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Background: The Mediterranean diet (MeD) plays a key role in the prevention of obesity. Among the genes involved in obesity, the Fat mass and obesity-associated gene (FTO) is one of the most known, but its interaction with MeD remained uncertain so far.Methods: We carried out a study on a sample of 188 Italian subjects, analyzing their FTO rs9939609 alleles, and the difference in body composition between the baseline and a 4-weeks nutritional intervention. The sample was divided into two groups: the control group of 49 subjects, and the MeD group of 139 subjects.Results: We found significant relations between MeD and both variation of total body fat (ΔTBFat) (p = 0.00) and gynoid body fat (p = 0.04). ∆TBFat (kg) demonstrated to have a significant relation with the interaction diet-gene (p = 0.04), whereas FTO was associated with the variation of total body water (p = 0.02).Conclusions: MeD demonstrated to be a good nutritional treatment to reduce the body fat mass, whereas data about FTO remain uncertain. Confirming or rejecting the hypothesis of FTO and its influence on body tissues during nutritional treatments is fundamental to decide whether its effect has to be taken into consideration during both development of dietetic plans and patients monitoring. Trial Registration ClinicalTrials.gov Id: NCT01890070. Registered 01 July 2013, https://clinicaltrials.gov/ct2/show/NCT01890070. [ABSTRACT FROM AUTHOR]

Phthalates are ubiquitous environmental contaminants, massively used in industry as plasticizers and additives in cosmetics, which may impair the human endocrine system inducing fertility problems, respiratory diseases, obesity, and neuropsychological disorders. The aim of this study was to examine the influence of the monoethyl phthalate (MEP) and mono-(2-ethylhexyl) phthalate (MEHP) on the liver function and cardiometabolic risk factors in males. In this research, 102 male participants (51 normal weight and 51 overweight/obese) were enrolled and examined for phthalate metabolites exposure in urine samples after 12 h of fasting. MEP was found in 28.43% (29/102) volunteers, while MEHP was detected among 20.59% (21/102) participants. Statistically significant increment in transaminase serum levels was observed in MEP-positive normal weight subgroup. Linear correlation was obtained between MEP concentration in urine samples and triglyceride (TG) serum levels (r2 = 0.33; p < 0.01), visceral adiposity index (VAI) (r2 = 0.41; p < 0.01), lipid accumulation product (LAP) (r2 = 0.32; p < 0.01), and TG to high-density lipoprotein (HDL) ratio (r2 = 0.40, p < 0.01) among the obese. The MEHP-positive normal weight volunteers had statistically significant increment of body mass index (p = 0.03) compared to MEHP-negative participants. Urine MEHP concentrations were negatively correlated with HDL serum levels (r2 = 0.31; p < 0.05) in the normal weight subgroup. The phthalates exposure may be related to statistically significant ALT and AST serum levels increment as well as with increased BMI, while the phthalate levels in the urine may be correlated with increased TG and decreased HDL cholesterol serum levels and associated with indicators of cardiometabolic risk and insulin resistance as LAP and VAI. [ABSTRACT FROM AUTHOR]

Context.--The novel coronavirus disease 2019 (COVID-19) pandemic is significantly changing methodologic approaches in all branches of the health system. From a forensic point of view, this event is partly changing the manner in which forensic pathologists and all those who work in autopsy services operate, but above all, it is changing the patterns established for years by which cadavers are analyzed postmortem. Objective.--To present a review of the literature and a proposal for COVID-19 autopsy protocols. To contain the infection risk, a revision of all the protocols that until now have been applied to the examination of bodies that require autopsy services is required. Data Sources.--Currently, the diagnosis and postmortem analysis of positive or suspected COVID-19 cases plays a crucial role in scientific research. A review of the main recommendations proposed by international scientific societies regarding the risk of infection during autopsy was carried out. Scientific papers currently available via the PubMed NCBI search engine on COVID-19 postmortem diagnosis were also examined. Conclusions.--Throughout the history of medicine, autopsy has been fundamental to the understanding of multiple pathogenic processes that are investigated postmortem. The purpose of the study is to propose an operating protocol that can be useful for all clinical and forensic autopsies, with particular reference to the correct methods to be applied to the examination of positive or suspected COVID-19 cases, regarding both the autopsy procedure and the collection and analysis of biological samples. [ABSTRACT FROM AUTHOR]

