Canadian Electricity Association

Evidence suggests that the gut microbiome may play a role in multiple sclerosis (MS). However, the majority of the studies have focused on gut bacterial communities; none have examined the fungal microbiota (mycobiota) in persons with pediatric-onset multiple sclerosis (POMS). We examined the gut mycobiota in persons with and without POMS through a cross-sectional examination of the gut mycobiota from 46 participants' stool samples (three groups: 18 POMS, 13 acquired monophasic demyelinating syndromes [monoADS], and 15 unaffected controls). Using metataxonomic sequencing of the fungal internal transcribed spacer region 2, the fungal profiles were compared between participants using visualizations, statistical tests, and predictive analysis. While the mycobiome α- (Shannon and inverse Simpson indices) and β-diversity differed across the three groups [analysis of variance (ANOVA), p < 0.05], further post-hoc analysis of the β-diversity identified a difference between monoADS vs. POMS participants [p = 0.005 (adjusted)]. At the genus level of taxonomy, 7 out of 10 of the majority of abundant genera were similar among all three groups, with Saccharomyces spp. and Candida spp. being in the highest abundance. The Agaricus genus was especially high in POMS participants, dominated primarily due to the species Agaricus bisporus (widely consumed as white button mushrooms). The commonality of high abundance fungi found in our cohort suggests a possible connection to diet. Predictive modeling of differential abundance associated with Candida albicans, Cyberlindera jadinii, and Fusarium poae revealed that these fungi were strongly associated with the POMS participants. Our study provides novel insight into the fungal gut mycobiota in POMS. While findings indicate that the gut mycobiome of participants with POMS may largely comprise fungi considered transient from the diet, the differential predictive analysis suggested rare or under-detected fungal markers being of potential importance, warranting consideration in future mycobiome-MS-related studies.

BackgroundHelicobacter pylori infection is prevalent worldwide and can lead to peptic ulcer disease (PUD) and gastric cancer. Effective diagnosis and treatment of H. pylori infection by gastroenterologists and family physicians is crucial. However, there are differing views on optimal diagnosis and treatment. The objective of this study is to understand the impressions of Canadian physicians regarding H. pylori diagnosis and treatment and whether impressions differ between gastroenterologists and family physicians. A second objective is to understand physician perspectives on rising antibiotic resistance and how that guides empiric management.MethodsA survey facilitated via REDCap was administered to Canadian gastroenterologists and family physicians. A total of 105 participants completed the survey, including 43 gastroenterologists and 62 family physicians. Gastroenterologists were recruited from across the country and family physicians were recruited from Manitoba.ResultsFor diagnosis of H. pylori, 67% of gastroenterologists reported endoscopic biopsies for histology assessment as most common and 73% of family physicians reported serology as their main diagnostic test. While nearly all gastroenterologists believed antibiotic resistance to be a problem, nearly one quarter of family physicians did not believe it was a problem.ConclusionsThere is variability in practices among both gastroenterologists and family physicians regarding diagnosis of H. pylori infection. There was consensus that local antibiotic resistance patterns should guide management. If known, the degree and patterns of antibiotic resistance could bring a more uniform consensus to H. pylori management. Greater education of physicians, especially family physicians regarding management of H pylori is needed.

Knowledge of time to positivity (TTP) for blood cultures is useful to assess timing of discontinuation of empiric antimicrobials for suspected bacteremia with no focus. An audit of positive blood cultures from the Children's Hospital of Eastern Ontario (CHEO) from November 1, 2019, to October 31, 2020, was performed to determine TTP, defined as the start of incubation to a positive signal from automated incubators. Three hundred seventy-six positive blood cultures were identified from 248 patients (average age: 6.27 [SD 6.24] years). Of these, 247 isolates were speciated; 90 (36.4%) were definitive/probable (DP) pathogens (median TTP 12.75 hours) and 157 (63.6%) possible/probable (PP) contaminants (median TTP 24.08 hours). At each time point, the adjusted rate of positive blood culture was significantly higher for DP pathogens compared to PP contaminants (hazard ratio [HR] 1.80 [95% CI 1.37, 2.36]) and for children ≤27 days old compared to the oldest age group (HR 1.94 [95% CI 1.19, 3.17]). By 36 hours, the proportion of positive cultures was significantly higher in the youngest age group (≤27 days) compared with the 3-11 years old age group (91.7% [95% CI 68.6%, 97.8%] versus 58.2% [95% CI 46.91%, 68.06%]). Across all ages, the TTP was significantly shorter for blood cultures with DP pathogens compared to those with PP contaminants (HR 1.80 [95% CI 1.37, 2.36]). In newborns, 90% of blood cultures were positive by 36 hours supporting this re-assessment time for empiric antimicrobials. TTP was longer in children ≥12 months, possibly related to other factors such as blood culture volume.

