Single-unit unrelated cord blood transplantation versus HLA-matched sibling transplantation in adults with advanced myelodysplastic syndrome: A registry-based study from the adult MDS working group of the Japanese society for transplantation and cellular therapy.

Allogeneic hematopoietic stem cell transplantation (HCT) remains the only potential curative therapeutic modality for advanced myelodysplastic syndrome (MDS). Within HCT, the advancement of cord blood transplantation (CBT) procedures has resulted in a drastic expansion of CBT as a donor source for MDS. However, data comparing matched sibling donors (MSDs) HCT with CBT for advanced MDS, which was defined as refractory anemia with an excess of blasts (RAEB)-1 and RAEB-2 according to the World Health Organization classification at the time of HCT, have not been explored. We retrospectively compared survival and other posttransplant outcomes in 999 adult patients with advanced MDS after receiving allogeneic HCT in Japan between 2011 and 2020, using either MSD (n = 331) or single-unit unrelated cord blood (UCB) (n = 668). In the multivariate analysis, there were no significant differences in overall survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.90-1.34; P = 0.347), disease-free survival (HR, 1.01; 95% CI, 0.84-1.23; P = 0.845), relapse (HR, 0.88; 95% CI, 0.68-1.15; P = 0.370), or non-relapse mortality (HR, 1.15; 95% CI, 0.87-1.50; P = 0.310) between MSD recipients and UCB recipients. UCB was significantly associated with lower neutrophil (HR, 0.28; 95% CI, 0.24-0.33; P < 0.001) and lower platelet (HR, 0.29; 95% CI, 0.23-0.36; P < 0.001) recovery compared to MSD. UCB was significantly associated with a lower incidence of chronic graft-versus-host disease (GVHD) (HR, 0.57; 95% CI, 0.44-0.75; P < 0.001) and extensive chronic GVHD (HR, 0.46; 95% CI, 0.32-0.67; P < 0.001) compared to MSD. Similar results were observed after adjusting for differences between MSD and UCB recipients by propensity score matching analysis. Our study demonstrated that single CBT and MSD HCT had similar survival outcomes for adult patients with advanced MDS despite the lower hematopoietic recovery in CBT recipients and higher chronic GVHD in MSD recipients.

Primary pulmonary diffuse large B-cell lymphoma presenting multiple nodules mimicking metastasis: A case report.

Primary pulmonary diffuse large B-cell lymphoma is a rare entity. We describe a case of pulmonary lymphoma with multiple nodules mimicking metastases in a treated patient with rheumatoid arthritis. A 73-year-old man was diagnosed with rheumatoid arthritis at the age of 30. He was treated with leflunomide. He was followed up for a nontuberculous mycobacterial infection. He underwent percutaneous coronary intervention for acute myocardial infarction at the age of 70. In April 2022, routine follow-up revealed new-onset multiple nodules on chest computed tomography (CT). A position emission tomography/CT scan with 18F-fluorodeoxyglucose showed a low-high maximum standardized uptake value by multiple nodules. Pathologic examination of a video-assisted thoracic surgical biopsy revealed pulmonary diffuse large B-cell lymphoma. Systemic chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisolone reduced and eliminated multiple nodules. Pulmonary lymphoma should be considered as a differential diagnosis in the case of multiple nodules on a chest CT.

Increased cleavage of von Willebrand factor by ADAMTS13 may contribute strongly to acquired von Willebrand syndrome development in patients with essential thrombocythemia.

