Toronto General Hospital Research Articles

Long-term clinical outcomes and patterns of follow-up after cardiogenic shock: insights from an advanced heart failure referral center registry

Abstract Background Inpatient mortality of patients with cardiogenic (CS) has been reported as high as 50%. Those who present in CS are at high risk of having recurrent admissions to hospital or requiring advanced heart failure (HF) therapies. The Toronto General Hospital (TGH) is a quaternary cardiac center, providing mechanical circulatory support (MCS) and heart transplantation (HT), serving as a regional CS transfer hub for a population of over 8 million people. While inpatient management of CS patients has been studied extensively, there is little data on where or how these patients are followed after their discharge. We aimed to determine the long-term clinical outcomes and nature of follow up after a CS admission. Methods This was a retrospective cohort study of CS patients admitted to TGH between 2014 and 2023. We collected data regarding survival to discharge and the type of follow up patients received after their index CS admission. Survival was compared using Kaplan-Meier methods. Results 1582 patients were admitted during the study. The mean age was 59.9 + 16.1 years, including 474 (30.0%) females and 335 (21.2%) patients with acute myocardial infarction CS. In-hospital mortality was 32.4%, with a further 17 (1.8%) patients transferred to palliative care during their index CS admission. After excluding patients who underwent heart transplantation (HT) or durable MCS implant, 679 patients were discharged alive, with median follow-up of the 307 (range 0 – 3436) days. Overall mortality was 57.0%. Among discharged patients, 396 (56.8%) were followed at the regional hub hospital. A further 54 (8.0%) patients were followed by a cardiology provider at a referring community center. A total of 202 (29.7%) patients did not have outpatient follow up arranged at the time of their discharge and no details of further care were available. Median survival during follow-up was higher among patients with confirmed follow-up at the time of their discharge, but not statistically significant (1798 vs 1775 days, p=0.067). There was a significant survival benefit among CS patients followed at a heart function clinic compared with those who were not, (1821 vs. 1775 days, p= 0.020). In terms of candidacy for advanced therapies, having outpatient follow up was associated with receiving durable MCS or HT (6.3% vs. 0.5%, p=0.003). Conclusion Despite advances in the management of CS, overall mortality remains high at 57.0%. Follow-up after CS admission is of essential importance- both in improvement of long-term outcomes, and access to advanced heart failure therapies. There was a survival benefit among patients who were followed in a specialized heart function clinic. Additionally, having outpatient follow up was significantly associated with receiving advanced therapies. Further research is needed to identify the barriers to accessing post discharge follow-up care.

Propofol and Fentanyl Pharmacokinetics and Pharmacodynamics in Extracorporeal Membrane Oxygenation.

Despite the potential risks associated with sedation, there is a paucity of pharmacokinetic/pharmacodynamic (PK/PD) data for propofol and fentanyl in patients supported with veno-venous extracorporeal membrane oxygenation (V-V ECMO). Describe propofol and fentanyl PK/PD profiles in V-V ECMO patients. Prospective, single-center, open-label PK/PD study at the Toronto General Hospital ICU between July 2022 and January 2023. Using high-performance liquid chromatography-tandem mass spectrometry, propofol and fentanyl total concentrations were measured during V-V ECMO. Sequential PK/PD modeling, using sex as a covariate, was conducted with processed electroencephalography (PSI) for sedation, and expiratory occlusion pressure (Pocc), and airway occlusion pressure during the first 0.1 seconds (P0.1) for respiratory effort. Eleven patients underwent 106 evaluations over a median (IQR) follow-up of 146 (116-146) hours. Patient's average (±SD) age was 43 (±13) years, and 55% were female. Propofol and fentanyl PK were best described by a two-compartment model. Propofol-PSI PD was described using an effect compartment, with a coefficient of determination (ρ2) of 0.78. There was a significant increase in propofol (p=0.01) and fentanyl (p=0.03) clearance within 10 minutes of ECMO initiation, plateauing after 8 hours of ECMO support. Despite this, patient over-sedation (PSI<40) occurred in 74% of the observations. Females exhibited higher sedative central volume of distribution and lower propofol clearance. ECMO initiation resulted in a time-limited increased sedative clearance. PSI accurately described sedative PD, but variable respiratory effort was observed irrespective of sedative plasma concentrations. Sex-based differences were found in sedative PK/PD parameters.