Background: Studies that evaluated endocan levels in nonalcoholic fatty liver disease (NAFLD) and liver fibrosis are scarce. We aimed to explore endocan levels in relation to different stages of liver diseases, such as NAFLD, as determined with fatty liver index (FLI) and liver fibrosis, as assessed with BARD score. Methods: A total of 147 participants with FLI>60 were compared with 64 participants with FLI <30. An FLI score was calculated using waist circumference, body mass index, gam ma-glutamyl transferase and triglycerides. Patients with FLI >60 were further divided into those with no/mild fibrosis (BARD score 0-1 point; n=23) and advanced fibrosis (BARD score 2-4 points; n=124). BARD score was calculated as follows: diabetes mellitus (1 point) + body mass index>28 kg/m2 (1 point) + aspartate aminotransferase/alanine aminotransferase ratio>0.8 (2 points). Results: Endocan was independent predictor for FLI and BARD score, both in univariate [OR=1.255 (95% Cl = 1.104-1.426), P= 0.001; OR=1.208 (95% Cl=1.029-1.419), P=0.021, respectively] and multivariate binary logistic regression analysis [OR=1.287 (95% CI=1.055-1.570), P=0.013; OR=1.226 (95% Cl=1.022-1.470), P=0.028, respectively]. Endocan as a single predictor showed poor discriminatory capability for steatosis/fibrosis [AUC=0.648; (95% 0=0.568-0.727), P=0.002; AUC= 0.667 (95% 0=0.555-0.778), P=0.013, respectively], whereas in a Model, endocan showed an excellent clinical accuracy [AUC=0.930; (95% 0=0.886-0.975), P<0.001, AUC=0.840 (95% 0=0.763-0.918), P<0.001, respectively]. Conclusions: Endocan independently correlated with both FLI and BARD score. However, when tested in models (with other biomarkers), endocan showed better discriminatory ability for liver steatosis/fibrosis, instead of its usage as a single biomarker. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Non-alcoholic Fatty Liver Disease and Cardiovascular Risk: Metabolic Aspects and Novel Treatments," by E. Scorletti, P.C. Calder, C.D. Byrne in the previous issue.

Presents a letter to the editor related to celiac disease and skin disorders.

Presents a letter to the author about the use of psychological support counseling to increase gluten-free diet compliance in celiac patients.

Presents a letter to the editor on the effects of GABAB receptor agonists on parameters of alcohol self-administration in ethanol-naive and self-administering mice.

Marfan Syndrome (MFS) is an autosomal dominant disease caused in most cases by mutations in the FNB1 gene, which encodes for fibrillin 1. MFS does not alway shows typical phenotypic signs. Indeed, the occurrence of sudden death of unknown cause is increasingly seen in young adults without ante mortem preexisting pathology to explain the event. In many cases the diagnosis of Marfan Syndrome (MFS) is carried out post mortem, especially in cases where the disease’s external phenotype is absent. Here is reported a case of a young woman who died during a twin pregnancy investigated with medico-legal and forensic anthropological procedures. The autopsy showed the absence of a typical marfanoid habitus and the presence of a dissecting aneurysm of the aorta with histopathological degeneration of the aortic elastic fibers. The genetic investigation revealed two previously undetected de novo mutations of the FBN1 gene: c.T6181C: p.C2061R and c.G1415A: p.C472Y. This new mutations, together with a comprehensive analysis, demonstrates the existence of a causal relationship between these mutations and the dissecting aneurysm of the aorta. This also stresses the importance of a combined multidisciplinary approach to this condition which includes morphological and genetic studies. [ABSTRACT FROM AUTHOR]

The gut microbiota‐brain axis has been recognized as a network of connections that provides communication between the gut microflora and both central and autonomic nervous system. The gut microbiota alteration has been targeted for therapy in various neurodegenerative and psychiatric disbalances. Psychobiotics are probiotics that contribute beneficially to the brain function and the host mental health as a result of an interaction with the commensal gut bacteria, although their mechanism of action has not been completely revealed. In this state‐of‐art review, the findings about the potential therapeutic effects of the psychobiotics alone or in combination with conventional medicine in the treatment of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, as well as in some psychiatric diseases like depression, schizophrenia, and bipolar disorder, have been summarized. The evidence of the psychobiotics therapeutic outcomes obtained in preclinical and clinical trials have been given respectively for the observed neurodegenerative and psychiatric disorders. [ABSTRACT FROM AUTHOR]

