Search

Low-grade endotoxemia by lipopolysaccharide (LPS) has been detected in COVID-19 and could favor thrombosis via eliciting a pro-inflammatory and pro-coagulant state. The aim of this study was to analyze the mechanism accounting for low-grade endotoxemia and its relationship with oxidative stress and clotting activation thrombosis in COVID-19. We measured serum levels of sNOX2-dp, zonulin, LPS, D-dimer, and albumin in 175 patients with COVID-19, classified as having or not acute respiratory distress syndrome (ARDS), and 50 healthy subjects. Baseline levels of sNOX2-dp, LPS, zonulin, D-dimer, albumin, and hs-CRP were significantly higher in COVID-19 compared to controls. In COVID-19 patients with ARDS, sNOX2-dp, LPS, zonulin, D-dimer, and hs-CRP were significantly higher compared to COVID-19 patients without ARDS. Conversely, concentration of albumin was lower in patients with ARDS compared with those without ARDS and inversely associated with LPS. In the COVID-19 cohort, the number of patients with ARDS progressively increased according to sNOX2-dp and LPS quartiles; a significant correlation between LPS and sNOX2-dp and LPS and D-dimer was detected in COVID-19. In a multivariable logistic regression model, LPS/albumin levels and D-dimer predicted thrombotic events. In COVID-19 patients, LPS is significantly associated with a hypercoagulation state and disease severity. In vitro, LPS can increase endothelial oxidative stress and coagulation biomarkers that were reduced by the treatment with albumin. In conclusion, impaired gut barrier permeability, increased NOX2 activation, and low serum albumin may account for low-grade endotoxemia and may be implicated in thrombotic events in COVID-19. [ABSTRACT FROM AUTHOR]

Objectives: This study intends to evaluate early hemorrhagic complications after holmium laser enucleation of the prostate (HoLEP) in patients undergoing antithrombotic therapy. Methods: The data of patients undergoing HoLEP between January 2020 and February 2023 were retrospectively analysed. Patients were clustered into three groups: (1) no antithrombotic therapy; (2) antiplatelet (AP) therapy; and (3) anticoagulant (AC) therapy. Pre-, intra-, and post-operative variables were compared. A logistic regression model was built to identify predictors of post-operative hemorrhagic complications. Results: A total of 338 patients underwent HoLEP, including 212 who received no antithrombotic therapy (62.7%), 76 who received AP (22.5%), and 50 who received AC (14.8%). Intra-operative outcomes did not show any significant difference. A significant difference was observed in terms of catheterisation time (p = 0.001) and length of hospital stay (p < 0.001), favouring patients who did not receive antithrombotic therapy. Early post-operative hemorrhagic complications (<30 days) included re-admissions for macrohematuria (3.5%), transfusions (2.4%), and endoscopic re-interventions for bleeding (1.2%). A comparison between the groups showed significant differences for both re-admission (p < 0.001) and transfusion rates (p = 0.01), favouring patients who did not receive antithrombotic therapy. The re-intervention rate did not show any significant difference between the groups (p = 0.1). In multivariate analysis, AC therapy was identified as an independent predictor of those complications (OR 4.9, p = 0.005). Conclusions: HoLEP is a safe and effective procedure for patients undergoing antithrombotic therapy. Both AP and AC therapies are associated with longer catheterisation and hospitalisation times. AC therapy is shown to be a predictor of minor post-operative hemorrhagic complications. [ABSTRACT FROM AUTHOR]

