Study of the Treatment Effects of Compound Tufuling Granules in Hyperuricemic Rats Using Serum Metabolomics

The study aimed to investigate the mechanism of the effect of Compound Tufuling Granules (CTG) to lower the serum uric acid level in a rat model of hyperuricemia. The rat model was established by administering hypoxanthine through oral gavage and potassium oxonate through intraperitoneal injection. Rats were divided into the normal group, model group, CTG group, and allopurinol group. Serum uric acid, creatinine, urea nitrogen, and inflammatory cytokine levels were determined in each group. In the model group, ultrahigh performance liquid chromatography-mass spectrometry was used to analyze the metabolic profiles and delineate the action mechanism of CTG; in addition, the orthogonal projection method was used to perform latent structure-discrimination analysis to screen the related metabolites. The results indicated significant differences in the metabolic profiles between the model and normal groups. A total of seven related metabolites were identified through screening in the model group, mainly related to the pathways of bile secretion, pyrimidine, purine, and phenylalanine metabolism, pantothenate and CoA biosynthesis, and pentose and glucuronate interconversions; these related pathways were reversed in the CTG group. In the metabolic networks, uracil and acetyl-coenzyme A were the nodal molecules. In addition, the test results of the evaluation of serum biochemical and inflammatory factors confirmed that CTG had significant effect in reducing the levels of serum uric acid and protecting renal function. These results confirmed that CTG primarily regulated the recruitment of nodal molecules to achieve anti-inflammatory effects, reduced uric acid level, and renal protection.

https://ift.tt/2NKpSwA

Peri-Implant Bone Resorption during Healing Abutment Placement: The Effect of a 0.20 Chlorhexidine Gel vs. Placebo—A Randomized Double Blind Controlled Human Study

Introduction. Peri-implant marginal bone loss (MBL) seems to be more pronounced in the first year of loading despite all the studies and changes implemented to reduce it. Among the different causes, the presence of a microgap makes the interface between fixture and abutment colonizable by bacteria, causing an inflammatory response and consequent bone resorption. To reduce this several local antiseptics like chlorhexidine digluconate (CHX) were used after surgical procedures. Aim. The objective was to radiologically compare the MBL when a 0.20% CHX gel or a placebo gel was applied to the implant-abutment interface during all surgical and prosthetic phases and for a follow-up period up to 12 months. Method. 32 patients (16 for each Group A and B) were enrolled and rehabilitated with a single implant (Cortex classic, Cortex, Shalomi, Israel). During each of the clinical stages a gel containing 0.20% CHX (Plak ®Gel; Polifarma Wellness Srl, Rome, Italy) or a placebo gel (Placebo, Polifarma Wellness Srl, Rome, Italy) was used as indicated by the randomization chart. In order to compare radiographic modification intraoral radiographs was taken. Also, clinical data regarding implant or prosthetic failure and gingival index were recorded. Data were presented as means and standard deviations (SD) and used for the statistical analysis. Results. All implants showed no bleeding on probing and a very small plaque score at the 1 year of follow-up. MBL was statistically significantly different between the groups in every stage. Conclusion. Results obtained showed that the use of CHX gel inside the connection significantly reduces MBL during the first year. A rigid disinfection protocol with 0.20% CHX from the time of implant insertion to crown delivery is recommended to reduce host inflammatory response and consequently MBL. This trial is registered with ClinicalTrials.gov Identifier: (Registration Number: NCT03431766).

https://ift.tt/2CNrzbU

Cladribine Tablets for the First-Line Treatment of Relapsing-Remitting Multiple Sclerosis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

As part of the single technology appraisal process, the National Institute for Health and Care Excellence invited Merck to submit evidence for the clinical and cost effectiveness of cladribine tablets (cladribine) for the treatment of relapsing-remitting multiple sclerosis (RRMS). Rapidly evolving severe (RES) and sub-optimally treated (SOT) RRMS were specified by the National Institute for Health and Care Excellence as subgroups of interest. The Liverpool Reviews and Implementation Group at the University of Liverpool was the Evidence Review Group. This article summarises the Evidence Review Group's review of the company's evidence submission for cladribine and the Appraisal Committee's final decision. The final scope issued by the National Institute for Health and Care Excellence listed the following disease-modifying treatments as comparators: alemtuzumab, daclizumab, fingolimod and natalizumab. At the time of the company submission, a licence was anticipated for low-dose cladribine. The main clinical evidence (the CLARITY trial) in the company submission focused on the efficacy of low-dose cladribine vs. placebo. The CLARITY trial showed a statistically significant reduction in relapse rate for cladribine in the RES-RRMS subgroup (n = 50) but not in the SOT-RRMS subgroup (n = 19). Cladribine showed a numerical, but not a statistically significant, advantage in delaying disability progression at 6 months in the RES-RRMS subgroup. Disability progression benefits could not be estimated for those in the SOT-RRMS subgroup because of few events. The Evidence Review Group's main concern regarding the clinical evidence was the small sample size of the subgroups. To compare the effectiveness of cladribine to other disease-modifying treatments, the company conducted network meta-analyses, which showed cladribine and its comparators to be equally effective. The Evidence Review Group considered the results of the disease-modifying treatments to be unreliable because few trials were in the network. The company's cost-effectiveness evidence showed cladribine to be cheaper and more effective than other disease-modifying treatments in the RES-RRMS arm and the SOT-RRMS arm. The results were most sensitive to treatment effect on disability progression at 6 months. The Evidence Review Group was concerned that there was insufficient evidence to conclude that cladribine was superior to placebo in delaying disability progression. The Evidence Review Group amended the company's economic model to allow alternative estimates for the treatment effect of cladribine and its comparators on relapse rate and disability progression at 6 months. The Evidence Review Group made other changes to the company model. After implementing all the amendments, cladribine remained cost effective in the RES-RRMS and SOT-RRMS subgroups. The Appraisal Committee recognised the uncertainty in the available data but concluded that cladribine could be considered a cost-effective use of National Health Service resources.

https://ift.tt/2NJvBmg

9 issues stroke systems of care must address to improve outcomes

EMS triage and destination, emergency department, transfer and stroke team protocols are essential to rapid definitive treatment for ischemic stroke

https://ift.tt/2AdOJ8R

A smoking cessation and pain management program for cancer survivors

Abstract

Purpose

Many cancer survivors continue to smoke. Further, most survivors also report high levels of persistent pain and smoke in response to pain. The investigators tested the feasibility, acceptability, and preliminary efficacy of a smoking cessation program paired with a pain management program for cancer survivors.

