Τρίτη 13 Δεκεμβρίου 2016

Out-of-pocket medical costs and third-party healthcare costs for children with Down syndrome

Prior analyses have estimated the lifetime total societal costs of a person with Down syndrome (DS); however, no studies capture the expected medical costs that patients with DS can expect to incur during childhood. The study utilized the OptumHealth Reporting and Insights administrative claims database from 1999 to 2013. Children with a diagnosis of DS were identified, and their time was divided into clinically relevant age categories. Patients with DS in each age category were matched to controls without chromosomal conditions. Out-of-pocket medical costs and third-party expenditures were compared between the patient-age cohorts with DS and matched controls. Patients with DS had significantly higher mean annual out-of-pocket costs than their matched controls within each age and cost category. Total annual incremental out-of-pocket costs associated with DS were highest among individuals from birth to age 1 ($1,907, P < 0.001). The main drivers of the incremental out-of-pocket costs associated with DS were inpatient costs in the 1st year of life ($925, P <0.001) and outpatient costs in later years (ranging $183–$623, all P < 0.001). Overall, patients with DS incurred incremental out-of-pocket medical costs of $18,248 between birth and age 18 years; third-party payers incurred incremental costs of $230,043 during the same period. Across all age categories, mean total out-of-pocket annual costs were greater for individuals with DS than those of matched controls. On average, parents of children with DS pay an additional $84 per month for out-of-pocket medical expenses when costs are amortized over 18 years. © 2016 Wiley Periodicals, Inc.



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Implications of cellular models of dopamine neurons for disease

This review addresses the present state of single-cell models of the firing pattern of midbrain dopamine neurons and the insights that can be gained from these models into the underlying mechanisms for diseases such as Parkinson's, addiction, and schizophrenia. We will explain the analytical technique of separation of time scales and show how it can produce insights into mechanisms using simplified single-compartment models. We also use morphologically realistic multicompartmental models to address spatially heterogeneous aspects of neural signaling and neural metabolism. Separation of time scale analyses are applied to pacemaking, bursting, and depolarization block in dopamine neurons. Differences in subpopulations with respect to metabolic load are addressed using multicompartmental models.



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Specific connectivity between photoreceptors and horizontal cells in the zebrafish retina

The functional and morphological connectivity between various horizontal cell (HC) types (H1, H2, H3, and H4) and photoreceptors was studied in zebrafish retina. Since HCs are strongly coupled by gap junctions and feedback from HCs to photoreceptors depends strongly on connexin (Cx) hemichannels, we characterized the various HC Cxs (Cx52.6, Cx52.7, Cx52.9, and Cx55.5) in Xenopus oocytes. All Cxs formed hemichannels that were conducting at physiological membrane potentials. The Cx hemichannels differed in kinetic properties and voltage dependence, allowing for specific tuning of the coupling of HCs and the feedback signal from HCs to cones. The morphological connectivity between HC layers and cones was determined next. We used zebrafish expressing green fluorescent protein under the control of Cx promoters. We found that all HCs showed Cx55.5 promoter activity. Cx52.7 promoter activity was exclusively present in H4 cells, while Cx52.9 promoter activity occurred only in H1 cells. Cx52.6 promoter activity was present in H4 cells and in the ventral quadrant of the retina also in H1 cells. Finally, we determined the spectral sensitivities of the HC layers. Three response types were found. Monophasic responses were generated by HCs that contacted all cones (H1 cells), biphasic responses were generated by HCs that contacted M, S, and UV cones (H2 cells), and triphasic responses were generated by HCs that contacted either S and UV cones (H3 cells) or rods and UV cones (H4 cells). Electron microscopy confirms that H4 cells innervate cones. This indicates that rod-driven HCs process spectral information during photopic and luminance information during scotopic conditions.



