Effect of Washed Microbiota Transplantation on Patients With Dyslipidemia in South China.

Background and Aims: Although the manual crude fecal microbiota transplantation (FMT) reduces blood lipids in animal models of hyperlipidemia, its clinical effect on blood lipid metabolism in patients with hyperlipidemia and hypolipidemia remains unclear, especially in the Chinese population. It was reported that washed microbiota transplantation (WMT) was safer, more precise, and more quality-controllable than the crude FMT by manual. This study aimed to investigate the feasibility and effectiveness of WMT on lipid metabolism in the Chinese population. Methods: Clinical data of patients with various indications who received WMT for 1-3 treatment procedures were collected. Changes in blood lipids before and after WMT, namely, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), homeostasis model assessment of insulin resistance (HOMA-IR), liver fat attenuation, and liver stiffness measurement, were compared. Results: A total of 177 patients (40 cases of hyperlipidemia, 87 cases with normal blood lipids, and 50 cases of hypolipidemia) were enrolled in the First Affiliated Hospital of Guangdong Pharmaceutical University. WMT has a significant therapeutic effect in reducing blood lipid levels (TC and TG) in the short- and medium term in patients with hyperlipidemia (p <0.05). Hyper blood lipid decreased to normal in the short-term (35.14%; p <0.001), and LDL-C changed to normal in the medium term (33.33%; p = 0.013). In the hypolipidemia group, 36.36% and 47.06% changed to normal in the short-term (p = 0.006) and medium term (p = 0.005) of therapeutic effects based on blood lipid levels. In the normal blood lipid group and the low-risk group of atherosclerotic cardiovascular disease (ASCVD), the change was not statistically significant, indicating that WMT does not increase the risk of blood lipid and ASCVD in the long-term. Conclusions: WMT treatment changes blood lipids in patients with hyperlipidemia and hypolipidemia without serious adverse events, with no risk for increasing blood lipids and ASCVD in the long-term. There were significant decreased TC, TG, and LDL-C levels in the medium term of WMT treatment for hyperlipidemia. Therefore, the regulation of gut microbiota by WMT may indicate a new clinical method for the treatment of dyslipidemia.

Roles of microRNAs in carbohydrate and lipid metabolism disorders and their therapeutic potential.

MicroRNAs (miRNAs) are small (∼21 nucleotides), endogenous, non-coding RNA molecules implicated in the post-transcriptional gene regulation performed through target mRNA cleavage or translational inhibition. In recent years, several investigations have demonstrated that miRNAs are involved in regulating both carbohydrate and lipid homeostasis in humans and other organisms. Moreover, it has been observed that the dysregulation of these metabolism-related miRNAs leads to the development of several metabolic disorders, such as type 2 diabetes, obesity, nonalcoholic fatty liver, insulin resistance, and hyperlipidemia. Hence, in this current review, with the aim to impulse the research arena of the micro-transcriptome implications in vital metabolic pathways as well as to highlight the remarkable potential of miRNAs as therapeutic targets for metabolic disorders in humans, we provide an overview of the regulatory roles of metabolism-associated miRNAs in humans and murine models.

Pediatric Lipid Disorders.

Current scientific evidence has proven that atherosclerosis is a process that begins in childhood and tracks into adulthood, likely culminating in adverse cardiovascular events such as coronary artery disease, peripheral artery disease, and stroke. In addition, the obesity epidemic and increasing awareness of genetic lipid disorders has made the understanding and management of lipid disorders necessary for pediatricians. Childhood offers a unique opportunity for preventing, modifying, or eliminating risk factors and, in doing so, reversing or slowing the process of atherosclerosis. In general, management involves targeted lifestyle interventions such as strict dietary changes and increases in physical activity. In some circumstances, pharmacotherapy, even in childhood, is warranted. [Pediatr Ann. 2021;50(3):e105-e112.].

Gene therapy: An updated overview on the promising success stories.

