An easy assay to detect autoantibodies neutralizing cytokines in subjects with critical infections.

Autoantibodies against type I interferon (IFN) are associated with a worse outcome in COVID-19. The measurement of cytokine-neutralizing autoantibodies has been limited, hindering understanding of their role in clinical practice. We showed that an easy and reliable assay can be reproduced and validated to measure the neutralizing potency of autoantibodies directed to type I or type II IFN.

Bloodstream Infection in an Adult Patient with COVID-19 and Alcohol Use Disorder: A Unique Case and a Systematic Review of the Literature.

is an uncommon species causing invasive fungemia. This yeast is mainly associated with the colonisation of intravascular catheters, complicated intra-abdominal infections, and infections in the paediatric population. Here, we report a case of bloodstream infection in a 53-year-old man.

Direct-acting antiviral agents for hepatitis C virus-mixed cryoglobulinaemia: dissociated virological and haematological responses.

The hepatitis C virus-positive (HCV+) mixed cryoglobulinaemia (MC) is associated with haematological alterations such as monoclonal B-cell lymphocytosis or non-Hodgkin lymphomas (NHLs). Antiviral therapy for MC, based on interferon and ribavirin, has been shown to be able to eliminate the viral replication as well as the B-cell monoclonal alterations. Many studies have reported the efficacy of direct-acting antivirals (DAAs) in the treatment of HCV+ MC.

Survival and Prognostic Factors in Mixed Cryoglobulinemia: Data from 246 Cases.

Introduction: The clinical and therapeutic management of mixed cryoglobulinemia (MC) remains a subject of controversy. In addition, most studies have not recorded the long-term follow-up and the outcome of these cases.

Material And Methods: We enrolled 246 patients affected by MC who were consecutively admitted to our Department from January 1993 to February 2013.

Hepatitis C virus and non-Hodgkin's lymphomas: Meta-analysis of epidemiology data and therapy options.

Hepatitis C virus (HCV) is a global health problem affecting a large fraction of the world's population: This virus is able to determine both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, a B-cell "benign" lymphoproliferative disorders, represents the most closely related as well as the most investigated HCV-related extrahepatic disorder. Since this virus is able to determine extrahepatic [non-Hodgkin's lymphoma (NHL)] as well as hepatic malignancies (hepatocellular carcinoma), HCV has been included among human cancer viruses.

No evidence of Polyomavirus and EBV infections in Italian patients with mixed cryoglobulinemia infected chronically with HCV.

Mixed cryoglobulinemia is a lymphoproliferative disorder associated with hepatitis C virus (HCV). In patients chronically affected by HCV the prevalence of mixed cryoglobulinemia is variable ranging from 0% to 56%. To verify whether polyomaviruses (PyV) play a role in this disorder a total of 222 blood samples from 63 HCV chronic patients, 43 with mixed cryoglobulinemia, 59 chronic lymphocytic leukemia, 50 polytransfused patients, and 50 blood donors were evaluated for Merkel (MCPyV), BKV, JCV, and SV40.

Platelet production and destruction in liver cirrhosis.

Background & Aims: Thrombocytopenia is common in liver cirrhosis (LC) but the mechanisms are not fully understood. The purpose of our work was to evaluate platelet kinetics in LC with different etiologies by examining platelet production and destruction.

Methods: Ninety-one consecutive LC patients (36 HCV, 49 alcoholics, 15 HBV) were enrolled.

Whey protein ingestion enhances postprandial anabolism during short-term bed rest in young men.

We tested the relative ability of rapidly digested whey and slowly digested casein to stimulate net whole-body protein synthesis during prolonged physical inactivity. We studied 8 young male volunteers after they consumed isonitrogenous casein or whey mixed meals on d 12 or d 14 of experimental bed rest. Rates of phenylalanine hydroxylation were measured by primed-constant oral administration of L[2-(2)H(2)]tyrosine and L[ring-(2)H(5)]phenylalanine for 3 h in the postabsorptive state and 6 h after an isonitrogenous bolus meal containing sucrose (0.

Etiologic treatment of hepatitis C virus-associated mixed cryoglobulinemia.

The treatment of mixed cryoglobulinemia (MC) includes several drugs--steroids, cyclosporins, colchicine, plasmapheresis--but given the documented association between MC and hepatitis C virus (HCV), the treatment of choice seems to be antiviral therapy. Several authors have reported the efficacy of interferon (IFN) alpha in the inhibition of HCV replication and reduction of cryoglobulin levels. The therapy with IFN as monotherapy in MC shows a complete response rate in only 10 -12% of cases.

Activation of naïve B lymphocytes via CD81, a pathogenetic mechanism for hepatitis C virus-associated B lymphocyte disorders.

Infection with hepatitis C virus (HCV), a leading cause of chronic liver diseases, can associate with B lymphocyte proliferative disorders, such as mixed cryoglobulinemia and non-Hodgkin lymphoma. The major envelope protein of HCV (HCV-E2) binds, with high affinity CD81, a tetraspanin expressed on several cell types. Here, we show that engagement of CD81 on human B cells by a combination of HCV-E2 and an anti-CD81 mAb triggers the JNK pathway and leads to the preferential proliferation of the naïve (CD27-) B cell subset.

Muscle glutamine depletion in the intensive care unit.

Glutamine is primarily synthesized in skeletal muscle and enables transfer of nitrogen to splanchnic tissues, kidneys and immune system. Discrepancy between increasing rates of glutamine utilization at whole body level and relative impairment of de novo synthesis in skeletal muscle leads to systemic glutamine deficiency and characterizes critical illness. Glutamine depletion at whole body level may contribute to gut, liver and immune system disfunctions, whereas its intramuscular deficiency may directly contribute to lean body mass loss.

