years or older. Twenty-two young participants and 10 elderly participants met DSM-IV criteria for MDD or dysthymia. Age-related deficits were found for lure identification and speed of response. Differences in speed of responses to lure images were found for younger depressed participants, and depressive symptom severity was found to be negatively associated with lure identification accuracy in the elderly. These findings may be viewed as putative behavioral correlates of decreased pattern separation ability, which may be indicative of altered hippocampal neurogenesis in aging and depression.

The higher prevalence of truncal obesity and diabetes in American than Chinese patients with chronic hepatitis C might contribute to more rapid progression to advanced liver disease.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is the leading cause of cirrhosis and hepatocellular carcinoma (HCC) in the United States (US) and an emerging cause in China. AIM: To compare the clinical characteristics of hepatitis C patients in the US and China, and factors influencing disease stage. METHODS: Prospective study of 2 cohorts of HCV patients recruited at 1 site in the US and 3 sites in China. Standardised questionnaire on risk factors and medical history were used and diagnosis of cirrhosis and HCC was based on pre-defined criteria. RESULTS: One thousand nine hundred and fifty seven patients (1000 US and 957 China) were enrolled. US patients were more likely to be men (61.4% vs 48.5%), older (median age 57 vs 53 years), obese (38.4% vs 16.8%) and diabetic (21.8% vs 10.8%). A significantly higher per cent of US patients had cirrhosis (38.2% vs 16.0%) and HCC (14.1% vs 2.7%). Investigator estimated time at infection in US was 10 years earlier than in Chinese patients but US patients were more likely to have advanced disease even after stratifying for duration of infection. Study site in the US, older age, truncal obesity, diabetes and prior HCV treatment were significant predictors of advanced disease on multivariate analysis. CONCLUSIONS: HCV patients in the US had more advanced liver disease than those in China. We speculate that underlying fatty liver disease may be a major contributor to this difference, and management of glycometabolic abnormalities should occur in parallel with anti-viral therapy to achieve optimal outcomes.

Good for the lung but bad for the liver? Garlic-induced hepatotoxicity following liver transplantation.

WHAT IS KNOWN AND OBJECTIVE: Limited data exist surrounding the metabolism and safety of garlic supplements. CASE DESCRIPTION: A patient with a history of hepatopulmonary syndrome (HPS) and orthotopic liver transplantation was admitted to our surgery transplant service with severe hypoxaemia. The patient was started on high-dose Garlicin Cardio® (Allium sativum) for HPS and soon after had elevated liver function tests. Garlicin Cardio® was discontinued and liver enzymes normalized. A liver biopsy revealed mild periportal cholestatic reaction suggesting potential drug-induced aetiology. WHAT IS NEW AND CONCLUSION: This is the first description of liver injury secondary to garlic supplementation. Therefore, this garlic supplement should be listed as a potential cause of acute drug-induced liver injury.

The Natural History of Severe Acute Liver Injury.

OBJECTIVES: Acute liver failure (ALF) is classically defined by coagulopathy and hepatic encephalopathy (HE); however, acute liver injury (ALI), i.e., severe acute hepatocyte necrosis without HE, has not been carefully defined nor studied. Our aim is to describe the clinical course of specifically defined ALI, including the risk and clinical predictors of poor outcomes, namely progression to ALF, the need for liver transplantation (LT) and death. METHODS: 386 subjects prospectively enrolled in the Acute Liver Failure Study Group registry between 1 September 2008 through 25 October 2013, met criteria for ALI: International Normalized Ratio (INR)≥2.0 and alanine aminotransferase (ALT)≥10 × elevated (irrespective of bilirubin level) for acetaminophen (N-acetyl-p-aminophenol, APAP) ALI, or INR≥2.0, ALT≥10x elevated, and bilirubin≥3.0 mg/dl for non-APAP ALI, both groups without any discernible HE. Subjects who progressed to poor outcomes (ALF, death, LT) were compared, by univariate analysis, with those who recovered. A model to predict poor outcome was developed using the random forest (RF) procedure. RESULTS: Progression to a poor outcome occurred in 90/386 (23%), primarily in non-APAP (71/179, 40%) vs. only 14/194 (7.2%) in APAP patients comprising 52% of all cases (13 cases did not have an etiology assigned; 5 of whom had a poor outcome). Of 82 variables entered into the RF procedure: etiology, bilirubin, INR, APAP level and duration of jaundice were the most predictive of progression to ALF, LT, or death. CONCLUSIONS: A majority of ALI cases are due to APAP, 93% of whom will improve rapidly and fully recover, while non-APAP patients have a far greater risk of poor outcome and should be targeted for early referral to a liver transplant center.

p14ARF interacts with the focal adhesion kinase and protects cells from anoikis.

