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Background: The Italian population’s habits changed dramatically during the “COVID- 19 lockdown” due to physical distancing and self-isolation. Moreover, medical consultations of patients with chronic diseases, such as type 2 diabetes (T2D), were suspended or postponed, unless urgent or semi-urgent, for several consecutive months. Thus, it is expected that the lockdown could have affected glucometabolic control in T2D. Purpose: The aim of the study was to assess changes in glucometabolic control in a cohort of T2D patients before (T1) and after (T2) the COVID-19 lockdown (March-May 2020). Methods: The study was approved by the Ethics Committee of the University of Bari, and all patients provided informed written consent to participate. Medical history, complete physical examination, and laboratory assessment were conducted as real-life clinical practice. Changes in clinical and laboratory variables between T1 and T2 were calculated. Results: In detail, 13 patients were on metformin as monotherapy, 36 on GLP-1RA, 12 on sodiumglucose transporter 2 inhibitors (SGLT-2i), and 2 on dipeptidyl-peptidase 4 inhibitors (DPP4i). The mean age was 65.3 years (43-83). Study participants were mainly men (73%). The body weight (BW) ranged from 56 to 145 kg, and the waist circumference ranged from 88 to 146 cm. The mean HbA1c was 51.0 mmol/mol. At T2, no statistically significant changes were observed from baseline except for BW [-1.6 (-2.60 to -0.62)] and HbA1c [-2.90 (-4.69; -1.12)]. Conclusion: We evaluated the effects of the COVID-19 lockdown on glucometabolic control in patients with background well-controlled T2D. We found that the lockdown had no adverse effects on metabolic profile regardless of background clinical characteristics and antihyperglycemic management. Despite limitations due to the nature of this study (sample size, retrospective observation, lack of data on lifestyle changes in our patients' everyday lives), T2D patients managed in our Diabetes Centers faced the lockdown-related restrictions without any detrimental consequence.

Aims: Metformin is the most widely used drug for the first-line treatment of type 2 diabetes mellitus (T2DM), but its use and schedule have been poorly investigated in elderly patients. Methods: We conducted an observational, cross-sectional, multicentric study on metformin in T2DM outpatients older than 65 years who were taking the drug for at least 6 months and referred to Italian Endocrinology and Diabetology Services. The primary endpoint was daily metformin dose, and secondary endpoints were the correlations between metformin dose and age, comorbidities, and concomitant use of other drugs. The study was open to all members of AME (Associazione Medici Endocrinologi). Results: Fifteen Italian centers recruited 751 consecutive participants (42.9% older than 75 years, 48.6% females). T2DM duration was 12.9 ± 9.7 years (longer than 10 years in 53.8%). Metformin had been used for 10.3 ± 6.8 years (longer than 10 years in 52.4%). Metformin dose was 1.6 ± 0.9 g/day (>1.5 g/day in 63.4%). As compared to the youngest, participants older than 75 years did not differ for metformin daily dose or number of administrations. Metformin dose was significantly directly correlated to eGFR, diabetes duration, and metformin treatment duration. Conclusion: In this real-world study, the minimum daily effective dose of metformin was prescribed in more than half of older T2DM outpatients.

Background: Evidence shows that a low-grade inflammation sustains type 2 diabetes (T2D). Pancreatic macrophages release cytokines and chemokines that play a fundamental role in the pathophysiology of islet damage and destruction of beta-cells. Pathogenesis: The authors discuss the main mechanism by which resident (pancreatic) and circulating macrophages regulate beta-cell development and survival in several scenarios, including T2D, type 1 diabetes mellitus, obesity, and insulin resistance. Data are mostly related to in vitro and animal studies. Natural Products: Lastly, an overview of the role of the Mediterranean diet components (i.e., polyphenols, polyunsaturated fatty acids, prebiotics, probiotics, and vitamins) will be illustrated as potential agents for reducing inflammation and oxidative stress in patients with T2D when used along with antihyperglycemic treatments.

Background: Due to the COVID-19 pandemic, current epidemiological conditions may exacerbate the risk of new-onset, recurrence and relapse of eating disorders. This perspective aims to better analyse the phenomenon. Results: Some data suggest that new-onset and recurrence/relapse of eating disorders are increasing due to the pandemic. Government restrictions, self-confinement, social isolation, restriction to healthcare facilities access, delayed access to diagnosis and cure, fear of contagion, distress and difficulties related to the telemedicine approach contribute to this burden. The Immune system dysfunction usually observed in undernourishment (e.g., anorexia nervosa) could delay the diagnosis of respiratory infections, including COVID-19, and predispose to possible bacterial superinfections. Conversely, patients with binge eating, obesity or metabolic syndrome are susceptible to high-grade systemic inflammation and poor prognosis once the infection has occurred. Discussion: More detailed data combining research on eating disorders and COVID-19 are required despite some evidence. Many data show that telemedicine has beneficial aspects, but its impact on long-term mental health is still poorly understood. Short- and long-term consequences of COVID-19 in patients with eating disorders are unknown, but they will likely become more apparent over time. Conclusion: Working on emotion regulating strategies in a post-pandemic world, when people have inadequate control over the background of negative emotions, could be a future treatment strategy. Long-term studies with a larger sample size are essential to assess the long-term consequences of the blockade on patients and their healthcare providers and identify useful strategies to improve clinical management.

Background Erectile function depends on a complex interaction between demographic, metabolic, vascular, hormonal, and psychological factors that trigger erectile dysfunction (ED). In the present study we carried out a cross-sectional study assessing the impact of non-communicable chronic diseases (NCDs), male hypogonadism, and demographic factors in characterizing men with ED. Four hundred thirty-three consecutive outpatients with ED were extracted from the electronic database from January 2017 to December 2019. The International Index of Erectile Function (IIEF) 5 score was used to diagnose ED and stratify its severity, standardized values of serum testosterone (10.5 nM/L) and luteinizing hormone (LH 9.4 IU/L) to diagnose and classify male hypogonadism and the Charlson Comorbidity Index (CCI) to weigh the role of each NCD on ED. Results Forty-six percent of participants were eugonadal (EuG), 13% had organic hypogonadism (OrH), and the remaining 41% had functional hypogonadism (FuH). Hypogonadal men had a significantly lower IIEF 5 score (p p p p Conclusion Serum FT, SHBG, and CCI are the leading determinants of ED severity. Besides overt hypogonadism, a relevant burden of severe NTCDs in middle-aged or older adults features the patient’s characteristics who will suffer from severe ED. Appropriate clinical approaches and, when necessary, treatments are required in these clusters of patients.

