McGill University Health Centre Research Articles

Integration of Radiomic and Multi-omic Analyses Predicts Survival of Newly Diagnosed IDH1 Wild-Type Glioblastoma.

Predictors of patient outcome derived from gene methylation, mutation, or expression are severely limited in IDH1 wild-type glioblastoma (GBM). Radiomics offers an alternative insight into tumor characteristics which can provide complementary information for predictive models. The study aimed to evaluate whether predictive models which integrate radiomic, gene, and clinical (multi-omic) features together offer an increased capacity to predict patient outcome. A dataset comprising 200 IDH1 wild-type GBM patients, derived from The Cancer Imaging Archive (TCIA) (n = 71) and the McGill University Health Centre (n = 129), was used in this study. Radiomic features (n = 45) were extracted from tumor volumes then correlated to biological variables and clinical outcomes. By performing 10-fold cross-validation (n = 200) and utilizing independent training/testing datasets (n = 100/100), an integrative model was derived from multi-omic features and evaluated for predictive strength. Integrative models using a limited panel of radiomic (sum of squares variance, large zone/low gray emphasis, autocorrelation), clinical (therapy type, age), genetic (CIC, PIK3R1, FUBP1) and protein expression (p53, vimentin) yielded a maximal AUC of 78.24% (p = 2.9 × 10−5). We posit that multi-omic models using the limited set of ‘omic’ features outlined above can improve capacity to predict the outcome for IDH1 wild-type GBM patients.

A new era in research on the epididymis

After meetings in Hong Kong, Robertson (Australia), Charlottesville (Virginia), Chatel-Guyon (France), Sao Palo (Brazil), and Shanghai (China), the 7th International Conference on the Epididymis was held in Montreal (Canada) from September 20 to 23, 2018. One hundred scientists from 11 countries gathered to present their most recent findings on this critically important tissue in male reproduction, one that has received far less attention than it deserves. Special presentations were made to honor two of the founding ‘parents’ of our modern understanding of the epididymis (Fig. 1). The Plenary lecture, named after Dr. Marie-Claire Orgebin-Crist, was delivered by Dr. Louis Hermo. Dr. Patricia Cuasnicu presented the remarkable achievements of Dr. Michael Bedford, who passed away earlier in 2018. We are fortunate to have a picture of these two pioneers that was taken at the previous Conference on the Epididymis. The outstanding suggestions from members of the Program Committee (Avellar MC—Brazil, Breton S—USA, Cornwall G—USA, Cuasnicu P—Argentina, Drevet J—France, Hinton BT—USA, Robaire B—Canada, and Zhang Y—China) allowed us to bring together leaders researching every facet of ‘the tissue’. The main themes of the meeting were as follows: development of the Wolffian duct and the epididymis; physiology of the epididymis; epididymal sperm maturation and contraception; non-coding RNAs in the epididymis; infections of and defense by the epididymis; immune system and the epididymis; toxicants and epididymal function; the human epididymis; and clinical aspects of epididymal dysfunction. Excellent presentations were provided by 22 invited speakers and in 51 posters, covering a remarkably rich variety of novel and exciting developments regarding our understanding of how this tissue functions and is regulated. A PDF of the program and of abstracts may be found at: http://www.medicine.mcgill.ca/pharma/robairelab/Documents/Epididymis7_FinalProgram.pdf This issue of Andrology contains 19 articles, representing nearly 90% of the presentations delivered by invited speakers. Each of these peer-reviewed articles contributes new dimensions to our understanding of the complexity of this remarkably long tube that creates and provides continuously changing environments for spermatozoa as they mature and are then stored. The dynamic interactions with the immune system, the interface between the epithelial cells and spermatozoa via epididymosomes, our evolving understanding of the roles of non-coding RNAs and other small molecules, are all opening new avenues that are likely to provide new opportunities for the development of male contraceptives and the treatment of male infertility. The success of this meeting would not have been possible without the untiring efforts of Ms. Elise Boivin-Ford and Dr. Anais Noblanc and the financial contributions from the Male Contraceptive Initiative, Canadian Institutes for Health Research, Society for the Study of Reproduction, American Society of Andrology, International Society of Andrology, Reseau Quebecois en Reproduction, McGill University, McGill University Health Centre, Centre for Research in Reproduction and Development, Université de Montréal, Université Laval, Institut National de Recherche en Santé, and Fluxion.

Assessing the Content Validity of a New Patient-Reported Measure of Barriers to Antiretroviral Therapy Adherence for Electronic Administration in Routine HIV Care: Proposal for a Web-Based Delphi Study.

