Human T-cell Lymphotropic Virus Type-1-associated Bronchioloalveolar Disorder with Non-necrotizing Granulomas: A Case Report and Literature Review.

Human T-cell lymphotropic virus type-1 (HTLV-1)-associated bronchioloalveolar disorder (HABA) is a pulmonary disorder characterized by lymphocytic infiltration of the peribronchiolar space and interstitium in HTLV-1 carriers and in adult T-cell leukemia/lymphoma (ATLL). We herein report an 85-year-old woman carrying HTLV-1 with HABA who presented with a miliary pattern of micronodules in both lungs on high-resolution computed tomography and a lymphocytic infiltrate with non-necrotizing granulomas on pathology. This rare case of HABA should be differentiated from sarcoidosis, hypersensitivity pneumonitis, or miliary tuberculosis.

Exploring the Multifaceted Nexus of Uric Acid and Health: A Review of Recent Studies on Diverse Diseases.

The prevalence of patients with hyperuricemia or gout is increasing worldwide. Hyperuricemia and gout are primarily attributed to genetic factors, along with lifestyle factors like consuming a purine-rich diet, alcohol and/or fructose intake, and physical activity. While numerous studies have reported various comorbidities linked to hyperuricemia or gout, the range of these associations is extensive. This review article focuses on the relationship between uric acid and thirteen specific domains: transporters, genetic factors, diet, lifestyle, gout, diabetes mellitus, metabolic syndrome, atherosclerosis, hypertension, kidney diseases, cardiovascular diseases, neurological diseases, and malignancies. The present article provides a comprehensive review of recent developments in these areas, compiled by experts from the Young Committee of the Japanese Society of Gout and Uric and Nucleic Acids. The consolidated summary serves to enhance the global comprehension of uric acid-related matters.

[A case of progressive multifocal leukoencephalopathy associated with daratumumab, bortezomib, and dexamethasone for multiple myeloma].

An 83-year-old man presented with visual disturbance and right hemiparalysis, one month after daratumumab, bortezomib, and dexamethasone administration for multiple myeloma (MM). Blood screens revealed a CD4+ T-lymphocyte count of 132/µl. Diffusion weighted and fluid-attenuated inversion-recovery MR imaging showed high intensity signals in the both occipital lobes and left precentral area. The patient had no history of human immunodeficiency virus infection. Cerebrospinal fluid (CSF) JC virus (JCV) was positive (83 copies/ml), as indicated by PCR. The patient was diagnosed with progressive multifocal leukoencephalopathy (PML). MM treatment was discontinued, and mefloquine and mirtazapine therapy was started. However, the CSF JCV-DNA PCR count did not improve (111 copies/ml) after 30 days from starting mefloquine and mirtazapine therapy. The patient died six months after symptom onset. Conclusively, patients with decreased CD4+ T lymphocyte counts following DBd therapy for MM, the possibility of PML should be considered.

Clinical outcomes of gemtuzumab ozogamicin for relapsed acute myeloid leukemia: single-institution experience.

We retrospectively evaluated the clinical efficacy and toxicity of gemtuzumab ozogamicin (GO) in patients with relapsed acute myeloid leukemia (AML). Nineteen patients (median 70 years) received GO (9 mg/m2, days 1 and 15) as salvage therapy in our institution between 2006 and 2017. The primary endpoint was the response rate. The secondary endpoint was the occurrence of adverse events. Thirteen patients had de novo AML, and 6 patients had secondary AML. Most of the patients had received salvage treatments more than once prior to GO. Six patients responded to the treatment (31.6%) with 3 complete remissions (15.8%). Five patients had stable disease, and 8 patients did not show any response. GO was more efficacious among the patients with fewer numbers of prior salvage treatments. CD33 positivity of leukemic cells was higher in responders than in nonresponders. Peripheral WT1 mRNA levels mostly decreased over time in the responders. The adverse event most commonly seen was febrile neutropenia (84%). No patient presented with veno-occlusive disease. Three patients died by day 30 (mortality rate 15.8%), one due to acute respiratory distress syndrome and the other two due to sepsis. GO remains an effective salvage treatment.

Successful treatment of disseminated intravascular coagulation by recombinant human soluble thrombomodulin in patients with acute myeloid leukemia.

Disseminated intravascular coagulation (DIC) is a life-threatening condition that frequently occurs in patients with hematologic malignancies. Currently, recombinant human soluble thrombomodulin (rTM) is a therapeutic DIC drug that is manufactured and sold in Japan only. We evaluated the efficacy of rTM compared to that of gabexate mesilate (GM), which was previously used routinely for treating DIC in Japan, in patients with acute myeloid leukemia (AML). This retrospective study enrolled 43 AML patients, including 17 with acute promyelocytic leukemia (APL), that was complicated with DIC. DIC resolution rates in non-APL AML and rTM-treated APL patients were 68.4% and 81.8%, respectively. In non-APL AML patients, the duration of rTM administration was significantly shorter than that of GM (7 vs 11 days), suggesting that rTM could improve DIC earlier than GM, although rTM was used in patients with more severe DIC. Moreover, treatment with rTM significantly improved DIC score, fibrinogen, fibrin/fibrinogen degradation product (FDP), and prothrombin time (PT) ratio. Conversely, treatment with GM only improved the DIC score and FDP. In APL patients, the duration of rTM administration was also significantly shorter than that of GM. No severe side effects associated with the progression of bleeding were observed during rTM administration. These findings suggest that rTM is safe, and its anti-DIC effects are more prompt than GM for treating AML patients with DIC.

