The Probiotic Lactobacillus reuteri Preferentially Synthesizes Kynurenic Acid from Kynurenine.

The gut-brain axis is increasingly understood to play a role in neuropsychiatric disorders. The probiotic bacterium Lactobacillus (L.) reuteri and products of tryptophan degradation, specifically the neuroactive kynurenine pathway (KP) metabolite kynurenic acid (KYNA), have received special attention in this context. We, therefore, assessed relevant features of KP metabolism, namely, the cellular uptake of the pivotal metabolite kynurenine and its conversion to its primary products KYNA, 3-hydroxykynurenine and anthranilic acid in L. reuteri by incubating the bacteria in Hank's Balanced Salt solution in vitro. Kynurenine readily entered the bacterial cells and was preferentially converted to KYNA, which was promptly released into the extracellular milieu. De novo production of KYNA increased linearly with increasing concentrations of kynurenine (up to 1 mM) and bacteria (107 to 109 CFU/mL) and with incubation time (1-3 h). KYNA neosynthesis was blocked by two selective inhibitors of mammalian kynurenine aminotransferase II (PF-048559989 and BFF-122). In contrast to mammals, however, kynurenine uptake was not influenced by other substrates of the mammalian large neutral amino acid transporter, and KYNA production was not affected by the presumed competitive enzyme substrates (glutamine and α-aminoadipate). Taken together, these results reveal substantive qualitative differences between bacterial and mammalian KP metabolism.

An observational study evaluating the impact on prostate patient outcomes and experiences when radiation therapists use a standard grading system tool to assess and document treatment-related toxicities and interventions.

BACKGROUND/PURPOSE: Men undergoing radiation therapy (RT) treatment for prostate cancer (PC) often experience acute urinary, bowel, sexual, and hormonal toxicities. Timely screening, management, and documentation of these toxicities is an integral part of clinician practice, ensuring patients receive the care they require. Various screening tools, completed by either the patient or the clinician, are available, which allow clinicians to collect and respond to these toxicity outcomes; however there is a paucity of literature regarding the effective use and timing of these tools during RT treatment. This study aims to evaluate the feasibility of conducting comprehensive toxicity screening and symptom management using a toxicity screening tool in one of the busiest RT departments in Canada. Specifically, the use of a toxicity screening tool and its effect on the quality of toxicity documentation, operational impact, and patient reported outcomes (PRO). METHODS: 90 consented patients were allocated to either the structured or non-structured arm. Patients in the structured arm were assessed weekly by radiation therapists for 13 toxicities across four domains (bladder, bowel, hormonal, and sexual), using an in-house developed structured questionnaire, known as the Grid, to complete the National Cancer Institute's Common Toxicity Criteria for Adverse Events v3 (CTCAEv3). Patients in the non-structured arm were assessed and had free text clinical documentation charted according to current department policy. The Expanded Prostate Cancer Index Composite (EPIC), a PRO tool to evaluate patient function and bother after prostate cancer treatment, was completed by all study patients on a weekly basis. Statistical analysis compared documentation completeness, EPIC scores, patient satisfaction, and operational impact between study arms, as well as evaluated optimal timing of toxicity assessments. RESULTS: Assessment of the non-structured arm for completeness revealed an inconsistent and insufficient amount of documentation for the bladder and bowel domains. As for both the sexual and hormonal domains, documentation was largely absent. There was no difference in EPIC scores and patient satisfaction scores between the structured arm and the non-structured arm. Evaluation of the timing of PROs showed significant week to week change for the bladder and bowel toxicities, but not the sexual and hormonal toxicities. Finally, the use of the Grid revealed no significant impact on daily operations, only increasing average treatment times by seven seconds, and did not create any additional workload for the oncologists. CONCLUSIONS: Use of the Grid increased documentation completeness without negatively impacting clinical flow or operations, despite the fact that PROs were not improved. Based on EPIC PRO scores, bladder and bowel toxicities should be evaluated on a weekly basis during RT treatment, while sexual and hormonal toxicities need only be evaluated monthly.

Consistency of Organ Geometries during Prostate Radiotherapy with Two Different Bladder and Bowel Regimens.

BACKGROUND: The majority of Ontario cancer centres incorporate bladder and bowel preparation protocols for the treatment of prostate cancer with radical radiotherapy. Differing methods are used to achieve a full bladder and empty rectum for planning and treatment. We compared the effects of two different bladder and bowel preparation regimens on bladder, rectum, and prostate +/- seminal vesicle geometries through a course of radiotherapy. An optimal preparation would achieve reliable spatial arrangements and a high therapeutic ratio. METHODS: This prospective longitudinal study involved 59 prostate cancer patients treated with radical radiotherapy, of which half followed cohort 1 (laxative cohort) and the other cohort 2 (consistent timing cohort) bladder and bowel preparation regimen. Participants were asked to maintain an empty rectum for both planning and daily treatment appointments in cohort 1 through a fleet enema the morning of the planning appointment, and intake milk of magnesium during daily treatments. No specific bowel preparation was provided to cohort 2 patients. Instead, their appointment times were aligned with their natural bowel habits. This information was collected through a prescreening tool before treatment booking. All cohort 1 and 2 participants were asked to drink 250 mL of water 1 hour before planning and daily treatment appointments. Cohort 2 participants who identified no pre-existing urinary conditions were also asked to drink 2 L of water within 24 hours before the planning session and to continue this during treatment trajectory unless unable to do so because of treatment-induced bladder toxicities later in the treatment. A total of 1,335 structures (bladder, rectum +/- gas, and prostate +/- seminal vesicles) were contoured on the cone beam computerized tomography scans by three radiotherapists. A stringent quality assurance process was performed to assure quality and consistency of contours. Organ volumes were measured and evaluated for consistency over time from planning to completion of radiotherapy. Data analysis included the Fischer exact test and mixed effect modelling for total and subvolumes for bladder, rectum, rectal gas, and prostate +/- seminal vesicles. RESULTS: Baseline total volumes for bladder ranged from 132 mL to 501 mL with means of 325 mL and 315 mL in cohorts 1 and 2, respectively. Bladder volume declined 3.6 mL per fraction and 2.4 mL per fraction in cohorts 1 and 2, respectively. The volume of the bladder structure inside the planning target volume (PTV) on simulation showed no difference by cohort (P = .095) but there was an effect of time (linear P < .0005). Baseline total volumes for rectum ranged from 19.2 mL to 106.3 mL with means of 52.0 mL and 54.7 mL in cohorts 1 and 2, respectively. The volume of the rectum inside the PTV on simulation showed no difference by cohort (P = .12) or time (P = .30) during the treatment course. Volume of gas in the rectum did not vary by cohort (P = .6) or time (P = .08). Baseline total volumes for the clinical prostate +/- seminal vesicles target ranged from 37.1 mL to 167.5 mL with means of 76.2 mL and 66.0 mL in cohorts 1 and 2, respectively. The clinical target decreased by 3% in total volume during the course of radiotherapy in both cohorts, with similar rates of the target falling outside the planned PTV structure. CONCLUSIONS: No significant difference was found between cohorts for rectal volume, gas volume, target coverage, and rectal and bladder volumes in the PTV. Hence, patients should be offered a choice between cohort 1 and 2 bowel preparation regimens to allow for patient preference customization. Cohort 2 bladder preparation regimen was shown to be superior for consistency with slightly larger volume over time.