Background: In the first section of this review, we examined the neuroanatomical and neurochemical data on hunger and satiety centers, glucose receptors, sensorial influences on eating behavior, and regulation of energy requirements. The second section is devoted to orexigenic and anorexigenic hormones. Objective: This paper aimed to overview and summarize data regarding the role of neuroendocrine regulation of food intake and eating behavior. Methods: Appropriate keywords and MeSH terms were identified and searched in MEDLINE/PubMed. References of original articles and reviews were examined. Discussion and conclusion: Hunger and satiety center are located in the lateral (LH) and ventromedial hypothalamus (VMH). Lasting aphagia has been observed following a lesion of LH, while hyperphagia is induced by LH stimulation. On the other hand, increased food intake after VMH lesion and aphagia following VMH stimulation in hungry animals has also been reported. Intracellular glucopenia triggers food intake by reducing neuronal activity at the satiety center level. Moreover, sensory influences are regulated by food palatability as the positive hedonic evaluation of food and energy requirement indicates the average amount of food energy needed to balance energy expenditure. Orexigenic and anorexigenic hormones secreted from the gastrointestinal tract and adipose tissue regulate brain areas involved in eating behavior via gastric afferent vagal nerve, circumventricular organ area postrema, or transporter system. Finally, oxytocin (OT) plays a role in reward-related eating by inhibiting sugar intake and decreasing palatable food intake by suppressing the reward circuitry in the brain. Moreover, the anorectic effect of nesfatin-1 is abolished by an OT antagonist.

Background Nirmatrelvir/ritonavir, the first severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protease inhibitor, reduces the risk of hospitalization and death by coronavirus disease 2019 (COVID-19) but has been associated with symptomatic rebound after therapy completion. Methods Six individuals with relapse of COVID-19 symptoms after treatment with nirmatrelvir/ritonavir, 2 individuals with rebound symptoms without prior antiviral therapy and 7 patients with acute Omicron infection (controls) were studied. Soluble biomarkers and serum SARS-CoV-2 nucleocapsid protein were measured. Nasal swabs positive for SARS-CoV-2 underwent viral isolation and targeted viral sequencing. SARS-CoV-2 anti-spike, anti–receptor-binding domain, and anti-nucleocapsid antibodies were measured. Surrogate viral neutralization tests against wild-type and Omicron spike protein, as well as T-cell stimulation assays, were performed. Results High levels of SARS-CoV-2 anti-spike immunoglobulin G (IgG) antibodies were found in all participants. Anti-nucleocapsid IgG and Omicron-specific neutralizing antibodies increased in patients with rebound. Robust SARS-CoV-2–specific T-cell responses were observed, higher in rebound compared with early acute COVID-19 patients. Inflammatory markers mostly decreased during rebound. Two patients sampled longitudinally demonstrated an increase in activated cytokine-producing CD4+ T cells against viral proteins. No characteristic resistance mutations were identified. SARS-CoV-2 was isolated by culture from 1 of 8 rebound patients; Polybrene addition increased this to 5 of 8. Conclusions Nirmatrelvir/ritonavir treatment does not impede adaptive immune responses to SARS-CoV-2. Clinical rebound corresponds to development of a robust antibody and T-cell immune response, arguing against a high risk of disease progression. The presence of infectious virus supports the need for isolation and assessment of longer treatment courses. Clinical trials registration NCT04401436.

BACKGROUND: Prospective genetic evaluation of patients at our referral research hospital presents clinical research challenges. OBJECTIVE: This study sought not only a single-gene explanation for participants’ immune-related presentations, but viewed each participant holistically, with the potential to have multiple genetic contributions to their immune-phenotype and other heritable comorbidities relevant to their presentation and health. METHODS: We developed a program integrating exome sequencing, chromosomal microarray, phenotyping, results return with genetic counseling, and reanalysis in 1505 individuals from 1000 families with suspected or known inborn errors of immunity. RESULTS: Probands were 50.8% female, 71.5% ≥18 years, and had diverse immune presentations. Overall, 327/1000 probands (32.7%) received 361 molecular diagnoses. These included 17 probands with diagnostic copy number variants, 32 probands with secondary findings, and 31 probands with multiple molecular diagnoses. Reanalysis added 22 molecular diagnoses, predominantly due to new disease-gene associations (9/22, 40.9%). One-quarter of the molecular diagnoses (92/361) did not involve immune-associated genes. Molecular diagnosis was correlated with younger age, male sex, and a higher number of organ systems involved. This program also facilitated the discovery of new gene-disease associations such as SASH3-related immunodeficiency. A review of treatment options and ClinGen actionability curations suggest that at least 251/361 (69.5%) of these molecular diagnoses could translate into ≥1 management option. CONCLUSION: This program contributes to our understanding of the diagnostic and clinical utility whole exome analysis on a large scale.

Background People with HIV and mycobacterial infections can develop immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy (ART). Severe mycobacterial IRIS has an overlapping clinical phenotype with hemophagocytic lymphohistiocytosis (HLH). We evaluated the pathophysiologic similarities between mycobacterial IRIS and HLH to identify clinical and immune predictors of mycobacterial IRIS severity. Methods HLH criteria were applied to a longitudinal cohort of 80 patients with HIV (CD4 Results HLH-IRIS patients required corticosteroids more frequently (OR: 21.5; 95%CI: 5.6–114.8) and for longer duration (21.2; 95%CI: 10.7–31.7 weeks) than those not meeting HLH criteria. Utilizing decision tree analyses, hemoglobin Conclusions Severe mycobacterial IRIS and HLH have an overlapping pathogenesis involving IFNγ and unopposed T-cell activation causing severe inflammatory disease clinically distinguished by hyperferritinemia (hyperferritinemic IRIS [FIRIS]). Hemoglobin, ferritin, CXCL9, and sCD25 identify high-risk patients and may improve risk stratification and therapeutic strategies for mycobacterial IRIS.

