Evaluation of clinical effects of a multidisciplinary-collaborated cancer support team for gastrointestinal cancer chemotherapy: prospective observational study protocol of M-CAST study.

BACKGROUND: Although the multidisciplinary-collaborated team approach in cancer treatment has recently become popular, prospectively evaluated evidence is limited. We started a multidisciplinary-collaborated cancer support team (MCST) to facilitate cooperation across multidisciplinary medical staff in our hospital and established clinical evidence of supportive care. This study aimed to prospectively evaluate the clinical activity and effect of MCST in patients with gastrointestinal cancer receiving chemotherapy. METHODS: This is a single-center, single-arm, observational study. Patients with gastrointestinal cancer scheduled to receive chemotherapy are enrolled and supported by the MCST. The primary endpoints are the number of interventions by medical staff and the number of patients who showed improvement in side effects. The secondary endpoints are the severity of side effects, medical expenses, number of consultations, the acceptance rate of prescription recommendations, adjuvant chemotherapy completion rates, dose intensity, and time required for co-medical intervention. In addition, medical staff and attending physicians evaluate all adverse events. DISCUSSION: This study is expected to contribute to establishing new cancer-supportive care teams for patients with gastrointestinal cancer receiving chemotherapy and those with cancer receiving chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCT1030220495. The date of first registration, 29/11/2022, https://jrct.niph.go.jp/search.

Study protocol of a single-arm phase 2 study evaluating the preventive effect of topical hydrocortisone for capecitabine-induced hand-foot syndrome in colorectal cancer patients receiving adjuvant chemotherapy with capecitabine plus oxaliplatin (T-CRACC study).

BACKGROUNDS: Clinical evidence of the preventive effectiveness of medium-class topical corticosteroids for capecitabine-induced hand foot syndrome (HFS) is limited. Although the pathogenesis and mechanism of HFS are unclear, inflammatory reactions are thought to be involved in HFS development. This study aimed to evaluate the preventive effect of medium-class topical corticosteroids (hydrocortisone butyrate 0.1% topical therapy) for capecitabine-induced HFS in patients with colorectal cancer receiving adjuvant chemotherapy with capecitabine plus oxaliplatin. METHODS: This is a single-center, single-arm, phase 2 study. Patients with colorectal cancer scheduled to receive adjuvant chemotherapy with capecitabine plus oxaliplatin are enrolled, and topical hydrocortisone butyrate 0.1% is applied prophylactically in addition to standard moisturizing therapy. The primary endpoint is the incidence of grade ≥ 2 HFS within three months. The secondary endpoints are the time to onset of HFS, rates of dose reduction, schedule delay, discontinuation caused by capecitabine-induced HFS, and other adverse events. All adverse events are evaluated by clinical pharmacists and attending physicians. DISCUSSION: This study is expected to contribute to the establishment of new supportive care for preventing HFS, not only for colorectal cancer patients receiving adjuvant chemotherapy, but also for various cancer patients receiving capecitabine-based chemotherapy. TRIAL REGISTRATION: This trial was registered in the Japan Registry of Clinical Trials (jRCT) as jRCTs031220002. Registered 5 April 2022, https://jrct.niph.go.jp/search Protocol version V.1.0, 16 February 2022.

Possible involvement of TRPM2 activation in 5-fluorouracil-induced myelosuppression in mice.

Transient receptor potential melastatin 2 (TRPM2) is an oxidative stress-sensitive Ca2+-permeable channel. The activation of TRPM2 by H2O2 causes cell death in various types of cells. 5-Fluorouracil (5-FU) is an important anticancer drug, but myelosuppression is one of the most frequent adverse effects. The involvement of oxidative stress in 5-FU-induced myelosuppression has been reported, and bone marrow cells are known to express TRPM2. The aim of this study was to investigate whether TRPM2 is involved in 5-FU-induced myelosuppression. Enhancement of H2O2-induced intracellular Ca2+ concentration ([Ca2+]i) increase by 5-FU treatment was observed in human embryonic kidney 293 (HEK) cells stably expressing TRPM2 but not in HEK cells, indicating that 5-FU stimulates TRPM2 activation. In CD117 positive cells from wild type (WT) mouse bone marrow, 5-FU also enhanced the H2O2-induced [Ca2+]i increases, but not in cells from Trpm2 knockout (KO) mice. In the CFU-GM colony assay, the 5-FU-induced reduction of colony number was alleviated by Trpm2 deficiency. Moreover, the reduction of leukocytes in blood by administration with 5-FU in WT mice was also alleviated in Trpm2 KO mice. The activation of TRPM2 in bone marrow cells seems to be involved in 5-FU-induced myelosuppression.

[Therapeutic Effects of Intranasal Sumatriptan for Cluster Headache].

