Clinical and Investigative Medicine最新文献

Purpose: Over the past 20 years, much of the research on diabetes has focused on pancreatic beta cells. In the last 10 years, interest in the important role of pancreatic alpha cells in the pathogenesis of diabetes, which had previously received little attention, has grown. We aimed to summarize and visualize the hotspot and development trends of pancreatic alpha cells through bibliometric analysis and to provide research direction and future ideas for the treatment of diabetes and other islet-related diseases.

Methods: We used two scientometric software packages (CiteSpace 6.1.R6 and VOSviewer1.6.18) to visualize the information and connection of countries, institutions, authors, and keywords in this field.

Results: A total of 532 publications, published in 752 institutions in 46 countries and regions, were included in this analysis. The United States showed the highest output, accounting for 39.3% of the total number of published papers. The most active institution was Vanderbilt University, and the authors with highest productivity came from Ulster University. In recent years, research hotspots have concentrated on transdifferentiation, gene expression, and GLP-1 regulatory function. Visualization analysis shows that research hotspots mainly focus on clinical diseases as well as physiological and pathological mechanisms and related biochemical indicators.

Conclusions: This study provides a review and summary of the literature on pancreatic alpha cells through bibliometric and visual methods and shows research hotspot and development trends, which can guide future directions for research.

Purpose: The COVID-19 pandemic has resulted in a significant diagnostic, screening, and procedure backlog in Ontario. Engagement of key stakeholders in healthcare leadership positions is urgently needed to inform a comprehensive provincial recovery strategy.

Methods: A list of 20 policy recommendations addressing the diagnostic, screening and procedure backlog in Ontario were transformed into a national online survey. Policy recommendations were rated on a 7-point Likert scale (strongly agree to strongly disagree) and organized into those retained (≥75% strongly agree to somewhat agree), discarded (≥80% somewhat disagree to strongly disagree), and no consensus reached. Survey participants included a diverse sample of healthcare leaders with the potential to impact policy reform.

Results: Of 56 healthcare leaders invited to participate, there were 34 unique responses (61% response rate). Participants were from diverse clinical backgrounds, including surgical subspecialties, medicine, nursing, and healthcare administration and held institutional or provincial leadership positions. A total of 11 of 20 policy recommendations reached the threshold for consensus agreement with the remaining 9 having no consensus reached.

Conclusion: Consensus agreement was reached among Canadian healthcare leaders on 11 policy recommendations to address the diagnostic, screening, and procedure backlog in Ontario. Recommendations included strategies to address patient information needs on expected wait times, expand health and human resource capacity, and streamline efficiencies to increase operating room output. No consensus was reached on the optimal funding strategy within the public system in Ontario or the appropriateness of implementing private funding models.

Purpose: Despite the impact of physician-scientists on scientific discovery and translational medicine, several reports have signalled their declining workforce, reduced funding, and insufficient protected research time. Given the paucity of outcome data on Canadian MD/PhD programs, this study presents a national portrait of the sociodemographic characteristics, training trajectories, productivity, and satisfaction in trainees and alumni from Canadian MD/PhD and MD/MSc programs.

Methods: Quantitative data were collected in a national survey launched in 2021. Respondents included 74 MD/PhD alumni and 121 trainees across 12 Canadian MD/PhD and MD/MSc programs.

Results: Among MD/PhD alumni, 51% were independent practitioners/researchers while others underwent residency training. Most trainees (88%) were in MD/PhD programs. Significantly more alumni identified as men than did trainees. Significantly more alumni conducted clinical and health services research, while more trainees conducted basic science research. Average time to MD/PhD completion was 8 years, with no correlation to subsequent research outcomes. Self-reported research productivity was highest during MD/PhD training. Concerning training trajectories, most alumni completed residency, pursued additional training, and practised in Canada. Finally, regression models showed that trainees and alumni were satisfied with programs, with significant moderators in trainee models.

Conclusion: Survey findings showed Canadian MD/PhD and MD/MSc programs recruit more diverse cohorts of trainees than before, provide productive research years, and graduate alumni who pursue training and academic employment in Canada. Both alumni and trainees are largely satisfied with these training programs. The need to collect in-depth longitudinal data on Canadian MD/PhD graduates to monitor diversity and success metrics is discussed.

Introduction: We aimed to investigate the association of iron metabolism-related parameters with 60-day mortality in critically ill patients with sepsis.

Methods: Serum or urine concentrations of iron metabolism-related parameters on intensive care unit admission were measured in a prospective cohort of 133 eligible patients with sepsis according to the Sepsis-3 criteria, and these values were compared between survivors and nonsurvivors, categorized according to their 60-day survival status. Cox regression analyses were performed to examine the association between iron parameters and 60-day mortality. Kaplan-Meier methods were used to illustrate the differences in survival between different iron parameters.

Results: Of the 133 patients included in the study, 61 (45.8%) had died by day 60. After adjusting for confounding variables, higher concentrations of serum iron (cut-off 9.5 μmol/mL) and higher concentrations of urine neutrophil gelatinase-associated lipocalin (uNGAL; cut-off 169.3 ng/mL) were associated with a significantly greater risk of death in the Cox regression analysis. These two biomarkers combined with Sequential Organ Failure Assessment (SOFA) scores increased the area under the receiver operating characteristic (AUROC) curve to 0.85.

