Role of triglyceride-glucose index in metabolic assessment of sarcoidosis patients.

Sarcoidosis is a rare granulomatous disease that can affect any organ. It leads to an increased risk of metabolic syndrome and insulin resistance, due to biochemical pathways involved in low-grade inflammation in both diseases. The aim of our retrospective case-control study was to evaluate the utility of triglyceride-glucose (TyG) index, a surrogate of insulin resistance, for metabolic assessment of sarcoidosis patients. A cohort of 90 sarcoidosis patients and a cohort of 90 control subjects were enrolled. Clinical, anamnestic, and biochemical data were collected. Results showed that TyG index values were higher in the sarcoidosis cohort than in the control group (p < 0.001), even after excluding the influence of diabetes and metabolic syndrome (p = 0.018). In the sarcoidosis cohort, TyG index was not correlated with clinical phenotyping (p = 0.358), gender (p = 0.139), radiological stage (p = 0.656), glucocorticoids cumulative dose (p = 0.682) or treatment regimen (p = 0.093), while significant positive correlations with waist circumference (p < 0.001), systolic and diastolic pressure (p = 0.041 and p = 0.029, respectively), Framingham score (p = 0.007) were found. Receiving operating characteristics curve analysis identified a TyG index optimal cut-off value of 8.64 (66.7% sensitivity, 77.8% specificity, area under the curve -AUC- 75%, 95% confidence interval -CI- 65-85, p < 0.001) to detect metabolic syndrome and a cut-off value of 8.69 (64.1% sensitivity, 70.6% specificity; AUC 67%, 95% CI 55-78, p = 0.007) to detect an intermediate cardiovascular risk according to Framingham risk score. Concluding, TyG index can be considered a useful tool for the metabolic assessment of sarcoidosis patients, given its capacity to predict metabolic syndrome and cardiovascular risk.

Fasting hyperglycaemia and fatty liver drive colorectal cancer: a retrospective analysis in 1145 patients.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents the hepatic manifestation of increased adiposopathy, whose pathogenetic features have been proposed as tumourigenic triggers for colorectal cancer (CRC). We aim to identify specific metabolic signatures involved in CRC development that may be used as non-invasive biomarkers, paving the way for specific and personalized strategies of CRC prevention and early detection. METHODS: We retrospectively assessed CRC onset during a time frame of 8 years in a cohort of 1145 out-patients individuals who had previously been evaluated for Metabolic Syndrome. RESULTS: 28 patients developed CRC. No association between CRC development and visceral and general obesity was detected, while baseline fasting plasma glucose (FPG) and non-invasive liver fibrosis scores were significantly higher in patients with CRC, compared to those who did not develop cancer. Liver steatosis and MASLD were more frequently diagnosed in patients who developed CRC compared to no cancer developers. Canonical correlations among metabolic biomarkers were not present in CRC developers, differently from no cancer group. In ROC analysis, FPG and non-invasive scores also showed good sensitivity and specificity in predicting colon cancer. We then calculated ORs for metabolic biomarkers, finding that higher FPG and non-invasive scores were associated with an increased risk of developing CRC. CONCLUSION: MASLD and increased FPG may play a role in the clinical background of CRC, bringing to light the fascinating possibility of a reversed gut-liver axis communication in the pathogenesis of CRC. Thus, the use of non-invasive scores of fatty liver may be helpful to predict the risk of CRC and serve as novel prognostic factors for prevention and therapeutic strategies.

Low Adherence to Mediterranean Diet Characterizes Metabolic Patients with Gastrointestinal Cancer.

Background. Gastrointestinal (GI) cancers are one of the most relevant causes of death globally, frequently associated with poor dietary patterns. The Mediterranean Diet (MedDiet) contributes to cancer prevention. To assess adherence to MedDiet, our research group validated a new score, the Chrono Med Diet Score (CMDS), that captures increased visceral adiposity. Methods. We enrolled 401 subjects who underwent an evaluation for metabolic diseases and specific screening procedures according to current guidelines and were asked to answer CMDS. A total of 71 new cancer cases were recorded, including 40 GI and 31 non-gastrointestinal (NON-GI) cancers. Results. We found that CMDS was reduced in subjects who were diagnosed with cancers. Patients who reported a CMDS score of 12 or less had an over three times increased risk of being diagnosed with GI cancers and presented increased waist circumference and triglycerides and reduced HDL cholesterol compared to adherent subjects. Conclusions. Low CMDS values capture the risk for cancer diagnosis, especially for GI cancers. Thus, CMDS, along with waist circumference, can be considered as a bona fide marker for increased risk of cancer, requiring anticipated screening procedures for the detection of premalignant and early stage GI cancers in patients with low adherence to MedDiet.