Introduction: The umbrella term "human gut microbiota" describes the complex ecosystem harboring our gut. It includes bacteria, viruses, protozoa, archaea, fungi, and yeasts. This taxonomic classification does not describe its functions, which encompass nutrients digestion and absorption, immune system regulation, and host metabolism. "Gut microbiome" indicates instead the genome belonging to these "microbes" actively involved in these functions. However, the interaction between the host genome and the microbial ones determines the fine functioning of our organism. Methods: We reviewed the data available in the scientific literature on the definition of gut microbiota, gut microbiome, and the data on human genes involved in the interaction with the latter. We consulted the main medical databases using the following keywords, acronyms, and their associations: gut microbiota, gut microbiome, human genes, immune function, and metabolism. Results: Candidate human genes encoding enzymes, inflammatory cytokines, and proteins show similarity with those included in the gut microbiome. These findings have become available through newer artificial intelligence (AI) algorithms allowing big data analysis. From an evolutionary point of view, these pieces of evidence explain the strict and sophisticated interaction at the basis of human metabolism and immunity regulation in humans. They unravel more and more physiopathologic pathways included in human health and disease. Discussion: Several lines of evidence also obtained through big data analysis support the bi-directional role of gut microbiome and human genome in host metabolism and immune system regulation. [ABSTRACT FROM AUTHOR]

The article describes the case of a 52-year-old woman who presented with severe abdominal pain. The patient has a 20-year history of rheumatoid arthritis. She was initially diagnosed with Crohn's disease, but seven months later she was back in hospital for acute abdominal pain. After a series of examination, the patient was found to have a little cellular tree inside a bubble of pneumatosis.

A letter to the editor on the association between Behçet's disease and celiac disease is presented.

Presents a letter to the editor in response to the article about the use of baclofen for alcohol delirium tremens treatment that was previously published in the journal "Archives of the Internal Medicine."

BACKGROUND: Severe acute respiratory syndrome-related Coronavirus 2 (SARS-CoV-2) іnfection induces a pro-inflammatory state of an organism with long-term systemic consequences as a result. Systemic inflammation, characterized by a high circulating level of inflammatory cytokines, is a significant factor influencing articular cartilage metabolism in osteoarthritis (OA). This study aimed to determine the levels of pro-inflammatory and anti-inflammatory cytokines in plasma of patients with OA following SARS-CoV-2 infection and to compare them with those of healthy controls. METHODS: The experiment involved patients of the Orthopedic Specialty Clinic aged 46 to 69 diagnosed with knee OA. Among persons with joint pathology a group of convalescent patients from 6-9 months after COVID-19 was identified. The control group involved relatively healthy donors. The plasma levels of pro-inflammatory (IL-1β, IL-6, IL-8, IL-12β, tumor necrosis factor α [TNF-α], interferon-gamma [IFN-γ]) and anti-inflammatory (IL-4 and IL-10) cytokines were determined by enzyme-linked immunosorbent assay. RESULTS: It was established that in patients with OA, as well as after suffering from SARS-CoV-2 infection, an increase in the plasma levels of IL-1β was observed against the background of a decrease in the levels of IL-4, IL-8, IL-10, IL- 12β, TNF-α and IFN-γ, compared to the healthy controls. COVID-19 more significantly influenced the plasma levels of pro-inflammatory cytokines IL-1β and IL-12β. CONCLUSIONS: The results indicate the imbalance of pro- and anti-inflammatory cytokines in the plasma in patients with OA for a long post- COVID. Сhanges in the levels of inflammatory mediators suggest distinct immunoregulatory mechanisms involved in the pathogenesis of both joint pathology and systemic disorders caused by SARS-CoV-2. [ABSTRACT FROM AUTHOR]

