Acute chest syndrome (ACS) is a common complication and reason for hospital admission in patients with sickle cell disease (SCD). It is also the most common cause of death in this patient population. Most of the time, the trigger for ACS in an individual patient cannot be identified. However, although infection is the most common identifiable cause for ACS, other important triggers are vaso‐occlusive crisis (VOC) and asthma. This comprehensive review will focus on the pathogenesis, clinical characteristics, complications and treatment available to manage ACS. But importantly, this review will highlight new possible etiologies, with the goal of improving oxygenation and, therefore, a reduction in sickling and lung damage in this patient population.
We previously reported durable complete responses following brief courses of rituximab and prednisone with or without cyclophosphamide in four patients with autoimmune haemophilia and inhibitor titres of 5-60 BU. We report here responses to this monoclonal anti-CD20 antibody in four additional patients, including two patients with inhibitor titres >200 BU. Factor VIII levels became normal 2-35weeks after 4 or 8 weekly doses of rituximab, brief courses of prednisone and in one patient immunoglobulin. Complete responses are ongoing at 10 months in two patients. Two patients relapsed: a patient whose initial inhibitor titre was 525 BU relapsed at 3.5 months and a long-term prednisone-dependent patient at 8.5 months. Both responded to second courses of rituximab and prednisone and are in remission. Our experience suggests that rituximab is a safe and effective addition to immunosuppression with prednisone and cyclophosphamide to treat autoimmune haemophilia, and may permit early discontinuation or even avoidance of these potentially toxic agents. High-titre inhibitor patients, however, may require multiple courses of rituximab or the addition of cyclophosphamide. Pending randomized studies, we propose an algorithm based on our experience and other reports for incorporating rituximab in the treatment of this rare disorder.
PURPOSE Pulmonary embolism is incidentally diagnosed in up to 5% of patients with cancer on routine imaging scans. The clinical relevance and optimal therapy for incidental pulmonary embolism, particularly distal clots, is unclear. The aim of the current study was to assess current treatment strategies and the long-term clinical outcomes of incidentally detected pulmonary embolism in patients with cancer. PATIENTS AND METHODS We conducted an international, prospective, observational cohort study between October 22, 2012, and December 31, 2017. Unselected adults with active cancer and a recent diagnosis of incidental pulmonary embolism were eligible. Outcomes were recurrent venous thromboembolism, major bleeding, and all-cause mortality during 12 months of follow-up. Outcome events were centrally adjudicated. RESULTS A total of 695 patients were included. Mean age was 66 years and 58% of patients were male. Most frequent cancer types were colorectal (21%) and lung cancer (15%). Anticoagulant therapy was initiated in 675 patients (97%), of whom 600 (89%) were treated with low-molecular-weight heparin. Recurrent venous thromboembolism occurred in 41 patients (12-month cumulative incidence, 6.0%; 95% CI, 4.4% to 8.1%), major bleeding in 39 patients (12-month cumulative incidence, 5.7%; 95% CI, 4.1% to 7.7%), and 283 patients died (12-month cumulative incidence, 43%; 95% CI, 39% to 46%). The 12-month incidence of recurrent venous thromboembolism was 6.4% in those with subsegmental pulmonary embolism compared with 6.0% in those with more proximal pulmonary embolism (subdistribution hazard ratio, 1.1; 95% CI, 0.37 to 2.9; P = .93). CONCLUSION In patients with cancer with incidental pulmonary embolism, risk of recurrent venous thromboembolism is significant despite anticoagulant treatment. Patients with subsegmental pulmonary embolism seemed to have a risk of recurrent venous thromboembolism comparable to that of patients with more proximal clots.
SummaryOral immunization with an attenuated Salmonella typhimurium recombinant containing the fulllength Plasmodium berghei circumsporozoite (CS) gene induces protective immunity against P. berghei sporozoite challenge in the absence of antibody. We found that this immunity was mediated through the induction of specific CD8+ T cells since in vivo elimination of CD8+ cells abrogated protection. In vitro studies revealed that this Salmonella-P. berghei CS recombinant induced class I-restricted CD8+ cytotoxic T cells that are directed against the P berghei CS peptide epitope spanning amino acids 242-253 . This is the same peptide that previously was identified as the target of cytotoxic T lymphocytes (CTL) induced by sporozoite immunization. Salmonella-P. fkiparum CS recombinants were constructed that contained either the full-length CS gene or a repeatless gene consisting of CS flanking sequences . Both of these vaccines were able to induce CD8+ CTL directed against P. fakiparum CS peptide 371-390, which is identical to the target of CTL induced by sporozoites and vaccinia CS recombinants. These results directly demonstrate the ability of an intracellular bacteria such as Salmonella to induce class I-restricted CD8+ CTL and illustrate the importance of CD8 + CTL in immunity to malaria .
The WB isolate of Giardia lamblia expresses a cysteine-rich 170-kD surface antigen (CRP170) that undergoes antigenic variation. An (6E7), cytotoxic for isolates expressing CRP170, was used in another study to select antigenic variants from clones of the WB isolate of Giardia. CRP170 was replaced by surface-labeled bands ranging in size from approximately 50 to 170 kD. In this study, mAb 6E7 was used to isolate a 1-kb portion of the CRP170 gene (M2-1) from a lambda gt 11 expression library. The M2-1 clone hybridized to a 5.4-kb transcript from isolates expressing CRP170 but did not hybridize to RNA from antigenic variants. Evidence was found for frequent rearrangements at the CRP170 gene locus. DNA sequencing of the M2-1 clone revealed the presence of long tandem repeats. The putative amino acid sequence of M2-1 reveals a 12% cysteine content, and CRP170 is readily labeled in vivo with cysteine.
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