Gut Microbiota Modulation and Its Implications on Neuropathic Pain: A Comprehensive Literature Review.

Neuropathic pain (NP) is a chronic pain disorder arising from somatosensory nervous system impairment. Extensive evidence supports the notion that the gut microbiota (GM) is crucial in maintaining human health by performing vital tasks. At the same time, its disruption has been linked to the emergence and advancement of an expanding range of disorders, including NP, in which GM could play a role in its pathophysiology. The crosstalk between the nervous system and GM happens through immune mediators, metabolites, and nervous structures and involves both central and peripheral nervous systems. This literature review aims to thoroughly investigate the function of modulating GM in the treatment of NP. It will achieve this by integrating existing knowledge, identifying underlying mechanisms, and evaluating the possible clinical consequences of exploiting the gut-brain axis. We will cover the main therapeutic applications of the described GM-modulators, such as probiotics, faecal microbiota transplantation, dietary supplements and emotional support, to the main kinds of NP in which any evidence, even if only pre-clinical, has been unravelled in recent years. The explored NP areas include chemotherapy-induced peripheral neuropathy, diabetic neuropathy, trauma-induced neuropathic pain, trigeminal neuralgia, postherpetic neuralgia and low back pain.

RNA sequencing unravels novel L cell constituents and mechanisms of GLP-1 secretion in human gastric bypass-operated intestine.

AIMS/HYPOTHESIS: Roux-en-Y gastric bypass surgery (RYGB) frequently results in remission of type 2 diabetes as well as exaggerated secretion of glucagon-like peptide-1 (GLP-1). Here, we assessed RYGB-induced transcriptomic alterations in the small intestine and investigated how they were related to the regulation of GLP-1 production and secretion in vitro and in vivo. METHODS: Human jejunal samples taken perisurgically and 1 year post RYGB (n=13) were analysed by RNA-seq. Guided by bioinformatics analysis we targeted four genes involved in cholesterol biosynthesis, which we confirmed to be expressed in human L cells, for potential involvement in GLP-1 regulation using siRNAs in GLUTag and STC-1 cells. Gene expression analyses, GLP-1 secretion measurements, intracellular calcium imaging and RNA-seq were performed in vitro. OGTTs were performed in C57BL/6j and iScd1-/- mice and immunohistochemistry and gene expression analyses were performed ex vivo. RESULTS: Gene Ontology (GO) analysis identified cholesterol biosynthesis as being most affected by RYGB. Silencing or chemical inhibition of stearoyl-CoA desaturase 1 (SCD1), a key enzyme in the synthesis of monounsaturated fatty acids, was found to reduce Gcg expression and secretion of GLP-1 by GLUTag and STC-1 cells. Scd1 knockdown also reduced intracellular Ca2+ signalling and membrane depolarisation. Furthermore, Scd1 mRNA expression was found to be regulated by NEFAs but not glucose. RNA-seq of SCD1 inhibitor-treated GLUTag cells identified altered expression of genes implicated in ATP generation and glycolysis. Finally, gene expression and immunohistochemical analysis of the jejunum of the intestine-specific Scd1 knockout mouse model, iScd1-/-, revealed a twofold higher L cell density and a twofold increase in Gcg mRNA expression. CONCLUSIONS/INTERPRETATION: RYGB caused robust alterations in the jejunal transcriptome, with genes involved in cholesterol biosynthesis being most affected. Our data highlight SCD as an RYGB-regulated L cell constituent that regulates the production and secretion of GLP-1.

Thyroid nodule malignancy is associated with increased non-invasive hepatic fibrosis scores in metabolic subjects.

