HERACLIS-HDV cohort for the factors of underdiagnosis and prevalence of hepatitis D virus infection in HBsAg-positive patients.

BACKGROUND AND AIMS: Hepatitis D virus (HDV) underdiagnosis remains common. We assessed the HDV screening and prevalence rates in HBsAg-positive patients seen at tertiary liver centres throughout Greece as well as factors affecting HDV diagnosis. METHODS: All adult HBsAg-positive patients seen within the last 5 years were included. Non-screened patients who visited or could be recalled to the clinics over a 6-month period were prospectively tested for anti-HDV. RESULTS: Of 5079 HBsAg-positive patients, 53% had anti-HDV screening (41% before and 12% after study initiation). Pre-study (8%-88%) and total screening rates (14%-100%) varied widely among centres. Screening rates were associated with older age, known risk group, elevated ALT, centre location and size and period of first visit. Anti-HDV prevalence was 5.8% without significant difference in patients screened before (6.1%) or after study initiation (4.7%, p = 0.240). Anti-HDV positivity was associated with younger age, parenteral drug use, born abroad, advanced liver disease and centre location. Overall, HDV RNA detectability rate was 71.6% being more frequent in anti-HDV-positive patients with elevated ALT, advanced liver disease and hepatitis B therapy. CONCLUSIONS: Anti-HDV screening rates and recall capabilities vary widely among Greek liver clinics being higher in HBsAg-positive patients of known risk group with active/advanced liver disease seen at smaller centres, while non-medical factors are also important. Anti-HDV prevalence varies throughout Greece being higher in patients born abroad with younger age, parenteral drug use and advanced liver disease. Viremia is more frequently but not exclusively detected in anti-HDV-positive patients with elevated ALT and advanced liver disease.

Gut Microbiota and Its Role in the Brain-Gut-Kidney Axis in Hypertension.

PURPOSE OF REVIEW: The role of the gut microbiota in modulating blood pressure is increasingly being recognized, currently. The purpose of this review is to summarize recent findings about the mechanisms involved in hypertension with regard to the phenomenon of "gut dysbiosis." RECENT FINDINGS: Gut dysbiosis, i.e., the imbalance between the gut microbiota and the host, is characterized by a disruption of the tight junction proteins, such as occludins, claudins, and JAMs (junctional adhesion molecules), resulting in increased gut permeability or the so called "leaky gut." Due to the influence of genetic as well as environmental factors, various metabolites produced by the gut microbiota, such as indole and p-cresol, are increased. Thereby, uremic toxins, such as indoxyl sulfates and p-cresol sulfates, accumulate in the blood and the urine, causing damage in the podocytes and the tubular cells. In addition, immunological mechanisms are implicated as well. In particular, a switch from M2 macrophages to M1 macrophages, which produce pro-inflammatory cytokines, occurs. Moreover, a higher level of Th17 cells, releasing large amounts of interleukin-17 (IL-17), has been reported, when a diet rich in salt is consumed. Therefore, apart from the aggravation of uremic toxins, which may account for direct harmful effects on the kidney, there is inflammation not only in the gut, but in the kidneys as well. This crosstalk between the gut and the kidney is suggested to play a crucial role in hypertension. Notably, the brain is also implicated, with an increasing sympathetic output. The brain-gut-kidney axis seems to be deeply involved in the development of hypertension and chronic kidney disease (CKD). The notion that, by modulating the gut microbiota, we could regulate blood pressure is strongly supported by the current evidence. A healthy diet, low in animal protein and fat, and low in salt, together with the utilization of probiotics, prebiotics, synbiotics, or postbiotics, may contribute to our fight against hypertension.

Immunotherapy in Head and Neck Cancer: Where Do We Stand?