Gene therapy is a method of treatment of disease aimed at its molecular level. The progress of gene therapy, however, was as promising as it was tardy mainly due to the limitations in the resources and financial part of its development as well as owing to the rarity of most diseases it can offer its benefits to. The methods of gene therapy can vary depending on factors such as the physiology of tissue of interest, affinity of vectors to a certain type of cells, depth and accessibility of the tissue of interest, and size of the gene to be replaced or edited. The concept behind gene therapy has inspired scientists and clinicians alike leading to a rapid expansion of its clinical utility that has become so widespread to not only include diseases of monogenic origin, but also polygenic diseases, albeit not so commonly. This article delves into notable success stories of gene therapy which has been regarded as the beacon of medical novelty expected to blossom in the near future to provide a holistic, targeted, precise, and individualistic personalised-medicine as well as laying out the future hopes of gene therapy in the treatment of debilitating diseases such as solid tumours, AIDS, Tuberculosis, Diabetes Mellitus, psychiatric illnesses, which are still at a standstill, from a gene therapy point of view.

Carnitine Palmitoyl Transferase Deficiency in a University Immunology Practice.

PURPOSE: This report describes the clinical manifestations of 35 patients sent to a University Immunology clinic with a diagnosis of fatigue and exercise intolerance who were identified to have low carnitine palmitoyl transferase activity on muscle biopsies. RECENT FINDINGS: All of the patients presented with fatigue and exercise intolerance and many had been diagnosed with fibromyalgia. Their symptoms responded to treatment of the metabolic disease. Associated symptoms included bloating, diarrhea, constipation, gastrointestinal reflux symptoms, recurrent infections, arthritis, dyspnea, dry eye, visual loss, and hearing loss. Associated medical conditions included Hashimoto thyroiditis, Sjogren's syndrome, seronegative arthritis, food hypersensitivities, asthma, sleep apnea, and vasculitis. This study identifies clinical features that should alert physicians to the possibility of an underlying metabolic disease. Treatment of the metabolic disease leads to symptomatic improvement.

JCL roundtable: Pediatric lipidology.

This JCL Roundtable discussion probes the knowledge of 3 experts in pediatric lipidology, an emerging discipline both in the United States and internationally. In the 1990s, only 3 US institutions could be said to have dedicated pediatric lipid clinics; that number has grown to 25 today. The Pediatric Atherosclerosis Prevention and Lipidology Group of the National Lipid Association has regular teleconferences to support advocacy and convey best practices. Guidelines for pediatric lipidology initially focused on low-density lipoprotein cholesterol in 1992 as part of the National Cholesterol Education Program. Today the most comprehensive coverage comes from the 2011 National Heart Lung and Blood Institute Pediatric Guidelines. Universal screening was recommended for children between ages 9 and 11 years and teenagers/young adults between 17 to 21 years, a position echoed as "may be recommended" by the 2018 AHA/ACC/Multisociety Cholesterol Guidelines. While pediatric lipidologists continue to treat uncommon genetic disorders, they increasingly confront an issue of epidemic proportions-dyslipidemia as the initial presentation of metabolic dysregulation associated with obesity. Consequences of such altered metabolism extend to atherosclerosis, diabetes, liver disease, and other serious problems in adult life. Pediatric lipid science and practice differ from adult experience in several ways, including importance of family and birth history as well as genetics/epigenetics, lack of general pediatricians' familiarity with lipid drugs, value of family counseling, need for biomarkers of early metabolic dysregulation, and anticipation of endpoints in adult life not fully defined by randomized clinical trials in children.

Control del perfil lipídico global / Control of the overall lipid profile

Se revisa la importancia del control lipídico global en la prevención cardiovascular. Diversos estudios y metaanálisis demuestran que el control del colesterol LDL mantiene aún un elevado riesgo cardiovascular, que se relaciona con la presencia de lipoproteínas ricas en triglicéridos, y por ello con aumento de los triglicéridos plasmáticos y de los valores de apolipoproteína B que contienen estas lipoproteínas. La importancia de esta relación se debe al cambio ocurrido en los últimos años en el perfil lipídico de nuestra población, relacionado con el aumento de obesidad y de resistencia a la insulina; este perfil se denomina dislipidemia aterogénica. Así, la hipertrigliceridemia debe ser considerada factor de riesgo cardiovascular, especialmente cuando se han alcanzado los objetivos deseables del colesterol LDL. Se describen las indicaciones del tratamiento con fibratos, en prevención primaria y secundaria, basadas en recomendaciones según la medicina basada en la evidencia, así como su importancia en la reducción del riesgo cardiovascular. Finalmente, se establecen las indicaciones del tratamiento combinado estatina-fibrato, siempre tras los cambios del estilo de vida