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Spontaneous activity is correlated with coding density in primary auditory cortex

Sensory neurons across sensory modalities and specific processing areas have diverse levels of spontaneous firing rates (SFRs) in the absence of sensory stimuli. However, the functional significance of this spontaneous activity is not well-understood. Previous studies in the auditory system have demonstrated that different levels of spontaneous activity are correlated with a variety of physiological and anatomic properties, suggesting that neurons with differing SFRs make unique contributions to the encoding of auditory stimuli. Additionally, altered SFRs are a correlate of tinnitus, arising in several auditory areas after exposure to ototoxic substances and noise trauma. In this study, we recorded single-unit activity from primary auditory cortex of awake marmoset monkeys while delivering wide-band random-spectrum stimuli and white Gaussian noise (WGN) to examine any divergences in stimulus encoding properties across SFR classes. We found that higher levels of spontaneous activity were associated with both higher levels of activation relative to suppression across a variety of wide-band stimuli and higher driven rates in response to WGN. Moreover, response latencies to WGN were negatively correlated with the level of activation in response to both stimulus types. These findings are consistent with a novel view of the role spontaneous spiking may play during normal stimulus processing in primary auditory cortex and how it may malfunction in cases of tinnitus.



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AZATHIOPRINE FOR REFRACTORY ULCERATIVE PROCTITIS: A RETROSPECTIVE MULTICENTER STUDY

Efficacy of azathioprine (AZA) in refractory ulcerative proctitis (UP) is unknown.

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AZATHIOPRINE FOR REFRACTORY ULCERATIVE PROCTITIS: A RETROSPECTIVE MULTICENTER STUDY

Efficacy of azathioprine (AZA) in refractory ulcerative proctitis (UP) is unknown.

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The Effects of Early Exercise on Motor, Sense, and Memory Recovery in Rats With Stroke.

Objective: Exercise is an effective, inexpensive, home-based, and accessible intervention strategy for stroke treatment, and early exercise after stroke has attracted a great deal of attention in recent years. However, the effects of early exercise on comprehensive functional recovery remain poorly understood. The present study investigated the effect of early exercise on motor, sense, balance, and spatial memory recovery. Design: Adult Sprague-Dawley rats were subjected to unilateral middle cerebral artery occlusion (MCAO) and were randomly divided into early exercise group (EE), non-exercise group (NE), and sham group. EE group received 2 weeks of exercise training initiated at 24 hours after operation. The recovery of motor, sense, and balance function was evaluated every 3 days after MCAO. Spatial memory recovery was detected from 21 to 25 days after MCAO. Results: The results showed that early exercise significantly promoted the motor and spatial memory recovery with statistical differences. The rats in EE group have a better recovery in sense and balance function, but there is no statistically significant difference about these results. Conclusion: Our results showed that early moderate exercise can significantly promote motor and spatial memory recovery, but not the sense and balance functions. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Effectiveness of Extracorporeal Shock Wave Therapy Without Local Anesthesia in Patients With Recalcitrant Plantar Fasciitis: A Meta-Analysis of Randomized Controlled Trials.

Objective: The objective of this meta-analysis was to investigate the efficacy of extracorporeal shock wave therapy in the treatment of recalcitrant plantar fasciitis without local anesthesia. Methods: The Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched from inception to September 2015 for randomized controlled trials comparing ESWT without local anesthesia versus placebo for treatment of plantar fasciitis in adults. The primary outcome was the 12-week post-intervention success rate of reducing the visual analog scale score by 60% from baseline at the first step in the morning, reducing the VAS score by 60% from baseline during daily activities, reducing the Roles and Maudsley score, reducing overall heel pain, and reducing pain after applying a force meter. Results: Nine studies were included in the meta-analysis. Compared with placebo, ESWT significantly improved the success rate of reducing overall heel pain, reducing the VAS score by 60% at the first step in the morning and during daily activities, improving the Roles and Maudsley score to excellent or good, and reducing heel pain after application of a pressure meter. Conclusions: ESWT seems to be particularly effective in relieving pain associated with RPF. ESWT should be considered when traditional treatments have failed. To Claim CME Credits: Complete the self-assessment activity and evaluation online at http://ift.tt/1l80W45 CME Objectives: Upon completion of this article, the reader should be able to (1) understand the recovery rates for nonsurgical treatment of plantar fasciitis, (2) understand the role of extracorporeal shockwave therapy (ESWT) in the treatment of recalcitrant plantar fasciitis, and (3) understand the indications to incorporate ESWT in the treatment plan of recalcitrant plantar fasciitis. Level: Advanced Accreditation: The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s)(TM). Physicians should only claim credit commensurate with the extent of their participation in the activity. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved.