BackgroundAdherence to lifesaving antiretroviral therapy (ART) for HIV infection remains a challenge for many patients. Routine screening for barriers to ART adherence could help make HIV care more patient-centered and prevent virologic rebound or failure. Our team is currently developing a new HIV-specific patient-reported outcome measure (PROM) of these barriers for use in Canada and France along with a digital app for its electronic administration. In our previous work, we developed the PROM’s multidimensional conceptual framework and generated 100 English items, which have been translated to French.ObjectiveThis study aims to use a Web-based Delphi to help validate and select the content of this new HIV-specific PROM, based on the perspective of anglophone and francophone patients and providers in Canada and France. Here, we present the proposal for this Delphi.MethodsThis modified Delphi will involve a diverse panel of patients (n=32) and providers (n=52) recruited especially from the 9 sites of the PROM development study (site locations in Canada: Montreal, Toronto, Vancouver; in France: Paris, Nantes, Clermont-Ferrand, Saint-Martin, Cayenne). Overall, 2 rounds of Web-based questionnaires will be conducted. The threshold for consensus is set at 60% and will determine which items are carried forward to the second round. Per item, 3 aspects will be rated: importance as a barrier to ART adherence, relevance for HIV care, and clarity. In both rounds, space will be available for free text comments. Overall comprehensiveness will be assessed in the second round.ResultsThis study has undergone a methodological review by experts in patient-oriented research. It has received approval from a research ethics board of the McGill University Health Centre. It is financially supported, in part, by the Canadian Institutes of Health Research’s Strategy for Patient-Oriented Research-Quebec Support Unit (M006). As of May 21, 2019, 15 people living with HIV and 25 providers completed the first round of the Delphi (24 from Canada and 16 from France).ConclusionsTo our knowledge, this is the first Delphi to seek consensus on the most relevant and clinically actionable barriers to ART adherence, collecting opinions on an extensive list of barriers. Drawing on a relatively large and diverse panel of HIV patients and providers, it essentially engages key stakeholders in decision making about the PROM’s final content, helping to ensure its utility and adoption.International Registered Report Identifier (IRRID)PRR1-10.2196/12836

A survey of health care professionals and oncology patients at the McGill University Health Centre reveals enthusiasm for establishing a postmortem rapid tissue donation program.

In the early developmental phase of a postmortem rapid tissue donation (rtd) program for patients with metastatic cancer, we surveyed health care professionals (hcps) and oncology patients at the McGill University Health Centre (muhc) to assess their knowledge and attitudes pertaining to rtd from metastatic cancer patients for research purposes. A 23-item survey was developed and distributed to hcps at tumour board meetings, and a related 26-item survey was developed and distributed to oncology patients at the muhc Cedars Cancer Centre. The survey attracted participation from 73 hcps, including 37 attending physicians, and 102 oncology patients. Despite the fact that 88% of hcps rated their knowledge of rtd as none or limited, 42% indicated that they would feel comfortable discussing rtd with their cancer patients. Of the responding hcps, 67% indicated that their current knowledge of rtd would affect their decision to discuss such a program with patients, which implies the importance of education for hcps to facilitate enrolment of patients into a rtd program. Of responding patients, 78% indicated that they would not be uncomfortable if their doctor discussed rtd with them, and 61% indicated that they would like it if their doctor were to discuss rtd with them. The hcps and patients felt that the best time for patients to be approached about consenting to a rtd program would be at the transition to palliative care when no treatment options remain. At the muhc, hcps and patients are generally enthusiastic about adopting a rtd program for patients with metastatic cancer. Education of hcps and patients will be an important determinant of the program's success.

Echocardiographic Characteristics of Heart Failure Patients with Severe Tricuspid Regurgitation

Introduction The proportion of patients with heart failure (HF) and severe tricuspid regurgitation (TR) that are potential candidates for a percutaneous tricuspid valve intervention is unknown. The aim of this study was to evaluate in a real-world setting the echocardiographic characteristics of Heart Failure HF patients with severe TR. Methods This was a retrospective cohort study of 2133adult patients enrolled in the HF clinic at the McGill University Health Center from 2007 to 2017, totaling 10 300 echocardiograms. Included in our study were patientswith a clinical diagnosis of HF and available echocardiographic follow up. All data after heart transplant or ventricular assist device was excluded. The severity of TR was classified according to the American Society of Echocardiography guidelines. All patients who never had severe TR during their follow-up were included in the control group. Results There were 321 patients with severe TR at any time during the follow-up period (mean age 66±16 years; 61% male), whereas 1812 patients did not have severe TR (mean age 60±15 years; 60% male). Among patients with severe TR, left ventricular ejection fraction (LVEF) was low (≤50%) in 76%, compared to the control group in which LVEF was low in 71% (p=0.07). Severe mitral regurgitation (MR) was present in 26% of the severe TR group compared to 5% in the control group (p 50mmHg) was present in 53% of the severe TR group, compared to 20% in control group (p Conclusions In patients with HF, severe TR is associated with worse echocardiographic parameters including severe MR, pulmonary hypertension, RV dilatation and RV systolic dysfunction. Half of patients with severe TR could be eligible for tricuspid valve intervention.

