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Acquired hemophilia A (AHA) is a rare, life-threatening bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). Immunosuppressive therapy for AHA aims to arrest bleeding by eliminating FVIII inhibitors. Factor VIII activity overshoot after complete remission (CR) has been reported anecdotally, but details remain unclear. We retrospectively analyzed data from 17 patients with AHA who achieved CR under immunosuppressive therapy between 2009 and 2019 at Gunma University Hospital. FVIII activity overshoot was defined as ≥ 150%. All 17 patients had low FVIII activity (median 2.1%; range < 1.0-8.9%) due to FVIII inhibition (median 14.7 BU/mL; range 2.0-234.0) and all achieved CR within a median of 39 (range 19-173) days. Overshoot occurred in 11 (64.7%) patients and maximal FVIII activity reached > 200% in six of them. The median duration from CR to overshoot was 13 (range 0-154) days. The FVIII overshoot was transient (72.7%) or persistent (27.3%). Venous thromboembolism developed as a complication of overshoot in one patient due to iliac vein compression by a massive hematoma. Overshoot of FVIII activity after CR occurs more frequently than previously expected in patients with AHA.

Purpose: The clinical efficacies of some antiretroviral drugs are known to not depend on its concentration in blood. To establish a method of dosage adjustment for darunavir (DRV) based on pharmacokinetic theory, we analyzed the correlation between DRV levels in peripheral blood mononuclear cells (PBMCs) and plasma., Methods: The concentrations of DRV and ritonavir (RTV) in plasma and PBMCs of 31 samples obtained from 19 patients were analyzed. An in vitro kinetic study using MOLT-4 cells was performed to assess the contribution of RTV to the intracellular accumulation of DRV., Results: DRV levels in PBMCs varied between 7.91 and 29.36 ng/10 6 cells (CV 37.5%), while those in plasma were greater. No significant correlation was found between the trough level of DRV in plasma and that in PBMCs (p = 0.575). The inter-day difference in DRV levels in PBMCs seemed smaller than that in plasma (- 41.6-23.0% vs - 83.3-109.1%). In the in vitro study, the elimination half-life of cellular efflux of DRV was 15.7 h in the absence of RTV and extended to 47.6 h in the presence of RTV., Conclusions: We found a poor correlation between intracellular DRV and plasma DRV levels in patients receiving highly active antiretroviral therapy. The efflux rate of DRV from cells was slow; therefore, the concentration of DRV in PBMCs may reflect average exposure to the drug and clinical efficacy.

An HIV-infected man in his 30s was transferred to our hospital after the discontinuation of antiretroviral therapy (ART) for 4 years. An intraoral tumor was identified, and a biopsy was performed. The diagnosis was Kaposi's sarcoma (KS) and disseminated lesions were detected in his respiratory tract and both lungs on computed tomography (CT) and 2-[18F] fluoro-2-deoxy-D-glucose positron-emission tomography (FDG/PET) imaging with increasing standardized uptake volume (SUV: max 7.4). On the 7th day, he was intubated to maintain his airway, then antiretroviral therapy and chemotherapy with pegylated liposomal doxorubicin were immediately initiated. After a period of remission, pulmonary lesions were detected again. We regarded them as a manifestation of immune reconstitution inflammatory syndrome (IRIS) and gave him short term corticosteroids. The lesions were then successfully controlled without additional chemotherapy. This case suggests that early induction of ART and intensive care can result in the survival of patients with KS having serious stenosis of the respiratory tract. Furthermore, this presenting case suggested that the use of corticosteroids could be a candidate to control IRIS even in patients with Kaposi's sarcoma.

