Medicine by Alexandros G.Sfakianakis: 11/25/15

Τετάρτη 25 Νοεμβρίου 2015

Prenatal stress and early-life exposure to fluoxetine have enduring effects on anxiety and hippocampal BDNF gene expression in adult male offspring

ABSTRACT

With the growing use of selective serotonin reuptake inhibitor medications (SSRIs) for the treatment of depression during the perinatal period, questions have been raised about the longterm impact of these medications on development. We aimed to investigate how developmental SSRI exposure may alter affect-related behaviors and associated molecular processes in offspring using a rodent model of maternal stress and depression. For this purpose, prenatally stressed or non-stressed male offspring were exposed to fluoxetine (5 mg/kg/day) or vehicle, via lactation, until weaning. Primary results show that postnatal fluoxetine exposure differentially altered anxiety-like behavior by increasing anxiety in non-stressed offspring and decreasing anxiety in prenatally stressed offspring. In the hippocampus, developmental fluoxetine exposure decreased BDNF IV and TrkB mRNA expression. Prenatal stress alone also decreased escape behaviors and decreased hippocampal BDNF IV mRNA expression. These data provide important evidence for the long-term programming effects of early-life exposure to SSRIs on brain and behavior. © 2015 Wiley Periodicals, Inc. Dev Psychobiol 9999: 1–12, 2015.

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The distribution of probability values in medical abstracts: an observational study

Background: A relatively high incidence of p values immediately below 0.05 (such as 0.047 or 0.04) compared to p values immediately above 0.05 (such as 0.051 or 0.06) has been noticed anecdotally in published medical abstracts. If p values immediately below 0.05 are over-represented, such a distribution may reflect the true underlying distribution of p values or may be due to error (a false distribution). If due to error, a consistent over-representation of p values immediately below 0.05 would be a systematic error due either to publication bias or (overt or inadvertent) bias within studies. Methods: We searched the Medline 2012 database to identify abstracts containing a p value. Two thousand abstracts out of 80,649 abstracts were randomly selected. Two independent researchers extracted all p values. The p values were plotted and compared to a predicted curve. Chi square test was used to test assumptions and significance was set at 0.05. Results: 2798 p value ranges and 3236 exact p values were reported. 4973 of these (82 %) were significant (<0.05). There was an over-representation of p values immediately below 0.05 (between 0.01 and 0.049) compared to those immediately above 0.05 (between 0.05 and 0.1) (p = 0.001). Conclusion: The distribution of p values in reported medical abstracts provides evidence for systematic error in the reporting of p values. This may be due to publication bias, methodological errors (underpowering, selective reporting and selective analyses) or fraud.

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Combination therapy can prevent cytostatic resistance

Researchers at Karolinska Institutet have found a new way of preventing resistance to cytostatics used in the treatment of cancers such as medulloblastoma, the most common form of malignant brain tumour in children. The promising results of this experimental study are based on a combination of the drug temozolomid and other extant drugs that inhibit an enzyme instrumental in DNA repair in cancer cells. The study, which is published in the journal Nature Communications, was conducted on human tumour cells and on mice, and offers hope of a much improved therapy for a severe form of cancer. This says the research team is particularly valuable for children, whose brains are still developing and who thus run the highest risk of injury from the radiotherapy often used against malignant brain tumours. "Now that we've tested already available drugs, the published results enable us to move on to clinical trials relatively quickly, which is very good news indeed," says Dr Malin Wickström, one of the researchers behind the study. The treatment of cancer often involves different forms of cytostatic drugs as well as surgery and radiotherapy. However, tumour cells develop strategies for resisting these drugs, most commonly to produce more of a particular protein or enzyme able to repair the DNA damage caused by the chemotherapy. In the present experimental study, the researchers have sought means of inhibiting the DNA-repair enzyme MGMT (O6-methylguanine-DNA-methyltransferase), which plays a key part in cytostatic resistance. One finding was that a cell signal pathway called Wingless and its central signal molecule, beta-catenin, can regulate the production of MGMT in the tumour cell. Common form of paediatric brain tumour Blocking Wingless/beta-catenin also inhibits the MGMT enzyme, which in turn prevents cytostatic resistance. This was particularly the case for temozolomid, which is often used to treat medulloblastoma, the most common form of paediatric brain tumour. "By combining temozolomid with Wingless inhibitors, we've been able to cancel out the resistance developed by the tumour, rendering it susceptible to the tumour-killing effect of temozolomid," says principal investigator and docent, Dr John Inge Johnsen. "We hope that the results will give rise to a new drug combination therapy and improve prospects for a very vulnerable patient group." Dr Wickström and Dr Johnsen work at the paediatric oncology unit of the Department of Women's and Children's Health at Karolinska Institutet. The study was done in cooperation with Dr. Ninib Baryawno at Harvard University in the US, and financed with grants from the Swedish Childhood Cancer Foundation, the Swedish Research Council, the Swedish Cancer Society, the Swedish Foundation for Strategic Research, the Märta and Gunnar V. Philipson Foundation, the Mary Béve Foundation for Childhood Cancer Research, the Dämman Foundation and the Erna and Olav Aakre Foundation for Cancer Research. Further information on childhood medulloblastoma Publication Wnt/β-catenin pathway regulates MGMT gene expression in cancer and inhibition of Wnt signalling prevents chemoresistance Malin Wickström, Cecilia Dyberg, Jelena Milosevic, Christer Einvik, Raul Calero, Baldur Sveinbjörnsson, Emma Sandén, Anna Darabi, Peter Siesjö, Marcel Kool, Per Kogner, Ninib Baryawno, John Inge Johnsen Nature Communications, online 25 November 2015, doi:10.1038/ncomms9904

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Tc-99m-CXCL8 SPECT to monitor disease activity in inflammatory bowel disease

Rationale: Inflammatory bowel diseases (IBD) are defined as chronic relapsing immune-mediated disorders of the gastrointestinal tract. IBD exacerbations are characterized by recruitment of mainly CXCL8-receptor expressing activated neutrophils into the intestinal wall, leading to severe damage. Considering its chronic relapsing character, accurate and timely diagnosis of an exacerbation is pivotal for early adaptation of the treatment and reduction of the disease burden. However, endoscopic evaluation is invasive and associated with an increased risk of perforation. We previously developed a Tc-99m-labeled CXCL8 preparation in preclinical models including colitis and clinical studies. Methods: In this study, we investigate the accuracy of Tc-99m-CXCL8 SPECT to detect and localize disease activity in a prospective series of patients with IBD. A total of 30 patients (15 Crohns' disease, 15 Ulcerative colitis) participated and 92 segmental pairs of histology and Tc-99m-CXCL8 scan were studied. Imaging was performed after injection of 400 MBq Tc-99m-CXCL8. Planar and SPECT acquisitions of the abdomen were performed at 30 min and 4 h after the injection. Results: The overall sensitivity and specificity on a per patient basis for the detection of active disease was 95% and 44% for Tc-99m-CXCL8 scan and 71% and 70% for endoscopy. The degree of Tc-99m-CXCL8 accumulation correlated to the degree of neutrophilic influx in affected mucosa. Sensitivity and specificity on a per segment basis, calculated from the 92 segmental pairs, was 82% and 72%, negative predictive value was 81% and the overall positive predictive value was 74%. Using different cut-offs, specificity could be increased at the expense of sensitivity. In 74 segmental pairs, overall sensitivity and specificity for endoscopy was 74% and 85%, and PPV of 81% and NPV of 79%. Conclusion: Tc-99m-CXCL8 SPECT provides a novel imaging technique to target neutrophil recruitment to the intestinal wall, especially in moderate to severe exacerbations of IBD. Further validation studies are warranted to potentiate Tc-99m-CXCL8 SPECT as a biomarker to scale up or step down treatment with immune modulating drugs in a personalized fashion.

