The ACA index has the ability to stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of elderly patients with DLBCL treated with R-CHOP. 2017;22:554-560 IMPLICATIONS FOR PRACTICE: Currently, little is known regarding how to identify elderly patients with diffuse large B-cell lymphoma who may tolerate a full dose of chemotherapy or to what extent cytotoxic drugs should be reduced in some specific conditions. The Society of Lymphoma Treatment in Japan developed a host-dependent prognostic model consisting of higher age (>75 years), hypoalbuminemia (<3.7 g/dL), and higher Charlson Comorbidity Index score (≥3) for such elderly patients. This model can stratify the prognosis, tolerability to cytotoxic drugs, and adherence to treatment of these patients and thus help clinicians in formulating personalized treatment strategies for this growing patient population.

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1. To investigate the pharmacological effects of T-1095, this novel derivative of phlorizin was administered to GK rats for 8 weeks. T-1095 treatment significantly lowered plasma glucose and glycosylated haemoglobin (HbA1c) levels, but did not significantly affect bodyweight. 2. T-1095 treatment did not affect 3.3 mmol/L glucose-induced insulin secretion in the isolated perfused pancreas of GK rats. 3. The peak insulin release in T-1095-treated GK rats was significantly higher during the first phase than in untreated GK rats (3-4 min after beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted during the first phase in T-1095-treated GK rats was significantly higher than in untreated GK rats (35.3 +/- 1.4 vs. 27.3 +/- 2.5 ng in T-1095-treated compared with untreated rats, respectively). 4. During the second phase, insulin release in T-1095-treated GK rats was somewhat higher than in untreated GK rats (7-30 min after beginning 16.7 mmol/L glucose perfusion). The total amount of insulin secreted during the second phase in T-1095-treated GK rats was significantly higher than in untreated GK rats (88.2 +/- 6.1 vs. 68.1 +/- 5.7 ng, respectively). 5. The total amount of insulin secreted during perfusion in T-1095-treated GK rats was significantly higher than in untreated GK rats (123.5 +/- 7.3 vs. 95.4 +/- 7.7 ng, respectively). 6. These data show that the metabolic indices, plasma glucose and HbA1c levels and insulin secretion are significantly improved by T-1095 treatment in GK rats, which are spontaneously diabetic rats, suggesting its usefulness as a novel oral therapeutic antidiabetic agent.

OBJECTIVE:To investigate the association of the promoter region 73826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the b3 adrenergic receptor (b3AR). SUBJECTS: Three-hundred and forty-nine young (mean age 20.4 AE 2.1 y old), healthy Japanese males. MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability. RESULTS: UCP1 or b3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of b3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was signi®cantly lower than normal (AA, 203.2 AE 50.3 vs 462.2 AE 83.6 ms 2 ; mean AE s.e., P 0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG. CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with b3AR polymorphism in decreasing sympathetic nervous system activity.

The standard CHOP therapy for peripheral T-cell lymphoma has resulted in unsatisfactory outcomes and it is still not clear what is the optimal front-line therapy. We conducted a multicenter phase II study of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone (EPOCH) for untreated peripheral T-cell lymphoma patients. In this prospective study, 41 patients were treated with dose-adjusted-EPOCH as initial therapy: peripheral T-cell lymphoma-not otherwise specified, n=21; angioimmunoblastic T-cell lymphoma, n=17; anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, n=2; and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, n=1. Median patient age was 64 years (range: 32–79 years). According to the International Prognostic Index criteria, 51.2% were at high-intermediate or high risk. The overall response and complete response rates were 78.0% [95% confidence interval (CI): 62.4–89.4%] and 61.0% (95%CI: 44.5–75.8%), respectively. At the median follow up of 24.0 months, the 2-year progression-free survival and overall survival were 53.3% (95%CI: 36.4–67.5%) and 73.2% (95%CI: 56.8–84.1%), respectively. The younger patients (≤ 60 years old) had a high response rate (overall response 94.1% and complete response 70.6%) and survival rate (progression-free survival 62.5% and overall survival 82.4%). The most common grade ≥ 3 adverse events were neutropenia (74.5%), anemia (40.8%), thrombocytopenia (22.0%), and febrile neutropenia (9.0%). Dose-adjusted-EPOCH had a high response rate with a tolerable toxicity profile. Our results indicate that dose-adjusted-EPOCH is a reasonable first-line approach for peripheral T-cell lymphoma patients and may improve outcomes.