BACKGROUND: Patients with essential thrombocythemia (ET) often experience bleeding associated with acquired von Willebrand syndrome (AVWS) when the platelet count is markedly increased. OBJECTIVE: We investigated whether von Willebrand factor (VWF) degradation is enhanced in patients with ET. METHODS: Seventy patients with ET underwent VWF multimer (VWFM) analysis and measurement of VWF-related parameters. We calculated the VWFM index, defined as the ratio of intensities of a patient's molecular weight-categorized VWFMs, and those of a healthy subject's, using densitometric analysis. VWF degradation product (DP) was measured via ELISA using a monoclonal antibody that specifically recognizes Y1605 at the C-terminal boundary, which is exposed following ADAMTS13-mediated cleavage of the Y1605-M1606 bond of the VWF A2 domain. RESULTS: Patients with higher platelet counts had a significantly reduced high molecular weight (HMW)-VWFM index and an increased VWF-DP:VWF antigen (Ag) ratio compared to those with lower platelet counts. On multivariate analysis, the VWF-DP/VWF:Ag ratio was an independent predictor of the HMW-VWFM index. Patients who underwent cytoreductive therapy had a significantly higher HMW-VWFM index and lower VWF-DP/VWF:Ag ratio than those who did not. Among individual patients, there was also a significant increase in the HMW-VWFM index and a decrease in the VWF-DP/VWF:Ag ratio after cytoreductive therapy compared to pre-therapy values. CONCLUSION: In patients with ET, an increased platelet count is associated with enhanced cleavage of VWF at the Y1605-M1606 bond, primarily by ADAMTS13, leading to AVWS. Cytoreductive therapy reduces the platelet count, prevents excessive VWF cleavage, and improves VWFM distributions.

Successful Treatment of Antibody-mediated Pure Red Cell Aplasia Induced by Continuous Erythropoietin Receptor Activator with Prednisolone.

Pure red cell aplasia (PRCA) associated with erythropoiesis-stimulating agents (ESAs), which were first reported in 1998, usually occurs with subcutaneous administration of epoetin alfa (Eprex®). Improvements in ESA storage, handling, and administration methods have reduced the PRCA incidence. Continuous erythropoietin receptor activator (CERA) is a third-generation ESA that is rarely reported to induce PRCA. We herein report a case of CERA-induced PRCA presenting with positive anti-erythropoietin (EPO) and anti-CERA antibodies, which was successfully treated with prednisolone. Clinicians should be aware of the possibility of antibody-mediated PRCA induced by an ESA in CKD patients with anemia with reticulocytopenia and low serum EPO levels.

[Development of thrombocytopenic purpura following BNT162b2 mRNA COVID-19 vaccination].

Because the coronavirus disease 2019 (COVID-19) pandemic is still rampant, vaccination is being promoted worldwide. However, the safety of various COVID-19 vaccines remains poorly understood. We herein report the case of a 37-year-old woman who experienced thrombocytopenia following BNT162b2 mRNA COVID-19 vaccination. The patient presented with purpura on the extremities 10 days after the first vaccination. She had marked thrombocytopenia and no thrombosis. Thrombocytopenia resolved spontaneously. Given the possibility of occurrence of post-vaccination thrombocytopenia, vaccinated persons should be instructed to consult a medical institution if they experience bleeding symptoms.

[Development of disseminated cryptococcosis during chemotherapy for plasmacytoma].

A 71-year-old male developed plasmacytoma on September 2015. He received radiotherapy, followed by posterior spinal fusion, at Th5 and L3 and was subsequently administered lenalidomide plus dexamethasone (Ld) from January 2016. After the 9th course of Ld, the patient complained of epigastric discomfort and papules on the face. FDG-PET showed duodenum 3rd potion and indicated nodular lesions with high glucose uptake on the lower lobe of the right lung and third portion of the duodenum. Biopsy of the skin, duodenum, and lung revealed Grocott's stain positive circular bodies, and the patient was subsequently diagnosed with disseminated cryptococcosis. Although disseminated cryptococcosis often causes encephalomeningitis, gastrointestinal involvement is rarely reported. The underlying conditions of disseminated cryptococcosis include AIDS, hematological malignancies, and steroid and immunosuppressant use. The sites of infections are the esophagus, stomach, small intestine, and colon. Disseminated cryptococcosis is diagnosed by abdominal pain, bloody stool, and gastrointestinal perforation. However, disseminated cryptococcosis may be asymptomatic; therefore, it is imperative that there is no delay in its diagnosis.

[An autopsy case of B lymphoblastic leukemia/lymphoma with hemophagocytic syndrome infiltrating in the central nervous systems].