Monitoring quality indicators (QIs) is an important part of laboratory quality assurance (QA). Here, the Canadian Society of Clinical Chemists (CSCC) Point of Care Testing (POCT) and QI Special Interest Groups describe a process for establishing and monitoring QIs for POCT glucose testing. Key, error prone steps in the POCT glucose testing process were collaboratively mapped out, followed by risk assessment for each step. Steps with the highest risk and ability to detect a non-conformance were chosen for follow-up. These were positive patient identification (PPID) and repeat of critically high glucose measurements. Participating sites were asked to submit aggregate data for these indicators from their site(s) for a one-month period. The PPID QI was also included as part of a national QI monitoring program for which fifty-seven sites submitted data. The percentage of POCT glucose tests performed without valid PPID ranged from 0-87%. Sites without Admission-Discharge-Transfer (ADT) connectivity to POCT meters were among those with the highest percentage of POCT glucose tests performed without valid PPID. The percentage repeated critically high glucose measurements ranged from 0-50%, indicating low compliance with this recommendation. A high rate of discordance was also noted when critically high POCT glucose measurements were repeated, demonstrating the importance of repeat testing prior to insulin administration. Here, a process for establishing these QIs is described, with preliminary data for two QIs chosen from this process. The findings demonstrate the importance of QIs for identification and comparative performance monitoring of non-conformances to improve POCT quality.

Patient zinc stores are quantified with plasma or red blood cell (RBC) measures. The relationship between these 2 measures of zinc status has not been determined in a broad population of hospitalized patients. Both plasma zinc and RBC zinc were prospectively collected and measured in 252 consenting patients admitted urgently to hospital. Plasma and RBC zinc levels were measured within 48 h of admission. We collected demographic, vitals, and laboratory data for use in multivariate regression models that included markers of acute disease severity and systemic inflammation. Plasma zinc and RBC zinc levels were low in 63% and 10% of hospitalized patients, respectively. Categorized zinc levels based on normal intervals for plasma and RBC zinc values were not related (χ2 0.47 [2 df] P = 0.79). The Pearson correlation coefficient between plasma zinc and RBC zinc was -0.09 (P = 0.15). After adjustments for multiple clinical covariates, the correlation coefficient remained insignificant (r = -0.11, P = 0.08). Plasma zinc was inversely associated with markers of inflammation including the neutrophil-to-lymphocyte ratio and temperature. Patient-specific plasma and RBC zinc are unrelated in hospitalized patients, possibly due to decreased values with acute illness seen in the former but not the latter. Future studies are required to determine which of these measures best predicts outcomes in hospitalized patients.

605 Background: The INVINCIBLE study is a randomized, Phase 2 presurgical Window-Of-Opportunity trial for IT INT230-6 (comprising VINblastine (VIN) Cisplatin (VIN)) evaluating clinical and BioLogical Effects in patients with early-stage operable Breast Cancer. INT230-6 also contains a dispersion enhancer molecule designed to facilitate diffusion of the cytotoxic agents into cancer cells and cause tumor necrosis. We have previously demonstrated that INT230-6 halts cancer cell replication and induces apoptosis while maturing dendritic cells and recruiting T-cells to the tumor microenvironment. In this trial, IT injections of INT230-6 are conducted to 1) exploit the potential of regional cytotoxic chemotherapy on breast cancer in vivo and 2) assess the potential for an immune response in the tumor microenvironment and host prior to surgical resection. Methods: Up to 90 women with newly diagnosed operable early-stage intermediate or high-grade T1-T2 invasive breast cancers are randomly allocated (2:1) prior to resection to IT injections of INT230-6, no treatment or saline sham. This study has two parts. Part I (N=29) was a randomized trial comparing 1-3 doses of INT230-6 injected weekly vs no treatment prior to surgery to evaluate safety, feasibility, and optimal drug dosing. Part II is a double-blinded randomized trial of up to 60 patients where patients will receive one IT dose of INT230-6 vs saline injection (2:1). The primary endpoint is to estimate the proportion of patients who achieve a complete cell cycle arrest post-surgery compared to the diagnosis biopsy. Secondary endpoints include an evaluation of the rate of pathological complete response, the percent of residual cancer, and safety. The study will also profile changes in CD4/CD8 and the T-cell repertoire. Results: Part I demonstrated feasibility, safety and tolerability of presurgical IT injections in breast cancer patients. Twenty patients with tumors ranging from 1-4.4cm were injected with at least one dose up to 48 hours prior to surgery. No surgeries were delayed or altered and the most common (&gt;10%) AEs were injection site pain (100%), infusion site extravasation, injection site reaction and vomiting (10% each). Preliminary data show histologic evidence of up to 95% tumor necrosis in varying biologic subtypes and an increase in intratumoral TILs in injected tumors compared to controls. Part II is ongoing. Conclusions: Preliminary evidence shows that a single dose of INT230-6 can cause intratumoral necrosis and stimulate an immune response in breast cancers prior to surgery with minimal adverse effects and good tolerability. The results of Part II of the study will further evaluate the potential cytotoxic, immunomodulatory and other biologic effects of INT230-6 and its role as a potential cancer therapy in breast cancer patients awaiting surgery. Clinical trial information: NCT04781725.