Prescribing Challenges after Bariatric Surgery

Obesity is an increasing problem in the UK, with over half the population being overweight or obese. The use of gastric surgery is increasing, with a 5% increase in 2016/17 compared to 2015/16. However, little is known about ideal drug formulations after bariatric surgery. An exploratory literature search of research databases was carried out to address this. We found that there was a dearth of high-quality primary studies available, with many studies using low numbers of participants. The major finding was of the need for increased vigilance and monitoring of patients after surgery

Development of diagnostic system for atherosclerosis based on intrinsic fluorescence using multispectral imaging

Composition of atherosclerotic arterial walls is rich in lipids such as cholesterol; unlike normal arterial walls. In this study, we aimed to utilize this difference to diagnose atherosclerosis via multispectral imaging, which allows for identification of fluorescence originating from the substance in the arterial wall. The inner surface of extracted arteries (rabbit abdominal aorta, human coronary aorta) was illuminated by an excitation light and multispectral fluorescence images were obtained. The fluorescence spectra in atherosclerotic sites were shown to be different from those in normal sites. A ratio of fluorescence intensity at a wavelength of two significant differences was then calculated for each pixel and ratio images were reconstructed. As a result, we succeeded in “disease mapping”, by which atherosclerotic sites can be discriminated from normal sites. The differences in fluorescence spectra may be attributed to the differences in fluorophores contained in the intima/media of the artery

Clinical practice guidelines of the European Association for Endoscopic Surgery (EAES) on bariatric surgery: update 2020 endorsed by IFSO-EC, EASO and ESPCOP

Background: Surgery for obesity and metabolic diseases has been evolved in the light of new scientific evidence, long-term outcomes and accumulated experience. EAES has sponsored an update of previous guidelines on bariatric surgery. Methods: A multidisciplinary group of bariatric surgeons, obesity physicians, nutritional experts, psychologists, anesthetists and a patient representative comprised the guideline development panel. Development and reporting conformed to GRADE guidelines and AGREE II standards. Results: Systematic review of databases, record selection, data extraction and synthesis, evidence appraisal and evidence-to-decision frameworks were developed for 42 key questions in the domains Indication; Preoperative work-up; Perioperative management; Non-bypass, bypass and one-anastomosis procedures; Revisional surgery; Postoperative care; and Investigational procedures. A total of 36 recommendations and position statements were formed through a modified Delphi procedure. Conclusion: This document summarizes the latest evidence on bariatric surgery through state-of-the art guideline development, aiming to facilitate evidence-based clinical decisions

HTLV-1 Tax Mediated Downregulation of miRNAs Associated with Chromatin Remodeling Factors in T Cells with Stably Integrated Viral Promoter

RNA interference (RNAi) is a natural cellular mechanism to silence gene expression and is predominantly mediated by microRNAs (miRNAs) that target messenger RNA. Viruses can manipulate the cellular processes necessary for their replication by targeting the host RNAi machinery. This study explores the effect of human T-cell leukemia virus type 1 (HTLV-1) transactivating protein Tax on the RNAi pathway in the context of a chromosomally integrated viral long terminal repeat (LTR) using a CD4+ T-cell line, Jurkat. Transcription factor profiling of the HTLV-1 LTR stably integrated T-cell clone transfected with Tax demonstrates increased activation of substrates and factors associated with chromatin remodeling complexes. Using a miRNA microarray and bioinformatics experimental approach, Tax was also shown to downregulate the expression of miRNAs associated with the translational regulation of factors required for chromatin remodeling. These observations were validated with selected miRNAs and an HTLV-1 infected T cells line, MT-2. miR-149 and miR-873 were found to be capable of directly targeting p300 and p/CAF, chromatin remodeling factors known to play critical role in HTLV-1 pathogenesis. Overall, these results are first in line establishing HTLV-1/Tax-miRNA-chromatin concept and open new avenues toward understanding retroviral latency and/or replication in a given cell type

HTLV-1 Evades Type I Interferon Antiviral Signaling by Inducing the Suppressor of Cytokine Signaling 1 (SOCS1)

Human T cell leukemia virus type 1 (HTLV-1) is the etiologic agent of Adult T cell Leukemia (ATL) and the neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Although the majority of HTLV-1–infected individuals remain asymptomatic carriers (AC) during their lifetime, 2–5% will develop either ATL or HAM/TSP, but never both. To better understand the gene expression changes in HTLV-1-associated diseases, we examined the mRNA profiles of CD4+ T cells isolated from 7 ATL, 12 HAM/TSP, 11 AC and 8 non-infected controls. Using genomic approaches followed by bioinformatic analysis, we identified gene expression pattern characteristic of HTLV-1 infected individuals and particular disease states. Of particular interest, the suppressor of cytokine signaling 1—SOCS1—was upregulated in HAM/TSP and AC patients but not in ATL. Moreover, SOCS1 was positively correlated with the expression of HTLV-1 mRNA in HAM/TSP patient samples. In primary PBMCs transfected with a HTLV-1 proviral clone and in HTLV-1-transformed MT-2 cells, HTLV-1 replication correlated with induction of SOCS1 and inhibition of IFN-α/β and IFN-stimulated gene expression. Targeting SOCS1 with siRNA restored type I IFN production and reduced HTLV-1 replication in MT-2 cells. Conversely, exogenous expression of SOCS1 resulted in enhanced HTLV-1 mRNA synthesis. In addition to inhibiting signaling downstream of the IFN receptor, SOCS1 inhibited IFN-β production by targeting IRF3 for ubiquitination and proteasomal degradation. These observations identify a novel SOCS1 driven mechanism of evasion of the type I IFN antiviral response against HTLV-1

Severe hypertriglyceridemia and colchicine intoxication following suicide attempt

Shaul Lev,1 David Snyder,2 Carmil Azran,3 Victor Zolotarsky,1 Arik Dahan4 1Intensive Care Unit, Rabin Medical Center, Petah-Tikva, 2Sackler School of Medicine NY/American Program, Tel-Aviv University, Tel Aviv, 3Clinical Pharmacy, Herzliya Medical Center, Herzliya, 4Department of Clinical Pharmacology, School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel Abstract: Colchicine overdose is uncommon but potentially life threatening. Due to its serious adverse systemic effects, overdose must be recognized and treated. We report a case of an 18-year-old female who ingested 18 mg (~0.4 mg/kg) of colchicine in a suicide attempt. The patient’s clinical manifestations included abdominal cramps, vomiting, pancytopenia, hypocholesterolemia, and rhabdomyolysis. Two unique manifestations of toxicity in this patient were profound and persistent, severe hypertriglyceridemia and electrolyte imbalance, mainly hypophosphatemia, with no other evident cause except the colchicine intoxication. Following intensive supportive treatment, including ventilator support, N-acetylcysteine, granulocyte colony stimulating factor, electrolyte repletion, and zinc supplementation, the patient made a complete recovery. Colchicine intoxication is a severe, life-threatening situation that should be followed closely in intensive care units. Severe changes in body functions can rapidly develop, as previously described in the literature. To our knowledge, this extremely elevated triglyceride level has never been reported without the administration of propofol, and requires further evaluation. Keywords: colchicine, intoxication, hypophosphatemia, hypertriglyceridemia&nbsp