Introduction: Hereditary hemochromatosis (HH), associated with C282Y or H63D mutations in the HFE gene, is the commonest genetic disorder in Canada. The majority of HH cases are attributable to C282Y homozygosity which can precipitate iron overload and organ damage, but with low penetrance. Elevated transferrin saturation (TSat) and ferritin levels are key biochemical indicators of iron overload in C282Y homozygotes. This retrospective study examined TSat and ferritin levels as predictors of C282Y homozygosity in genotyped patients. Methods: This study included 23,432 individuals from Maritime provinces who underwent HFE genotyping from 2009 to 2022. Those with available biomarkers (TSat, ferritin, ALT) were included in the study sample. C282Y and H63D variants were identified based on HFE genotying. Median values for each biomarker were compared across genotypes and their diagnostic performance in predicting C282Y homozygosity evaluated using ROC analysis. Results: 1241 individuals (5.3 %) showed C282Y homozygosity, marking the largest North American study cohort. C282Y homozygotes showed significantly higher median TSat and ferritin levels than wildtypes. TSat showed the best diagnostic performance in detecting C282Y homozygosity (AUC = 0.82, 95 % CI: 0.78-0.85), outperforming ferritin (AUC = 0.54, 95 % CI: 0.50-0.58) and ALT (AUC = 0.59, 95 % CI: 0.56-0.63). TSat thresholds of 32 % (females) and 35 % (males) had a 90 % sensitivity for C282Y homozygosity. Using thresholds of TSat <= 46 % and ferritin <= 370 mu g/L (females), and TSat <= 49 % and ferritin <= 703 mu g/L (males) reduced the need for genotyping by up to 50 % without missing significant biochemical iron overload cases. Implementing this strategy across 23,432 tests could save $1,701,163 and potentially reduce unnecessary downstream management. Conclusion: Our study suggests significant efficiency savings by implementing an algorithm to reduce unnecessary HFE genotyping and alleviate unwarranted genetic testing anxiety.
Background and Aims:Plastic biliary endoprosthesis is widely used because of its high efficacy and low cost. Delays in the removal or exchange of plastic biliary stents may lead to stent occlusion and subsequent sepsis,1,2 with consensus recommendation of stent removal or exchange within 3 months.3-7 We postulated that delayed plastic biliary stent removal observed during the pandemic would increase stent-related adverse events. We aim to report our single-center experience with adverse events arising from delayed plastic biliary stent removal. Methods:All individuals who had ERCP-guided plastic biliary stent placement in the Queen Elizabeth II Health Sciences Center hospital in Halifax, Nova Scotia, between December 2019 and March 2022 were included. Stent lifespan was defined as days between stent deployment and removal. Kaplan-Meier survival analysis was used to represent the duration of stent patency. Only 10F-diameter stents were studied. Linear regression was used to analyze possible predictors of stent-related adverse events. Results:In total, 286 cases were analyzed, of which 187 had delayed stent removal. Overall, 216 stents were removed without adverse events; 21 cases required urgent reintervention for adverse events; and in 26 cases, patients died of non-stent-related causes. Twenty-one stents had fully migrated out without causing adverse events. There was no difference in overall adverse events between the nondelayed versus delayed groups (23.2% vs 21.4%; odds ratio [OR], 0.899). Stent adverse events and emergent removal were marginally increased, at an OR of 1.21 and OR of 1.18, respectively, in indications related to stone disease. Conclusions:A significant increase was not observed in stent-related adverse events in individuals with stents removed after 90 days. Plastic biliary stent longevity may be longer than previously thought. Our findings suggest that the majority of inserted plastic biliary stents remain patent up to 6 months without adverse outcomes. Larger studies are required to better characterize other predictors of biliary stent obstruction.