BACKGROUND: one of the major challenges in clinical practice on the management of heart failure is to predict the clinical evolution from common light symptoms to severe cardiovascular events. An association between the inflammatory processes, matrix metalloproteinases (MMPs) production and activation under cardiovascular disease has been reported. In a prospective study we assessed the levels of circulating MMP-2 and MMP-9 in patients with coronary heart disease (CHD), in correlation with some inflammatory parameters, including interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). METHODs: our study included forty-three patients with different forms of CHD, such as stable angina (N.=18), unstable angina (N.=15), and myocardial infarction (N.=10). Plasma levels of MMP-2 and MMP-9 gelatinases were evaluated by immunoassay, while their activities were analyzed by means of SDS-PAGE with gelatin as a substrate. RESULTS: Our results revealed that MMP-2 as well as MMP-9 plasma levels, significantly increased only in patients with myocardial infarction, the more severe form of CHD. on the other hand, MMP-9 proteolytic activity was elevated in all groups of CHD patients, while, increased MMP-2 activity was associated with myocardial infarction. We observed a strong positive correlation between plasma levels of studied proteolytic enzymes and those of proinflammatory cytokines, such as IL-6 and TNF-α. CONCLUSIOS: Based on the results obtained we can hypothesize that MMP-9 might be a promising biomarker to identify CHD patients in the early stage of disease, while MMP-2 is more predictable in case of CHD clinical evolution to the more severe form. Further studies are required to confirm relationships between MMPs and the risk of cardiovascular diseases and to explore the involvement of MMPs in atherosclerosis plaque destabilization or cardiac remodeling processes. [ABSTRACT FROM AUTHOR]

Half of the global overweight/obese adult population have metabolic-dysfunction-associated fatty liver disease (MAFLD),1 with prevalence rising, even among non-obese individuals.2,3 This increase is observed globally and mostly in low- and low-middle-income countries of Africa, Asia and South America and represents a great worldwide burden on healthcare expenditures.4-7 Lifestyle changes and a healthy diet are still the cornerstone in the clinical management of these patients as approved medications are presently lacking.4,8 In clinical settings, most patients with fatty liver disease are first identified and subsequently followed up in the community by primary care practitioners (PCPs).9 There is unequivocal evidence of the health-promoting influence of primary care and its role in the prevention of illness and death.10 In addition, in contrast to speciality care, primary care is characterized by a more equitable distribution as a healthcare service for all populations.10 In this context, primary care is central and may therefore help or hinder optimal chronic disease care. In fact, since PCPs play a crucial role in the early detection of fatty liver disease and the prevention of clinical progression and potential complications, their appropriate evaluation of fatty liver disease is paramount. Simplification of the diagnostic criteria for fatty liver disease suitable for a busy primary care environment is needed to enable treatment expansion into primary care at a larger scale.34 These criteria need to be both useful and practical, and their content should be guided by input from clinicians involved in the daily care of these patients, particularly PCPs. Therefore, it is crucial to understand PCP perspectives regarding the proposed redefinition of fatty liver disease as well as the implications for the primary care of patients. [Extracted from the article]

Microelements represent an emerging resource for medicine and its preventive branch. Zinc is the second most abundant element in our organism with peculiar physiologic functions and pathophysiologic implications in systemic and gastrointestinal (GI) diseases. It interacts very often with gut microbiota (GM) and can affect natural course of GI diseases through a bidirectional relationship with intestinal bugs. We aimed to review literature data regarding zinc chemistry, role in health, and GI diseases in man with a special focus on its interaction with GM. We conducted a search on the main medical databases for original articles, reviews, meta‐analyses, randomized clinical trials and case series using the following keywords and acronyms and their associations: zinc, microelements, gut microbiota, gut health, and COVID‐19. Zinc has a rapid and simple metabolism and limited storage within our body. Its efficacy on immune system modulation reflects on improved response to pathogens, reduced inflammatory response, and improved atopic/allergic reactions. Zinc is also involved in cell cycle regulation (namely, apoptosis) with potential anti‐cancerogenic effects. All these effects are in a "symbiotic" relationship with GM. Finally, zinc shows preliminary viral antireplicative effects. Zinc seems to gain more and more evidences on its efficacy in allergic, atopic and infectious diseases treatment, and prevention. COVID‐19 can be the booster for research on future applications of zinc as perfect "postbiotic" in medicine. [ABSTRACT FROM AUTHOR]