The hemophagocytic syndrome(HPS) after the hematopoietic stem cell transplantation(SHCT) may be triggered by the reactivation of virus such as Epstein-Barr virus (EBV) or cytomegalovirus (CMV) under immunosuppressive state. The present case was a 17-year old man who was diagnosed as B lymphoblastic leukemia. Bone marrow aspiration showed 96.4% of lymphoblasts with positive for CD19 and CD20, negative for CD66 and POX, and dot staining for PAS. E2A/PBX1 chimeric mRNA was positive as assessed by RT-PCR method. He received three courses of induction chemotherapy followed by allo-bone marrow transplantation (BMT) from his sister, but had a relapse three months after allo-BMT. He received allo peripheral blood-SCT (PBSCT) from his mother. The hematopoietic cells successfully engrafted, but the mixed chimerism of 2 donors persisted. On day 149, he had a fever, and hemophagocytosis was found by bone marrow aspiration. EBV genomic DNA was detected for 1.62 x 10(3) copies. CMV and fungus were negative in blood. On day 165, the patient had been observed disturbance of consciousness, neck stiffness, and died on day 170 due to multiple organ failure. Autopsy examination showed infiltration of CD20+ leukemic cells into the perivascular space of cerebrum, brainstem and spinal cord, with hemophagocytosis by CD6+ macrophages. In situ hybridization of EB-virus encoded small RNA (EBER) confirmed EBV infection of B-lymphoblastic cells infiltrated in the cerebrum. HPS was considered to be triggered by the reactivation of EBV, due to hematopoietic dysfunction based on long-term immunosuppressive treatment and mixed chimerism derived from a HSCT from 2 donors.

Autopsy case of primary myelofibrosis in which myeloid sarcoma was the initial manifestation of tumor progression.

Myeloid sarcoma (MyS) is defined as an extramedullary tumor-forming neoplasm consisting of immature myeloid cells with/without maturation. We experienced a case involving a 68-year-old Japanese male patient who had been followed-up for four years with a diagnosis of chronic idiopathic myelofibrosis/primary myelofibrosis (PMF) and noticed a painful mass in his left axilla. A wedge biopsy characterized the lesion as MyS that displayed megakaryoblastic/megakaryocytic differentiation. As his complete blood count included a few myeloid blasts (1% of WBC) and a bone marrow biopsy detected fibrosis without evidence of acute myelogenous leukemia (AML), a diagnosis of extramedullary blastic transformation of PMF was made, which was confirmed later by V617F mutation in Janus kinase-2 in both initial bone marrow biopsy and axillary tumor biopsy specimens. The patient died of pneumonia eight months after developing the axillary tumor. At autopsy, multiple MyS masses were detected in his soft tissue, but his bone marrow only contained fibrosis. Although MyS rarely develops before the leukemic transformation of PMF, no evidence of AML could be found in the patient's bone marrow at any point during the course of his disease. Thus, it is possible that the blasts in his peripheral blood were derived from the remaining MyS. Furthermore, the present case indicates that extramedullary blastic transformation, which is occasionally seen in CML, can also occur in PMF. Therefore, it is important to recognize that there is a wide variation in the pathogeneses of MyS and PMF.

Regulation of adipocytokine secretion and adipocyte hypertrophy by polymethoxyflavonoids, nobiletin and tangeretin.

AIMS: The polymethoxyflavonoids nobiletin and tangeretin possess several important biological properties such as neuroprotective, antimetastatic, anticancer, and anti-inflammatory properties. The present study was undertaken to examine whether nobiletin and tangeretin could modulate adipocytokine secretion and to evaluate the effects of these flavonoids on the hypertrophy of mature adipocytes. MAIN METHODS: All experiments were performed on the murine preadipocyte cell line 3T3-L1. We studied the formation of intracellular lipid droplets in adipocytes and the apoptosis-inducing activity to evaluate the effects of polymethoxyflavonoids on adipocyte differentiation and hypertrophy, respectively. The secretion of adipocytokines was measured using ELISA. KEY FINDINGS: We demonstrated that the combined treatment of differentiation reagents with nobiletin or tangeretin differentiated 3T3-L1 preadipocytes into adipocytes possessing less intracellular triglyceride as compared to vehicle-treated differentiated 3T3-L1 adipocytes. Both flavonoids increased the secretion of an insulin-sensitizing factor, adiponectin, but concomitantly decreased the secretion of an insulin-resistance factor, MCP-1, in 3T3-L1 adipocytes. Furthermore, nobiletin was found to decrease the secretion of resistin, which serves as an insulin-resistance factor. In mature 3T3-L1 adipocytes, nobiletin induced apoptosis; tangeretin, in contrast, did not induce apoptosis, but suppressed further triglyceride accumulation. SIGNIFICANCE: Our results suggest that nobiletin and tangeretin are promising therapeutic candidates for the prevention and treatment of insulin resistance by modulating the adipocytokine secretion balance. We also demonstrated the different effects of nobiletin and tangeretin on mature adipocytes.

