Early benralizumab for eosinophilic myocarditis in eosinophilic granulomatosis with polyangiitis

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Effectiveness of Immunoglobulin Replacement Therapy on Clinical Outcome in Patients with Primary Antibody Deficiencies: Results from a Multicenter Prospective Cohort Study

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Dual stimulation by autoantigen and CpG fosters the proliferation of exhausted rheumatoid factor-specific CD21low B cells in hepatitis C virus-cured mixed cryoglobulinemia

Hepatitis C virus (HCV) causes mixed cryoglobulinemia (MC) by driving clonal expansion of B cells expressing B cell receptors (BCRs), often encoded by the VH1-69 variable gene, endowed with both rheumatoid factor (RF) and anti-HCV specificity. These cells display an atypical CD21low phenotype and functional exhaustion evidenced by unresponsiveness to BCR and Toll-like receptor 9 (TLR9) stimuli. Although antiviral therapy is effective on MC vasculitis, pathogenic B cell clones persist long thereafter and can cause virus-independent disease relapses. MethodsClonal B cells from patients with HCV-associated type 2 MC or healthy donors were stimulated with CpG or heath-aggregated IgG (as surrogate immune complexes) alone or in combination; proliferation and differentiation were then evaluated by flow cytometry. Phosphorylation of AKT and of the p65 NF-kB subunit were measured by flow cytometry. TLR9 was quantified by qPCR and by intracellular flow cytometry, and MyD88 isoforms were analyzed using RT-PCR. DiscussionWe found that dual triggering with autoantigen and CpG restored the capacity of exhausted VH1-69pos B cells to proliferate. The signaling mechanism for this BCR/TLR9 crosstalk remains elusive, since TLR9 mRNA and protein as well as MyD88 mRNA were normally expressed and CpG-induced phosphorylation of p65 NF-kB was intact in MC clonal B cells, whereas BCR-induced p65 NF-kB phosphorylation was impaired and PI3K/Akt signaling was intact. Our findings indicate that autoantigen and CpG of microbial or cellular origin may unite to foster persistence of pathogenic RF B cells in HCV-cured MC patients. BCR/TLR9 crosstalk might represent a more general mechanism enhancing systemic autoimmunity by the rescue of exhausted autoreactive CD21low B cells

MR-proADM as prognostic factor of outcome in COVID-19 patients

17siMid Regional pro-ADM (MR-proADM) is a promising novel biomarker in the evaluation of deteriorating patients and an emergent prognosis factor in patients with sepsis, septic shock and organ failure. It can be induced by bacteria, fungi or viruses. We hypothesized that the assessment of MR-proADM, with or without other inflammatory cytokines, as part of a clinical assessment of COVID-19 patients at hospital admission, may assist in identifying those likely to develop severe disease. A pragmatic retrospective analysis was performed on a complete data set from 111 patients admitted to Udine University Hospital, in northern Italy, from 25th March to 15th May 2020, affected by SARS-CoV-2 pneumonia. Clinical scoring systems (SOFA score, WHO disease severity class, SIMEU clinical phenotype), cytokines (IL-6, IL-1b, IL-8, TNF-α), and MR-proADM were measured. Demographic, clinical and outcome data were collected for analysis. At multivariate analysis, high MR-proADM levels were significantly associated with negative outcome (death or orotracheal intubation, IOT), with an odds ratio of 4.284 [1.893–11.413], together with increased neutrophil count (OR = 1.029 [1.011–1.049]) and WHO disease severity class (OR = 7.632 [5.871–19.496]). AUROC analysis showed a good discriminative performance of MR-proADM (AUROC: 0.849 [95% Cl 0.771–0.730]; p < 0.0001). The optimal value of MR-proADM to discriminate combined event of death or IOT is 0.895 nmol/l, with a sensitivity of 0.857 [95% Cl 0.728–0.987] and a specificity of 0.687 [95% Cl 0.587–0.787]. This study shows an association between MR-proADM levels and the severity of COVID-19. The assessment of MR-proADM combined with clinical scoring systems could be of great value in triaging, evaluating possible escalation of therapies, and admission avoidance or inclusion into trials. Larger prospective and controlled studies are needed to confirm these findings.openopenSozio E.; Tascini C.; Fabris M.; D'Aurizio F.; De Carlo C.; Graziano E.; Bassi F.; Sbrana F.; Ripoli A.; Pagotto A.; Giacinta A.; Gerussi V.; Visentini D.; De Stefanis P.; Merelli M.; Saeed K.; Curcio F.Sozio, E.; Tascini, C.; Fabris, M.; D'Aurizio, F.; De Carlo, C.; Graziano, E.; Bassi, F.; Sbrana, F.; Ripoli, A.; Pagotto, A.; Giacinta, A.; Gerussi, V.; Visentini, D.; De Stefanis, P.; Merelli, M.; Saeed, K.; Curcio, F