Background & Aims Biochemical response to ursodeoxycholic acid (UDCA) therapy is associated with good prognosis in people living with primary biliary cholangitis (PBC). Biochemical response is typically assessed early in disease and it is not known what proportion of patients lose previously attained biochemical response, nor whether this impacts long-term liver-transplant-free survival. Methods We identified all UDCA-treated patients with PBC from the Canadian Network for Autoimmune Liver disease with biochemical measurements at one year, and evaluated their liver biochemistry over time. Inadequate biochemical response was defined as serum alkaline phosphatase ≥ 1.67xULN or abnormal serum total bilirubin at one year of UDCA therapy and all time points thereafter. Multistate Markov models were used to estimate transition rates between biochemical response states and from each state to liver transplantation (LT) or death. Results were validated in an external cohort (GLOBAL PBC registry). Results A total of 823 patients from 8 centers were included. Mean age at diagnosis was 53 years, 91% were female, 33% had inadequate biochemical response to UDCA at one year (n = 269). Patients who retained initial adequate response had lower rates of LT or death compared to patients who subsequently lost response (relative rate 0.102, 95%CI 0.047-0.223). Patients who regained adequate response had lower rates than patients who did not (0.016, 0.001-0.568), and patients who lost response once more (0.010, 0.001-0.340). Patients who regained adequate response for a third time also had lower rates than patients who did not (0.151, 0.040-0.566). Analyses in the GLOBAL PBC registry (n=2237) validated these results. Conclusion Loss of biochemical response at any time is associated with heightened risks of liver transplantation or death in people living with PBC. Achievement of biochemical response is an important goal throughout follow-up, regardless of biochemical response profile early in therapy.
Background Primary healthcare providers play a critical role in diagnosing and managing digestive disorders. Standardized clinical care guidelines have been developed, but with limited and inconsistent implementation. An evidence-based gastroenterology clinical care pathway (GUTLINK) has been proposed in one region of Canada; however, little is known in the medical literature about potential barriers to pathway implementation within primary care. We aimed to identify behavioral and environmental barriers and facilitators to implementation of evidence-based care pathways for undifferentiated lower gastrointestinal tract symptoms in primary care. Methods One-on-one semi-structured interviews were conducted with primary healthcare providers between September 2021 and May 2022. Interview script development was guided by the COM-B framework. Interviews were transcribed and data were analyzed using an inductive thematic analysis approach. Results A total of 15 primary healthcare provider interviews were conducted. Several key barriers to GUTLINK implementation were identified in all three domains of the COM-B framework. Key barriers included Capability (e.g., Physician Knowledge and Access to Allied Health), Opportunity (e.g., Access to diagnostic tools), and Motivation (e.g., Comfort with managing cases and optimism). Some of these barriers have not previously been identified in medical literature. Conclusions Evidence-based clinical care pathways have the potential to support access to quality gastroenterology care, yet primary healthcare providers in this study identified several barriers to implementation. Potential solutions exist at the individual and clinic levels (e.g., greater education, improved provider-specialist communication), but must be supported with systems-level changes (e.g., increased funding for gastrointestinal care and e-Health platforms) to support pathway implementation and improve quality of care.
