Whole-genome sequencing surveillance of Siberian tick-borne encephalitis virus (TBEV) identifies an additional lineage in Kyrgyzstan.

Tick-borne encephalitis virus (TBEV) is the most prevalent tick-borne viral disease in Europe and Asia. There are three main subtypes of the virus: European, Siberian, and Far Eastern, each of which having distinctive ecology, clinical presentation, and geographic distribution. In recent years, other TBEV subtypes have been described, namely the Himalayan and Baikalian subtypes.

Development of targeted whole genome sequencing approaches for Crimean-Congo haemorrhagic fever virus (CCHFV).

Crimean-Congo haemorrhagic fever (CCHF) is the most prevalent human tick-borne viral disease, with a reported case fatality rate of 30 % or higher. The virus contains a tri-segmented, negative-sense RNA genome consisting of the small (S), medium (M) and large (L) segments encoding respectively the nucleoprotein (NP), the glycoproteins precursor (GPC) and the viral RNA-dependent RNA polymerase (RDRP). CCHFV is one of the most genetically diverse arboviruses, with seven distinct lineages named after the region they were first reported in and based on S segment phylogenetic analysis.

Third International Conference on Crimean-Congo Hemorrhagic Fever in Thessaloniki, Greece, September 19-21, 2023.

The Third International Conference on Crimean-Congo Hemorrhagic Fever (CCHF) was held in Thessaloniki, Greece, September 19-21, 2023, bringing together a diverse group of international partners, including public health professionals, clinicians, ecologists, epidemiologists, immunologists, and virologists. The conference was attended by 118 participants representing 24 countries and the World Health Organization (WHO). Meeting sessions covered the epidemiology of CCHF in humans; Crimean-Congo hemorrhagic fever virus (CCHFV) in ticks; wild and domestic animal hosts; molecular virology; pathogenesis and animal models; immune response related to therapeutics; and CCHF prevention in humans.

Recovery of complete genome sequences of Crimean-Congo haemorrhagic fever virus (CCHFV) directly from clinical samples: A comparative study between targeted enrichment and metagenomic approaches.

Crimean-Congo haemorrhagic fever (CCHF) is the most prevalent human tick-borne viral disease, endemic to the Balkans, Africa, Middle East and Asia. There are currently no licensed vaccines or effective antivirals against CCHF. CCHF virus (CCHFV) has a negative sense segmented tripartite RNA genome consisting of the small (S), medium (M) and large (L) segments.

Investigating the effect of ribavirin treatment on genetic mutations in Crimean-Congo haemorrhagic fever virus (CCHFV) through next-generation sequencing.

Crimean-Congo haemorrhagic fever (CCHF) is the most widespread tick-borne viral haemorrhagic fever affecting humans, and yet a licensed drug against the virus (CCHFV) is still not available. While several studies have suggested the efficacy of ribavirin against CCHFV, current literature remains inconclusive. In this study, we have utilised next-generation sequencing to investigate the mutagenic effect of ribavirin on the CCHFV genome during clinical disease.

Risk of rehospitalization for patients using clopidogrel with a proton pump inhibitor.

Background: Recent pharmacodynamic and retrospective clinical analyses have suggested that proton pump inhibitors (PPIs) may modify the antiplatelet effects of clopidogrel bisulfate.

Methods: We conducted a retrospective cohort study of persons enrolled in a multistate health insurance plan with commercial and Medicare clients to evaluate adverse clinical outcomes in patients using clopidogrel plus a PPI compared with clopidogrel alone. Patients who were discharged from the hospital after myocardial infarction (MI) or coronary stent placement and treated with clopidogrel plus a PPI (n = 1033) were matched 1:1 (using propensity scoring) with patients with similar cardiovascular risk factors treated with clopidogrel alone.

Way to go live: a framework for new IT implementation.

Implementation of a health IT system is an initiative that requires a clear game plan. That plan should entail: Careful initiative planning and vendor selection led by an individual with the appropriate technical expertise, Contract negotiations led by an individual who understands the inherent traps and pitfalls of such negotiations, Choice of a qualified project manager, Ongoing monitoring of the project's status. Implementation including conversion of the right amount of legacy data at the right time, Assignment of a point person or persons to monitor results following implementation.

Bleeding disorders in Noonan syndrome: three case reports and review of the literature.

Purpose: Noonan syndrome (NS) is a congenital disorder characterized by various phenotypic features and congenital anomalies. Bleeding disorders are among the more serious, common, yet poorly defined complications associated with NS. As a means of focusing on these complications, we report three patients with stigmata of NS, each of whom had a combination of different hemostatic disorders, and review the literature on bleeding disorders in NS.

AIDS-associated non-Hodgkin's lymphomas as primary and secondary AIDS diagnoses in hemophiliacs. Hemophilia Malignancy Study Group.

We studied the characteristics and temporal trends of AIDS- associated non-Hodgkin's lymphoma (AIDS-NHL) in individuals with hemophilia. Prospective data were collected on 33 HIV-positive hemophiliacs with AIDS-NHL enrolled in the Hemophilia Malignancy Study (HMS), of whom 21 had primary and 12 had secondary or subsequent AIDS-defining illnesses, and analyzed for frequency and temporal trends. As compared with primary AIDS- NHL, secondary AIDS-NHL occurred at an older mean age, 37 versus 29 years (p = 0.

T lymphocyte proliferative responses induced by recombinant factor VIII in hemophilia A patients with inhibitors.