Cardiovascular risk factors, anxiety symptoms and inflammation markers: Evidence of association from a cross-sectional study

Introduction Anxiety disorders and Cardiovascular (CV) diseases, among the most common disorders in Western World, are often comorbid. A chronic systemic inflammatory state might be a shared underlining pathophysiological mechanism. Aims To investigate the association between anxiety symptoms, CV risks factors and inflammatory markers in an outpatient sample. Methods Cross-sectional study. Inclusion criteria: outpatients aged ≥40 years, attending colonoscopy after positive faecal occult blood test, negative medical history for cancer. Collected data: blood pressure, glycaemia, lipid profile, waist circumference, BMI, PCR (C Reactive Protein), LPS (bacterial Lipopolysaccharide). Psychometric tests: HADS, TCI, IMSA, SF36. Statistical analysis performed with STATA13. Results Fifty four patients enrolled (27 males, 27 females). Sixteen patients (30.19%) were positive for anxiety symptoms. Thirty-three patients (61.11%) had hypertension, 14 (25.93%) hyperglycaemia and 64.81% were overweight, with frank obesity (BMI≥ 30) in 11 subjects (20.37%). Anxiety symptoms were associated with low hematic HDL values (OR = 0.01; P = 0.01) and high concentration of triglycerides (OR = 0.023; P = 0.02) at the multiple regression model. At the univariate logistic analysis, anxiety was associated with LPS (OR = 1.06; P = 0.04). Conclusions Further evidence over the epidemiological link between common mental disorders and CV diseases was collected, with possible hints on pathophysiology and causative mechanisms related to inflammation. The importance of screening for anxiety and depression in medical populations is confirmed. Suggestions on future availability of screening tools based on inflammatory-related indicators should be the focus of future research

How are personality traits and physical activity involved in colorectal carcinogenesis? A cross-sectional study on patients undergoing colonoscopy

Introduction Inflammatory state of the large bowel is a key factor for the development of colorectal cancer (CRC). It has multifactorial aetiology, including psychological determinants. Physical activity may have a protective function against CRC via anti-inflammatory properties; on the contrary, personality traits correlate with an unhealthy and dangerous lifestyle. Objective To measure the association between personality traits, lifestyle and colonoscopy outcome. Methods Cross sectional study. Patients undergoing colonoscopy aged 40 or more, with a negative history for cancer or inflammatory bowel disease, were enrolled. Data collected: colonoscopy outcome, smoke, alcohol, physical activity, presence/absence of Metabolic Syndrome, personality traits assessed by the Temperament & Character Inventory (TCI). Results In a sample of 53 subjects (females = 24, 45.3%), the mean age was 60.66 ± 9.08. At least one adenoma was found to 23 patients (43.3%). Twenty patients were smokers (37.74%), 36 (67.92%) drank alcohol at least weekly; approximately 60% reported regular physical activity. At the multivariate regression, the outcome was associated to: TCI Self Transcendence domain (ST) (OR = 1.36, P = 0.04) and physical activity (OR = 0.14, P = 0.03). Conclusion People with ST's characteristic personality traits and sedentary life style are more likely to have precancerous colorectal lesions. This confirms the protective role of physical activity, and suggests to further explore the role of personality in cancerogenesis