Background Hereditary haemochromatosis protein (HFE)-related haemochromatosis, an inherited iron overload disorder caused by insufficient hepcidin production, results in excessive iron absorption and tissue and organ injury, and is treated with first-line therapeutic phlebotomy. We aimed to investigate the efficacy and safety of rusfertide, a peptidic mimetic of hepcidin, in patients with HFE-related haemochromatosis. Methods This open-label, multicentre, proof-of-concept phase 2 trial was done across nine academic and community centres in the USA and Canada. Adults (aged >= 18 years) with HFE-related haemochromatosis on a stable therapeutic phlebotomy regimen (maintenance phase) for at least 6 months before screening and who had a phlebotomy frequency of at least 025 per month (eg, at least three phlebotomies in 12 months or at least four phlebotomies in 15 months) and less than one phlebotomy per month, with serum ferritin of less than 300 ng/mL and haemoglobin of more than 115 g/dL, were eligible. Patients initiated 24 weeks of subcutaneous rusfertide treatment within 7 days of a scheduled phlebotomy at 10 mg once weekly. Rusfertide doses and dosing schedules could be adjusted to maintain serum transferrin iron saturation (TSAT) at less than 40%. During rusfertide treatment, investigators were to consider the need for phlebotomy when the serum ferritin and TSAT values exceeded the patient's individual pre-phlebotomy serum ferritin and TSAT values. No primary endpoint or testing hierarchy was prespecified. Prespecified efficacy endpoints included the change in the frequency of phlebotomies; the proportion of patients achieving phlebotomy independence; change in serum iron, TSAT, serum transferrin, serum ferritin, and liver iron concentration (LIC) as measured by MRI; and treatment-emergent adverse events (TEAEs). The key efficacy analyses for phlebotomy rate and LIC were conducted by use of paired t tests in the intention-to-treat population, defined as all patients who received any study drug and who had pretreatment and at least one post-dose measurement. We included all participants who received at least one dose of rusfertide in the safety analyses. This trial is closed and completed and is registered with ClinicalTrials.gov, NCT04202965. Findings Between March 11, 2020, and April 23, 2021, 28 patients were screened and 16 (ten [63%] men and six [38%] women) were enrolled. 16 were included in analyses of phlebotomy endpoints and 14 for the LIC endpoint. 12 (75%) patients completed 24 weeks of treatment. The mean number of phlebotomies was significantly reduced during the 24-week rusfertide treatment (006 phlebotomies [95% CI -007 to 020]) compared with 24 weeks pre-study (231 phlebotomies [95% CI 177 to 285]; p<00001). 15 (94%) of 16 patients were phlebotomy-free during the treatment period. Mean LIC in the 14 patients in the intention-to-treat population was 14 mg iron per g dry liver weight (95% CI 10 to 18) at screening and 11 mg iron per g dry liver weight (95% CI 09 to 13) at the end of treatment (p=0068). Mean TSAT was 453% (95% CI 332 to 573) at screening, 367% (242 to 492) after the pretreatment phlebotomy, 218% (158 to 279) 24 h after the first dose of rusfertide, 404% (271 to 538) at the end of treatment, and 326% (250 to 401) over the treatment duration. Mean serum iron was 246 mu mol/L (95% CI 186 to 306), 201 mu mol/L (148 to 253), 119 mu mol/L (92 to 147), 225 mu mol/L (159 to 291), and 190 mu mol/L (153 to 226) at these same timepoints, respectively. Mean serum ferritin was 833 mu g/L (522 to 114.4), 655 mu g/L (321 to 989), 628 mu g/L (338 to 919), 1500 mu g/L (866 to 213.3), and 943 mu g/L (549 to 133.6) at these same timepoints, respectively. There were only minor changes in serum transferrin concentration. 12 (75%) patients had at least one TEAE, the most common of which was injection site pain (five [31%] patients). All TEAEs were mild or moderate in severity, except for a serious adverse event of pancreatic adenocarcinoma, which was considered severe and unrelated to treatment and was pre-existing and diagnosed 21 days after starting rusfertide treatment. Interpretation Rusfertide prevents iron re-accumulation in the absence of phlebotomies and could be a viable therapeutic option for selected patients with haemochromatosis.
