Bleeding Risk of Acupuncture for Patients with Hematological Malignancies Accompanying Thrombocytopenia: A Retrospective Chart Review.

Introduction: In recent years, it has been reported that acupuncture is useful for alleviating the symptoms of patients with hematological malignancies, but the safety of acupuncture for such patients has not been established. This study evaluated the risk of bleeding from acupuncture in patients with hematological malignancies accompanying thrombocytopenia. Methods: The authors performed a retrospective investigation of the medical records of patients with hematological malignancies who received acupuncture during hospitalization at the hematology department of a single medical center in Japan. The bleeding risk at the acupuncture site was evaluated in the following four groups according to the platelet count measured on the day of acupuncture treatment: (1) <20 × 103/µL, (2) 20-49 × 103/µL, (3) 50-99 × 103/µL, and (4) 100 × 103/µL or more. Occurrence of grade 2 or higher bleeding according to the Common Terminology Criteria for Adverse Events, version 5.0, within 24 h from the acupuncture session or before the next session was defined as an event, and the risk of occurrence of bleeding was examined in each group. Results: Of 2423 acupuncture sessions conducted on 51 patients with hematological malignancies, 815 were included in the analysis. Ninety sessions were performed in the <20 × 103/µL platelet count group, 161 in the 20-49 × 103/µL group, 133 in the 50-99 × 103/µL group, and 431 in the 100 × 103/µL or more group. No bleeding event according to the authors' definition occurred in any of these groups. Conclusions: This study is the largest to date to assess the bleeding risk of acupuncture in patients with hematological malignancies accompanying thrombocytopenia. The authors considered that acupuncture could be safely performed without causing serious bleeding for patients with hematological malignancies accompanying thrombocytopenia.

Correlation of toxicities and efficacies of pemetrexed with clinical factors and single-nucleotide polymorphisms: a prospective observational study.

BACKGROUND: Pemetrexed is an efficacious multi-targeted antifolate with acceptable toxicity for non-squamous non-small cell lung cancer (non-Sq NSCLC) and malignant pleural mesothelioma. Vitamin B12 and folic acid as premedication can reduce the frequency of severe toxicities of pemetrexed chemotherapy. However, adverse effects are frequent in clinical settings. In this study, we aimed to identify the clinical factors and single-nucleotide polymorphisms (SNPs) associated with the toxicity and efficacy of pemetrexed chemotherapy. METHODS: This observational study was conducted from October 2012 to December 2019; we evaluated the toxicities and efficacies of pemetrexed chemotherapy using multivariate logistic or Cox regression analysis. In total, 106 patients received pemetrexed chemotherapy. SNPs were analyzed for four patients with malignant pleural mesothelioma and 67 with non-Sq NSCLC. RESULTS: The median progression-free survival (PFS) and overall survival of 63 patients with non-Sq NSCLC, excluding four in the adjuvant setting, were 6.8 and 33.3 months, respectively. Per propensity-score-adjusted multivariate Cox analyses, favorable factors for PFS were folic acid level ≥ 9.3 ng/mL before premedication, platinum combination, bevacizumab combination, vitamin B12 level < 1136 pg/mL before chemotherapy, A/A + A/G of BHMT (742 G > A), and A/A + A/C of DHFR (680 C > A). Favorable prognostic factors included good performance status, low smoking index, body mass index ≥ 20.66 kg/m2, folic acid level ≥ 5.55 ng/mL before premedication, higher retinol-binding protein before chemotherapy, and A/G of MTRR (66 A > G). Among the 71 patients who were analyzed for SNPs, the frequencies of hematologic toxicities and non-hematologic toxicities in Grades 3-4 were 38% and 36.6%, respectively. Per propensity-score-adjusted multivariate logistic analyses, risk factors for Grades 3-4 hematologic toxicities were vitamin B12 level < 486 pg/mL before premedication, leucocyte count < 6120 /µL before chemotherapy, folic acid level < 15.8 ng/mL before chemotherapy, status with a reduced dose of chemotherapy, and C/T + T/T of MTHFR (677 C > T). Risk factors for Grades 2-4 non-hematologic toxicities were homocysteine levels ≥ 11.8 nmol/mL before premedication, transthyretin level < 21.5 mg/dL before chemotherapy, C/C + T/T of MTHFR (677 C > T), and A/A + G/G of SLC19A1 [IVS2 (4935) G > A]. CONCLUSION: The information on metabolites and SNPs of the folate and methionine cycle will help predict the toxicities and efficacies of pemetrexed. TRIAL REGISTRATION: This trial was retrospectively registered with the University hospital Medical Information Network (UMIN000009366) on November 20, 2012.

