Juri Alessandro Giannotta

Bio: Juri Alessandro Giannotta is an academic researcher from Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico. The author has contributed to research in topics: Autoimmune hemolytic anemia & Medicine. The author has an hindex of 9, co-authored 39 publications receiving 217 citations. Previous affiliations of Juri Alessandro Giannotta include University of Milan.

New Insights in Autoimmune Hemolytic Anemia: From Pathogenesis to Therapy Stage 1.

Abstract: Autoimmune hemolytic anemia (AIHA) is a highly heterogeneous disease due to increased destruction of autologous erythrocytes by autoantibodies with or without complement involvement. Other pathogenic mechanisms include hyper-activation of cellular immune effectors, cytokine dysregulation, and ineffective marrow compensation. AIHAs may be primary or associated with lymphoproliferative and autoimmune diseases, infections, immunodeficiencies, solid tumors, transplants, and drugs. The direct antiglobulin test is the cornerstone of diagnosis, allowing the distinction into warm forms (wAIHA), cold agglutinin disease (CAD), and other more rare forms. The immunologic mechanisms responsible for erythrocyte destruction in the various AIHAs are different and therefore therapy is quite dissimilar. In wAIHA, steroids represent first line therapy, followed by rituximab and splenectomy. Conventional immunosuppressive drugs (azathioprine, cyclophosphamide, cyclosporine) are now considered the third line. In CAD, steroids are useful only at high/unacceptable doses and splenectomy is uneffective. Rituximab is advised in first line therapy, followed by rituximab plus bendamustine and bortezomib. Several new drugs are under development including B-cell directed therapies (ibrutinib, venetoclax, parsaclisib) and inhibitors of complement (sutimlimab, pegcetacoplan), spleen tyrosine kinases (fostamatinib), or neonatal Fc receptor. Here, a comprehensive review of the main clinical characteristics, diagnosis, and pathogenic mechanisms of AIHA are provided, along with classic and new therapeutic approaches.

The Physiopathology of T- Cell Acute Lymphoblastic Leukemia: Focus on Molecular Aspects

Abstract: T-cell acute lymphoblastic leukemia/lymphoma is an aggressive hematological neoplasm whose classification is still based on immunophenotypic findings. Frontline treatment encompass high intensity combination chemotherapy with good overall survival; however, relapsing/refractory patients have very limited options. In the last years, the understanding of molecular physiopathology of this disease, lead to the identification of a subset of patients with peculiar genetic profile, namely "early T-cell precursors" lymphoblastic leukemia, characterized by dismal outcome and indication to frontline allogeneic bone marrow transplant. In general, the most common mutations occur in the NOTCH1/FBXW7 pathway (60% of adult patients), with a positive prognostic impact. Other pathogenic steps encompass transcriptional deregulation of oncogenes/oncosuppressors, cell cycle deregulation, kinase signaling (including IL7R-JAK-STAT pathway, PI3K/AKT/mTOR pathway, RAS/MAPK signaling pathway, ABL1 signaling pathway), epigenetic deregulation, ribosomal dysfunction, and altered expression of oncogenic miRNAs or long non-coding RNA. The insight in the genomic landscape of the disease paves the way to the use of novel targeted drugs that might improve the outcome, particularly in relapse/refractory patients. In this review, we analyse available literature on T-ALL pathogenesis, focusing on molecular aspects of clinical, prognostic, and therapeutic significance.

Autoimmune hemolytic anemia in adults: primary risk factors and diagnostic procedures

Abstract: Autoimmune hemolytic anemia (AIHA) is due to autoantibodies against erythrocytes that may arise either because of primary tolerance breakage or along with several associated conditions, including g...

