Conventional myelosuppressive chemotherapy for non-haematological malignancy disrupts the intestinal microbiome.

BACKGROUND: The gut microbiota influences many aspects of host physiology, including immune regulation, and is predictive of outcomes in cancer patients. However, whether conventional myelosuppressive chemotherapy affects the gut microbiota in humans with non-haematological malignancy, independent of antibiotic exposure, is unknown. METHODS: Faecal samples from 19 participants with non-haematological malignancy, who were receiving conventional chemotherapy regimens but not antibiotics, were examined prior to chemotherapy, 7-12 days after chemotherapy, and at the end of the first cycle of treatment. Gut microbiota diversity and composition was determined by 16S rRNA gene amplicon sequencing. RESULTS: Compared to pre-chemotherapy samples, samples collected 7-12 days following chemotherapy exhibited increased richness (mean 120 observed species ± SD 38 vs 134 ± 40; p = 0.007) and diversity (Shannon diversity: mean 6.4 ± 0.43 vs 6.6 ± 0.41; p = 0.02). Composition was significantly altered, with a significant decrease in the relative abundance of gram-positive bacteria in the phylum Firmicutes (pre-chemotherapy median relative abundance [IQR] 0.78 [0.11] vs 0.75 [0.11]; p = 0.003), and an increase in the relative abundance of gram-negative bacteria (Bacteroidetes: median [IQR] 0.16 [0.13] vs 0.21 [0.13]; p = 0.01 and Proteobacteria: 0.015 [0.018] vs 0.03 [0.03]; p = 0.02). Differences in microbiota characteristics from baseline were no longer significant at the end of the chemotherapy cycle. CONCLUSIONS: Conventional chemotherapy results in significant changes in gut microbiota characteristics during the period of predicted myelosuppression post-chemotherapy. Further study is indicated to link microbiome changes during chemotherapy to clinical outcomes.

Intestinal microbiology and urinary tract infection associated risk in long-term aged care residents.

BACKGROUND: Urinary tract infections (UTI) are the most frequently diagnosed infection in residents of long-term care and are a major risk factor for urosepsis, hospitalisation, and death. Translocation of gut pathobionts into the urinary tract is the presumed cause of most UTIs. While specific gut microbiota characteristics have been linked to UTI risk in younger adults, their relevance in aged care residents remains uncertain. METHODS: The faecal microbiome was assessed in 54 long-term aged care residents with a history of UTIs and 69 residents without a UTI history. Further comparisons were made to microbiome characteristics in 20 younger adults without UTIs. Microbiome characteristics were examined in relation to prior and subsequent UTIs, as well as antibiotic therapy. RESULTS: In long-term aged care residents, prior UTI history and exposure to UTI-exclusive antibiotics do not significantly affect microbiome composition or functional capacity. However, exposure to antibiotics unrelated to UTI treatment is associated with distinct microbiota compositional traits. Adjustment for dementia, incontinence, diabetes, and prior antibiotic use finds no microbiota characteristic linked to UTI development. However, prior UTI is identified as a predictor of future UTIs. Comparison with younger adults identifies greater within-participant dispersion in aged care residents, as well as lower microbiota diversity and altered microbiome functional potential. CONCLUSIONS: No association between the gut microbiome and UTI incidence, as has been reported in younger individuals, is evident in long-term aged care residents. Considerable variability in gut microbiome characteristics, relating to high antibiotic exposure and age-related physiological and immunological factors, could mask such a relationship. However, it cannot be discounted that increased UTI risk in the elderly is independent of microbiome-mediated mechanisms.

Urinary tract infections (UTIs) are common in residents of long-term aged care facilities, posing serious health risks. Harmful bacteria moving from the gut to the urinary tract is thought to cause most UTIs. It is still unclear, however, how differences in gut bacteria contribute to UTI risk in older adults. Here, we investigate the gut bacteria of aged care residents, both with and without a history of UTIs, and compare them to younger adults. While prior UTIs did not alter gut bacteria, antibiotic use did. We observed greater variability in gut bacteria among aged care residents compared to younger adults. These observations suggest that both high antibiotic exposure and age-related factors may mask any potential relationship between gut bacteria and UTI risk in this population. Understanding these factors could lead to improved UTI prevention and treatment strategies for elderly individuals.

Quality of transition to end-of-life care for cancer patients in the intensive care unit.

BACKGROUND: There have been few studies that have evaluated the quality of end-of-life care (EOLC) for cancer patients in the ICU. The aim of this study was to explore the quality of transition to EOLC for cancer patients in ICU. METHODS: The study was undertaken on medical patients admitted to a specialist cancer hospital ICU over 6 months. Quantitative and qualitative methods were used to explore quality of transition to EOLC using documentary evidence. Clinical parameters on ICU admission were reviewed to determine if they could be used to identify patients who were likely to transition to EOLC during their ICU stay. RESULTS: Of 85 patients, 44.7% transitioned to EOLC during their ICU stay. Qualitative and quantitative analysis of the patients' records demonstrated that there was collaborative decision-making between teams, patients and families during transition to EOLC. However, 51.4 and 40.5% of patients were too unwell to discuss transition to EOLC and DNACPR respectively. In the EOLC cohort, 76.3% died in ICU, but preferred place of death known in only 10%. Age, APACHE II score, and organ support, but not cancer diagnosis, were identified as associated with transition to EOLC (p = 0.017, p < 0.0001 and p = 0.001). CONCLUSIONS: Advanced EOLC planning in patients with progressive disease prior to acute deterioration is warranted to enable patients' wishes to be fulfilled and ceiling of treatments agreed. Better documentation and development of validated tools to measure the quality EOLC transition on the ICU are needed.