Superior retinaculoplasty for recurrent dislocation of peroneal tendons.

BACKGROUND: Although dislocation of peroneal tendons is an uncommon injury, if it does occur, daily and sports activities may be restricted because of snapping of the tendons and pain in the posterolateral aspect of the ankle joint. Many operative procedures have been reported for this pathology, including anatomic reattachment of the retinaculum, bone block procedures, tissue-transfer procedures, and groove-deepening. However, no procedure has been established as the "gold standard." Successful results were reported after anatomic reattachment of the detached superior peroneal retinaculum and periosteum of the fibula. We have modified the procedure to reduce operative invasiveness and introduced a method to determine proper tension when suturing the retinaculum to the fibula. METHODS: In our retinaculoplasty, the false pouch was opened through one incision, and the retinaculum was sutured to the fibula while measuring the tension, avoiding too tight or too loose suturing. We performed this procedure in 20 patients with symptomatic dislocation of peroneal tendons in whom conservative treatment had failed. We followed them over 2 years, and clinical results were evaluated. RESULTS: No patient had re-dislocation of the peroneal tendons during the followup period. Fifteen of 18 patients who had been involved in sports activities returned to their previous activities without reducing their activity levels. All patients acquired full range of motion of the ankle joint postoperatively. The preoperative American Orthopaedic Foot and Ankle Society (AOFAS) scores improved significantly (p value < 0.01) postoperatively. CONCLUSIONS: This study demonstrated that the described repair successfully treated patients with symptomatic dislocation of the peroneal tendon and should be considered for this pathology.

Efficiency of magnetic liposomal transforming growth factor-beta 1 in the repair of articular cartilage defects in a rabbit model.

We evaluated the efficacy of a magnetic liposomal delivery system of transforming growth factor (TGF)-beta(1) in the treatment of articular cartilage defects in a rabbit model. Articular cartilage defects were created in the patellar groove of rabbits, and a permanent magnet or a nonmagnetic alloy was implanted in the defect site. Magnetic liposomal drugs, prepared by the conventional film method and sonication, were injected into the defect site 1 week after surgery. First, the efficacy of the magnetic liposomal delivery system was evaluated by using a model compound fluorescence-labeled dextran 40,000 (FD-40). Then, the therapeutic efficiency of magnetic liposomal TGF-beta(1) was evaluated by cartilage histological scoring at 4, 8, and 12 weeks after surgery. The injected magnetic liposomal FD-40 accumulated at the target site where a permanent magnet had been implanted. The histological score showed that the injection of magnetic liposomal TGF-beta(1) under magnetic force was significantly effective in the repair of the defect site over 12 weeks after surgery. Injection of TGF-beta(1) into the cartilage defect was effective as a magnetic liposomal preparation under magnetic force, resulting in acceleration of the cartilage repair, probably because of the desirable accumulation of TGF-beta(1) at the target site.

The peripheral blood Valpha24+ NKT cell numbers decrease in patients with haematopoietic malignancy.

Valpha24TCR+ CD161+ NKT (Valpha24+ NKT) cells are activated by alpha-galactosylceramide and can exert anti-tumor activity against a variety of tumor cells. In this study, we assessed the Valpha24+ NKT cell numbers in peripheral blood (PB) from 30 healthy donors and 70 patients with haematopoietic malignancy including chronic myelogenous leukemia (CML), malignant lymphoma (ML), acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). Here, we demonstrated that PB Valpha24+ NKT cell numbers were significantly decreased in all the patients with haematopoietic malignancy in comparison with that in healthy donors (P < 0.005). In particular CD4- CD8- Valpha24+ NKT cell numbers were more significantly decreased in the patients with haematopoietic malignancy (P < 0.0001).

