Colchicine for Secondary Cardiovascular Prevention: A Systematic Review

Despite advancements in medical and interventional therapy, patients with cardiovascular disease (CVD) continue to have residual risk for recurrent cardiovascular events. Colchicine has a unique antiinflammatory mechanism that has generated interest in its potential use as a secondary cardiovascular preventive therapy. The objective of this systematic review was to evaluate the evidence for long-term (6 months or more) colchicine therapy in patients with established CVD. A search of Medline and Embase from inception to February 2020 was performed. Included were randomized controlled trials (RCTs) or propensity score-matched observational studies that compared colchicine (at any dose) with placebo or no treatment. Outcomes of interest included any major adverse cardiovascular event, cardiovascular hospitalization, coronary artery restenosis, cardiovascular death, or all-cause death. Five RCTs were included. The dose of colchicine ranged from 0.5 mg/day to 0.6 mg twice/day, and follow-up ranged from ~6–36 months. Two trials (one double blind and one single blind) showed a reduction in composite outcomes of major adverse cardiovascular events. One study failed to demonstrate a benefit with colchicine in restenosis or recurrent ischemia after angioplasty; however, it was conducted before the routine use of modern percutaneous coronary intervention and medical therapies. In contrast, a more recent trial found that colchicine reduced the rate of in-stent restenosis in patients who received a bare metal stent. Finally, one trial in patients with heart failure with reduced ejection fraction did not observe a benefit in death or heart failure hospitalization with colchicine despite a reduction in inflammatory markers. No trial demonstrated a reduction in cardiovascular or all-cause death, and most trials showed an increase in the rate of diarrhea with colchicine. Overall, colchicine has demonstrated promising results for the secondary prevention of CVD; however, further studies are required to confirm these findings before colchicine can be routinely recommended in practice.     

Evaluation of the antiparasitic activities of imidazol-2-ylidene–gold(I) complexes

A series of cationic gold(I)–carbene complexes with various 4,5-diarylimidazolylidene ligands were either newly prepared or repurposed for testing against protozoal Leishmania major, Toxoplasma gondii, and Trypanosoma brucei parasites. The syntheses of the new complexes 1b and 1c were described. Ferrocene compound 1a showed the highest activities against L. major amastigotes and T. gondii and distinct selectivity for T. gondii cells when compared with the activity against nonmalignant Vero cells. The ferrocene derivatives 1a–c are generally more active against the L. major amastigotes and the T. gondii tachyzoites than the other tested anisyl gold complexes and the approved drugs atovaquone and amphotericin B. Compounds 1a and 1e showed the highest selectivities for L. major amastigotes. Compounds 1d and 1f showed the highest selectivities for L. major promastigotes; 1f was the most active compound against L. major promastigotes of this series of compounds. The 3,4,5-trimethoxyphenyl analog 1b also exhibited a much greater selectivity for T. b. brucei cells when compared with its activity against human HeLa cells.     

炎症性肠病的MRI进展

炎症性肠病（IBD）是一组病因不明的慢性炎症性肠病,包括克罗恩病（CD）和溃疡性结肠炎（UC）,常导致肠腔狭窄或穿透性肠损伤,其病程发展过程中需要经常评估疾病的活动性和并发症,以便制定正确的治疗方案。MRI软组织分辨力高,可以获得肠壁的动态信息,已应用于对IBD的检出、评估病变活动性、判断病变纤维化程度及鉴别CD与UC等。就MR小肠成像、扩散加权成像、动态增强MRI及磁化传递成像等在IBD中的应用进展予以综述。     

Combating mutations in genetic disease and drug resistance: understanding molecular mechanisms to guide drug design

Introduction: Mutations introduce diversity into genomes, leading to selective changes and driving evolution. These changes have contributed to the emergence of many of the current major health concerns of the 21st century, from the development of genetic diseases and cancers to the rise and spread of drug resistance. The experimental systematic testing of all mutations in a system of interest is impractical and not cost-effective, which has created interest in the development of computational tools to understand the molecular consequences of mutations to aid and guide rational experimentation.

Areas covered: Here, the authors discuss the recent development of computational methods to understand the effects of coding mutations to protein function and interactions, particularly in the context of the 3D structure of the protein.

Expert opinion: While significant progress has been made in terms of innovative tools to understand and quantify the different range of effects in which a mutation or a set of mutations can give rise to a phenotype, a great gap still exists when integrating these predictions and drawing causality conclusions linking variants. This often requires a detailed understanding of the system being perturbed. However, as part of the drug development process it can be used preemptively in a similar fashion to pharmacokinetics predictions, to guide development of therapeutics to help guide the design and analysis of clinical trials, patient treatment and public health policy strategies.     