Suboptimal Immunization Coverage among Canadian Rheumatology Patients in Routine Clinical Care.

To assess vaccination coverage and predictors of vaccination among a Canadian population of rheumatology patients in routine clinical care. In this cross-sectional study, consecutive adult patients presenting to a tertiary rheumatology clinic at the McGill University Health Center between May and September 2015 were asked to fill a survey on vaccination. Patients self-identified as having rheumatoid arthritis (RA), systemic autoimmune rheumatic diseases (SARD), spondyloarthropathies (SpA), or other diseases (OD). Multivariate logistical regression analyses were performed to evaluate patient and physician factors associated with various vaccinations [for influenza, pneumococcus, and hepatitis B virus (HBV)]. Published Quebec general population influenza and pneumococcal vaccination rates in those aged ≥ 65 years were used as comparative baseline rates. Three hundred fifty-two patients were included in the analysis (RA: 136, SARD: 113, SpA: 47, OD: 56). Vaccination rates were reported as follows: (1) influenza: RA 48.5%, SARD 42.0%, SpA 31.9%, OD 88.9%, Quebec general population 58.5%; (2) pneumococcal: RA 42.0%, SARD 37.8%, SpA 29.7%, OD 33.3%, Quebec general population 53.2%; (3) HBV: RA 33.6%, SARD 55.6%, SpA 73.5%, OD 36.8%; and (4) herpes zoster: RA 5.6%, SARD 28.6%, SpA 25.0%, OD 16.7%. Physician recommendation was the strongest independent predictor of vaccination across all vaccine types (influenza: OR 8.56, 95% CI 2.80-26.2, p < 0.001; pneumococcal: OR 314, 95% CI 73.0-1353, p < 0.001; HBV: OR 12.8, 95% CI 5.27-31.1, p < 0.001). Disease group, disease duration, comorbidities, treatment type, and being followed by a primary care physician were not significantly associated with vaccination. There is suboptimal immunization coverage among ambulatory rheumatology patients. An important role for patient and physician education is highlighted in our study, especially because physician recommendation of vaccination was strongly predictive of vaccine uptake.

Incidence and Predictors of Intracardiac Thrombus on Pre-electrophysiological Procedure Transesophageal Echocardiography

BackgroundCerebral thromboembolism is a potentially devastating complication of atrial fibrillation (AF) and atrial flutter (AFl). The use of transesophageal echocardiogram (TEE) before electrophysiological procedures in anticoagulated patients is variable. Our objective was to determine the incidence and identify predictors of intracardiac left atrial appendage (LAA) thrombus on TEE in patients with AF/AFl before electrical cardioversion or ablation. MethodsWe reviewed TEEs of 401 patients undergoing an electrical cardioversion, AF, or AFl ablation from April 2013 to September 2015 at the McGill University Health Center. Clinical and echocardiographic variables were collected at the time of the TEE and follow-up visits. Multivariate logistic regression was used to determine predictors of LAA thrombus. ResultsOf 401 patients, 11.2% had LAA thrombus on TEE. The majority (87%) of patients were anticoagulated for at least 3 weeks before the TEE. The incidence of LAA thrombus was 21% (23/110) in patients taking warfarin vs 6.4% (15/236) in patients taking direct oral anticoagulants. Multivariate analysis identified prior stroke (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.1-6.9) and heart failure (OR, 2.2; 95% CI, 1.0-4.7) as predictors of thrombus, whereas direct oral anticoagulant use (OR, 0.4; 95% CI, 0.2-0.8) was associated with reduced odds of thrombus. ConclusionsLAA thrombus was identified in a significant proportion of patients undergoing TEE before cardioversion or ablation of AF/AFl despite preprocedural anticoagulation. Patients at increased risk of LAA thrombus (heart failure and prior stroke) may benefit from TEE before cardioversion, AF, or AFl ablation.

What Patients Want in a Smartphone App That Supports Colonoscopy Preparation: Qualitative Study to Inform a User-Centered Smartphone App.