Regulatory T and B cells in peripheral blood of subcutaneous immunotherapy-treated Japanese cedar pollinosis patients.

AIM: The aim of this study was to clarify whether there are more regulatory T (Treg) and regulatory B (Breg) cells, and higher levels of IL-10-related transcription factors in subcutaneous immunotherapy (SCIT)-treated pollinosis patients than in non-SCIT-treated patients. METHODS: Japanese cedar pollinosis patients undergoing SCIT had received treatment for at least 2.8 years. Peripheral blood mononuclear cells were used for flow cytometer analyses and mRNA measurement. RESULTS: The numbers of type 1 regulatory T (Tr1)-like cells and Breg cells, and expression of E4BP4 mRNA by peripheral blood mononuclear cells in SCIT-treated patients were higher than those in non-SCIT-treated patients. CONCLUSION: Tr1-like cells, Breg cells and E4BP4 may be involved in the effectiveness of SCIT.

Polyphenols extracted from black tea (Camellia sinensis) residue by hot-compressed water and their inhibitory effect on pancreatic lipase in vitro.

Polyphenols, retained in black tea wastes following the commercial production of tea beverages, represent an underutilized resource. The purpose of this study was to investigate the potential use of hot-compressed water (HCW) for the extraction of pancreatic lipase-inhibiting polyphenols from black tea residues. Black tea residues were treated with HCW at 10 °C intervals, from 100 to 200 °C. The resulting extracts were analyzed using high-performance liquid chromatography-mass spectrometry and assayed to determine their inhibitory effect on pancreatic lipase activity in vitro. Four theaflavins (TF), 5 catechins, 2 quercetin glycosides, quinic acid, gallic acid, and caffeine were identified. The total polyphenol content of extracts increased with increasing temperature but lipase inhibitors (TF, theaflavin 3-O-gallate, theaflavin 3'-O-gallate, theaflavin 3,3'-O-gallate, epigallocatechin gallate, and epicatechin gallate) decreased over 150 °C. All extracts inhibited pancreatic lipase but extracts obtained at 100 to 140 °C showed the greatest lipase inhibition (IC(50) s of 0.9 to 1.3 µg/mL), consistent with the optimal extraction of TFs and catechins except catechin by HCW between 130 and 150 °C. HCW can be used to extract pancreatic lipase-inhibiting polyphenols from black tea waste. These extracts have potential uses, as dietary supplements and medications, for the prevention and treatment of obesity.

Dietary histidine ameliorates murine colitis by inhibition of proinflammatory cytokine production from macrophages.

BACKGROUND & AIMS: Elemental diet (ED) is effective for human Crohn's disease (CD). Although some of this effectiveness may be due to its low antigenic load and low fat content, the mechanisms remain unclear. We sought to assess the role of histidine, one of the constituent amino acids of ED, in controlling colitis. METHODS: The interleukin (IL)-10-deficient (IL-10(-/-)) cell transfer model of colitis was used. SCID mice with colitis induced by transfer of IL-10(-/-) cells were maintained on experimented diets containing either single amino acids or a mixture. The severity of colitis was assessed by wet colon weight. Colonic tumor necrosis factor (TNF)-alpha messenger RNA (mRNA) expression was detected by quantitative reverse-transcription polymerase chain reaction. Mouse peritoneal macrophages were stimulated by lipopolysaccharides (LPS), with or without amino acids. The concentration of cytokines in the supernatant was determined by enzyme-linked immunosorbent assay. Inhibitor of nuclear factor (NF)-kappaB-alpha and nuclear p65 were confirmed by immunoblotting. RESULTS: In the IL-10(-/-) transfer model, dietary histidine, but not alanine, reduced histologic damage and colon weight and TNF-alpha mRNA expression. Histidine inhibited LPS-induced TNF-alpha and IL-6 production by mouse macrophages in a concentration-dependent manner, whereas alanine or histidine-related metabolites had no such effect. Histidine inhibited LPS-induced NF-kappaB in macrophages. CONCLUSIONS: These results showed that histidine could be a novel therapeutic agent for CD by inhibition of NF-kappaB activation, following down-regulation of proinflammatory cytokine production by macrophages. Thus, our studies provided new insights into the roles of amino acid metabolism in the pathophysiology of CD and for therapeutic strategies.