Medicine by Alexandros G.Sfakianakis: 10/06/17

Παρασκευή 6 Οκτωβρίου 2017

Substrate Specificity of the Kinase P-TEFb towards the RNA Polymerase II C-Terminal Domain

The positive transcription elongation factor b (P-TEFb) promotes transcription elongation through phosphorylation of the RNA polymerase II C-terminal domain. This process is not well understood, partly due to difficulties in determining the specificity of P-TEFb toward the various heptad repeat motifs within the C-terminal domain. A simple assay using mass spectrometry was developed to identify the substrate specificity of the Drosophila melanogaster P-TEFb (DmP-TEFb) in vitro. This assay demonstrated that DmP-TEFb preferentially phosphorylates Ser5 and, surprisingly, that pre-phosphorylation or conserved amino acid variation at the 7-position in the heptad can alter DmP-TEFb specificity, leading to the creation of distinct double-phosphorylation marks.

http://ift.tt/2yuU2Ru

Rational Inference of Beliefs and Desires From Emotional Expressions

Abstract

We investigated people's ability to infer others' mental states from their emotional reactions, manipulating whether agents wanted, expected, and caused an outcome. Participants recovered agents' desires throughout. When the agent observed, but did not cause the outcome, participants' ability to recover the agent's beliefs depended on the evidence they got (i.e., her reaction only to the actual outcome or to both the expected and actual outcomes; Experiments 1 and 2). When the agent caused the event, participants' judgments also depended on the probability of the action (Experiments 3 and 4); when actions were improbable given the mental states, people failed to recover the agent's beliefs even when they saw her react to both the anticipated and actual outcomes. A Bayesian model captured human performance throughout (rs ≥ .95), consistent with the proposal that people rationally integrate information about others' actions and emotional reactions to infer their unobservable mental states.

http://ift.tt/2giY8S8

427 Music in Emergent Settings: A Randomized Controlled Trial

To investigate the impact of live preferential music (LPM) on patients receiving care in a level 1 trauma center and academic emergency department and to determine if LPM can affect the need for and utilization of pain medication among emergency department patients

http://ift.tt/2yNxIPf

386 Withdrawn

http://ift.tt/2yOCGuK

354 Biomechanical Aspect of Two-Finger Versus Two-Thumb Chest Compression for Cardiopulmonary Resuscitation in Infant Manikin Model

Previous studies has evaluated the quality of different external chest compression (ECC) methods delivered in infant cardiopulmonary resuscitation (CPR). However, the extent of loading force applied during infant ECC remains unknown. The objective of this crossover study was to quantify actual forces applied by two-finger (TF) and two-thumb (TT) methods.

http://ift.tt/2krMSqM

378TF Interactive Curriculum for Learning Pediatric Emergency Medicine Radiology

Radiology studies can significantly influence management in the emergency department. We noted that our pediatric emergency medicine (PEM) fellows often wait for a radiologist's interpretation instead of reviewing their patients' images. Our needs assessment revealed that 2 main factors limited the fellows' comfort with interpreting their own images: 1) lack of exposure to reading x-rays and CTs (pediatric-trained fellows) and 2) lack of confidence reading pediatric images (emergency medicine-trained fellows).

http://ift.tt/2ksWS3k

1EMF Take-Home Naloxone Rescue Kits Following Heroin Overdose in the Emergency Department to Prevent Opioid Overdose-Related Repeat Emergency Department Visits, Hospitalization, and Death: A Pilot Study

The United States is facing an epidemic of drug overdose deaths of unprecedented scale. Since 2000, our nation has seen a 137% increase in overdose-related death, including a 200% increase in overdose deaths from opioids. Opioid overdose morbidity and mortality can be prevented by early administration of naloxone hydrochloride. It has been shown that providing take-home naloxone rescue kits (NRK) to at-risk patients in the community setting reduces mortality from opioid overdose and is cost effective under highly conservative estimates.

http://ift.tt/2yNDdxk

390 Pilot Study to Test and Refine an Emergency Department Trigger Tool

Quality and safety review methods used in many EDs are decades old, porous and inefficient for identifying adverse events (AEs). Trigger Tools (TTs) popularized by the Institute for Healthcare Improvement, use 2-level reviews: a 1st level (L1) nurse review searching for the presence of triggers (thought to increase the likelihood of an AE) and if present, in-depth review for an AE, followed by a 2nd level physician review (L2) for putative AEs. TTs have been developed for a variety of clinical specialties.

http://ift.tt/2kuD4fN

382 Lifevac: A Novel Device for the Resuscitation of the Adolescent Choking Victim

Choking remains a leading cause of tragic death in children and adolescents. Currently there are no devices that assist in the resuscitation of an adolescent choking victim. Therefore we studied the Lifevac, a new apparatus that previously has been shown in a simulator model to successfully resuscitate an adult choking victim, in an adolescent simulator model.

http://ift.tt/2yOdYLo

366 Point-of-Care Ultrasound for Identifying Safe Tube Thoracostomy Insertion Sites

Open and Seldinger technique tube thoracostomies are common emergency department procedures. Identification of tube thoracostomy insertion location is currently performed using a blind, landmark-based approach based on either the fifth intercostal space or inframammary crease in the midaxillary line. Previous research has shown that physicians have difficulty applying the landmark-based approach to accurately identify safe locations for tube thoracostomy insertion. Approximately 30% of tube thoracostomies result in some sort of complication.

http://ift.tt/2kvrDEu

358 Impact of a Pharmacist-Driven Four-Factor Prothrombin Complex Concentrate Protocol in the Emergency Department at a Large Urban Academic Medical Center

Advancements in the treatment of warfarin-induced intracranial hemorrhage (ICH) include the use of four-factor prothrombin complex concentrate (4F-PCC), which has demonstrated more rapid reversal of the international normalized ratio (INR) when compared with fresh frozen plasma. A pharmacist-driven protocol for 4F-PCC was implemented within our institution which allows for pharmacist approval of 4F-PCC in patients diagnosed with warfarin-induced ICH and an INR ≥2. The pharmacist is responsible for determining the appropriate dose of 4F-PCC, preparing the product, bedside delivery, and entering the order into the electronic medical record.

http://ift.tt/2yNW1fN

431 Facilitating an Emergency Department Take-Home Naloxone Program Through Involvement of Community-Based Harm Reductionists

Opioid overdose is a significant cause of morbidity and mortality in the United States. For decades, peer-led harm reduction organizations have prevented overdoses through provision of naloxone, an opioid antagonist, directly to those at highest risk of overdose after training them in overdose emergency response. More recently, some emergency departments (EDs) have started similar programs, but take-home naloxone from EDs has yet to become widespread. Common barriers to implementation include limited clinician time, lack of exposure to harm reduction, and uncertainty about liability.

http://ift.tt/2yMOIoI

Laparoscopic cholecystectomy versus transvaginal natural orifice transluminal endoscopic surgery cholecystectomy: results of a prospective-comparative single-center study

Laparoscopic cholecystectomy (LC) in female individuals has been recently challenged by transvaginal NOTES cholecystectomy (TVC). TVC has not been widely accepted as a standard procedure, even though it is reported to be a safe and painless alternative to LC. This prospective-comparative study aims to not only prove equality of TVC and LC but to underline the advantages of TVC over LC with regard to postoperative pain.

http://ift.tt/2ghzwZR

Endoscopic submucosal dissection for early Barrett’s neoplasia: a meta-analysis

The role of endoscopic submucosal dissection (ESD) in Barrett's esophagus (BE) is not well established. This meta-analysis aimed to evaluate the safety and efficacy of ESD for the management of early BE neoplasia.

http://ift.tt/2hTCK9I

Rebamipide solution: a novel submucosal injection material to promote healing speed and healing quality of ulcers induced by endoscopic submucosal dissection

Rebamipide was administered perorally to protect the gastric mucosa. We assessed the efficacy and safety of a novel rebamipide solution as a submucosal injection material for endoscopic submucosal dissection (ESD) using an in vivo porcine model.

http://ift.tt/2gjze4A

Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: An analysis of patients treated on the RICOVER-60 trial

Abstract

Background

The prognosis of elderly patients with aggressive B-NHL after first lymphoma-related treatment failure (TF-L) is not well described.

Methods

We analysed patient characteristics including presence of MYC rearrangements and MYC-expression (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 to 80 years who had been treated on the RICOVER-60 trial.