BackgroundThe preparation for colonoscopy is elaborate and complex. In the context of colorectal cancer screening, up to 11% of patients do not keep their colonoscopy appointments and up to 33% of those attending their appointments have inadequately cleansed bowels that can delay cancer diagnosis and treatment. A smartphone app may be an acceptable and wide-reaching tool to improve patient adherence to colonoscopy.ObjectiveThe aim of this qualitative study was to employ a user-centered approach to design the content and features of a smartphone app called colonAPPscopy to support individuals preparing for their colonoscopy appointments.MethodsWe conducted 2 focus group discussions (FGDs) with gastroenterology patients treated at the McGill University Health Centre in Montreal, Canada. Patients were aged 50 to 75 years, were English- or French-speaking, and had undergone outpatient colonoscopy in the previous 3 months; they did not have inflammatory bowel disease or colorectal cancer. FGDs were 75 to 90 min, conducted by a trained facilitator, and audiotaped. Participants discussed the electronic health support tools they might use to help them prepare for the colonoscopy, the content needed for colonoscopy preparation, and the features that would make the smartphone app useful. Recordings of FGDs were transcribed and analyzed using thematic analysis to identify key user-defined content and features to inform the design of colonAPPscopy.ResultsA total of 9 patients (7 male and 2 female) participated in one of 2 FGDs. Main content areas focused on bowel preparation instructions, medication restrictions, appointment logistics, communication, and postcolonoscopy expectations. Design features to make the app useful and engaging included minimization of data input, reminders and alerts for up to 7 days precolonoscopy, and visual aids. Participants wanted a smartphone app that comes from a trusted source, sends timely and tailored messages, provides reassurance, provides clear instructions, and is simple to use.ConclusionsParticipants identified the need for postcolonoscopy information as well as reminders and alerts in the week before colonoscopy, novel content, and features that had not been included in previous smartphone-based strategies for colonoscopy preparation. The ability to tailor instructions made the smartphone app preferable to other modes of delivery. Study findings recognize the importance of including potential users in the development phase of building a smartphone app.

A survey of healthcare professionals and oncology patients at the McGill University Health Centre reveals enthusiasm towards establishing a post-mortem rapid tissue donation program.

e23005 Background: In the early developmental phase of a post-mortem Rapid Tissue Donation (RTD) program for metastatic cancer patients, we surveyed health care professionals (HCPs) and oncology patients at the McGill University Health Centre (MUHC) to assess their knowledge and attitudes pertaining to RTD from metastatic cancer patients for research purposes. Methods: A 23-item survey was developed and distributed to HCPs at tumour board meetings, and a related 26-item survey was developed and distributed to oncology patients at the MUHC Cedars Cancer Centre. Results: 73 HCPs, including 37 attending physicians, and 102 oncology patients participated in the study. Despite the fact that 88% of HCPs rated their knowledge of RTD as none or limited, 42% indicated that they would feel comfortable discussing RTD with their cancer patients. 67% of HCPs indicated that their current knowledge of RTD would impact their decision to discuss such a program with patients, implying the importance of educating HCPs to facilitate enrolment of patients into an RTD program. 78% of patients indicated that they would not be uncomfortable if their doctor discussed RTD with them, and 61% indicated that they would like for their doctor to discuss RTD with them. HCPs and patients felt that the best time for patients to be approached about consenting to an RTD program is in the transition to palliative care when there are no treatment options remaining. Conclusions: HCPs and patients at the MUHC are generally enthusiastic about adopting an RTD program for metastatic cancer patients. Education of HCPs and patients will be an important determinant of the program’s success.

Implementation of an On-line Incident Learning System in a Radiation Medicine Program

Incident learning is an important aspect of quality improvement in health care. This work describes the implementation and customization of the on-line Safety Incident Learning System (SaILS) at our centre. SaILS was developed at the Ottawa Hospital and further refined at the McGill University Health Centre. Prior to implementation of SaILS at our centre, incidents were reported using a soft copy form that was circulated via email to the incident investigation team. Investigation findings were entered into the same soft copy form and summaries transcribed manually to a spreadsheet for further analysis. Objectives of this work were to streamline incident reporting and investigation and to align the language with which incidents are described with the National System for Incident Reporting – Radiation Therapy (NSIR-RT) taxonomy. A process map was developed to illustrate the many steps and handoffs of the existing incident learning process. The McGill University SaILS user-code was installed locally and a new work-flow was developed using various SaILS functions. The program was customized to ensure that all necessary steps and handoffs were handled appropriately and supplementary applications, such as the user dashboard and task assignment, were added. Tutorials were provided to radiation medicine program team members to examine the new process map and provide an overview of SaILS functionality. Implementation of SaILS is anticipated to improve the efficiency of incident reporting and learning. Incident investigation team members will be able to view the progress of incident investigations within the SaILS environment and the time required to track the incident investigation progress will be reduced. It will no longer be required to transcribe an incident summary to a spreadsheet as SaILS is enabled to perform the required analytics. File management needs are also reduced as there is a single incident record in SaILS rather than multiple soft copies circulated via email for each incident. The transition to this new system will be challenging to staff as the process and the language used to describe incidents have changed. Implementation of an on-line incident learning system using the NSIR-RT taxonomy will streamline incident reporting and investigation. Future work will include automated submission of the reports to the NSIR-RT database as required by Cancer Care Ontario.