Predictors of refractoriness to therapy and healthcare resource utilization in 378 patients with primary autoimmune hemolytic anemia from eight Italian reference centers

Abstract: REFERENCES 1. Al-Nouri ZL, Reese JA, Terrell DR, Vesely SK, George JN. Drug-induced thrombotic microangiopathy: a systematic review of published reports. Blood. 2015;125:616-618. 2. Reese JA, Bougie DW, Curtis BR, et al. Drug-induced thrombotic microangiopathy: experience of the Oklahoma registry and the blood Center of Wisconsin. Am J Hematol. 2015;90:406-410. 3. Miller PJ, Farland AM, Knovich MA, Batt KM, Owen J. Successful treatment of intravenously abused oral Opana ER-induced thrombotic microangiopathy without plasma exchange. Am J Hematol. 2014;89: 695-697. 4. Hunt R, Yalamanoglu A, Tumlin J, et al. A mechanistic investigation of thrombotic microangiopathy associated with IV abuse of Opana ER. Blood. 2017;129:896-905. 5. Yui JC, Dispenzieri A, Leung N. Ixazomib-induced thrombotic microangiopathy. Am J Hematol. 2017;92:E53-E55. 6. George JN, Morton JM, Liles NW, Nester CM. After the party's over. N Engl J Med. 2017;371:74-80.

Venetoclax penetrates in cerebrospinal fluid and may be effective in chronic lymphocytic leukemia with central nervous system involvement.

Abstract: Venetoclax, a selective inhibitor of BCL2, has shown promising efficacy in chronic lymphocytic leukemia (CLL) both as single agent or in combination therapy.[1][1] Central nervous system involvement (CNSi) is a rare complication of CLL[2][2],[3][3] and is reported in approximately 0.4% of patients.[

Prevalence and Associated Risk Factors of Mortality Among COVID-19 Patients: A Meta-Analysis.

Abstract: The main aim of this study was to find the prevalence of mortality among hospitalized COVID-19 infected patients and associated risk factors for death. Three electronic databases including PubMed, Science Direct and Google Scholar were searched to identify relevant cohort studies of COVID-19 disease from January 1, 2020, to August 11, 2020. A random-effects model was used to calculate pooled prevalence rate (PR), risk ratio (RR) and 95% confidence interval (CI) for both effect measures. Cochrane chi-square test statistic Q, $${I}^{2}$$ , and $${\tau }^{2}$$ tests were used to measure the presence of heterogeneity. Publication bias and sensitivity of the included studies were also tested. In this meta-analysis, a total of 58 studies with 122,191 patients were analyzed. The pooled prevalence rate of mortality among the hospitalized COVID-19 patients was 18.88%, 95% CI (16.46–21.30), p 65 years vs. < 65 years) [RR 3.59, 95% CI (1.87–6.90), p < 0.001], gender (male vs. female) [RR 1.63, 95% CI (1.43–1.87), p < 0.001], ICU admitted patients [RR 3.72, 95% CI (2.70–5.13), p < 0.001], obesity [RR 2.18, 95% CI (1.10–4.34), p < 0.05], hypertension [RR 2.08,95% CI (1.79–2.43) p < 0.001], diabetes [RR 1.87, 95% CI (1.23–2.84), p < 0.001], cardiovascular disease [RR 2.51, 95% CI (1.20–5.26), p < 0.05], and cancer [RR 2.31, 95% CI (1.80–2.97), p < 0.001]. In addition, significant association for high risk of mortality were also found for cerebrovascular disease, COPD, coronary heart disease, chronic renal disease, chronic liver disease, chronic lung disease and chronic kidney disease. This meta-analysis revealed that the mortality rate among COVID-19 patients was highest in the European region and older age, gender, ICU patients, patients with comorbidity had a high risk for case fatality. Those findings would help the health care providers to reduce the mortality rate and combat this pandemic to save lives using limited resources.

An update on the association of vitamin D deficiency with common infectious diseases.

Abstract: Vitamin D plays an important role in modulating the immune response to infections. Deficiency of vitamin D is a common condition, affecting both the general population and patients in health care facilities. Over the last decade, an increasing body of evidence has shown an association between vitamin D deficiency and an increased risk for acquiring several infectious diseases, as well as poorer outcomes in vitamin D deficient patients with infections. This review details recent developments in understanding the role of vitamin D in immunity, the antibacterial actions of vitamin D, the association between vitamin D deficiency and common infections (like sepsis, pneumonia, influenza, methicillin-resistant Staphylococcus aureus, human immunodeficiency virus type-1 (HIV), and hepatitis C virus (HCV)), potential therapeutic implications for vitamin D replacement, and future research directions.