The importance of overall lipid control in cardiovascular prevention is reviewed. Several studies and meta-analyses show that the control of LDL cholesterol (LDL-C) still maintains a high cardiovascular risk, which is related to the presence of triglyceride-rich lipoproteins, and therefore with an increase in plasma triglycerides and the values of apolipoprotein B (apoB) containing these lipoproteins. The importance of this relationship is due to the change in the lipid profile of our population in recent years. This is related to the increase in obesity and insulin resistance, and is called atherogenic dyslipidaemia. Thus, hypertriglyceridaemia should be considered a cardiovascular risk factor, especially when the desirable objectives of LDL-C have been achieved. The indications for treatment with fibrates in primary and secondary prevention, using the medical evidence-based recommendations, are described, along with its importance in the reduction of cardiovascular risk. Finally, the established indications of the combined statin-fibrate treatment are presented, always after changes in lifestyle

Pancreatic steatosis: an update.

PURPOSE OF REVIEW: Pancreatic steatosis is a clinical entity with emerging significance and impacts patient health in a multitude of ways. It has a high prevalence in the global population with predilections for different demographics by age, sex and ethnicity. Understanding the pathophysiology, clinical features and complications of this entity may be important to understanding the consequences of the ongoing obesity global epidemic. RECENT FINDINGS: Obesity and metabolic syndrome contribute to metabolic derangements that result in lipid mishandling by adipocytes. Adipocytokine imbalances in circulation and in the pancreatic microenvironment cause chronic, low-grade inflammation. The resulting beta cell and acinar cell apoptosis leads to pancreatic endocrine and exocrine dysfunction. Furthermore, these adipocytokines regulate cell growth, differentiation, as well as angiogenesis and lymphatic spread. These consequences of adipocyte infiltration are thought to initiate carcinogenesis, leading to pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma. SUMMARY: Obesity will lead to millions of deaths each year and pancreatic steatosis may be the key intermediate entity that leads to obesity-related complications. Enhancing our understanding may reveal strategies for preventing mortality and morbidity related to the global epidemic of obesity. Further research is needed to determine the pathophysiology, long-term complications and effective treatment strategies for this condition.

Recent advances in novel therapies for lipid disorders.

The prevalence of lipid disorders is alarmingly increasing in the Western world. They are the result of either primary causes, such as unhealthy lifestyle choices or inherited risk factors, or secondary causes like other diseases or medication. Atypical changes in the synthesis, processing and catabolism of lipoprotein particles may lead to severe hypercholesterolemia, hypertriglyceridemia or elevated Lp(a). Although cholesterol-lowering drugs are the most prescribed medications, not all patients achieve guideline recommended cholesterol levels with the current treatment options, emphasising the need for new therapies. Also, some lipid disorders do not have any treatment options but rely only on stringent dietary restriction. Patients with untreated lipid disorders carry a severe risk of cardiovascular disease, diabetes, non-alcoholic fatty liver disease and pancreatitis among others. To achieve better treatment outcome, novel selective gene expression and epigenetic targeting therapies are constantly being developed. Therapeutic innovations employing targeted RNA technology utilise small interfering RNAs, antisense oligonucleotides, long non-coding RNAs and microRNAs to regulate target protein production whereas viral gene therapy provides functional therapeutic genes and CRISPR/Cas technology relies on gene editing and transcriptional regulation. In this review, we will discuss the latest advances in clinical trials for novel lipid-lowering therapies and potential new targets in pre-clinical phase.

Update on the diagnosis, treatment and management of rare genetic lipid disorders.

Rare genetic lipid disorders affect the levels of cholesterol and/or triglyceride in the circulation and, if untreated, can often lead to severe multisystem complications. The field of rare lipid disorders is evolving and increasing awareness of these conditions, along with the systematic integration of recent advances or knowledge into clinical practice, is crucial to improve patient outcomes. The aim of this review is to provide an overview of selected rare genetic lipid disorders, focusing on the recommended diagnostic strategies and contemporary treatment and management options.