Abstract: Angiosarcoma is a rare malignant tumor occurring in less than 2% of soft tissue sarcomas. Angiosarcoma involving the kidney usually represents metastasis from skin or visceral primary lesions, while angiosarcoma primarily occurring in the kidney is a very rare neoplasm. In the English literature, from 1942 to the present, only 19 cases of primary kidney angiosarcoma have been reported. A case of primary renal angiosarcoma presenting as a large kidney mass and flank pain occurring after traumatism is reported. The present case represents further evidence of a rare malignancy. [Copyright &y& Elsevier]

Craving plays an important role in the pathogenesis of alcohol dependence and relapse. In this review we have tried to analyse how many contrasting theories have been formulated in order to clarify the concept of craving. Many complex neurobiochemical mechanisms are implicated in the etiology of craving; these mechanisms involve several neurotransmitters, such us dopamine, opioids, glutamate, and serotonin. On the other hand comportamental and/or cognitive aspects could also play a role in the etiology of craving. The coexistence of many and often contrasting theories can indicate that different subtypes of patients could have different mechanisms at the basis of alcohol craving, suggesting that it could be advisable to personalize the anti-craving therapy. [ABSTRACT FROM AUTHOR]

Crohn disease is an inflammatory bowel disorder affecting children and adults. With its increasing prevalence, healthcare providers need adequate resources to assist with diagnosis and management. This article discusses early diagnosis, disease severity and classification, familial predisposition and genomics, and clinical management in the primary care setting. [ABSTRACT FROM AUTHOR]

Background/aim. Biologics represent a key therapeutic option in inflammatory bowel disease (IBD), but are associated with several side effects. Post-marketing surveillance, through a spontaneous adverse drug reactions (ADRs) monitoring system, is essential to assess the safety profile of biologics. The aim of the study was to prospectively evaluate the occurrence of ADRs in IBD patients treated with biologics from a single centre in Southern Italy. Methods. Data from patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) who underwent biological therapy were prospectively collected. ADRs were classified according to the Medical Dictionary for Regulatory Activities (MedDRA®). Results. Overall, 68 (54% male, 68% with UC and 32% with CD) biologic-na ïve IBD patients underwent biological therapy. Mean follow-up was 11.7 ± 6.2 months. As a results of switches, for 68 patients we obtained 96 biologic prescriptions. Overall, 45 ADRs occurred in 36 (53%) patients, distributed as follows (ADRs/prescriptions): 19/37 with IFX-Remicade, 5/12 with IFX-Remsima, 8/9 with GOL, 11/26 with ADA, and 2/12 with VDZ. Mild ADRs were 29 (64%), moderate 15 (34%) and 1 (2%) severe. General disorders and administration related reactions were the most frequent ADRs (35%), followed by skin and subcutaneous tissue disorders (20%), infections (15%), musculoskeletal (11%), respiratory (6%) blood (4%), gastrointestinal (4%), and vascular disorders (2%). In 9 cases (20%) the ADRs resulted in definitive discontinuation of biologic therapy. Conclusion. In a prospective cohort of IBD patients, more than half experienced ADRs during biologic therapy. General disorders and administration related reactions were the most common ADRs, while infections were less common and rarely led to discontinuation of therapy. Findings underline the importance of surveillance in management of IBD patients during biologic therapy and implementing safety protocols with data from real-life settings. [ABSTRACT FROM AUTHOR]

BACKGROUND: Osteoarthritis (OA) is one of the most common pathologies of the musculoskeletal system. Recent studies have shown the involvement of oxidative stress in both pathogenesis of OA and the effects of therapeutic agents used for its treatment. The aim of this study was to investigate the combined effect of chondroitin sulfate and multiprobiotic on the oxidative-antioxidant blood system of rats under conditions of OA. METHODS: Experimental OA was induced in male rats by injection of sodium monoiodoacetate (MIA; Sigma-Aldrich, Munich, Germany) into the knee joint. Chondroitin sulfate (CS) (Drastop®, World Medicine, UK) and probiotic (PB) composition (Multiprobiotic Simbiter®, O.D. Prolisok, Kiev, Ukraine) were used as therapeutic agents. The blood sampling was conducted on the 30th day of the experiment. The levels of reactive oxygen species (ROS) such as superoxide anion, hydrogen peroxide, lipid peroxidation products, antioxidant enzymes activity and parameters of glutathione-dependent antioxidant system were measured. RESULTS: It was established that under conditions of MIA-induced OA the content of ROS and products of lipid peroxidation increases in the blood serum of rats. The antioxidant defense system is composed of the superoxidedismutase (SOD) activity decreases while the catalase activity increases compared to control. There is a decrease in the content of reduced glutathione, an increase in the content of oxidized glutathione and the inactivation of glutathione-dependent enzymes in the blood serum of rats with experimental OA. CONCLUSIONS: The results indicated disorders of the oxidative-antioxidant balance and the development of oxidative stress in the organism of rats during experimental OA. The combined administration of CS and PB to animals with OA resulted in positive changes in the investigated parameters approaching the values of control group. [ABSTRACT FROM AUTHOR]