Results

TF-L occurred in 301 of 1222 (24.6%) patients; 297 patients could be analyzed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (≤12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared to CHOP (23.0% vs. 36.4% at 2 years, p = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% vs. 0% at 2 years, p < 0.001) or negative MYC-IHC (41.0% vs. 16.8% at 2 years, p = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (p < 0.001). The benefit of R was significant after first-line CHOP (2-year-OS 49.6% vs. 19.1%, p < 0.001) as well as after R-CHOP (2-year-OS 33.1% and 22.5%, p = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen.

Conclusion

MYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy, however survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.

http://ift.tt/2hUemEK

Role of CYP3A in Oral Contraceptives Clearance

http://ift.tt/2fYp2BI

Cancer-directed therapy and potential impact on survivals in nonresected hepatocellular carcinoma: SEER-Medicare population study

Future Oncology, Ahead of Print.

http://ift.tt/2fYntnk

Latest advances in adult gastrointestinal stromal tumors

Future Oncology, Ahead of Print.

http://ift.tt/2fXyHsb

Sanger Institute series: uncovering the genetics of cancer: an interview with David Adams

Future Oncology, Ahead of Print.

http://ift.tt/2fYnoA2

PD-L1 in immune-escape of breast and prostate cancers: from biology to therapy

Future Oncology, Ahead of Print.

http://ift.tt/2y6GH0w

Prognostic impact of germline mutations in inherited cancer syndromes

Future Oncology, Ahead of Print.

http://ift.tt/2fZa9PI

Why should we perform a D2 lymphadenectomy in gastric cancer?

Future Oncology, Ahead of Print.

http://ift.tt/2y6GBGc

Effects of storage temperature and duration on bioactive concentrations in the seed and oil of Brassica napus (canola)

Abstract

The effects of storage temperature and duration on phytosterol, tocopherol and carotenoid concentrations were assessed in canola seed, and oil extracted using two different techniques, over a 10 month period. Increases to oxidation indices (K₂₃₂, K₂₇₀, and δK) were observed in the solvent extracted oils, and in the seed stored at 40 °C, indicating the formation of primary and secondary oxidation products. Only small decreases in the concentrations of γ-tocopherol and β-carotene were observed across the 10 month period. Phytosterol concentration decreased over time, with similar degradation rates observed in both seed and oils. α-tocopherol and lutein were well preserved up to 7 months in all samples, despite oil oxidation, and further research will be needed to identify the cause for retention of bioactives. The results indicate that in order to preserve phytosterols, tocopherols and carotenoids in seed stored in bulk for extended periods, storage temperatures should remain at or below 21°C. Moreover, oil stored at 4°C or -18°C, resulted in high bioactive concentrations and slowed the onset of oil oxidation, compared to oil stored at room temperature.

Practical applications: Industrial storage conditions have been shown to greatly influence the chemical processes that occur with canola seed and oil. However, the effects of typical storage conditions on phytosterols, tocopherols and carotenoids in canola seed and extracted oil, are not yet known. This study presents the effects of typical seed and oil storage conditions on phytosterol, tocopherol and carotenoid concentrations, whilst monitoring oxidation indices and FFA, and thus provides information to seed handlers and oil processors on storage conditions that may preserve these bioactives. Moreover, the different behaviours of bioactives are examined relative to the oil extraction technique used, and present opportunities to optimise oil extraction techniques. The high retention of bioactives observed in this study warrants further investigation into the enhancement of bioactive concentrations in the seed, and preservation during commercial oil processing, to achieve bioactive enhancement in edible canola oil.

http://ift.tt/2xorhkz

Regional patterns of olmesartan prescription and the prevalence of duodenal villous atrophy throughout the united states

http://ift.tt/2gi67yx

Improved Bone Microarchitecture in Patients With Celiac Disease After 3 years on a Gluten-free Diet

http://ift.tt/2gi63ih

Twenty-year Comparative Analysis of Patients With Autoimmune Liver Diseases on Transplant Waitlists

The rarity of autoimmune liver disease poses challenges to epidemiology studies. However, waitlists for liver transplantation can be used to study patients with end-stage liver diseases. We used these waitlists to assess trends in numbers and demographics patients awaiting liver transplant for primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or autoimmune hepatitis (AIH).

http://ift.tt/2yvfYft

Neuronal activity patterns in the ventral thalamus: comparison between Parkinson’s disease and cervical dystonia

The thalamus plays a crucial role in many brain functions, serving as an information gate for afferent sensory signals, efferent programmes and intercortical interactions. Along with a complex inner structure, the thalamus has widespread connections with subcortical structures (basal ganglia, cerebellum, midbrain and others), different cortical regions and the peripheral nervous system (Jones, 2007; Sherman and Guillery, 2013). Thus, such extensive connectivity implies a complexity and diversity of neuronal activity patterns.

http://ift.tt/2y6e3fQ

Progression of adverse effects over consecutive sessions of transcranial direct current stimulation

We read the paper by Antal et al. (2017) with great interest, and felt that it provided an excellent overview of the safety aspects of transcranial electrical stimulation (tES). However, we noticed that while multi-day stimulation studies were discussed, potential changes in adverse effects (AEs) over consecutive sessions were not, and the lack of knowledge on the matter was pointed out by the authors. We recently completed an experiment in which we investigated this issue.

http://ift.tt/2gia8TV

Super-selective cervical nerve root stimulation in contralateral C7 transfer: an intraoperative study

Intraoperative electrophysiological examination of the healthy brachial plexus in contralateral C7 transfer (cC7) procedures contributed substantially to the anatomical understanding of functional motor innervation of cervical nerve roots (Gu 1997; Gu et al. 2003; Hu et al. 2008; Li et al. 2011; Yin et al. 2012; Zhang et al. 2012). Results of intraoperative cervical nerve root stimulation showed that C5 mainly innervates the deltoid (axillary nerve), C6 the biceps brachii (musculocutaneous nerve), C7 the triceps brachii (radial nerve), and C8 the flexor digitorum superficialis and profundus muscles (median nerve) (Gu 1997).

http://ift.tt/2y5L7o0

iMAX: a new tool to assess peripheral motor axonal hypoexcitability

In routine electrodiagnostic procedures, classical parameters allow assessment of motor unit loss/reinnervation (CMAP amplitude) and motor conduction slowing (motor distal latency, motor conduction velocity, F waves), but none evaluates peripheral motor axon hypoexcitability. Yet everyone has experienced that in a demyelinating neuropathy it is often necessary to increase above normal the amount of current to obtain a supramaximal motor response. Excitability properties of human peripheral nerves can be assessed by various neurophysiological methods (Brismar, 1985; Kiernan et al, 2000; Burke et al, 2001), but they are not often used in daily practice because they are time consuming and they require a specific collection system and software.

http://ift.tt/2giAsgn

Added clinical value of the inferior temporal EEG electrode chain

In 1958, the standardized 10-20 EEG electrode positioning system was proposed by Herbert H. Jasper and his co-workers (Jasper, 1958), and in 1999 this has been reported as a guideline of the International Federation of Clinical Neurophysiology (Klem et al. 1999). Distances were measured from prominent skull landmarks (nasion, inion, preauricular points) and evenly distributed electrode positions were determined using 10% and 20% segments of these distances (Klem et al. 1999). Jasper's 10-20 system was developed using cadaver skulls.

http://ift.tt/2y6iG9s

Learned control over spinal nociception: Transfer and stability of training success in a long-term study

The descending pain inhibition is a system of endogenous pain control, able to reduce incoming nociceptive signals at the spinal dorsal horn level (Fields and Basbaum, 2006). It can be modulated by cognitive and emotional processes (Tracey and Mantyh, 2007; Bingel and Tracey, 2008; Wiech and Tracey, 2009). Recently, we have shown that healthy young adults can learn to use cognitive-emotional strategies to suppress their spinal nociception as quantified by the nociceptive flexor reflex (RIII reflex) when they are given visual feedback on their RIII reflex size, likely by learning to deliberately activate their descending pain inhibition (Ruscheweyh et al., 2015a; Ruscheweyh et al., 2015b).

http://ift.tt/2gjrb7O

Effects of Homocysteine on white matter diffusion parameters in Alzheimer’s disease

The clinical features of Alzheimer's disease (AD) are related to brain network degeneration, and hyperhomocysteinemia is related to greater white matter hyperintensities. We investigated the changes in four di...

