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In Japan, clinical genetic services became available in the 1970s, and genomic medicine, including genetic counseling (GC), developed rapidly. However, research on the outcomes of GC in Japan is limited. Japan has a unique cultural context, and appropriate GC methods have not yet been optimized for this population. The current study aimed to evaluate the psychological status of Japanese patients and their companions undergoing GC and the outcomes of GC. We used the Quality of Care Through the Patients' Eyes‐gene cancer (QUOTE‐geneCA), the Genetic Counseling Outcome Scale‐24 (GCOS‐24), and the State‐Trait Anxiety Inventory (STAI) to evaluate patients and their companions' needs and preferences regarding GC, empowerment, and anxiety, respectively. We evaluated stress status during GC by measuring saliva cortisol levels. QUOTE‐geneCA results for patients (n = 69) and a group of patients and their companions (n = 96) revealed that participants felt that it was important that skilled medical staff explained medical information and provided advice in an easily understandable manner. Japanese patients and their companions regarded the procedural aspects of counseling as most important and their autonomy in decision‐making as less important. GCOS‐24 results revealed a significant increase in empowerment scores in 38 patients (by 9.63 points) from pre‐ to post‐GC (p < 0.001; Cohen's d = 0.79). STAI results revealed a significant decrease in state anxiety for patients (6.11 points; p < 0.001; Cohen's d = 0.66). Cortisol levels in patients significantly decreased after GC (p = 0.001). The improvement of empowerment scores from pre‐ to post‐GC among patients and their companions were significantly negatively correlated with pre‐GC empowerment scores (p < 0.001), trait anxiety scores (p = 0.001), and the number of people living together (p = 0.011). The change of cortisol levels during GC in patients and their companions was significantly positively correlated with trait anxiety score (p = 0.027). This study suggested that these characteristics of Japanese patients and their companions may predict GC outcomes. [ABSTRACT FROM AUTHOR]

It was reported that high‐dose cyclosporine at 500 mg daily increases edoxaban exposure. We investigated whether cyclosporine <500 mg daily leads to edoxaban‐induced bleeding in the clinical setting. This case series study included patients receiving edoxaban and cyclosporine at Mie University Hospital. The outcomes were bleeding and anticoagulant markers, including activated partial thromboplastin time (APTT), prothrombin time (PT), and the international normalized ratio of prothrombin time (PT‐INR). We examined the genotypes of cytochrome P450 3A5 (CYP3A5), multidrug resistance 1 (ABCB1), and solute carrier organic anion transporter 1B1 (SLCO1B1). Trends in anticoagulant markers were analyzed. Thirteen patients received edoxaban (standard dose; n = 3 and reduced dose; n = 10) and cyclosporine (1.94 ± 1.42 mg/kg). A bleeding event occurred in one patient receiving a standard dose of edoxaban plus cyclosporine of 25 mg daily (HAS‐BLED score of 2 and genotypes; CYP3A5*3/*3, ABCB1 3435CT, and SLCO1B1*1a/*1b). After edoxaban treatment, anticoagulant markers were prolonged (APTT; 27.95 ± 3.64 s vs. 31.11 ± 3.90 s, p < 0.001, PT; 11.53 ± 1.01 s vs. 13.03 ± 0.98 s, p = 0.002, PT‐INR; 0.98 ± 0.09 vs. 1.11 ± 0.11, p = 0.007). In summary, the genotypes of CYP3A5, ABCB1, and SLCO1B1 and the dosage of edoxaban may affect the risk of bleeding by edoxaban when co‐administered with cyclosporine, even at low doses. [ABSTRACT FROM AUTHOR]

Mutation analysis of peripheral blood revealed a I CALR i type 1 mutation and a I JAK2 i V617F mutation with allele frequencies of 36% and 15%, respectively. These results suggested that additional I JAK2 i V617F mutations occurred in HSC populations and that myeloid and erythroid progenitors with I JAK2 i / I CALR i double mutations might have a growth advantage over the I CALR i single-mutated populations. Keywords: genetic analysis; myelofibrosis; myeloproliferative disease EN genetic analysis myelofibrosis myeloproliferative disease e89 e92 4 09/02/21 20210901 NES 210901 Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) share three common driver mutations in the Janus kinase I 2 i ( I JAK2 i ), calreticulin ( I CALR i ) and myeloproliferative leukaemia oncogene ( I MPL i ) genes.1 Although these driver mutations are thought to be mutually exclusive, rare cases of MPN with two or more co-existing driver mutations have been reported: I JAK2 i V617F/ I JAK2 i exon 12,2 I JAK2 i V617F/ I CALR i ,2-8 I JAK2 i V617F/ I MPL i ,2,4,7,9-11 I CALR i / I MPL i 2,12,13 and I JAK2 i V617F/ I CALR i / I MPL i .14 Clonogenic evaluation studies indicated these mutations mostly co-existed in separate clones. [Extracted from the article]

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The involvement of copy number variation (CNV) in the development of PCD is largely unknown. Methods: We examined 93 Japanese patients with clinically suspected PCD from 84 unrelated families. CNV was examined either by exome sequencing of a PCD gene panel or by whole‐exome sequencing (WES). The identified alterations were validated by PCR and Sanger sequencing. Nasal ciliary ultrastructure was examined by electron microscopy. Results: Analysis of CNV by the panel or WES revealed a biallelic deletion in the dynein regulatory complex subunit 1 (DRC1) gene in 21 patients, which accounted for 49% of the PCD patients in whom a disease‐causing gene was found. Sanger sequencing of the PCR product revealed a 27,748‐bp biallelic deletion including exons 1–4 of DRC1 with identical breakpoints in all 21 patients. The ciliary ultrastructure of the patients with this CNV showed axonemal disorganization and the loss or gain of central microtubules. Conclusion: The deletion of DRC1 is the major cause of PCD in Japan and this alteration can cause various ciliary ultrastructural abnormalities. [ABSTRACT FROM AUTHOR]

Serum tumor markers, including α-fetoprotein ( AFP) and des-γ-carboxy prothrombin ( DCP), are currently used in the diagnosis of hepatocellular carcinoma ( HCC). There is, however, an aberrant increase in serum DCP in patients with obstructive jaundice, vitamin K deficiency or who are taking warfarin, resulting from a problem with the current methodology for measurement of this marker. This study aimed to elucidate the utility of a new biomarker, NX-PVKA, for early diagnosis of HCC. A total of 96 patients were included in the HCC group. The control group included 138 liver cirrhosis ( LC) patients without HCC. Serum concentrations of conventional DCP, AFP, AFP-L3 and NX-PVKA were measured. The NX-PVKA ratio was calculated by dividing DCP by NX-PVKA. In patients not taking warfarin, the area under the curve values of DCP, NX-PVKA ratio, AFP and AFP-L3 were 0.715, 0.690, 0.737 and 0.654, respectively, confirming the clinical utility of these markers in detecting HCC. In cases with DCP > 35 mAU/mL in particular, a significant increase in the NX-PVKA ratio was observed in patients with HCC. In those cases, the cut-off value for the NX-PVKA ratio that was optimized by the receiver operating characteristic ( ROC) curve was 1.15. In addition, the sensitivity and specificity for diagnosing HCC were 69.2% and 75.9%, respectively. Patients with HCC had higher NX-PVKA ratios compared to patients with LC taking warfarin ( P = 0.063). These results suggest that, when used in combination with DCP, the NX-PVKA ratio is a promising novel marker for the detection of HCC. [ABSTRACT FROM AUTHOR]