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124I PET/CT to predict the outcome of blind 131I treatment in patients with biochemical recurrence of differentiated thyroid cancer; results of a multicenter diagnostic cohort study (THYROPET)

Patients with suspected recurrence from differentiated thyroid carcinoma (DTC), based on an increased thyroglobulin (Tg) level and negative neck ultrasound (US), pose a clinical dilemma. Since standard imaging has a low yield identifying potential recurrence, 'blind' ¹³¹I treatment is often applied. However, a tumor-negative ¹³¹I whole body scintigraphy (WBS) prevails in 38-50% of patients. We performed a prospective multicenter observational cohort study to test the hypothesis that ¹²⁴I PET/CT can identify the patients with a tumor negative post-therapy ¹³¹I WBS. Methods: Our study was designed to include 100 patients with detectable Tg and a negative neck US, who were planned for 'blind' ¹³¹I therapy. All patients underwent ¹²⁴I PET/CT after rhTSH stimulation. Subsequently, after 4-6 weeks of thyroid hormone withdrawal patients were treated with 5.5-7.4 GBq ¹³¹I, followed by WBS a week later. The primary endpoint was the number of ¹³¹I therapies that could have been omitted using the predicted outcome of the ¹²⁴I PET/CT, operationalized as the concordance of tumor detection by ¹²⁴I PET/CT, using post-¹³¹I therapy WBS as the reference test. The study would be terminated if three patients had a negative ¹²⁴I PET/CT and a positive post-therapy ¹³¹I. Results: After inclusion of 17 patients we terminated the study preliminarily, as the stopping rule had been met. Median Tg-level at ¹³¹I therapy was 28 μg/L (interquartile range: 129). Eight post-therapy WBS were negative (47%), all of which correctly predicted by negative ¹²⁴I PET/CT. Nine post-therapy WBS showed iodine avid tumor, of which four also had positive ¹²⁴I PET/CT findings. Sensitivity, specificity, negative predictive value and positive predictive value of ¹²⁴I PET/CT were 44% (CI 14-79%), 100% (CI 63-100%), 62% (CI 32-86%) and 100% (CI 40-100%), respectively. Implementation of ¹²⁴I PET in this setting would have led to 47% (8/17) less futile ¹³¹I treatments, but 29% of patients (5/17) would have been denied potentially effective therapy. Conclusion: In patients with biochemical evidence of recurrent DTC and a tumor negative neck ultrasound, the high false negative rate of rhTSH stimulated ¹²⁴I PET/CT as implemented in this study precludes its use as a scouting procedure to prevent futile blind ¹³¹I therapy.

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Age-related gender-specific changes in the brain metabolism and morphology

With a large database, we aimed to evaluate gender-specific distinctive changes of brain glucose metabolism and morphology during normal aging using Magnetic resonance imaging (MRI) and ¹⁸F-FDG positron emission tomography (PET). Methods: A total of 963 cognitively healthy adults were included in this study. All subjects underwent medical questionnaire, mini mental state examination (MMSE) and whole-body examinations including brain MRI and whole-body ¹⁸F-FDG PET. We performed statistical analysis of the MR and PET images using three-dimensional stereotactic surface projection (3D-SSP). All images were corrected by whole brain pixel value to identify the brain regions with significant changes and regions of interest (ROI) were set up with reference to the Brodmann Area (BA). We evaluated morphological and glucose metabolic changes by the cross-sectional analysis. The baseline database consisted of the subjects from 30 to 40 years old and the age-step for comparison was each 5 years. We also compared gender-specific differences of MR and PET images in each generation. Results: In age-related changes, the brain atrophy was observed in the lateral frontal and parietal regions, and the glucose hypometabolism was observed in the medial frontal regions in both genders. Between-gender comparison revealed significant sex differences in these parameters, showing that parallel changes in volume and metabolism were manifested in the medial frontal cortex in men and in the lateral and medial temporal cortex in women. By contrast, metabolism-dominant reductions were manifested in the lateral and medial parietal cortex in men and in the ventrolateral prefrontal cortex, including the Broca area, in women. These differences became insignificant in individuals aged 66 years and older. Conclusion: Our brain mapping study with a large number of normal human brain data demonstrates age-related, parallel changes between morphology and metabolism in the medial frontal regions, and gender-specific hypometabolism in the parietal (male) and the ventrolateral prefrontal (female) cortices. These findings may suggest a presence of aging vulnerability of gender-specific brain regions; the parietal cortex for the visuospatial ability in men and the Broca area for speech communication in women.

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Feasibility of 18F-fluoromisonidazole kinetic modeling in head and neck cancer using shortened acquisition times

¹⁸F-fluoromisonidazole dynamic positron emission tomography (dPET) is used to identify tumor hypoxia non-invasively. Its routine clinical implementation, however, has been hampered by the long acquisition times required. We investigated the feasibility of kinetic modeling using shortened acquisition times in ¹⁸F-fluoromisonidazole dPET, with the goal of expediting the clinical implementation of ¹⁸F-fluoromisonidazole dPET protocols. Methods: Six patients with squamous cell carcinoma of the head and neck and ten HT29 colorectal carcinoma-bearing nude rats were studied. In addition to an ¹⁸F-fluorodeoxyglucose PET scan, each patient underwent a 45-min ¹⁸F-fluoromisonidazole dPET scan, followed by 10 min acquisitions at 96±4 and 163±17 min post-injection. Ninety-minute ¹⁸F-fluoromisonidazole dPET acquisitions were performed in animals. Intra-tumor voxels were classified into 4 clusters based on their kinetic behavior using k-means clustering. Kinetic modeling was carried out using the foregoing full datasets (FD) and repeated for each of two shortened datasets corresponding to the first ~100 min (SD1; patients only) or the first 45 min (SD2) of dPET data. The kinetic rate constants (KRCs) as calculated with a 2-compartment model for both SD1 and SD2 were compared to those derived from FD by correlation (Pearson), regression (Passing-Bablok), deviation (Bland-Altman) and classification (area under receiver operating characteristic curve; AUC) analyses. Simulations were performed to assess uncertainties due to statistical noise. Results: Strong correlation (r≥0.75, p<0.001) existed between all KRCs deduced from both SD1 and SD2, and from FD. Significant differences between KRCs were only found for FD-SD2 correlations in patient studies. K1 and k3 were reproducible to within ~6% and ~30% (FD-SD1; patients) and ~4% and ~75% (FD-SD2; animals). AUC values for classification of patient clusters as hypoxic, using a tumor-to-blood ratio>1.2, were 0.91 (SD1) and 0.86 (SD2). The percentage standard deviation in estimating K1 and k3 from 45-min shortened datasets due to noise was <1% and between 2-12% respectively. Conclusion: Using single-session 45-min shortened ¹⁸F-fluoromisonidazole dynamic PET datasets appears to be adequate for the identification of intra-tumor regions of hypoxia. However, k3 was significantly overestimated in the clinical cohort. Further studies are necessary to evaluate the clinical significance of differences between the results as calculated from full and shortened datasets.

