Inflammation in the Pathogenesis of Arrhythmogenic Cardiomyopathy: Secondary Event or Active Driver?

Arrhythmogenic cardiomyopathy (ACM) is a rare inherited cardiac disease characterized by arrhythmia and progressive fibro-fatty replacement of the myocardium, which leads to heart failure and sudden cardiac death. Inflammation contributes to disease progression, and it is characterized by inflammatory cell infiltrates in the damaged myocardium and inflammatory mediators in the blood of ACM patients. However, the molecular basis of inflammatory process in ACM remains under investigated and it is unclear whether inflammation is a primary event leading to arrhythmia and myocardial damage or it is a secondary response triggered by cardiomyocyte death. Here, we provide an overview of the proposed players and triggers involved in inflammation in ACM, focusing on those studied using in vivo and in vitro models. Deepening current knowledge of inflammation-related mechanisms in ACM could help identifying novel therapeutic perspectives, such as anti-inflammatory therapy.

Pancreaticopleural fistula: An insidious cause of pleural effusion –case report

Pancreaticopleural fistulas (PPF) are a rare etiology of pleural effusions. We describe a case of a 61-year-old man, with left chest pain with six months of progression who presented with a large volume unilateral pleural effusion. A thoracentesis was performed, which showed a dark reddish fluid(exudate) and high content of pancreatic amylase. After that an abdominal computed tomography (CT)and magnetic resonance cholangiopancreatography (MRCP) was done, revealing fistulous pathways that originated in the pancreas. The patient was admitted for conservative and endoscopic treatment by Endoscopic Retrograde Cholangiopancreatography (ERCP) and a prosthesis was placed on a fistulous path. He was discharged without complications, with the resolution of the pleural effusion and fistula.The interest of this case lies in the rarity of the event and absence of symptoms of the probable primary event (acute pancreatitis). The possible iatrogenic association with several drugs of his usual medication makes it even more complex.

Neurovascular Unit: A New Target for Treating Early Stages of Diabetic Retinopathy

The concept of diabetic retinopathy as a microvascular disease has evolved and is now considered a more complex diabetic complication in which neurovascular unit impairment plays an essential role and, therefore, can be considered as a main therapeutic target in the early stages of the disease. However, neurodegeneration is not always the apparent primary event in the natural story of diabetic retinopathy, and a phenotyping characterization is recommendable to identify those patients in whom neuroprotective treatment might be of benefit. In recent years, a myriad of treatments based on neuroprotection have been tested in experimental models, but more interestingly, there are drugs with a dual activity (neuroprotective and vasculotropic). In this review, the recent evidence concerning the therapeutic approaches targeting neurovascular unit impairment will be presented, along with a critical review of the scientific gaps and problems which remain to be overcome before our knowledge can be transferred to clinical practice.

Pain management in major pediatric trauma and burns

Pain management in major pediatric trauma and burns remains challenging. The care phases include prehospital, the Emergency Department, ward, and intensive care, with multiple operative and procedural interventions (as inpatients and, later, outpatients). Distress, anxiety, post-traumatic stress disorder (from the primary event, and in-hospital and postdischarge course), itch, deranged sleep, nociceptive and neuropathic pain occur frequently and can persist. This chapter presents the pharmacological and nonpharmacological interventions employed during the various phases to address pain and associated issues in major trauma and burns patients.

Forensic Biochemical Markers to Evaluate the Agonal Period: A Literature Review

Currently, forensic research is multidisciplinary with new methods and parameters useful to define the cause and time of death as well as survival/agony times. The identification of biochemical markers able to estimate agonal period has been studied by many forensic researchers. It is known that the estimation of agonal time in different types of death is not always easy, hence our interest in literature’s data. The studies analyzed in this review confirm the important role of thanatobiochemistry for the estimation of survival times. Regardless of the death cause, the survival/agony time between the primary event and death influences markers concentrations in biological samples (e.g., blood, urine, cerebrospinal fluid). Different biomarkers can be used for qualitative evaluations in deaths with short and long agony (e.g., C-reactive protein, ferritin, GFAP, etc.). Instead, the quantitative interpretation showed limits due to the lack of reference cut-offs. Thanatobiochemistry is a useful tool to confirm what emerged from autopsies findings (macroscopic and histological analysis), but further studies are desirable to confirm the evidence emerging from our review of the literature.

Frequency of Hyperlipidemia in the Diagnosed Type 2 Diabetic Patients

OBJECTIVES: The primary event in the development of type-2 diabetes is directly associated with lipid metabolism derangement occurring due to insulin resistance. The aim of this study was to find out the prevalence of hyperlipidemia in the newly diagnosed type-2 DM. METHODOLOGY: This hospital based descriptive study was conducted in the year 2018 to 2019, on 100 newly diagnosed type-2 diabetic patients attending medical O.P.D or admitted in medial wards of Naseer Ullah Khan Babar Memorial Hospital Kohat Road Peshawar. RESULTS: The incidence of hyperlipidemia in newly diagnosed diabetic patients was 29%. About 71% patients were having normal lipid profile. Our study also revealed that the frequency of hyperlipidemia increases with age. Half of the patients having age more than 60 years developed hyperlipidemia. Among hyperlipidemic patients, hypercholesterolemia was present in 36% and hypertriglyceridemia in 64% patients CONCLUSION: The study suggests that hyperlipidemia is very common in newly diagnosed type-2 diabetic patients in this part of the world.