PURPOSEOF REVIEW: Head and neck cancer (HNC) comprises a group of malignancies, amongst which squamous cell carcinoma accounts for more than 90% of the cases. HNC has been related to tobacco use, alcohol consumption, human papillomavirus, Epstein-Barr virus, air pollution, and previous local radiotherapy. HNC has been associated with substantial morbidity and mortality. This review aims to summarize the recent findings regarding immunotherapy in HNC. RECENT FINDINGS: The recent introduction of immunotherapy, with the use of programmed death 1 (PD-1) inhibitors pembrolizumab and nivolumab, which have been FDA approved for the treatment of metastatic or recurrent head and neck squamous cell carcinoma, has changed the field in metastatic or recurrent disease. There are many ongoing trials regarding the use of novel immunotherapeutic agents, such as durvalumab, atezolizumab, avelumab, tremelimumab, and monalizumab. In this review, we focus on the therapeutic potential of novel immunotherapy treatment modalities, such as combinations of newer immune-checkpoint inhibitors; the use of tumor vaccines such as human papillomavirus-targeted vaccines; the potential use of oncolytic viruses; as well as the latest advances regarding adoptive cellular immunotherapy. As novel treatment options are still emerging, a more personalized approach to metastatic or recurrent HNC therapy should be followed. Moreover, the role of the microbiome in immunotherapy, the limitations of immunotherapy, and the various diagnostic, prognostic, and predictive biomarkers based on genetics and the tumor microenvironment are synopsized.

Diabetes type 1: Can it be treated as an autoimmune disorder?

Type 1 Diabetes Mellitus (T1DM) is characterized by progressive autoimmune-mediated destruction of the pancreatic beta-cells leading to insulin deficiency and hyperglycemia. It is associated with significant treatment burden and necessitates life-long insulin therapy. The role of immunotherapy in the prevention and management of T1DM is an evolving area of interest which has the potential to alter the natural history of this disease.In this review, we give insight into recent clinical trials related to the use of immunotherapeutic approaches for T1DM, such as proinflammatory cytokine inhibition, cell-depletion and cell-therapy approaches, autoantigen-specific treatments and stem cell therapies. We highlight the timing of intervention, aspects of therapy including adverse effects and the emergence of a novel lymphocyte crucial in T1DM autoimmunity. We also discuss the role of cardiac autoimmunity and its link to excess CVD risk in T1DM.We conclude that significant advances have been made in development of immunotherapeutic targets and agents for the treatment and prevention of T1DM. These immune-based therapies promise preservation of beta-cells and decreasing insulin dependency. In their current state, immunotherapeutic approaches cannot yet halt the progression from a preclinical state to overt T1DM nor can they replace standard insulin therapy in existing T1DM. It remains to be seen whether immunotherapy will ultimately play a key role in the prevention of progression to overt T1DM and whether it may find a place in our therapeutic armamentarium to improve clinical outcomes and quality of life in established T1DM.

Multiple mononeuritis with peripheral blood eosinophilia in a patient with Q fever: An unusual presentation: Case report and review of the literature.

Coxiella burnetii is a gram-negative bacterium that typically lives and multiplies within monocytes and macrophages of the host, being the etiologic agent of the zoonosis Q fever. Q fever is usually divided into acute and chronic forms, with a significant percentage of patients being asymptomatic. In the wide spectrum of the disease, neurological involvement seems to be extremely rare and peripheral neuropathy presenting with mononeuritis multiplex is one of the possible presentations with low rates of occurrence. Hereby, we present an unusual case of a 55-year-old male with fever and multiple mononeuritis attributed to Q fever and we summarize a short review of C. burnetii infection.

ANGPTL3 Inhibitors　- Their Role in Cardiovascular Disease Through Regulation of Lipid Metabolism.