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Significance of a single time point hybrid-protocol for somatostatin receptor SPECT including multiphase CT in the diagnostic work-up of gastroenteoropancreatic neuroendocrine Neoplasms (GEP-NEN)

Aim: This prospective study compared a one-day hybrid-SPECT/CT protocol (incl. multiphase CT-scans) to the commonly used three-day protocol for somatostatin receptor scintigraphy (SRS) in patients suffering from gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). Additionally, the SPECT/CT-influence on patient management was evaluated. Methods: From 10/2011 to 10/2012 all GEP-NEN-patients undergoing restaging with SRS with a modern SPECT/CT-device SPECT/CT (Discovery NM/CT670, GE) were enrolled in this study. The examination-protocol consisted of planar scanning 4, 24 and 48 h p.i., whole-body low-dose SPECT/CT-imaging at 24 and 48 h (SPECT-ldCT24, SPECT-ldCT48) and diagnostic multiphase CT (dCT24) at 24 h coregistered to the corresponding SPECT (SPECT-ldCT24). All imaging data-components were reassessed by three blinded readers (R1, R2, R3). The results were compared to a reference standard (RS) based on all clinical, imaging and histopathology follow-up data available (24-36, mean 29.9 months). RS was defined by a study-specific interdisciplinary tumor board (SITB) that also reassessed treatment decisions. Results: 31 patients (m, n = 18; f, n = 13; mean age, 60.4 years) were eligible for analysis. 10/31 patients had no imaging sign of disease and remained disease-free during follow-up. 21/31 patients had persistent/recurrent disease (n = 82 lesions: liver n = 24; lymph-node n = 21; bone n = 16; pancreas n = 12; others n = 9). A lesional detection rate of 51.9%(R1), 49.4%(R2) and 71.6%(R3) for SPECT-ldCT24, 51.9%(R1), 55.6%(R2) and 67.9%(R3) for SPECT-ldCT48 and 63.0%(R1), 70.4%(R2) and 85.2%(R3) for dCT24 was observed, respectively. SPECT-dCT24 yielded the highest detection rate with 77.8%(R1), 84.0%(R2) and 88.9%(R3), respectively. Interobserver agreement was moderate for SPECT-dCT24 (=0.44), dCT24 (=0.43), SPECT-ldCT48 (=0.61) and for SPECT-ldCT24 (=0.55). For planar scans it was fair after 48 h (=0.36) and 24 h (=0.38), respectively, and moderate after 4 h (=0.42). Every lesion present in planar or SPECT-ldCT-imaging was also detectable in SPECT-dCT24, which also showed a great complementarity, as 34/82 (41.4%) lesions were detected by a single submodality only. Integrated SPECT/CT reading influenced therapeutic management in 8/31 (25.8%) patients. Conclusion: The highest detection rates are achieved by SPECT-dCT24. Thus, a more patient-friendly one-day-examination protocol is feasible. Furthermore, the multiphase hybrid-SPECT/CT-examination impacted on patient management in about one fourth of all patients.

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RGD PET: From Lesion Detection to Therapy Response Monitoring

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Differences in Sympathetic Nervous Stimulation of Brown Adipose tissue between the young and old and the lean and obese.

Brown adipose tissue (BAT) could facilitate weight loss by increasing energy expenditure. Cold is a potent stimulator of BAT, activating BAT primarily through the sympathetic nervous system (SNS). Older or overweight individuals have less metabolic BAT activity than the lean and young, but the role of the SNS in this decline is unknown. We aimed to determine whether this lower metabolic BAT activity in older or overweight individuals can be explained by a lower SNS response to cold. Methods: This was a prospective observational study. We included 10 young obese, 11 old lean and 14 young lean healthy males. All subjects underwent a ¹⁸F-Fluorodeoxyglucose (¹⁸F-FDG) PET-CT and a ¹²³I-meta-iodobenzylguanidine (¹²³I-mIBG) SPECT-CT after an overnight fast and two hours of cold exposure. Metabolic BAT activity was expressed as volume and as maximal standardised uptake value (SUV_max) of ¹⁸F-FDG. BAT SNS activity was expressed as volume and as the ratio between ¹²³I-mIBG uptake in BAT and a reference region (SQUVmax of ¹²³I-mIBG). Results: SUV_max, BAT volume and SQUVmax were significantly different between young and old (SUV_max 7.9[4.2-17.3] vs. 2.9[0.0-4.0], volume 124.8[10.9-338.8] vs 3.4 [0.0-10.9] and SQUVmax 2.7[1.9-4.7] vs 0.0[0.0-2.2] all p<0.01) but not between lean and obese (SUV_max 7.9[4.2-17.3] vs 4.0[0.0-13.5] P = 0.69; volume 124.8[10.9-338.8] vs 11.8 [0.0-190.2] P = 0.64 and SQUVmax 2.7[1.9-4.7]vs 1.7[0-3.5] P = 0.69). We found a strong positive correlation between BAT activity measured with ¹⁸F-FDG and ¹²³I-mIBG in the whole group of BAT positive subjects (=0.82, p<0.01). Conclusion: We conclude that both sympathetic drive and BAT activity are lower in older but not in obese males.

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PET response criteria (PERCIST) predict progression-free survival and overall survival after radioembolization for liver metastases from pancreatic cancer

We evaluated the prognostic accuracy of established positron emission tomography (PET) response criteria in patients with liver metastases from pancreatic cancer (LMPAC) after treatment with ⁹⁰Y-Yttrium microspheres. Methods: 17 patients underwent ¹⁸F-2-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) PET/CT before and three months after radioembolization for LMPAC. Overall survival (OS), progression-free survival (PFS), and time to intrahepatic progression (TTPliver) were among other factors correlated with metabolic response revealed by declining SUVpeak and total lesion glycolysis (TLG5), as defined by PET Response Criteria in Solid Tumors 1.0 (PERCIST). Results: Metabolic response by SUVpeak (n = 7/17) and TLG5 (n = 7/17) were predictors for OS (P = 0.039; HR 0.24, 95%CI 0.06-0.93), PFS (P = 0.016; HR 0.15, 95%CI 0.03-0.69) and TTPliver (P = 0.010; HR 0.16, 95%CI 0.04-0.65). A summed baseline CT diameter of the two largest liver metastases <8cm predicted TTPliver (P = 0.013; HR 0.21, 95%CI 0.06-0.72), but did not predict OS or PFS. Other parameters, including baseline SUVpeak, baseline TLG5, as well as baseline to follow-up change in the serum level of CEA or CA19-9, did not predict patient outcome (each p>0.05). Conclusion: Metabolic response by ¹⁸F-FDG PET/CT predicts overall survival, progression-free survival and time to intrahepatic progression after radioembolization for liver metastases from pancreatic cancer.