Introduction: Autoimmune hepatitis (AIH) and Primary Biliary Cholangitis (PBC) are the 2 main immune-mediated liver diseases. Occasionally, AIH can present with features of PBC. This overlap syndrome (OS) lacks standard diagnostic criteria and management strategies. “Paris criteria” (1998) is the most recognized diagnostic criteria for OS. The frequency of OS in literature has been reported between 7% and 13%. Our study will aim to evaluate the clinical characteristics and outcomes of OS patients in a multicentric Canadian cohort study. Methods: This cohort study included 198 patients originally diagnosed as OS in the Canadian Network for Autoimmune Liver Disease (CaNAL) registry which collects data from multiple tertiary centres across Canada. Available biochemical results and biopsy reports were reviewed and the diagnosis of OS for patients was reviewed based on Paris criteria (1998). Results: 57 patients (29%) did not have enough data to apply the criteria. 78 patients (55%) have met the Paris criteria for OS, of which 69 (88%) exhibited true OS on biopsy and 9 (12%) exhibited only AIH on biopsy. Sixty-three patients (45%) did not meet criteria for OS, with 22 (35%) exhibiting PBC on biopsy and 19 (30%) exhibiting AIH on biopsy. 16 patients (25%) showed OS on biopsy despite not meeting Paris criteria. Of those that met the Paris criteria for OS, the majority were female (88%) and 9 patients (12%) received liver transplant. Conclusion: Our results show that OS tend to be over-diagnosed which raises concerns that patients with PBC could be unnecessarily exposed to steroids as a result. In our cohort, OS patients exhibited female predominance. Further analysis of OS patients will be performed to determine clinical characteristics, outcomes of treatment, biochemical response, prognosis at 1 year, progression to cirrhosis and need for liver transplantation or death from liver failure. We will also compare outcomes to those diagnosed as either AIH or PBC in our cohort.
Abstract Background Telehealth and telemedicine have become indispensable healthcare delivery tools during the COVID-19 pandemic. Older individuals with cirrhosis have complex medical needs that are currently unmet due to the growing disease burden and decreased access to care. Delivering timely specialist care virtually to older adults with cirrhosis will likely be beneficial and acceptable to such patients; however, this has not yet been prospectively evaluated. Purpose The primary goal is to pilot the delivery of dual specialist care from a hepatologist and geriatrician, delivered virtually, for older adults living with liver cirrhosis who are at high risk of geriatric syndromes (age >/= 65 with frailty, undifferentiated cognitive impairment from dementia or hepatic encephalopathy, recurrent falls, risk factors for polypharmacy and moderate to severe malnutrition). Care is delivered using a dedicated hepatology-geriatric referral pathway. Primary objectives include evaluating the impact of this approach on emergency care and inpatient utilization, along with patient attitude and satisfaction to the virtual interdisciplinary care delivery model. Method This pilot quality improvement study was conducted in Halifax, Nova Scotia. Ethics approval was obtained from the Nova Scotia Health Research Ethics Board and the University of Alberta Research Ethics Board. Fifty to one hundred participants (age 65 years or older with at least one geriatric syndrome; diagnosis of liver cirrhosis by liver elastography or liver biopsy, or Fibrosis-4 Index for Liver Fibrosis greater than three and having radiological features of cirrhosis and/or portal hypertension) were recruited between September 2022 to December 2022 at the time of their hepatology consultation. After consent and screening, each patient underwent a telehealth appointment by zoom with a geriatrician within four weeks of their initial hepatology assessment. Follow-up by telephone using a standardized survey regarding ease of access and quality of their telehealth experience then occurred at 3-4 weeks, 3 months and 6 months for emergency room visits and hospital admission status. Result(s) Pending Conclusion(s) Pending Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding; Pfizer Canada Disclosure of Interest J. Zhu Grant / Research support from: Pfizer Canada, F. Carr Grant / Research support from: Pfizer Canada, P. Tian: None Declared, M. McLeod: None Declared, M. MacFarlane: None Declared, S. De Coutere: None Declared, M. Sun: None Declared, K. Peltekian: None Declared
BACKGROUND: Primary biliary cholangitis (PBC) is a rare, chronic autoimmune, cholestatic liver disease affecting approximately 318 per million Canadians. There is limited information regarding the characterization of this patient population in Canada. Consequently, we aim to describe a cohort of PBC patients managed across liver centres serving this type of population. METHODS: A cross-sectional examination of 1,125 PBC patient charts at 15 liver centres across Canada was conducted between January 2016 and September 2017. RESULTS: Data from 1,125 eligible patients were collected from 7 Canadian provinces. The patient population was largely female (90.2%), had a median overall age of 61.3 years, and a median overall time since diagnosis of 6.4 years. Of the patients included in the study, 89% were on ursodeoxycholic acid (UDCA) therapy at a median dose of 14.0 mg/kg/day and 4.4% were previously treated with UDCA, whereas 6.6% were never treated with UDCA. Of the patients with available data (n = 1067), 289 (27.1%) presented with alkaline phosphatase (ALP) levels ≥200 IU/L and/or total bilirubin levels ≥21 µmol/L. Assessment of UDCA treatment response revealed that 26.6% and 38.3% of patients were inadequate responders according to the Toronto and Paris-II criteria, respectively. Mortality occurred in 1.2% (14) of patients, with liver-related adverse outcomes being more commonly observed in patients who discontinued UDCA compared to those who are currently on treatment (36.3% and 19.6%, respectively). CONCLUSION: This study showed that Canadian PBC patients present with demographics and features commonly reported in the literature for this disease. Over one third of PBC patients had inadequate response to UDCA treatment or were not currently being treated with UDCA. Consequently, there is a significant unmet therapeutic need in this Canadian PBC population.