To clarify the associated factors for negative response to sumatriptan nasal spray in patients with cluster headache, we investigated the involvement of clinical information, such as the characteristics of headaches, before commencing sumatriptan nasal spray treatment. There were 18 male patients and 4 female patients. A total of 17 responders and 5 non-responders to sumatriptan nasal spray participated in the present study. Three factors for negative response to sumatriptan nasal spray, "young age of onset", "psychiatric disorder", and "the headache is not in the orbit," were found. Oxygen inhalation and/or subcutaneous injection were effective for nonresponsive cases. Therefore, these factors are considered to be useful for predicting therapy before applying sumatriptan nasal spray.

[A Questionnaire Survey on Cooperation between Community Pharmacies and Hospitals in Outpatient Chemotherapy-Comparison of Roles of Pharmacists in Community Pharmacy and Hospitals].

　Previous reports suggested that sharing outpatient information during chemotherapy is very important for managing pharmaceutical usage between community pharmacies and hospitals. We herein examined using a questionnaire survey whether pharmaceutical management for outpatient chemotherapy is desired by community and hospital pharmacists. The response rates were 44.3% (133/300) for pharmacists in community pharmacies and 53.7% (161/300) for pharmacists in hospitals. Prescriptions for outpatients during chemotherapy were issued at 88.2% of the hospitals. Currently, 28.9% of hospital pharmacists rarely provide pharmaceutical care, such as patient guidance and adverse effect monitoring, for outpatients receiving oral chemotherapy. Furthermore, whereas 93.7% of hospital pharmacists conducted prescription audits based on the chemotherapy regimen, audits were only performed by 14.8% of community pharmacists. Thus, outpatients, particularly those on oral regimens, were unable to receive safe pharmaceutical care during chemotherapy. Community pharmacists suggested that hospital pharmacists should use "medication notebooks" and disclose prescription information when providing clinical information to community pharmacists. They also suggested sending clinical information to hospital pharmacists by fax. On the other hand, hospital pharmacists suggested the use of "medication notebooks" and electronic medical records when providing clinical information to community pharmacists. In addition, they suggested for community pharmacists to use electronic medical records when providing clinical information to hospital pharmacists. As there may be differences in opinion between community and hospital pharmacists, mutual preliminary communication is important for successful outpatient chemotherapy.

Efforts by Pharmacists in Community Pharmacy in Peacetime for Headache Medical Care in Emergencies, Such as Great Earthquake and Disaster.

We herein analyzed the issues that pharmacists in a community pharmacy in peacetime need to prepare for regarding headache medical care in emergencies (the state that supply of medical supplies is difficult) using a questionnaire intended for doctors and pharmacists in a community pharmacy. Recovery rates were 48.0% (96/200) for doctors and 37.3% (112/300) for pharmacists. In order to distinguish between patients for whom pharmacists need to "recommend OTC drugs" and those who need to be encouraged "to consult a hospital or clinic", doctors indicated that pharmacists need to use an "assistance tool to diagnosis headaches, such as a migraine screener" and "guidelines for chronic headaches". However, few pharmacists used these tools. Approximately 66.7% of doctors indicated that it is "meaningful" for pharmacists to distinguish patients with headaches. Moreover, doctors indicated the need for guidance by pharmacists in peacetime regarding headache medical care in emergencies. Although 73.2% of pharmacists instructed the patients with headaches of the importance of medication notebooks in emergencies, guidance ("understanding the triggers of headaches", "understanding the importance of removing the cause of the headache", "standing OTC drugs" and "standing prescription drugs") by pharmacists to prepare for an emergency was insufficient. These results provide useful information to improve the efforts by pharmacists in community pharmacies in peacetime for headache medical care in emergencies.

Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload.

Sustained cardiac pressure overload induces mitochondrial dysfunction and apoptosis of cardiomyocytes leading to pathological cardiac hypertrophy and dysfunction. Mitochondrial nitric oxide synthase (NOS) appears to cause uncoupling, which produces reactive oxygen species (ROS) instead of nitric oxide (NO), by a decrease in the cofactor tetrahydrobiopterin (BH4). This study focused on examining the changes in mitochondrial BH4 levels during cardiac pressure overload. Chronic cardiac pressure overload was generated by abdominal aortic banding in rats. Levels of BH4 and its oxidized form were measured in the mitochondria isolated from the left ventricle (LV) and the post-mitochondrial supernatants. Chronic aortic banding increased blood pressure, and induced cardiac hypertrophy and fibrosis. Notably, the BH4 levels were decreased while its oxidized forms were increased in LV mitochondria, but not in the post-mitochondrial supernatants containing the cytosol and microsome. Anti-neuronal NOS antibody-sensitive protein was detected in the cardiac mitochondria. Moreover, continuous administration of BH4 to rats with pressure overload increased mitochondrial BH4 levels and reduced cardiac fibrosis and matrix metallopeptidase activity, but not cardiac hypertrophy. These findings show the possibility that NOS uncoupling by decreased cardiac mitochondrial BH4 levels is implicated, at least in part, in the development of cardiac fibrosis, leading to cardiac dysfunction induced by pressure overload.