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Postdischarge mortality in children with acute infectious diseases: derivation of postdischarge mortality prediction models

Objectives

To derive a model of paediatric postdischarge mortality following acute infectious illness.

Design

Prospective cohort study.

Setting

2 hospitals in South-western Uganda.

Participants

1307 children of 6 months to 5 years of age were admitted with a proven or suspected infection. 1242 children were discharged alive and followed up 6 months following discharge. The 6-month follow-up rate was 98.3%.

Interventions

None.

Primary and secondary outcome measures

The primary outcome was postdischarge mortality within 6 months following the initial hospital discharge.

Results

64 children died during admission (5.0%) and 61 died within 6 months of discharge (4.9%). Of those who died following discharge, 31 (51%) occurred within the first 30 days. The final adjusted model for the prediction of postdischarge mortality included the variables mid-upper arm circumference (OR 0.95, 95% CI 0.94 to 0.97, per 1 mm increase), time since last hospitalisation (OR 0.76, 95% CI 0.61 to 0.93, for each increased period of no hospitalisation), oxygen saturation (OR 0.96, 95% CI 0.93 to 0·99, per 1% increase), abnormal Blantyre Coma Scale score (OR 2.39, 95% CI 1·18 to 4.83), and HIV-positive status (OR 2.98, 95% CI 1.36 to 6.53). This model produced a receiver operating characteristic curve with an area under the curve of 0.82. With sensitivity of 80%, our model had a specificity of 66%. Approximately 35% of children would be identified as high risk (11.1% mortality risk) and the remaining would be classified as low risk (1.4% mortality risk), in a similar cohort.

Conclusions

Mortality following discharge is a poorly recognised contributor to child mortality. Identification of at-risk children is critical in developing postdischarge interventions. A simple prediction tool that uses 5 easily collected variables can be used to identify children at high risk of death after discharge. Improved discharge planning and care could be provided for high-risk children.

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The disciplined healthcare professional: a qualitative interview study on the impact of the disciplinary process and imposed measures in the Netherlands

Objective

It is known that doctors who receive complaints may have feelings of anger, guilt, shame and depression, both in the short and in the long term. This might lead to functional impairment. Less is known about the impact of the disciplinary process and imposed measures. Previous studies of disciplinary proceedings have mainly focused on identifying characteristics of disciplined doctors and on sentencing policies. Therefore, the aim of this study is to explore what impact the disciplinary process and imposed measures have on healthcare professionals.

Design

Semistructured interview study, with purposive sampling and inductive qualitative content analysis.

Participants

16 healthcare professionals (9 medical specialists, 3 general practitioners, 2 physiotherapists and 2 psychologists) that were sanctioned by the disciplinary tribunal.

Setting

The Netherlands.

Results

Professionals described feelings of misery and insecurity both during the process as in its aftermath. Furthermore, they reported to fear receiving new complaints and provide care more cautiously after the imposed measure. Factors that may enhance psychological and professional impact are the publication of measures online and in newspapers, media coverage, the feeling of treated as guilty before any verdict has been reached, and the long duration of the process.

Conclusions

This study shows that the disciplinary process and imposed measures can have a profound psychological and professional impact on healthcare professionals. Although a disciplinary measure is meant to have a corrective effect, our results suggest that the impact that is experienced by professionals might hamper optimal rehabilitation afterwards. Therefore, organising emotional support should be considered during the disciplinary process and in the period after the verdict.

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Acculturation, sociodemographic and lifestyle factors associated with compliance with physical activity recommendations in the Mexican-American Mano A Mano cohort

Objectives

Being physically active is important for health, and few Mexican-Americans meet national US physical activity recommendations. The aim of this study was to investigate sociodemographic, acculturation and lifestyle factors that were associated with meeting physical activity recommendations in this group.

Design and setting

A cross-sectional analysis of a large population-based cohort study in southern Texas, USA.

Participants

Between 2001 and 2011, 21 551 adult members of the Mexican-American Mano A Mano cohort completed baseline questionnaires on physical activity and other lifestyle factors.

Outcomes

Meeting US physical activity recommendations was defined as participating in 150 min of moderate, or 75 min of vigorous, activity per week. Factors contributing to the likelihood of meeting physical activity recommendations were examined by sex and country of birth in multivariate logistic regression models.

Results

Less than half of all men and less than a quarter of all women met US physical activity recommendations. Having some college education, greater acculturation and current alcohol use were each associated with greater odds of meeting physical activity recommendations in all groups except US-born men. Higher body mass index was associated with lower odds of meeting recommendations in US-born and Mexico-born women.

Conclusions

Results demonstrate that factors associated with meeting physical activity recommendations differ by sex and country of birth. Tailored interventions to increase Mexican-Americans' activity levels to achieve health benefits should consider education, acculturation and alcohol use.

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Specialised teams or personal continuity across inpatient and outpatient mental healthcare? Study protocol for a natural experiment

Introduction

Mental healthcare organisation can either pursue specialisation, that is, distinct clinicians and teams for inpatient and outpatient care or personal continuity of care, that is, the same primary clinician for a patient across the two settings. Little systematic research has compared these approaches. Existing studies subject have serious methodological shortcomings. Yet, costly reorganisations of services have been carried out in different European countries, inconsistently aiming to achieve specialisation or personal continuity of care. More reliable evidence is required on whether specialisation or continuity of care is more effective and cost-effective, and whether this varies for different patient groups and contexts.

Design and methods

In a natural experiment, we aim to recruit at least 6000 patients consecutively admitted to inpatient psychiatric care in Belgium, Germany, Italy, Poland, and the UK. In each country, care approaches supporting specialisation and personal continuity coexist. Patients will be followed up at 1 year to compare outcomes, costs and experiences. Inclusion criteria are: 18 years of age or older; clinical diagnosis of psychosis, affective disorder or anxiety/somatisation disorder; sufficient command of the language of the host country; absence of cognitive deterioration and/or organic brain disorders; and capacity to provide informed consent.

Ethics and dissemination

Ethical approval was obtained in all countries: (1) England: NRES Committee North East—Newcastle & North Tyneside (ref: 14/NE/1017); (2) Belgium: Comité d'Ethique hospitalo-facultaire des Cliniques St-Luc; (3) Germany: Ethical Board, Technische Universität Dresden; (4) Italy: Comitati Etici per la sperimentazione clinica (CESC) delle provincie di Verona, Rovigo, Vicenza, Treviso, Padova; (5) Poland: Komisja Bioetyczna przy Instytucie Psychiatrii i Neurologii w Warszawie. We will disseminate the findings through scientific publications and a study-specific website. At the end of the study, we will develop recommendations for policy decision-making, and organise national and international workshops with stakeholders.