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Angiotensin II reduces the surface abundance of KV1.5 channels in arterial myocytes to stimulate vasoconstriction

Smooth muscle cells (myocytes) of resistance-size arteries express several different voltage-dependent K+ (KV) channels, including KV1.5 and KV2.1, which regulate contractility. Myocyte KV currents are inhibited by vasoconstrictors, including angiotensin II (Ang II), but mechanisms involved are unclear. Here, we tested the hypothesis that Ang II inhibits KV currents by reducing the plasma membrane abundance of KV channels in myocytes. Ang II (2 h) reduced surface and total KV1.5 protein in rat mesenteric arteries. In contrast, Ang II did not alter total or surface KV2.1, or KV1.5 or KV2.1 cellular distribution, measured as the percentage of total protein at the surface. Bisindolylmaleimide (BIM), a protein kinase C (PKC) blocker, a PKC inhibitory peptide, or bafilomycin A, a lysosomal degradation inhibitor, each blocked the Ang II-induced decrease in total and surface KV1.5. Immunofluorescence also suggested that Ang II reduced surface KV1.5 protein in isolated myocytes; an effect inhibited by BIM. Arteries were exposed to Ang II or Ang II plus BIM (2 h), after which these agents were removed and contractility measurements performed or myocytes isolated for patch-clamp electrophysiology. Ang II reduced both whole-cell KV currents and currents inhibited by psora-4, a KV1.5 channel blocker. Ang II also reduced vasoconstriction stimulated by psora-4 or 4-aminopyridine, another KV channel inhibitor. These data indicate that Ang II activates PKC, which stimulates KV1.5 channel degradation, leading to a decrease in surface KV1.5, a reduction in whole-cell KV1.5 currents and a loss of functional KV1.5 channels in myocytes of pressurized arteries.

This article is protected by copyright. All rights reserved



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Huddles and Debriefings

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Publication date: Available online 12 December 2016
Source:Anesthesiology Clinics
Author(s): Emily McQuaid-Hanson, May C.M. Pian-Smith

Teaser

Interprofessional teams work together on the labor and delivery unit, where clinical care is often unscheduled, rapidly evolving, and fast paced. Effective communication is key for coordinated delivery of optimal care and for fostering a culture of community and safety in the workplace. The preoperative huddle allows for information sharing, cross-checking, and preparation before the start of surgery. Postoperative debriefings allow the operative team to engage in ongoing process improvement. Debriefings after adverse events allow for shared understanding, mutual healing, and help mitigating the harm to potential "second victims."


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Update in the Management of Patients with Preeclampsia

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Publication date: Available online 12 December 2016
Source:Anesthesiology Clinics
Author(s): Nerlyne K. Dhariwal, Grant C. Lynde

Teaser

Hypertensive disorders of pregnancy complicate approximately 10% of all deliveries in the United States and are a leading cause of maternal and fetal morbidity and mortality. Preeclampsia is defined as hypertension in association with proteinuria, thrombocytopenia, impaired liver function, renal insufficiency, pulmonary edema, or new-onset cerebral or visual disturbances. The greatest risk factor for the development of preeclampsia is a history of preeclampsia. There currently is no effective means for the prevention of preeclampsia. Approximately 39% of patients diagnosed with preeclampsia have hypertension and approximately 20% have proteinuria 3 months postpartum. Preeclampsia increases the risk of patients developing hypertension later in life.


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General Anesthesia During the Third Trimester

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Publication date: Available online 12 December 2016
Source:Anesthesiology Clinics
Author(s): Annemaria De Tina, Arvind Palanisamy

Teaser

Rodent studies on the effect of general anesthesia during the third trimester on neurocognitive outcomes are mixed, but primate studies suggest that a clinically relevant exposure to anesthetic agents during the third trimester can trigger neuronal and glial cell death. Human studies are conflicting and the evidence is weak. This is an up-to-date review of the literature on the neurodevelopmental effects of anesthetic agents administered during the third trimester. Early brain development and critical periods of neurodevelopment as it relates to neurotoxicity are highlighted. Rodent, nonhuman primate, and population studies are discussed and placed in the context of clinical practice.