http://ift.tt/2xnuPYT

Identification of VPS35 p.D620N mutation-related Parkinson’s disease in a Taiwanese family with successful bilateral subthalamic nucleus deep brain stimulation: a case report and literature review

Vacuolar protein sorting 35 (VPS35) was recently reported to be a genetic cause for late-onset autosomal dominant Parkinson's disease (PD). However, VPS35 mutations are rarely reported in Asian populations. Herei...

http://ift.tt/2kvgLqa

Subtrochanteric fractures: Issues and challenges

Publication date: October 2017
Source:Injury, Volume 48, Issue 10
Author(s): Michalis Panteli, Cyril Mauffrey, Peter V. Giannoudis

http://ift.tt/2hTten0

The risk of suprascapular and axillary nerve injury in reverse total shoulder arthroplasty: An anatomic study

Publication date: October 2017
Source:Injury, Volume 48, Issue 10
Author(s): Tim Leschinger, Michael Hackl, Eduard Buess, Sebastian Lappen, Martin Scaal, Lars Peter Müller, Kilian Wegmann
PurposeImplantation of a reverse total shoulder arthroplasty (rTSA) places the axillary and suprascapular nerves at risk. The aim of this anatomic study was to digitally analyse the location of these nerves in relation to bony landmarks in order to predict their path and thereby help to reduce the risk of neurological complications during the procedure.MethodsA total of 22 human cadaveric shoulder specimens were used in this study. The axillary and suprascapular nerves were dissected, and radiopaque threads were sutured onto the nerves without mobilizing the nerves from their native paths. Then, 3D X-ray scans of the specimens were performed, and the distance of the nerves to bony landmarks at the humerus and the glenoid were measured.ResultsThe distance of the inferior glenoid rim to the axillary nerve averaged 13.6mm (5.8–27.0mm, ±5.1mm). In the anteroposterior direction, the distance between the axillary nerve and the humeral metaphysis averaged 8.1mm (0.6–21.3mm, ±6.5mm).The distance of the glenoid centre to the suprascapular nerve passing point under the transverse scapular ligament measured 28.4mm (18.9–35.1mm, ±3.8mm) in the mediolateral direction and 10.8mm (−4.8 to 25.3mm, ±6.1mm) in the anteroposterior direction. The distance to the spinoglenoid notch was 16.6mm (11.1–24.9mm, ±3.4mm) in the mediolateral direction and −11.8mm posterior (−19.3 to −4.7mm, ±4.7mm) in the anteroposterior direction.ConclusionsImplantation of rTSA components endangers the axillary nerve because of its proximity to the humeral metaphysis and the inferior glenoid rim. Posterior and superior drilling and extraosseous screw placement during glenoid baseplate implantation in rTSA place the suprascapular nerve at risk, with safe zones to the nerve passing the spinoglenoid notch of 11mm and to the suprascapular notch of 19mm.

http://ift.tt/2krszK4

Editorial Board/Publication Information

Publication date: October 2017
Source:Injury, Volume 48, Issue 10

http://ift.tt/2ks0Adr

The pivotal role of the coronal fracture line for a new three-dimensional CT-based fracture classification of bicondylar proximal tibial fractures

Publication date: October 2017
Source:Injury, Volume 48, Issue 10
Author(s): Robert Pätzold, Jan Friederichs, Christian von Rüden, Stephanie Panzer, Volker Bühren, Peter Augat
IntroductionClassical fracture classifications (AO/OTA, Schatzker) are commonly used to characterize bicondylar proximal tibial fractures. However, none of these classifications allows for a treatment algorithm. The aim of our study was to use 3D appearance of these fractures in CT imaging to improve the clinical value of the classification.Materials and methods3D appearance of 81 CT scans of bicondylar proximal tibial fractures were systematically analyzed and were classified in 3 subtypes, based on the fracture lines orientation. The novel classification was compared for reliability and for clinical relevance with AO and Schatzker classification.ResultsA total of 159 fracture lines were identified which were most frequently oriented in sagittal (89/159), and in coronal (41/159) direction. Based on the orientation of the major fracture lines three fracture types were defined. A special emphasis was drawn to the coronal fracture line of the medial plateau leading to a surgical treatment algorithm. Interobserver reliability was analyzed for all 81 patients resulting in an excellent reliability of К=0.936 for the 3D classification scheme compared to К=0.720 for the AO/OTA, К=0.785 for the Schatzker classification. Correlations with clinical parameters were only observed for the 3D classification.DiscussionThe presented classification scheme based on the 3D geometry of bicondylar proximal tibial fractures demonstrates a good reliability of clinical relevance.

http://ift.tt/2hUDYS5

Institutional profile: translational pharmacogenomics at the Icahn School of Medicine at Mount Sinai

Pharmacogenomics, Ahead of Print.

http://ift.tt/2giqEmS

Corrigendum

Pharmacogenomics, Ahead of Print.

http://ift.tt/2hTOuc9

Inhibition of p300/CBP Suppresses Castration-Resistant Prostate Cancer [Research Watch]

A virtual ligand screen led to generation of A-485, a potent selective p300/CBP catalytic inhibitor.

http://ift.tt/2hUwEFS

Chromosome 1q21.3 Amplification Is Linked to Breast Cancer Recurrence [Research Watch]

The 1q21.3 amplification can be detected in cfDNA from most patients with recurrent breast cancer.

http://ift.tt/2ghXRPl

METTL3 Increases m6A to Block Differentiation and Promote Leukemogenesis [Research Watch]

METTL3 is upregulated in acute myeloid leukemia compared with other tumors and normal HSPCs.

http://ift.tt/2giWrEd

The Splicing Regulator PRMT5 Is Critical for Glioblastoma Proliferation [Research Watch]

PRMT5 regulates the splicing of detained introns in proliferation-associated genes in GBM.

http://ift.tt/2hSSl9u

Loss of FOXO1 cooperates with TMPRSS2-ERG overexpression to promote prostate tumorigenesis and cell invasion

E26 transformation-specific (ETS) transcription factor ERG is aberrantly overexpressed in approximately 50% of all human PCa due to TMPRSS2-ERG gene rearrangements. However, mice with prostate-specific transgenic expression of PCa-associated ERG alone fail to develop PCa, highlighting that ERG requires other lesions to drive prostate tumorigenesis. Forkhead box (FOXO) transcription factor FOXO1 is a tumor suppressor that is frequently inactivated in human PCa. Here we demonstrate that FOXO1, but not other FOXO proteins (FOXO3 and FOXO4), binds and inhibits the transcriptional activity of PCa-associated ERG independently of FOXO1 transcriptional activity. Knockdown of endogenous FOXO1 increased invasion of TMPRSS2-ERG fusion positive VCaP cells, an effect completely abolished by ERG knockdown. Patient specimen analysis demonstrated that FOXO1 and ERG protein expression inversely correlated in a subset of human PCa. Although human ERG transgene expression or homozygous deletion of Foxo1 alone in the mouse prostate failed to promote tumorigenesis, concomitant ERG transgene expression and Foxo1 deletion resulted in upregulation of ERG target genes, increased cell proliferation and formation of high-grade prostatic intraepithelial neoplasia (HGPIN). Overall, we provide biochemical and genetic evidence that aberrantly activated ERG cooperates with FOXO1 deficiency to promote prostate tumorigenesis and cell invasion. Our findings enhance understanding of PCa etiology and suggest that the FOXO1-ERG signaling axis can be a potential target for treatment of PCa.

http://ift.tt/2z4X6Rh

Chemotherapeutic dose scheduling based on tumor growth rates provide a case for low-dose metronomic high entropy therapies

We extended the classical tumor regression models such as Skipper's laws and the Norton-Simon hypothesis from instantaneous regression rates to the cumulative effect over repeated cycles of chemotherapy. To achieve this end, we used a stochastic Moran process model of tumor cell kinetics coupled with a prisoner's dilemma game-theoretic cell-cell interaction model to design chemotherapeutic strategies tailored to different tumor growth characteristics. Using the Shannon entropy as a novel tool to quantify the success of dosing strategies, we contrasted maximum tolerated dose (MTD) strategies as compared with low-dose, high-density metronomic strategies (LDM) for tumors with different growth rates. Our results show that LDM strategies outperformed MTD strategies in total tumor cell reduction (TCR). This advantage was magnified for fast growing tumors that thrive on long periods of unhindered growth without chemotherapy drugs present and was not evident after a single cycle of chemotherapy but grew after each subsequent cycle of repeated chemotherapy. The evolutionary growth/regression model introduced in this paper agrees well with murine models. Overall, this model supports the concept of designing different chemotherapeutic schedules for tumors with different growth rates and develops quantitative tools to optimize these schedules for maintaining low volume tumors.