Prolonged effectiveness of 12-month exercise-plus-diet intervention in Japanese adults at risk of impaired glucose or lipid metabolism.

BACKGROUND AND OBJECTIVES: To investigate the prolonged effects of a 12-month exercise-plus-diet intervention in Japanese adults at risk of impaired glucose or lipid metabolism. METHODS AND STUDY DESIGN: A total of 180 participants were randomly divided into an intervention group (n=94), and a control group (n=86). An exercise-plus- diet intervention was conducted on the intervention group for 12 months. The effects were evaluated by questionnaire, physical examinations, and blood tests at baseline, 3 months, 12 months (the end of intervention), and 24 months (one year after the end of intervention). The control group took only the same examinations as the intervention group. RESULTS: At the end of the 12-month intervention, body weight, waist circumference, fasting glucose, HbA1c, triglycerides, and LDL-cholesterol were improved in the intervention group compared to the control group (all p<0.05). One year after the end of the intervention, body weight, waist circumference, fasting glucose, triglycerides, and LDL-cholesterol were still decreased in the intervention group compared to the control group (all p<0.05), especially among non-overweight participants. Among overweight persons, only body weight in the intervention group was lower than the control group. The personal behaviours of physical activity and diet in the intervention group were also improved. CONCLUSIONS: The 12-month exercise-plus-diet programs were found to be effective in improving glucose and lipid metabolism, as well as personal behaviour one year after completion of the intervention.

Austrian Lipid Consensus on the management of metabolic lipid disorders to prevent vascular complications: A joint position statement issued by eight medical societies. 2016 update.

In 2010, eight Austrian medical societies proposed a joint position statement on the management of metabolic lipid disorders for the prevention of vascular complications. An updated and extended version of these recommendations according to the current literature is presented, referring to the primary and secondary prevention of vascular complications in adults, taking into consideration the guidelines of other societies. The "Austrian Lipid Consensus - 2016 update" provides guidance for individualized risk stratification and respective therapeutic targets, and discusses the evidence for reducing vascular endpoints with available lipid-lowering therapies. Furthermore, specific management in key patient groups is outlined, including subjects presenting with coronary, cerebrovascular, and/or peripheral atherosclerosis; diabetes mellitus and/or metabolic syndrome; nephropathy; and familial hypercholesterolemia.

Inercia terapéutica en el manejo de pacientes con diabetes mellitus tipo 2 en el ámbito de la Atención Primaria / Therapeutic inertia in the management of type 2 diabetic patients in Primary Health Care

Objetivo. Valorar la inercia terapéutica (IT) en el manejo de los pacientes diabéticos tipo 2 (DM2) respecto al control glucémico y lipídico. Material y métodos. Se estudiaron 2 grupos de pacientes. Grupo 1: todos los pacientes mayores de 14 años con registro de DM2 hasta el 28-02-2013 y con la última determinación de HbA1c ≥ 8,5%. Grupo 2: todos los pacientes menores de 60 años con diagnóstico de DM2 realizado entre el 1-01-2011 y el 31-12-2012, sin complicaciones crónicas de la enfermedad y con la última determinación de HbA1c ≥ 6,5%. Resultados. Grupo 1: fueron incluidos 253 pacientes (13% de los DM2 registrados). La IT fue del 43% para la DM2, del 83% para el colesterol LDL y del 80% para los triglicéridos. La IT fue inferior (p = 0,037) en los pacientes con HbA1c ≥ 10%. La IT en el manejo del perfil lipídico no fue diferente dependiendo de los niveles de HbA1c. Grupo 2: fueron valorados todos los pacientes con DM2 (n = 53) que cumplían criterios de inclusión (2,7% de los casos de DM2 registrados). Porcentaje de visitas en las que se practicó IT: 55% para la DM2, 63% para el colesterol LDL y 64% para los triglicéridos. Se observó una mayor intensificación de la terapia en pacientes con HbA1c > 7,5% en 3 de las 5 visitas realizadas. Conclusiones. En ambos grupos la IT fue elevada, existiendo un infrarregistro de los motivos de la misma. Es importante mejorar la actitud y las condiciones laborales de los profesionales que atienden a la población diabética (AU)

