Genetic Variants of Human Granzyme B Predict Transplant Outcomes after HLA Matched Unrelated Bone Marrow Transplantation for Myeloid Malignancies

Serine protease granzyme B plays important roles in infections, autoimmunity, transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant that encodes three amino substitutions (Q48R, P88A, and Y245H) has been reported to have altered biological functions. In the polymorphism rs8192917 (2364A>G), the A and G alleles represent wild type QPY and RAH mutant variants, respectively. In this study, we analyzed the impact of granzyme B polymorphisms on transplant outcomes in recipients undergoing unrelated HLA-fully matched T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The granzyme B genotypes were retrospectively analyzed in a cohort of 613 pairs of recipients with hematological malignancies and their unrelated donors. In patients with myeloid malignancies consisting of acute myeloid leukemia and myelodysplastic syndrome, the donor G/G or A/G genotype was associated with improved overall survival (OS; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41–0.89; P = 0.01) as well as transplant related mortality (TRM; adjusted HR, 0.48; 95% CI, 0.27–0.86, P = 0.01). The recipient G/G or A/G genotype was associated with a better OS (adjusted HR, 0.68; 95% CI, 0.47–0.99; P = 0.05) and a trend toward a reduced TRM (adjusted HR, 0.61; 95% CI, 0.35–1.06; P = 0.08). Granzyme B polymorphism did not have any effect on the transplant outcomes in patients with lymphoid malignancies consisting of acute lymphoid leukemia and malignant lymphoma. These data suggest that there is an association between the granzyme B genotype and better clinical outcomes in patients with myeloid malignancies after unrelated BMT

Etiological factors in primary hepatic B-cell lymphoma

Sixty-four cases of malignant lymphoma involving the liver were examined. Of these, 20 cases were histologically confirmed to be primary hepatic B-cell lymphoma. Twelve of these 20 cases were diffuse large B-cell lymphoma (DLBCL) and eight cases were mucosa-associated lymphoid tissue (MALT) lymphoma. Of the 12 cases of DLBCL, six were immunohistologically positive for CD10 and/or Bcl6 (indicating a germinal center phenotype), six were positive for Bcl2, and five were positive for CD25. Eight of the 12 DLBCL cases (66.7%) and two of the eight MALT lymphoma cases (25%) had serum anti-hepatitis C virus (HCV) antibodies and HCV RNA. The incidence of HCV infection was significantly higher in the hepatic DLBCL cases than in systemic intravascular large B-cell cases with liver involvement (one of 11 cases, 9.1%) and T/NK-cell lymphoma cases (one of 19 cases, 5.3%) (p < 0.01 for both). Two hepatic DLBCL cases (16.7%) had rheumatoid arthritis treated with methotrexate, and four MALT lymphoma cases (50%) had Sjögren’s syndrome, primary biliary cirrhosis, or autoimmune hepatitis; one case in each of these two groups was complicated by chronic HCV-seropositive hepatitis. Although primary hepatic lymphoma is rare, persistent inflammatory processes associated with HCV infection or autoimmune disease may play independent roles in the lymphomagenesis of hepatic B cells

Achieving LDL cholesterol target levels <1.81 mmol/L may provide extra cardiovascular protection in patients at high risk: Exploratory analysis of the Standard Versus Intensive Statin Therapy for Patients with Hypercholesterolaemia and Diabetic Retinopathy study

Aims To assess the benefits of intensive statin therapy on reducing cardiovascular (CV) events in patients with type 2 diabetes complicated with hyperlipidaemia and retinopathy in a primary prevention setting in Japan. In the intension-to-treat population, intensive therapy [targeting LDL cholesterol = 2.59 to = 100 to = 2.59 to <3.10 mmol/L in patients with hypercholesterolaemia and diabetic retinopathy