The ARF protein functions as an important sensor of hyper-proliferative stimuli restricting cell proliferation through both p53-dependent and -independent pathways. Although to date the majority of studies on ARF have focused on its anti-proliferative role, few studies have addressed whether ARF may also have pro-survival functions. Here we show for the first time that during the process of adhesion and spreading ARF re-localizes to sites of active actin polymerization and to focal adhesion points where it interacts with the phosphorylated focal adhesion kinase. In line with its recruitment to focal adhesions, we observe that hampering ARF function in cancer cells leads to gross defects in cytoskeleton organization resulting in apoptosis through a mechanism dependent on the Death-Associated Protein Kinase. Our data uncover a novel function for p14ARF in protecting cells from anoikis that may reflect its role in anchorage independence, a hallmark of malignant tumor cells.

Thin layered drawing media probed by THz time-domain spectroscopy.

Dry and wet drawing materials were investigated by THz time-domain spectroscopy in transmission mode. Carbon-based and iron-gall inks have been studied, some prepared following ancient recipes and others using current synthetic materials; a commercial ink was studied as well. We measured the THz signals on the thin films of liquid inks deposited on polyethylene pellicles, comparing the results with the thick pellets of dried inks blended with polyethylene powder. This study required the implementation of an accurate experimental method and data analysis procedure able to provide a reliable extraction of the material transmission parameters from a structured sample composed of thin layers, down to a thickness of a few tens of micrometers. THz measurements on thin ink layers enabled the determination of both the absorption and the refractive index in an absolute scale in the 0.1-3 THz range, as well as the layer thickness. THz spectroscopic features of a paper sheet dyed by using one of the iron-gall inks were also investigated. Our results showed that THz time-domain spectroscopy enables the discrimination of various inks on different supports, including the application on paper, together with the proper determination of the absorption coefficients and indices of refraction.

HBsAg kinetics in chronic hepatitis D during interferon therapy: on-treatment prediction of response.

BACKGROUND: Therapy of chronic hepatitis D with Interferon is successful when testing for HDV-RNA turns negative. This end-point is disputed. AIM: To assess the role of serum hepatitis B surface antigen (HBsAg) in the clearance of HDV-RNA in pegylated interferon (Peg-IFN)-treated chronic hepatitis D (CHD). METHODS: Sixty-two patients with CHD, treated with Peg-IFN, were considered. The patients belonged to three groups: 14 patients cleared the HBsAg and HDV-RNA (responders, R), 12 cleared the HDV-RNA remaining positive for HBsAg (partial responders, PR) and 36 cleared neither the HBsAg nor the HDV-RNA (nonresponders, NR). RESULTS: In responders, at baseline the median value (mv) of HBsAg and HDV-RNA was 1187 and 188 663 IU/mL. By month 6 of therapy, HBsAg declined to less than 1000 IU/mL and HDV-RNA was undetectable in 12 patients. In NR, the pre-therapy median value of HBsAg and HDV viremia was 6577 and 676 319 IU/mL. There was no significant reduction of antigen at month 6; after a decline, HDV-RNA rebounded to baseline levels. In PR, the median value of baseline HBsAg was 7031 IU/mL; it declined at month 6 in the majority. HDV-RNA progressively declined from an initial median value of 171 405 IU/mL. HBsAg <1000 IU/mL at month 6 discriminated responders and PR from NR (P < 0.001). By ROC curve, the threshold of 0.105 log reduction of HBsAg associated with 1.610 log reduction of HDV-RNA from baseline to month 6 predicted the clearance of this marker. CONCLUSIONS: A reduction of serum HBsAg is mandatory for the definitive clearance of the HDV-RNA. Quantitative HBsAg may predict the long-term response to Peg-IFN therapy and provide a guide to prolong or stop treatment.

Exhaled nitric oxide in relation to asthma control: A real-life survey

BACKGROUND: Asthma is characterised by chronic airway inflammation, a complex cascade of events, mostly sustained by eosinophil recruitment and activation. Fractional exhaled nitric oxide (FeNO) is a surrogate marker of airway inflammation closely associated with bronchial eosinophilia. FeNO is used to define asthma phenotype, to assess eosinophilic inflammatory severity and to predict corticosteroid responsiveness. OBJECTIVE: The aim of this study was to investigate whether FeNO may be associated with some clinical and functional factors in asthmatics evaluated in a real life setting. METHODS: Globally 363 patients (150 males, mean age 46.3 years) with asthma were consecutively evaluated. The following parameters were assessed: history, including comorbidities, physical examination, body mass index (BMI), lung function, asthma control grade, asthma control test (ACT), and FeNO. RESULTS: FeNO values were significantly higher in patients with poorly controlled asthma (p < 0.01), asthma symptoms (p = 0.015), wheezing (p < 0.001), rhinitis diagnosis, (p = 0.049) and rhinitis symptoms (p = 0.019), but lower in patients with GERD (p = 0.024) and pneumonia history (p = 0.048). FeNO values increased in patients with the lowest corticosteroid dose (p = 0.031). FeNO values > 25 ppb were associated with poorly controlled asthma (OR 3.71), asthma signs (OR 3.5) and symptoms (OR 1.79). A FeNO value cut-off of 29.9 ppb was fairly predictive of (AUC 0.7) poorly controlled asthma. CONCLUSIONS: FeNO assessment in clinical practice may be a useful tool for monitoring asthmatics as it is associated with several clinical factors, including asthma control