Efficacy of aprepitant for CHOP chemotherapy-induced nausea, vomiting, and anorexia.

The objective of this study was to evaluate whether aprepitant in addition to 5-HT3 receptor antagonist is useful for preventing chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients receiving CHOP therapy, and to evaluate the relationship between in vivo kinetics of plasma substance P and these adverse events. Patients with malignant lymphoma who received CHOP chemotherapy or THP (THP-ADR)-COP therapy were investigated for CINV and anorexia for 5 days after the start of chemotherapy. With the first course of chemotherapy, all patients received only granisetron on day1 as an antiemetic. Patients who experienced nausea, vomiting, or anorexia exceeding grade 1 in the first course received aprepitant for 3 days in addition to granisetron with the second course of CHOP chemotherapy. Plasma substance P concentrations at 24 and 72 hours after chemotherapy were measured. Nineteen patients were evaluated. Nausea, vomiting, or anorexia was observed with the first course in 7 of 19 patients. During the second course with aprepitant, no patients experienced vomiting, and the toxicity grade of nausea, vomiting, or anorexia was decreased compared with those in the first course. Substance P concentrations showed no differences after chemotherapy, in patients with nausea, vomiting, or anorexia and in patients without. The addition of aprepitant to 5-HT3 receptor antagonist appears effective for CINV or anorexia for patients who received CHOP chemotherapy.

Lobar Hemorrhage Induced by Acquired Factor XIII Deficiency in a Patient with Cerebral Amyloid Angiopathy.

A 68-year-old man presented with intracranial hemorrhage in the right frontal lobe, which rapidly increased the day after admission. We performed hematoma removal with a biopsy of the cortex around the hematoma. The day after the operation, a subcutaneous hematoma over the craniotomy appeared, and the computed tomography showed a recurrent hemorrhage with an acute subdural hematoma. We were aware of a bleeding tendency, and a detailed hematologic examination by hematologists revealed autoimmune acquired factor XIII deficiency due to an antifactor XIII antibody. Specimens taken around the hematomas were pathologically diagnosed as cerebral amyloid angiopathy (CAA) on immunohistochemical examination. We considered that acquired factor XIII deficiency had induced lobar hemorrhage in the frontal lobe affected with CAA, and the coagulation disorder induced postoperative rebleeding. The patient died from repeated lobar hemorrhage 3 years after the surgery. There is no routine screening coagulation test including the active partial thromboplastin time and the prothrombin time for factor XIII deficiency. It is important for neurologists and neurosurgeons to be aware of this rare disease in patients with a bleeding tendency.

High Risk of Tumor Lysis Syndrome in Symptomatic Patients with Multiple Myeloma with Renal Dysfunction Treated with Bortezomib.

BACKGROUND/AIM: Tumor lysis syndrome (TLS) is a life-threatening complication associated with cancer chemotherapy. We retrospectively evaluated the risk of developing TLS in patients with symptomatic multiple myeloma undergoing chemotherapy. PATIENTS AND METHODS: Sixty-four patients (median age=71 years, range=48-87 years, 35 males/29 females) who were treated at our Institution between April 2006 and December 2015 were evaluated. RESULTS: A total of 124 chemotherapy courses were administered, of which 63 courses were bortezomib-based regimens and 34 courses were immunomodulatory drug (IMiD)-based regimens. TLS occurred in 13 (10.5%) out of 124 chemotherapy courses with five (4.0%) cases of laboratory TLS and eight (6.5%) cases of clinical TLS. The incidences of TLS were 17.5% for bortezomib-containing regimens and 3.2% for non-bortezomib-based regimens. No TLS occurred in the patients treated with IMiD-containing regimens. TLS occurred more frequently in the patients with elevated uric acid, creatinine, or beta-2-microglobulin levels at baseline. The patients with disease classified as advanced International Staging System also developed TLS more frequently. All the patients who developed clinical TLS received bortezomib-containing regimens (8/63, 12.7%). Among them, patients with elevated values of uric acid or creatinine developed clinical TLS more often than those without such elevation. The incidence of clinical TLS was 33.3% if the patients had renal dysfunction at baseline and were subsequently treated with bortezomib-based regimens (8/24 cases). CONCLUSION: Patients with renal dysfunction or a high uric acid level receiving bortezomib-based chemotherapy have a high risk of developing TLS.