A Case of Crouzon's Syndrome with a True Human Tail

A human tail complicated by Crouzon syndrome is extremely rare, with only eight reported cases of human tails associated with Crouzon syndrome. A human tail is defined as a true human tail or a pseudo-human tail according to the presence or absence of the bone tissue. A 4-year-old boy had a true caudal sacral protrusion from birth and was also diagnosed with Crouzon syndrome. There were no neurological symptoms or vesico-rectal disturbances. The patient underwent a human tail resection at 4 years and 7 months. The postoperative course was uneventful, and there was no recurrence at 6 months postoperatively. Some reports suggested that Crouzon syndrome and the human tail are associated with FGFR2 gene mutation, but the details are currently unknown. Further genetic searches for cases of the combined human tail and Crouzon syndrome in the future are likely to reveal further associations

Effects of Home-Based Robotic Therapy Involving the Single-Joint Hybrid Assistive Limb Robotic Suit in the Chronic Phase of Stroke: A Pilot Study

Introduction. Robotic therapy has drawn attention in the rehabilitation field including home-based rehabilitation. A previous study has reported that home-based therapy could be more effective for increasing upper limb activity than facility-based therapy. The single-joint hybrid assistive limb (HAL-SJ) is an exoskeleton robot developed according to the interactive biofeedback theory, and several studies have shown its effectiveness for upper limb function in stroke patients. A study of home-based robotic therapy has shown to enhance rehabilitation effectiveness for stroke patient with a paretic upper limb. However, home-based therapy involving a HAL-SJ in stroke patients with paretic upper limbs has not been investigated. The present study aimed to investigate paretic upper limb activity and function with home-based robotic therapy involving a HAL-SJ in stroke patients. Materials and Methods. A home-based robotic therapy program involving a HAL-SJ was performed for 30 min per session followed by standard therapy for 30 min per session, 2 times a week, for 4 weeks (i.e., completion of all 8 sessions involved 8 h of rehabilitation), at home. After the intervention, patients were followed up by telephone and home visits for 8 weeks. The paretic upper limb activity and function were assessed using the Motor Activity Log (MAL; amount of use (AOU)), arm triaxial accelerometry (laterality index (LI)), the Fugl–Meyer assessment (FMA), and the action research arm test (ARAT), at baseline and week 4 and week 12 after the start of training. Results. The study included 10 stroke patients (5 men; mean age, 61.1 ± 7.1 years). The AOU scores and LI significantly improved at week 4 after the start of training (p<0.05). However, no significant changes were observed in the LI at week 12 (p=0.161) and the FMA scores at both week 4 and week 12 (p=0.059 and p=0.083, respectively). The ARAT scores significantly improved at both week 4 and week 12 (p<0.05). Conclusion. Home-based robotic therapy combined with conventional therapy could be a valuable approach for increasing paretic upper limb activity and maintaining paretic upper limb function in the chronic phase of stroke

A Study of the Prognostic Factors for Late Cervical Lymph Node Metastasis and Distant Metastasis in Patients with cT1-2N0 Tongue Cancer

Background: Early-stage tongue cancer has a good prognosis in general; however, high-risk patients with late cervical lymph node and distant metastases have a poor prognosis. Elective neck dissection and postoperative chemoradiotherapy are considered for these patients, although no clear criteria have been identified for their evaluation. Methods: This retrospective observational study aimed to determine the predictive factors for late cervical lymph node and distant metastases in 102 patients with cT1-2N0 tongue cancer. The data regarding the demographic characteristics, as well as the depth of invasion, tumor budding, histological grade, and tumor–stromal ratio, among other things, were extracted from medical records. Results: We found that the potential lymph node metastasis rate was 27.5%. The significant clinical predictors of late cervical lymph node metastasis were the tumor thickness and endophytic growth pattern and the significant histopathological factors were poorly and moderately differentiated tumors and ≥3 tumor buds. In addition, the prognostic factors for distant metastasis included ≥4 lymph node metastases, ≥7 tumor budding, and moderate and poor tumor differentiation. Conclusions: The usefulness of tumor budding as a predictor of metastasis for tongue cancer was suggested. The findings of this study can help establish the criteria for evaluating the metastasis risk and prognosis of patients with tongue cancers