P064: A randomized trial comparing telephone tree, text messaging, and instant messaging app for emergency department staff recall for disaster response

Introduction: A crucial component of a hospital's disaster plan is an efficient staff recall communication method. Many hospitals use a “calling tree” protocol to contact staff members and recall them to work. Alternative staff recall methods have been proposed and explored. Methods: An unannounced, multidisciplinary, randomized emergency department (ED) staff recall drill was conducted at night - when there is the greatest need for back-up personnel and staff is most difficult to reach. The drill was performed on December 14, 2017 at 4:00AM and involved ED staff members from three hospitals which are all part of the McGill University Health Centre (MUHC; Montreal, Quebec, Canada). Three tools were compared: manual phone tree, instant messaging application (IMA), and custom-made hospital Short Message Service (SMS) system. The key outcome measures were proportion of responses at 45 minutes and median response time. Results: One-hundred thirty-two participants were recruited. There were 44 participants in each group after randomization. In the manual phone tree group, 18 (41%) responded within 45 minutes. In the IMA group, 11 participants (25%) responded in the first 45 minutes. In the SMS group, seven participants responded in the first 45 minutes (16%). Manual phone tree was significantly better than SMS with an effect size of 25% (95% confidence interval for effect: 4.6% to 45.0%; P = .018). Conversely, there was no significant difference between manual phone tree and IMA with an effect size of 16% (95% confidence interval for effect: -5.7% to 38.0%; P = .17) There was a statistically significant difference in the median response time between the three groups with the phone tree group presenting the lowest median response time (8.5 minutes; range: 2.0 to 8.5 minutes; P = .000006). Conclusion: Both the phone tree and IMA groups had a significantly higher response rate than the SMS group. There was no significant difference between the proportion of responses at 45 minutes in the phone tree and the IMA arms. This study suggests that an IMA may be a viable alternative to the traditional phone tree method. Limitations of the study include volunteer bias and the fact that there was only one communication drill, which did not allow staff members randomized to the IMA and SMS groups to fully get familiar with the new staff recall methods.

Quantifying Population-Level Sexual Mixing by HIV Status and Pre-Exposure Prophylaxis Use Among Men Who Have Sex with Men: Implications for Combination HIV Prevention

Background: Sexual mixing patterns influence HIV transmission dynamics. We quantified the population-level sexual mixing by two attributes (HIV status and pre-exposure prophylaxis (PrEP) use). Methods: We used data from Engage-Montreal (2017-2018), a cross-sectional survey of men who have sex with men (MSM) ≥16 year-old recruited using respondent-driven sampling. MSM with ≥1 anal/oral sex partners in the past 6 months (P6M) reported their own and partners' HIV status and PrEP use. Within P6M-partnerships across all MSM, we compared observed seroconcordance to what would have been expected by chance under proportionate mixing-if zero individual serosort. Within recent partnerships where both individuals were HIV-negative, we compared observed concordance in PrEP use at last sex to that expected by chance. We used chi-squared tests for comparisons, and calculated the excess fraction of concordance beyond chance. Findings: Of the 11,883 P6M-partnerships by 1137 respondents, 56.3% comprised partners' of known-status. Compared with by chance and among partners of known-status, HIV-positive respondents (n=207) had a higher proportion of HIV-positive partners (66.4% vs. 23.9%; p<0.001); both HIV-negative (n=831) and respondents of unknown-status (n=99) had higher proportions of HIV-negative partners (87.9%, and 92.7%, respectively, vs. 76.1%; p<0.001). HIV-negative respondents on PrEP had a higher proportion of HIV-positive partners than those not on PrEP (17.1% vs. 9.3%; p<0.001). They also had a higher proportion of partners on PrEP among their HIV-negative partners compared with by chance (50.6% vs. 28.5%; p<0.001). Excess fractions of seroconcordance beyond chance were 64.0%, 8.9%, and 10.7% for HIV-positive, HIV-negative on PrEP, and HIV-negative not on PrEP MSM, respectively. The excess fraction of concordance in PrEP use beyond chance was 43.7%. Interpretation: The high degree of population-level serosorting and PrEP matching, and the influence of PrEP on sexual mixing patterns should be considered in the implementation of PrEP within the context of combination HIV prevention. Funding: Canadian Institutes of Health Research [TE2-138299, CTN-300, FN-13455]; Canadian Foundation for AIDS Research [Engage]; Canadian Blood Services [MSM2017LPOD]; Ontario HIV Treatment Network [1051]; Ryerson University; and Public Health Agency of Canada [4500370314]. Declaration of Interest: No conflict of interest to declare. Ethical Approval: The following institutional ethics review boards approved the study: Ryerson University, St. Michael’s Hospital, University of Toronto, University of Windsor, University of British Columbia, University of Victoria, the Simon Fraser University, and the Research Institute of the McGill University Health Centre.