Abstract: Obesity is a growing pandemic. Endocrine-disrupting chemicals are widespread in the en-vironment. In this perspective, the authors examine the issue related to the exposure to several chem-icals with endocrine-disrupting properties as promoting factors to obesity. Data show that Phthalates, Bisphenol compounds, Persistent Organic Pollutants (POPs), solvents, and personal care products can modify metabolic properties in a dose-response and sex-specific manner. Phthalates and bi-sphenol compounds increase body mass index, waist circumference, waist to height ratio, and the sum of skinfold thicknesses in women and not in men. Low-dose exposure to Persistent Organic Pol-lutants is strongly associated with increased body mass index in men and decreased this parameter in women. The mechanism through which these compounds act on anthropometric parameters is not entirely understood. Several studies suggest a possible interference in gonadotropin secretion and the thyroid axis. These inspire a decrease in both total and free testosterone levels in men and FT3 and FT4 levels in women, particularly after a pregnancy. The impact of endocrine disruptor chemicals on adipose tissue inflammation and future cardio-metabolic disorders remains to be elucidated. There-fore, studies involving both healthy and obese individuals are needed to unambiguously confirm re-sults from in vitro and animal models.

Background: Sexual disorders are the most common clinical manifestations of hypogonadism. Functional hypogonadism is the most frequent form, and clomiphene citrate (CC) has been recently introduced as a possible off-label therapeutic option for these patients. Objective: This study aimed to evaluate the effects of CC on the overall sexual function in dysmetabolic obese men with low testosterone (T) levels. Methods: This was a sub-study of a randomized, double-blind, cross-over, placebo-controlled trial that included twenty-four obese or overweight subjects with impaired glucose tolerance or type 2 diabetes and confirmed low total T (≤10.4 nmol/l) levels. Subjects were treated with CC or placebo (Plac) for 12 weeks, with an interval wash-out period of 6 weeks between treatments. All subjects were on metformin 2gr/day and a low-calorie diet. The between-treatment difference in the overall sexual function was assessed by IIEF-15 and a qADAM questionnaire. Results: IIEF-15 and qADAM questionnaire data were available for 18 individuals. In unadjusted analyses, CC was associated with lower IIEF-15 total, erectile function, and intercourse satisfaction domain scores than Plac. After adjustments for multiple variables, CC was associated with a higher IIEF-15 sexual desire domain score (+0.9 ± 0.8; p Discussion: The clinical significance of the absolute changes in IIEF-15 and qADAM scores during CC versus Plac is limited. However, CC has a reliable effect on sexual desire and is also as safe as Plac. According to the sample size, duration of follow-up, and inclusion criteria defined for the main study, further studies are therefore needed to assess the long-term efficacy of CC. Conclusion: Compared to Plac, CC was found to be associated with a neutral effect on overall sexual function.

Plasmodium ovale is a cause of non-falciparum malaria infection that is endemic in tropical Western Africa. The life cycle of Plasmodium ovale includes hypnozoites, which are dormant stages in the liver. These stages can be reactivated after weeks, months, or years from the initial infection, causing disease relapse. This paper reports the case of a female adolescent who presented with high fever and abdominal pain. The girl was referring to a single travel to Nigeria 4 years ago. On that occasion she showed short-term gastrointestinal symptoms, without fever. The blood test revealed thrombocytopenia (76,000/µl) and she was unexpectedly diagnosed with ma-laria through blood smear. Considering the geographical area of her previous travel, a parasitemia by Plasmodium ovale was suspected. The diagnosis was soon confirmed by the positivity of the PCR. The literature describes some cases of recrudescence of the infection from the first episode. The diagnosis of Plasmodium ovale malaria can be challenging because of its possible delayed presentation.

Background: Endocrine Disrupting Chemicals (EDCs) are ubiquitous and may significantly contribute in environmental pollution, thus contaminating humans and wildlife. Environmental pollutants could interfere with bone homeostasis by means of different mechanisms, which include hormonal imbalance, direct osteoblasts toxicity and enanchment of osteoclasts activity, thus leading to osteopenia or osteoporosis. Among these, bisphenols, dioxins, polycyclic aromatic hydrocarbons, polychlorobiphenyls, poly- and perfluoroalkyls, phthalates, parabens, organotins and cadmium may play a role in bone distuption. Methods: PubMed/MEDLINE, ISI-web of knowledge and Google scholar databases were searched for medical subject headings terms and free-text word related to the aforementioned classes of chemicals and bone metabolism and remodelling for better clarifying and understanding the main mechanisms of bone disruption. Results: Several of EDCs act as xenoestrogens. Considering that estrogens play a significant role in regulating bone remodeling, most of these chemicals generate hormonal imbalance with possible detrimental consequences on bone tissue structure and its mechanical and non-mechanical properties. Discussion: A lot of evidences about bone distruptors came from in vitro studies or animal models, and conduct to equivocal results. In addition, a few data derived form humans and most of these data focused on the impact of EDCs on bone mineral density without considering their influence on long-term fracture risk. Moreover, it should be taken into account that humans are exposed to a mixture of EDCs and the final effect on bone metabolism might be the result of either a synergism or antagonist effects among them. Age of first exposure, cumulative dose exposure over time, and the usually observed non-monotonic dose-response curve for EDCs should be considered as other important variable influencing the final effect on bone metabolism. Conclusion: Taking into account these variables, observational studies are needed to better analyze this issue both for echological purpose and to preserve bone health.

Background: Foam cells, mainly derived from monocytes-macrophages, contain lipid droplets essentially composed of cholesterol in their cytoplasm. They infiltrate the intima of arteries, contributing to the formation of atherosclerotic plaques. Pathogenesis: Foam cells damage the arterial cell wall via the release of proinflammatory cytokines, free radicals, and matrix metalloproteinases, enhancing the plaque size up to its rupture. Therapy: A correct dietary regimen seems to be the most appropriate therapeutic approach to minimize obesity, which is associated with the formation of foam cells. At the same time, different types of antioxidants have been evaluated to arrest the formation of foam cells, even if the results are still contradictory. In any case, a combination of antioxidants seems to be more efficient in the prevention of atherosclerosis.