Introduction: Thyroid cancer incidence is increasing, and adiposity-related conditions are gaining space in its pathogenesis. In this study, we aimed to detect any anthropometric, biohumoral, and clinical features that might be associated with thyroid nodule malignancy, potentially representing novel non-invasive markers of thyroid cancer. Materials and methods: The study was conducted in a group of 142 consecutive outpatients (47 men and 95 women) who underwent fine-needle aspiration biopsy/cytology (FNAB/C) due to suspicion of malignancy from January 2018 to September 2022. We compared lipid and glycemic blood profiles as well as non-invasive liver fibrosis indexes such as aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio (AAR), AST to platelet ratio index (APRI), and fibrosis index based on four factors (FIB-4) between patients with benign and malignant newly diagnosed nodules. Then, we performed receiver operating characteristic (ROC) analysis to assess their best cutoff values for discrimination of malignant nodules and chi-squared test to evaluate the association of specific dysmetabolic conditions with malignancy. To understand whether and to what degree dysmetabolic conditions increased the risk of thyroid nodule malignancy, we also calculated the odds ratio (OR) of the main biomarkers. Results: After FNAB/C, 121 (85%) patients were diagnosed with benign thyroid nodules, while 21 (15%) individuals were diagnosed with thyroid cancer. Comparing patients with benign and malignant nodules, we found that individuals with thyroid cancer exhibited increased body mass index (BMI) (p = 0.048) and fasting plasma glucose (p = 0.046). Intriguingly, considering non-invasive scores for liver fibrosis, subjects with thyroid cancer presented increased AAR (p < 0.001) and APRI (p = 0.007), and these scores were associated with malignancy (p < 0.005) with OR = 7.1 and OR = 5, respectively. Moreover, we showed that only in the cancer group, low levels of vitamin D correlated with stigmata of impaired metabolism. Discussion: In our study, AAR and APRI scores were associated with thyroid nodule malignancy and could be used to predict it and to speed up the diagnostic process. From a pathogenic point of view, we speculated that metabolic-associated fatty liver disease (MAFLD) along with hyperglycemia and vitamin D deficiency may represent putative drivers of thyroid carcinogenesis.

Gut microbiota in the pathogenesis and therapeutic approaches of diabetes.

The gut-liver axis plays a prominent role in the pathogenesis and therapy of metabolic diseases such as diabetes. The intestinal specific origin of several hormones that guide both inter- and post-prandial metabolism of carbohydrates and lipids, drives the attention of scientists and clinicians on the gut as a major site to intervene with novel diagnostic or prognostic markers. The role of intestinal ecology in the metabolic syndrome was postulated when gut microbiota was directly connected with inflammation, hyperinsulinemia, and diabetes. There have been several discoveries with the role of gut microbiota and gut-liver axis in diabetes. Also, there are several trials ongoing on the therapeutic efficacy of probiotic administration in diabetes and its complications. Here we point to the metabolic action of microbiota and discuss the actual state of the art on gut microbiota as a novel prognostic biomarker with a putative therapeutic role in diabetes.

Intestinal Pgc1α ablation protects from liver steatosis and fibrosis.

Background & Aims: The gut-liver axis modulates the progression of metabolic dysfunction-associated steatotic liver disease (MASLD), a spectrum of conditions characterised by hepatic steatosis and a progressive increase of inflammation and fibrosis, culminating in metabolic dysfunction-associated steatohepatitis. Peroxisome proliferator-activated receptor-gamma coactivator 1α (Pgc1α) is a transcriptional co-regulator of mitochondrial activity and lipid metabolism. Here, the intestinal-specific role of Pgc1α was analysed in liver steatosis and fibrosis. Methods: We used a mouse model in which Pgc1α was selectively deleted from the intestinal epithelium. We fed these mice and their wild-type littermates a Western diet to recapitulate the major features of liver steatosis (after 2 months of diet) and metabolic dysfunction-associated steatohepatitis (after 4 months of diet). The chow diet was administered as a control diet. Results: In humans and mice, low expression of intestinal Pgc1α is inversely associated with liver steatosis, inflammation, and fibrosis. Intestinal disruption of Pgc1α impairs the transcription of a wide number of genes, including the cholesterol transporter Niemann-Pick C1-like 1 (Npc1l1), thus limiting the uptake of cholesterol from the gut. This results in a lower cholesterol accretion in the liver and a decreased production of new fatty acids, which protect the liver from lipotoxic lipid species accumulation, inflammation, and related fibrotic processes. Conclusions: In humans and mice, intestinal Pgc1α induction during Western diet may be another culprit driving hepatic steatosis and fibrosis. Here, we show that enterocyte-specific Pgc1α ablation protects the liver from steatosis and fibrosis by reducing intestinal cholesterol absorption, with subsequent decrease of cholesterol and de novo fatty acid accumulation in the liver. Impact and implications: Liver diseases result from several insults, including signals from the gut. Although the incidence of liver diseases is continuously increasing worldwide, effective drug therapy is still lacking. Here, we showed that the modulation of an intestinal coactivator regulates the liver response to a Western diet, by limiting the uptake of dietary cholesterol. This results in a lower accumulation of hepatic lipids together with decreased inflammation and fibrosis, thus limiting the progression of liver steatosis and fibrosis towards severe end-stage diseases.

