Byrnelist1977

The patient was a 68-year-old woman, diagnosed with acute myelomonocytic leukemia with normal karyotype and FLT3-ITD-negative status in May 2019. She had achieved complete remission (CR) after "7+3" intensive induction chemotherapy and maintained CR by consolidation chemotherapy. However, she relapsed with swelling of the lips and gums in January 2020. She did not achieve CR by salvage chemotherapy with cytarabine-aclarubicin-G-CSF regimen. Comprehensive genomic analysis of leukemic cells revealed the presence of FLT3-N676K mutation, which was undetectable by companion diagnostics at the time. Complete remission with incomplete count recovery was obtained on day 28 after initiation of gilteritinib monotherapy, and the lip and gum swelling improved rapidly. However, she relapsed on day 106 after gilteritinib administration, and gilteritinib was discontinued. Genomic analysis at recurrence revealed NRAS mutation for the first time. Finally, the patient died of the uncontrolled primary disease. This is a case in which comprehensive gene mutation analysis was useful in determining a treatment strategy.Post-transplant cyclophosphamide (PTCy) has improved the efficacy of HLA-mismatched hematopoietic cell transplantation (HCT) by decreasing the risk of graft-versus-host disease (GVHD) and nonrelapse mortality. If an HLA-matched donor is not available, GVHD prophylaxis with PTCy can also be used for HLA-mismatched HCT in patients with pediatric aplastic anemia (AA). We report two cases of pediatric AA that were treated with HLA-mismatched HCT with reduced-intensity conditioning and PTCy. We administered 50 mg/kg/day Cy for GVHD prophylaxis on days 3 and 4, and tacrolimus and mycophenolate mofetil (or methotrexate) were initiated from day 5. In both the cases, the time to engraftment was favorable and GVHD and infection were controllable. PTCy probably allows us to expand donor candidates in pediatric AA when an HLA-matched donor is not available; however, further studies regarding optimal conditioning regimens and late complications are required.Graft-versus-host disease (GVHD) is a life-threating complication of allogeneic hematopoietic cell transplantation (allo-HCT). Prior studies have shown that gastrointestinal (GI) GVHD is associated with a reduction in intestinal microbiota diversity and a change in microbial metabolites. We conducted fecal metabolome analyses using a murine bone marrow transplantation. From this analysis, 290 metabolites were identified; of these, 18 metabolites were significantly or specifically higher and 12 were significantly or specifically lower in the allogeneic group than in the syngeneic one. Particularly, several metabolites in the choline metabolism and tryptophan metabolism were altered in the allogeneic group. Hierarchical clustering analysis demonstrated that the changed metabolites in the allogeneic group had similar profiles. Conclusively, we suggest that alloimmune responses are related to microbial metabolites in recipients receiving allo-HCT. The relationship between metabolites involved in GI GVHD and the intestinal microbiota and its physiological significance warrant further investigations.Monoclonal gammopathy of undermined significance (MGUS) is usually asymptomatic, and untreated follow-up is the standard treatment. However, MGUS progresses to multiple myeloma or related malignancy at a frequency of 1.5% per year. selleck chemical It is sometimes difficult to diagnose the progression of the disease via usual examinations. We herein report a case wherein rapid renal dysfunction led to a diagnosis of disease progression to multiple myeloma in a patient with MGUS that was asymptomatic for a long time. A 66-year-old woman developed rapid renal dysfunction requiring continuous hemodiafiltration 8 years after the diagnosis of IgA-κ type MGUS. A complete examination led to the diagnosis of IgA-κ type multiple myeloma. Chemotherapy was not effective, and she died due to sepsis on the 19th day of admission. A pathological autopsy revealed systemic amyloidosis and multiple abscesses positive for Staphylococcus aureus. An abnormal free light chain κ/λ ratio and M protein other than IgG are reportedly risk factors of disease progression of MGUS. In cases with these risk factors, it is important to always keep in mind the possibility of disease progression and to monitor the patient carefully for an early diagnosis.At initial diagnosis, central nervous system (CNS) involvement in acute promyelocytic leukemia (APL) is rare. Here, we report a case of newly diagnosed APL with CNS involvement that was successfully treated with all-trans retinoic acid (ATRA)-combined chemotherapy. A 64-year-old woman was referred to our hospital to evaluate a bleeding tendency, and she was diagnosed with APL. Induction chemotherapy with ATRA via a nasogastric tube was initiated under mechanical ventilation because of respiratory failure and disturbance of consciousness. Although her respiratory condition improved a few days after initiating treatment, the disturbance of consciousness remained. Brain magnetic resonance imaging showed mixed signals of tumor infiltration and acute cerebral infarction with a focus on the right cerebellum. The patient was diagnosed with CNS involvement of APL and acute cerebral infarction. Three months after the initiation of induction therapy, her consciousness improved along with the reduction in CNS involvement, and complete molecular remission was achieved. Thus, patients with APL can have CNS involvement at initial diagnosis. Administering ATRA via nasogastric tube can be a good therapeutic option in patients with difficulty swallowing due to disturbance of consciousness.Immunosuppressive therapies, including antithymocyte globulin and cyclosporine (CsA), are used for the treatment of aplastic anemia, but they reportedly cause lymphoproliferative diseases. Here, we report two cases of aplastic anemia in which diffuse large B-cell lymphoma developed during treatment with CsA. In both the cases, CsA was discontinued and combination therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisolone) plus the thrombopoietin receptor agonist eltrombopag was initiated. Furthermore, supportive care, including blood transfusion and granulocyte colony-stimulating factor, was provided. After six or eight courses of R-CHOP therapy, a complete metabolic response was achieved without serious adverse events. These cases illustrate the safety of combining R-CHOP with eltrombopag therapy in patients at a high risk of severe pancytopenia.A 60-year-old woman developed a fifth thoracic spine fracture with progressive paraplegia and underwent posterior spine fusion in June 2018. Based on the histopathological analysis of the surgical specimen, she was diagnosed with KIT D816V-positive systemic mastocytosis (SM). In June 2019, peripheral blood examination revealed remarkable eosinophilia. She was given prednisolone, which resulted in the resolution of eosinophilia. In May 2020, she developed acute myeloid leukemia (AML). Induction therapy was initiated and complete remission achieved. Subsequently, she received one course of consolidation therapy and allogeneic hematopoietic stem cell transplantation (allo-SCT). Although the residual mast cell tumor aggravated during chemotherapy for AML, the tumor regressed after allo-SCT, suggesting a graft-versus-mastocytosis effect. Nine months after the transplantation, the patient is alive and healthy without recurrence of AML and SM.The JAK2V617F mutation is a driver mutation of myeloproliferative neoplasms (MPNs). V617F allele burden is considered a risk factor for complications associated with MPNs and is a predictor of prognosis. In Japan, V617F allele burden has been measured in laboratory settings using the i-densyTM IS-5320 genetic analyzer with the quenching probe-Tm (QP-Tm) method. However, since 2020, allele-specific quantitative PCR (AS-qPCR) is being performed in clinical settings for measuring V617F allele burden. To investigate the clinical usefulness of the QP-Tm method in patients with MPNs, we evaluated the V617F allele burden measured by both the methods. A good correlation was observed between the V617F allele burden determined using QP-Tm and that determined using AS-qPCR (P less then 0.001, rs=0.952). The median mutant allele burden, as determined using the QP-Tm method, was significantly higher in patients with polycythemia vera than in those with essential thrombocythemia. The results of this study suggested that the QP-Tm method will continue to be useful clinical ancillary test for measuring V617F allele burden.