Elevated plasma lipid levels are linked to atherosclerosis, a hallmark for coronary artery disease (CAD), documented by animal studies as well as angiographic and clinical studies. The ability to treat hyperlipidemia through lifestyle changes and lipid-lowering agents has been related to the slow progression of atherosclerosis and decreased incidence of major coronary events. Angiopoietin-like proteins (ANGPTLs) are a family of secreted glycoproteins expressed in the liver that share common domain characteristics with angiopoietins, the main regulators of angiogenesis. Although ANGPTLs cannot bind the angiopoietin receptors expressed on endothelial cells, 2 ANGPTL family members (ANGPTL3 and ANGPTL4) have clinical importance because of their unambiguous effects on lipoprotein metabolism in mice and humans. The regulation of plasma lipid levels by ANGPTL3 is controlled via affecting lipoprotein lipase and endothelial lipase-mediated hydrolysis of triglycerides (TGs) and phospholipids. ANGPTL 3, along with the other 2 members, 4 and 8, is a key to balancing the distribution of circulating TGs between white adipose tissue (WAT) and oxidative tissues. Thus, ongoing trials with newly discovered medications in the form of monoclonal antibodies or antisense oligonucleotides with novel targets are under analysis and may represent a fresh frontier in the treatment of hyperlipidemia and CAD.

Adenosine-Guided Pulmonary Vein Antral Isolation for Paroxysmal Atrial Fibrillation: A Randomized Study.

OBJECTIVES: The prognostic significance of adenosine-mediated pulmonary vein (PV) dormant conduction and whether such conduction should be eliminated still remain controversial. This randomized study aimed to investigate whether adenosine-guided ablation of the reconnection gaps improves the long-term outcomes of pulmonary vein antral isolation (PVAI) for paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: Consecutive patients with paroxysmal AF were randomly assigned to undergo (n = 80, group 1) or not (n = 81, group 2) adenosine testing following PVAI. Adenosine-mediated PV dormant conduction was unmasked in 26 patients (32.5%) of group 1. Successful elimination of the reconnection gaps was subsequently performed in all patients. During a mean follow-up period of 11.39 ± 5.10 months, 30 patients of group 1 (37.5%), and 27 patients of group 2 (33.3%) experienced arrhythmia recurrence. The Kaplan-Meier arrhythmia free survival curves failed to demonstrate any significant differences between study groups (log rank 0.217, P = 0.642). Fourteen of 26 (53.8%) patients with adenosine-mediated dormant conduction and subsequent elimination of reconnection gaps experienced AF recurrence during follow-up. On the contrary, only 16 of 54 patients without dormant conduction (29.6%) displayed arrhythmia recurrence (P = 0.049). Logistic regression analysis showed that adenosine-mediated PV reconnection (hazard ratio 0.292, 95% confidence interval 0.122-0.483; P = 0.01) was an independent predictor of AF recurrence. CONCLUSION: In this patients' cohort, adenosine-mediated PV reconnection is predictive of future arrhythmic events. Elimination of dormant conduction with additional ablation lesions does not improve the long-term outcome of the procedure compared to the standard PVAI.

The influence of environmental factors on premature ovarian insufficiency and ovarian aging.

Premature ovarian insufficiency and ovarian aging are complex conditions that affect women's reproductive health and overall well-being. They are both characterized by hypergonadotropic hypogonadism and infertility, and together affect about 1 in 100 women by the age of 40. This review explores the influence of environmental factors on the development and progression of premature ovarian insufficiency and ovarian aging. When referring to environmental factors, we include a wide range of external agents and conditions, including chemicals, socioeconomic factors and lifestyle choices. Through a review of the literature, we attempt to highlight the link between environmental factors and ovarian health. We examine the impact of endocrine-disrupting chemicals, such as bisphenol A and phthalates, on ovarian function and investigate the mechanisms by which these chemicals can disrupt hormone signaling pathways, leading to alterations in ovarian reserve, oocyte quality, and folliculogenesis. Moreover, we explore lifestyle factors like obesity, stress, smoking and alcohol in relation to their effects on ovarian aging. Epigenetic changes may play a crucial role in the prevalence of premature ovarian insufficiency. Understanding the impact of environmental factors on premature ovarian insufficiency and ovarian aging is very important in public and clinical health contexts. By identifying risk factors, healthcare providers can develop targeted and strategic prevention and intervention plans. Furthermore, this knowledge can promote reproductive health and minimize exposure to harmful environmental agents.

NAFLD in the 21st Century: Current Knowledge Regarding Its Pathogenesis, Diagnosis and Therapeutics.