http://ift.tt/2y5ZMjk

Astrocytes promote medulloblastoma progression through hedgehog secretion

Astrocytes, the most abundant type of glial cells in the brain, play critical roles in supporting neuronal development and brain function. While astrocytes have been frequently detected in brain tumors, including medulloblastoma (MB), their functions in tumorigenesis are not clear. Here we demonstrate that astrocytes are essential components of the MB tumor microenvironment. Tumor-associated astrocytes (TAA) secreted the ligand sonic hedgehog (Shh), which is required for maintaining MB cell proliferation despite the absence of its primary receptor Patched-1 (Ptch1). Shh drove expression of Nestin in MB cells through a Smoothened-dependent, Gli1-independent mechanism. Ablation of TAA dramatically suppressed Nestin expression and blocked tumor growth. These findings demonstrate an indispensable role for astrocytes in MB tumorigenesis and reveal a novel Ptch1-independent Shh pathway involved in MB progression.

http://ift.tt/2z3H7CV

Substrate Specificity of the Kinase P-TEFb towards the RNA Polymerase II C-Terminal Domain

Can STN DBS protect both nigral somata and innervation of the striatum?

http://ift.tt/2y5QjZn

Reply to Can STN DBS protect both nigral somata and innervation of the striatum?

http://ift.tt/2xoVC2k

The impact of frailty on outcomes in dialysis

Purpose of review: Frailty is highly prevalent in the dialysis population and is associated with mortality. Recent studies have suggested that other dialysis outcomes are compromised in frail individuals. While we do not yet have a consensus as to the best measure of frailty, identification of these poor outcomes and their magnitude of association with frailty will help improve prognostication, allow for earlier interventions, and improve provider-to-patient communication. Recent findings: The most widely used assessment of frailty is Fried's physical performance criteria. However, regardless of assessment method, frailty remains highly associated with mortality. More recently, frailty has been associated with falls, fractures, cognitive impairment, vascular access failure, and poor quality of life. Recent large cohort studies provide strong evidence that frailty assessment can provide important prognostic information for providers and patients both before and after initiation of dialysis. Trials aimed at improving frailty are limited and show the promise of augmenting quality of life, although more studies are needed to firmly establish mortality benefits. Summary: We underscore the importance of frailty as a prognostic indicator and identify other recently established consequences of frailty. Widespread adoption of frailty assessment remains limited and researchers continue to find ways of simplifying the data collection process. Timely and regular assessment of frailty may allow for interventions that can mitigate the onset of poor outcomes and identify actionable targets for dialysis providers.

http://ift.tt/2y6nSKJ

A patient-centred approach to measuring quality in kidney care: patient-reported outcome measures and patient-reported experience measures

Purpose of review: Chronic kidney disease (CKD) is associated with symptoms that can significantly reduce the health-related quality of life (HRQOL) of patients. Patient-reported outcome and experience measures (PROMs and PREMs) may assist with the evaluation of HRQOL and quality of care from the patient perspective. This review focuses on evidence from recent studies exploring the role of PROMs and PREMs in the measurement of quality in CKD care. Recent findings: PROMs are increasingly used in CKD research as measures of clinical effectiveness, whereas the current use of PROMs in routine clinical settings and PREMs in all settings is more limited. Electronic PROMs may be sensitive enough to detect clinically relevant patient-reported outcomes changes. Patients on frequent shorter-hours daily haemodialysis may experience better HRQOL compared with those on conventional haemodialysis. PROM data may correlate significantly with clinical parameters. PREMs are being utilized by healthcare professionals to inform service improvements. Summary: PROMs and PREMs may facilitate the measurement of quality in renal care and aid the tailoring of care to individual patients. PROMs may have a potential role as prognostic markers.

http://ift.tt/2y5UWTd

Digital pathology in nephrology clinical trials, research, and pathology practice

Purpose of review: In this review, we will discuss (i) how the recent advancements in digital technology and computational engineering are currently applied to nephropathology in the setting of clinical research, trials, and practice; (ii) the benefits of the new digital environment; (iii) how recognizing its challenges provides opportunities for transformation; and (iv) nephropathology in the upcoming era of kidney precision and predictive medicine. Recent findings: Recent studies highlighted how new standardized protocols facilitate the harmonization of digital pathology database infrastructure and morphologic, morphometric, and computer-aided quantitative analyses. Digital pathology enables robust protocols for clinical trials and research, with the potential to identify previously underused or unrecognized clinically useful parameters. The integration of digital pathology with molecular signatures is leading the way to establishing clinically relevant morpho-omic taxonomies of renal diseases. Summary: The introduction of digital pathology in clinical research and trials, and the progressive implementation of the modern software ecosystem, opens opportunities for the development of new predictive diagnostic paradigms and computer-aided algorithms, transforming the practice of renal disease into a modern computational science.

http://ift.tt/2y5ux7L

Editorial introductions

No abstract available

http://ift.tt/2y5JS8p

MicroRNAs as biomarkers in chronic kidney disease

Purpose of review: This review summarizes recent data supporting the concept that urinary microRNAs are a useful new class of biomarker. They may improve capacity to stratify patients with chronic kidney disease according to risk of progression, and may also inform about response to therapy. Recent findings: MicroRNAs are present, stable and readily quantifiable in tissues and body fluids, including urine, and have widespread importance as regulators in the kidney. Urinary microRNAs are typically released from the nephron or downstream structures, and their abundance may reflect altered microRNA expression in the kidney, or release into the lumen by the cells comprising the different regions of the nephron. As a consequence, abundance of specific microRNAs in the urine may change in various pathological states. Large-scale studies are now needed, to test the capacity of specific microRNAs to inform about risk and response to therapy. Summary: Urinary microRNAs appear useful sentinels for pathological processes occurring in the kidney and may enable a 'personalized medicine' approach to the management and stratification of renal disease.

http://ift.tt/2y5azdk

Recurrent glomerular disease after kidney transplantation

Purpose of review: With improving short-term kidney transplant outcomes, recurrent glomerular disease is being increasingly recognized as an important cause of chronic allograft failure. Further understanding of the risks and pathogenesis of recurrent glomerular disease enable informed transplant decisions, along with the development of preventive and treatment strategies. Recent findings: Multiple observational studies have highlighted differences in rates and outcomes for various recurrent glomerular diseases, although these rates have not markedly improved over the last decade. Emerging evidence supports use of rituximab to treat recurrent primary membranous nephropathy and possibly focal segmental glomerulosclerosis (FSGS), whereas eculizumab is effective in glomerular diseases associated with complement dysregulation [C3 glomerulopathy (C3G) and atypical hemolytic uremic syndrome (aHUS)]. Summary: Despite the potential for recurrence in the allograft, transplant remains the optimal therapy for patients with advanced chronic kidney disease (CKD) secondary to primary glomerular disease. Biomarkers and therapeutic options necessitate accurate pretransplant diagnoses with opportunities for improved surveillance and treatment of recurrent glomerular disease posttransplant.

http://ift.tt/2y5TujL

Ischemic conditioning in solid organ transplantation: is it worth giving your right arm for?

