Microbiome-gut-brain axis in cancer treatment-related psychoneurological toxicities and symptoms: a systematic review.

PURPOSE: The microbiome-gut-brain (MGB) axis provides a dynamic model to understand associations between the gut microbiota and psychoneurological comorbidities. The role of the MGB axis in cancer treatment-related psychoneurological symptoms (PNS) remains unknown. The purpose of this study was to conduct a systematic review of the existing literature to identify the influence of the gut microbiota on cancer and cancer treatment-related PNS and toxicities mediated by the MGB axis. METHODS: We searched the databases of PubMed, Embase, and Web of Science from their earliest records to October 2019. All studies identified in the database searches were screened by title and abstract, followed by a review of the full texts. The Johns Hopkins Nursing Evidence-Based Practice Model was adopted to assess the evidence levels and qualities; the Joanna Briggs Institute critical appraisal tools were used to assess the methodological quality and the possibility of bias for each included study. All the study findings were combined, synthesized, and presented through narrative format. RESULTS: Six studies were included in this systematic review. These studies primarily focused on cancer survivorship while receiving chemotherapy, and they were conducted between 2016 and 2019. The gut microbiome was assessed via fecal samples, which were analyzed using 16S rRNA sequencing approaches. With small-scale studies, the gut microbiota was associated with cancer treatment-related PNS, including fatigue, anxiety, depression, sleep disturbance, cognitive impairment, and chemotherapy-induced peripheral neuropathy. A higher relative abundance of Bacteroides was associated with a higher level of fear of cancer recurrence but a higher relative abundance of Lachnospiraceae.g and Ruminococcus was associated with a lower level in fear of cancer recurrence. Changes in fatigue interference were associated with the frequency of genera Faecalibacterium and Prevotella, and changes in anxiety were associated with the frequency of genera Coprococcus and Bacteroides. CONCLUSIONS: The gut microbiota showed significant associations with cancer treatment-related PNS. Recent work regarding the MGB axis in cancer psychoneurological toxicities focused primarily on individual toxicity and symptoms in cancer survivors with chemotherapy exposure. Associations between the gut microbiota and PNS should be further studied in cancer populations across different ages, cancer types, and treatment modalities.

Hemophilia prophylaxis adherence and bleeding using a tailored, frequency-escalated approach: The Canadian Hemophilia Primary Prophylaxis Study.

BACKGROUND: Standard of care for persons with severe hemophilia A includes regular replacement of factor VIII (FVIII). Prophylaxis regimens using standard half-life (SHL) FVIII concentrates, while effective, are costly and require frequent intravenous infusions. AIM: This study evaluated the adherence of 56 boys with severe hemophilia A to tailored, frequency-escalated prophylaxis with an SHL recombinant FVIII concentrate. METHODS: We reviewed the factor infusion and bleeding logs of study subjects. Adherence to the prescribed regimen was calculated on a weekly basis, and bleeding rates were determined from self/proxy-reported bleeding logs. The primary outcome was adherence to the prescribed prophylaxis regimen. RESULTS: The median (range of values [ROV]) weekly adherence to prophylaxis was 85.7% (37.4%-99.8%). The median (ROV) adherent weeks on steps 1 (weekly), 2 (twice weekly), and 3 (alternate-day) were 92.9% (50%-100%), 80.3 (32%-96%), and 72.6% (14%-98%); relative to step 1, subjects were less likely to be adherent on steps 2 and 3 (P < 0.00). On step 1, our cohort had higher adherence than previously reported rates. The median (ROV) adherence to the breakthrough bleeding protocol was 47.1% (0%-100%). At any given time, bleeding risk was reduced by 15% for each 10% increase in adherence during the preceding 12 weeks (hazard ratio, 0.85; 95% confidence interval, 0.81-0.90). CONCLUSION: This cohort had high rates of adherence to the prescribed prophylaxis regimen. Initiating prophylaxis with once-weekly infusions facilitated adherence to the prophylaxis regimen in this cohort of boys with severe hemophilia A started on primary prophylaxis at a very young age.