Research progress of multi-target HDAC inhibitors blocking the BRD4-LIFR-JAK1-STAT3 signaling pathway in the treatment of cancer.

Histone deacetylase inhibitors (HDACis) show beneficial effects on different hematological malignancy subtypes. However, their impacts on treating solid tumors are still limited due to diverse resistance mechanisms. Recent studies have found that the feedback activation of BRD4-LIFR-JAK1-STAT3 pathway after HDACi incubation is a vital mechanism inducing resistance of specific solid tumor cells to HDACis. This review summarizes the recent development of multi-target HDACis that can concurrently block BRD4-LIFR-JAK1-STAT3 pathway. Moreover, our findings hope to shed novel lights on developing novel multi-target HDACis with reduced BRD4-LIFR-JAK1-STAT3-mediated drug resistance in some tumors.

Validation of "Care of the Dying Evaluation" in Emergency Medicine (CODE-EM): pilot phase of end-of-life management protocol offered within emergency room (EMPOWER) study.

BACKGROUND: An increasing number of patients who present to emergency departments are at their end-of-life phase and have significant palliative care needs such as in symptom control for pain and dyspnoea. Evaluating quality of care provided is imperative, yet there is no suitable tool validated in the emergency and Asian settings. We aim to examine the face and construct validity, and reliability of a newly developed questionnaire, Care of the Dying Evaluation - Emergency Medicine, for measuring the quality of end-of-life care in an Asian emergency context. METHODS: A mixed methods pilot study was conducted. Participants composed of the next-of-kin to thirty dying patients who presented to the emergency departments of three public hospitals in Singapore. Qualitative evaluation, using cognitive "think-aloud" interviews, and quantitative analysis were employed. Percentage agreement and κ statistic were measured to evaluate temporal stability of the questionnaire. Cronbach's α and item-total correlations were used to assess internal consistency within the constructs. Confirmatory factor analysis was performed for construct validity. RESULTS: All participants reported clear understanding of the questionnaire with no ambiguity; a minority felt the questions caused emotional distress (7/30, 23.3%). The questions showed moderate to good test-retest reliability. Internal consistencies within the constructs were good for "ENVIRONMENT" and "CARE", and moderate for "COMMUNICATION". Factor loadings range from 0.40 to 0.99. CONCLUSIONS: The Care of the Dying Evaluation - Emergency Medicine questionnaire may be valid and reliable for use in an Asian emergency setting. Our prospective multicentre study using this evaluation tool may provide more insight on the quality of care rendered to dying patients and identify areas for improvement. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03906747).

End-of-life management protocol offered within emergency room (EMPOWER): study protocol for a multicentre study.

BACKGROUND: Patients at their end-of-life (EOL) phase frequently visit the emergency department (ED) due to their symptoms, yet the environment and physicians in ED are not traditionally equipped or trained to provide palliative care. This multicentre study aims to measure the current quality of EOL care in ED to identify gaps, formulate improvements and implement the improved EOL care protocol. We shall also evaluate healthcare resource utilisation and its associated costs. METHODS AND ANALYSIS: This study employs a quasiexperimental interrupted time series design using both qualitative and quantitative methods, involving the EDs of three tertiary hospitals in Singapore, over a period of 3 years. There are five phases in this study: (1) retrospective chart reviews of patients who died within 5 days of ED attendance; (2) pilot phase to validate the CODE questionnaire in the local context; (3) preimplementation phase; (4) focus group discussions (FGDs); and (5) postimplementation phase. In the prospective cohort, patients who are actively dying or have high likelihood of mortality this admission, and whose goal of care is palliation, will be eligible for inclusion. At least 140 patients will be recruited for each preimplementation and postimplementation phase. There will be face-to-face interviews with patients' family members, review of medical records and self-administered staff survey to evaluate existing knowledge and confidence. The FGDs will involve hospital and community healthcare providers. Data obtained from the retrospective cohort, preimplementation phase and FGDs will be used to guide prospective improvement and protocol changes. Patient, family and staff relevant outcomes from these changes will be measured using time series regression. ETHICS AND DISSEMINATION: The study protocol has been reviewed and ethics approval obtained from the National Healthcare Group Domain Specific Review Board, Singapore. The results from this study will be actively disseminated through manuscript publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03906747.

Effect of probiotics on small intestinal bacterial overgrowth in patients with gastric and colorectal cancer.

BACKGROUND/AIMS: Small intestinal bacterial overgrowth (SIBO) may be related to the presence of gastrointestinal cancer. The exact link, however, between SIBO and cancer prevalence as well as cancer symptoms remains unclear, especially in Asian populations. In addition, there is a paucity of data documenting the influence of probiotic treatment of SIBO on cancer symptoms. Here, the aims were to correlate the presence of SIBO with cancer prevalence and cancer symptoms, as well as to investigate the effect of probiotic intervention on SIBO and cancer symptoms. MATERIALS AND METHODS: Employing a case-control design, 112 gastric and 88 colorectal cancer patients were evaluated. Questionnaires were used to assess gastrointestinal symptoms and a glucose-H2-breath test (GHBT) was used to determine SIBO status. Patients with SIBO were administered Bifidobacterium triple viable capsule therapy or placebo. Subsequently, SIBO status and gastrointestinal symptom scores were reanalyzed. RESULTS: In our study group, 63.0% of patients versus 16.3% of controls was tested positive for SIBO. In patients with cancer, SIBO was associated with proton pump inhibitor (PPI) use. Bifidobacterium triple viable capsule was effective in combating SIBO and was associated with a significant improvement in gastrointestinal cancer-related symptoms. CONCLUSION: In a Chinese cohort, SIBO is associated with gastrointestinal cancer. Based on the preliminary intervention study, we conclude that probiotic intervention combats SIBO in patients with gastrointestinal cancer and alleviates its symptoms.