AST/ALT-to-platelet ratio (AARPRI) predicts gynaecological cancers: a 8-years follow-up study in 653 women.

Non-alcoholic fatty liver disease (NAFLD), specifically liver steatosis and fibrosis with steatohepatitis (NASH), is often associated with visceral adiposopathy, whose pathogenetic features have been proposed as tumorigenic triggers. We performed a prospective analysis in 653 metabolic women to reveal any conditions that may predict and concur to cancer development during a 8-years period of follow-up. Among clinical and biochemical variables, only AST and non-invasive liver fibrosis scores (AARPRI, APRI, FIB-4, mFIB4) significantly distinguished cancer-developer women (n = 62, 9.5%) from those who did not develop cancer (p < 0.001). In ROC analysis, these scores also showed good sensitivity and specificity in differentiating women who developed cancer (all p < 0.001). We then calculated OR for these indexes finding that increased AARPRI was associated with the highest risk (OR = 6, p < 0.001) of gynaecological cancers development. We further validated these cut-off values in women who had developed other types of cancer, confirming that AARPRI is able to identify the risk for cancer development (OR = 5, p < 0.001). Our findings support the hypothesis that NAFLD, more than obesity per se, is directly associated with the clinical and pathogenic metabolic scenario of gynaecological cancers and encourage the use of liver fibrosis indexes to detect risk of cancer onset in women. Preventing adiposopathy and NAFLD through lifestyle and therapies may represent an instrumental strategy for cancer prevention and/or co-treatment in oncology.

The interplay between dietary fatty acids and gut microbiota influences host metabolism and hepatic steatosis.

Dietary lipids can affect metabolic health through gut microbiota-mediated mechanisms, but the influence of lipid-microbiota interaction on liver steatosis is largely unknown. We investigate the impact of dietary lipids on human gut microbiota composition and the effects of microbiota-lipid interactions on steatosis in male mice. In humans, low intake of saturated fatty acids (SFA) is associated with increased microbial diversity independent of fiber intake. In mice, poorly absorbed dietary long-chain SFA, particularly stearic acid, induce a shift in bile acid profile and improved metabolism and steatosis. These benefits are dependent on the gut microbiota, as they are transmitted by microbial transfer. Diets enriched in polyunsaturated fatty acids are protective against steatosis but have minor influence on the microbiota. In summary, we find that diets enriched in poorly absorbed long-chain SFA modulate gut microbiota profiles independent of fiber intake, and this interaction is relevant to improve metabolism and decrease liver steatosis.

Total serum FGF-21 levels positively relate to visceral adiposity differently from its functional intact form.