Trial registration number

ISRCTN registry: ISRCTN40256812.

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Bereaved relatives experiences during the incurable phase of cancer: a qualitative interview study

Objective

To examine bereaved relatives' experiences from time of diagnosis of incurable cancer until death with specific emphasis on their role in the (end-of-life) decision-making concerning chemotherapy.

Design

Qualitative interview study.

Setting

Hospital-based.

Participants and methods

In-depth interviews with 15 close relatives of patients who died from non-small cell lung cancer or pancreatic cancer, using a thematic content analysis.

Results

All relatives reported that patients' main reason to request chemotherapy was the possibility to prolong life. Relatives reported that patients receiving chemotherapy had more difficulty to accept the incurable nature of their disease than patients who did not. They mostly followed the patients' treatment wish and only infrequently suggested ceasing chemotherapy (because of side effects) despite sometimes believing that this would be a better option. Relatives continuously tried to support the patient in either approaching the death or in attaining hope to continue life satisfactorily. Most relatives considered the chemotherapy period meaningful, since it sparked patients' hope and was what patients wanted. Cessation of chemotherapy caused a relief but coincided with physical deterioration and an increased caregivers' role; many relatives recalled this latter period as more burdensome.

Conclusions

Relatives tend to follow patients' wish to continue or cease chemotherapy, without expressing their own feelings, although they were more inclined to opt cessation. They experience a greater caregiver role after cessation and their feelings of responsibility associated with the disease can be exhausting. More attention is needed to reduce relatives' distress at the end of life, also to fully profit from this crucial form of (informal) healthcare.

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Are suicide deaths under-reported? Nationwide re-evaluations of 1800 deaths in Scandinavia

Objective

Valid mortality statistics are important for healthcare planning and research. Suicides and accidents often present a challenge in the classification of the manner of death. The aim of this study was to analyse the reliability of the national suicide statistics by comparing the classification of suicide in the Scandinavian cause of death registers with a reclassification by 8 persons with different medical expertise (psychiatry, forensic pathology and public health) from each of the 3 Scandinavian countries.

Methods

The cause of death registers in Norway, Sweden and Denmark retrieved available information on a sample of 600 deaths in 2008 from each country. 200 were classified in the registers as suicides, 200 as accidents or undetermined and 200 as natural deaths. The reclassification comprised an assessment of the manner and cause of death as well as the level of certainty.

Results

In total, 81%, 88% and 90% of deaths registered as suicide in the official mortality statistics were confirmed by experts using the Swedish, Norwegian and Danish data sets, respectively. About 3% of deaths classified as accidents or natural deaths in the cause of death registers were reclassified as suicides. However, after a second reclassification based on additional information, 9% of the natural deaths and accidents were reclassified as suicides in the Norwegian data set, and 21% of the undetermined deaths were reclassified as suicides in the Swedish data set. In total, the levels of certainty of the experts were 87% of suicides in the Norwegian data set, 77% in the Swedish data set and 92% in Danish data set; the uncertainty was highest in poisoning suicides.

Conclusions

A high percentage of reported suicides were confirmed as being suicides. Few accidents and natural deaths were reclassified as suicides. Hence, reclassification did not increase the overall official suicide statistics of the 3 Scandinavian countries.

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Methods for estimating causal relationships of adverse events with dietary supplements

Objective

Dietary supplement use has increased over past decades, resulting in reports of potentially serious adverse events. The aim of this study was to develop optimised methods to evaluate the causal relationships between adverse events and dietary supplements, and to test these methods using case reports.

Design

Causal relationship assessment using prospectively collected data.

Setting and participants

4 dietary supplement experts, 4 pharmacists and 11 registered dietitians (5 men and 14 women) examined 200 case reports of suspected adverse events using the modified Naranjo scale and the modified Food and Drug Administration (FDA) algorithm.

Primary outcome measures

The distribution of evaluation results was analysed and inter-rater reliability was evaluated for the two modified methods employed using intraclass correlation coefficients (ICC) and Fleiss' .

Results

Using these two methods, most of the 200 case reports were categorised as 'lack of information' or 'possible' adverse events. Inter-rater reliability among entire assessors ratings for the two modified methods, based on ICC and Fleiss' , were classified as more than substantial (modified Naranjo scale: ICC (95% CI) 0.873 (0.850 to 0.895); Fleiss' (95% CI) 0.615 (0.615 to 0.615). Modified FDA algorithm: Fleiss' (95% CI) 0.622 (0.622 to 0.622).

Conclusions

These methods may help to assess the causal relationships between adverse events and dietary supplements. By conducting additional studies of these methods in different populations, researchers can expand the possibilities for the application of our methods.

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Neighbourhood urban form and individual-level correlates of leisure-based screen time in Canadian adults

Objectives

Despite evidence for an association between the built environment and physical activity, less evidence exists regarding relations between the built environment and sedentary behaviour. This study investigated the extent to which objectively assessed and self-reported neighbourhood walkability, in addition to individual-level characteristics, were associated with leisure-based screen time in adults. We hypothesised that leisure-based screen time would be lower among adults residing in objectively assessed and self-reported 'high walkable' versus 'low walkable' neighbourhoods.

Setting

The study was undertaken in Calgary, Alberta, Canada in 2007/2008.

Participants

A random cross-section of adults who provided complete telephone interview and postal survey data (n=1906) was included. Captured information included leisure-based screen time, moderate-intensity and vigorous-intensity physical activity, perceived neighbourhood walkability, sociodemographic characteristics, self-reported health status, and self-reported height and weight. Based on objectively assessed built characteristics, participant's neighbourhoods were identified as being low, medium or high walkable.

Primary and secondary outcome measures

Using multiple linear regression, hours of leisure-based screen time per day was regressed on self-reported and objectively assessed walkability adjusting for sociodemographic and health-related covariates.

Results

Compared to others, residing in an objectively assessed high walkable neighbourhood, women, having a college education, at least one child at home, a household income ≥$120 000/year, and a registered motor vehicle at home, reporting very good-to-excellent health and healthy weight, and achieving 60 min/week of vigorous-intensity physical activity were associated (p<0.05) with less leisure-based screen time. Marital status, dog ownership, season, self-reported walkability and achieving 210 min of moderate-intensity physical activity were not significantly associated with leisure-based screen time.

Conclusions

Improving neighbourhood walkability could decrease leisure-based television and computer screen time. Programmes aimed at reducing sedentary behaviour may want to consider an individual's sociodemographic characteristics, physical activity level, health status and weight status, in addition to the walkability of their neighbourhood as these factors were found to be important independent correlates of leisure-based screen time.

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How common is isolated dysphasia among patients with stroke treated with intravenous thrombolysis, and what is their outcome? Results from the SITS-ISTR

Objectives

To describe the frequency and outcome of isolated dysphasia among patients treated with intravenous thrombolysis (IVT).

Design

Patients registered in the SITS International Stroke Thrombolysis Register (SITS-ISTR).