Non-alcoholic fatty liver disease (NAFLD) is a major public health issue worldwide. It is the most common liver disease in Western countries, andits global prevalence is estimated to be up to 35%. However, its diagnosis may be elusive, because liver biopsy is relatively rarely performed and usually only in advanced stages of the disease. Therefore, several non-invasive scores may be applied to more easily diagnose and monitor NAFLD. In this review, we discuss the various biomarkers and imaging scores that could be useful in diagnosing and managing NAFLD. Despite the fact that general measures, such as abstinence from alcohol and modulation of other cardiovascular disease risk factors, should be applied, the mainstay of prevention and management is weight loss. Bariatric surgery may be suggested as a means to confront NAFLD. In addition, pharmacological treatment with GLP-1 analogues or the GIP agonist tirzepatide may be advisable. In this review, we focus on the utility of GLP-1 analogues and GIP agonists in lowering body weight, their pharmaceutical potential, and their safety profile, as already evidenced inanimal and human studies. We also elaborate on other options, such as the use of vitamin E, probiotics, especially next-generation probiotics, and prebiotics in this context. Finally, we explore future perspectives regarding the administration of GLP-1 analogues, GIP agonists, and probiotics/prebiotics as a means to prevent and combat NAFLD. The newest drugs pegozafermin and resmetiron, which seem to be very promising, arealso discussed.

ApoB100 and Atherosclerosis: What's New in the 21st Century?

ApoB is the main protein of triglyceride-rich lipoproteins and is further divided into ApoB48 in the intestine and ApoB100 in the liver. Very low-density lipoprotein (VLDL) is produced by the liver, contains ApoB100, and is metabolized into its remnants, intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL). ApoB100 has been suggested to play a crucial role in the formation of the atherogenic plaque. Apart from being a biomarker of atherosclerosis, ApoB100 seems to be implicated in the inflammatory process of atherosclerosis per se. In this review, we will focus on the structure, the metabolism, and the function of ApoB100, as well as its role as a predictor biomarker of cardiovascular risk. Moreover, we will elaborate upon the molecular mechanisms regarding the pathophysiology of atherosclerosis, and we will discuss the disorders associated with the APOB gene mutations, and the potential role of various drugs as therapeutic targets.

The Interplay Between Dietary Choline and Cardiometabolic Disorders: A Review of Current Evidence.

PURPOSE OF REVIEW: Choline is an essential nutrient for human health and cellular homeostasis as it is necessary for the synthesis of lipid cell membranes, lipoproteins, and the synthesis of the neurotransmitter acetylcholine. The aim of this review is to analyze the beneficial effects of choline and its significance in cellular metabolism and various inflammatory pathways, such as the inflammasome. We will discuss the significance of dietary choline in cardiometabolic disorders, such as non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), and chronic kidney disease (CKD) as well as in cognitive function and associated neuropsychiatric disorders. RECENT FINDINGS: Choline deficiency has been related to the development of NAFLD and cognitive disability in the offspring as well as in adulthood. In sharp contrast, excess dietary intake of choline mediated via the increased production of trimethylamine by the gut microbiota and increased trimethylamine-N-oxide (TMAO) levels has been related to atherosclerosis in most studies. In this context, CVD and CKD through the accumulation of TMAO, p-Cresyl-sulfate (pCS), and indoxyl-sulfate (IS) in serum may be the result of the interplay between excess dietary choline, the increased production of TMAO by the gut microbiota, and the resulting activation of inflammatory responses and fibrosis. A balanced diet, with no excess nor any deficiency in dietary choline, is of outmost importance regarding the prevention of cardiometabolic disorders as well as cognitive function. Large-scale studies with the use of next-generation probiotics, especially Akkermansia muciniphila and Faecalibacterium prausnitzii, should further examine their therapeutic potential in this context.

"Failing kidneys in a failing planet; CKD of unknown origin".