Methods

The investigators conducted a two-arm, wait-list randomized controlled pilot study in which they delivered a combined smoking cessation and pain management intervention.

Results

The investigators randomized 30 survivors (14 intervention and 16 wait-list control). Seventy-one percent of the survivors who received the intervention rated it as extremely useful (5 out of 5) in helping them quit smoking. Further, 86% would recommend the program to other survivors. Although we could not conduct inferential statistics, 14% of those in the intervention arm, compared to 6% in the control condition had biochemically validated cessation at 2-months post-randomization. Survivors in the intervention also reported less pain, had improvements in depressive symptoms, and better physical function than those in the control arm.

Conclusions

Our pilot data suggest the feasibility, acceptability, and preliminary efficacy of this approach. The next step is to conduct a large randomized controlled trial to fully test the efficacy of the intervention.

Implications for Cancer Survivors

A combined smoking cessation and pain program might help improve both issues simultaneously.

https://ift.tt/2J15arK

Abiraterone acetate treatment in patients with castration-resistant prostate cancer with visceral metastases: a real-world experience

In the pre-chemotherapy (CT) and post-CT settings of metastatic castration-resistant prostate cancer (mCRPC), abiraterone acetate plus prednisone (AAP) significantly extended median overall survival and radiographic progression-free survival (PFS) compared with prednisone alone. Yet, few data are available on therapy efficacy in the subgroup with visceral metastases, who represent a small population with poor prognosis. The aim of this study was to describe the clinical experience of AAP in patients with mCRPC with liver and/or lung metastases in real-world setting. We retrospectively reviewed the clinical records of patients with mCRPC with liver and/or lung metastases treated at the National Cancer Institute 'Fondazione G. Pascale' from September 2011 to May 2017. Co-primary end points were overall survival and radiographic PFS. Survival estimates were computed using Kaplan–Meier method. Secondary end points were response rate and safety. Of 143 patients with mCRPC treated, 18.9% (N=27) had visceral metastases: 85.2% (N=23) of the lung, 11.1% (N=3) of the liver and 3.7% (N=1) of both. Median PFS was 13.1 months [95% confidence interval (CI): 4.8–NA] in the pre-CT setting (N=11, median follow-up: 12.9 months), and 10.5 months (95% CI: 4.4–16.6) in the post-CT setting (N=16, median follow-up: 17.2 months). Pre-CT and post-CT patients with lung metastases had a median PFS of 16.5 months (95% CI: 4.3–NA) and 11.4 months (95% CI: 4.2–17.0), respectively. AAP tolerability was consistent with that previously reported in patients with mCRPC, without new safety concerns. Our finding provides preliminary evidence that AAP in real-world setting is a potential effective and safe therapeutic option for patients with mCRPC with a more advanced disease associated with the presence of visceral metastases, in both the pre-CT and post-CT settings. Correspondence to Gaetano Facchini, MD, Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale, Via M. Semmola 80131, Napoli, Italy Tel: +39 081 590 3641; e-mail: g.facchini@istitutotumori.na.it Received May 1, 2018 Accepted September 24, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2PC24wO

Co-operation of ABT-199 and gemcitabine in impeding DNA damage repair and inducing cell apoptosis for synergistic therapy of T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is a high-risk subtype of acute lymphoblastic leukemia with limited therapeutic options available. Here, we evaluated the therapeutic potential of the combination of the Bcl-2 antagonist ABT-199 and cytotoxic agent gemcitabine in T-ALL cell lines. Our results showed that the combination of ABT-199 and gemcitabine exhibited synergistic cytotoxicity and induced significant apoptosis in human T-ALL cell lines (Jurkat and Molt4). The augmented apoptosis induced by combination treatment was accompanied by the greater extent of mitochondrial depolarization and enhanced DNA damage. Importantly, single agent induced DNA damage alone but did not inhibit RAD51/BRCA1-mediated repair for DNA double-strand breaks. In contrast, the combination of ABT-199 and gemcitabine disrupted RAD51/BRCA1-dependent DNA repair and remarkably activated caspase-3 and PARP to trigger apoptosis. Moreover, ABT-199 exerted an antagonistic action towards Bcl-2 and Bcl-xL, but to a certain extent moderately increased Mcl-1 level that could be compromised by gemcitabine. In conclusion, our study showed that the combination of ABT-199 and gemcitabine exhibited synergistic cytotoxicity in T-ALL cells by cooperatively targeting DNA damage repair pathway and Bcl-2 family proteins. *Zhu Xiufeng, Zhao Haijun and Bi Silei contributed equally to the writing of this article. Correspondence to Xu Bing, MD, PhD, Department of Hematology, The First Affiliated Hospital of Xiamen University and Institute of Hematology, Medical College of Xiamen University, Xiamen 361003, People's Republic of China Tel: +86 187 5091 8842; fax: +86 05 922 137 177; e-mail: xubingzhangjian@126.com Received January 20, 2018 Accepted September 18, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

https://ift.tt/2P40Mxx