Psychiatric Neurosurgery: A Survey on the Perceptions of Psychiatrists and Residents.

To evaluate the attitudes and perceptions of psychiatrists and psychiatry residents regarding neurosurgical procedures for treating psychiatric disorders and to identify potential barriers to patient referral. A survey consisting of 25 questions was created using SurveyMonkey and was distributed to psychiatrists and psychiatry residents in Quebec. The study was approved by the McGill University Health Center's Research Ethics Board. Descriptive statistics and Friedman's test were performed using SPSS software. A total of 99 participants, including 64 residents and 35 psychiatrists, completed more than 75% of the survey and were included in data analysis. Overall, participants were significantly (p &lt; 0.0005) more comfortable in referring patients suffering from treatment-resistant obsessive-compulsive disorder than from treatment-resistant major depressive disorder and preferred to refer patients for deep brain stimulation (DBS) rather than for anterior cingulotomy/capsulotomy (AC). Only 11.43% of psychiatrists had ever referred a patient for AC or DBS, and 34.69% of respondents felt that these procedures were dangerous. Lack of knowledge (82.83%) was viewed as the principal limiting factor, and 57.58% of respondents identified ≥6 different barriers to patient referral. The majority of participants (69.39%) were interested in improving their knowledge on psychiatric neurosurgery, and 82.65% felt that this subject should be included in the psychiatry residency curriculum. Overall, participants acknowledged having many limitations to referring patients for neurosurgical interventions. While informative conferences discussing neuromodulation/neuroablation could easily address many barriers, further studies are required to assess how these could change attitudes and patterns of referral.

Effect of metformin on the size of the HIV reservoir in non-diabetic ART-treated individuals: single-arm non-randomised Lilac pilot study protocol

IntroductionPeople living with HIV (PLWH) on antiretroviral therapy (ART) do not progress to AIDS. However, they still suffer from an increased risk of inflammation-associated complications. HIV persists in long-lived CD4+...

High Adherence to Surveillance Guidelines in Inflammatory Bowel Disease Patients Results in Low Colorectal Cancer and Dysplasia Rates, While Rates of Dysplasia are Low Before the Suggested Onset of Surveillance.

Patients with Crohn's disease [CD] and ulcerative colitis [UC] are at increased risk for colorectal dysplasia [CRD] and colorectal cancer [CRC]. Adherence to CRC surveillance guidelines is reportedly low internationally. To evaluate surveillance practices at the tertiary IBD Center of the McGill University Health Center [MUHC] and to determine CRD/CRC incidence. A representative inflammatory bowel disease cohort with at least 8 years of disease duration [or with primary sclerosing cholangitis] who visited the MUHC between July 1 and December 31, 2016 were included. Adherence to surveillance guidelines was compared to modified 2010 British Society of Gastroenterology guidelines. Incidence rates of CRC, high-grade dysplasia [HGD], low-grade dysplasia [LGD] and colorectal adenomas [CRA] were calculated based on pathology. In total, 1356 CD and UC patients (disease duration: 12 [interquartile range: 6-22) and 10 [interquartile range: 5-19] years) were identified. The surveillance cohort consisted of 680 patients [296 UC and 384 CD]. Adherence to surveillance guidelines was 76/82% in UC/colonic CD. An adequate number of biopsies were taken in 54/54% of UC/colonic CD patients. The incidence of CRC/HGD in UC and CD with colonic involvement was 19.5/58.5 and 25.1/37.6 per 100,000 patient-years, respectively. The incidence of dysplasia before 8 years of disease duration was low in both UC/CD [19.5 and 12.5/100,000 patient-years] with no CRC detected. The CRA rate was 30/38% in UC/colonic CD. High adherence to surveillance guidelines and low CRC and dysplasia, but not CRA rates were found, suggesting that adhering to updated, stratified, surveillance recommendations may result in low advanced neoplasia rates. The incidence of dysplasia before the start of surveillance was low.