Characterization of Ganciclovir Dosing for the Management of Cytomegalovirus in Solid Organ Transplant Recipients Receiving Sustained Low-Efficiency Dialysis.

The optimal dosing of intravenous ganciclovir in patients receiving sustained low-efficiency dialysis (SLED) remains unclear. The primary objective is to characterize the dosing of ganciclovir for treating and preventing cytomegalovirus (CMV) in Solid Organ Transplant Recipients receiving SLED. The secondary objective is to evaluate the safety and efficacy of the dosing practices described in this study. Retrospective review of electronic medical records from solid organ transplant recipients (SOTRs) admitted to the Medical Surgical Intensive Care Unit at the Toronto General Hospital (TGH) between November 28, 2016, and September 1, 2021, was conducted. Patients concurrently receiving ganciclovir and SLED were included. Among the 27 encounters for CMV prevention, 18 patients underwent 8-hour SLED, 6 underwent 24-hour SLED, and 3 received other SLED durations. Most patients (80%) on 8-hour SLED began ganciclovir at 2.5 mg/kg/d, whereas 80% of those on 24-hour SLED started at 5 mg/kg/d. No breakthrough viremia occurred at 5 mg/kg/d, with 1 instance at 2.5 mg/kg/d. Cytopenia rates were higher at 5 mg/kg/d (33% vs 20%). For treatment (n = 20), 16 patients underwent 8-hour SLED, 2 underwent 24-hour SLED, and 2 underwent 12-hour SLED. Most (75%) on 8-hour SLED started at 2.5 mg/kg/d, whereas all on 24-hour SLED began at 5 mg/kg/d. Viral eradication rates were 75% and 60% at 2.5 and 5 mg/kg/d, respectively, with higher cytopenia rates at 5 mg/kg/d (37.5% vs 0%). Dose adjustments were primarily in response to refractory disease or cytopenia. At our institution, ganciclovir dosing patterns suggest that for patients requiring 8-hour SLED, there is clinician comfort in using 2.5 mg/kg/d for prevention and 5 mg/kg/d for treatment. In 24-hour SLED, 5 mg/kg/d may be considered for prevention. Higher doses may be considered for CMV treatment; however, we found greater variability in the dosing practices for these patients. Further research with larger sample sizes and ganciclovir drug-level assessments is needed to optimize dosing strategies for CMV treatment.

One-year opioid consumption trajectories among individuals receiving multidisciplinary postsurgical care: a single-center observational study from the Toronto General Hospital Transitional Pain Service

IntroductionThe Transitional Pain Service (TPS) is an innovative, personalized approach to postsurgical opioid consumption and pain management. The objectives of this study were to identify trajectories of opioid consumption and...

Long-Term Outcomes of Recipients of Liver Transplants from Living Donors Treated with a Very Low-Calorie Diet.

The increasing prevalence of steatotic liver disease (SLD) in potential living donors is concerning, as it limits donor's availability amid rising demand. OPTIFAST very low-calorie diet (VLCD), a meal replacement product, effectively reduces weight and hepatic steatosis before transplantation. However, data on the outcomes of recipients of VLCD-treated donors are lacking. We conducted a single-center, retrospective study on 199 living donor liver transplant recipients at Toronto General Hospital, Canada, between January 2015 and January 2020. We compared the 1-year posttransplant outcomes between recipients who received organs from donors treated with VLCD (N = 34) for either weight loss or steatosis reduction, with those who did not require treatment (N = 165). Our analysis revealed no statistically significant differences in the rates of postoperative complications (23% vs 32.4%, p=0.3) or intensive care unit stays (70.9% vs 70.6%, p=1) between recipients of non-VLCD and VLCD grafts. Following adjusted multivariate logistic regression, receipt of VLCD grafts was not associated with increased hospital length of stay. In addition, one-year mortality did not differ between the two groups (4.2% non-VLCD recipients vs 2.9% VLCD recipients, p=0.6). OPTIFAST VLCD treatment for liver donors demonstrates positive and safe outcomes in recipients, expanding the pool of potential living donors for increased organ availability.

Implications of High Sensitivity Troponin Levels After Lung Transplantation.

