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Hemophilia A is a hemorrhagic disorder caused by insufficient or inadequate coagulation factor VIII activity. Two different forms are described: congenital, hereditary X-linked, and acquired. Acquired hemophilia A (AHA) is a rare condition and it is defined by the production of autoantibodies neutralizing factor VIII, known as inhibitors. We report the case of a 72-year-old man with a clinical diagnosis of AHA after SARS-CoV-2 infection, which has been described in association with several hematological complications. SARS-CoV-2 infection could represent the immunological trigger for the development of autoantibodies. In our patient, SARS-CoV-2 infection preceded the hemorrhagic complications by 15 days. This lag time is in line with the other cases reported and compatible with the development of an intense immune response with autoantibody production. It is possible that since our patient was affected by type 1 diabetes mellitus, he was more prone to an immune system pathological response against self-antigens. A prompt, appropriate therapeutic intervention with activated recombinant factor VII administration and cyclophosphamide has led to rapid remission of clinical and laboratory findings.

The development of preventive and therapeutic vaccines has played a crucial role in preventing infections and treating chronic and non-communicable diseases, respectively. For a long time, the influence of sex differences on modifying health and disease has not been addressed in clinical and preclinical studies. The interaction of genetic, epigenetic, and hormonal factors plays a role in the sex-related differences in the epidemiology of diseases, clinical manifestations, and the response to treatment. Moreover, sex is one of the leading factors influencing the gut microbiota composition, which could further explain the different predisposition to diseases in men and women. In the same way, differences between sexes occur also in the immune response to vaccines. This narrative review aims to highlight these differences, focusing on the immune response to vaccines. Comparative data about immune responses, vaccine effectiveness, and side effects are reviewed. Hence, the intricate interplay between sex, immunity, and the gut microbiota will be discussed for its potential role in the response to vaccination. Embracing a sex-oriented perspective in research may improve the efficacy of the immune response and allow the design of tailored vaccine schedules.

All-cause mortality related to the SARS-CoV-2 infection has declined from the first wave to subsequent waves, probably through vaccination programs and the availability of effective antiviral therapies. Our study aimed to evaluate the impact of the SARS-CoV-2 vaccination on the prognosis of infected patients. Overall, we enrolled 545 subjects during the Delta variant wave and 276 ones during the Omicron variant wave. Data were collected concerning vaccination status, clinical parameters, comorbidities, lung involvement, laboratory parameters, and pharmacological treatment. Outcomes were admission to the intensive care unit (ICU) and 30-day all-cause mortality. Overall, the final sample included 821 patients with a mean age of 62 +/- 18 years [range 18-100], and 59% were men. Vaccinated patients during the Delta wave were 37% (over 3/4 with two doses), while during the Omicron wave they were 57%. Vaccinated patients were older (68 vs. 57 years), and 62% had at least one comorbidity Admission to the ICU was 20%, and the mortality rate at 30 days was 14%. ICU admissions were significantly higher during the Delta wave than during Omicron (OR 1.9, 95% CI 1.2-3.1), while all-cause mortality did not differ. Unvaccinated patients had a higher risk of ICU admission (OR 2.0, 95% CI 1.3-3.1) and 30-day all-cause mortality (OR 1.7, 95% CI 1.3-2.7). Results were consistent for both Delta and Omicron variants. Overall, vaccination with at least two doses was associated with a reduced need for ICU admission. Even one shot of the vaccine was associated with a significantly reduced 30-day mortality.

Vaccines are among the most effective health measures and have contributed to eradicating some diseases. Despite being very effective, response rates are low in some individuals. Different factors have been proposed to explain why some people are not as responsive as others, but what appears to be of critical importance is the presence of a healthy functioning immune system. In this respect, a key factor in modulating the immune system, both in its adaptive and innate components, is the microbiota. While microbiota can be modulated in different ways (i.e., antibiotics, probiotics, prebiotics), an effective and somewhat obvious mechanism is via nutrition. The science of nutrients and their therapeutic application is called immunonutrition, and it is increasingly being considered in several conditions. Our review will focus on the importance of nutrition and microbiota modulation in promoting a healthy immune system while also discussing the overall impact on vaccination response.