Transcatheter aortic valve implantation (TAVI) is increasingly being performed in very elderly patients, although its efficacy and validity remain unclear. This study evaluated real-world TAVI outcomes in Japanese nonagenarians with severe aortic stenosis.Methods and ResultsThis single-center study retrospectively assessed the early and long-term clinical outcomes of TAVI in nonagenarians (n=35) and in patients aged <90 years (group Y; n=171). There were no in-hospital deaths in either group. The device success rate and early safety were comparable between the 2 groups. The 5-year rates of freedom from cardiac events and deaths were equivalent in both groups. The cumulative survival rate at 5 years was non-significantly lower in nonagenarians (32.6% in nonagenarians vs. 57.5% in patients aged <90 years, P=0.49). There were no differences in the 5-year survival between nonagenarians after TAVI and the sex- and age-matched populations (P=0.18). The Cox regression model revealed that lower hemoglobin levels were associated with all-cause mortality (P=0.02), and age ≥90 years was not associated with all-cause mortality.

The early and long-term clinical outcomes of TAVI for selected Japanese nonagenarians were comparable to those in patients aged <90 years. Nonagenarians who underwent TAVI achieved an acceptable prognosis compared to the sex- and age-matched population; thus, TAVI appears to be effective for treating aortic stenosis in Japanese nonagenarians.

The early and long-term clinical outcomes of TAVI for selected Japanese nonagenarians were comparable to those in patients aged less then 90 years. Nonagenarians who underwent TAVI achieved an acceptable prognosis compared to the sex- and age-matched population; thus, TAVI appears to be effective for treating aortic stenosis in Japanese nonagenarians.Since cast titanium prostheses have many drawbacks, multi-directionally forged titanium grade 2 (MDF) was developed, and the application of the milling process was proposed for improving the titanium clasp. This in vitro study evaluated milled titanium clasps, including MDF titanium. Milling clasps were manufactured with commercially pure (CP) titanium grade 2 (CP 2), grade 4 (CP 4), Ti-6-Al-4V, and MDF. As a control, a CP 2 cast titanium clasp was fabricated in the conventional manner. No porosities and catastrophic failures were observed in the four milled titanium clasps. Fitness accuracy and retentive forces of milled CP 2 and CP 4 tended to be worse, and the milled MDF showed the higher retentive forces (12.45 N) than did cast and milled CP 2 clasps (9.32 N and 4.42 N). Milled titanium clasps can be recommended for longer-term clinical use as compared to cast clasps.