Assessing the efficacy and safety of magnesium sulfate for management of autonomic nervous system dysregulation in Vietnamese children with severe hand foot and mouth disease.

BACKGROUND: Brainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO4) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension). METHODS: During a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death. RESULTS: Between June 2014 and September 2016, 14 and 12 participants received MgSO4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used. CONCLUSION: Although we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013). Trial sponsor: University of Oxford

Evaluating the initial result of transanal and transvaginal NOTES for colorectal cancer

Objective: Natural Orifice Transluminal Endoscopic Surgery (NOTES) is an important evolution in minimally invasive surgery (MIS) nowaday. This paper presents the techniques and early results of the pure transanal and transvaginal laparoscopies (NOTES) used for the treatment of colorectal cancer. Material and method: Prospective studies were conducted at Hue Central Hospital, Vietnam. Patients: From December 2013 to September 2015, 22 cololorectal cancer patients (18 rectum, 3 sigmoid tumors and 1 descending colon), adenocarcinoma, T≤ T3N1M0. Methods: The patients were placed in lithotomy and Trendelenburg positions, and the lone-star retractor was placed in the anus (rectum cancer) or vagina (sigmoid cancer). The surgical cavity was then inflated with CO 2 and set at 12 mm/Hg. Dissection was continued until inside of the abdominal cavity (transanal technique). After that, the rectum was pushed into the abdominal cavity. The IMA and IMV were divided (TME included) in both techniques. After finishing dissection, the specimens were pulled out through the anus or vagina to prepare anastomosis. Coloanal and colorectal anastomosis were either hand-sewn (6 cases) or sealed with EEA staplers (16 cases). Results: 2 patients needed one more 5 mm umbilical port in RLQ, 2 patients needed two 5 mm trocars (post radiation hemorrhage, and urethral perforation). One patient converted to open and 1 patient converted to the HYBRID-NOTES procedure. The operation time was 258±40 (190-300) minutes. All patients required minimal analgesia. Bowel movement returned on the first day to 16 patients (average: two days, maximum: three days). The hospital stay was 7±2.8 (4-14) days. Kirwan classification (sphincter function) was very good (stage I: 18). Conclusions: Pure transanal and transvaginal laparoscopies for the treatment of colorectal cancer are feasible and safe. We believe that this is the first pure transvaginal laparoscopy (NOTES) for human in the world. A multicentric study in a large numbers of patients and a long follow-up is necessary

Improvement in neoantigen prediction via integration of RNA sequencing data for variant calling

IntroductionNeoantigen-based immunotherapy has emerged as a promising strategy for improving the life expectancy of cancer patients. This therapeutic approach heavily relies on accurate identification of cancer mutations using DNA sequencing (DNAseq) data. However, current workflows tend to provide a large number of neoantigen candidates, of which only a limited number elicit efficient and immunogenic T-cell responses suitable for downstream clinical evaluation. To overcome this limitation and increase the number of high-quality immunogenic neoantigens, we propose integrating RNA sequencing (RNAseq) data into the mutation identification step in the neoantigen prediction workflow.MethodsIn this study, we characterize the mutation profiles identified from DNAseq and/or RNAseq data in tumor tissues of 25 patients with colorectal cancer (CRC). Immunogenicity was then validated by ELISpot assay using long synthesis peptides (sLP).ResultsWe detected only 22.4% of variants shared between the two methods. In contrast, RNAseq-derived variants displayed unique features of affinity and immunogenicity. We further established that neoantigen candidates identified by RNAseq data significantly increased the number of highly immunogenic neoantigens (confirmed by ELISpot) that would otherwise be overlooked if relying solely on DNAseq data.DiscussionThis integrative approach holds great potential for improving the selection of neoantigens for personalized cancer immunotherapy, ultimately leading to enhanced treatment outcomes and improved survival rates for cancer patients

Understanding Viscoelasticity: An Introduction to Rheology

This book presents an introduction to viscoelasticity; in particular, to the theories of dilute polymer solutions and dilute suspensions of rigid particles in viscous and incompressible fluids. These theories are important, not just because they apply to practical problems of industrial interest, but because they form a solid theoretical base upon which mathematical techniques can be built, from which more complex theories can be constructed, to better mimic material behaviour. The emphasis is not on the voluminous current topical research, but on the necessary tools to understand viscoelasticity at a first year graduate level. The main aim is to provide a still compact book, sufficient at the level of first year graduate course for those who wish to understand viscoelasticity and to embark in modeling of viscoelastic multiphase fluids. To this end, a new chapter on Dissipative Particle Dynamics (DPD) was introduced which is relevant to model complex-structured fluids. All the basic ideas in DPD are reviewed, with some sample problems to illustrate the methodology