Heart failure is a complex health issue, with important consequences on the overall wellbeing of patients. It can occur both in acute and chronic forms and, in the latter, the immune system appears to play an important role in the pathogenesis of the disease. In particular, in the forms with preserved ejection fraction or with only mildly reduced ejection fraction, some specific associations with chronic inflammatory diseases have been observed. Another interesting aspect that is worth considering is the role of microbiota modulation, in this context: given the importance of microbiota in the modulation of immune responses, it is possible that changes in its composition may somewhat influence the progression and even the pathogenesis of heart failure. In this narrative review, we aim to examine the relationship between immunity and heart failure, with a special focus on the role of microbiota in this pathological condition.

Purpose: The pandemic diffusion of Coronavirus Disease 2019 (COVID-19) has highlighted significant genderrelated differences in disease severity. Despite several hypotheses being proposed, how the genetic background of COVID-19 patients might impact clinical outcomes remains largely unknown. Methods: We collected blood samples from 192 COVID-19 patients (115 men, 77 women, mean age 67 +/- 19 years) admitted between March and June 2020 at two different hospital centers in Italy, and determined the allelic distribution of nine Single Nucleotide Polymorphisms (SNPs), located at the 3 ' Regulatory Region (3 ' RR)-1 in the immunoglobulin (Ig) heavy chain locus, including *1 and *2 alleles of polymorphic hs1.2 enhancer region. Results: In COVID-19 patients, the genotyped SNPs exhibited strong Linkage Disequilibrium and produced 7 specific haplotypes, associated to different degrees of disease severity, including the occurrence of pneumonia. Additionally, the allele *2, which comprises a DNA binding site for the Estrogen receptor alpha (ER alpha) in the polymorphic enhancer hs1.2 of 3 ' RR-1, was significantly enriched in women with a less severe disease. Conclusions: These findings document genetic variants associated to individual clinical severity of COVID-19 disease. Most specifically, a novel genetic protective factor was identified that might explain the sex-related differences in immune response to Sars-COV-2 infection in humans.

Systemic autoinflammatory diseases (SAIDs) are defined by recurrent febrile attacks associated with protean manifestations involving joints, the gastrointestinal tract, skin, and the central nervous system, combined with elevated inflammatory markers, and are caused by a dysregulation of the innate immune system. From a clinical standpoint, the most known SAIDs are familial Mediterranean fever (FMF); cryopyrin-associated periodic syndrome (CAPS); mevalonate kinase deficiency (MKD); and periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome. Current guidelines recommend the regular sequential administration of vaccines for all individuals with SAIDs. However, these patients have a much lower vaccination coverage rates in ‘real-world’ epidemiological studies than the general population. The main purpose of this review was to evaluate the scientific evidence available on both the efficacy and safety of vaccines in patients with SAIDs. From this analysis, neither serious adverse effects nor poorer antibody responses have been observed after vaccination in patients with SAIDs on treatment with biologic agents. More specifically, no new-onset immune-mediated complications have been observed following immunizations. Post-vaccination acute flares were significantly less frequent in FMF patients treated with colchicine alone than in those treated with both colchicine and canakinumab. Conversely, a decreased risk of SARS-CoV-2 infection has been proved for patients with FMF after vaccination with the mRNA-based BNT162b2 vaccine. Canakinumab did not appear to affect the ability to produce antibodies against non-live vaccines in patients with CAPS, especially if administered with a time lag from the vaccination. On the other hand, our analysis has shown that immunization against Streptococcus pneumoniae, specifically with the pneumococcal polysaccharide vaccine, was associated with a higher incidence of adverse reactions in CAPS patients. In addition, disease fla

The Mediterranean diet (MedD) has been shown to have beneficial effects on health, well-being, and mental status. It potentially modulates gene expressions linked to oxidative stress, contributing to its beneficial effects on overall health. The aim of this study was to assess the effects of MedD treatment in healthy human volunteers on the expression of ten genes related to oxidative stress and inflammation in women and men. Of 30 enrolled subjects, 17 were eligible, 10 women and 7 men. All of them received the same MedD treatment. Before and after 8 weeks of MedD treatment, an evaluation of body composition, blood tests, and anthropometric and clinical parameters was performed. Furthermore, 10 genes were amplified and analyzed. The study showed significant differences between females and males in body composition and biochemical parameters before and after MedD treatment. Significant differences between females and males in Resistance Force (p < 0.009) and Diastolic Blood Pressure (p < 0.04) before MedD treatment, and in High-Density Lipoprotein (p < 0.02) after MedD treatment, were observed. Moreover, a significant upregulation of Apolipoprotein E and Angiotensin I-Converting Enzyme in females has been shown. Sex differences impact MedD treatment response, and influence the genetic expression of genes related to oxidative stress; our findings may help to personalize diet therapy and contribute to overall health and well-being.