Background. Adipose tissue macrophages (ATMs) and mast cells (MCs) play a role in immune responses. More recently, their involvement in tumor angiogenesis and chronic inflammatory conditions in patients with obesity has been discovered. Furthermore, a higher BMI (Body Mass Index) value corresponds to a higher inflammatory state. In particular, gastric tissue in obesity (GTO) is characterized by Macrophages, Mast Cells Positive to Triptase (MCPT), and neo-formed microvessels (MVD). Materials and Methods. We collected gastric tissue samples from December 2021 to December 2022. The patients selected had a BMI > 35 kg/m2 with different comorbidities. Regarding the surgery, surgeons executed a Laparoscopic Sleeve Gastrectomy (LapSG). Gastric tissue was analyzed by immunohistochemistry and morphometrical assay, comparing "obese-related" gastric tissue to normal gastric tissue. Furthermore, tissue parameters were correlated with important clinicopathological features. Results. We collected thirty gastric tissue samples from thirty patients with obesity. Blood tests, Electrocardiogram (ECG), esophagogastroduodenoscopy (EGDS) associated with a urea breath test, and chest X.R. were performed. A significant correlation between ATMs, MCPT, MVD, and BMI was found in GTO. Pearson t-test analysis was conducted (r ranged from 0.67 to 0.71; p-value < 0.05). Conclusions. These preliminary data suggest that ATMs, MCPT, and MVD related to BMI can play a role in both gastric tissue angiogenesis and inflammation inducing a tissue change that could lead to gastric inflammation or cancer diseases. [ABSTRACT FROM AUTHOR]

This paper aims to verify the effectiveness of a process of superficial protection based on nanotechnologies produced by 4Ward360 and specifically developed for aeronautical applications on composite material aircraft. The Dardo aircraft, a composite VLA category manufactured by CFM Air, was taken as a reference case and two application/investigation areas were identified. The potential anticorrosive behavior of the nanotechnology treatment was investigated when applied to the metal joints of the aircraft, such as the wing–fuselage attachments usually made of Al-2024-T3 aluminum alloy. Furthermore, the potential increased effectiveness in cleaning was investigated as another possible application concerning the parts made of composite material both solid and in a sandwich configuration and the plexiglass parts of the canopy. [ABSTRACT FROM AUTHOR]

Syncope is a highly prevalent clinical condition characterized by a rapid, complete, and brief loss of consciousness, followed by full recovery caused by cerebral hypoperfusion. This symptom carries significance, as its potential underlying causes may involve the heart, blood pressure, or brain, leading to a spectrum of consequences, from sudden death to compromised quality of life. Various factors contribute to syncope, and adhering to a precise diagnostic pathway can enhance diagnostic accuracy and treatment effectiveness. A standardized initial assessment, risk stratification, and appropriate test identification facilitate determining the underlying cause in the majority of cases. New technologies, including artificial intelligence and smart devices, may have the potential to reshape syncope management into a proactive, personalized, and data-centric model, ultimately enhancing patient outcomes and quality of life. This review addresses key aspects of syncope management, including pathogenesis, current diagnostic testing options, treatments, and considerations in the geriatric population. [ABSTRACT FROM AUTHOR]

In 2022, three antiviral drugs—molnupiravir, remdesivir and nirmatrelvir/ritonavir—were introduced for treatment of mild-to-moderate COVID-19 in high-risk patients. The aim of this study is the evaluation of their effectiveness and tolerability in a real-life setting. A single-center observational study was set up, with the involvement of 1118 patients, with complete follow-up data, treated between the 5th of January and the 3rd of October 2022 at Santa Maria Goretti's hospital in Latina, Central Italy. A univariable and a multivariable analysis were performed on clinical and demographic data and composite outcome, the persistence of symptoms at 30 days and time to negativization, respectively. The three antivirals showed a similar effectiveness in containing the progression of the infection to severe COVID-19 and a good tolerability in the absence of serious adverse effects. Persistence of symptoms after 30 days was more common in females than males and less common in patients treated with molnupiravir and nirmatrelvir/r. The availability of different antiviral molecules is a strong tool and, if correctly prescribed, they can have a significant role in changing the natural history of infection for frail persons, in which vaccination could be not sufficient for the prevention of severe COVID-19. [ABSTRACT FROM AUTHOR]

