Efficacy of Anti-CD38 Monoclonal Antibodies for Relapsed or Refractory Multiple Myeloma in Stem Cell Transplant-Ineligible Patients Aged over 65 Years: A Propensity Score-Matched Study.

Background: The development of newer agents, including anti-CD38 monoclonal antibodies (mAbs), has significantly improved overall survival (OS) in patients with relapsed or refractory multiple myeloma (RRMM). However, the treatment of older patients with RRMM who are transplant-ineligible remains challenging.

Methods: We retrospectively evaluated OS in 78 transplant-ineligible patients with RRMM who were aged ≥ 65 years and treated at our institution between February 2012 and November 2023.

Final Analysis Results from the AGEHA Study: Emicizumab Prophylaxis for Acquired Hemophilia A with or without Immunosuppressive Therapy.

Background:  Primary analysis of the phase III AGEHA study suggested a favorable benefit-risk profile for emicizumab prophylaxis in patients with acquired hemophilia A (PwAHA); however, only patients undergoing immunosuppressive therapy (IST; Cohort 1) were included.

Objectives:  To present final analysis results of AGEHA, including data on IST-ineligible patients (Cohort 2) and on long-term prophylaxis with emicizumab.

Methods:  For patients in both Cohorts 1 and 2, emicizumab was administered subcutaneously at 6 mg/kg on Day 1, 3 mg/kg on Day 2, and 1.

Enhanced ALOX12 Gene Expression Predicts Therapeutic Susceptibility to 5-Azacytidine in Patients with Myelodysplastic Syndromes.

5-azacytidine (AZA), a representative DNA-demethylating drug, has been widely used to treat myelodysplastic syndromes (MDS). However, it remains unclear whether AZA's DNA demethylation of any specific gene is correlated with clinical responses to AZA. In this study, we investigated genes that could contribute to the development of evidence-based epigenetic therapeutics with AZA.

[Successful immunosuppressive therapy in female hemophilia A developing inhibitor after perioperative administration of factor VIII products].

A 62-year-old woman was diagnosed as a hemophilia A carrier (factor VIII activity 35%) on preoperative examination of an ovarian tumor. A total of 35,600 units of recombinant factor VIII products was administered perioperatively. On postoperative day 95, a subcutaneous hematoma formed and immunosuppressive therapy with prednisolone was started based on an APTT of 66 seconds, factor VIII (FVIII) activity of 3%, and FVIII inhibitor of 1 BU/ml.

A prospective, multicenter, open-label phase III study of emicizumab prophylaxis in patients with acquired hemophilia A.

Background: Emicizumab is a bispecific antibody that mimics the cofactor function of activated factor (F) VIII. It prevents bleeds in patients with congenital hemophilia A regardless of the inhibitor status; however, no prospective clinical studies have been conducted for emicizumab in patients with acquired hemophilia A (PwAHA).

Objectives: To describe the primary analysis results from a prospective, multicenter, open-label phase III study evaluating the efficacy, safety, and pharmacokinetics of emicizumab in PwAHA (AGEHA; JapicCTI-205151).

Factor VII Deficiency Due to Compound Heterozygosity for the p.Leu13Pro Mutation and a Novel Mutation in the HNF4 Binding Region (-58G>C) in the F7 Promoter.

We investigated the molecular basis of factor VII (FVII) deficiency in a Japanese patient and identified compound heterozygous mutations. Factor VII activity and antigen levels in the patient were less than 5.0% and 6.

Late-onset non-islet cell tumor hypoglycemia: A case report.

Background: Hypoglycemia due to non-insulin-producing tumors is referred to as non-islet cell tumor hypoglycemia (NICTH). As NICTH is a rare lesion, the natural course of NICTH is not well understood. We report a case of NICTH that was observed 30 years before the onset of hypoglycemia.

Ipragliflozin-induced improvement of liver steatosis in obese mice may involve sirtuin signaling.

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors are newly developed oral antidiabetic drugs. SGLT2 is primarily expressed in the kidneys and reabsorbs approximately 90% of the glucose filtered by the renal glomeruli. SGLT2 inhibitors lower glucose levels independently of insulin action by facilitating urinary glucose excretion.

Successful correction of factor V deficiency of patient-derived iPSCs by CRISPR/Cas9-mediated gene editing.

Background: Factor V (FV) deficiency is a monogenic inherited coagulation disorder considered to be an ideal indication for gene therapy. To investigate the possibility of therapeutic application of genome editing, we generated induced pluripotent stem cells (iPSCs) from a FV-deficient patient and repaired the mutation of factor V gene (F5) using a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9).

Methods: The patient's peripheral blood mononuclear cells were reprogrammed for iPSCs.

Regulation of the KCNJ5 gene by SF-1 in the adrenal cortex: Complete genomic organization and promoter function.

Activating mutations in the KCNJ5 gene are responsible for the significant number of aldosterone-producing adenomas. To elucidate the molecular mechanisms underlying KCNJ5 expression, we characterized the entire human KCNJ5 gene. The gene spanned approximately 29.

CRISPR/Cas9-mediated gene correction in hemophilia B patient-derived iPSCs.

