Measurement of coagulation factor antibody levels is useful for diagnosis and determining therapeutic efficacy in hemorrhagic patients with autoantibodies to coagulation factor VIII and factor V: results from a single center in Japan.

Coagulation factor inhibitors (CFIs) sometimes cause fatal bleeding conditions. Determination of an inhibitor titer (INH-titer) using the Bethesda method is essential for diagnosing diseases associated with CFIs and examining the effects of immunosuppressive therapy. We reviewed 17 cases with CFIs (acquired hemophilia A, n = 11; FV inhibitor, n = 6) to examine the usefulness of determining quantities of an autoantibody to a coagulation factor (CF-IgG) by ELISA for diagnosis and therapeutic efficacy, as compared with INH-titer. One patient with an INH-titer and no evidence of CF-IgG was lupus anticoagulant (LA)-positive, and thus the positive INH-titer may have been a false positive caused by LA. Although INH-titer alone was insufficient to correctly identify patients with CFI, determination of CF-IgG appeared to be useful. In addition, even after INH-titer disappearance, hemorrhagic conditions recurred when CF-IgG was detected. These findings suggest that the presence of a clearance antibody against the coagulation factor might reduce the activity of that coagulation factor even after disappearance of the corresponding neutralizing antibody. Although the diagnosis and therapeutic efficacy can also be determined by INH-titer disappearance and improvement of corresponding coagulation factor activity, determination of CF-IgG by ELISA can improve the accuracy of these assessments.

[Treatment of secondary engraftment failure with granulocyte colony-stimulating factor and eltrombopag after allogeneic peripheral blood stem cell transplantation in adult T-cell leukemia/lymphoma].

A 67-year-old woman diagnosed with adult T-cell leukemia/lymphoma received an induction chemotherapy and showed a partial response. She then underwent allogeneic peripheral blood stem cell transplantation from an HLA-identical sibling donor. Although cyclosporine (CS) was stopped at 120 days after transplantation, chronic graft-versus-host disease (cGVHD) of the skin developed. She was treated with a topical steroid, without exacerbation of the GVHD. She was admitted to our hospital due to the sudden development of pancytopenia at 212 days after the transplantation. She had an EB virus-associated post-transplant lymphoproliferative disorder (PTLD) in the hilum of the lung. The cGVHD of the skin resolved after the administration of prednisolone and CS. However, pancytopenia and PTLD persisted. Treatment with four cycles of rituximab (4×375 mg/m2/week) led to the complete resolution of PTLD, but transfusion-dependent cytopenia did not improve. Secondary engraftment failure was diagnosed, and granulocyte colony-stimulating factor (G-CSF) and eltrombopag (100 mg/day) were administered, leading to gradual improvement of pancytopenia. It was observed that persistent pancytopenia was caused by secondary engraftment failure due to cGVHD in this case. This case suggested that the treatment with G-CSF and eltrombopag is effective for cGVHD-associated secondary engraftment failure.

Successful Treatment with Nivolumab in a Patient with Metastatic Salivary Duct Carcinoma.

Salivary duct carcinoma (SDC) is a rare and highly aggressive malignancy. A 58-year-old man presented with a right-sided submandibular mass and metastatic lesions in the right supraclavicular and inferior internal jugular nodes. He underwent right submandibulectomy and right neck dissection followed by adjuvant chemoradiotherapy. However, relapse occurred in the hilar lymph node and lumbar spine. Although radiotherapy was performed, a second relapse appeared in the hilar lymph nodes and sacral bone. Immunohistochemical analysis revealed negativity for programmed death ligand-1 (PD-L1) in the primary tumor specimen. The patient then received the anti-programmed death-1 (PD-1) antibody nivolumab. His metastatic lesions were completely eliminated after 48 weeks of therapy. This case reveals that anti-PD-1 antibodies are effective even against PD-L1-negative SDC.

Increase in hydrophobicity of Bacillus subtilis spores by heat, hydrostatic pressure, and pressurized carbon dioxide treatments.

The effects of heat treatment (HT), hydrostatic pressure treatment (HPT), and pressurized carbon dioxide treatment (CT) on surface hydrophobicity of B. subtilis 168 spores were investigated. The spore surface hydrophobicity was measured by determining the ratio of hydrophobic spores (RHS) that were partitioned into the n-hexadecane phase from the aqueous spore suspension. The RHS after HT generally increased in a temperature-dependent manner and reached approximately 10% at temperatures above 60°C. The effects of pressurization by HPT and accompanying temperature on increased RHS were complex. The highest RHS after HPT was approximately 17%. Following CT, RHS reached approximately 80% at 5 MPa at 80°C for 30 min. An increased treatment temperature enhanced RHS by CT. The increase in RHS by CT led to the formation of spore clumps and adhesion of spores to hydrophobic surfaces. Acidification of spore suspension to pH 3.2, expected pH during CT, by HCl also increased the adhesion of spores at the similar degree with CT. The spore surface zeta potential distribution was not changed by CT. Furthermore, spores with increased RHS after CT had germination-like phenomena including loss of their refractility and enhanced staining by 4',6-diamidino-2-phenylindole. Physiological germination that was induced by the addition of l-alanine also increased the RHS. From these results, it is clear that CT under heating considerably increases RHS. CT under heating considerably increases RHS. This increase in RHS may be due to acidification or germination-like phenomena during CT.