In this retrospective comparative study, we evaluated the effectiveness of remdesivir (RDSV) in patients with SARS-CoV-2 pneumonia. Individuals hospitalized between March 2020 and August 2022 at S.M. Goretti Hospital, Latina, with a positive test for SARS-CoV-2 and, concomitantly, pneumonia, were included. The overall survival was the primary endpoint. The composite secondary endpoint included death or progression in severe ARDS at 40 days. The study population was stratified according to treatment into two groups: the RDSV group (patients treated with RDSV-based regimens) and the no-RDSV group (patients treated with any other, not RDSV-based, regimens). Factors associated with death and progression to severe ARDS or death were assessed by multivariable analysis. A total of 1153 patients (632 belonging to the RDSV group and 521 to the no-RDSV group) were studied. The groups were comparable in terms of sex, PaO2/FiO2 at admission, and duration of symptoms before hospitalization. Further, 54 patients (8.5%) in the RDSV group and 113 (21.7%) in the no-RDSV group (p < 0.001) died. RDSV was associated with a significantly reduced hazard ratio (HR) of death (HR, 0.69 [95% CI, 0.49–0.97]; p = 0.03), compared to the no-RDSV group, as well as a significantly reduced OR of progression in severe ARDS or death (OR, 0.70 [95% CI 0.49–0.98]; p = 0.04). An overall significantly higher survival rate was observed in the RDSV group (p < 0.001, by log-rank test). These findings reinforce the survival benefit of RDSV and support its routine clinical use for the treatment of COVID-19 patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Mast cell leukemia (MCL) is a rare and aggressive subtype of systemic mastocytosis (SM). MCL diagnosis requires fulfillment of diagnostic criteria for SM plus at least 20% immature/atypical mast cells on bone marrow smear. Based on different clinicopathological characteristics, MCL is subdivided into the following variants: primary (de novo) or secondary (from a prior SM form); acute with C-findings (where C-findings represent organ damage requiring cytoreductive treatment) or chronic without C-findings; and finally, MCL with or without an associated hematological neoplasm. The latter category was renamed MCL with an associated myeloid neoplasm in the 2022 International Consensus Classification (ICC). The relevance of the distinction between the leukemic and aleukemic forms, based on the percentage of circulating mast cells, is under discussion. In this study, we review the current knowledge on MCL with the aim of increasing clinicians' and pathologists' awareness of this rare, still incompletely understood disease with a grim prognosis. Mast cell leukemia (MCL) is the leukemic form of SM with at least 20% mostly immature mast cells on bone marrow aspirate. MCL may develop de novo, in the absence of a prior SM, or it may represent a progression from a previous SM. MCL may be sub-divided into the more frequent, aggressive acute form with signs of organ damage (C-findings) and the chronic form lacking C-findings and presenting a more stable course, although over time, progression to acute MCL is common. The 2022 WHO subtype of MCL with an associated hematological neoplasm was renamed MCL with an associated myeloid neoplasm in the 2022 International Consensus Classification (ICC). The relevance of the distinction between the leukemic and aleukemic forms based on the percentage of circulating mast cells is a matter of debate. The current knowledge on MCL is restricted mainly to single reports or case series with a limited number of larger studies. Our aim is to provide a comprehensive overview of this rare disease in terms of clinical manifestations, morphology, phenotype, molecular characteristics, differential diagnosis, outcome and treatment. A general overview on mastocytosis is also included. [ABSTRACT FROM AUTHOR]

We investigated specific humoral and T-cell responses in people living with HIV (PLWH) before (T0), after two (T1) and after six months (T2) from the third dose of the BNT162b2 vaccine. Healthy donors (HD) were enrolled. The specific humoral response was present in most PLWH already after the second dose, but the third dose increased both the rate of response and its magnitude. Collectively, no significant differences were found in the percentage of responding T-cells between PLWH and HD. At T0, stratifying PLWH according to CD4 cell count, a lower percentage of responding T-cells in <200 cells/µL subgroup compared to >200 cells/µL one was observed. At T1, this parameter was comparable between the two subgroups, and the same result was found at T2. However, the pattern of co-expression of IFNγ, IL2 and TNFα in PLWH was characterized by a higher expression of TNFα, independently of CD4 cell count, indicating a persistent immunological signature despite successful ART. mRNA vaccination elicited a specific response in most PLWH, although the cellular one seems qualitatively inferior compared to HD. Therefore, an understanding of the T-cell quality dynamic is needed to determine the best vaccination strategy and, in general, the capability of immune response in ART-treated PLWH. [ABSTRACT FROM AUTHOR]