Patients suffering from acute lung injury (ALI) are at a high risk of developing cardiac arrhythmias. Our recent study demonstrated that bleomycin (Bleo)-induced ALI in rats exhibited significantly more spontaneous premature ventricular contractions (PVCs) from one to three weeks post induction. Although spontaneous PVCs disappeared at 4 weeks post ALI, PVCs were evoked again by electrical stimulation of the decentralized stellate ganglia in Bleo-exposed rats but not in normal rats. In the current study, we aimed to utilize non-biased RNA-Seq analysis to identify potential gene candidates in cardiac tissues, which may be associated with cardiac arrhythmia during the recovery from ALI. We created an ALI rat model using a single tracheal instillation of bleomycin (2.5 mg/kg), with saline as a vehicle (Veh) control. Blood troponin level was measured between Veh- and Bleo-treated rats at Week 1 (W1) post Veh/Bleo. Cardiac tissues were harvested at W4 post Veh/Bleo for RNA-seq analysis and following PCR validation. At W1 post ALI, cardiac troponin level was significantly increased in Bleo-treated rats whereas it was undetectable in Veh-treated (Control) rats. RNA-seq analysis indicated 11 downregulated (AABR07045427, Habp2, AC130862, Per2, Coch, Phactr3, Angptl7, LOC103690108, Mthfd2, Sorcs1, U6) and 13 upregulated (Calhm5, Metazoa_SRP, Tgm1, Pcare, Drd4, Selplg, AABR07027722; Rn5-8s, 5_8S_rRNA) genes in cardiac tissues at 4 weeks post ALI vs Veh. PCR validated that the gene expressions of Habp2, Coch, Phactr3, LOC103690108, Mthfd2 were significantly downregulated and the gene expressions of Pcare, Drd4 were significantly upregulated in the hearts of Bleo-treated rats at W4 post ALI. Our study demonstrated that multiple gene changes in cardiac tissues are associated with cardiac injury and arrhythmogenesis in bleomycin-induced ALI in male rats. Future studies will further determine the cause-effect relationship between these altered genes and cardiac arrhythmia post ALI. This study was supported by NIH grant R01 HL-152160 and in part, by NIH grants R01 HL126796. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Introduction: Atherosclerotic Cardiovascular Diseases (CVD) are among the most relevant causes of morbidity and mortality worldwide, especially in aged people. Statins are one of the leading pharmacological interventions against atherosclerosis and are widely used to reduce the risk of occurring coronary artery diseases and related outcomes in both primary and secondary prevention. The management of chronic diseases is improved considerably over time, leading to an increase in life expectancy despite heavier comorbidity-related burdens in the elderly. Aims: The paper focused on the role of statins in the management of atherosclerosis and related burdens in elderly patients. Results: Statins are essential in reducing the risk of CVD in secondary and primary prevention, particularly in high-risk individuals. Guidelines encourage using specific algorithms with age-specific cut-offs to assess individual cardiovascular risk irrespective of baseline age, as the expansion of life expectancy produces favorable effects of statin treatment in those over 70. Discussion: Besides the estimation of baseline CV risk, a specific age-related assessment is also necessary before prescribing statin treatment in aged people focusing on frailty, potential pharmacological interactions due to polypharmacotherapy, cognitive impairment, and background chronic comorbidities, such as diabetes mellitus. Before starting statin therapy, an accurate choice of type and dose of statins is needed as potential adverse events are more prevalent with high-dose than low-to-moderate-dose regimens and with lipophile than hydrophile statins (e.g., potential implication on intra-cerebral cholesterol metabolism). Conclusion: Despite possible adverse events, elderly patients should receive statins, when appropriate, to avoid the first occurrence of recurrent cardiovascular events and related burdens.

People with HIV (PWH) and mycobacterial infections can develop immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy. The pathophysiology of mycobacterial-IRIS overlaps with primary hemophagocytic lymphohistiocytosis (pHLH). To assess possible genetic predisposition to IRIS, protein-altering variants in genes associated with HLH were evaluated in 82 PWH and mycobacterial infections who developed IRIS (n = 56) or did not develop IRIS (n = 26). Protein-altering variants in cytotoxicity genes were found in 23.2% of IRIS patients compared to only 3.8% of those without IRIS. These findings suggest a possible genetic component in the risk of mycobacterial IRIS in PWH. Clinical Trials Registration. NCT00286767, NCT02147405.

OBJECTIVE: HIV infection disrupts the cytokine network and this disruption is not completely reversed by antiretroviral therapy (ART). Characterization of cytokine changes in blood and genital secretions is important for understanding HIV pathogenesis and the mechanisms of HIV sexual transmission. Here, we characterized the cytokine network in individuals longitudinally sampled before they began ART and after achieving suppression of HIV RNA. METHODS: We measured concentrations of 34 cytokine/chemokines using multiplex bead-based assay in blood and seminal plasma of 19 men with HIV-1 prior to and after viral suppression. We used Partial Least Squares Discriminant Analysis (PLS-DA) to visualize the difference in cytokine pattern between the time points. Any cytokines with VIP scores exceeding 1 were deemed important in predicting suppression status and were subsequently tested using Wilcoxon Signed Rank Tests. RESULTS: PLS-DA projections in blood were fairly similar before and after viral suppression. In contrast, the difference in PLS-DA projection observed in semen emphasizes that the immunological landscape and immunological needs are very different before and after ART in the male genital compartment. When tested individually, four cytokines were significantly different across time points in semen (MIG, IL-15, IL-7, I-TAC), and two in blood (MIG and IP-10). CONCLUSIONS: Viral suppression with ART impacts the inflammatory milieu in seminal plasma. In contrast, the overall effect on the network of cytokines in blood was modest, but consistent with prior analyses. These results identify specific changes in the cytokine networks in semen and blood as the immune system acclimates to chronic, suppressed HIV infection.

Background: Bone health relies on the equilibrium between resorption and new bone generation. Postmenopausal osteoporosis depends on estrogen deficiency which favorite bone resorption and elevated risk of fractures. Moreover, osteoporosis is characterized by a high release of proinflammatory cytokines suggesting the role of the immune system in the pathogenesis of this complex disease (immunoporosis). Aims: To review the pathophysiology of osteoporosis from an endocrinological and immunological viewpoint and treatments with a specific focus on nutraceuticals. Methods: PubMed/MEDLINE, Scopus, Google Scholar, and institutional web site were searched. Original articles and reviews were screened and selected by September 2022. Results: The activation of the Gut Microbiota-Bone Axis contributes to bone health by releasing several metabolites, including short-chain fatty acids (SCFAs), that facilitate bone mineralization directly and indirectly by the induction of T regulatory cells, triggering anti-inflammatory pathways. Conclusion: Treatments of postmenopausal osteoporosis are based on lifestyle changes, calcium and vitamin D supplementation, and anti-resorptive and anabolic agents, such as bisphosphonates, Denosumab, Teriparatide, Romosozumab. However, phytoestrogens, polyphenols, probiotics, and polyunsaturated fatty acids may improve bone health by several mechanisms, including anti-inflammatory properties. Specific clinical trials are needed to assess the efficacy/effectiveness of the possible anti-osteoporotic activity of natural products as add on to background treatment.