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Awareness and Aortocaval Obstruction in Obstetric Anesthesia

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Publication date: Available online 12 December 2016
Source:Anesthesiology Clinics
Author(s): Nathaniel Hsu, Robert Gaiser

Teaser

Awareness during general anesthesia for cesarean delivery continues to be a major problem. The key to preventing awareness is strict attention to anesthetic technique. The prevalence and implications of aortocaval compression have been firmly established. Compression of the vena cava is a real occurrence when assuming the supine position. Relief of this compression most likely does not occur until the patient is turned 30°, which is not feasible for performing cesarean delivery. Although it is still wise to tilt the patient, the benefit of this tilt may not be as great as once thought.


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Optimal Pain Management After Cesarean Delivery

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Publication date: Available online 12 December 2016
Source:Anesthesiology Clinics
Author(s): Caitlin Dooley Sutton, Brendan Carvalho

Teaser

Cesarean delivery rates are increasing worldwide, and effective postoperative pain management is a key priority of women undergoing cesarean delivery. Inadequate pain management in the acute postoperative period is associated with persistent pain, greater opioid use, delayed functional recovery, and increased postpartum depression. In addition to pain relief, optimal management of patients after cesarean delivery should address the goals of unrestricted maternal mobility, minimal maternal and neonatal side effects, rapid recovery to baseline functionality, and early discharge home. Multimodal analgesia should include neuraxial morphine in conjunction with nonopioid adjuncts, with additional oral or intravenous opioids reserved for severe breakthrough pain.


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Epidural Analgesia for Labor

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Publication date: Available online 12 December 2016
Source:Anesthesiology Clinics
Author(s): Onyi C. Onuoha

Teaser

Despite the traditional practice to maintain labor analgesia with a combination of continuous epidural infusion and patient-controlled epidural analgesia using an automated epidural pump; compelling data now shows that bolus injection through the epidural catheter may result in better distribution of anesthetic solution in the epidural space. The programmed intermittent epidural bolus technique is proposed as a better maintenance mode and may represent a more effective mode of maintaining epidural analgesia for labor, especially prolonged labor. Additional prospective and adequately powered studies are needed to confirm findings and determine the optimal combination of volume, rate, time, and drug concentration.


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Epigenomics: Deciphering non-coding variation with 3D epigenomics

Nature Reviews Genetics 18, 4 (2017). doi:10.1038/nrg.2016.161

Author: Darren J. Burgess

The majority of disease-associated genetic variants identified by genome-wide association studies (GWAS) are in non-coding regions of the genome. This indicates a pathological regulatory role for these variants, but identifying mechanisms of action and their corresponding target genes is often challenging. As part of the



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Gene therapy: In vivo gene editing in non-dividing cells

Nature Reviews Genetics 18, 1 (2017). doi:10.1038/nrg.2016.158

Author: Denise Waldron

Targeted gene integration in non-dividing cells presents a great challenge, as existing genome editing techniques typically rely on the homology-directed repair (HDR) pathway, which is most active during DNA replication. In a new study published in Nature, scientists have developed a technique that enables



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Cancer genomics: Single-cell RNA-seq to decipher tumour architecture

Nature Reviews Genetics 18, 2 (2017). doi:10.1038/nrg.2016.151

Author: Ross Cloney

Tumours consist of a mix of cells with different morphological and phenotypic characteristics, and a greater understanding of the source of this heterogeneity could greatly influence therapeutic strategies. Now, Tirosh and Venteicher et al. used a comprehensive single-cell RNA sequencing (RNA-seq) approach on oligodendroglioma



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DNA elements: The ins and outs of enhancer validation

Nature Reviews Genetics 18, 2 (2017). doi:10.1038/nrg.2016.155

Author: Linda Koch

Comprehensive, functionally validated enhancer data sets for different tissues and cell types enable the systematic exploration of the roles of these regulatory elements in biology and disease. A new study by Inoue et al. now raises concerns about the validity of using episomal reporter



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From profiles to function in epigenomics

Nature Reviews Genetics 18, 51 (2017). doi:10.1038/nrg.2016.138

Authors: Stefan H. Stricker, Anna Köferle & Stephan Beck

Myriads of epigenomic features have been comprehensively profiled in health and disease across cell types, tissues and individuals. Although current epigenomic approaches can infer function for chromatin marks through correlation, it remains challenging to establish which marks actually have causative roles in gene regulation and