Simple Summary: Chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of specific hematological diseases, but is unsuccessful in around 60% of patients. The objective of the Bio-CAR-T BS study is to improve our understanding of the lymphocyte harvest to maximize the quality of the CAR-T cell product. We show here that "pre-emptive" lymphocyte apheresis (Ly-apheresis) of selected high-risk DLBCL patients may preserve the fitness of lymphocytes for CAR-T cell infusion. Specifically, the "pre-emptive" Ly-apheresis strategy resulted in a significantly higher CD4/CD8 ratio, significantly higher absolute counts and frequency of CD4+ naïve T cells, and a significantly higher frequency of CD8+ naïve T cells compared with the standard Ly-apheresis strategy (i.e., relapsed/refractory after two lines of treatments). Moreover, patients who underwent "pre-emptive" Ly-apheresis had a significantly lower frequency of CD8+ terminally differentiated T cells compared with standard Ly-apheresis. The development of chimeric antigen receptor (CAR)-T cell therapy has revolutionized the treatment of hematological diseases. However, approximately 60% of patients relapse after CAR-T cell therapy, and no clear cause for this failure has been identified. The objective of the Bio-CAR-T BS study (ClinicalTrials.gov: NCT05366569) is to improve our understanding of the lymphocyte harvest to maximize the quality of the CAR-T cell product. Of the 14 patients enrolled, 11 were diagnosed with DLBCL, 2 with PMBCL, and 1 with ALL. Five of 11 DLBCL patients met the criteria for "pre-emptive" Lymphocytes-apheresis (being at high risk of second relapse), and 6 were included in the standard-of-care Lymphocytes-apheresis group. Previous autologous stem cell transplantation (ASCT) and age were significantly different between the two groups. At the time of Lymphocyte-apheresis, patients in the "pre-emptive" group had more "fit" lymphocytes (higher CD4+/CD8+ ratio; higher naïve T cells levels) compared with standard group, probably due to the impact of ASCT. At the same time, also being older than 60 years results in a more "exhausted" lymphocyte profile. Overall, "pre-emptive" Ly-apheresis in DLBCL patients at high risk of relapse appears to be feasible and may allow the timely collection of "fit" lymphocytes for CAR-T cell manufacturing. [ABSTRACT FROM AUTHOR]

In the direct-acting antiviral (DAA) era, it is important to understand the immunological changes after HCV eradication in HCV monoinfected (mHCV) and in HIV/HCV coinfected (HIV/HCV) patients. In this study, we analyzed sub-populations of monocytes, dendritic cells (DCs), T-lymphocytes and inflammatory biomarkers following initiation of DAA in 15 mHCV and 16 HIV/HCV patients on effective antiretroviral therapy at baseline and after sustained virological response at 12 weeks (SVR12). Fifteen age- and sex-matched healthy donors (HD) were enrolled as a control group. Activated CD4+ and CD8+ T-lymphocytes, mDCs, pDCs, MDC8 and classical, non-classical and intermediate monocytes were detected using flow cytometry. IP-10, sCD163 and sCD14 were assessed by ELISA while matrix metalloproteinase-2 (MMP-2) was measured by zymography. At baseline, increased levels of IP-10, sCD163 and MMP-2 were found in both HIV/HCV and mHCV patients compared to HD, whereas sCD14 increased only in HIV/HCV patients. After therapy, IP-10, sCD163 and sCD14 decreased, whereas MMP-2 persistently elevated. At baseline, activated CD8+ T-cells were high in HIV/HCV and mHCV patients compared to HD, with a decrease at SVR12 only in HIV/HCV patients. Activated CD4+ T-cells were higher in HIV/HCV patients without modification after DAAs therapy. These results suggest complex interactions between both viruses and the immune system, which are only partially reversed by DAA treatment. [ABSTRACT FROM AUTHOR]

A fall is an event where a person unintentionally and traumatically finds themselves on the floor or a lower level. Falls are very common, especially in the older adult population. One in four people falls at least once a year after age 65. Because of falls, there can be injuries, whereby there can be an impairment of health status. Fractures, reduced mobility, disability, and the need for institutionalization are potential consequences after falls. In older adult patients, especially frail ones, these types of complications are more common. There are several risk factors for falls. Falls generally result from a combination of factors operating simultaneously. Sarcopenia, cognitive impairment, or poly-pharmacotherapy are just a few examples of risk factors that are common in the older people. Through careful clinical evaluation, it is possible to identify risk factors and conditions predisposing to falls. In some cases, it is possible to correct these factors. Several types of treatment are available to restore the health status before the fall and prevent subsequent falls. Using multi-component interventions, the risk of falls can be effectively reduced. Aware that this review will not be exhaustive of such a broad topic, the purpose of this narrative review is to summarize relevant and recent evidence in the current literature to encapsulate fall-related risk factors, risk identification, fall prevention, and management, including various rehabilitation techniques. This article conforms to the Scale for Assessment of Narrative Review Articles (SANRA) guidelines. [ABSTRACT FROM AUTHOR]