Background: Mannose-binding lectin (MBL) plays an important role in innate immunity. The aim of this study was to determine whether genetic variants of MBL confer susceptibility to Pneumocystis pneumonia (PCP) in patients with advanced human immunodeficiency virus (HIV) infections., Objective: HIV patients (n = 53) having CD4 counts <200/μL who were admitted to our hospital were analyzed. Of these 53 patients, 30 had PCP at admission, and 23 did not. Genotypes at six single nucleotide polymorphisms (SNP) in MBL2 gene and serum MBL levels were determined for each patient, and compared between patients with or without PCP. We also examined whether MBL enhances phagocytosis of macrophages against rat-type Pneumocystis organism in vitro., Results: Genotypes associated with low production of MBL were significantly more common in the PCP group than in the non-PCP group (P = 0.049, odds ratio 2.17, 95% CI 1.02-4.63). Serum MBL levels were significantly higher in the non-PCP group (P = 0.039). Findings from in vitro experiments indicated that MBL act as a direct opsonin enhancing macrophage-mediated phagocytosis of Pneumocystis organisms., Conclusion: Genetic variation of MBL production influences susceptibility to PCP in patients with advanced HIV infection, and can be regarded as a risk factor for PCP., (Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Secondary metabolite phenotypes in nine species of the Hamigera clade were analysed to assess their correlations to a multi-gene species-level phylogeny. High-pressure-liquid-chromatography-based chemical analysis revealed three distinctive patterns of secondary metabolite production: (1) the nine species could be divided into two groups on the basis of production of the sesquiterpene tricinonoic acid; (2) the tricinonoic acid-producing group produced two cyclic peptides avellanins A and B; (3) the tricinonoic acid-non-producing group could be further divided into two groups according to the production of avellanins A and B. The chemical phenotype was consistent with the phylogeny of the species, although metabolite patterns were not diagnostic at the species level. In addition, the taxonomy of the Hamigera clade was updated with the new combination Hamigera ingelheimensis proposed for Merimbla ingelheimensis , so that all species in the clade are now in the same genus.

We present a case of a 74-year-old male, who had a relapse of minimal change nephrotic syndrome (MCNS) as the initial presentation of acquired hemophilia A. MCNS had been maintained in remission with prednisolone 10 mg for 15 years. In early December 2005, the patient developed edema of the right leg, was admitted to a local general hospital, and was diagnosed as having a relapse of MCNS based on massive proteinuria (urine protein 6.1 g/day). One week later, severe anemia (hemoglobin 4.4 g/dl) and acute renal failure (creatinine 2.0 mg/dl) developed, and a CT scan of the abdomen revealed a hematoma in the left iliopsoas muscle. He was referred to our hospital with bleeding tendency. Laboratory examination revealed prolonged APTT 80.5 seconds), reduced factor VIII activity (<1%) and thepresence of factor VIII inhibitor at a titer of 19 Bethesda units/ml, based on which he was diagnosed as having acquired hemophilia A. With recombinant activated FVII, hemostasis was obtained and prednisolone administration 60 mg/day (1 mg/kg) was started. Both the acquired hemophilia A and MCNS responded well to the treatment with prednisolone. Six weeks after initiation of the treatment, factor VIII inhibitor and urine protein disappeared. This patient is considered to be a rare case; to the best of our knowledge, this is the third report of acquired hemophilia A with nephrotic syndrome.

Inherited macrothrombocytopenia is a rare illness that is often misdiagnosed as idiopathic thrombocytopenia (ITP), a more widespread acquired disease. Automated blood cell counters in routine clinical use usually miss giant platelets and underestimate mean platelet volume (MPV). Incorrect diagnoses might expose patients to a risk of unnecessary treatment. The ADVIA 120 hematology counter efficiently detects large platelets based on two-dimensional laser light scatter. The present study measures and re-evaluates MPV using the ADVIA 120 in 112 patients who had initially been diagnosed with ITP. We identified 11 unrelated patients as having probable macrothrombocytopenia (average MPV of 19.2+/-3.8 fL; normal range 7.8-10.2). Functional, phenotypical and DNA analyses confirmed that three of these patients had Bernard-Soulier syndrome and one had MYH9-related disease, both of which are the most common forms of inherited macrothrombocytopenia. We stress that a conventional automated hematology analyzer had overlooked giant platelets in these patients, and that all of them had received high-dose steroid therapy and/or splenectomy before this study according to a diagnosis of ITP. Thus, checking MPV using the ADVIA 120 in thrombocytopenic patients is a useful method of correctly diagnosing inherited macrothrombocytopenia, and thus avoiding patient exposure to unnecessary and sometimes toxic treatment.