BackgroundChronic heart failure (CHF) affects the health care system with high social and economic costs due to recurrent hospital admissions or frequent ambulatory reassessments. Subclinical hypothyroidism (SCH) is commonly observed in patients with CHF and negatively affects myocardial function and remodeling and, ultimately, increases the risk of hospitalizations and all-cause and cardiovascular (CV) mortality. The role of levothyroxine replacement on relevant CV outcomes in patients with SCH and CHF is unclear.ObjectiveTo assess the effect of levothyroxine (compared to placebo or no treatment) on the incidence of all-cause and CV mortality, major adverse CV events, and heart failure in patients with SCH and CHF.MethodsPubMed/MEDLINE, Cochrane Library, and ClinicalTrial.gov were searched for randomized clinical trials, non-randomized observational, multicentric, and comparative studies. No language restrictions were included. After duplicate removal, articles were screened and extracted for the synthesis according to a hierarchical strategy that included title, abstract, and full-text appraisal. The risk of bias was assessed by RoB2 and ROBIN-I tools. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to rate the quality of evidence and grade the strength of recommendations.ResultsTwo trials were included in the systematic review with considerable indirectness and inaccuracy that down-graded the level of evidence.DiscussionNo evidence supports the use of levothyroxine for treating SCH in CHF due to the lack of reliable and well-designed clinical trials.ConclusionCV outcome and dose-response trials are needed to understand better the role of levothyroxine replacement treatment for a safer prescription in this clinical setting.

Clonal hematopoiesis (CH) describes the disproportionate expansion of a hematopoietic stemcell (HSC) and its progeny, in association with leukemia-associated somatic mutations, mostcommonly affecting the genes for epigenetic regulators DNMT3A, TET2 and ASXL1.The prevalence and size of such clones rise with age, in association with changes in the driver gene landscape.10 CH is associated with an increased risk of hematologic malignancies, but also of cardiovascular disease (CVD), independently of other known CVD risk factors.11,12 The basis forthis increased CVD risk has been linked to hyperinflammatory positive feedback loops driven by increased cytokine release from clonal myeloid cells, particularly interleukin IL-6 and IL-1β.

Chronic heart failure represents a relevant concern for public health. The endocrine system is heavily involved in the induction and progression of chronic heart failure. Among endocrine disorders, the most relevant alterations are related to the growth hormone-insulin like growth factor 1 axis, serum testosterone, dehydroepiandrosterone sulfate, triiodothyronine levels, insulin resistance, and type 2 diabetes mellitus. It is currently debated whether these changes might be simple adaptive mechanisms or, instead, they may deteriorate myocardial pump function over time. In this commentary on a recently published paper by Antonio Cittadini et al. (Eur J Prev Cardiol. 2021), we briefly presented and discussed data form the “Trattamento Ormonale nello Scompenso CArdiaco; Hormone Treatment in Heart Failure (TOSCA) Registry”. One or more hormonal deficiencies or metabolic disorders, including insulin resistance and diabetes mellitus, were more commonly diagnosed in patients with heart failure (358 patients, 75% of study group). The presence of multiple hormone deficiency identified a subset of patients at increased risk of hospitalization and death, with a graded relation between the number of deficiencies and total events. This finding suggests a possible causal role of hormone deficiencies in CHF progression. Screening of hormonal and metabolic imbalances in CHF patients would be an interesting opportunity for improving the prognosis of patients with heart failure as it would identify high-risk patients requiring an additional medical management of the underlying endocrine and metabolic disorders.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the pandemic respiratory infectious disease COVID-19. However, clinical manifestations and outcomes differ significantly among COVID-19 patients, ranging from asymptomatic to extremely severe, and it remains unclear what drives these disparities. Here, we studied 159 sequentially enrolled hospitalized patients with COVID-19-associated pneumonia from Brescia, Italy using the VirScan phage-display method to characterize circulating antibodies binding to 96,179 viral peptides encoded by 1,276 strains of human viruses. SARS-CoV-2 infection was associated with a marked increase in immune antibody repertoires against many known pathogenic and non-pathogenic human viruses. This antiviral antibody response was linked to longitudinal trajectories of disease severity and was further confirmed in additional 125 COVID-19 patients from the same geographical region in Northern Italy. By applying a machine-learning-based strategy, a viral exposure signature predictive of COVID-19-related disease severity linked to patient survival was developed and validated. These results provide a basis for understanding the role of memory B-cell repertoire to viral epitopes in COVID-19-related symptoms and suggest that a unique anti-viral antibody repertoire signature may be useful to define COVID-19 clinical severity.

We evaluated the clinical impact, in daily clinical practice, of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) therapies in patients with type 2 diabetes. Data from 500 unselected consecutive patients were retrospectively analyzed. Only those with a full assessment at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment with SGLT2i or GLP1RA were included in the study (n = 167). At baseline, patients had a high mean body weight (BW), abdominal circumference (AC), body mass index (BMI), and HOMA index. Despite normal C-peptide values, 39 patients were being treated with insulin (up to 120 IU/day). During therapy, a progressive improvement in BW, BMI, and AC was observed with both the molecules. Fasting glucose and glycated Hb decrease was already significant at T3 in all patients, while the HOMA index selectively improved with SGLT2i therapy. Renal function parameters remained stable regardless of the drug used. Finally, SGLT2i reduced serum uric acid and improved the lipid profile, while GLP1RA reduced serum levels of liver enzymes. Both the therapeutic regimens allowed a significant reduction or complete suspension of unnecessary insulin therapies. Our real life data confirm the results obtained from randomized clinical trials and should be taken as a warning against inappropriate use of insulin in patients with preserved β-cell function.