Carboplatin is the cornerstone of ovarian cancer (OC) treatment, while platinum-response, dependent on interindividual variability, is the major prognostic factor for long-term outcomes. This retrospective study was focused on explorative search of genetic polymorphisms in the Absorption, Distribution, Metabolism, Excretion (ADME) genes for the identification of biomarkers prognostic/predictive of platinum-response in OC patients. Ninety-two advanced OC patients treated with carboplatin-based therapy were enrolled at our institution. Of these, we showed that 72% of patients were platinum-sensitive, with a significant benefit in terms of OS (p = 0.001). We identified an inflammatory-score with a longer OS in patients with lower scores as compared to patients with the maximum score (p = 0.001). Thirty-two patients were genotyped for 1931 single nucleotide polymorphisms (SNPs) and five copy number variations (CNVs) by the DMET Plus array platform. Among prognostic polymorphisms, we found a potential role of UGT2A1 both as a predictor of platinum-response (p = 0.01) and as prognostic of survival (p = 0.05). Finally, we identified 24 SNPs related to OS. UGT2A1 correlates to an "inflammatory-score" and retains a potential prognostic role in advanced OC. These data provide a proof of concept that warrants further validation in follow-up studies for the definition of novel biomarkers in this aggressive disease. [ABSTRACT FROM AUTHOR]

It is recognized that stress conditions play an important role in the definition of individual wellness and represent a major risk factor for most non-communicable diseases. Most studies focus on the evaluation of response to maximal stress conditions while a few of them reports results about the detection/monitoring of response to mild stimulations. In this study, we investigate the capability of some physiological signs and indicators (including Heart Rate, Heart Rate Variability, Respiratory Rate, Galvanic Skin Response) to recognize stress in response to moderate cognitive activation in daily life settings. To achieve this goal, we built up an unobtrusive platform to collect signals from healthy volunteers (10 subjects) undergoing cognitive activation via Stroop Color Word Test. We integrated our dataset with data from the Stress Recognition in the Automobile Drivers dataset. Following data harmonization, signal recordings in both datasets were split into five-minute blocks and a set of 12 features was extracted from each block. A feature selection was implemented by two complementary approaches: Sequential Forward Feature Selection (SFFS) and Auto-Encoder (AE) neural networks. Finally, we explored the use of Self-Organizing Map (SOM) to provide a flexible representation of an individual status. From the initial feature set we have determined, by SFFS analysis, that 2 of them (median Respiratory Rate and number peaks in Galvanic Skin Response signals) can discriminate activation statuses from resting ones. In addition, AE experiments also support that two features can suffice for recognition. Finally, we showed that SOM can provide a comprehensive but compact description of activation statuses allowing a fine prototypical representation of individual status. [ABSTRACT FROM AUTHOR]

Mast cells and macrophages can play a role in tumor angiogenesis by stimulating microvascular density (MVD). The density of mast cells positive to tryptase (MCDPT), tumor-associated macrophages (TAMs), and MVD were evaluated in a series of 86 gastric cancer (GC) tissue samples from patients who had undergone potential curative surgery. MCDPT, TAMs, and MVD were assessed in tumor tissue (TT) and in adjacent normal tissue (ANT) by immunohistochemistry and image analysis. Each of the above parameters was correlated with the others and, in particular for TT, with important clinico-pathological features. In TT, a significant correlation between MCDPT, TAMs, and MVD was found by Pearson t-test analysis (p ranged from 0.01 to 0.02). No correlation to the clinico-pathological features was found. A significant difference in terms of mean MCDPT, TAMs, and MVD between TT and ANT was found (p ranged from 0.001 to 0.002). Obtained data suggest MCDPT, TAMs, and MVD increased from ANT to TT. Interestingly, MCDPT and TAMs are linked in the tumor microenvironment and they play a role in GC angiogenesis in a synergistic manner. The assessment of the combination of MCDPT and TAMs could represent a surrogate marker of angiogenesis and could be evaluated as a target of novel anti-angiogenic therapies in GC patients. [ABSTRACT FROM AUTHOR]