Objective. To assess therapeutic inertia (TI) in the management of type 2 diabetic patients (DM2), as regards glycemic and lipid control. Materials and methods. Two groups of patients were studied. Group 1: All the patients were older than 14 years, diagnosed with DM2 up to 28th February 2013, and their last determination of HbA1c was ≥ 8.5%. Group 2: All patients, under 60 years old, diagnosed with DM2 between the 1st January 2011 and the 31st December 2012, with no chronic complications and their last determination of HbA1c was ≥ 6.5%. Results. Group 1: 253 patients were included (13% of DM2 diagnosed). TI was 43% for DM2, 83% for LDL cholesterol, and 80% for triglycerides. TI was lower (P = .037) in patients with HbA1c ≥ 10%. There was no difference in TI as regards the management of lipid profile depending on the HbA1c levels. Group 2: All DM2 patients (n = 53) who met inclusion criteria were assessed (2.7% of DM2 diagnosed). Percentage of visits of those patients that had TI: 55% for DM2, 63% for LDL cholesterol and 64% for triglycerides. A more intense therapy was observed in patients with HbA1c > 7.5% in 3 of the 5 visits made. Conclusions. TI in both groups was high and there is a lack of recording the reasons for this. It is important to improve the attitude of the professionals who care for the diabetic population (AU)

Lipoprotein-apheresis: Austrian consensus on indication and performance of treatment.

The prevalence of familial disorders of lipid metabolism in Europe is higher than believed so far. In severely affected patients in whom conventional combined lipid lowering agents are insufficient to achieve target values, patients being intolerant to all the available members of the statin family as well as in patients with elevated lipoprotein(a) (100 mg/dl) and progression of atherosclerotic vascular disease, despite even normal low-density lipoproteins (LDL)-cholesterol values, lipoprotein-apheresis treatment is indicated. The Austrian Apheresis Consensus compares the inclusion criteria for patients to be treated in Austria with those from Italy, Germany, Spain, Japan, UK and the United States. The cut off level of 100 mg/dl for lipoprotein(a) is higher in Austria as compared to the aforementioned countries (50 or 60 mg/dl, respectively). The available clinical data reveal that regular weekly lipoprotein apheresis not only results in a significant lowering of the respective atherogenic lipid and lipoprotein parameters, but also in a significant decrease in clinical events and interventions. The underlying mechanisms such as non-lipid effects, side effects as well as the different available treatment principles are compared. For patients meeting the inclusion criteria, lipoprotein apheresis is a safe and effective therapy significantly reducing vascular events.

Use of microRNAs as Anti-Atherosclerosis.

MicroRNAs are a class of non-coding RNA molecules that have been reported to play a crucial role in cell signaling via post-transcriptional regulation of gene expression. There is increasing evidence showing that this class of RNA is involved in the pathogenesis of cardiovascular diseases, including atherosclerosis. More recently, it has been demonstrated that microRNAs can function to protect against the development of atherosclerosis. The primary goal of this review is to discuss the discovery, mechanism, and therapeutic use of microRNA molecules as atheroprotective agents.

Adeno-associated virus-mediated gene therapy for metabolic myopathy.

Metabolic myopathies are a diverse group of rare diseases in which impaired breakdown of stored energy leads to profound muscle dysfunction ranging from exercise intolerance to severe muscle wasting. Metabolic myopathies are largely caused by functional deficiency of a single gene and are generally subcategorized into three major types of metabolic disease: mitochondrial, lipid, or glycogen. Treatment varies greatly depending on the biochemical nature of the disease, and unfortunately no definitive treatments exist for metabolic myopathy. Since this group of diseases is inherited, gene therapy is being explored as an approach to personalized medical treatment. Adeno-associated virus-based vectors in particular have shown to be promising in the treatment of several forms of metabolic myopathy. This review will discuss the most recent advances in gene therapy efforts for the treatment of metabolic myopathies.