Abstract Background The COVID-19 pandemic has placed the Canadian healthcare system under substantial strain requiring rapid and systemic changes to healthcare delivery in gastroenterology ambulatory care, including a shift to providing synchronous clinical visits virtually. It is important to describe and evaluate the impact of this care delivery change on patients, providers and the healthcare system in order to improve the quality of virtual care in the future. Aims As part of a larger quality improvement initiative, the aim of this project was to better understand the health system impact of the shift from in-person to virtual care delivery in the Division of Digestive Care & Endoscopy in Halifax, NS. Methods Using a before-and-after observational study design, outpatient encounters from January-March 2020 (Pre-COVID) were compared to encounters after the pandemic restrictions began April-June 2020 (COVID-Impacted). The primary objective was to compare the proportion of synchronous clinic encounters in the gastroenterology ambulatory space conducted virtually before versus after pandemic restrictions were implemented. Secondary objectives were to determine whether patient, disease, or provider-specific factors were associated with virtual care visits or changed with the implementation of pandemic restrictions. Endoscopic encounters were excluded. Descriptive statistics were used to compare patient and encounter characteristics in the Pre-COVID and COVID-Impacted periods. Multiple logistic regression modeling was used to evaluate the association between patient and provider characteristics and use of virtual care delivery. Unadjusted and adjusted odds ratio with associated 95% CI were estimated. Results A total of 4,923 unique patients (60.1% Pre-COVID and 39.9% in the COVID-Impacted period) and 6,659 encounters were identified. The proportion of synchronous clinical visits conducted virtually increased after February 2020, increasing from 25% (Pre-COVID) to 91% (COVID-Impacted). The Pre-COVID versus COVID-Impacted periods also differed with respect to median patient age (56 vs. 59, P = 0.000), mean proximity to the hospital (40km vs. 48km, P = 0.007) and proportion of new consults deemed urgent (9.8% vs. 20.0%, P = 0.000). Patients with family physicians, return visits, and patient age greater than 65 years were associated with the use of synchronous virtual care visits. Conclusions This project details the abrupt and significant disruption in in-person ambulatory, non-endoscopic digestive care and the dramatic uptake in virtual care delivery as a result of COVID-19 restrictions in Halifax, NS. Future research will explore virtual care use as pandemic restrictions ease to inform how virtual care is integrated into post-pandemic practice to guide new standards of care. Funding Agencies None
Abstract Background In liver transplantation (LT) for PSC, pre-transplant colectomy may lower the risk of PSC recurrence (rPSC), and well-controlled or lack of IBD may protect against rPSC, however, these findings are not consistent across all studies. It is unknown whether recipient/donor sex plays a role in rPSC. Aims To study factors associated with PSC recurrence in the post-transplant population. Methods This is a retrospective study on adults who received an LT for PSC in Halifax NS from 1985 to 2020. Graft and patient outcomes are analyzed by logistic regression models. Results A total of 92 patients underwent deceased donor LT for PSC with a mean follow-up time of 9.2 yrs (SD 7.1). Fifty-three remain active in the program, 2 were lost to follow up and 37 died. The mean age at transplant was 43 (SD13, range 18.9–67.8). Seven patients had a second