Purpose of review: Ischemia reperfusion injury (IRI) is an inevitable complication in solid organ transplantation. Limiting this injury can increase patient and graft survival and can decrease complications associated with transplantation. We provide an extensive literature review analyzing the available evidence for ischemic conditioning in solid organ transplantation, including kidney, liver, heart, and lung. Recent findings: Ischemic conditioning strategies are a group of interventions, characterized by episodes of ischemia and reperfusion to an organ which confirm tissue protection. Arguably, transplantation is the ideal setting to use this novel strategy due to the predictable timing and duration of the ischemic insult. Liver transplantation has provided us with the most number of clinical trials, followed by kidney transplantation. Most of these trials have been negative but the methodology has been variable, making comparison difficult. Summary: Despite the promising results seen in animal models, translating these results in clinical trials has proved to be difficult. The promising effects of ischemic conditioning are present in some trials with weaker positive signals existing in other trials. We believe that tailoring trials to allow better comparison will provide positive results in the future.

http://ift.tt/2y5UUL5

The role of parathyroidectomy in the management of secondary hyperparathyroidism

Purpose of review: Parathyroidectomy (PTX) is often used to treat severe secondary hyperparathyroidism (SHPT) in patients receiving maintenance dialysis. However, most evidence for the proposed benefits of PTX originates from observational studies, which cannot demonstrate causality. A reconsideration of the potential role of PTX might help guide its appropriate use. Recent findings: Several large observational studies have suggested that PTX can reduce mortality risk. However, these studies generally suffer from bias and confounding, tempering conclusions and suggesting that the true effects of PTX may not be known. PTX has been reported to be associated with a 2% 30-day mortality, a substantial risk for what is generally an elective procedure. Additionally, biochemical control after PTX in a subset of patients may be suboptimal. The optimal surgical approach to PTX in specific clinical scenarios is also uncertain. Summary: PTX may be beneficial for certain patients with severe SHPT and clinical symptoms, but identifying patients in whom the benefits are likely to outweigh the risks is a substantial challenge. Further, great care must be taken to monitor symptoms and laboratory values in patients who undergo PTX in the immediate postoperative period and, in many cases, well beyond.

http://ift.tt/2y5NnvM

The treatment of paraprotein-related kidney disease

Purpose of review: Myeloma kidney and amyloid light-chain (AL) amyloidosis remain the principal kidney complications of paraproteins. In this review, we update readers to many of the recent advances which have occurred in the care and outcomes for patients with these presentations. Recent findings: Myeloma kidney has historically caused a severe acute kidney injury with very poor outcomes. The combination of new diagnostic techniques, enabling a rapid diagnosis and novel chemotherapy agents has transformed these poor outcomes for the better. Two multicentre randomized controlled trials have recently evaluated if the removal of free light chains by high cut-off haemodialysis improves renal outcomes beyond effective chemotherapy alone. Although we await the full articles of these studies to be published, abstracts suggested the studies will have contradictory primary results. In the field of AL amyloidosis, there are now novel criteria for the risk stratification of kidney outcomes which can be used in combination with markers of early kidney response to provide clinicians with powerful tools to guide patient discussions. Summary: Across both AL amyloidosis and myeloma kidney patient outcomes continue to improve. Principally this improvement has been driven by the continuing development of novel chemotherapy agents in this field.

http://ift.tt/2y5npbu

Incorporating supportive care into the hemodialysis unit

Purpose of review: Advance care planning is underutilized in patients with dialysis-dependent kidney failure and the provision of high intensity rather than supportive care is a standard practice in most hemodialysis units wherever challenges to incorporating palliative or supportive care into unit processes remain formidable. Recent findings: The practice of advance care planning empowers patients, families and physicians and drives decisions about future treatment that align with patients' values, wishes and changing clinical circumstances. Barriers to incorporating supportive care exist; however, advance care planning optimizes the chance for future care that is smooth, compassionate, timely and supportive. Summary: Care that is palliative in nature may be desired by dialysis patients suffering from escalating comorbid illness and ongoing clinical decline. Advance care planning addresses wishes for future treatment and serves as a prerequisite to the provision of patient-centered care. Nephrologists are uniquely poised to promote a culture that incorporates shared decision-making and support for palliative treatment into dialysis unit care.

http://ift.tt/2y5lNi4

Causes and management of postrenal transplant diarrhea: an underappreciated cause of transplant-associated morbidity

Purpose of review: This review highlights the current literature on both infectious and noninfectious diarrhea in renal transplant recipients and provides a diagnostic algorithm for the evaluation of posttransplant diarrhea. Recent findings: Renal transplant recipients share certain predisposing characteristics for the development of posttransplant diarrhea, including a generalized immunosuppressed state and exposure to polypharmacy, most notably broad-spectrum antimicrobial therapy. The main causes of diarrhea after transplantation are infections, immunosuppressive drugs, antibiotics and other drugs. As the cause of posttransplant diarrhea varies greatly depending on several factors, recommending a single optimal diagnostic algorithm is extremely difficult. Summary: Physicians should be familiar with common causes that result in posttransplant diarrhea. A directed approach to diagnosis and treatment will not only help to resolve diarrhea, but also prevent potentially life-threatening consequences, such as loss of the graft. Prospective studies are needed to better assess true prevalence, risk factors and complications of diarrhea by norovirus, rotavirus and adenovirus in kidney transplant patients.

http://ift.tt/2y5SPhZ

Incremental dialysis: review of recent literature

Purpose of review: There are clinical, physiological, financial, and practical reasons to perform incremental hemodialysis in selected patients, incident to end-stage renal disease. Recent papers inform us further, especially in the large database studies. Recent findings: Small studies suggested, then a larger study corroborated, that incremental hemodialysis was associated with preservation of residual kidney function whenever compared with conventional hemodialysis. The well tolerated nutritional status of incremental hemodialysis was questioned in a small study but a larger study was more reassuring. The mortality rate of patients undergoing incremental hemodialysis is similar to that in conventional hemodialysis, but only if the comorbidity burden is low. Summary: Incremental hemodialysis in incident patients can be performed safely, and probably is associated with preserved residual kidney function and a similar mortality rate to convention initiation of hemodialysis. Patients must be prudently selected and managed for this approach to the initiation of dialysis.

http://ift.tt/2y5nqMA

The Rhythm is Going to Get’Cha (o eh, o eh, o eh, oo aah)

Recent research out of McGill University has demonstrated that motor regions of the brain actually sharpen sound perception and this effect is increased when we move in rhythm with the sound.

The investigators examined participants as they listened to a complex tone sequence when the participant was still or tapped in rhythm with the target, all while magnetoencephalography (MEG) was recorded.

http://ift.tt/2y5Z7OX

Magnetic Resonance Elastography to Assess Fibrosis in Kidney Allografts

Background and objectives

Fibrosis is a major cause of kidney allograft injury. Currently, the only means of assessing allograft fibrosis is by biopsy, an invasive procedure that samples <1% of the kidney. We examined whether magnetic resonance elastography, an imaging-based measure of organ stiffness, could noninvasively estimate allograft fibrosis and predict progression of allograft dysfunction.

Design, setting, participants, & measurements

Kidney allograft recipients >1 year post-transplant undergoing an allograft biopsy first underwent free-breathing, flow-compensated magnetic resonance elastography on a 3.0-T magnetic resonance imaging scanner. Each patient had serial eGFR measurements after the elastography scan for a follow-up period of up to 1 year. The mean stiffness value of the kidney allograft was compared with both the histopathologic Banff fibrosis score and the rate of eGFR change during the follow-up period.

Results

Sixteen patients who underwent magnetic resonance elastography and biopsy were studied (mean age: 54±9 years old). Whole-kidney mean stiffness ranged between 3.5 and 7.3 kPa. Whole-kidney stiffness correlated with biopsy-derived Banff fibrosis score (Spearman rho =0.67; P<0.01). Stiffness was heterogeneously distributed within each kidney, providing a possible explanation for the lack of a stronger stiffness-fibrosis correlation. We also found negative correlations between whole-kidney stiffness and both baseline eGFR (Spearman rho =–0.65; P<0.01) and eGFR change over time (Spearman rho =–0.70; P<0.01). Irrespective of the baseline eGFR, increased kidney stiffness was associated with a greater eGFR decline (regression r²=0.48; P=0.03).

Conclusions

Given the limitations of allograft biopsy, our pilot study suggests the potential for magnetic resonance elastography as a novel noninvasive measure of whole-allograft fibrosis burden that may predict future changes in kidney function. Future studies exploring the utility and accuracy of magnetic resonance elastography are needed.

http://ift.tt/2y6cleL

Rethinking End Points in Clinical Trials of Renoprotective Medication

http://ift.tt/2xZbrAU

Perspectives on the Nephrology Match for Fellowship Applicants

http://ift.tt/2gitHLU

Contemporary Management of Hepatitis C in Patients with CKD

http://ift.tt/2xZbcWw

Effectiveness of Treatment Modalities on Kidney Stone Recurrence

Background and objectives

Quality improvement interventions have enhanced care for other chronic illnesses, but their effectiveness for patients with CKD is unknown. We sought to determine the effects of quality improvement strategies on clinical outcomes in adult patients with nondialysis-requiring CKD.