Trends in high-sensitivity cardiac troponin I (hs-cTnI) after lung transplant (LT) and its clinical value are not well stablished. This study aimed to determine kinetics of hs-cTnI after LT, factors impacting hs-cTnI and clinical outcomes. LT recipients from 2015 to 2017 at Toronto General Hospital were included. Hs-cTnI levels were collected at 0-24h, 24-48h and 48-72h after LT. The primary outcome was invasive mechanical ventilation (IMV) >3days. 206 patients received a LT (median age 58, 35.4% women; 79.6% double LT). All patients but one fulfilled the criteria for postoperative myocardial infarction (median peak hs-cTnI = 4,820ng/mL). Peak hs-cTnI correlated with right ventricular dysfunction, >1 red blood cell transfusions, bilateral LT, use of EVLP, kidney function at admission and time on CPB or VA-ECMO. IMV>3days occurred in 91 (44.2%) patients, and peak hs-cTnI was higher in these patients (3,823 vs. 6,429ng/mL, p < 0.001 after adjustment). Peak hs-cTnI was higher among patients with had atrial arrhythmias or died during admission. No patients underwent revascularization. In summary, peak hs-TnI is determined by recipient comorbidities and perioperative factors, and not by coronary artery disease. Hs-cTnI captures patients at higher risk for prolonged IMV, atrial arrhythmias and in-hospital death.

Safety of hyperbaric oxygen therapy in patients with heart failure: A retrospective cohort study.

Hyperbaric oxygen therapy (HBOT) has several hemodynamic effects including increases in afterload (due to vasoconstriction) and decreases in cardiac output. This, along with rare reports of pulmonary edema during emergency treatment, has led providers to consider HBOT relatively contraindicated in patients with reduced left ventricular ejection fraction (LVEF). However, there is limited evidence regarding the safety of elective HBOT in patients with heart failure (HF), and no existing reports of complications among patients with HF and preserved LVEF. We aimed to retrospectively review patients with preexisting diagnoses of HF who underwent elective HBOT, to analyze HBOT-related acute HF complications. Research Ethics Board approvals were received to retrospectively review patient charts. Patients with a history of HF with either preserved ejection fraction (HFpEF), mid-range ejection fraction (HFmEF), or reduced ejection fraction (HFrEF) who underwent elective HBOT at two Hyperbaric Centers (Toronto General Hospital, Rouge Valley Hyperbaric Medical Centre) between June 2018 and December 2020 were reviewed. Twenty-three patients with a history of HF underwent HBOT, completing an average of 39 (range 6-62) consecutive sessions at 2.0 atmospheres absolute (ATA) (n = 11) or at 2.4 ATA (n = 12); only two patients received fewer than 10 sessions. Thirteen patients had HFpEF (mean LVEF 55 ± 7%), and seven patients had HFrEF (mean LVEF 35 ± 8%) as well as concomitantly decreased right ventricle function (n = 5), moderate/severe tricuspid regurgitation (n = 3), or pulmonary hypertension (n = 5). The remaining three patients had HFmEF (mean LVEF 44 ± 4%). All but one patient was receiving fluid balance therapy either with loop diuretics or dialysis. Twenty-one patients completed HBOT without complications. We observed symptoms consistent with HBOT-related HF exacerbation in two patients. One patient with HFrEF (LVEF 24%) developed dyspnea attributed to pulmonary edema after the fourth treatment, and later admitted to voluntarily holding his diuretics before the session. He was managed with increased oral diuretics as an outpatient, and ultimately completed a course of 33 HBOT sessions uneventfully. Another patient with HFpEF (LVEF 64%) developed dyspnea and desaturation after six sessions, requiring hospital admission. Acute coronary ischemia and pulmonary embolism were ruled out, and an elevated BNP and normal LVEF on echocardiogram confirmed a diagnosis of pulmonary edema in the context of HFpEF. Symptoms subsided after diuretic treatment and the patient was discharged home in stable condition, but elected not to resume HBOT. Patients with HF, including HFpEF, may develop HF symptoms during HBOT and warrant ongoing surveillance. However, these patients can receive HBOT safely after optimization of HF therapy and fluid restriction.

Interobserver Variability of Coronary Stenosis Characterized by Coronary Angiography: A Single-Center (Toronto General Hospital) Retrospective Chart Review by Staff Cardiologists.