The effect of the American Joint Committee on Cancer eighth edition on breast cancer staging and prognostication

IntroductionBreast cancer staging has been developed to quantify prognosis and guide treatment. The American Joint Committee on Cancer eighth edition manual (AJCC8) departed from traditional anatomic staging by incorporating biological factors such as grade, hormone and HER2 receptor status into a novel prognostic staging model. The aim of this study was to externally validate AJCC8 prognostic staging. MethodsThis retrospective cohort investigated patients diagnosed between 2010 and 2013 at the McGill University Health Center. Patients were classified using both anatomic and prognostic staging systems according AJCC8. Overall survival analysis using a multivariate Cox-proportional hazard model was performed and model accuracy was evaluated using the Harrell concordance index (C-index) and Akaike Information Criterion (AIC). ResultsThe cohort included 1703 women. Anatomic and prognostic stage assignments displayed discrepancies for 46.2% of patients, where 38.8% were downstaged and 7.5% were upstaged with prognostic staging. Patients with anatomic stages IB, IIA, IIB, IIIA and IIIC had high rates of downstaging (64.6–96.5%), as opposed to anatomic stages IA and IIIB where 93.1% and 75.0% of patients stage remained unchanged, respectively. The prognostic stage displayed increased prognostic accuracy with respect to overall survival, where the C-index was significantly higher compared to anatomic staging (0.810 vs 0.799, p < 0.05). In addition, prognostic staging displayed an improved model fit with a lower AIC (983.9) compared to anatomic staging (995.2). ConclusionPrognostic and anatomic staging differ in their classification of patients, where prognostic staging displays improved accuracy, supporting its use in informing patient prognosis and guiding treatment decisions.

Perceived Quality of Care is Associated with Disease Activity, Quality of Life, Work Productivity, and Gender, but not Disease Phenotype: A Prospective Study in a High-volume IBD Centre.

Measuring quality of care [QoC] in inflammatory bowel diseases [IBD] has become increasingly important, yet complex assessment of QoC from the patients' perspective is rare. We evaluated perceived QoC using the Quality of Care Through the Patient's Eyes-IBD [QUOTE-IBD] questionnaire, and investigated associations between QoC, disease phenotype, work productivity, and health-related quality of life [HRQoL] in a high-volume IBD centre. Consecutive patients attending McGill University Health Centre [MUHC]-IBD Centre completed the QUOTE-IBD, Short Inflammatory Bowel Disease Questionnaire [SIBDQ], IBD-Control, and Work Productivity and Activity Impairment [WPAI] questionnaires. The QUOTE-IBD comprises 23 questions, each rated by a quality impact [QI] score. QI scores were calculated for the evaluation of IBD specialists, general practitioners [GPs], and hospital care. In all, 525 patients completed the questionnaire. Total QI scores for IBD specialists, GPs, and hospital care were 8.57, 8.70, and 8.33, respectively. The lowest QI scores were related to 'accessibility' for both IBD specialists and GPs. Female gender, current disease activity, poor HRQoL [SIBDQ score ≤50], and poor disease control [IBD-Control score <13] were associated with lower mean QI scores [p <0.001 for all]. Disease phenotype was not associated with QI scores in either Crohn's disease [CD] or ulcerative colitis [UC] [p = 0.69, p = 0.791, respectively]. An inverse correlation was found between total QI scores and work productivity loss [IBD specialist: p <0.001; GP: p = 0.004]. Overall patient satisfaction with QoC was good; however, improving patient accessibility to care is warranted. Disease phenotype was not associated with patient satisfaction, whereas female gender, current disease activity, HRQoL, and work productivity loss were associated with patients' quality assessment, underlining that perceived QoC could be partly subjective regarding disease control and quality of life.

Low endoscopy bleeding risk in patients with congenital bleeding disorders.

Haemophilia A and haemophilia B, von Willebrand disease (VWD), factor VII deficiency and factor XI deficiency are congenital bleeding disorders predisposing to bleeding during invasive procedures. The ageing population of people with congenital bleeding disorders will likely increasingly require gastrointestinal endoscopy. The bleeding risk postgastrointestinal endoscopy and optimal prophylactic treatment regimens are not well described. We performed a retrospective chart review at the McGill University Health Centre. Adult patients with haemophilia A or B, VWD, FVII deficiency and FXI deficiency who underwent gastrointestinal endoscopic procedures were included. Bleeding prophylaxis included combinations of plasma-derived factor (VWD) or recombinant factor (haemophilia A and haemophilia B), desmopressin and/or tranexamic acid. Our primary outcome was the 72-hour postendoscopy bleeding rate. One hundred and four endoscopies were performed in 48 patients. Haemophilia A (45.3% of endoscopies) was the most common bleeding disorder, followed by VWD (38.5%), FXI deficiency (8.7%), haemophilia B (4.8%) and FVII deficiency (2.9%). All patients were reviewed by the Haemophilia Treatment Center with peri-procedure treatment protocols put in place as required. The overall 72-hour bleeding rate was 0.96%, confidence interval (CI) 95% (0.17%-5.25%). The colonoscopic postpolypectomy bleeding rate was 1/21 (4.8%, CI 95% (0.9%-22.7%)) in comparison with the general population rate of 0.3%-10% for high-risk endoscopy (including colonoscopic polypectomy). To the best of our knowledge, this is the largest study describing patients with inherited bleeding disorders undergoing gastrointestinal endoscopy. The bleeding risk is not significantly higher to the general population when haemostatically managed by a team experienced in bleeding disorders.