Mast Cells (MCs) play a role in immune responses and more recently MCs have been involved in tumoral angiogenesis. In particular MCs can release tryptase, a potent in vivo and in vitro pro-angiogenic factor via proteinase-activated receptor-2 (PAR-2) activation and mitogen-activated protein kinase (MAPK) phosphorylation. MCs can release tryptase following c-Kit receptor activation. Nevertheless, no data are available concerning the relationship among MCs Density Positive to Tryptase (MCDPT) and Microvascular Density (MVD) in both primary gastric cancer tissue and loco-regional lymph node metastases. A series of 75 GC patients with stage T2-3N2-3M0 (by AJCC for Gastric Cancer Seventh Edition) undergone to radical surgery were selected for the study. MCDPT and MVD were evaluated by immunohistochemistry and by image analysis system and results were correlated each to other in primary tumor tissue and in metastatic lymph nodes harvested. Furthermore, tissue parameters were correlated with important clinico-pathological features. A significant correlation between MCDPT and MVD was found in primary gastric cancer tissue and lymph node metastases. Pearson t-test analysis (r ranged from 0.74 to 0.79; p-value ranged from 0.001 to 0.003). These preliminary data suggest that MCDPT play a role in angiogenesis in both primary tumor and in lymph node metastases from GC. We suggest that MCs and tryptase could be further evaluated as novel targets for anti-angiogenic therapies. [ABSTRACT FROM AUTHOR]

While gastric cancer is a well established angiogenesis driven tumor, no data has been published regarding angiogenesis stimulated by mast cells (MCs) positive for tryptase in bone metastases from gastric cancer patients (BMGCP). It is well established that MCs play a role in immune responses and more recently it was demonstrated that MCs have been involved in tumor angiogenesis. We analyzed infiltrating MCs and neovascularization in BMGCP diagnosed by histology. A series of 15 stage T3-4N2-3M1 (by AJCC for Gastric Cancer Staging 7th Edition) BMGCP from bone biopsies were selected. Tumour tissue samples were evaluated by mean of immunohistochemistry and image analysis methods in terms of MCs density positive to tryptase (MCDPT), MCs area positive to tryptase (MCAPT), microvascular density (MVD) and endothelial area (EA). A significant correlation between MCDPT, MCAPT, MVD and EA groups to each other was found by Pearson and t-test analysis (r ranged from 0.68 to 0.82; p-value ranged from 0.00 to 0.02). Our very preliminary data suggest that infiltrating MCs positive for tryptase may play a role in BMGCP angiogenesis, and could be further evaluated as a novel target of anti-angiogenic therapy. [ABSTRACT FROM AUTHOR]

Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in people coinfected with human immunodeficiency virus (HIV). Several studies have shown that HIV infection promotes accelerated HCV hepatic fibrosis progression, even with HIV replication under full antiretroviral control. The pathogenesis of accelerated hepatic fibrosis among HIV/HCV coinfected individuals is complex and multifactorial. The most relevant mechanisms involved include direct viral effects, immune/cytokine dysregulation, altered levels of matrix metalloproteinases and fibrosis biomarkers, increased oxidative stress and hepatocyte apoptosis, HIV-associated gut depletion of CD4 cells, and microbial translocation. In addition, metabolic alterations, heavy alcohol use, as well drug use, may have a potential role in liver disease progression. Understanding the pathophysiology and regulation of liver fibrosis in HIV/HCV co-infection may lead to the development of therapeutic strategies for the management of all patients with ongoing liver disease. In this review, we therefore discuss the evidence and potential molecular mechanisms involved in the accelerated liver fibrosis seen in patients coinfected with HIV and HCV. [ABSTRACT FROM AUTHOR]