Purpose: The presence of many asymptomatic COVID-19 cases may increase the risks of disease dissemination, mainly for physicians. There are numerous reports on the frequent findings of sudden anosmia or hyposmia, before or at the same time of the typical COVID-19 symptoms onset. The aim of this study was to verify the association of olfactory impairment and COVID-19, providing a basis for subsequent research in the field of COVID-19 clinical heterogeneity. Methods: We developed a 15-item online questionnaire on "Sudden Olfactory Loss (SOL) and COVID-19" that was administered during March 2020 to Italian general practitioners registered to a social media group. Results: One hundred and eighty responses were received. SOL was identified as a significant sign of infection in COVID-19 patients, mainly aged between 30 and 40 years, even in the absence of other symptoms. SOL was present as an initial symptom in 46.7% of subjects, and in 16.7%, it was the only symptom. Among the COVID-19 confirmed cases, SOL occurred as the only symptom in 19.2% of patients. Conclusion: SOL could represent a possible early symptom in otherwise asymptomatic COVID-19 subjects. Subjects affected by SOL should be considered as potential COVID-19 cases. Level of evidence: 4. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) has a negative impact on patients' physical and psychological well-being, social performance, and working capacity, thereby worsening their health-related quality of life (HRQoL). Clinicians should take care of the patients' global health, including the psychological, social, and emotional spheres. We aimed to investigate the reality of patient-reported outcomes of HRQoL in a series of IBD patients. Consecutive Crohn´s disease (CD) and ulcerative colitis (UC) patients in clinical remission were recruited. The survey consisted of the Short Inflammatory Bowel Disease Questionnaire (S-IBDQ), the Hospital Anxiety and Depression Scale (HADS), the Brief Illness Perception Questionnaire (B-IPQ), and a questionnaire dealing with impact of IBD on patients' lives. Demographic and clinical characteristics were recorded. Of 202 participants (29% CD and 71% UC; 54% male; median age 48 years; mean disease duration 14 ± 11 years), 52% had poor HRQoL, 45% anxiety/depression, and 35% sleep disturbance and a high perception of disease (mean score 42.8 ± 14.3). In the multivariate analysis, a low HRQoL was rather associated with UC than CD (p = 0.037), IBD surgery (p = 0.010), disease duration (p = 0.01), sleep disturbance (p = 0.014), anxiety/depression (p = 0.042), and high illness perception (p = 0.006). IBD affected working performance and social activities in 62% and 74% of patients, respectively. Satisfaction regarding quality of care, biologics, and surgery approach were claimed in 73%, 69%, and 76% of patients, respectively. Although 84% of patients trusted their gastroenterologist, only 66% of them discussed IBD impact on HRQoL during visit. In a series of IBD patients in remission, the low HRQoL was significantly associated with surgery, disease duration, sleep disturbance, anxiety/depression, and high illness perception. Even though patients were satisfied with the quality of their care, it appears that clinicians should pay more attention to patients' emotional status. [ABSTRACT FROM AUTHOR]