The reliability of interpretation of coronary angiography as a diagnostic tool was investigated. Furthermore, the impact of interobserver variability of coronary lesions on clinical decision-making was assessed. One of our motivations to do this research was the research gaps and our aim to have up-to-date information regarding interobserver variability among different cardiologists. Our objective was to quantify interobserver variability among cardiologists who have seen angiograms independently. Disagreement among cardiologists in the visual assessment of invasive coronary angiography of coronary artery stenosis is not uncommon in previous studies. Three cardiologists with extensive experience in coronary angiography, including the primary cardiologist of each patient, read the angiograms of 200 patients from Toronto General Hospital independently. Our research showed the mean agreement among all participating observers was 77.4%; therefore, the interobserver variability of coronary angiography interpretation was 22.6%. Coronary angiography is still the gold-standard technique for guidance regarding coronary lesions. Sometimes, coronary angiography results in underestimation or overestimation of a lesion's functional severity. Interobserver variability should also be considered when interpreting the severity of coronary stenoses via invasive coronary angiography. This research shows that interobserver variability regarding coronary angiograms is still present (22.6%).

Cannabis Use, Perspectives, and Experiences Among Patients Receiving Hemodialysis: A Descriptive Patient Survey.

Patients with chronic kidney disease experience high burden of symptoms, negatively affecting their quality of life. Medication therapy is often initiated to address these symptoms but is limited by variable efficacy and high pill burden. There is interest among clinicians and patients to explore cannabis and cannabinoids as an alternative treatment to manage symptoms related to kidney disease. The objectives were to characterize cannabis use among patients receiving maintenance hemodialysis (HD), to describe patient perspectives on cannabis, and to explore patient experiences with their kidney health care team related to cannabis. This was a descriptive, cross-sectional paper-based patient survey. Patients receiving maintenance HD at Toronto General Hospital in the ambulatory setting between July and August 2020 were included. A 33-item questionnaire was developed to address the study questions based on existing cannabis questionnaires and input from kidney specialist physicians, pharmacists, kidney nurse practitioners, and patients. The questionnaire was distributed to patients during their in-center HD session. Patients who chose to participate in the study completed the questionnaire and returned it to the study team. In total, there were 52 respondents, of which 11 (21%) reported cannabis use in the preceding 3 months, and 23 (44%) reported historical cannabis use. Baseline characteristics were similar between those who used cannabis and those who did not, with a possible trend of cannabis users being younger. The most commonly reported reasons for using cannabis were recreation and symptom management. Those who reported using cannabis for symptom management were doing so without medical authorization or documentation. Common symptoms that cannabis was used to self-treat were insomnia, anxiety, and/or non-neuropathic pain. Dried flower was the most common type of product used, and smoking was the most common route. Care gaps and opportunities to improve patient care related to cannabis use were identified, related to monitoring and management of adverse effects, management of drug interactions, harm reduction strategies, informed decision-making, and prescriber education. The overall participation rate was low, at approximately 17%, possibly related to the COVID-19 pandemic, lack of interest, or fear of revealing cannabis use. Non-response bias is a possible limitation as this was a voluntary survey. The questionnaire was limited to multiple-choice and Likert scale questions, therefore limiting the depth of patient responses. Our study showed that cannabis use among patients receiving HD is common and comparable with the general population. Patients may be using cannabis to self-manage symptoms related to kidney disease, without the involvement of the health care team. Multiple opportunities to improve patient care related to cannabis use were identified.

Predictors of early and long-term readmissions and their association with survival after liver transplantation

BackgroundThe impact of post liver transplantation (LT) readmissions on mortality has not been well described. Thus, the primary objective of our study was to determine predictors of readmissions post-LT and assess impact on survival. MethodsSingle center retrospective observational study investigating adult patients who underwent LT between January 1, 2010 – December 31, 2019 at Toronto General Hospital (TGH). Time-dependent cox regression model was used to investigate risk factors for 30-day, 30–90-day, and >90-day readmissions to hospital. The effect of readmission on survival was assessed with the Kaplan–Meier estimator. Results987 patients fulfilled inclusion criteria. Significant predictors of 30-day readmissions were BMI > 30 kg/m2 (HR=0.64; CI 0.42–0.98; p-value 0.04) and autoimmune/cholestatic liver disease (HR=1.86; CI 1.01–3.42; p = 0.046) at 30-days. Post-LT length of stay (HR=1.05; CI 1.02–1.08; p<0.001) at 30–90 days. Meanwhile, living donor LT (HR=1.41; CI 1.06–1.89; p = 0.02) and distance from LT center (HR=1.05; CI 1.01–1.09; p = 0.011) after 90 days. Infection was the main reason for readmission across three time periods. An inpatient readmission across any time period was found to be significantly associated with mortality (HR=2.4; 1.6–3.6; p<0.0001). ConclusionHospital readmissions post-LT are associated with increased mortality. Although infection is a common risk factor for readmission other modifiable risk factors may be an area for target of interventions to reduce post-LT readmission.