Known multiple sclerosis (MS) susceptibility variants can only explain half of the disease's estimated heritability, whereas low-frequency and rare variants may partly account for the missing heritability. Thus, here we sought to determine the occurrence of rare functional variants in a large Italian MS multiplex family with five affected members. For this purpose, we combined linkage analysis and next-generation sequencing (NGS)-based whole exome and whole genome sequencing (WES and WGS, respectively). The genetic burden attributable to known common MS variants was also assessed by weighted genetic risk score (wGRS). We found a significantly higher burden of common variants in the affected family members compared to that observed among sporadic MS patients and healthy controls (HCs). We also identified 34 genes containing at least one low-frequency functional variant shared among all affected family members, showing a significant enrichment in genes involved in specific biological processes—particularly mRNA transport—or neurodegenerative diseases. Altogether, our findings point to a possible pathogenic role of different low-frequency functional MS variants belonging to shared pathways. We propose that these rare variants, together with other known common MS variants, may account for the high number of affected family members within this MS multiplex family. [ABSTRACT FROM AUTHOR]

As a complex disease, Multiple Sclerosis (MS)'s etiology is determined by both genetic and environmental factors. In the last decade, the gut microbiome has emerged as an important environmental factor, but its interaction with host genetics is still unknown. In this review, we focus on these dual aspects of MS pathogenesis: we describe the current knowledge on genetic factors related to MS, based on genome-wide association studies, and then illustrate the interactions between the immune system, gut microbiome and central nervous system in MS, summarizing the evidence available from Experimental Autoimmune Encephalomyelitis mouse models and studies in patients. Finally, as the understanding of influence of host genetics on the gut microbiome composition in MS is in its infancy, we explore this issue based on the evidence currently available from other autoimmune diseases that share with MS the interplay of genetic with environmental factors (Inflammatory Bowel Disease, Rheumatoid Arthritis and Systemic Lupus Erythematosus), and discuss avenues for future research. [ABSTRACT FROM AUTHOR]

Background: Mast cells (MCs) contain proangiogenic factors, in particular tryptase, associated with increased angiogenesis in several tumours. With special reference to pancreatic cancer, few data have been published on the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma tissue (PDAT) and adjacent normal tissue (ANT). In this study, density of mast cells positive for c-Kit receptor (MCDP-c-KitR), density of mast cells positive for tryptase (MCDPT), area of mast cells positive for tryptase (MCAPT), and angiogenesis in terms of microvascular density (MVD) and endothelial area (EA) were evaluated in a total of 45 PDAT patients with stage T2–3N0–1M0. Results: For each analysed tissue parameter, the mean ± standard deviation was evaluated in both PDAT and ANT and differences were evaluated by Student's t-test (p ranged from 0.001 to 0.005). Each analysed tissue parameter was then correlated to each other one by Pearson t-test analysis (p ranged from 0.01 to 0.03). No other correlation among MCDP-c-KitR, MCDPT, MCAPT, MVD, EA and the main clinical–pathological characteristics was found. Conclusions: Our results suggest that tissue parameters increased from ANT to PDAT and that mast cells are strongly associated with angiogenesis in PDAT. On this basis, the inhibition of MCs through tyrosine kinase inhibitors, such as masitinib, or inhibition of tryptase by gabexate mesylate may become potential novel antiangiogenetic approaches in pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is defined as a progressive loss of muscle mass and muscle strength associated to increased adverse events, such as falls and hip fractures. The aim of this systematic review is to analyse diagnosis methods of sarcopenia in patients with hip fracture and evaluate prevention and treatment strategies described in literature. Methods: Three independent authors performed a systematic review of two electronic medical databases using the following inclusion criteria: Sarcopenia, hip fractures, diagnosis, treatment, and prevention with a minimum average of 6-months follow-up. Any evidence-level studies reporting clinical data and dealing with sarcopenia diagnosis, or the treatment and prevention in hip fracture-affected patients, were considered. Results: A total of 32 articles were found. After the first screening, we selected 19 articles eligible for full-text reading. Ultimately, following full-text reading, and checking of the reference list, seven articles were included. Conclusions: Sarcopenia diagnosis is challenging, as no standardized diagnostic and therapeutic protocols are present. The development of medical management programs is mandatory for good prevention. To ensure adequate resource provision, care models should be reviewed, and new welfare policies should be adopted in the future. [ABSTRACT FROM AUTHOR]