Insights from the T.O.S.CA. Registry: Echocardiographic hallmarks and cardiopulmonary exercise test (CPET) results were evaluated at baseline and after an average time of 36 months. T2D patients exhibited a greater intraventricular septum (IVS) thickness (11±2 mm, 10±2 mm, 10±2 mm, in T2D, IR, and EU, respectively; p Commentary: The study findings suggest that the right ventricle structure, function, and cardiopulmonary performance deteriorate with IR and, more evidently, due to chronic exposure to hyperglycemia in T2D. Impaired exercise tolerance, poor cardiorespiratory fitness, diastolic dysfunction, and left atrial enlargement predispose patients to poor quality of life, suboptimal adherence to physical activity, and an overall increase in the risk of all-cause and cardiovascular mortality. In addition, chronic hyperglycemia accelerates the progression of these alterations, especially in patients with poor glycemic control over time. Highly selective and even more non-selective sodium glucose transporter type 2 inhibitors and glucagon-like peptide 1 receptor agonists should be considered as the first-line therapy for improving CV outcomes in T2D and CHF. Further studies are needed to understand the role of these molecules in treating pre-clinical conditions, such as IR and metabolic syndrome.

BackgroundThe detection of thyroid nodules has been increasing over time, resulting in an extensive use of fine-needle aspiration (FNA) and cytology. Tailored methods are required to improve the management of thyroid nodules, including algorithms and web-based tools.Study aimsTo assess the performance of the Thyroid Nodule App (TNAPP), a web-based, readily modifiable, interactive algorithmic tool, in improving the management of thyroid nodules.MethodsOne hundred twelve consecutive patients with 188 thyroid nodules who underwent FNA from January to December 2016 and thyroid surgery were retrospectively evaluated. Neck ultrasound images were collected from a thyroid nodule registry and re-examined to extract data to run TNAPP. Each nodule was evaluated for ultrasonographic risk and suitability for FNA. The sensitivity, specificity, positive and negative predictive values, and overall accuracy of TNAPP were calculated and compared to the diagnostic performance of the other two algorithms by the American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi (AACE/ACE/AME), which it was derived from the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS).ResultsTNAPP performed better in terms of sensitivity (>80%) and negative predictive value (68%) with an overall accuracy of 50.5%, which was similar to that found with the AACE/ACE/AME algorithm. TNAPP displayed a slightly better performance than AACE/ACE/AME and ACR TI-RADS algorithms in selectively discriminating unnecessary FNA for nodules with benign cytology (TIR 2 - Bethesda class II: TNAPP 32% vs. AACE/ACE/AME 31% vs. ACR TI-RADS 29%). The TNAPP reduced the number of missed diagnoses of thyroid nodules with suspicious and highly suspicious cytology (TIR 4 + TIR 5 - Bethesda classes V + VI: TNAPP 18% vs. AACE/ACE/AME 26% vs. ACR TI-RADS 20.5%). A total of 14 nodules that would not have been aspirated were malignant, 13 of which were microcarcinomas (92.8%).DiscussionThe TNAPP algorithm is a reliable, easy-to-learn tool that can be readily employed to improve the selection of thyroid nodules requiring cytological characterization. The rate of malignant nodules missed because of inaccurate characterization at baseline by TNAPP was lower compared to the other two algorithms and, in almost all the cases, the tumors were microcarcinomas. TNAPP’s use of size >20 mm as an independent determinant for considering or recommending FNA reduced its specificity.ConclusionTNAPP performs well compared to AACE/ACE/AME and ACR-TIRADS algorithms. Additional retrospective and, ultimately, prospective studies are needed to confirm and guide the development of future iterations that incorporate different risk stratification systems and targets for diagnosing malignancy while reducing unnecessary FNA procedures.

Concerns over the earth’s ability to sustain itself over the long term as a consequence of human consumption of natural resources points towards sustainable development. Since a large proportion of human consumption is linked to buildings and construction, this means managing the construction process in more sustainable ways. Strategies that target greater material efficiency and which promote circular economy concepts are among several approaches that are gaining in popularity. The adoption of life-cycle thinking and practices in design, construction and end of life through the reuse of construction components and materials is one such action to achieve a sustainable built environment. Reuse is not a new concept and technical solutions do exist; however, practical realization is hampered by many interrelated challenges. This review paper is the result of a literature review for an exploratory study that aims to identify obstacles to the reuse of building components and materials. The context is industrialized housing, particularly timber-based construction, as this is a sector where modern manufacturing and onsite practices have become established. The main obstacles identified and corroborated in the literature, along with their potential solutions, are summarized and conclusions drawn on the future direction of research needs.

Chronic heart failure (CHF) leads to an excess of urgent ambulatory visits, recurrent hospital admissions, morbidity, and mortality regardless of medical and non-medical management of the disease. This excess of risk may be attributable, at least in part, to comorbid conditions influencing the development and progression of CHF. In this perspective, the authors examined and described the most common endocrine disorders observed in patients with CHF, particularly in individuals with reduced ejection fraction, aiming to qualify the risks, quantify the epidemiological burden and discuss about the potential role of endocrine treatment. Thyroid dysfunction is commonly observed in patients with CHF, and sometimes it could be the consequence of certain medications (e.g., amiodarone). Male and female hypogonadism may also coexist in this clinical context, contributing to deteriorating the prognosis of these patients. Furthermore, growth hormone deficiency may affect the development of adult myocardium and predispose to CHF. Limited recommendation suggests to screen endocrine disorders in CHF patients, but it could be interesting to evaluate possible endocrine dysfunction in this setting, especially when a high suspicion coexists. Data referring to long-term safety and effectiveness of endocrine treatments in patients with CHF are limited, and their impact on several “hard” endpoints (such as hospital admission, all-cause, and cardiovascular mortality) are still poorly understood.