A re-usable, locally manufactured, half-face respirator provides better protection than fitted disposable N95 masks

BACKGROUND The coronavirus disease 2019 pandemic has led to persistent shortages of respiratory protective equipment in many jurisdictions. Re-usable industrial respirators have been proposed and deployed as an alternative, but also face severe supply limitations. Numerous respirator designs have been proposed since the start of the current pandemic, but few have been systematically tested on healthcare workers (HCWs). OBJECTIVE In this paper, we describe a locally manufactured respirator named ‘Duo’ that includes separate, valved, inspiratory and expiratory pathways and accommodates up to two filters. Duo was compared with the disposable commercial N95 in a cohort of 41 HCWs using standardised quantitative fit-testing. DESIGN A prospective observational cross-sectional study. SETTING Conducted between May and June 2020 among HCWs at Toronto General Hospital. PARTICIPANTS Forty-one HCWs of both sexes working at Toronto General Hospital. MAIN OUTCOME MEASURES Quantitative fit-testing involving seven tests as prescribed by Canadian standard CSA Z94.4-18. We measured the median overall fit-factors; the individual manoeuvre fit-factors and pass rate. RESULTS The median [IQR] overall fit-factors were 2947 [2228 to 4405] and 77.2 [51.9 to 152.1] for the Duo and disposable N95 respirators respectively (P &lt; 0.0001). The overall pass rate of quantitative fit-testing fitted disposable N95 was 58.5% (24/41), and 100% for the Duo. CONCLUSIONS A re-usable, locally manufactured, half-face respirator performs better than fitted disposable N95 masks as assessed by quantitative fit-testing. This can help address the global supply disruption for a better response to future pandemics. The device requires further modification and testing to optimise exhalation flow resistance, and full conformance with technical standards is required for regulatory approval.

Premature termination of inpatient eating disorder treatment: Does timing matter?

BackgroundPremature termination of treatment is a serious problem in the treatment of eating disorders. Prior research attempting to differentiate patients who are able to complete treatment from those who terminate early has yielded mixed results. One proposed explanation for this is a failure to examine the time course of treatment termination. This study was designed to explore associations between baseline patient characteristics and timing of treatment termination.MethodsParticipants were 124 eating disorder patients admitted voluntarily to the inpatient program at Toronto General Hospital between 2009 and 2015. At admission, all patients completed measures of eating disorder symptoms, eating disorder cognitions, depressive symptoms and emotional dysregulation. Body weight was measured weekly. Data analyses were completed using one-way ANOVAs and Chi Square tests.ResultsResults showed significant associations between timing of treatment termination and eating disorder diagnosis, severity of eating disorder cognitions and severity of depressive symptoms. Post-hoc analyses revealed that patients who left treatment early had more severe depressive symptoms, eating disorder cognitions related to eating and difficulties engaging in goal directed behaviors when emotionally dysregulated.ConclusionsPatients who terminated inpatient treatment early in their admissions differ from patients who terminated later and those who completed treatment. These differences have potential clinical implications for the clinical management of patients with severe eating disorders requiring inpatient admission.Trial registration This paper is not associated with a clinical trial.