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DNA repair: RNA–DNA hybrids: double-edged swords

Nature Reviews Genetics 18, 3 (2017). doi:10.1038/nrg.2016.153

Author: Denise Waldron

RNA–DNA hybrids are associated with DNA damage and genome instability and are thus typically thought of as harmful. A paper in Cell now reports that RNA–DNA hybrids have a functional role in the homologous recombination (HR)-mediated repair of double strand DNA breaks (DSBs) and



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Microbial genome-wide association studies: lessons from human GWAS

Nature Reviews Genetics 18, 41 (2017). doi:10.1038/nrg.2016.132

Authors: Robert A. Power, Julian Parkhill & Tulio de Oliveira

The reduced costs of sequencing have led to whole-genome sequences for a large number of microorganisms, enabling the application of microbial genome-wide association studies (GWAS). Given the successes of human GWAS in understanding disease aetiology and identifying potential drug targets, microbial GWAS are likely to



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Loss-of-function genetic tools for animal models: cross-species and cross-platform differences

Nature Reviews Genetics 18, 24 (2017). doi:10.1038/nrg.2016.118

Authors: Benjamin E. Housden, Matthias Muhar, Matthew Gemberling, Charles A. Gersbach, Didier Y. R. Stainier, Geraldine Seydoux, Stephanie E. Mohr, Johannes Zuber & Norbert Perrimon

Our understanding of the genetic mechanisms that underlie biological processes has relied extensively on loss-of-function (LOF) analyses. LOF methods target DNA, RNA or protein to reduce or to ablate gene function. By analysing the phenotypes that are caused by these perturbations the wild-type function of



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Paramutation and related phenomena in diverse species

Nature Reviews Genetics 18, 5 (2017). doi:10.1038/nrg.2016.115

Author: Jay B. Hollick

Paramutation describes a process that results in heritable epigenetic changes of gene regulation and trans-homologue interactions. Recent discoveries in model organisms have highlighted roles for the respective nuclear systems that regulate transposons via small RNA molecules both for paramutation and for defining transgenerational inheritance. Differences



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Surgical intervention for paediatric liver injuries is almost history - A 12-year cohort from a major Scandinavian trauma centre

Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine

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Hepatitis B virus infection and risk of gallstones: A systematic review and meta-analysis

European Journal of Gastroenterology & Hepatology

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Blood test hope for bowel diseases

University of Edinburgh College of Medicine News

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Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma: Age is not a problem

European Journal of Gastroenterology & Hepatology

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Imaging features predict prognosis of patients with combined hepatocellular-cholangiocarcinoma

Clinical Radiology

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Dietary quality of the US child and adolescent population: Trends from 1999 to 2012 and associations with the use of federal nutrition assistance programs

American Journal of Clinical Nutrition

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Keratin 19 as a key molecule in progression of human hepatocellular carcinomas through invasion and angiogenesis

BMC Cancer

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Association of serum albumin and aspartate transaminase with 5-year all-cause mortality in HIV/hepatitis C virus coinfection and HIV monoinfection

AIDS

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Application of the combined FibroMeter VCTE algorithm in Chinese patients with nonalcoholic fatty liver disease

Journal of Gastroenterology and Hepatology

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Differential radiographic appearance of BRAF V600E-mutant metastatic colorectal cancer in patients matched by primary tumor location

Journal of the National Comprehensive Cancer Network

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Abdominal obesity, gender and the risk of rheumatoid arthritis – A nested case–control study

Arthritis Research & Therapy

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Prognostic and predictive significance of long interspersed nucleotide element-1 methylation in advanced-stage colorectal cancer

BMC Cancer

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Early prediction of thiopurine-induced hepatotoxicity in inflammatory bowel disease

Alimentary Pharmacology and Therapeutics

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Prognostic durability of liver fibrosis tests and improvement in predictive performance for mortality by combining tests

Journal of Gastroenterology and Hepatology

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Predictive value of CT for first esophageal variceal bleeding in patients with cirrhosis: Value of para-umbilical vein patency

European Journal of Radiology

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Left lobe auxiliary liver transplantation for end-stage hepatitis b liver cirrhosis

American Journal of Transplantation

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Assessing colonic anatomy normal values based on air contrast enemas in children younger than 6 years