Design, setting, participants, & measurements

We conducted a systematic review of randomized trials, searching Medline and the Cochrane Effective Practice and Organization of Care database from January of 2003 to April of 2015. Eligible studies evaluated one or more of 11 prespecified quality improvement strategies, and prespecified study outcomes included at least one process of care measure, surrogate outcome, or hard clinical outcome. We used a random effects model to estimate the pooled risk ratio (RR; dichotomous data) or the mean difference (continuous data).

Results

We reviewed 15 patient-level randomized trials (n=3298 patients), and six cluster-randomized trials (n=30,042 patients). Quality improvement strategies reduced dialysis incidence (seven trials; RR, 0.85; 95% confidence interval [95% CI], 0.74 to 0.97) and LDL cholesterol concentrations (four trials; mean difference, –17.6 mg/dl; 95% CI, –28.7 to –6.5), and increased the likelihood that patients received renin-angiotensin-aldosterone system inhibitors (nine trials; RR, 1.16; 95% CI, 1.06 to 1.27). We did not observe statistically significant effects on mortality, cardiovascular events, eGFR, glycated hemoglobin, and systolic or diastolic BP.

Conclusions

Quality improvement interventions yielded significant beneficial effects on three elements of CKD care. Estimates of the effectiveness of quality improvement strategies were limited by study number and adherence to quality improvement principles.

Podcast

This article contains a podcast at http://ift.tt/2xY1FiG

http://ift.tt/2gih3fA

ANCA Glomerulonephritis and Vasculitis

ANCA vasculitis has an associated autoimmune response that produces ANCAs that induce distinct pathologic lesions. Pauci-immune necrotizing and crescentic GN is a frequent component of ANCA vasculitis. ANCA vasculitis is associated with ANCA specific for myeloperoxidase (MPO-ANCA) or proteinase 3 (PR3-ANCA). A diagnosis of ANCA vasculitis should always specify the serotype as MPO-ANCA positive, PR3-ANCA positive, or ANCA-negative. To fully characterize a patient, the serotype also should be accompanied by the clinicopathologic variant if this can be determined: microscopic polyangiitis, granulomatosis with polyangiitis (Wegener), eosinophilic granulomatosis with polyangiitis (Churg–Strauss), or renal-limited vasculitis. ANCA vasculitis is most prevalent in individuals >50 years old. There are racial/ethnic and geographic influences on the prevalence, serotype frequencies, and clinicopathologic phenotypes. There is clinical, in vitro, and animal model evidence that ANCAs cause disease by activating neutrophils to attack small vessels. Immunomodulatory and immunosuppressive therapies are used to induce remission, maintain remission, and treat relapses. Over recent years, there have been major advances in optimizing treatment by minimizing toxic therapy and utilizing more targeted therapy.

http://ift.tt/2gigXoe

Effect of Sofosbuvir-Based Hepatitis C Virus Therapy on Kidney Function in Patients with CKD

Background and objectives

Hepatitis C virus infection is common in patients with CKD and leads to accelerated progression to ESRD. Sofosbuvir is a potent direct-acting antiviral therapy against hepatitis C virus; however, there are concerns about its safety in patients with CKD. The objective of our study was to determine the safety and efficacy of sofosbuvir in patients with CKD.

Design, setting, participants, & measurements

We studied a retrospective observational cohort of patients with CKD defined by eGFR<60 ml/min per 1.73 m², ≥30 mg albuminuria per 1 g creatinine, or ≥200 mg proteinuria per 1 g creatinine who received sofosbuvir-based therapy in a large health care system. Regression models were constructed to predict likelihood of sustained virologic response, detect adverse events, and examine changes in eGFR from baseline to follow-up.

Results

Ninety-eight patients with CKD (42% stage 1 or 2 CKD and 58% stage 3 CKD) were included. Mean age was 62 years old, 78% were men, and 65% were white. Additionally, 49% of patients had diabetes, 38% of patients had cirrhosis, and 33% of patients had prior solid organ transplant. Overall sustained virologic response was 81% and varied by regimen used and viral genotype. Average baseline eGFR was equivalent to average on-treatment eGFR, but seven patients experienced a rise in creatinine ≥1.5 times baseline while taking sofosbuvir; all but one recovered. In patients with eGFR<60 ml/min per 1.73 m² at baseline (stage 3 CKD), regression models showed that hepatitis C cure was associated with a 9.3 (95% confidence interval, 0.44 to 18) ml/min per 1.73 m² improvement in eGFR during the 6-month post-treatment follow-up period. Adverse events were common (81%), but serious adverse events (17%) and treatment discontinuations (8%) were uncommon.

Conclusions

Sofosbuvir-based direct-acting antiviral therapy is safe and effective in a cohort of patients with CKD infected with hepatitis C.

http://ift.tt/2xY1unw

A Patient with a Novel Gene Mutation Leading to Autosomal Dominant Polycystic Kidney Disease

http://ift.tt/2gigP8e

Epidemiology and Natural History of the Cardiorenal Syndromes in a Cohort with Echocardiography

Background and objectives

It is unknown whether echocardiographic parameters are independently associated with the cardiorenal syndrome. No direct comparison of the natural history of various cardiorenal syndrome types has been conducted.

Design, setting, participants, & measurements

Our retrospective cohort study enrolled adult patients with at least one transthoracic echocardiography between 2004 and 2014 at a single health care system. Information on comorbidities was extracted using condition-specific diagnostic codes. All-cause mortality was the primary outcome among patients with cardiorenal syndrome types 1–4. Myocardial infarction and stroke were the secondary outcomes.

Results

In total, 30,681 patients were included, and 2512 (8%) developed at least one of the cardiorenal syndromes: 1707 patients developed an acute form of the syndrome (type 1 or 3), 128 patients developed type 2, and 677 patients developed type 4. In addition, 16% of patients with type 2 and 20% of patients with type 4 also developed an acute cardiorenal syndrome, whereas 14% of patients with acute cardiorenal progressed to CKD or chronic heart failure. Decreasing left ventricular ejection fraction, increasing pulmonary artery pressure, and higher right ventricular diameter were independently associated with higher incidence of a cardiorenal syndrome. Acute cardiorenal syndrome was associated with the highest risk of death compared with patients with CKD without cardiorenal syndrome (hazard ratio, 3.13; 95% confidence interval, 2.72 to 3.61; P<0.001). Patients with cardiorenal type 4 had better survival than patients with acute cardiorenal syndrome (hazard ratio, 0.48; 95% confidence interval, 0.37 to 0.61; P<0.001). Patients with acute cardiorenal syndrome and type 4 had increased risk of myocardial infarction and stroke compared with patients with CKD without cardiorenal syndrome.

Conclusions

Up to 19% of patients with a chronic form of cardiorenal syndrome will subsequently develop an acute syndrome. Development of acute or type 4 cardiorenal syndrome is independently associated with mortality, the acute form having the worst prognosis.

http://ift.tt/2xY1kfU

DNA Polymerase Activity Assay Using Near-infrared Fluorescent Labeled DNA Visualized by Acrylamide Gel Electrophoresis

This protocol describes the characterization of DNA polymerase synthesis of modified DNA through observation of changes to near-infrared fluorescently labeled DNA using gel electrophoresis and gel imaging. Acrylamide gels are used for high resolution imaging of the separation of short nucleic acids, which migrate at different rates depending on size.

http://ift.tt/2ggG4Ib

The Surgical Apgar Score Predicts Not Only Short-Term Complications But Also Long-Term Prognosis After Esophagectomy

Abstract

Background

The surgical Apgar score (SAS) quantifies three intraoperative factors and predicts postoperative complications, but few reports describe its usefulness in esophagectomy, and no studies to date show its correlation with long-term prognosis after esophagectomy.

Methods

This study investigated 400 cases in which esophagectomy was performed on esophageal malignant tumors at the authors' hospital from January 2007 to January 2017. In this study, SAS was defined as the sum of the scores of three parameters, namely, estimated blood loss, lowest mean arterial pressure, and lowest heart rate, with values extracted from medical records. Postoperative complications classified as Clavien–Dindo grade 3 or higher were also extracted. The study retrospectively compared the relationship of SAS to postoperative complications and survival.