Participants

Patients with stroke (N=58 293) treated with IVT between December 2002 and December 2012.

Setting

A multinational, prospective, observational monitoring register.

Main outcome measures

Isolated dysphasia and modified Rankin Scale (mRS).

Methods

We identified patients presenting with isolated dysphasia by reviewing items within the baseline National Institutes of Health Stroke Scale (NIHSS). We performed descriptive statistics for baseline and demographic data, and reported patients' characteristics, radiological data and changes in their NIHSS score within 7 days and mRS score at 3 months. We also reported corresponding data from the general SITS-ISTR cohort.

Results

We found isolated dysphasia at baseline in 1.14% (663/58 293) of all patients treated with IVT patients. Patients with isolated dysphasia had a longer onset to treatment time, lower proportion of visible infarctions on admission imaging scan and atrial fibrillation, and were less often classified as having large vessels causing strokes, in comparison with the rest of the SITS-ISTR. Symptomatic intracerebral haemorrhage occurred in 2.3% of patients per SITS-MOST definition and fatal outcome in 5.5%. At 7 days, 50% of patients with isolated dysphasia recovered completely and at 3 months, 86.3% patients were functionally independent (mRS score 0–2), 71.7% had an excellent outcome (mRS score 0–1) and 45.5% had an mRS score of 0.

Conclusions

A low proportion of patients with isolated dysphasia are treated with IVT. Half of these patients were fully recovered at 7 days.

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Assessing potentially inappropriate prescribing (PIP) and predicting patient outcomes in Ontarios older population: a population-based cohort study applying subsets of the STOPP/START and Beers criteria in large health administrative databases

Introduction

Adverse drug events (ADEs) are common in older people and contribute significantly to emergency department (ED) visits, unplanned hospitalisations, healthcare costs, morbidity and mortality. Many ADEs are avoidable if attention is directed towards identifying and preventing inappropriate drug use and undesirable drug combinations. Tools exist to identify potentially inappropriate prescribing (PIP) in clinical settings, but they are underused. Applying PIP assessment tools to population-wide health administrative data could provide an opportunity to assess the impact of PIP on individual patients as well as on the healthcare system. This would open new possibilities for interventions to monitor and optimise medication management on a broader, population-level scale.

Methods and analysis

The aim of this study is to describe the occurrence of PIP in Ontario's older population (aged 65 years and older), and to assess the health outcomes and health system costs associated with PIP—more specifically, the association between PIP and the occurrence of ED visits, hospitalisations and death, and their related costs. This will be done within the framework of a population-based retrospective cohort study using Ontario's large health administrative and population databases. Eligible patients aged 66 years and older who were issued at least 1 prescription between 1 April 2003 and 31 March 2014 (approximately 2 million patients) will be included.

Ethics and dissemination

Ethical approval was obtained from the Ottawa Health Services Network Ethical Review Board and from the Bruyère Research Institute Ethics Review Board. Dissemination will occur via publication, presentation at national and international conferences, and ongoing exchanges with regional, provincial and national stakeholders, including the Ontario Drug Policy Research Network and the Ontario Ministry of Health and Long-Term Care.

Trial registration number

Registered with clinicaltrials.gov (registration number: NCT02555891).

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Genitourinary tuberculosis, CA-125 and tuberculin anergy in disseminated tuberculosis

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Pretibial myxedema

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Sister Mary Joseph nodule

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Bilateral sutural cataract

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Aortic aneurysm and the split eggshell sign

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Toxic effects of hydrogen sulfide: experience with three simultaneous patients

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Brachial artery mycotic aneurysm and splenic infarction associated with infective endocarditis

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Running, ischaemic stroke and carotid artery dissection

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Cookie bite cortical osteolytic lesions: a hint of skeletal metastasis from bronchogenic carcinoma

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The use of adjunctive traditional Chinese medicine therapy and survival outcome in patients with head and neck cancer: a nationwide population-based cohort study

Background: Traditional Chinese medicine (TCM) is widely used in the treatment of patients with several types of cancer. However, no large-scale clinical studies have evaluated whether TCM is associated with better survival in patients with head and neck cancer (HNC).

Methods: The Taiwan National Health Insurance Research Database was used to conduct a retrospective cohort study of patients with HNC between 2001 and 2011. The patients with HNC were separated into TCM users and non-users, and Cox regression models were applied to determine the association between the use of TCM and survival outcome.

Results: The TCM and comparison cohorts comprised data for 2966 and 2670 patients, respectively. The mean age was 51.3 years in the TCM cohort and 51.7 years in the comparison cohort. Multivariate analysis demonstrated that the use of TCM was significantly associated with lower risk of all-cause mortality by 32% (adjusted hazard ratio, 0.68; 95% confidence interval, 0.62–0.75). Patients with longer TCM use had a lower mortality rate (P for trend < 0.001).

Conclusions: Our study showed that adjunctive therapy with TCM is associated with higher survival outcome. However, some limitations exist, such as the lack of information of cancer stage. In addition, causality cannot be assessed with this retrospective study. A randomized controlled trial to test the effect of adjunctive TCM therapy in HNC patients is needed.

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Leptospirosis and Jarisch-Herxheimer reaction

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Relatives and staffs experience of patients dying in ICU

Background: Intensive care units (ICUs) exist to support patients through acute illness that threatens their life. Although ICUs aim to save life, they are also a place where a significant proportion of patients die with international mortality rates ranging from 15% to 24%.

Aim: To explore the experience of relatives and staff of patients dying in ICU using qualitative approach.

Design: Consecutive patients were identified who were dying in the ICU. The researcher met the families prior to the patient's death. The ICU nurse and doctor most involved were interviewed within 48 h of the death. The families were interviewed 2 weeks later. Interviewees described their experience of the patient's dying and death. Recruitment until data saturation and thematic analysis occurred concurrently.

Results: Ten families, nurses and doctors were interviewed in relation to 10 patients. In caring for the patients who are dying in the ICU and their families, nurses practice to their satisfaction with creativity and autonomy, although concerned about continuity of care at handover. Families appreciate kindness and regular sensitive communication. Families would like more contact with the ICU doctors. Limiting access to the patient according to ICU protocol is distressing for relatives. Doctors struggle with decision making, determining prognosis and witnessing the grief of relatives. Some doctors wish to have a greater part in care of the dying patient.

Conclusion: Distress among nurses reported in the ICU literature and attributed to disenfranchisement by doctors was not evident. In contrast, some doctors struggle to practice what they value. Adherence to ICU protocols needs flexibility when a patient is dying.

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CFTR regulates acute inflammatory responses in macrophages

Background: Mutation of cystic fibrosis transmembrane conductance regulator (CFTR) in the airway epithelial cells can lead to recurrent airway inflammation in cystic fibrosis (CF). Dysfunction of CFTR in neutrophils could contribute to LPS-induced acute lung inflammation. Deficiency of CFTR could also facilitate platelet aggregation and neutrophil–platelet interaction and promote inflammation.