Magnitud y características del riesgo residual lipídico en pacientes con antecedentes de revascularización coronaria: estudio ICP- Bypass / Magnitude and characteristics of residual lipid risk in patients with a history of coronary revascularization: The ICP-Bypass study

Introducción y objetivos. El riesgo residual lipídico se define como el exceso de complicaciones cardiovasculares en pacientes con buen control del colesterol unido a liproteínas de baja densidad y se atribuye fundamentalmente al colesterol unido a lipoproteínas de alta densidad y los triglicéridos. El objetivo del estudio fue describir la magnitud y las características asociadas al riesgo residual lipídico en pacientes con antecedentes de revascularización coronaria. Métodos. Estudio multicéntrico, transversal y observacional. Se definió riesgo residual lipídico por la presencia de colesterol unido a lipoproteínas de alta densidad < 40mg/dl y/o triglicéridos > 150mg/dl en pacientes con colesterol unido a liproteínas de baja densidad < 100mg/dl. Resultados. Se incluyó a 2.292 pacientes, con una media de edad de 65,5±12,4 años. El 94,1% estaba en tratamiento con estatinas y el 4,8% no recibía ningún tratamiento hipolipemiante; el tratamiento únicamente con estatinas (74%) fue la estrategia más común, seguida de la combinación con ezetimiba (17%). La prevalencia de colesterol unido a lipoproteínas de alta densidad < 40mg/dl fue del 35,8%; la de hipertrigliceridemia, del 38,9%, y la de colesterol unido a liproteínas de baja densidad > 100mg/dl, 44,9%. El 29,9% de los pacientes constituyeron el colectivo de riesgo residual lipídico. Estos pacientes presentaron un perfil clínico similar, salvo por una media de edad ligeramente inferior, más diabetes y sexo masculino. El análisis multivariable identificó asociación positiva de la diabetes y el sexo masculino con riesgo residual lipídico; diabetes, tabaquismo activo, sexo masculino y el tratamiento con fibratos se asociaron al colesterol unido a lipoproteínas de alta densidad < 40mg/dl; y diabetes, tabaquismo, obesidad abdominal y el tratamiento con fibratos, a la hipertrigliceridemia. Conclusiones. Casi una tercera parte de los pacientes con antecedentes de revascularización coronaria presentan colesterol unido a liproteínas de baja densidad < 100mg/dl y colesterol unido a lipoproteínas de alta densidad bajo y/o triglicéridos elevados en la práctica clínica diaria, el denominado riesgo residual lipídico (AU)

Introduction and objectives. Residual lipid risk has been defined as the excess of cardiovascular events observed in patients with adequate control of low-density lipoprotein cholesterol and has been mainly attributed to high-density lipoprotein cholesterol and triglycerides. The aim of our study was to describe the clinical features and the magnitude and characteristics associated with residual lipid risk in patients with a history of coronary revascularization. Methods. Multicenter, observational, cross-sectional study of patients with a history of coronary revascularization. Residual lipid risk was defined as the presence of high-density lipoprotein cholesterol <40 mg/dL and/or triglycerides >150 mg/dL in patients with low-density lipoprotein cholesterol <100 mg/dL. Results. We included 2292 patients with a mean age of 65.5 (12.4) years; 94.1% were receiving no statin therapy and 4.8% no lipid therapy. Statin-only therapy (74%) was the most common strategy, followed by combination with ezetimibe (17%). The prevalence of high-density lipoprotein cholesterol <40 mg/dL was 35.8%, hypertriglyceridemia 38.9%, and low-density lipoprotein cholesterol >100 mg/dL 44.9%; the residual lipid risk group included 29.9% of all patients. This patient group had a similar clinical profile except for slightly lower mean age, higher incidence of diabetes, and higher proportion of men. Multivariate analysis identified positive associations of diabetes and male sex with residual lipid risk; current smoking, male sex, and fibrate therapy were associated with high-density lipoprotein cholesterol <40 mg/dL; current smoking, abdominal obesity, and fibrate therapy were associated with hypertriglyceridemia. Conclusions. In daily clinical practice, almost one-third of patients with a history of coronary revascularization have low-density lipoprotein cholesterol <100 mg/dL plus low high-density lipoprotein cholesterol and/or hypertriglyceridemia, a concept known as residual lipid risk (AU)