Performance evaluation of a North American center using the established global benchmark for laparoscopic liver resections: A retrospective study

BackgroundThe global benchmark cut-offs were set for laparoscopic liver resection procedures: left lateral sectionectomy, left hepatectomy, and right hepatectomy. We aimed to compare the performance of our North American center with the established global benchmarks. MethodsThis is a single-center study of adults who underwent laparoscopic liver resection between 2010 to 2022 at the Toronto General Hospital. Fourteen benchmarking outcomes were assessed: operation time, intraoperative blood transfusion, estimated blood loss, blood loss ≥500 mL, blood loss ≥1000mL, open-conversion, postoperative length of stay, return to operation, postoperative morbidity, postoperative major-morbidity, 30-day mortality, 90-day mortality, R1 resection, and failure to rescue. Low-risk benchmark cases were defined as follows: patients aged 18 to 70 years, American Society of Anesthesiologist score ≤ 2, tumor size <10 cm, and Child–Pugh score ≤A. Cases involving bilio-enteric anastomosis, hilar dissection, or concomitant major procedures were excluded from the low-risk category. Cases that did not meet the criteria for low-risk selection were considered high-risk cases. ResultsA total of 178 laparoscopic liver resection cases were analyzed (109 left lateral sectionectomies, 45 left hepatectomies, 24 right hepatectomies). Forty-four (25%) cases qualified as low-risk cases (23 left lateral sectionectomies, 16 left hepatectomies, 5 right hepatectomies). The postoperative major morbidity and 90-day mortality after left lateral sectionectomy, left hepatectomy, and right hepatectomy for the low-risk cases were 0%, 0%, and 0%, and 0%, 0%, and 0%, respectively. For the high-risk cases post-2017, the outcomes in the same order were 0%, 0%, and 12%; 0%, 0%, and 0%, respectively. For the high-risk cases operated pre2017, the outcomes in the same order were 9%∗, 16%∗, and 18%; 2%∗, 0%, and 9%∗ (asterisks indicate not meeting the global cut-off), respectively. ConclusionA North American center was able to achieve outcomes comparable to the established global benchmark for laparoscopic liver resection.

Prevalence and Risk Factors for Chronic Postsurgical Pain After Thoracic Surgery: A Prospective Cohort Study

Thoracic surgery is associated with one of the highest rates of chronic postsurgical pain (CPSP) among all surgical subtypes. Chronic postsurgical pain carries significant medical, psychological, and economic consequences, and further interventions are needed to prevent its development. This study aimed to determine the prevalence, characteristics, and risk factors associated with CPSP after thoracic surgery. A prospective cohort study. Single-center tertiary care hospital. This study included 285 adult patients who underwent thoracic surgery at Toronto General Hospital in Toronto, Canada, between 2012 and 2020. Demographic, psychological, and clinical data were collected perioperatively, and follow-up evaluations were administered at 3, 6, and 12 months after surgery to assess CPSP. Chronic postsurgical pain was reported in 32.4%, 25.4%, and 18.2% of patients at 3, 6, and 12 months postoperatively, respectively. Average CPSP pain intensity was rated to be 3.37 (SD 1.82) at 3 months. Features of neuropathic pain were present in 48.7% of patients with CPSP at 3 months and 71% at 1 year. Multivariate logistic regression models indicated that independent predictors for CPSP at 3 months were scores on the Hospital Anxiety and Depression Scale (adjusted odds ratio [aOR] of 1.07, 95% CI of 1.02 to 1.14, p=0.012) and acute postoperative pain (aOR of 2.75, 95% CI of 1.19 to 6.36, p=0.018). None. Approximately 1 in 3 patients will continue to have pain at 3 months after surgery, with a large proportion reporting neuropathic features. Risk factors for pain at 3 months may include preoperative anxiety and depression and acute postoperative pain.

Creation of bioengineered lung using induced lung progenitor cells

In organ engineering, by combining stem cells, biomaterials and bioreactors, it may be possible for scientists to produce bioengineered organs for transplantation, as well as advancing understanding of organs and diseases. Researchers from the Department of Thoracic Surgery at Tohoku University in Japan and the University of Toronto in Canada are conducting multidisciplinary international research led by thoracic surgeon Assistant Professor Takaya Suzuki (Tohoku University) to create a bioengineering lung using induced lung progenitor cells. The research revolves around designing the respiratory system and involves utilising progenitor-generating cellular reprogramming using transient gene transfection. Ultimately, the researchers are seeking to identify a way to intentionally control the developmental clock of the human body and Suzuki believes that this will be possible if the team can unveil the key mechanisms that govern this clock. Suzuki is working closely with Professor Thomas K Waddell at the University of Toronto and Toronto General Hospital. It was in Waddellâ–™s lab that the concept of partial reprogramming was conceived, alongside global leading stem cell scientist Professor Andras Nagy. Alongside his collaborators, Suzuki is seeking to transform the landscape of transplantation medicine. As partial reprogramming can be employed in various organs and cells, any kind of organ bioengineering can benefit from the research.