Objective: Increased Fibroblast Growth Factor-21 (FGF-21) circulating levels have been described in obesity. In this observational study, we analysed a group of subjects with metabolic disorders to unravel the putative link between visceral adiposity and FGF-21 serum levels. Methods: Total and intact serum FGF-21 concentration was measured with an ELISA assay respectively in 51 and 46 subjects, comparing FGF-21 levels in dysmetabolic conditions. We also tested Spearman's correlations between FGF-21 serum levels and biochemical and clinical metabolic parameters. Results: FGF-21 was not significantly increased in high-risk conditions such as visceral obesity, Metabolic Syndrome, diabetes, smoking, and atherosclerosis. Waist Circumference (WC), but not BMI, positively correlated with total FGF-21 levels (r=0.31, p <0.05), while HDL-cholesterol (r=-0.29, p <0.05) and 25-OH Vitamin D (r=-0.32, p <0.05) showed a significant negative correlation with total FGF-21. ROC analysis of FGF-21 in prediction of increased WC, showed that patients with total FGF-21 level over cut-off value of 161.47 pg/mL presented with impaired FPG. Conversely, serum levels of the intact form of FGF-21 did not correlate with WC and other metabolic biomarkers. Conclusion: Our newly calculated cut-off for total FGF-21 according to visceral adiposity identified subjects with fasting hyperglycemia. However, waist circumference correlates with total FGF-21 serum levels but does not correlate with intact FGF-21, suggesting that functional FGF-21 does not necessarily relate with obesity and metabolic features.

Impact of a Pro-Active Infectious Disease Consultation on the Management of a Multidrug-Resistant Organisms Outbreak in a COVID-19 Hospital: A Three-Months Quasi-Experimental Study.

BACKGROUND: Antimicrobial and diagnostic stewardship (AS/DS) principles are crucial for the management of multidrug-resistant organisms (MDROs) infections. We evaluated the impact of a pro-active Infectious Disease (ID) consultation on the mortality risk of patients during an MDROs outbreak in a COVID-19 hospital. METHODS: A quasi-experimental study was performed in a dedicated COVID-19 hospital, including patients with suspected/confirmed infection and/or colonization by MDROs, which were managed as follows: (i) according to the standard of care during the pre-phase and (ii) in collaboration with a dedicated ID team performing a pro-active bedside evaluation every 48-72 h in the post-phase. RESULTS: Overall, 112 patients were included (pre-phase = 89 and post-phase = 45). The AS interventions included the following: therapy optimization (33%), de-escalation to narrow the spectrum (24%) or to lessen toxic drugs (20%), and discontinuation of antimicrobials (64%). DS included the request of additional microbiologic tests (82%) and instrumental exams (16%). With the Cox model, after adjusting for age, sex, COVID-19 severity, infection source, etiological agents, and post-phase attendance, only age predicted an increased risk of mortality, while attendance in the post-phase resulted in a decreased risk of mortality. CONCLUSIONS: Implementation of AS and DS intervention through a pro-active ID consultation may reduce the risk of 28-day mortality of COVID-19 patients with MDROs infections.

Identification of a Novel Score for Adherence to the Mediterranean Diet That Is Inversely Associated with Visceral Adiposity and Cardiovascular Risk: The Chrono Med Diet Score (CMDS).

Adherence to the Mediterranean diet (MedDiet) leads to reduction of mortality from all causes, especially in subjects with cardiovascular disease, obesity, and diabetes. Numerous scores have been proposed to evaluate the adherence to MedDiet, mainly focused on eating habits. In this study, we verified whether existing validated MedDiet scores, namely, MEDI-LITE and the Mediterranean Diet Score (MDS), could be associated with visceral adiposity. Failing to find a significant association with adiposity, we proposed the validation of a new, easy-to-use adherence questionnaire, the Chrono Med-Diet score (CMDS). CMDS contains eleven food categories, including chronobiology of dietary habits and physical activity. Compared to the MEDI-LITE score and MDS, low values of CMDS are linked to increased waist circumference (WC) and dysmetabolic conditions. CMDS was also inversely correlated with cardiovascular risk (CVR), as well as Fatty Liver Index (FLI). In conclusion, the CMDS is a novel questionnaire to study the adherence to the MedDiet that, focusing on type and timing of carbohydrates intake, has the peculiar capability of capturing subjects with abdominal obesity, thus being an easy-to-use instrument of personalized medicine.

Relationship between oral lesions and severe SARS-CoV-2 infection in intensive care unit patients.