Neuromyelitis optica spectrum disorders and systemic lupus erythematosus: A case series from a university center

Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory diseases of the central nervous system (CNS), which preferentially affect the optic nerves and the spinal cord. Anti-aquaporin 4 antibody is a specific serological marker. Systemic lupus erythematosus (SLE) is a rheumatologic disease that may affect the CNS. There are several reports about the coexistence of NMOSD and autoimmune diseases, mainly those of rheumatologic origin. We describe three different cases in which SLE and NMOSD subsequently occurred, drawing attention to the clinical heterogeneity, the challenge and the importance of recognizing this possible association.     

Immunoglobulin shortage: Practice modifications and clinical outcomes in a reference centre

BackgroundGrowing numbers of indications for intravenous immunoglobulins (IVIg) in recent years has resulted in an increase in the consumption of these products. A lack of raw material has led to IVIg shortage. The objective of this work was to evaluate the impact of this situation on patient care in one French referral centre considering practice modifications and clinical impact.MethodsAll patients treated with IVIg for chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy and myasthenia gravis from October 2017 to October 2018 were included.ResultsOut of 142 patients, 111 (78%) had a modification of their IVIg treatment. We noted that 75 (68%) patients had a delay in IVIg treatment, 41 (37%) patients had a decrease in IVIg doses and 31 (28%) experienced IVIg treatment interruption. Thirty percent of patients for whom IVIg treatment was discontinued were switched to other treatments mainly plasma exchange (16%) or corticosteroids (13%). Switches to plasma exchange or corticosteroids were carried out in order to save immunoglobulins for patients who had no other alternatives. Fifty-eight (52%) patients presented a deterioration of their clinical score after IVIg treatment changes including 31 (28%) patients who had a moderate or a clinically significant deterioration. Concerning practice modifications, we noted a substantial though not significant decrease in median IVIg dose for myasthenia gravis and a significant increase in the delay between IVIg courses for chronic inflammatory demyelinating polyneuropathy and multifocal motor neuropathy (P = 0.011 and P = 0.018 respectively).ConclusionOur study showed a rather important number of changes in IVIg treatment related to IVIg shortage during the period considered. These changes had a negative impact on the clinical status of some patients.     

Estudio exploratorio sobre gastrostomía en pacientes con enfermedades neurológicas: utilidad e impacto

IntroductionPercutaneous endoscopic gastrostomy (PEG) is a useful intervention for patients with impaired swallowing and a functional gastrointestinal system. Neurological diseases that cause neuromotor dysphagia, brain tumors, and cerebrovascular disease are the most frequent indications; complications are rare, and morbidity and mortality rates are low.ObjectiveTo describe the usefulness of PEG in patients with neurological diseases, and its impact on care, survival, and costs and benefits.Material and methodsWe performed a retrospective observational study, reviewing clinical files of patients hospitalised at the National Institute of Neurology and Neurosurgery (years 2015-2017) who underwent PEG placement.ResultsThe sample included 51 patients: 62.7% were women and the mean (SD) age was 54.4 (18.6) years (range, 18-86). Diagnosis was tumor in 37.3% of cases and cerebrovascular disease in 33.3%. Sixteen patients (33.3%) died and 11 presented minor complications. The PEG tube remained in place for a mean of 9.14 months; in 52.9% of patients it was removed due to lack of improvement and/or tolerated oral intake, with removal occurring after a mean of 5.1 (4.4) months. Among patients’ family members, 78.4% reported a great benefit, 43.1% reported difficulty caring for the PEG, and 45.1% reported complicated care in general. The monthly cost of maintaining the PEG was €175.78 on average (range, 38.38-293.45).Discussion and conclusionsThis preliminary study reveals that PEG was well indicated in patients with neurological diseases, with survival rates similar to those reported in other studies with long follow-up periods. In patients with cerebrovascular disease, the PEG tube remained in place a mean of 9.14 months, during recovery of swallowing function; however, the cost is high for our population.     

Schwann cell-derived exosomes: Janus-faced mediators of regeneration and disease

The phenotypic plasticity of Schwann cells (SCs) has contributed to the regenerative potential of the peripheral nervous system (PNS), but also pathological processes. This double-sided effect has led to an increasing attention to the role of extracellular vesicles (EVs) or exosomes in SCs to examine the intercellular communication between SCs and their surroundings. Here, we first describe the current knowledge of SC and EV biology, which forms the basis for the updates on advances in SC-derived exosomes research. We seek to explore in-depth the exosome-mediated molecular mechanisms involved in the regulation of SCs and their microenvironment. This review concludes with potential applications of SC-derived exosomes as delivery vehicles for therapeutics and biomarkers. The goal of this review is to emphasize the crucial role of SC-derived exosomes in the functional integration of the PNS, highlighting an emerging area in which there is much to explore and re-explore.