Cardiac allograft vasculopathy and survival in pediatric heart transplant recipients transitioned to adult care

Cardiac allograft vasculopathy (CAV) is an important cause of mortality after pediatric heart transplantation (HT) but there is a paucity of data regarding its incidence and impact on survival in pediatric recipients transitioned to adult care. We conducted a retrospective review of consecutive pediatric HT patients from 1989-2017 at the Hospital for Sick Children who transitioned to adult care at ≥18 years at Toronto General Hospital. We evaluated the incidence of ISHLT CAV grade ≥1 using competing risk models. We assessed the association between all-cause mortality and CAV using Cox proportional hazards and used Kaplan Meier methods to evaluate all-cause mortality stratified by CAV and transplant era (1989-2001, 2002-2017). 96 patients were transitioned to adult care by 01/2022, of which 53 underwent repeat coronary angiography as adults. CAV was newly diagnosed in 49% patients after transition to adult care. The overall incidence of CAV was 3.9 cases per 100 person-years. There was no difference in the adjusted incidence of CAV according to transplant era (SHR = 1.17, 95% CI 0.54-2.66). CAV was associated with a higher risk of death in the early era (HR 10.29, 95% CI 2.16-49.96), but not in the recent era (HR 1.61, 95% 0.35-7.47). There is a role for continued CAV surveillance after the transition to adult care. The implications of diagnosing CAV after the transition to adult care requires further study, particularly because the risk of death in pediatric HT recipients diagnosed with CAV in the more recent era may be attenuated compared to the earlier HT era.

Outcomes of Patients Transported in the Prone Position to a Regional Extracorporeal Membrane Oxygenation Center: A Retrospective Cohort Study.

The primary objective of this retrospective cohort study was to describe the early outcomes of ARDS patients transported in prone position for evaluation at a regional ECMO center. A secondary objective was to examine the safety of their transport in the prone position. Retrospective cohort study. This study used patient charts from Ornge and Toronto General Hospital in Ontario, Canada, between February 1, 2020, and November 31, 2021. Patient with ARDS transported in the prone position for ECMO evaluation to Toronto General Hospital. Descriptive analysis of patients transported in the prone position and their outcomes. One hundred fifteen patients were included. Seventy-two received ECMO (63%) and 51 died (44%) with ARDS and sepsis as the most common listed causes of death. Patients were transported primarily for COVID-related indications (93%). Few patients required additional analgesia (8%), vasopressors (4%), or experienced clinically relevant desaturation during transport (2%). This cohort of patients with severe ARDS transported in prone position had outcomes ranging from similar to better compared with existing literature. Prone transport was performed safely with few complications or escalation in treatments. Prone transport to an ECMO center should be regarded as safe and potentially beneficial for patients with ARDS and refractory hypoxemia.

A deep learning framework for personalised dynamic diagnosis of graft fibrosis after liver transplantation: a retrospective, single Canadian centre, longitudinal study