The 'alarm clock' for human beings in the era of climate medicine has rung. Original diseases have appeared, that could not be explained and attributed to common causes, which are suggested to be linked to global warming and environmental factors. Such an indolent disease is the chronic kidney disease of unknown cause (CKDu), introduced also as Mesoamerican or Uddanam nephropathy. Scientists equate the climate impact on kidneys with the canary in the coal mine; coal miners used to carry caged canaries with them, so that if poisonous gases, such as methane or carbon monoxide leaked into the mine-shaft, the gases would kill the canary before killing the miners; similarly, kidneys are injured before devastating and lethal complications occur in humans. In some regions of Central America, the deaths due to chronic kidney disease increased by 177% with a death toll being as high as over 20,000. It was first documented in animals that periodic heat and dehydration have a major role in causing chronic kidney disease. Based on that observation, it is advocated that young male agricultural workers in Central America and South Asia, develop renal disease by getting exposed to extreme heat repeatedly. The clinico-pathological characteristics of this type of kidney injury, do not belong to an existing classification, even though a form of tubulo-interstitial renal disease has been proposed. In this review, we will discuss about CKDu, its epidemiology and pathophysiological mechanisms, clinical presentation and diagnostic biomarkers and examine potential therapeutic options.

Mechanisms of sarcopenia in liver cirrhosis and the role of myokines.

Sarcopenia is a syndrome characterized by a decline in skeletal muscle quantity and/or quality, strength and performance, leading to unfortunate events, such as injurious falls or even death. It is not identical to frailty and malnutrition, even though there is a significant overlap among these syndromes. In patients with liver cirrhosis (LC), sarcopenia is classified as secondary and has been associated with increased morbidity and mortality during the pre- and post-transplantation period. It can be a result of malnutrition, hyperammonemia, low physical activity, endocrine abnormalities, accelerated starvation, metabolic disturbances, altered gut function leading to chronic inflammation, and alcohol abuse. Myokines are peptides mainly synthesized by contracting muscle and adipose tissue cells and may play a key role in the pathophysiology of sarcopenia. More than a hundred myokines have been recognized, but only a few have been investigated. They can be classified as negative regulators, such as myostatin, tumor growth factor-ß, activins, growth differentiation factor-11, and positive regulators of muscle growth including follistatin, bone morphogenic proteins, and irisin. So far, only myostatin, follistatin, irisin and decorin have been studied in LC-associated sarcopenia. In this review, we focused on the mechanisms of cirrhosis-related sarcopenia and the role of myokines that have already been studied in the literature, either as markers helping in the diagnostic evaluation of sarcopenia, or as prognostic factors of survival. Standard therapeutic options to prevent or treat sarcopenia in LC are also being reported, as well as the possible therapeutic implication of myokines.

The Presence of Myosteatosis Is Associated with Age, Severity of Liver Disease and Poor Outcome and May Represent a Prodromal Phase of Sarcopenia in Patients with Liver Cirrhosis.

BACKGROUND/AIMS: Myosteatosis implies impaired muscle quality. The aim of the study was to investigate the association of myosteatosis with other muscle abnormalities and its role in the prognosis of liver cirrhosis (LC). METHOD: Skeletal muscle index (SMI) and myosteatosis were measured by computed tomography. Myosteatosis was defined as muscle radiodensity and evaluated according to dry body mass index (BMI). Median values and interquartile range were used for continuous and count (percentage) for categorical variables. RESULTS: A total of 197 consecutive patients were included (age 61 (IQR 52-68); 67% male; MELD score 11 (interquartile range 7.5-16)). Myosteatosis was identified in 73.6% and sarcopenia in 44.6% of patients. Myosteatosis was positively associated with age (p = 0.024) and Child-Pugh (p = 0.017) and inversely associated with SMI (p = 0.026). Patients with myosteatosis exhibited lower 360-day survival (log-rank p = 0.001) compared to those without it. MELD (p < 0.001) and myosteatosis (p = 0.048) emerged as negative prognostic factors of survival in multivariate model. Individuals combining low muscle strength and impaired muscle quality and quantity displayed more advanced LC, impaired muscle performance, lower BMI (p < 0.001 each) and a three times higher mortality rate compared to those with low muscle quality alone. CONCLUSIONS: The presence of myosteatosis was associated with advanced age, low skeletal mass and more severe LC. Myosteatosis was associated with poor prognosis and may represent a prodromal phase of muscle degeneration before the development of sarcopenia.