Aim: To study whether inhibition or mutation of CFTR in alveolar macrophages (AMs) or peritoneal macrophages (PMs) would promote their proinflammatory responses and whether dysfunction of CFTR would deteriorate acute E. coli-induced lung or peritoneal inflammation.

Design: Laboratory study.

Methods: ELISA was used to determine production of proinflammatory cytokines in the CFTR inhibited or mutated macrophages under LPS challenge. Lung or peritoneum lavage was used to analyze proinflammatory parameters and cell differentiation. Excess lung water and lung vascular permeability were measured for evaluating severity of acute lung inflammation.

Results: Escherichia coli LPS simulation in AMs increased CFTR expression. Inhibition or mutation of CFTR in both AMs and PMs enhanced production of tumor necrosis factor alpha (TNF-α) and macrophage inflammatory protein-2 (MIP-2). Mutation of CFTR in macrophages exaggerated production of cytokines through NF-kB and p38 MAPK. Inhibition of CFTR by MalH2 or CFTR_inh-172 deteriorates E. coli-induced acute lung inflammation. Deficiency of CFTR promotes migration of monocytes and neutrophils in E. coli pneumonia and peritonitis mouse models.

Conclusions: CFTR expressed by alveolar or peritoneal macrophages regulates acute proinflammatory responses.

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Association of the clinical frailty scale with hospital outcomes

Background: the clinical frailty scale (CFS) was validated as a predictor of adverse outcomes in community-dwelling older people. In our hospital, the use of the CFS in emergency admissions of people aged ≥ 75 years was introduced under the Commissioning for Quality and Innovation payment framework.

Aim: we retrospectively studied the association of the CFS with patient characteristics and outcomes.

Design: retrospective observational study in a large tertiary university National Health Service hospital in UK.

Methods: the CFS was correlated with transfer to specialist Geriatric ward, length of stay (LOS), in-patient mortality and 30-day readmission rate.

Results: between 1st August 2013 and 31st July 2014, there were 11 271 emergency admission episodes of people aged ≥ 75 years (all specialties), corresponding to 7532 unique patients (first admissions); of those, 5764 had the CFS measured by the admitting team (81% of them within 72 hr of admission). After adjustment for age, gender, Charlson comorbidity index and history of dementia and/or current cognitive concern, the CFS was an independent predictor of in-patient mortality [odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.48 to 1.74, P < 0.001], transfer to Geriatric ward (OR = 1.33, 95% CI: 1.24 to 1.42, P < 0.001) and LOS ≥ 10 days (OR = 1.19, 95% CI: 1.14 to 1.23, P < 0.001). The CFS was not a multivariate predictor of 30-day readmission.

Conclusions: the CFS may help predict in-patient mortality and target specialist geriatric resources within the hospital. Usual hospital metrics such as mortality and LOS should take into account measurable patient complexity.

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Medicine,New Articles,November 25th,2015

Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease

Alexandros G. SfakianakisστοΚοσμητική ΟδοντοΙατρική και ΓναθοΧειρουργικήΠριν από 2 ώρες

Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease: Cardiovascular diseases are chronic inflammatory diseases that affect a large segment of society. Coronary heart disease (CHD), the most common cardiovascular disease, progresses over several years and affects millions of people worldwide. Chronic infections may contribute to the systemic inflammation and enhance the risk for CHD. Periodontitis is one of the most common chronic infections that affects up to 50% of the adult population. Under inflammatory...περισσότερα »

„Okkulte“ metastasierte Melanome?

Alexandros G. SfakianakisστοOtoRhinoLaryngology - Alexandros G. SfakianakisΠριν από 2 ώρες

„Okkulte“ metastasierte Melanome?: Zusammenfassung FalldarstellungWir berichten über 2 Patienten, die uns im vergangenen Jahr mit der Diagnose metastasiertes okkultes Melanom vorgestellt wurden. Bei einer 60-jährigen Patientin fand sich im Bereich der Labia majora rechts ein livider derber Tumor. Die histologische Untersuchung ergab ein ulzeriertes noduläres Schleimhautmelanom mit Satellitenmetastasen. Bei einem 60-jährigen Patienten fanden sich im Bereich des Digitus (D) I der rechten Hand eine subunguale Hyperkeratose mit schwärzlichen Pigmenteinsprenkelungen und ein hautfarbene... περισσότερα »

Sleep disturbance as a proximal predictor of suicidal intent in recently hospitalized attempters

Alexandros G. SfakianakisστοΥπνική Άπνοια και Διαταραχές ΎπνουΠριν από 2 ώρες

• A total of 127 hospitalised suicide attempters were interviewed within 2 weeks post-attempt.• The suicide attempters retrospectively assessed insomnia and mean sleep time for 2 weeks pre-attempt.• Insomnia, short sleep, and insomnia with short sleep predicted suicidal intent.• Insomnia and short sleep partially mediated various predictors' effect on intent.• Improving sleep in suicidal subjects may reduce the lethality of suicidal acts. from #SleepMedicine via ola Kala on Inoreader http://ift.tt/1lILITJ via IFTTT

Neutrophil proteolytic activation cascades: a possible mechanistic link between chronic periodontitis and coronary heart disease

Alexandros G. SfakianakisστοAllergy Rhinology Immunology AsthmaΠριν από 2 ώρες

Cardiovascular diseases are chronic inflammatory diseases that affect a large segment of society. Coronary heart disease (CHD), the most common cardiovascular disease, progresses over several years and affects millions of people worldwide. Chronic infections may contribute to the systemic inflammation and enhance the risk for CHD. Periodontitis is one of the most common chronic infections that affects up to 50% of the adult population. Under inflammatory conditions the activation of endogenous degradation pathways mediated by immune responses leads to the release of destructive ce... περισσότερα »

Genome-wide transcriptome induced by Porphyromonas gingivalis LPS supports the notion of host-derived periodontal destruction and its association with systemic diseases

Alexandros G. SfakianakisστοAllergy Rhinology Immunology AsthmaΠριν από 2 ώρες

Chronic periodontitis (CP) is a prevalent pathogen-associated inflammatory disorder characterized by the destruction of tooth-supporting tissues, and linked to several systemic diseases. Both the periodontopathogen *Porphyromonas gingivalis* (*Pg*), and the genetically determined host immune response, are hypothesized to play a crucial role in this association. To identify new target genes for CP and its associated systemic diseases, we investigated the transcriptome induced by *Pg* in human monocytes using a genome-wide approach. Monocytes were isolated from healthy male volunteer... περισσότερα »

Increased Proportion of Hematopoietic Stem and Progenitor Cell Population in Cord Blood of Neonates Born to Mothers with Gestational Diabetes Mellitus

Alexandros G. SfakianakisστοCell and Tissue Research by Alexandros G. SfakianakisΠριν από 2 ώρες

Stem Cells and Development , Vol. 0, No. 0. from Cell via ola Kala on Inoreader http://ift.tt/1LywbKY via IFTTT

Association between age, gender and multimorbidity level and receiving home health care: a population-based Swedish study