Discussion: These findings suggest that higher concentrations of serum iron and uNGAL are each associated with higher 60-day mortality, and they add significant accuracy to this prediction in combination with SOFA. Abbreviations: uNGAL: urine neutrophil gelatinase-associated lipocalin; ICU: intensive care unit; SOFA: Sequential Organ Failure Assessment; APACHE II: the Acute Physiology and Chronic Health Evaluation II; ELISA: enzyme-linked immunosorbent assay; HR: hazard ratio; CIs: confidence intervals; WBC: white blood cell; TBIL: total bilirubin.

[Figure: see text] Dr. Natasha Kekre has been appointed to the Department of Medicine in the Division of Hematology, within the Transplant and Cellular Therapy Program at The Ottawa Hospital since 2015. She is also a scientist within the Ottawa Hospital Research Institute and an associate professor of medicine at the University of Ottawa. She completed her Bachelor's in Science at the University of Windsor then obtained her medical degree from the University of Ottawa. She trained at the University of Ottawa in Internal Medicine and Hematology, then did fellowship in stem cell transplantation at Dana Farber Cancer Institute in Boston, MA with a Masters in Public Health from Harvard University. Her research is focused on developing early phase clinical trials and moving home grown therapeutic strategies from the lab to patients in the clinic. She has collaborated with scientists and physicians across Canada to build a Canadian CAR-T cell platform (chimeric antigen receptor T cells are immune cells engineered to kill cancer cells), bringing this exciting new therapy to Canadian patients.

Introduction: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet counts and increased risk of bleeding. After corticosteroids with or without intravenous immune globulin (first-line treatment), second-line treatment options include rituximab, splenectomy, thrombopoietin receptor agonists (TPO-RAs), and fostamatinib. In Canada, the choice of second-line therapy is influenced by access to medications. The goals of this narrative review are to 1) summarize the evidence for the use of TPO-RAs and other second-line therapies in ITP and 2) highlight differences in public funding criteria for TPO-RAs across provinces and territories in Canada.

Methods: We conducted a literature review of second-line therapies for ITP. We solicited information on public funding programs for TPO-RAs in Canada from health care providers, pharmacists, and provincial ministries of health.

Results: Head-to-head trials involving TPO-RAs, rituximab, splenectomy, and fostamatinib are lacking. There is substantial evidence of effect for TPO-RAs in improving platelet count levels, health-related quality of life, bleeding, and fatigue from placebo-controlled trials and observational studies; however, access to TPO-RAs through provincial funding programs in Canada is variable. Splenectomy failure is a prerequisite for the funding of TPO-RAs in Ontario, Manitoba, and Saskatchewan, but not in Alberta or Quebec. Other provinces either do not have access to public funding or funding is provided on a case-by-case basis.

Discussion: TPO-RAs are effective second-line therapies for the treatment of ITP; however, access is variable across Canada, which results in health disparities and poor uptake of international treatment guidelines.

Background: Glucocorticoids are often used to treat acute respiratory distress syndrome (ARDS) and novel coronavirus disease 2019 (COVID-19). However, the efficacy and safety of glucocorticoids in the treatment of ARDS caused by COVID-19 are still controversial; therefore, we conducted this meta-analysis of the literature on this topic.

Methods: Four databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched from the establishment of the databases to August 16, 2023. Randomized controlled trials (RCTs) and cohort studies that compared glucocorticoid versus standard treatment for ARDS caused by COVID-19 were included. The Newcastle-Ottawa Scale (NOS) checklist and the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias. Review Manager 5.4 software and STATA 17.0 were used for meta-analy-sis, and the relative risk (RR), mean difference, and 95% confidence intervals (CIs) were then determined. Results: A total of 17 studies involving 8592 patients were evaluated, including 14 retrospective studies and 3 RCTs. Sixteen studies reported data on all-cause mortality. The results of the meta-analysis showed that glucocorticoids did not reduce all-cause (RR, 0.96; 95% CI 0.82-1.13, P = .62) or 28-day (RR, 1.01; 95% CI 0.78-1.32, P = .93) mortality. Subgroup analysis showed that only methylprednisolone reduced all-cause mortality. No matter whether glucocorticoid use was early or delayed, high-dose or low-dose, long-term or short-term, no regimen reduced all-cause mortality. Furthermore, there were no significant differences in length of intensive care unit (ICU) stay, length of hospital stay, hyperglycemia, and ventilator-associated pneumonia (VAP); how-ever, glucocorticoids increased the number of ventilator-free days.

Conclusions: Although methylprednisolone may reduce all-cause mortality from ARDS caused by COVID-19, this effect was not found with other types of glucocorticoids. At the same time, glucocorticoid use was associ-ated with more ventilator-free days, without increasing the incidence of hyperglycemic events or VAP. Con-sidering that almost all of the included studies were retrospective cohort studies, more RCTs are needed to confirm these findings.