The Role of the Respiratory Microbiome in the Pathogenesis of Aspiration Pneumonia: Implications for Diagnosis and Potential Therapeutic Choices.

Although the lungs were considered to be sterile until recently, the advent of molecular biology techniques, such as polymerase chain reaction, 16 S rRNA sequencing and metagenomics has led to our expanding knowledge of the lung microbiome. These methods may be particularly useful for the identification of the causative agent(s) in cases of aspiration pneumonia, in which there is usually prior administration of antibiotics. The most common empirical treatment of aspiration pneumonia is the administration of broad-spectrum antibiotics; however, this may result in negative cultures from specimens taken from the respiratory tract. Therefore, in such cases, polymerase chain reaction or metagenomic next-generation sequencing may be life-saving. Moreover, these modern molecular methods may assist with antimicrobial stewardship. Based upon factors such as age, altered mental consciousness and recent hospitalization, there is a shift towards the predominance of aerobes, especially Gram-negative bacteria, over anaerobes in aspiration pneumonia. Thus, the therapeutic choices should be expanded to cover multi-drug resistant Gram-negative bacteria in selected cases of aspiration pneumonia.

Therapeutic Potential of GLP-2 Analogs in Gastrointestinal Disorders: Current Knowledge, Nutritional Aspects, and Future Perspectives.

PURPOSE OF REVIEW: Although Glucagon-like peptide (GLP)-1 receptor agonists have been used for almost two decades in the treatment of diabetes mellitus type 2 and, lately, in obesity, recent years have seen an increasing interest in the pharmacological agonism of other proglucagon-derived peptides, including GLP-2. Herein, we aimed to review the available evidence on the effects of GLP-2 agonism from animal and clinical studies. Furthermore, we summarize the current clinical applications of GLP-2 agonists among patients with intestinal failure associated with short bowel syndrome (SBS-IF) as well as potential future expansion of their indications to other intestinal disorders. RECENT FINDINGS: Evidence from preclinical studies has highlighted the cellular trophic and functional beneficial actions of GLP-2 on small intestinal and colonic mucosa. Subsequently, pharmacologic agonism of GLP-2 has gathered interest for the treatment of patients with conditions pertaining to the loss of intestinal anatomical and/or functional integrity to a degree requiring parenteral support, collectively referred to as intestinal failure. GLP-2 analogs positively influence nutrient absorption in animal models and humans, although continued therapy is likely needed for sustained effects. The degradation-resistant GLP-2-analog teduglutide has received approval for the treatment of SBS-IF, in which it may decisively reduce patient dependency on parenteral support and improve quality of life. Another two longer-acting analogs, glepaglutide and apraglutide, are currently undergoing phase III clinical trials. The use of GLP-2 analogs is effective in the management of SBS-IF and may show promise in the treatment of other severe gastrointestinal disorders associated with loss of effective intestinal resorptive surface area.

Cardiac MRI in Autoimmune Diseases: Where Are We Now?

Cardiovascular magnetic resonance imaging (CMR) allows the early diagnosis of various cardiovascular pathophysiologic phenomena in autoimmune diseases. Preliminary studies suggest that CMR holds a promising role in initiating the necessary changes in anti-rheumatic and cardiac treatment among patients with autoimmune diseases and cardiovascular diseases (CVD). It is widely known that the presence of late gadolinium enhancement (LGE) has been related to a worse cardiovascular prognosis. CMR has been documented to be the most valuable tool for diagnosis and risk prediction of cardiac involvement in a sarcoidosis population, while in SLE, the gap between clinical and autopsy diagnosis of the myocardial disease could be narrowed with the implementation of CMR. In different connective tissue diseases, including SLE, LGE has been demonstrated to be present early after the initial diagnosis of SLE. Considering that CMR, including LGE identifies more patients with silent myocardial disease in SLE and other connective tissue diseases than echocardiography, CMR should be the preferred imaging modality, especially in the era of modern techniques with broader availability and expertise. In this review, we summarize the major indications, advantages and limitations of the use of CMR among patients with autoimmune disorders.