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Managing atypical and typical herpetic central nervous system infections: results of a multinational study.

There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral centres in 10 countries; 496 patients were found to be eligible for the analysis. Cerebrospinal fluid (CSF) analysis using a PCR assay yielded herpes simplex virus (HSV)-1 DNA in 351 patients (70.8%), HSV-2 DNA in 83 patients (16.7%) and undefined HSV DNA type in 62 patients (12.5%). A total of 379 patients (76.4%) had at least one of the specified characteristics of encephalitis, and we placed these patients into the encephalitis presentation group. The remaining 117 patients (23.6%) had none of these findings, and these patients were placed in the nonencephalitis presentation group. Abnormalities suggestive of encephalitis were detected in magnetic resonance imaging (MRI) in 83.9% of the patients and in electroencephalography (EEG) in 91.0% of patients in the encephalitis presentation group. In the nonencephalitis presentation group, MRI and EEG data were suggestive of encephalitis in 33.3 and 61.9% of patients, respectively. However, the concomitant use of MRI and EEG indicated encephalitis in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection.

Exhaled nitric oxide in relation to asthma control: A real-life survey.

BACKGROUND: Asthma is characterised by chronic airway inflammation, a complex cascade of events, mostly sustained by eosinophil recruitment and activation. Fractional exhaled nitric oxide (FeNO) is a surrogate marker of airway inflammation closely associated with bronchial eosinophilia. FeNO is used to define asthma phenotype, to assess eosinophilic inflammatory severity and to predict corticosteroid responsiveness. OBJECTIVE: The aim of this study was to investigate whether FeNO may be associated with some clinical and functional factors in asthmatics evaluated in a real life setting. METHODS: Globally 363 patients (150 males, mean age 46.3 years) with asthma were consecutively evaluated. The following parameters were assessed: history, including comorbidities, physical examination, body mass index (BMI), lung function, asthma control grade, asthma control test (ACT), and FeNO. RESULTS: FeNO values were significantly higher in patients with poorly controlled asthma (p<0.01), asthma symptoms (p=0.015), wheezing (p<0.001), rhinitis diagnosis, (p=0.049) and rhinitis symptoms (p=0.019), but lower in patients with GERD (p=0.024) and pneumonia history (p=0.048). FeNO values increased in patients with the lowest corticosteroid dose (p=0.031). FeNO values>25ppb were associated with poorly controlled asthma (OR 3.71), asthma signs (OR 3.5) and symptoms (OR 1.79). A FeNO value cut-off of 29.9ppb was fairly predictive of (AUC 0.7) poorly controlled asthma. CONCLUSIONS: FeNO assessment in clinical practice may be a useful tool for monitoring asthmatics as it is associated with several clinical factors, including asthma control.

A dynamic control algorithm based on physiological parameters and wearable interfaces for adaptive ventricular assist devices.

In this work we present an innovative algorithm for the dynamic control of ventricular assist devices (VADs), based on the acquisition of continuous physiological and functional parameters such as heart rate, blood oxygenation, temperature, and patient movements. Such parameters are acquired by wearable devices (MagIC & Winpack) and sensors implanted close to the VAD. The aim of the proposed algorithm is to dynamically control the hydraulic power of the VAD as a function of the detected parameters, patient's activity and emotional status. In this way, the cardiac dynamics regulated by the proposed autoregulation control algorithm for sensorized VADs, thus providing new therapy approaches for heart failure.

Comparative analysis of portal hepatic infiltrating leucocytes in acute drug-induced liver injury, idiopathic autoimmune and viral hepatitis.