Results

Univariate analysis showed that postoperative complications were significantly associated with hypertension (p = 0.017), thoracotomy (p = 0.012), and SAS ≤ 5 (p < 0.0001), and multivariate analysis showed that hypertension (p = 0.049) and SAS ≤ 5 (p < 0.0001) were significant predictive factors for complications. In the prognostic analysis, log-rank analysis showed that patients with an SAS ≤ 5 had a significantly poorer prognosis than those with a SAS > 5 (p = 0.043), especially for complications classified as clinical stage 2 or higher (p = 0.027). In the multivariate analysis, SAS ≤ 5 was identified as a significantly poor prognostic factor for complications classified as clinical stage 2 or higher (p = 0.029).

Conclusion

In this study, SAS was useful not only for predicting short-term complications, but also as a long-term prognostic factor after esophagectomy.

http://ift.tt/2hRxAe7

Total Mesenteric Peritonectomy for Peritoneal Metastases (with video)

ABSTRACT

Background

Complete cytoreductive surgery (CRS), combining organ resection and peritonectomy, is the only potentially curative treatment for patients with peritoneal metastases (PM).1 ^,2 Diffuse mesenteric PM usually represents a contraindication for CRS.3 This report presents a standardized total mesenteric peritonectomy, which provides a therapeutic option of complete CRS for patients with diffuse mesenteric PM.

Patient

A 73-year-old man had a diagnosis of PM caused by an urachal adenocarcinoma (signet cell type). Initial assessment found a 60-mm urachal tumor above the dome of the urinary bladder. Dedicated magnetic resonance imaging (MRI)4 and explorative laparoscopy confirmed the presence of diffuse mucinous PM suspected of pseudomyxoma peritonei arising from urachus. The patient was treated by a systemic induction chemotherapy including cisplatin, fluorouracil, and docetaxel, with an almost full regression of the PM shown on control MRI. The man then was treated with CRS and hyperthermic intraperitoneal chemotherapy.5

Technique

Exploration found persistent diffuse macro-nodular PM with a good response to chemotherapy, a 16/39 peritoneal cancer index,6 and no digestive tract or other organ involvement. The CRS procedure included complete urachus resection, together with appendicectomy, cholecystectomy, omentectomy, and a total parietal and mesenteric peritonectomy, with a completeness of cytoreduction score6 of 1, as illustrated in the video. At this writing, after 6 months of follow-up evaluation, the patient remains free of symptomatic peritoneal disease or local recurrence.

Conclusion

Total mesenteric peritonectomy can be safely performed with the reported technique irrespective of how widespread PM is along the mesentery as long as few small bowel serous membranes are involved.

http://ift.tt/2fQGVyR

Evaluation of Synapse Density in Hippocampal Rodent Brain Slices

A protocol for accurately identifying and analyzing synapses in hippocampal slices using immunofluorescence is outlined in this article.

http://ift.tt/2y5O3lb

Prevalence of positive coeliac disease serology and HLA risk genotypes in a multiethnic population of adults in Canada: a cross-sectional study

Objectives

Coeliac disease (CD) is a complex autoimmune disorder with known genetic risk factors. Approximately 1% of individuals of European ancestry have CD, but the prevalence among different ethnicities living in Canada remains unknown. The objective of the present study was to determine the prevalence of positive CD serology in a population of Canadian adults living in Toronto, and to determine whether the prevalence of CD seropositivity and predisposing human leucocyte antigen (HLA)-DQ2/DQ8 risk genotypes differ between major ethnocultural groups.

Design

Cross-sectional screening study of participants from the Toronto Nutrigenomics and Health and the Toronto Healthy Diet studies.

Setting

University campus and households across Toronto, Canada.

Participants: free-living

Adults (n=2832) of diverse ethnocultural backgrounds.

Main outcome measures

Prevalence of positive CD serology was determined by screening for antitissue transglutaminase antibodies in individuals with predisposing HLA-DQ2/DQ8 genotypes. HLA genotypes were determined using six single nucleotide polymorphisms in the HLA gene region.

Results

Of the 2832 individuals screened, a total of 25 (0.88%; 95% CI 0.57% to 1.30%) were determined to have positive CD serology. The majority of seropositive CD cases were undiagnosed (87%). Prevalence was highest among Caucasians (1.48%; 95% CI 0.93% to 2.23%), and similar in those of 'Other' (0.74%; 95% CI 0.09% to 2.63%) or 'Unknown' (0.43; 95% CI 0.01% to 2.36%) ethnicity. No cases of positive CD serology were identified among East Asian or South Asian individuals. East Asians had a lower prevalence of HLA risk genotypes than Caucasians and South Asians (p<0.005).

Conclusions

The prevalence of positive CD serology among Canadian adults living in Toronto is likely ~1%, with 87% of cases being undiagnosed. These findings suggest the need for better screening in high genetic risk groups.

Trial registration number

NCT00516620; Post-results.

http://ift.tt/2yvQrTj

Use of a Recombinant Mosquito Densovirus As a Gene Delivery Vector for the Functional Analysis of Genes in Mosquito Larvae

We report using an artificial intronic small RNA expression strategy to develop a non-defective recombinant Aedes aegypti densovirus (AaeDV) in vivo delivery system. A detailed procedure for the construction, packaging, and quantitative analysis of the rAaeDV vectors as well as for larval infection is described.

http://ift.tt/2yvKBBn

Low toxicity and favorable clinical and quality of life impact after non-myeloablative autologous hematopoietic stem cell transplant in Crohn’s disease

The incidence of adverse events in myeloablative transplant protocols is high in refractory Crohn's disease; this study used low doses of cyclophosphamide. Fourteen patients were submitted to non-myeloablative...

http://ift.tt/2g09P2Z

Immune thrombocytopenia with multi-organ dysfunction syndrome as a rare presentation of scrub typhus: a case report

Scrub typhus is an acute infectious illness caused by Orientia tsutsugamushi. It is endemic to a part of the world known as the "tsutsugamushi triangle". Humans are accidental hosts in this zoonotic disease. Abou...

http://ift.tt/2xXjtu9

A retrospective analysis of trends in maternal mortality in a Gambian tertiary health centre

Maternal mortality ratio (MMR) has been on the decline in the Gambia since 1990. However, there has been no steady decline in maternal mortality ratio in the Edward Francis Small Teaching Hospital, the only te...

http://ift.tt/2fY4Z6y

Acute suppurative appendicitis associated with Enterobius vermicularis: an incidental finding or a causative agent? A case report

Histological acute appendicitis patterns associated with Enterobius vermicularis is an extremely rare finding. The exact role of this parasite in acute appendicitis is controversial as usually resected specimens ...

http://ift.tt/2xZrDlI

Prognostic implications of blood lactate concentrations after cardiac arrest: a retrospective study

Elevated lactate concentration has been associated with increased mortality after out-of-hospital cardiac arrest (CA). We investigated the variables associated with high blood lactate concentrations and explor...

http://ift.tt/2wCkl3o

Effect of inspiratory synchronization during pressure-controlled ventilation on lung distension and inspiratory effort

In pressure-controlled (PC) ventilation, tidal volume (V T) and transpulmonary pressure (P L ) result from the addition...

http://ift.tt/2xZeG9k

Outcome of in- and out-of-hospital cardiac arrest survivors with liver cirrhosis

Organ failure increases mortality in patients with liver cirrhosis. Data about resuscitated cardiac arrest patients with liver cirrhosis are missing. This study aims to assess aetiology, survival and functiona...

http://ift.tt/2wCGnmS

Ultrasound assessment of rectus femoris and anterior tibialis muscles in young trauma patients

Quantitative and qualitative changes of skeletal muscle are typical and early findings in trauma patients, being possibly associated with functional impairment. Early assessment of muscle changes—as evaluated ...

http://ift.tt/2y08Qo4

Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction

Disruption of the endothelial glycocalyx contributes to acute lung injury in experimental sepsis but has not been well studied in humans. To study glycocalyx degradation in sepsis-induced ARDS, we measured pla...

http://ift.tt/2wBJvzd

Intralipid 20 Percent IV Fat Emulsion by Baxter: Recall - One Shipment of Product Exposed to Subfreezing Temperatures

Audience: Risk Manager, Pharmacy [Posted 10/06/2017] ISSUE: Baxter International Inc. announced today it is voluntarily recalling one shipment from a single lot of INTRALIPID 20% IV Fat Emulsion, 100 mL, distributed between 8/11/17 and 8/31/17 to...

http://ift.tt/2y585MB

Intralipid 20 Percent IV Fat Emulsion by Baxter: Recall - One Shipment of Product Exposed to Subfreezing Temperatures

Packing Density Necessary to Reach a High Complete Occlusion Rate in Circumferential Unruptured Intracranial Aneurysms Treated with Stent-Assisted Coil Embolization [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

This study is a homogeneous series of circumferential unruptured intracranial aneurysms with large necks treated with stent-assisted coil embolization. Our purpose was to demonstrate which value of packing density is required to produce a durable occlusion.