Cirrhotic Cardiomyopathy: The Interplay Between Liver and Cardiac Muscle. How Does the Cardiovascular System React When the Liver is Diseased?

It is widely known that liver cirrhosis, regardless of the etiologies is accompanied by severe hemodynamic changes. The principal pathophysiological mechanisms are the hyperdynamic circulation with increased cardiac output, heart rate along with reduced systemic vascular resistance. Thus, counteractive mechanisms may develop that eventually lead to systolic as well as diastolic dysfunction and rhythm disturbances, in order to keep a steady homeostasis in the human body. Literally, blunted contractile responsiveness to physical or pharmacological stress, impaired diastolic relaxation and electrophysiological changes, primarily QT interval prolongation, do occur progressively in a cirrhotic patient with no known preexisting cardiac disease. This condition is identified as cirrhotic cardiomyopathy (CCM), an entity different from that seen in alcoholic cardiac muscle disease. For the past decades, clinicians did study and attempt to understand the pathophysiology and clinical significance of this process. Indeed, various factors have been identified acting at the molecular and cellular level. Electrocardiography, echocardiography and various serum biomarkers are the main tools that help healthcare practitioners to point to the correct diagnosis. Noteworthy, the subjects that suffer from cirrhotic cardiomyopathy may progress to heart failure during invasive procedures such as surgery, insertion of a transjugular intrahepatic portosystemic shunting (TIPS) and liver transplantation. Besides, several studies have illustrated that CCM is a contributing factor, or even a precipitant, of hepatorenal syndrome (HRS), a conceivable reversible kidney failure in patients with liver cirrhosis and ascites. The treatment is the same as it is in the patients with liver cirrhosis and heart failure and there is no particular treatment for cirrhotic cardiomyopathy. Hence, it is of utmost importance to clearly comprehend the pathophysiology of this disease in order to design more accurate diagnostic tools and definitive treatments in a way to prevent the complications of cirrhosis and overt heart failure. The objective of this review is to describe in a comprehensive way the pathological alterations that occur in the cardiovascular system of cirrhotic patients. It will also point the limitations that remain in the diagnosis and treatment strategies and more importantly, this review will alert the clinicians in the modern era to further observe and record additional pathological changes in this subset of patients.

Diabetes mellitus in the era of climate change.

Worldwide, diabetes mellitus (DM) represents a major public-health problem due to its increasing prevalence in tandem with the rising trend of obesity. However, climate change, with its associated negative health effects, also constitutes a worrisome problem. Patients with DM are experiencing more visits to emergency departments, hospitalizations, morbidity and mortality during heat waves at ever-increasing numbers. Such patients are particularly vulnerable to heat waves due to impaired thermoregulatory mechanisms in conjunction with impaired autonomous nervous system responses at high temperatures, electrolyte imbalances and rapid deterioration of kidney function, particularly among those aged > 80 years and with preexisting chronic kidney disease (CKD). Moreover, exposure to cold temperatures is associated with increased rates of acute myocardial infarction as well as poor glycaemic control, although results are conflicting regarding cold-related mortality among patients with DM. In addition to extremes of temperature, air pollution as a consequence of the climate crisis may also be implicated in the increased prevalence and incidence of DM, particularly gestational DM (GDM), and lead to deleterious effects in patients with DM. Thus, more large-scale studies are now required to elucidate the association between specific air pollutants and risk of DM. This review presents the currently available evidence for the detrimental effects of climate change, particularly those related to weather variables, on patients with DM (both type 1 and type 2) and GDM. Specifically, the effects of heat waves and extreme cold, and pharmaceutical and therapeutic issues and their implications, as well as the impact of air pollution on the risk for DM are synthesized and discussed here.