Pediatric Radiology

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Poor outcomes of gastric cancer surgery after admission through the emergency department

Annals of Surgical Oncology

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Impact of low-energy CT imaging on selection of positive oral contrast media concentration

Abdominal Imaging

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Patient preferences for palliative treatment of locally advanced or metastatic gastric cancer and adenocarcinoma of the gastroesophageal junction: A choice-based conjoint analysis study from Germany

BMC Cancer

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Laparoscopic-assisted abdominoperineal resection combined with en-bloc prostatectomy using the trans-sacral approach for locally invasive rectal cancer: A case report

Abstract

Laparoscopic-assisted abdominoperineal resection and en-bloc prostatectomy using the trans-sacral approach for locally invasive rectal cancer that invades only the prostate is useful in order to avoid total pelvic exenteration. The patient was a 63-year-old man with cT4b (prostate) N1M0, stage IIIC rectal cancer. Curative resection was performed. Histopathological findings did not indicate definitive invasion into the prostate gland. The patient was discharged from the hospital on postoperative day 32 with an anastomotic leak and a ureteral catheter. The patient is able to urinate and has had no cancer recurrence. Laparoscopic bladder-preserving surgery for locally invasive rectal cancer can preserve postoperative quality of life and provides oncological curability.



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The activPAL TM Accurately Classifies Activity Intensity Categories in Healthy Adults.

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The activPALTM (AP) monitor is well established for distinguishing sitting, standing and stepping time. However, its validity in predicting time in physical activity intensity categories in a free-living environment has not been determined. Purpose: To determine the validity of the AP in estimating time spent in sedentary, light and moderate-to-vigorous physical activity (MVPA) in a free-living environment. Methods: Thirteen participants (mean (SD) age 24.8 y (5.2), BMI 23.8 kg.m2 (1.9)) were directly observed (DO) for three 10-hr periods wearing an AP. A custom R program was developed and used to summarize detailed active and sedentary behavior variables from the AP. AP estimates were compared to DO. Results: The AP accurately and precisely estimated time in activity intensity categories (bias (95% CI) sedentary = 0.8 min (-2.9, 4.5), light = 1.7 min (2.2, 5.7) and -2.6 min (-5.8, 0.7)). The overall accuracy rate for time in intensity categories was 96.2%. The AP also accurately estimated guideline minutes, guideline bouts, prolonged sitting minutes and prolonged sitting bouts. Conclusion: The AP can be used to accurately capture individualized estimates of active and sedentary behavior variables in free-living settings. (C) 2016 American College of Sports Medicine

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Study of cardiac arrhythmias in acute myocardial infarction within 48 hours

2016-12-13T00-40-50Z
Source: International Journal of Advances in Medicine
Vikash Kumar, Mrityunjay Pratap Singh, Pramod Kumar Agrawal, Atul Kumar, Sonu Chauhan.
Background: The profile of coronary artery disease is different in India in terms of incidence and risk factors. Indians show higher incidence of hospitalization, morbidity and mortality than other ethnic groups. Majority of deaths in acute myocardial infarction are due to arrhythmias. These would suggest that more aggressive identification and modulation of cardiac arrhythmias in acute myocardial infarction is necessary among Asian Indian. This study is undertaken to study the profile of arrhythmias in acute myocardial infarction within in 48 hours of hospitalization in our hospital. Methods: This study was conducted in KMCH, Katihar, Bihar, India. A total of 50 (38 males, 12 females) patients admitted to the coronary care unit with diagnosis of acute myocardial infarction were included to the study. Patients were monitored for 48 hours and pattern of arrhythmias were noted. Results: 38 males and 12 females were studied. 65% of the patients were thrombolysed. Arrhythmia was seen in 78% of the patients. 70% of the arrhythmias occurred during the first hour. 58% of the arrhythmias underwent spontaneous resolution. 23% of the patients had sinus bradycardia. Conclusions: The present study suggests that majority of the patients with acute myocardial infarction had arrhythmias. Sinus bradycardia was the commonest arrhythmia, followed by ventricular premature contractions. However ventricular premature contractions also occurred along with other arrhythmias.