In this study we sought to determine whether factor VIII-reactive T lymphocytes were present in hemophilia A patients with inhibitor antibodies. Peripheral blood mononuclear cells (MNC) were obtained from 12 severe hemophilia A patients having high titer inhibitors, 4 severe hemophilia A patients without inhibitors and 5 normal male subjects. B cell-depleted MNC were cultured in serum-free medium in the absence or presence of 2 micrograms of recombinant human factor VIII (rFVIII) per ml, and cellular proliferation was assessed after 5 days of culture by measuring 3H-thymidine incorporation.

Frequency of inhibitor development in haemophiliacs treated with low-purity factor VIII.

Clinical studies evaluating highly purified monoclonal-antibody-derived and recombinant-DNA-derived clotting factor concentrates in previously untreated (PUPS) severe factor VIII (FVIII) deficient haemophilia patients, have documented an increased frequency of inhibitors compared with that seen in patients who have received less pure products. However, a valid comparison of inhibitor frequency in patients treated with pure and less pure products has not been possible because appropriate studies have not been done in PUPS treated with the less pure products. To determine the frequency of inhibitor development in PUPS treated solely with less pure plasma-derived products (specific activities < 5 FVIII U/mg protein), we reviewed the records of all haemophilia patients born between 1975 and 1985 and treated with such products at any of seven centres.

Treatment of hemophilia A with a highly purified factor VIII concentrate prepared by anti-FVIIIc immunoaffinity chromatography.

To reduce the risk of pathogenic virus transmission associated with the therapeutic administration of plasma-derived anti-hemophilic factor (FVIIIc), a process utilizing anti-FVIIIc immunoaffinity chromatography to isolate FVIIIc has been developed. In addition, the starting cryoprecipitate solution has been treated with an organic solvent/detergent mixture to inactivate lipid-enveloped viruses. A final ion exchange chromatography step is used to further remove contaminants, e.

PROPLEX vs. PROPLEX SX: a controlled double blind study of the effectiveness in treating acute hemarthroses in hemophilia A patients with inhibitors to factor VIII.

A blinded randomized multicenter trial of two non-activated prothrombin complex concentrates was carried out to determine the clinical effectivity in the treatment of acute hemarthrosis in hemophiliac patients with inhibitors. The one product was prepared via DEAE Sephadex chromatography, while the second was fractionated via various precipitation procedures including polyethylene glycol. Equivalence of the two products was established with less than 15% difference in efficacy rates.

Immunologic abnormalities in patients with hemophilia A.

To assess the immunologic status of healthy persons with hemophilia A, we performed studies of T cell immunity in 21 patients, 10 given only cryoprecipitate and 11 given factor VIII concentrate. Patients in the factor VIII group had significantly decreased helper/suppressor T cell ratios. Both groups had diminished mononuclear cell response to phytohemagglutinin and normal mixed lymphocyte culture, compared with controls.

Iron deficiency in health and disease.

Iron deficiency is a common problem in otherwise healthy children and in children with systemic disease. We have reviewed the pathophysiology, laboratory diagnosis, and systemic effects of iron deficiency. We have emphasized that routine screening procedures do not efficiently predict those otherwise healthy children who will demonstrate a therapeutic response to iron.

Immunization of immunosuppressed patients with pneumococcal polysaccharide vaccine.

The antibody response after immunization with capsular polysaccharides of Streptococcus pneumoniae of patients with Hodgkin's disease or with carcinoma of the head and neck was studied. Patients with Hodgkin's disease who were immunized prior to the institution of immunosuppressive therapy were capable of responding to each of the pneumococcal polysaccharides evaluated. The level of antibody achieved by the patients is lower than that of normal control subjects.

Response to pneumococcal polysaccharide vaccine in patients with untreated Hodgkin's disease. Children's Cancer Study Group Report.

Patients with Hodgkin's disease (HD) have a high risk of overwhelming pneumococcal infections after splenectomy. Previous studies have shown that HD patients given polyvalent pneumococcal polysaccharide (PPS) vaccine after immunosuppressive therapy have a suboptimum antibody response. This study shows significant antibody response in HD patients to PPS vaccine given before radiation and chemotherapy.

G6PD San Francisco: a new variant of glucose-6-phosphate dehydrogenase associated with congenital nonspherocytic hemolytic anemia.

Congenital nonspherocytic hemolytic anemia in an adult male of Scandinavian ancestry was associated with virtual absence of G6PD activity in red cells. Characterization of G6PD purified from leukocytes using standard WHO techniques revealed diminished electrophoretic mobility, marked lability on heating at 46 degrees C, normal pH optimum and utilization of alternate substrates (2-deoxy G6P, D-amino NADP), elevated Km NADP, and striking susceptibility to NADPH inhibition. The variant G6PD, which appears to be unique, has been designated G6PD San Francisco.

Polyvalent pneumococcal-polysaccharide immunization of patients with sickle-cell anemia and patients with splenectomy.

To reduce the risk of infection from Streptococcus pneumoniae in hyposplenic patients we administered octavalent pneumococcal vaccine to 77 patients with sickle-cell disease and 19 asplenic persons and compared their response with 82 controls (38 age-matched normal persons and 44 normal black African children). Fifty micrograms each of pneumococcal-polysaccharide Types 1, 3, 6, 7, 14, 18, 19, and 23 were administered subcutaneously. Post-immunization serums (three to four weeks) were available from 52 of 77 patients with sickle-cell disease; the percent responding and the magnitude of the indirect hemagglutination response were comparable to those of the controls.