Drug-induced liver injury (DILI) is often caused by innate and adaptive host immune responses. Characterization of inflammatory infiltrates in the liver may improve understanding of the underlying pathogenesis of DILI. This study aimed to enumerate and characterize leucocytes infiltrating liver tissue from subjects with acute DILI (n = 32) versus non-DILI causes of acute liver injury (n = 25). Immunostains for CD11b/CD4 (Kupffer and T helper cells), CD3/CD20 (T and B cells) and CD8/CD56 [T cytotoxic and natural killer (NK) cells] were evaluated in biopsies from subjects with acute DILI, either immunoallergic (IAD) or autoimmune (AID) and idiopathic autoimmune (AIH) and viral hepatitis (VH) and correlated with clinical and pathological features. All biopsies showed numerous CD8(+) T cells and macrophages. DILI cases had significantly fewer B lymphocytes than AIH and VH and significantly fewer NK cells than VH. Prominent plasma cells were unusual in IAD (three of 10 cases), but were associated strongly with AIH (eight of nine) and also observed in most with AID (six of nine). They were also found in five of 10 cases with VH. Liver biopsies from subjects with DILI were characterized by low counts of mature B cells and NK cells in portal triads in contrast to VH. NK cells were found only in cases of VH, whereas AIH and VH both showed higher counts of B cells than DILI. Plasma cells were associated most strongly with AIH and less so with AID, but were uncommon in IAD.

Changes in characteristics of hepatitis C patients seen in a liver centre in the United States during the last decade.

With the approval of 2 direct-acting antivirals (DAAs) in 2011 and anticipation of interferon (IFN)-free regimens, more hepatitis C virus (HCV) chronically infected patients are now seeking treatment. To describe the characteristics of newly referred HCV patients in 2011-2012 (Era-2) and compare them to those seen in 1998-1999 (Era-1). Retrospective data were collected from HCV patients newly referred to our tertiary liver clinics. Advanced liver disease was defined as cirrhosis (based on histology or Aspartate aminotransferase-platelet-ratio index (APRI) >2), hepatic decompensation or hepatocellular carcinoma (HCC). A total of 1348 patients (538 in Era-1, 810 in Era-2) were included. Compared to Era-1, Era-2 patients were older (median age 56 vs 45 years), more likely to be black (17.2% vs 11.6%) and had a longer interval between diagnosis and referral (median 4 vs 2 years). Genotype (GT) 1 predominated in both Eras with a significant increase in GT1a from 39.9% in Era-1 to 53.8% in Era-2. A higher per cent of patients in Era-2 were treatment experienced, but 77% had never received treatment. Era-2 patients were more likely to have advanced disease at referral (61.6% vs 51.5%, P < 0.001), with an eightfold higher prevalence of HCC (21.6% vs 2.6%, P < 0.001). HCV patients newly referred in recent years were older, predominantly infected with GT1a and had more advanced liver disease yet only a quarter had received HCV treatment. Reduction in HCV disease burden will require development of treatment regimens targeted towards patients in the current Era as well as increase in diagnosis and referral of patients for treatment.

[Non palpable testicular tumors. Retrospective series]. / Tumeurs testiculaires non palpables. Série rétrospective.

OBJECTIVE: To report our experience in 13 cases with nonpalpable testicular tumors and review the literature. MATERIAL AND METHODS: From 1998 to 2012, 13 patients were diagnosed with nonpalpable testicular tumors. The data base was performed prospectively, and analyzed retrospectively. We evaluated demographic data, clinical presentation, ultrasound tumor features, tumor markers, frozen and final histopathological findings. All patients were also evaluated with serum tumor markers and the surgical approach was inguinal. RESULTS: The mean age was 46.4 years and the most frequent clinical presentation were orchialgia in six patients (46.1%) and infertility in three (23%). All masses were hypoechoic with an average tumor size of 8.9 mm. The serum tumor markers were negative in all patients and the final histopathological findings were six seminomas, two embryonal carcinomas, one seminiferous tubules atrophy, a segmental testicular infarction, a Sertoli cell tumor and a Leydig cell tumor. CONCLUSIONS: Nonpalpable testicular masses were benign in almost half of the cases; therefore, we recommend using the frozen section pathology as a tool to perform conservative surgery in selective cases.

An autoregulation unit for enabling adaptive control of sensorized left ventricular assist device.

This paper describes an integrated system for facing heart failures (HF) in an innovative way. Existing left ventricular assist devices (LVAD or VAD) are usually devoted to blood pumping without the possibility to adapt the speed to patient conditions during everyday activities. This is essentially due to the lack of sensorization, bulkiness, and the need of relying on device-specific controllers with reduced computing ability for the existing ventricular assist systems. In this work, an innovative integrated and portable device, the ARU, is presented for enhancing VADs applicability as a long-term solution to HF. The ARU is an universal device able to fulfill with the needs of sensorized VADs in terms of data storing, continuous monitoring, autoregulation and adaptation to patient condition changes during daily activities. The ARU is able to wirelessly interface wearable devices for offering additional monitoring features from remote. The ARU functionalities on bench have been tested by the interfacing with a sensorized VAD platform in order to prove the feasibility of the approach. Experiments of local and remote VAD speed changes and autoregulation algorithms have been successfully tested showing response time of 1 s.