PTX3 Intercepts Vascular Inflammation in Systemic Immune-Mediated Diseases

PTX3 is a prototypic soluble pattern recognition receptor, expressed at sites of inflammation and involved in regulation of the tissue homeostasis. PTX3 systemic levels increase in many (but not all) immune-mediated inflammatory conditions. Research on PTX3 as a biomarker has so far focused on single diseases. Here, we performed a multi-group comparative study with the aim of identifying clinical and pathophysiological phenotypes associated with PTX3 release. PTX3 concentration was measured by ELISA in the plasma of 366 subjects, including 96 patients with giant cell arteritis (GCA), 42 with Takayasu's arteritis (TA), 10 with polymyalgia rheumatica (PMR), 63 with ANCA-associated systemic small vessel vasculitides (AAV), 55 with systemic lupus erythematosus (SLE), 21 with rheumatoid arthritis (RA) and 79 healthy controls (HC). Patients with SLE, AAV, TA and GCA, but not patients with RA and PMR, had higher PTX3 levels than HC. PTX3 concentration correlated with disease activity, acute phase reactants and prednisone dose. It was higher in females, in patients with recent-onset disease and in those with previous or current active vasculitis at univariate analysis. Active small- or large- vessel vasculitis were the main independent variables influencing PTX3 levels at multivariate analysis. High levels of PTX3 in the blood can contribute to identify an increased risk of vascular involvement in patients with systemic immune-mediated diseases

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Analysis of shared common genetic risk between amyotrophic lateral sclerosis and epilepsy

Because hyper-excitability has been shown to be a shared pathophysiological mechanism, we used the latest and largest genome-wide studies in amyotrophic lateral sclerosis (n = 36,052) and epilepsy (n = 38,349) to determine genetic overlap between these conditions. First, we showed no significant genetic correlation, also when binned on minor allele frequency. Second, we confirmed the absence of polygenic overlap using genomic risk score analysis. Finally, we did not identify pleiotropic variants in meta-analyses of the 2 diseases. Our findings indicate that amyotrophic lateral sclerosis and epilepsy do not share common genetic risk, showing that hyper-excitability in both disorders has distinct origins

Treatment of immune thrombocytopenia (ITP) secondary to malignancy: a systematic review

Immune thrombocytopenia (ITP) can be associated with lymphoproliferative diseases (LPD) or solid tumors. A systematic review of published literature was conducted to evaluate response to treatment of ITP secondary to malignancy. Primary outcome was overall response (complete response+response) to first-line treatments [steroids alone or in combination with intravenous immunoglobulins (IVIg)]. Among secondary outcomes, overall response to second-line treatments [splenectomy, rituximab or thrombopoietin receptor agonists (TPO-RA)] and death were evaluated. Of the retrieved 238 text articles, 108 were analyzable, for a total of 154 patients: 142 in 105 case reports and 12 in 3 observational studies. Thirty-nine patients had solid tumors, 114 LPD, and 1 both. The median follow up was 19 months (IQR, 9–40). The overall response was 50% (62% in solid tumors, 46% in LPD) after steroids and 47% (67% in solid tumors, 36% in LPD) after steroids+IVIg, which are lower than historical responses observed in primary ITP (≈80%). The overall responses to rituximab (used in LPD only), splenectomy and TPO-RA (70%, 73% and 92%, respectively) were similar to those observed in primary ITP. Seven patients (6%) died due to bleeding events. ITP secondary to malignancy appears to be associated with unsatisfactory response to first-line treatments

Hepatocyte Aquaporins AQP8 and AQP9 Are Engaged in the Hepatic Lipid and Glucose Metabolism Modulating the Inflammatory and Redox State in Milk-Supplemented Rats

Milk is an important source of nutrients and energy, but there are still many uncertainties regarding the health effects of milk and dairy products consumption. Milk from different species varies in physicochemical and nutritional properties. We previously showed that dietary supplements with different milks in rats trigger significant differences in metabolic and inflammatory states, modulating mitochondrial functions in metabolically active organs such as the liver and skeletal muscle. Here, we have deepened the effects of isoenergetic supplementation of milk (82 kJ) from cow (CM), donkey (DM) or human (HM) on hepatic metabolism to understand the interlink between mitochondrial metabolic flexibility, lipid storage and redox state and to highlight the possible role of two hepatocyte aquaporins (AQPs) of metabolic relevance, AQP8 and AQP9, in this crosstalk. Compared with rats with no milk supplementation, DM- and HM-fed rats had reduced hepatic lipid content with enhanced mitochondrial function and decreased oxidative stress. A marked reduction in AQP8, a hydrogen peroxide channel, was seen in the liver mitochondria of DM-fed rats compared with HM-fed, CM-fed and control animals. DM-fed or HM-fed rats also showed reduced hepatic inflammatory markers and less collagen and Kupffer cells. CM-fed rats showed higher hepatic fat content and increased AQP9 and glycerol permeability. A role of liver AQP8 and AQP9 is suggested in the different metabolic profiles resulting from milk supplementation

Additional file 4: Table S3. of Chromogranin-A production and fragmentation in patients with Takayasu arteritis

CgA peptides in patients with TA stratified for therapy with steroids or immunosuppressive agents. (DOC 63 kb