An Italian observational study on subclinical cardiovascular risk factors and depressive symptomatology. A suggestion for the potential utility of a sinergic cardio-psychiatric perspective

Introduction Growing evidence has been collected over the complex, intertwined pathophysiological connection among subclinical cardiovascular (CV) disease, i.e. atherosclerosis, systemic low pro-inflammatory states and psychiatric disorders/symptomatology (anxiety, depression), with controversial results. Aim Aim of this study was to investigate the possible link between subclinical CV risk factors (atherosclerosis), depressive symptoms, and inflammation. Methods Cross-sectional study. Inclusion criteria: outpatients aged ≥40 years, attending colonoscopy after positive faecal occult blood test, negative medical history for cancer. Collected data: blood pressure, glycaemia, lipid profile, waist circumference, BMI, PCR (C reactive protein), LPS (bacterial lipopolysaccharide), ultrasound carotid intima-media thickness (c-IMT). Psychometric tests: HADS, TCI, IMSA, SF36. Statistical analysis performed with STATA13. Results The 54 patients enrolled were equally distributed by gender. CV risk factors were common in the study population, with 33 patients (61.11%) with hypertension, 14 (25.93%) with hyperglycaemia, 20 (37.4%) with hypertriglyceridemia, 19 (35.19%) with low HDL and 64.81% with overweight. High levels of PCR were found in 24 subjects (44.44%). Right c-IMT was increased in 26.41% of the sample, and 11.32% had an atheromatous plaque. Left c-IMT was increased in 24.53% of patients, with a plaque in 7.55% of them. Clinically relevant depressive symptoms were found in the 18.87% of the sample and were statistically significantly associated with PCR (OR = 28.63; P = 0.01). Conclusions Evidence contributing to the so-called “inflammation theory” of depression and supporting the association between mood and CV disorders was here collected, supporting the need for a multidisciplinary approach to the diagnosis and treatment of such conditions, assuming a clinically-translated PNEI (psycho-neuro-endocrino-immunological) perspective

Biodiversity amongst cultivable polycyclic aromatic hydrocarbon-transforming bacteria isolated from an abandoned industrial site

The characterisation of a microbial community of a polycyclic aromatic hydrocarbons (PAHs) contaminated site (formerly Carbochimica, Trento, Italy) was carried out. A preliminary evaluation of the heterogeneity and the metabolic activity of the microbial community were attempted by denaturing gradient gel electrophoresis (DGGE) and reverse transcriptase-denaturing gel electrophoresis (RT-DGGE). The presence of a heterogeneous and metabolically active microbial community was found. To evaluate the PAH-transforming potential of the soil bacterial community, enrichment cultures were set up. Taxonomically diverse bacteria, showing different biochemical PAH-transforming pathways were obtained. Some of the isolates showed not nah-homologous PAH-transforming genotypes

Might IgA be a biomarker of disease activity in Takayasu arteritis

Takayasu arteritis is a systemic vasculitis of the large vessels and mainly affects Japanese and Southeast Asian women in the second and third decades of life. Inflammatory infiltrate affects the full thickness of the vessel wall, inducing progressive lumen stenosis and occlusion. The main biomarkers of disease activity are the ESR, CRP and serum levels of circulating cytokines. This case report describes the clinical history of a young woman with Takayasu disease with high serum levels of IgA at onset. IgA remained elevated with persistence of disease activity, and normalized only when the patient was treated with an anti-TNF agent (infliximab), which also induced a clinical response in the vasculitis. IgA levels, together with other inflammatory parameters, may be considered a biomarker of disease activity. Learning points: This case report highlights the need to increase the number of humoral markers used to assess disease course in Takayasu arteritis (TA).IgA may be considered a biomarker of TA disease activity.Serum IgA levels may be helpful to identify TA patients not responding to traditional therapy