MATERIALS AND METHODS:

We retrospectively evaluated all patients with unruptured intracranial aneurysms who were treated with stent-assisted coil embolization having late angiographic control between 2004 and 2014, in a single large cerebrovascular referral center. To calculate the packing density, aneurysm volume, and coil volume, we used an on-line system.

RESULTS:

In 49 circumferential unruptured intracranial aneurysms treated with stent-assisted coil embolization, 38.7% (n = 19) had complete occlusion in the immediate control. Of those with incomplete occlusion, 80% (n = 24) progressed to complete occlusion in the late angiographic follow-up. At late angiographic control, 87.7% (n = 43) of aneurysms were completely occluded. All aneurysms with a packing density of ≥19% were completely occluded. Packing density was the only statistically significant predictor of complete occlusion. None of the aneurysms with complete occlusion at immediate control or at late angiographic control had recurrence.

CONCLUSIONS:

In circumferential aneurysms treated with stent-assisted coil embolization, packing density is the main predictor of complete occlusion. In this type of aneurysm, a packing density of ≥19% was enough to reach complete occlusion; knowing this is important to avoid higher packing densities that have more risk.

http://ift.tt/2hSABeh

In Vivo Imaging of Venous Side Cerebral Small-Vessel Disease in Older Adults: An MRI Method at 7T [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Traditional neuroimaging markers of small-vessel disease focus on late-stage changes. We aimed to adapt a method of venular assessment at 7T for use in older adults. We hypothesized that poorer venular morphologic characteristics would be related to other small-vessel disease neuroimaging markers and a higher prevalence of small-vessel disease–Alzheimer disease risk factors.

MATERIALS AND METHODS:

Venules were identified in periventricular ROIs on SWI and defined as tortuous or straight. The tortuosity ratio was defined as total tortuous venular length divided by total straight venular length. White matter hyperintensity burden (visually rated from 0 to 3) and the number of microbleeds (0, 1, >1) were determined. Differences in tortuous and straight venular lengths were evaluated. Relationships with demographic variables, allele producing the e4 type of apolipoprotein E (APOE4), growth factors, pulse pressure, physical activity, and Modified Mini-Mental State Examination were assessed via Spearman correlations.

RESULTS:

Participants had 42% more tortuous venular tissue than straight (median, 1.42; 95% CI, 1.13–1.62). APOE4 presence was associated with a greater tortuosity ratio ( = 0.454, P = .001), and these results were robust to adjustment for confounders and multiple comparisons. Associations of the tortuosity ratio with sex and vascular endothelial growth factor did not survive adjustment. Associations of the tortuosity ratio with other variables of interest were not significant.

CONCLUSIONS:

Morphologic measures of venules at 7T could be useful biomarkers of the early stages of small-vessel disease and Alzheimer disease. Longitudinal studies should examine the impact of apolipoprotein E and vascular endothelial growth factor on the risk of venular damage.

http://ift.tt/2fR5trm

Torgny Greitz, MD, PhD, FACR, Professor of Neuroradiology, Emeritus [other]

http://ift.tt/2fPDWGC

Yield of Image-Guided Needle Biopsy for Infectious Discitis: A Systematic Review and Meta-Analysis [SPINE]

BACKGROUND:

Image-guided biopsy is routinely conducted in patients with suspected discitis, though the sensitivity reported in the literature ranges widely.

PURPOSE:

We applied a systematic review and meta-analysis to estimate the yield of image-guided biopsy for infectious discitis.

DATA SOURCES:

We performed a literature search of 4 data bases: PubMed, Cochrane CENTRAL Register of Controlled Trials, Embase.com, and Scopus from data base inception to March 2016.

STUDY SELECTION:

A screen of 1814 articles identified 88 potentially relevant articles. Data were extracted for 33 articles, which were eligible if they were peer-reviewed publications of patients with clinical suspicion of discitis who underwent image-guided biopsy.

A protocol to expose bare fibers on the composite surface by eliminating resin rich area is presented. The fibers are exposed during fabrication of the composites, not by the post surface treatment. The exposed carbon composites exhibit high electrical conductivity in the through-thickness direction and high mechanical property.

http://ift.tt/2ytX0pw

Endocrine sensitivity of estrogen receptor-positive breast cancer is negatively correlated with aspartate-β-hydroxylase expression

Summary

Although prognostic markers for early estrogen receptor (ER)-positive breast cancer have been extensively developed, predictive markers for adjuvant endocrine therapy are still lacking. Focusing on the mechanisms underlying endocrine resistance, we investigated whether the endocrine sensitivity of ER-positive breast cancer cells was correlated with the expression of aspartate-β-hydroxylase (ASPH), which is involved in the development of hepatocellular carcinoma. ASPH expression in ER-positive and tamoxifen-resistant breast cancer cells was upregulated by the MAPK and phosphoinositide-3 kinase (PI3K) pathways, which both play pivotal roles in endocrine resistance. In the clinical setting, ASPH expression was negatively correlated with recurrence-free survival of luminal B breast cancer patients that received adjuvant endocrine therapy, but not in patients that did not receive adjuvant endocrine therapy. Luminal B breast cancer is one of the intrinsic molecular subtypes identified by the Prediction Analysis of Microarray 50 (PAM50) multiple gene classifier, and because of its poor response to endocrine therapy, chemotherapy in addition to endocrine therapy is generally required after surgical resection. Our results suggest that the endocrine sensitivity of luminal B breast cancer can be assessed by examining ASPH expression, which promotes the consideration of a prospective study on the association between ASPH expression at the mRNA and protein levels in luminal B breast cancer and subsequent response to endocrine therapy.

http://ift.tt/2xYWxsf

Esophageal adenocarcinoma microenvironment: peritumoral adipose tissue effects associated with chemoresistance

Abstract

Peritumoral microenvironment affects cancer development and chemoresistance, and visceral adipose tissue may play a critical role. We aimed to identify depot-specific adipose characteristics associated with carcinogenesis and resistance to neoadjuvant therapy, in esophageal adenocarcinoma (EAC). We analysed: 1) the peritumoral adipose tissue of rats, following the induction of esophageal carcinogenesis; 2) the peritumoral and distal (omental) adipose tissue of patients affected by EAC; 3) adipose-derived stem cells (ADSCs) isolated from healthy patients and treated with conditioned medium (CM), collected from tumoral and adipose tissue of patients with EAC. In peritumoral adipose tissue of rats, CD34, CD31 and VEGF expression increased progressively during EAC development. In patients with EAC, the expression of CD34, CD45, CD90 and Nucleostemin (NSTM) was higher in peritumoral than distal adipose tissue and decreased in the presence of neoadjuvant therapy. Moreover, the expression of NSTM, OCT-4 and VEGF was higher in peritumoral (but not distal) adipose tissue of chemoresistant patients. In ADSCs, the treatment with peritumoral adipose tissue CM increased the adipogenic potential and the expression of CD34, CD90, NSTM and OCT-4. These effects were similar to those induced by cancer-derived CM, but were not observed in ADSCs treated with distal adipose tissue CM and were partially reduced by a leptin antagonist. Lastly, ADSCs treated with peritumoral CM of chemoresistant patients, displayed increased expression of NSTM, OCT-4, leptin, leptin receptor, α-SMA, CD34 and VEGF. These results suggest that the peritumoral adipose tissue may promote, via paracrine signalling, the expression of depot-specific factors associated with therapeutic resistance.

http://ift.tt/2y4QYdw

Αρχειοθήκη ιστολογίου

Αναζήτηση αυτού του ιστολογίου

Παρασκευή 6 Οκτωβρίου 2017

Abstract

Abstract

Abstract

Background

Methods

Results

Conclusion

ABSTRACT

Background

Patient

Technique

Conclusion

Summary

Abstract