transplant. The five- and 10-year patient survival rate of the entire cohort was 78.7% and 66% respectively. In the active cohort, the prevalence of rPSC was 23.5% (12/51). Retransplantation for rPSC occurred in 8.3% (1/12). The prevalence of IBD was 82.4% (42/51), consisted of ulcerative pancolitis (64.7%, 33/51), ulcerative proctitis (3.9%), left-sided UC (2%) and Crohn’s disease (9.8%). Males are much more likely than females to undergo a colectomy at any time (OR 5.5, 95% CI 1.07–28.22, p 0.041). Refractory IBD was the predominant indication for a colectomy (10/16), followed by dysplasia or colon cancer (6/16). In the post-transplant period, 69% had stable IBD without therapy escalation, 11.9% were escalated to a biologic, 19% underwent a colectomy for active IBD symptoms. Pre-transplant colectomy negatively predicted rPSC, in this subgroup 0% (0/6) developed rPSC. Neither recipient sex (OR 1.14, 95% CI 0.26–5.0, p 0.86) or recipient age predicted the likelihood of rPSC. There was no association between donor sex on rPSC (OR 1.25, 95% CI 0.30–5.27, p 0.76). A trend towards increased rPSC was observed in male donors to female recipients versus female-to-female transplants (OR 6, 95% CI 0.33–107.42, p 0.224). Overall, having a post-transplant colectomy, subtotal or total, irrespective of timing, did not significantly impact rPSC (OR 0.389, 95% CI 0.09–1.66, p 0.20). Diagnosis of IBD was not associated with an increased risk of rPSC (OR 1.21, p 0.83). Conclusions Several factors were associated with rPSC after liver transplant in patients with PSC and IBD, pre-transplant colectomy was found to be protective, male donor to female recipient was a potential risk factor. It is important to study these factors in multi-centered cohorts to understand the pathogenesis of PSC. Pre-transplant total colectomy may be beneficial for several reasons, reducing rPSC, controlling IBD activities, and lowering dysplasia and colon cancer rates in the post-transplant population. Funding Agencies None
Background and Aims We investigated associations between ethnicity, survival, and disease severity in a diverse Canadian cohort of patients with primary biliary cholangitis (PBC). Approach and Results Patients with PBC were included from the Canadian Network for Autoimmune Liver Disease. Ethnicity was defined using a modified list adopted from Statistics Canada, and ethnicities with small samples were grouped. Clinical events were defined as liver decompensation, HCC, liver transplantation, or death. Clinical event-free and liver transplantation-free survival were analyzed using Cox regression. Trajectories of serum liver function tests were assessed over time using mixed-effects regression. Health-related quality of life was assessed using the Short Form 36, the PBC-40 questionnaire, and the 5-D Itch scale and analyzed using mixed-effects regression. The cohort included 1538 patients with PBC from six sites and was comprised of 82% White, 4.7% Indigenous, 5.5% East Asian, 2.6% South Asian, and 5.1% miscellaneous ethnicities. Indigenous patients were the only ethnic group with impaired liver transplant-free and event-free survival compared to White patients (HR, 3.66; 95% CI, 2.23-6.01; HR, 3.09; 95% CI, 1.94-4.92). Indigenous patients were more likely to have a clinical event before diagnosis (10%) than all other ethnic groups despite similar age at diagnosis. Indigenous patients presented with higher alkaline phosphatase, total bilirubin, and GLOBE scores than White patients; and these relative elevations persisted during follow-up. Conclusions Indigenous Canadians with PBC present with advanced disease and have worse long-term outcomes compared to White patients.