OBJECTIVE: Oral lesions received increased attention as likely new signs or secondary manifestations of COVID-19. Therefore, we clinically examined oral cavity of patients with COVID-19 and investigated oral lesions and patient comorbidities as possible risk factors of COVID-19 disease outcome. METHODS: From January to March 2022, a prospective study was conducted by recruiting all COVID-19 patients admitted to the Intensive Care Unit and Respiratory Intensive Care Unit of Maxi-Emergencies Hospital in Bari, Italy. RESULTS: From the enrolled 103 COVID-19 patients, 46.6% were females and 53.4% were males. Findings show that risk of presenting with severe COVID-19 disease was higher in patients who developed oral lesions related to COVID-19 than those with no oral lesions (RR = 7.998, p = .002). Next, patients with concomitant autoimmune diseases were at higher risk of a negative COVID-19 disease outcome than those without comorbidities (OR = 8.838, p = .026). CONCLUSIONS: COVID-19-related lesions of oral mucosa should not be ignored as they can be early and easily detectable signs of severe COVID-19 disease condition, thus, serving as a prevention measure for any potential unfortunate event. Findings of this study, without implying causation, offer a direction for future investigations that aim to confirm the presence of specific oral lesions in COVID-19 patients as signs of severe disease progression.

Low HDL-cholesterol levels predict hepatocellular carcinoma development in individuals with liver fibrosis.

Background & Aims: Dysmetabolic conditions could drive liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), increasing susceptibility to hepatocellular carcinoma (HCC). We therefore aimed to identify novel predictive biomarkers of HCC in patients with and without liver fibrosis. Methods: A total of 1,234 patients with putative metabolic conditions and NAFLD were consecutively assessed in our outpatient clinic. Clinical and biochemical data were recorded, and then liver ultrasonography was performed annually for 5 years to detect HCC onset. For the analysis, the population was first divided according to HCC diagnosis; then a further subdivision of those who did not develop HCC was performed based on the presence or absence of liver fibrosis at time 0. Results: Sixteen HCC cases were recorded in 5 years. None of our patients had been diagnosed with cirrhosis before HCC was detected. Compared to patients who did not develop HCC, those who did had higher liver transaminases and fibrosis scores at time 0 (p <0.001). In addition, they presented with increased glycated haemoglobin levels and lower 25-OH vitamin D levels (p <0.05). Intriguingly, patients with higher liver fibrosis scores who subsequently developed HCC had lower HDL-cholesterol (HDL-c) levels at time 0 (p <0.001). Furthermore, in the 484 patients presenting with lower HDL-c at baseline, we found that waist circumference, and then vitamin D and glycated haemoglobin levels, were significantly different in those who developed HCC, regardless of liver fibrosis (p <0.05). Conclusions: This study identifies HDL-c as a bona fide novel marker to predict HCC in patients with NAFLD. Increased waist circumference and deranged metabolic pathways represent additional predisposing factors among patients with low HDL-c, highlighting the importance of studying cholesterol metabolism and integrating clinical approaches with dietary regimens and a healthy lifestyle to prevent HCC. Impact and implications: Visceral adiposity and its associated conditions, such as chronic inflammation and insulin resistance, may play a pivotal role in hepatocellular carcinoma development in patients with non-alcoholic fatty liver disease. We provide new insights on the underlying mechanisms of its pathogenesis, shedding light on the involvement of low levels of "good" HDL-cholesterol. We recommend integrating dietary regimens and advice on healthy lifestyles into the clinical management of non-alcoholic fatty liver disease, with the goal of reducing the incidence of hepatocellular carcinoma.

The central role of the gut in intensive care.

Critically ill patients undergo early impairment of their gut microbiota (GM) due to routine antibiotic therapies and other environmental factors leading to intestinal dysbiosis. The GM establishes connections with the rest of the human body along several axes representing critical inter-organ crosstalks that, once disrupted, play a major role in the pathophysiology of numerous diseases and their complications. Key players in this communication are GM metabolites such as short-chain fatty acids and bile acids, neurotransmitters, hormones, interleukins, and toxins. Intensivists juggle at the crossroad of multiple connections between the intestine and the rest of the body. Harnessing the GM in ICU could improve the management of several challenges, such as infections, traumatic brain injury, heart failure, kidney injury, and liver dysfunction. The study of molecular pathways affected by the GM in different clinical conditions is still at an early stage, and evidence in critically ill patients is lacking. This review aims to describe dysbiosis in critical illness and provide intensivists with a perspective on the potential as adjuvant strategies (e.g., nutrition, probiotics, prebiotics and synbiotics supplementation, adsorbent charcoal, beta-lactamase, and fecal microbiota transplantation) to modulate the GM in ICU patients and attempt to restore eubiosis.