Endoscopic Submucosal Dissection for Esophageal Adenocarcinoma: A North American Perspective

BackgroundData are limited regarding the application of endoscopic submucosal dissection (ESD) in Western countries or for esophageal adenocarcinoma in any part of the world. We sought to review our experience employing ESD in patients with early esophageal cancer at a high volume North American esophageal cancer treatment center. MethodsA prospectively maintained database of all patients with esophageal cancer treated at the McGill University Health Center was used to identify ESDs performed for adenocarcinoma between 2012 and 2016. Patient demographics, pre-resection tumor characteristics, endoscopic resection technical variables, pathologic results, and short- and long-term outcomes were recorded. ResultsOf 650 patients in the database, 26 underwent 27 procedures. The majority (67%) had pre-treatment EUS. There were no post-ESD bleeding events requiring re-intervention. Perforation occurred in 2/27 (7%), one of which required operative repair. Complete RO resection was achieved in 18/27(67%). Salvage laparoscopic esophagectomy was performed in six patients. At a median follow-up of 18.5 (7–35) months, cancer recurrence occurred in only one patient who subsequently underwent successful repeat ESD. ConclusionsAlthough technically challenging, ESD represents a safe and effective treatment of early esophageal adenocarcinoma and has the potential to become a more important tool in management of these early lesions in Western countries.

Effects of cancer stage and grade on fertility preservation outcome and ovarian stimulation response.

Do the stage and grade of malignancy affect the fertility preservation outcome in females? Patients with high-grade cancer have a decreased number of retrieved mature oocytes and cryopreserved embryos. Cancer has local and systemic effects on the host. The effects of cancer spread and aggressiveness on the ovarian function and stimulation response remain unclear. Retrospective cohort study evaluating data of all fertility preservation treatment cycles among women with cancer at the reproductive unit of the McGill University Health Centre in the period from 2008 to 2017. Study inclusion criteria were age 18-38 years, first stimulation cycle, GnRH-antagonist protocol and early follicular phase stimulation start. Only one stimulation cycle per patient was included. Patients with ovarian pathology, previous ovarian surgery and previous chemo- or radiotherapy were excluded. The outcomes of women with low-stage cancer (local tumor Stage I-II, no lymph node involvement, no metastases) were compared with those with high-stage disease (local tumor Stage III-IV, lymph node involvement or metastases). Similarly we compared those with low-grade (G1-2) and high-grade (G3-4) malignancies. The primary outcome measure was the number of mature oocytes retrieved. The secondary outcomes included the total number of retrieved oocytes, the number of vitrified oocytes, and the number of frozen embryos. We used Student's t-test for normally distributed data and Wilcoxon test for skewed data. To determine factors associated with good fertility preservation outcome defined as over 10 retrieved mature oocytes, we used multivariate logistic regression. A total of 147 patients were included in the final analysis. Age, body mass index, ovarian reserve parameters of the study groups in stage- and grade-based analyses were similar. Compared to women with low-stage cancer (n = 83), those with high-stage cancer (n = 64) required a higher dose of gonadotropin (P = 0.02). The number of retrieved mature oocytes (9 (7-13) versus 8 (5-12); P = 0.37) and vitrified oocytes (10 (7-15) versus 10 (7-13); P = 0.53) were similar between the two groups. However, in cycles where fertilization of all retrieved oocytes was performed, the fertilization rate (82.7% versus 71.5%; P = 0.03) and the number of vitrified embryos (6.2 ± 3.2 versus 4.3 ± 2.1; P = 0.01) were higher in the low-stage group. Compared to patients with low-grade cancer (n = 62), those with high-grade disease (n = 85) had significantly lower number of retrieved mature oocytes (11 (7-15) versus 8 (5-11); P = 0.002) and vitrified oocytes (12 (8-15) versus 10 (7-11); P = 0.005). The number of vitrified embryos was lower in high-grade group (6.5 ± 3.5 versus 4.6 ± 2.3; P = 0.03) in cycles where the fertilization was performed. In multivariate logistical analysis, the low-grade cancer was significantly associated with retrieval of over 10 mature oocytes (OR = 4.26; 95% CI 1.82-9.98; P = 0.0009). The main limitations of the study include its retrospective design and the relatively small sample size in the embryological outcome analysis. The results of our study should be viewed with caution as different malignancy types were included in the study groups, although their distribution between the study groups was similar. Cancer grade seems to have a negative impact on the fertility preservation outcome and the ovarian stimulation response. Authors have not received any funding to support this study. There are no conflicts of interest to declare.