Master regulators in the foam cell formation; the role of phagocytosis

Background Foam cell formation caused by modified LDL is the earliest and most noticeable manifestation of atherosclerosis. The mechanisms of foam cell formation are not fully understood and can involve altered lipid uptake, impaired lipid metabolism, or both. 10 inflammation-related master regulators, which were involved in the cholesterol accumulation in cultured macrophages induced by the incubation with modified LDL, have been identified. Objective We hypothesised that the primary event occurring upon the interaction of modified LDL and macrophages is the stimulation of phagocytosis, which subsequently triggers the pro-inflammatory immune response. Methods Cholesterol accumulation was evaluated in primary macrophages with master regulator genes knock-downed by siRNA for either IL15, EIF2AK3, F2RL1, TSPYL2, or ANXA1. Analysis of enriched transcription factor binding sites in promoters of differentially expressed genes and identification of master regulators in the signal transduction network were performed with TRANSFAC and TRANSPATH databases. Results Genes which were up- or downregulated following the exposure of cultured cells to modified LDL or latex beads were determined. Most of the identified master regulators were involved in the innate immune response, and some of them were encoding major pro-inflammatory proteins. Comparative analysis of master regulators revealed similarities in the genetic regulation of the interaction of macrophages with naturally occurring LDL and desialylated LDL. Oxidized and desialylated LDL affected a different spectrum of genes than naturally occurring LDL. These observations suggest that desialylation is the most important modification of LDL occurring in vivo. Thus, modified LDL caused the gene regulation characteristic of the stimulation of phagocytosis. The knock-down of the EIF2AK3 and IL15 genes completely prevented cholesterol accumulation in cultured macrophages, whereas atherogenic naturally occurring LDL caused significant cholesterol accumulation in the control cells. The ANXA1 gene knock-down caused a further decrease in cholesterol content in cultured macrophages. At the same time, knock-down of F2RL1 and TSPYL2 did not cause an effect. Conclusions The results, showing that inflammatory response and the cholesterol accumulation are related, may confirm our hypothesis of atherogenesis development based on the following viewpoints: LDL particles undergo atherogenic modifications that, in turn, accompanied by the formation of self-associates; large LDL associates stimulate phagocytosis; as a result of phagocytosis stimulation, pro-inflammatory molecules are secreted; these molecules cause or at least contribute to the accumulation of intracellular cholesterol. Therefore, it became obvious that the primary event in this sequence is not the accumulation of cholesterol but an inflammatory response. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Russian Science Foundation

Disease burden of subsequent events among patients with atherosclerotic cardiovascular disease in Taiwan

Background/Introduction Patients with a history of cardiovascular disease are considered at high risk for cardiovascular (CV) events. Existing studies have indicated that a high proportion of patients developed secondary or tertiary atherosclerotic cardiovascular disease (ASCVD) events within a relatively short period of time. However, the whole picture regarding when and how these subsequent CV events occur is not well understood, particularly in Asia. Purpose To estimate the incidences, characteristics and mortality of subsequent ASCVD events among those with new-onset ASCVD events (index events). Methods We utilized National Health Insurance Research Database in Taiwan to identify patients with new-onset ASCVD events (index events), and further categorized them into those with incident coronary heart disease (CHD), cerebrovascular disease (CBVD) and peripheral artery disease (PAD) during 2012–2014. Re-admission due to ASCVD after the index event, defined as subsequent ASCVD event, was our main outcome of interest. All subsequent ASCVD events within 3-year period after the index ASCVD events were identified. Particularly, we intended to sequentially identify first and second subsequent ASCVD events. Descriptive statistics regarding proportion of developing subsequent ASCVD events as well as the type of subsequent ASCVD events were estimated. We also used Kaplan-Meier method to estimate crude survival curve of all-cause mortality following each subsequent ASCVD event. Results We identified 97,321, 120,914 and 14,794 patients with new-onset CHD, CBVD and PAD, respectively. The proportion of developing subsequent events increased with sequence of events occurred (for the first three subsequent event, the proportions of developing subsequent event were: 22.5, 25.6 and 30.9% for CHD, 21.0, 26.2 and 32.4% for CBVD, and 40.2, 41.4 and 43.6% for PAD). The majority of patients had the same type of ASCVD for their subsequent events to the primary event (proportions of having the same ASCVD type of subsequent event to the primary event ranged: 66–81% for CHD, 80–84% for CBVD, and 76–78% for PAD). The 1-year readmission rates increased if patients encountered more subsequent events. Among patients with new-onset CHD, the 1-year readmission rates following new-onset events, first subsequent events and second subsequent events were 43.1%, 47.6% and 55.3%, respectively. More subsequent events also worsened the survival. The 1-year survival rates following new-onset CHD events, first subsequent events and second subsequent events were 85.9%, 84.3% and 79.8%, respectively. Similar trend was observed for CBVD and PAD patients as well. Conclusions Compared with new-onset ASCVD events, subsequent ASCVD events posed a heavier disease burden in terms of readmission and mortality. These results highlighted the importance of prevention of secondary or tertiary ASCVD events. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen Taiwan Limited

Expansion and inflammation of white adipose tissue - focusing on adipocyte progenitors

Adipose tissue is an important organ in our body, participating not only in energy metabolism but also immune regulation. It is broadly classified as white (WAT) and brown (BAT) adipose tissues. WAT is highly heterogeneous, composed of adipocytes, various immune, progenitor and stem cells, as well as the stromal vascular populations. The expansion and inflammation of WAT are hallmarks of obesity and play a causal role in the development of metabolic and cardiovascular diseases. The primary event triggering the inflammatory expansion of WAT remains unclear. The present review focuses on the role of adipocyte progenitors (APS), which give rise to specialized adipocytes, in obesity-associated WAT expansion, inflammation and fibrosis.