The clustered regulatory interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system is an efficient genome-editing tool that holds potential for gene therapy. Here, we report an application of this system for gene repair in hemophilia B (HB) using induced pluripotent stem cells (iPSCs). We prepared targeting plasmids with homology arms containing corrected sequences to repair an in-frame deletion in exon 2 of the factor IX (F9) gene and transfected patient-derived iPSCs with the Cas9 nuclease and a guide RNA expression vector.

Central Hypothyroidism Related to Pituitary Adenomas: Low Incidence of Central Hypothyroidism in Patients With Acromegaly.

Context: The most frequent cause of central hypothyroidism (CeH) is pituitary adenomas, but the mechanisms remain unclear.

Objective: We investigated serum thyroid levels and GH/IGF-1 in central hypothyroidism in untreated patients with pituitary nonfunctioning and GH-secreting adenomas.

Design: This was a retrospective cross-sectional study of cases collected from Gunma University and Toranomon Hospitals between 2007 and 2016.

The augmented expression of the cytidine deaminase gene by 5-azacytidine predicts therapeutic efficacy in myelodysplastic syndromes.

5-Azacytidine (5AC), a hypomethylating agent, is clinically used for the treatment of patients with myelodysplastic syndromes (MDS). Cytidine deaminase (CDA) is a key enzyme in the detoxification of 5AC. We investigated whether the CDA expression could predict response to 5AC in MDS.

Transducin β-like 1, X-linked and nuclear receptor co-repressor cooperatively augment the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors.

Mutations in TBL1X, a component of the nuclear receptor co-repressor (N-CoR) and silencing mediator of retinoic acid and thyroid hormone receptor co-repressor complexes, have recently been implicated in isolated central hypothyroidism (CeH). However, the mechanisms by which TBL1X mutations affect negative feedback regulation in the hypothalamus-pituitary-thyroid axis remain unclear. N-CoR was previously reported to paradoxically enhance the ligand-independent stimulation of TRH and TSHβ gene promoters by thyroid hormone receptors (TR) in cell culture systems.

Pituitary NR4A1 is negatively regulated by thyroid hormone without direct binding of thyroid hormone receptors on the gene.

We previously reported that TRH stimulated pituitary TSHβ gene expression via an immediate increase in NR4A1 in thyrotrophs. We demonstrated that NR4A1 mRNA levels are regulated by thyroid hormone. Pituitary NR4A1 mRNA levels were decreased in mice injected with L-T4.

Factor X Deficiency with Heterozygous Mutations of Novel p.G435S and Known p.G244R in a Patient Presenting with Severe Umbilical Hemorrhage.

A 10-day-old male patient was referred to our hospital with severe umbilical bleeding. Prothrombin time (PT) and activated partial thromboplastin time (APTT) were prominently prolonged. Plasma coagulation factor X (FX) activity and antigen levels were 1% and 0.

Development of immersion vaccine for bacterial cold-water disease in ayu Plecoglossus altivelis.

Flavobacterium psychrophilum (F. psychrophilum) is the causative agent of bacterial cold-water disease (BCWD) that occurs in ayu Plecoglossus altivelis. Formalin-killed cell of F.

Characteristics of Japanese aldosterone-producing adenomas with KCNJ5 mutations.

Somatic mutations in KCNJ5 gene have been identified in patients with adrenal aldosterone-producing adenomas (APAs). We previously reported that Japanese patients with APAs had distinct characteristics from patients in Western countries; i.e.

HBA1C AND MEAN GLUCOSE DERIVED FROM SHORT-TERM CONTINUOUS GLUCOSE MONITORING ASSESSMENT DO NOT CORRELATE IN PATIENTS WITH HBA1C >8.

Objective: Optimum therapy for patients with diabetes depends on both acute and long-term changes in plasma glucose, generally assessed by glycated hemoglobin (HbA1c) levels. However, the correlation between HbA1c and circulating glucose has not been fully determined. Therefore, we carefully examined this correlation when glucose levels were assessed by continuous glucose monitoring (CGM).

A case of refractory multiple myeloma with proliferation of large granular lymphocytes by lenalidomide treatment and its association with clinical efficacy.

A 72-year-old Japanese male was diagnosed as having monoclonal gammopathy of undetermined significance and was followed up without therapy. Three years later, the patient progressed to symptomatic multiple myeloma. Melphalan + prednisolone was administered as first-line chemotherapy for ~6 years.

GNAS mutations in adrenal aldosterone-producing adenomas.

Mutations in GNAS, which encodes Gsα, have been documented in detail, particularly in human pituitary GH-secreting adenomas. Mutations have also recently been reported in adrenal cortisol-producing adenomas (CPAs), in addition to those in the PRKACA gene. However, mutations have not yet been examined in aldosterone-producing adenomas (APAs).

Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma.

Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1(+) DLBCL.

Changes in visceral and subcutaneous fat mass in patients with pheochromocytoma.

Context: Overproduction of catecholamine induces not only hypertension but also glucose intolerance and hyperlipidemia. However, little is known about its effect on visceral and subcutaneous fat.

Objective: Our objective was to investigate changes of metabolic factors including visceral and subcutaneous fat areas in patients with pheochromocytoma (Pheo).