Abstract Background Severe restrictions on in-person encounters and endoscopic procedures for digestive care have occurred as a result of the COVID-19 pandemic. This has exacerbated pre-existing barriers in access to gastroenterology (GI) care across Nova Scotia (NS) for patients and primary healthcare providers (PHCPs). In response, a provincial PHCP-GI consultative service (GUT LINK) was implemented at a single tertiary care center with the goal of supporting PHCPs in the management of non-urgent GI referral conditions. Aims To implement and evaluate the acceptability, feasibility, appropriateness, and early effectiveness of the GUT LINK PHCP-GI consultation service. Methods This is an ongoing prospective observational cohort study. All referrals received through the EMR-based referral and triage management system between May and November 2020 that were deemed to be amenable to management within primary care with specialist support were returned to the PHCP with the suggestion to arrange a GUT LINK telephone consultation. GUT LINK appointments were scheduled through an administrative support telephone line with the PHCP and a GI specialist. A post-consultation e-questionnaire was distributed to PHCPs who consented to participate. Feasibility (number of and indication for referrals, PHCP participation rates), acceptability and appropriateness (satisfaction, future use, likelihood to recommend) metrics and outcomes (case resolution, re-referrals, proportion requiring endoscopic investigations) were recorded. Patient charts were reviewed to determine whether the patient ultimately required GI speciality care. Analyses were descriptive and expressed as frequencies, means (+/-SD), medians (+/-SE), and proportions (%). Results A total of 45 GUT LINK consultations were completed between May and November 2020. Of these, 20% required GI specialist care and 80% have remained within primary care, with a median follow-up of 101 (+/-9.1) days. The indications for GUT LINK consultation included lower GI symptoms (64%), abnormal imaging or investigations (17%), and upper GI symptoms (19%). To date, 21 PHCP agreed to be contacted for the post-consultation survey and 10 have been completed. All PHCPs reported that GUT LINK consultation was easy to access, while 90% found the advice helpful and 80% reported that that it resolved the issue. Following the GUT LINK appointment, 80% felt they would not need to refer their patient to GI. Conclusions The implementation of GUT LINK was acceptable, feasible, and improved access to specialist support for management of undifferentiated GI symptoms. Future research will focus on comprehensive stakeholder engagement in order to design, implement, and evaluate GUT LINK PHCP care pathways. Funding Agencies CAG
Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer worldwide, with ever increasing incidence and mortality. While most patients can be treated successfully with surgical excision, cryotherapy, or radiation therapy, there exist a subset of patients with aggressive cSCC who lack adequate therapies. Among these patients are solid organ transplant recipients who due to their immunosuppression, develop cSCC at a dramatically increased rate compared to the normal population. The enhanced ability of the tumor to effectively undergo immune escape in these patients leads to more aggressive tumors with a propensity to recur and metastasize. Herein, we present a case of aggressive, multi-focal cSCC in a double organ transplant recipient to frame our discussion and current understanding of the immunobiology of cSCC. We consider factors that contribute to the significantly increased incidence of cSCC in the context of immunosuppression in this patient population. Finally, we briefly review current literature describing experience with localized therapies for cSCC and present a strong argument and rationale for consideration of an IL-2 based intra-lesional treatment strategy for cSCC, particularly in this immunosuppressed patient population.
Since December 2019, there are 30 million confirmed cases of a novel coronavirus disease (COVID-19) secondary to severe acute respiratory syndrome coronavirus 2. As of 2020, hepatitis B virus (HBV) affects more than 200 million people worldwide. Both are caused by viral agents. The short-term mortality rate from COVID-19 is much higher than that of HBV.We sought to understand the impact of HBV coinfection on hospitalized patients with COVID-19.Searches of the literature were conducted in the PubMed, Cochrane Library, and Embase electronic databases.We included cohort studies and randomized studies with information on rates of mortality and intensive care unit (ICU) admission from individuals coinfected by HBV and COVID-19.Data from six cohort studies with 2,015 patients were collected between January and April 2020, and the results were analyzed by meta-analysis.HBV coinfection did not lead to increased mortality or ICU admission rates among individuals hospitalized for COVID-19 (risk ratio 0.79, 95% CI 0.333-1.83, N = 2,015; adjusted OR = 0.79, 95% CI 0.31-1.98). During their hospital stay, coinfected patients did not appear to have an increased hospital length of stay or risk of hepatitis B reactivation.This systematic review and meta-analysis provides support that HBV is not a significant risk factor for serious adverse outcomes among patients hospitalized for COVID-19 infection.