Recurrent graft fibrosis after liver transplantation can threaten both graft and patient survival. Therefore, early detection of fibrosis is essential to avoid disease progression and the need for retransplantation. Non-invasive blood-based biomarkers of fibrosis are limited by moderate accuracy and high cost. We aimed to evaluate the accuracy of machine learning algorithms in detecting graft fibrosis using longitudinal clinical and laboratory data. In this retrospective, longitudinal study, we trained machine learning algorithms, including our novel weighted long short-term memory (LSTM) model, to predict the risk of significant fibrosis using follow-up data from 1893 adults who had a liver transplantation between Feb 1, 1987, and Dec 30, 2019, with at least one liver biopsy post transplantation. Liver biopsy samples with indefinitive fibrosis stage and those from patients with multiple transplantations were excluded. Longitudinal clinical variables were collected from transplantation to the date of last available liver biopsy. Deep learning models were trained on 70% of the patients as the training set and 30% of the patients as the test set. The algorithms were also separately tested on longitudinal data from patients in a subgroup of patients (n=149) who had transient elastography within 1 year before or after the date of liver biopsy. Weighted LSTM model performance for diagnosing significant fibrosis was compared against LSTM, other deep learning models (recurrent neural network and temporal convolutional network), and machine learning models (Random Forest, Support vector machines, Logistic regression, Lasso regression, and Ridge regression) and aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis-4 index (FIB-4), and transient elastography. 1893 people who had a liver transplantation (1261 [67%] men and 632 [33%] women) with at least one liver biopsy between Jan 1, 1992, and June 30, 2020, were included in the study (591 [31%] cases and 1302 [69%] controls). The median age at liver transplantation was 53·7 years (IQR 47·3-59·0) for cases and 55·3 years (48·0 to 61·2) for controls. The median time interval between transplant and liver biopsy was 21 months (5 to 71). The weighted LSTM model (area under the curve 0·798 [95% CI 0·790 to 0·810]) consistently outperformed other methods, including unweighted LSTM (0·761 [0·750 to 0·769]; p=0·031) Recurrent Neural Network (0·736 [0·721 to 0·744]), Temporal Convolutional Networks (0·700 [0·662 to 0·747], and Random Forest 0·679 [0·652 to 0·707]), FIB-4 (0·650 [0·636 to 0·663]) and APRI (0·682 [0·671 to 0·694]) when diagnosing F2 or worse stage fibrosis. In a subgroup of patients with transient elastography results, weighted LSTM was not significantly better at detecting fibrosis (≥F2; 0·705 [0·687 to 0·724]) than transient elastography (0·685 [0·662 to 0·704]). The top ten variables predictive for significant fibrosis were recipient age, primary indication for transplantation, donor age, and longitudinal data for creatinine, alanine aminotransferase, aspartate aminotransferase, total bilirubin, platelets, white blood cell count, and weight. Deep learning algorithms, particularly weighted LSTM, outperform other routinely used non-invasive modalities and could help with the earlier diagnosis of graft fibrosis using longitudinal clinical and laboratory variables. The list of most important predictive variables for the development of fibrosis will enable clinicians to modify their management accordingly to prevent onset of graft cirrhosis. Canadian Institute of Health Research, American Society of Transplantation, Toronto General and Western Hospital Foundation, and Paladin Labs.

Prevalence and Risk Factors for Chronic Post-Surgical Pain Following Cardiac Surgery: A Single-center Prospective Cohort Study.

Chronic post-surgical pain is a common complication of surgery. The role of psychological risk factors like depression and anxiety is substantially understudied in cardiac surgery. This study sought to identify perioperative factors associated with chronic pain at 3, 6, and 12 months after cardiac surgery. We hypothesize that baseline psychological vulnerabilities have a negative influence on chronic post-surgical pain. We prospectively collected demographic, psychological, and perioperative factors in a cohort of 1059 patients undergoing cardiac surgery at the Toronto General Hospital between 2012-2020. Patients were followed and completed chronic pain questionnaires at 3, 6, and 12 months after surgery. We included 767 patients who completed at least one follow-up questionnaire. The incidence of postsurgical pain (> 0 out of 10) at 3, 6, and 12 months after surgery was 191/663 (29%), 118/625 (19%), and 89/605 (15%), respectively. Notably, among patients reporting any pain, the incidence of pain compatible with a neuropathic phenotype increased from 56/166 (34%) at 3 months, to 38/97 (39%) at 6 months and 43/67 (64%) at 12 months. Factors associated with postsurgical pain scores at 3 months include female sex, pre-existing chronic pain, previous cardiac surgery, preoperative depression, baseline pain catastrophizing scores, and moderate-to-severe acute pain (≥4 out of 10) within 5 postoperative days. Nearly one in three patients undergoing cardiac surgery reported pain at 3 months follow-up, with ~15% reporting persistent pain at 1 year. Female sex, pre-existing chronic pain, and baseline depression were associated with postsurgical pain scores across all three time periods.

Considerations for the Measurement of Respiratory Compensation Point and Critical Power in COPD.

1School of Kinesiology, The University of Western Ontario, London, Ontario, CANADA 2Toronto General Research Institute, Toronto General Hospital, Toronto, Ontario, CANADA 3Lawson Health Research Institute, London, Ontario, CANADA 4Faculty of Kinesiology, The University of Calgary, Calgary, Alberta, CANADA