Treatment with peg-interferon alfa-2b and ribavirin of hepatitis C virus-associated mixed cryoglobulinemia: a pilot study.

Background/aims: The aim of this study is to verify the efficacy and safety of peg-interferon alfa-2b in combination with ribavirin for initial treatment of HCV-associated mixed cryoglobulinemia.

Methods: Eighteen patients (7 women and 11 men) affected by mixed cryoglobulinemia were included in the study and treated with peg-interferon alfa-2b 1.0 microg/kg once a week plus ribavirin (1000 mg daily) for 48 weeks, regardless of the HCV genotype.

Comparable functions of plasmacytoid and monocyte-derived dendritic cells in chronic hepatitis C patients and healthy donors.

Background/aims: Dendritic cells (DCs) play a key role in immune responses through antigen presentation and cytokine secretion. Hepatitis C virus (HCV) is able to escape elimination by the immune system and often establishes a chronic infection. To investigate whether DC dysfunction is involved in this process, we have studied monoycte-derived DCs (Mo-DCs) and plasmacytoid DCs (pDCs), which produce large amounts of IFN-alpha, from chronic HCV patients and healthy donors.

Interferon plus ribavirin in patients with hepatitis C virus positive mixed cryoglobulinemia resistant to interferon.

Objective: Only a small fraction of patients with hepatitis C virus (HCV) positive mixed cryoglobulinemia achieve longterm recovery after interferon (IFN) therapy; we evaluated the effectiveness and safety of combination therapy (interferon plus ribavirin) in nonresponders or those who relapsed after one or more courses of IFN.

Methods: Twenty-seven patients with HCV positive mixed cryoglobulinemia were studied. All were treated with IFN-a2b (3 MU 3 times weekly) for one year, plus daily oral ribavirin 1000 or 1200 mg.

Thalidomide in myelofibrosis with myeloid metaplasia: a pooled-analysis of individual patient data from five studies.

Trials to determine the effect of thalidomide in patients with Myelofibrosis with Myeloid Metaplasia (MMM) have produced inconclusive results due to different criteria for response and heterogeneous study participants. We undertook a pooled-analysis to assess the effects of such treatment on a larger series of cases and with a uniform assessment of response. We used updated data on 62 individual patients from 5 phase II trials that evaluated thalidomide therapy in MMM patients.

Thalidomide in myelodysplastic syndromes.

The myelodysplastic syndromes are a heterogeneous group of clonal diseases of haemopoiesis, which are a challenge for both biologists and clinicians. In this paper the current classification and the recent advances in the understanding the disease mechanisms are reviewed. The recent therapeutic advances are also indicated, such as intensive and low-dose chemotherapy, new drugs, erythropoietin and colony-stimulating factors.

Effectiveness of leukocyte interferon in patients affected by HCV-positive mixed cryoglobulinemia resistant to recombinant alpha-interferon.

Objective: Interferon is the first-choice therapy for HCV-positive mixed cryoglobulinemia, but only a small fraction of the patients show long-term recovery from the disease. In non-responders or relapsers, the second-line therapy (high dose interferon) generally is not effective. The aim of this study was to evaluate the effectiveness of leukocyte interferon as a second-line therapy in patients who are non-responders or relapsers to a first course of recombinant interferon.

The clinical and biological effects of thalidomide in patients with myelodysplastic syndromes.

Thirty patients with myelodysplastic syndromes (MDS) were treated with thalidomide at 100 mg/d p.o., increased as tolerated to 400 mg/d for 12 weeks.

Successful establishment of long-term bone marrow cultures in 103 patients with myelodysplastic syndromes.

We used bone marrow biopsies instead of mononuclear cells to maintain long-term cultures from 103 patients belonging to all five sub-categories of myelodysplastic syndromes (MDS), as well as 12 normal controls. By week 4, 30-50% confluency was reached and could be maintained for up to 12 weeks with 100% confluency. The four prominent cells were fibroblasts, macrophages, endothelial cells and adipocytes.

Thalidomide produces transfusion independence in long-standing refractory anemias of patients with myelodysplastic syndromes.

Thalidomide was administered to 83 patients with myelodysplastic syndrome (MDS), starting at 100 mg by mouth daily and increasing to 400 mg as tolerated. Thirty-two patients stopped therapy before 12 weeks (minimum period for response evaluation), and 51 completed 12 weeks of therapy. International Working Group response criteria for MDS were used to evaluate responses.

Haemochromatosis gene mutations in a clustered Italian population: evidence of high prevalence in people of Celtic ancestry.

Hereditary haemochromatosis is an inherited disorder characterised by an excessive iron absorption from the diet and is associated with several HFE gene mutations. One hypothesis is that these genetic mutations originated in the Celtic populations. The aim of this study is to determine the frequency of HFE gene mutations in a clustered Italian population of Celtic ancestry (Cimbri, Asiago plateau).

Human leucocyte interferon-alpha in the treatment of chronic hepatitis C.

Aim: To assess the efficacy of different schedules of human leucocyte interferon alpha in chronic hepatitis C.

Patients And Methods: A total of 213 naive patients with chronic hepatitis C were treated with 4 different schedules of human leucocyte interferon alpha. Sustained response was defined as persistently normal alanine amino transferase values with negative serum hepatitis C virus-RNA up to 12 months after therapy withdrawal.