OBJECTIVE: This study examines the role of MTHFR gene polymorphism (rs1801133) in women with lipedema (LIPPY) body composition parameters compared to a control group (CTRL). SUBJECTS AND METHODS: We carried out a study on a sample of 45 LIPPY and 50 women as a CTRL. Body composition parameters were examined by Dual-energy X-ray Absorptiome-try (DXA). A genetic test was performed for the MTHFR polymorphism (rs1801133, 677C>T) using a saliva sample for LIPPY and CTRL groups. Mann-Whitney tests evaluated statistically significant differences between four groups (carriers and non-carriers of the MTHFR polymorphism for LIPPY and CTRL groups) on anthropometric/body composition parameters to identify patterns. RESULTS: LIPPY showed significantly higher (p<0.05) anthropometric parameters (weight, BMI, waist, abdominal, hip circumferences) and lower waist/hip ratio (p<0.05) compared to the CTRL group. The association between the polymorphism alleles related to the rs1801133 MTHFR gene and the body composition values LIPPY carriers (+) showed an increase in fat tissue of legs and fat region of legs percentage, arm’s fat mass (g), leg’s fat mass (g), and leg’s lean mass (g) (p<0.05) compared to CTRL (+). Lean/ fat arms and lean/fat legs were lower (p<0.05) in LIPPY (+) than in CTRL (+). In the LIPPY (+), the risk of developing the lipedema disease was 2.85 times higher (OR=2.85; p<0.05; 95% confidence interval = 0.842-8.625) with respect to LIPPY (-) and CTRL. CONCLUSIONS: The presence or absence of MTHFR polymorphism offers predictive parameters that could better characterize women with lipedema based on the association between body composition and MTHFR presence.

This study aimed to identify adherence to the Mediterranean diet (MedDiet) and its effect on health and environmental and socioeconomic sustainability during the COVID-19 pandemic among a sample of the Italian population. Notably, it intended to assess the effect of adherence to the MedDiet on ecological footprints and food expenditure. A survey was conducted from the 5th to the 24th of April 2020 on Google Forms. The MEDAS questionnaire was used to determine the level of adherence to the MedDiet. The carbon footprint (CO2), water footprint (H2O), and food cost were calculated. In total, 3353 participants completed the questionnaire, ranging from 18 to 86 years old. A statistically significant difference was observed in the CO2 and H2O among BMI groups (p < 0.001). The low- and medium-MEDAS groups showed higher CO2 (p < 0.001). The food cost (EUR/week) resulted in statistically significant differences among the MEDAS groups. The CO2 results were significantly lower in organic-market buyers compared to non-organic-market buyers (p < 0.001). Public health must promote awareness of how adhering to a healthy lifestyle and making appropriate food choices can positively impact our health and social and economic well-being.

Vaccine immunogenicity still represents an unmet need in specific populations, such as people from developing countries and “edge populations”. Both intrinsic and extrinsic factors, such as the environment, age, and dietary habits, influence cellular and humoral immune responses. The human microbiota represents a potential key to understanding how these factors impact the immune response to vaccination, with its modulation being a potential step to address vaccine immunogenicity. The aim of this narrative review is to explore the intricate interactions between the microbiota and the immune system in response to vaccines, highlighting the state of the art in gut microbiota modulation as a novel therapeutic approach to enhancing vaccine immunogenicity and laying the foundation for future, more solid data for its translation to the clinical practice.

Inflammatory bowel diseases (IBDs) are characterized by a persistent low-grade inflammation that leads to an increased risk of colorectal cancer (CRC) development. Several factors are implicated in this pathogenetic pathway, such as innate and adaptive immunity, gut microbiota, environment, and xenobiotics. At the gut mucosa level, a complex interplay between the immune system and gut microbiota occurs; a disequilibrium between these two factors leads to an alteration in the gut permeability, called ‘leaky gut’. Subsequently, an activation of several inflammatory pathways and an alteration of gut microbiota composition with a proliferation of pro-inflammatory bacteria, known as ‘pathobionts’, take place, leading to a further increase in inflammation. This narrative review provides an overview on the principal Pattern Recognition Receptors (PRRs), including Toll-like receptors (TLRs) and NOD-like receptors (NLRs), focusing on their recognition mechanisms, signaling pathways, and contributions to immune responses. We also report the genetic polymorphisms of TLRs and dysregulation of NLR signaling pathways that can influence immune regulation and contribute to the development and progression of inflammatory disease and cancer.