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

Background: Home health care is an important part of primary health care. How delivery of home health care is organised is probably important for sustainability of the healthcare system as a whole. More than 50 % of individuals over 65 years old have multimorbidity, which increases with higher age, also influencing the needs of home health care. Our aim was to study the proportion of the population above 65 years receiving home health care according to age, gender and multimorbidity level. Methods: The study population comprised 32,130 people aged 65 or more, living in Blekinge Co... περισσότερα »

Effects of exercise on neuromuscular junction components across age: systematic review of animal experimental studies

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

Background: During almost one-third of our life, maturation of the nervous system promotes strength and muscle mass increase. However, as age advances, the nervous system begins to suffer a slow and continue reduction of its functions. Neuromuscular junction (NMJ) is one of the structures of which change due to aging process. Physical training leads to significant adjustments in NMJs of young and aged animals. Nevertheless, studies that aimed to investigate this effect have, in many cases, methodological variables that may have some influence on the result. Thus, this study aimed ...περισσότερα »

Surgical versus medical management of patients with acute ischemic mitral regurgitation: a systematic review

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

AimsAcute ischemic mitral regurgitation (MR) is seen in patients with myocardial infarction and is associated with increased morbidity and mortality. The optimal treatment strategy of this condition however, is not well established. The aim of this manuscript is to conduct a systematic review of the medical literature to assess the relative benefits and harms of mitral valve surgery with medical therapy versus medical management alone for patients with acute ischemic MR of at least moderate severity. Methods: We performed a literature search in MEDLINE, Embase.com, and Cochrane Ce... περισσότερα »

Ambient Mass Spectrometry Imaging Using Direct Liquid Extraction Techniques

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

[image: TOC Graphic] Analytical Chemistry DOI: 10.1021/acs.analchem.5b04188 [image: ancham?d=yIl2AUoC8zA] from #Medicine via ola Kala on Inoreader http://ift.tt/1XdUTwg via IFTTT

Protein Analysis by Ambient Ionization Mass Spectrometry Using Trypsin-Immobilized Organosiloxane Polymer Surfaces

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

[image: TOC Graphic] Analytical Chemistry DOI: 10.1021/acs.analchem.5b03669 [image: ancham?d=yIl2AUoC8zA] from #Medicine via ola Kala on Inoreader http://ift.tt/1XdURUY via IFTTT

Graphene Nanoribbon-Supported PtPd Concave Nanocubes for Electrochemical Detection of TNT with High Sensitivity and Selectivity

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

[image: TOC Graphic] Analytical Chemistry DOI: 10.1021/acs.analchem.5b03390 [image: ancham?d=yIl2AUoC8zA] from #Medicine via ola Kala on Inoreader http://ift.tt/1jiTmlY via IFTTT

Novel Fluorometric Method for the Determination of Production Rate and Steady-State Concentration of Photochemically Generated Superoxide Radical in Seawater Using 3′,6′-(Diphenylphosphinyl)fluorescein

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

[image: TOC Graphic] Analytical Chemistry DOI: 10.1021/acs.analchem.5b00917 [image: ancham?d=yIl2AUoC8zA] from #Medicine via ola Kala on Inoreader http://ift.tt/1XdUTfD via IFTTT

Acknowledgement to Referees

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

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Brinzolamide–brimonidine for POAG and OHT

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

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A Preliminary Genome-Wide Association Study of Acute Mountain Sickness Susceptibility in a Group of Nepalese Pilgrims Ascending to 4380 m

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

High Altitude Medicine & Biology , Vol. 0, No. 0. from #Medicine via ola Kala on Inoreader http://ift.tt/1jiTm5r via IFTTT

Detecting Arbitrary DNA Mutations Using Graphene Oxide and Ethidium Bromide

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

[image: TOC Graphic] Analytical Chemistry DOI: 10.1021/acs.analchem.5b03369 [image: ancham?d=yIl2AUoC8zA] from #Medicine via ola Kala on Inoreader http://ift.tt/1XdUQ3D via IFTTT

General Strategy for Enhancing Electrochemiluminescence of Semiconductor Nanocrystals by Hydrogen Peroxide and Potassium Persulfate as Dual Coreactants

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

[image: TOC Graphic] Analytical Chemistry DOI: 10.1021/acs.analchem.5b03890 [image: ancham?d=yIl2AUoC8zA] from #Medicine via ola Kala on Inoreader http://ift.tt/1TdyMQN via IFTTT

A Preliminary Genome-Wide Association Study of Acute Mountain Sickness Susceptibility in a Group of Nepalese Pilgrims Ascending to 4380 m

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

High Altitude Medicine & Biology , Vol. 0, No. 0. from #Medicine via ola Kala on Inoreader http://ift.tt/1jiTm5r via IFTTT

Chondrocalcinosis, Tumoral Calcinosis, - Everything You Need To Know - Dr. Nabil Ebraheim

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

Educational video describing the differences between Chondrocalcinosis, Tumoral Calcinosis, Synovial Chondromatosis, & Calcific Tendonitis Become a friend on facebook: http://ift.tt/1eMj35K Follow me on twitter: https://twitter.com/#!/DrEbraheim_UTMC Donate to the University of Toledo Foundation Department of Orthopaedic Surgery Endowed Chair Fund: http://ift.tt/1HCFAla from #Medicine via ola Kala on Inoreader https://www.youtube.com/watch?v=PUi8DjuNisc via IFTTT

SSVEP-based Experimental Procedure for Brain-Robot Interaction with Humanoid Robots

Αλέξανδρος ΣφακιανάκηςστοMedicine by Alexandros G.SfakianakisΠριν από 3 ώρες

[image: 53558eq1.jpg] The overall goal of this method is to establish an SSVEP-based experimental procedure by integrating multiple software programs to enable the study of brain-robot interaction with humanoid robots, which is prospective in assisting the sick and elderly as well as performing unsanitary or dangerous jobs. from #Medicine via ola Kala on Inoreader http://ift.tt/1XdUQQZ via IFTTT

Increased Proportion of Hematopoietic Stem and Progenitor Cell Population in Cord Blood of Neonates Born to Mothers with Gestational Diabetes Mellitus

Alexandros G. SfakianakisστοCell and Tissue Research by Alexandros G. SfakianakisΠριν από 4 ώρες

Stem Cells and Development , Vol. 0, No. 0. from Cell via ola Kala on Inoreader http://ift.tt/1LywbKY via IFTTT

Kidney transplantation in infantile myofibromatosis and fibromuscular dysplasia: a case report

Alexandros G. SfakianakisστοΟγκολογίαΠριν από 4 ώρες

[image: s13256-015-0756-8-1.gif] IntroductionWe report what we believe to be the first case of a child affected by two rare vascular diseases complicated by kidney failure and successfully treated by kidney transplantation.Case presentationA 3-year-old Caucasian girl with fibromuscular dysplasia and infantile myofibromatosis presented with arterial hypertension and renal failure. She received a deceased donor kidney transplantation distal to an iliac graft. The technical peculiarities of this transplantation are described, as well as her favorable long-term outcome. Conclusion: Kid... περισσότερα »