Background: Hypothyroidism is a frequently observed comorbidity in patients with chronic heart failure (CHF), possibly giving rise to unfavorable outcomes. Aim: The aim of the study was to evaluate the impact of TSH changes over time on cardiac function and prognosis of outpatients with CHF. Methods: Patients underwent clinical, electrocardiographic, and echocardiographic evaluations at baseline and after 12 months. Moreover, blood chemistry tests were performed to evaluate renal function, cardiac biomarkers, fT3, fT4, and TSH levels. Based on TSH serum levels, patients were retrospectively classified into four categories: Group 1, patients with improved thyroid function at one-year follow up vs. baseline; Group 2, patients with stable and mildly high TSH values (3.74 – 10 mUI/L); Group 3, patients with worsening thyroid function; Euthyroid patients Group, TSH levels within the normal range of reference at baseline as well as at 12 months follow-up. We considered as end-points: one-year changes of laboratory and echocardiographic parameters; hospitalizations due to worsening of HF (acute decompensated heart failure - ADHF); death for all causes. Results: Among 257 patients, 174 (67.7%) were euthyroid at baseline and after 12 months. Group 1 patients (n. 22, 8.6%) showed a significant improvement in systolic and diastolic function, filling pressures, NT-proBNP and Galectin-3. Group 2 patients (n. 34, 13.2%) did not exhibit significant modifications in studied parameters. Group 3 patients (n. 27, 10.5%) showed worsening of diastolic function and NT-proBNP and a greater risk of ADHF (HR: 2.12; 95%CI: 1.20-3.74; p: 0.009) and death (HR: 4.05; 95%CI: 2.01-8.15; p Conclusion: In patients with CHF, changes in thyroid function over time influenced echocardiographic parameters and biomarkers reflecting modifications of cardiac function and prognosis, thus suggesting the clinical relevance of thyroid deficiency screening and correction.

Thermal runaway is a major safety concern in the applications of Li-ion batteries, especially in the electric vehicle (EV) market. A key component to mitigate this risk is the separator membrane, a porous polymer film that prevents physical contact between the electrodes. Traditional polyolefin-based separators display significant thermal shrinkage (TS) above 100 degrees C, which increases the risk of battery failure; hence, suppressing the TS up to 180 degrees C is critical to enhancing the cell's safety. In this article, we deposited thin-film coatings (less than 10 nm) of aluminum oxide by atomic layer deposition (ALD) on three different types of separator membranes. The deposition conditions and the plasma pretreatment were optimized to decrease the number of ALD cycles necessary to suppress TS without hindering the battery performance for all of the studied separators. A dependency on the separator composition and porosity was found. After 100 ALD cycles, the thermal shrinkage of a 15 mu m thick polyethylene membrane with 50% porosity was measured to be below 1% at 180 degrees C, with ionic conductivity >1 mS/cm. Full battery cycling with NMC532 cathodes demonstrates no hindrance to the battery's rate capability or the capacity retention rate compared to that of bare membranes during the first 100 cycles. These results display the potential of separators functionalized by ALD to enhance battery safety and improve battery performance without increasing the separator thickness and hence preserving excellent volumetric energy.

Tirzepatide, a dual agonist of Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-Like Peptide 1 (GLP-1) receptors, improved glucose control and reduced body weight in different therapeutic approaches. Herein, we overviewed the role of GIP and GLP-1 in the pathophysiology of type 2 diabetes and systematically reviewed the efficacy and safety of injectable incretin-based therapy added to basal insulin in light of the results of the SURPASS-5 trial. We identified eleven randomized clinical trials. GLP-1 receptor agonists (GLP-1RAs) or Tirzepatide added to basal insulin than rigorously titrated basal insulin significantly ameliorates glucose control (Δ HbA1c = -1%, 95% CI -1.25; -0.74, I2 94%; Δ FPG = -14.6 mg/dL, 95% CI -21.6-; -7.6, I2 90%; chance to achieve HbA1c <7% = RR 2.62, 95% CI 2.10; 3.26, I2 89%), reduces body weight (Δ = -3.95 kg, 95% CI -5.1, -2.79, I2 96%) without increasing the risk of hypoglycemia (RR = 1.01, 95% CI 0.86; 1.18, I2 7.7%). Tirzepatide provides an impressive weight loss exceeding that observed with GLP-1RAs. Injectable incretin-based therapy plus basal insulin remains a potent and safe therapeutic approach in uncontrolled type 2 diabetes patients previously treated with basal insulin alone. Tirzepatide is expected to ameliorate the management of “diabesity” in this usually difficult-to-treat cluster of patients.

Background: Although FD may affect up to 10% of the general population, the therapy for FD is not standard. Recently, ginger-based food supplements have been proposed in order to restore FD symptoms. Our aim was to assess the efficacy of a new nutraceutical formulation containing extract of gingerol and thymus as a possible natural treatment in managing the symptoms of functional dyspepsia (FD). Methods: We retrospectively analyzed the efficacy and safety profiles of a nutraceutical formulation containing Zingiber officinalis root extract and a standardized Thymus extract. It was administered as 1 ml/day twice a day for 90 days. Patients were assessed at baseline and after 1, 2 and 3 months of treatment, following a month of pharmacological washout by completing a questionnaire reporting the trend of the following symptoms: epigastric pain, epigastric heaviness, early satiety, belching, and regurgitation. Every symptom was assessed by a Visual Analogic Scale (VAS), ranging from 0= absence to 10= maximal severity. Results: We enrolled 272 patients (99 males and 173 females; median IQR age 49.5, 36-64 yrs). Obesity (BMI>30) was present in 28 (12.5%) patients; smokers were 83 (30.5%); and comorbidities were present in 107 (39.3%) patients. Improvement of symptom scores during treatment and one month after its suspension was extremely significant (p Conclusion: This large study found that nutraceutical formulation could be one of the tools for an empirical approach to treat patients with FD, especially when a non-conventional drug treatment is preferable for the patient and considered suitable by the physician.

In this study, abnormal levels of myeloid activation, endothelial damage, and innate immune markers were associated with severe coronavirus disease 2019 (COVID-19), while higher levels of metabolic biomarkers (irisin, leptin) demonstrated a protective effect. These data support a model for COVID-19 immunopathogenesis linking robust inflammation and endothelial damage in metabolically predisposed individuals.

Clinical rebound of COVID-19 after nirmatrelvir/ritonavir treatment has been reported. We performed clinical, virologic, and immune measurements in seven patients with symptomatic rebound, six after nirmatrelvir/ritonavir treatment and one without previous treatment. There was no evidence of severe disease or impaired antibody and T-cell responses in people with rebound symptoms.