Acetabular osteosarcoma treated by irradiation-vascularized hybrid bone graft.

BACKGROUND: Periacetabular reconstruction after malignant bone tumor resection to preserve limb function is extremely challenging. The optimal reconstruction method has not yet received consensus and the functional outcomes still remain unsatisfactory. CASE REPORT: A thirteen-year-old girl who was suffering from acetabular osteosarcoma was treated with wide excision of the tumor, followed by periacetabular reconstruction with an autogenous extracorporeal irradiated osteoarticular graft combined with a vascularized fibula graft. Incorporation of the irradiated pelvic bone was achieved despite infection and limb function turned out to be acceptable. CONCLUSION: This is the first report on an irradiation-vascularized hybrid autograft to reconstruct massive bone loss in primary limb-sparing surgery.

Histological findings in a human autogenous pasteurized bone graft.

BACKGROUND: Autogenous bone graft after pasteurization is one of the most valuable procedures for reconstruction of large bone defects following excision of malignant musculoskeletal tumors. To date, there have been no documented histological reports on pasteurized bone grafts, apart from short-term histological results. CASE REPORT: We treated a 27-year-old male with a periosteal chondrosarcoma of the tibia by wide excision and reimplantation of the large pasteurized bone. Biopsy specimens harvested from the pasteurized bone over 3 years after reimplantation were evaluated histologically. The graft cortices remained totally necrotic with empty osseous lacuna, whereas the architecture of the acellular cortical bones was still maintained without microfractures. Deposited seams of woven bone existed focally on the surface of the acellular trabeculae. CONCLUSION: Our medium-term histological outcome suggests the limitations of incorporating a pasteurized hone graft, but also advocates its role as a useful temporary material for the reconstruction of massive bone defects.

Aging effects of sympathetic reflex activities on skin nerves.

BACKGROUND: Muscle sympathetic nerve activity (MSNA) at rest is widely known to increase with aging, but changes in skin sympathetic nerve activity (SSNA) with aging are less well defined. We examined the aging effects of reflex activities on SSNA, sympathetic skin response (SSR), and sympathetic flow response (SFR). OBJECTIVE: We studied the aging effect of reflex activities on SSNA, SSR and SFR. METHODS: SSNA, SSR and SFR were simultaneously recorded during randomly administered electrical stimuli. RESULTS: The mean SSNA reflex latency was 763.1 +/- 39.8 ms, mean SSNA amplitude was 12.6 +/- 6.3 microV, mean SSR reflex latency was 1,809.0 +/- 90.6 ms, mean SSR reflex amplitude was 0.519 +/- 0.449 mV, mean SFR reflex latency was 4,398.9 +/- 761.7 ms, and mean SFR reflex amplitude was 8.21 +/- 5.14 ml/min/100 g. None of these parameters were significantly affected by aging. The reflex bursts on SSNA could be recorded in all subjects studied. While the frequencies of SSR and SFR were recorded in more than 80% of young subjects under age 40 years, the frequencies of SSR were recorded in less than 25% of subjects over age 80 years, and the frequencies of SFR were recorded in less than 5%. CONCLUSION: There were no differences in electrical stimuli-induced reflex SSNA between young and older subjects, but effector organ responses such as SSR and SFR were diminished in older subjects.

A comparison of sympathetic outflow to muscles between cervical spondylotic amyotrophy and ALS.

To confirm the diagnostic usefulness of muscle sympathetic nerve activity (MSNA) in differentiation between cervical spondylotic amyotrophy (CSA) and amyotrophic lateral sclerosis (ALS) with cervical spondylosis (CS), MSNA, heart rate (HR) and blood pressure (BP) were recorded in 10 patients with CSA and ALS with CS, and age-matched healthy volunteers at rest and during head-up tilting. There were no differences in age, disability scores, pulmonary function, and HR or BP at rest between ALS and CSA groups. Resting MSNA was significantly greater in patients with ALS with CS than in comparison groups (P<0.001) with virtually no overlap between ALS and the CSA groups. During head-up tilting, changes in BP and MSNA were significantly less in patients with ALS than in patients with other subjects. MSNA at rest clearly differentiated CSA from ALS with CS, suggesting diagnostic utility.