Primary sclerosing cholangitis (PSC) is a predisposing factor for cholangiocarcinoma(CCA).Patients with CCA have poor outcomes post-transplant.Intrahepatic CCA is difficult to detect pre-operatively in cirrhosis.Few outcomes are reported among PSC transplant patients where CCA was incidental. To determine the incidence of incidental CCA (iCCA) in PSC liver explants and the impact of iCCA on post-transplant survival for patients with PSC This was a retrospective cohort study in which the medical records of PSC patients who underwent transplant at QEII Health Sciences Center in Halifax between January 1987 to March 2020 were reviewed. The incidence of iCCA was calculated. Survival analysis was performed to determine the mean time to survival among iCCA and non-iCCA groups A total of 94 patients were transplanted for PSC during the study period.The mean age was 43 years.Twenty-six percent were women and 74% were men.Three were iCCA, one hilar and two intrahepatic CCA. All iCCAs occurred prior to 2008. All iCCA patients had contrast enhanced CT, ERCP with cholangiogram and MRI.Two of the ERCPs reported CBD related strictures and the brushings had no evidence of malignancy.CA19-9 level was measured in one and reported as normal.Contrast enhanced MRI was not available prior to 2007. The PSC patients had 1, 5, and 10-year survival rates of 93.8%, 88.6% and 81.9% respectively.One patient required re-transplant for graft failure and died within 3 months post-transplant due to complications. In all other cases the cause of death was not identified. Among patients with iCCA, two deaths were due to metastatic cholangiocarcinoma and the other due to surgical complication in the immediate post-transplant period. None survived beyond 2 years. Observed PSC survival in this cohort was above national average in the same period.The 3 iCCA cases identified occurred before the availability of contrast enhanced MRI. Patients with iCCA and liver transplant had poor survival at 1 and 2 years.There were no iCCA identified after 2007.These findings suggest incidental cholangiocarcinoma was effectively reduced by the advent of high-resolution imaging modality, and improvements in pre-transplant screening, including tumor marker CA19-9 and stringent patient selection. Further study involving multiple centres is necessary to draw a definite conclusion. None
Background: Since December 2019, there are 30 million confirmed cases of a novel coronavirus disease (COVID-19) secondary to severe acute respiratory syndrome coronavirus 2. As of 2020, hepatitis B virus (HBV) affects more than 200 million people worldwide. Both are caused by viral agents. The short-term mortality rate from COVID-19 is much higher than that of HBV. Objective: We sought to understand the impact of HBV coinfection on hospitalized patients with COVID-19. Search Methods: Searches of the literature were conducted in the PubMed, Cochrane Library, and Embase electronic databases. Selection Criteria: We included cohort studies and randomized studies with information on rates of mortality and intensive care unit (ICU) admission from individuals coinfected by HBV and COVID-19. Data Collection and Analysis: Data from six cohort studies with 2,015 patients were collected between January and April 2020, and the results were analyzed by meta-analysis. Main Results: HBV coinfection did not lead to increased mortality or ICU admission rates among individuals hospitalized for COVID-19 (risk ratio 0.79, 95% CI 0.333-1.83, N = 2,015; adjusted OR = 0.79, 95% CI 0.31-1.98). During their hospital stay, coinfected patients did not appear to have an increased hospital length of stay or risk of hepatitis B reactivation. Conclusions: This systematic review and meta-analysis provides support that HBV is not a significant risk factor for serious adverse outcomes among patients hospitalized for COVID-19 infection.