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Dynamics of volume-averaged intracellular Ca2+ in a rat CNS nerve terminal during single and repetitive voltage-clamp depolarizations

Many aspects of short-term synaptic plasticity (STP) are controlled by relatively slow changes in the presynaptic intracellular concentration of free calcium ions ([Ca2+]i) that occur in the time range of a few milliseconds to several seconds. In nerve terminals, [Ca2+]i equilibrates diffusionally during such slow changes, such that the globally measured, residual [Ca2+]i that persists after the collapse of local domains is often the appropriate parameter governing STP. Here, we study activity-dependent dynamic changes in global [Ca2+]i at the rat calyx of Held nerve terminal in acute brainstem slices using patch-clamp and microfluorimetry. We use low concentrations of a low-affinity Ca2+ indicator dye (100 μM Fura-6F) in order not to overwhelm endogenous Ca2+ buffers. We first study voltage-clamped terminals, dialyzed with pipette solutions containing minimal amounts of Ca2+ buffers, to determine Ca2+ binding properties of endogenous fixed buffers as well as the mechanisms of Ca2+ clearance. Subsequently, we use pipette solutions including 500 μM EGTA in order to determine the Ca2+ binding kinetics of this chelator. We provide a formalism and parameters, which allow one to predict [Ca2+]i changes in calyx nerve terminals in response to a wide range of stimulus protocols. Unexpectedly, we find that the Ca2+-affinity of EGTA under the conditions of our measurements is substantially lower (KD = 543 ± 51 nM) than measured in vitro, mainly as a consequence of a higher then previously assumed dissociation rate constant (2.38 ± 0.20 s−1), which we need to postulate in order to model the measured presynaptic [Ca2+]i transients.

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Prediction of Opioid Analgesic Efficacy by Measurement of Pupillary Unrest.

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BACKGROUND: Pupillary unrest under ambient light (PUAL) is the fluctuation in pupil diameter in time around a mean value. PUAL is augmented by light and diminished by administration of opioids. We hypothesized that, because pupillary unrest is a marker of opioid effect, low levels of PUAL may be associated with reduced opioid efficacy, as measured by changes in the numerical rating scale (NRS) pain scores of patients in the postanesthesia care unit (PACU). METHODS: We used an infrared pupillometer to measure PUAL in patients recovering from ambulatory surgery at 2 different institutions. At both sites, PUAL was quantified using spectral analysis of the Fourier transform of pupil diameter versus time. We measured PUAL and pain scores before and after opioid administration. Protocols for total capture time and lighting conditions varied between the 2 sites. Correlations between PUAL and change in NRS scores were examined using significance testing of Pearson correlation coefficients. Correlations between change in PUAL and change in NRS scores were also examined. Patients were divided into high and low PUAL groups, and high and low response to opioid. A Fisher exact test was used to determine whether there was a significant association between PUAL and opioid response. RESULTS: For patients with pain in the PACU, low levels of pupillary unrest before opioid therapy were associated with minimal or no reduction in pain scores after opioid administration. We noted a significant correlation at both sites between PUAL and pain score reduction with opioids (r = 0.59, P = .0053, and r = 0.57, P = .022.) The Fisher exact test confirmed that patients with PUAL levels above the mean had a more beneficial analgesic effect from opioids than those with low PUAL levels (P = .018). We also noted that change in PUAL was significantly correlated with change in pain score at both sites (r = 0.56, P = .03 and r = 0.55, P = .01). CONCLUSIONS: We observe that the pretreatment magnitude of PUAL is correlated with the analgesic response to opioid therapy, and that patients who exhibit higher levels of PUAL change after opioid administration have a more beneficial analgesic effect from opioids. Larger studies with uniform measurement protocols are required to confirm these preliminary results. (C) 2016 International Anesthesia Research Society

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Sedation of Patients With Disorders of Consciousness During Neuroimaging: Effects on Resting State Functional Brain Connectivity.