Introduction: In primary biliary cholangitis (PBC), macrophages are involved in liver inflammation and fibrosis. The macrophage activation markers, soluble (s)CD163 and mannose receptor (sMR) are associated with liver disease severity and prognosis in other chronic liver diseases. We aimed to investigate sCD163 and sMR in patients with PBC. Methods: We investigated PBC patients from the Italian PBC Study Group cohort and measured macrophage activation markers in serum at study enrolment. Patients were followed from enrolment until they experienced an event or were censored at their last visit. Events were defined as follows: (a) death from a liver‐related cause; or (b) liver transplantation (LT) for PBC. We used Cox regression to investigate the association between sCD163 and sMR and long‐term prognosis. Results: In total, 202 PBC patients were included. Median age was 62 years (interquartile range (IQR), 53‐71) at enrolment and 93% were women. Median sCD163 was 3.43 mg/L (IQR 2.48‐5.35) and median sMR was 0.35 mg/L (IQR 0.28‐0.45). There was an increase in sCD163 and sMR with increasing alkaline phosphatase. Two hundred and one patients were followed for a median of 8.6 years, and sCD163 and sMR predicted long‐term risk of liver‐related death or LT in univariate analyses, while sCD163 was also associated with outcome after confounder adjusting (adjusted HR = 1.14, 95% CI 1.00‐1.30). Finally, we showed an increase in the prediction accuracy of poor outcome by adding sCD163 to the UK‐PBC risk score. Conclusion: The macrophage activation markers sCD163 and sMR represent a non‐invasive measure of PBC disease severity that provides useful long‐term prognostic information. [ABSTRACT FROM AUTHOR]

Purpose: Gut dysbiosis has been described in advanced, but not in initial stages of CKD. Considering the relevant impact of gut dysbiosis on renal and cardiovascular risk, its diagnosis and treatment are clinically relevant. Methods: We designed, open-label, placebo-controlled intervention study (ProbiotiCKD) to evaluate gut microbiota metabolism in a cohort of KDIGO CKD patients (n = 28) at baseline and after a randomly assigned treatment with probiotics or placebo. Gut microbiota status was evaluated on:. Results: Basal mean fecal Lactobacillales and Bifidobacteria concentrations were abnormally low in both groups, while urinary indican and 3-MI levels were, indicating a mixed (fermentative and putrefactive) dysbiosis. After treatment, mean fecal Lactobacillales and Bifidobacteria concentrations were increased, only in the probiotics group (p < 0.001). Conversely, mean urinary indican and 3-MI levels only in the group treated with probiotics (p < 0.001). Compared to placebo group, significant improvements of C-reactive protein (p < 0.001), iron (p < 0.001), ferritin (p < 0.001), transferrin saturation (p < 0.001), β2-microglobulin (p < 0.001), serum iPTH and serum calcium were observed only in the probiotics group. Conclusions: ProbiotiCKD is the first intervention study demonstrating that an intestinal mixed dysbiosis is present even in early CKD stage and can be effectively corrected by the novel mode of administration of high-quality probiotics with improvement of inflammatory indices, iron status and iPTH stabilization. [ABSTRACT FROM AUTHOR]

Background Recent evidence suggested a potential role of complement fraction C3 as a biomarker of nonalcoholic fatty liver disease ( NAFLD) in the general population. Aim of this study was to evaluate the performance of C3 for prediction of NAFLD in RA patients. Materials and methods For the present study, consecutive RA patients were recruited. NAFLD was diagnosed according to predefined ultrasonographic ( US) criteria. For comparison, the hepatic steatosis index ( HSI) was calculated. Results Of 164 consecutive RA patients, 41 (25%) were diagnosed with NAFLD. The NAFLD group had a significant lower proportion of females ( P = 0·04), higher BMI ( P < 0·0001), C-reactive protein ( P = 0·04), complement C3 ( P = 0·001) and HSI ( P = 0·003). In a logistic regression model, only male sex ( OR 2·65, 95% CI: 1·08-6·50, P = 0·03), increasing BMI ( OR 1·22, 95% CI: 1·02-1·46, P = 0·03) and complement C3 ( OR 5·05, 95% CI: 1·06-23·93, P = 0·04) were associated with higher likelihood of being diagnosed with NAFLD. Finally, we built ROC curves for BMI, complement C3 and their combination for prediction of having NAFLD. The best cut-off for BMI was 28·5 kg/m2 and yielded a sensitivity of 66% and a specificity of 71%; the best cut-off for complement C3 was 1·23 g/L and yielded a sensitivity of 76% and a specificity of 64% for classification of NAFLD cases. Conclusions Our results provide preliminary evidence for a potential role of complement C3 as a surrogate biomarker of NAFLD in RA patients. [ABSTRACT FROM AUTHOR]