Extra virgin olive oil extract rich in secoiridoids induces an anti-inflammatory profile in peripheral blood mononuclear cells from obese children.

Obesity represents an important public health challenge of the twenty first century reaching epidemic proportions worldwide; this is especially true for the pediatric population. In this context, bioactive compounds from foods are crucial to counteract chronic inflammation as a typical feature of obesity. In particular, extra virgin olive oil (EVOO) is one of the most important functional foods exerting, among others, an anti-inflammatory activity not only due to its major (monounsaturated fatty acids) but also to its minor (phenolics) components, as reported in the last years. However, only a limited number of studies were performed on pediatric population, and even fewer are those focusing on EVOO phenolics that investigate the correlation of the chemical characterization with the biological function. Thus, starting from our in vitro data identifying an EVOO chemical profile characterized by a high content of secoiridoids correlating with an anti-inflammatory effect, we studied the ability of an EVOO extract with the same chemical profile to retain this function ex vivo. Specifically, peripheral blood mononuclear cells (PBMCs) collected from obese children were treated with EVOO and olive oil extracts, characterized by a low polyphenol content, to study the ability of secoiridoids to dampen the inflammatory response. A reduction of pro-inflammatory CD14+CD16+ monocytes was detected by cytofluorimetric analysis when PBMCs were treated with EVOO as compared to olive oil extracts. According to this, a down modulation of CCL2 and CCL4 chemokines involved in the recruitment of inflammatory cells, was reported in the supernatants of EVOO relative to olive oil extracts treated PBMCs. Moreover, a high-throughput gene expression analysis revealed that PBMCs molecular profile from obese children is greatly modulated after the treatment with EVOO extract in terms of metabolic and inflammatory pathways. Importantly, some of the significantly modulated genes were involved in the pathways promoting the development of severe obesity. Overall, our ex vivo data demonstrated the ability of EVOO to reduce the inflammatory milieu of PBMCs from obese children both at protein and molecular levels. Of note, a good correlation between the EVOO chemical profile and the biological modulations in terms of anti-inflammatory activity was reported.

Liver Fibrosis Indices Predict the Severity of SARS-CoV-2 Infection.

Discovering novel risk and prognostic factors for COVID-19 may help not only in reducing severity and mortality but also in creating targeted therapies considering patients' individual features. Liver fibrosis is considered a complication in Non-alcoholic Fatty Liver Disease (NAFLD), it is a feature of steatohepatitis (NASH), and it has already been related to an increased risk for a wide range of diseases. Here, we aimed to define if any parameter assessing metabolic status has predictive power in identifying inpatients at risk for poorer prognosis and an increased mortality from COVID-19. This retrospective study was conducted at the Sub-Intensive Medicine Care Unit of the Presidio Maxi-Emergenze Fiera del Levante, Azienda Ospedaliero-Universitaria Policlinico di Bari, Italy. We evaluated 271 inpatients with moderate-to-severe SARS-CoV-2-related respiratory failure by comparing biochemical features and non-invasive liver fibrosis scores among discharged, transferred to Intensive Care Units (ICU) and non-survivor patients. Moreover, by performing ROC curves, we defined cut-off values to predict mortality and disease severity for each score. We found that non-invasive scores of liver fibrosis, obtained at day of admission, such as AAR (p < 0.001), FIB-4 and mFIB-4, FORNS, and AARPRI (p < 0.05) strongly predict not only in-hospital mortality but also the length of hospitalization and eventual admission to ICU. FIB-4 was the best score to identify non-survivor patients (sensitivity of 80% and specificity of 63%) and predict the need for ICU or mortality (71% of sensitivity and 65% of specificity), with a cut-off value of 1.94. Therefore, we present the predictive power and the cut-off values of several liver fibrosis scores here for disease severity and mortality in SARS-CoV-2 in-patients and we proposed the use of the present scores to identify ab initio the clinical therapeutic and diagnostic protocols for high-risk patients.