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BACKGROUND: To reduce head movement during resting state functional magnetic resonance imaging, post-coma patients with disorders of consciousness (DOC) are frequently sedated with propofol. However, little is known about the effects of this sedation on the brain connectivity patterns in the damaged brain essential for differential diagnosis. In this study, we aimed to assess these effects. METHODS: Using resting state functional magnetic resonance imaging 3T data obtained over several years of scanning patients for diagnostic and research purposes, we employed a seed-based approach to examine resting state connectivity in higher-order (default mode, bilateral external control, and salience) and lower-order (auditory, sensorimotor, and visual) resting state networks and connectivity with the thalamus, in 20 healthy unsedated controls, 8 unsedated patients with DOC, and 8 patients with DOC sedated with propofol. The DOC groups were matched for age at onset, etiology, time spent in DOC, diagnosis, standardized behavioral assessment scores, movement intensities, and pattern of structural brain injury (as assessed with T1-based voxel-based morphometry). RESULTS: DOC were associated with severely impaired resting state network connectivity in all but the visual network. Thalamic connectivity to higher-order network regions was also reduced. Propofol administration to patients was associated with minor further decreases in thalamic and insular connectivity. CONCLUSIONS: Our findings indicate that connectivity decreases associated with propofol sedation, involving the thalamus and insula, are relatively small compared with those already caused by DOC-associated structural brain injury. Nonetheless, given the known importance of the thalamus in brain arousal, its disruption could well reflect the diminished movement obtained in these patients. However, more research is needed on this topic to fully address the research question. (C) 2016 International Anesthesia Research Society

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Comparison Between Retrograde and Antegrade Peripheral Venous Cannulation in Intensive Care Unit Patients: Assessment of Thrombus Formation.

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BACKGROUND: Antegrade cannulation of peripheral veins is the usual practice. Blood stasis between a catheter and the wall of the vein or at its tip in addition to catheter-induced phlebitis may initiate a thrombosis. The use of retrograde ventriculojugular shunts against the direction of the blood flow with resultant decrease in the incidence of venous thrombosis encouraged us to compare retrograde versus conventional antegrade peripheral venous cannulation. METHODS: Monocentric, nonblinded, prospective observational cohort of 40 intensive care unit patients receiving 2 peripheral venous catheters in upper limbs, 1 inserted in the direction of blood flow (antegrade cannula) and the other inserted in an opposite direction to blood flow (retrograde cannula). Daily ultrasound assessment of the angle between the catheter and the vascular wall was done to detect onset and progression of thrombus formation. RESULTS: The study included 40 patients, aged 46.7 +/- 10.132 years. The incidence of thrombus formation was 100% in both techniques. The onset time of thrombus formation between the catheter and the wall of a vein was significantly longer with the retrograde catheters than with the antegrade catheters with median time (interquartile range [range]) 6 days (5-6.75 [4-8]) with 95% confidence interval (CI) 5.58-6.42 versus 3 days (3-4 [2-5]) with 95% CI (2.76-3.24), respectively, with a P value <.001. the time needed by recently detected thrombus to reach catheter tip determined ultrasound with or without failure was significantly longer in retrograde catheters than antegrade median range days ci versus respectively a p value conclusions: cannulation did not decrease incidence of formation but increased onset until and prolonged newly formed compared conventional cannulation. international anesthesia research society>

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The endothelial glycocalyx and perioperative lung injury.

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Purpose of review: Ventilator-induced lung injury is a major contributor to perioperative lung injury. The end-expiratory lung volume, regional lung overdistension, and tidal recruitment are known to be the main factors causing subsequent alveolar damage and inflammation. The alveolar-capillary membrane including the endothelial glycocalyx as an integral part of the vascular endothelium seems to play a major role in different kinds of lung injury. Recent findings: Recent studies underline the pivotal importance of the endothelial glycocalyx in lung injury. The glycocalyx regulates and modulates plasma endothelial cell interactions. Several triggers are known to deteriorate the gylcocalyx such as fluid overload, ischemia, and TRALI. The clinical manifestation is inflammation, capillary leak, and edema formation. Breakdown of the endothelial gylcocalyx is of gaining importance in the context of one-lung ventilation, known to be a major risk factor for postoperative lung injury. Studies suggest that volatile anesthetics may have a protective influence endothelial glycocalyx of pulmonary capillaries and reduced ischemia-reperfusion injury. This might be of clinical relevance for postoperative outcome. Summary: This review focuses on the involvement of the pulmonary endothelial glycocalyx in the context of perioperative lung injury. The pathophysiological mechanisms and trigger factors of glycocalyx deterioration are discussed, and prevention strategies are taken into consideration. Copyright (C) 2016 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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