Evaluating hepatic metabolic changes in people with HIV (PWH) with advanced disease, before and after antiretroviral therapy (ART) initiation, using [ 18 F]-fluorodeoxyglucose (FDG) PET-computed tomography (PET/CT). FDG PET/CT noninvasively quantifies glucose metabolism in organs.Forty-eight viremic PWH (CD4 + cell counts100 cells/μl) underwent FDG PET/CT at baseline and approximately 6 weeks after ART initiation (short-term). Twenty-seven PWH participants underwent follow-up scans 2 years after treatment (long-term). FDG PET/CT scans from 20 healthy controls were used for comparison. Liver FDG uptake was quantified from the PET/CT scans. Imaging findings as well as clinical, laboratory, and immune markers were compared longitudinally and cross-sectionally to healthy controls.Liver FDG uptake was lower at baseline and short-term in PWH compared with controls ( P 0.0001). At the long-term scan, liver FDG uptake of PWH increased relative to baseline and short-term ( P = 0.0083 and 0.0052) but remained lower than controls' values ( P = 0.004). Changes in FDG uptake correlated negatively with levels of glucagon, myeloperoxidase, sCD14, and MCP-1 and positively with markers of recovery (BMI, albumin, and CD4 + cell counts) ( P 0.01). In multivariable analyses of PWH values across timepoints, BMI and glucagon were the best set of predictors for liver FDG uptake ( P 0.0001).Using FDG PET/CT, we found decreased liver glucose metabolism in PWH that could reflect hepatocytes/lymphocytes/myeloid cell loss and metabolic dysfunction because of inflammation. Although long-term ART seems to reverse many hepatic abnormalities, residual liver injury may still exist within 2 years of treatment initiation, especially in PWH who present with low nadir CD4 + cell counts.

This study is aimed at defining the environmental status of the Mar Piccolo and Mar Grande basins, in the Taranto coastal area (Ionian Sea, Taranto Gulf, southern Italy), through the application of a multidisciplinary approach. The investigated coastal system was affected by intensive environmental changes due to the strong industrialization that has taken place since the second half of the XIX century. In addition, the area is characterized by intense human pressure (in terms of high-density urbanization and the presence of military harbor activities, industries, and aquaculture plants), which contributes to its environmental degradation. The area of Taranto is nowadays one of the most polluted sites in Italy and for this reason, it is included in the perimeter of the Site of National Interest “Taranto” (established by the National Law 426/1998 and delimited by the Ministerial Decree of 10/01/2000) for which urgent environmental remediation is required.The study is based on the integration of geophysical and chemical data acquired in the framework of the interdisciplinary activities funded by the “Special Commissioner for urgent measures of reclamation, environmental improvements, and redevelopment of Taranto” in 2015 and 2017.In this research, we proposed a methodological approach for the assessment of the spatial distribution of direct and indirect anthropogenic impact on the sea-floor, in terms of both presence of macro-litter (elements and/or traces) and chemical pollutants. Specifically, the results derived from the interpretation of the acoustic data (multibeam echosounder - MBES and Side Scan Sonar - SSS) acquired in both basins and chemical analysis, with particular reference to inorganic compounds, performed on the sediment samples of 19 continuous cores collected in the Mar Piccolo, were combined. Following the analytical procedure proposed in previous studies, seafloor morphologies were detected by interpreting the digital elevation model obtained by MBES and integrated by the interpretations of the SSS backscatter mosaic data while the distribution of toxic heavy metals in marine sediments has been explored by using different pollution indicators, generally considered as a useful tool for evaluating the degree of anthropogenic contamination.The integrated results obtained by the multiproxy analysis have allowed us to define the overall distribution of the anthropogenic impact along the Mar Piccolo and Mar Grande basins and to identify hotspot areas for which urgent remediation and management actions should be implemented.

New pieces of evidence suggest that combining basal insulin with glucagone-like peptide 1 receptor agonists (GLP-1RA) in patients with type 2 diabetes could promptly ameliorate glucose control and prevent both hypoglycemic events and unnecessary weight gain compared to more intensive insulin regimens. : To review the efficacy/effectiveness and safety of fixed-ratio combinations of basal insulin and GLP- 1RA (FRCs). : Authors searched PubMed/MEDLINE, ClinicalTrials.gov, Cochrane Library, and Google Scholar for freely available original articles, randomized clinical trials (RCTs), clinical reviews, and meta-analysis written in English until January 2020. : FRCs provide significative reductions in HbA1c levels in both insulin-naïve (-1.4% to -2%) and insulin- experienced (-1.5% to -2%) type 2 diabetic patients with moderate glucose impairment. More patients achieved the recommended glycemic targets on FRCs compared to those on mono-therapy with basal insulin or GLP-1RAs. The intensification with FRCs results in better glycemic control compared to basal insulin at fasting as well as during the postprandial state. The frequency of hypoglycemia is similar or lower in patients treated with FRCs than in those on basal insulin alone at a similar dose. Weight trend can be variable, ranging from -2.7 to +2 Kg for iDegLira and -0.7 to -1.3 Kg for iGlar- Lixi. However, a lower weight gain is obtained with iDegLira compared to iDeg (-2.2 to -2.5 Kg), iGlar (-1.7 to -3.2 Kg), and basal-bolus (-3.6 Kg) as well as with iGlarLixi compared to iGlar (-1.4 Kg). : FRCs should be considered to safely improve the metabolic control in type 2 diabetic patients with moderate glycemic impairment while on oral medications, basal oral regimen or GLP-1RAs. However, a few but significative pieces of evidence suggest that FRCs could be a safe and effective treatment instead of a low dose basal-bolus intensification for patients with mild or moderate glucose impairment in order to reduce the risk of hypoglycemia and unnecessary weight gain, and for simplifying treatment regimen as well.

Background: Obesity is a major public health problem worldwide. Bariatric surgery can reduce body weight, and it is one of the better ways to improve metabolic disease and lifestyle. The aim of this study was to explore a new cohort of patients with obesity and evaluate the gender differences and the steatosis status within the gender group. Methods: A cohort of 250 adult obese patients with BMI ≥ 30 and age >18 years, eligible for gastric bariatric surgery at Pineta Grande Hospital, Castel Volturno (Italy) was studied. Results: The prevalence in women was higher (72.40%) than men (27.60%). Overall, results indicated many statistically significant gender differences in hematological and clinical parameters. Analysis of the subcohorts based on the severity of steatosis revealed differences of this condition between the genders. Steatosis was more prevalent in the male subcohort, but female patients revealed greater within-group differences. Conclusions: Many differences were found not only in the total cohort but also between the gender subcohorts, both in the presence and absence of steatosis. We can conclude that the pathophysiological, genetic, and hormonal patterns affecting these patients delineate different individual profiles.