Clinical and Investigative Medicine最新文献

The 2020 Annual General Meeting (AGM) and Young Investigators’ Forum of the Canadian Society for Clinical Investigation / Société Canadienne de Recherches Clinique (CSCI/SCRC) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was the first meeting to be hosted virtually. The theme was “Navigating Uncertainty, Embracing Change and Empowering the Next Generation of Clinician-Scientists”, and the meeting featured lectures and workshops that were designed to provide knowledge and skills for professional development of clinician investigator trainees. The opening remarks were given by Jason Berman (President of CSCI/SCRC), Tina Marvasti (President of CITAC/ACCFC) and Nicola Jones (University of Toronto Clinician Investigator Program Symposium Chair). Dr. Michael Strong, President of the Canadian Institutes of Health Research, delivered the keynote presentation titled “CIHR’s COVID-19 Response and Strategic Planning”. Dr. John Bell (University of Ottawa) received the CSCI Distinguished Scientist Award, Dr. Stanley Nattel (Université de Montréal) received the CSCI-RCPSC Henry Friesen Award (RCPSC; Royal College of Physicians and Surgeons of Canada) and Dr. Meghan Azad (University of Manitoba) received the CSCI Joe Doupe Young Investigator Award. Each scientist delivered talks on their award-winning research. The interactive workshops were “Developing Strategies to Maintain Wellness”, “Understanding the Hidden Curriculum: Power and Privilege in Science and Medicine”, “Hiring a Clinician Scientist Trainee: What Leaders Are Looking For” and “COVID-19: A Case Study for Pivoting Your Research”. The AGM included presentations from clinician investigator trainees nationwide. Over 70 abstracts were showcased, most are summarized in this review, and six were selected for oral presentations.

Purpose: This study aimed to identify potential diagnostic and therapeutic biomakers for the development ofbreast cancer (BC).Methods: GSE86374 dataset containing 159 samples was acquired from the Gene Expression Omnibus (GEO) database followed by differentially expressed genes (DEGs) identification and cluster analysis. Corresponding functional enrichment and protein-protein interaction (PPI) network analyses were performed to identify hub genes. Prognostic evaluation using clinical information obtained from TCGA database and hub genes was conducted to screen for crucial indicators for BC progression. The risk model was established and validated.Results: In total, 186 DEGs were identified and grouped into four clusters: 96 in cluster 1; 69 in cluster 2; 16 in cluster 3; and 5 in cluster 4. Functional enrichment analysis showed that DEGs, including ADH1B in cluster 1, were dramatically enriched in the tyrosine and drug metabolism pathways, while genes in cluster 2, including SPP1 and RRM2, played crucial roles in PI3K-Akt and p53 signalling pathway. SPP1 and RRM2 served as hub genes in the PPI network, resulting in an support vector machine classifier with good accuracy and specificity.Ad ditionally, the results of prognostic analysis suggest that age, metastasis stage, SPP1 and ADH1B were correlated with risk of BC, which was validated by using the established risk model analysis.Conclusion: SPP1, RRM2 and ADH1B appear to play vital roles in the development of BC. Age and TNM stage were also preferentially associated with risk of developing BC. Evaluation of the risk model based on larger sample size and further experimental validation are required.

Purpose: To investigate the therapeutic effects of minocycline combined with tinidazole in the treatment of chronic periodontitis (CP).Methods: Seventy-three CP patients treated May 2018–December 2019 at Yuyao People’s Hospital (Yuyao, China) were enrolled in this study: 34 were treated with minocycline alone (control group; CG) and 39 were treated with a combination of minocycline and tinidazole (observation group; OG). Both groups were treated continuously for four weeks and plaque index (PLI), bleeding index (BI), periodontal pocket depth (PD), periodontal attachment level (PAL) and alveolar bone height were compared before and after treatment. Pain was evaluated using the visual analogue scale (VAS). Levels of TNF-α and IL-6 before and after treatment were determined using an enzyme-linked immunosorbent assay. Adverse reactions were compared.Results: In each group, PLI, BI, PD, PAL and alveolar bone height were lower after treatment (P<0.05), and those in OG were lower than those in CG (P<0.05). TNF-α and IL-6 levels in both groups were lower after treatment (P<0.05), and the levels in serum of the OG were lower than those of the CG (P<0.05). After treatment, the VAS in OG was lower than that of CG (P<0.05). There was no significant difference in adverse reactions between groups (P>0.05).Conclusion: Minocycline combined with tinidazole was more effective in treating CP than minocycline alone. This drug combination improved the periodontal indexes and inflammatory reaction of CP and relieved their pain. No significant difference in adverse reactions was seen.

Purpose: Obstructive sleep apnea (OSA) leads to endothelial dysfunction and platelet hyperactivity, which arelinked to increased risk of cardiovascular disease and implicated in the development of aspirin resistance. We hypothesized that aspirin resistance is prevalent among OSA patients and aimed to explore effects of continuous positive airway pressure (CPAP) therapy on aspirin responsiveness.Methods: In Phase 1, prevalence of aspirin resistance was determined cross-sectionally in a group of OSA patients (n=59) on daily low-dose aspirin (81 mg) taken before entering the study, for primary or secondary prevention. In Phase 2, aspirin responsiveness before and after initiation of CPAP therapy was compared and stratified by endothelial function in a cohort of aspirin-naïve patients with newly diagnosed OSA (n=18).Results: In Phase 1, prevalence of aspirin resistance was 17%; most patients (56%) were on CPAP therapy. In Phase 2, initiation of CPAP therapy was associated with significant improvement in endothelial function (p=0.03). The mean pre-CPAP aspirin resistance units (ARU) was 569 (SD=75). In subjects with endothelial dysfunction (44%), the mean decrease after initiation of CPAP therapy was 43 ARU (SD=81, p=0.18). In contrast, subjects with normal endothelial function experienced the mean decrease of 8 ARU (SD=116, p=0.83).Conclusion: Aspirin resistance may be prevalent among OSA patients. After initiation of CPAP therapy, we observed a trend towards improvement in aspirin responsiveness among patients with endothelial dysfunction. The role of endothelial dysfunction and aspirin resistance should be explored in further studies that focus on the effect of CPAP on cardiovascular outcomes.

While the separate roles of physicians and scientists are well defined, the role of a physician scientist is broad and variable. In today’s society, physician scientists are seen as a hybrid between the two fields and they are, therefore, expected to be key to the translation of biomedical research into clinical care. This article offers a narrative review on physician scientists and endeavours to answer whether there is an ongoing need for physician scientists today. The historical role of physician scientists is discussed and compared with physician scientists of the 21st century. Fundamental differences and similarities between the separate roles of physicians and scientists are examined as well as the current state of bench to bedside research. Finally, the ability of 21st century physician scientists to impact their respective medical and scientific fields in comparison to non-physician scientists will be discussed. This paper speculates as to why numbers of physician scientists are dwindling and uses the COVID-19 pandemic as an example of rapid translational research. Ultimately, we suggest that physician scientists are important and may have the most impact on their field by working to connect bedside and bench rather than simply working separately in the bedside and bench. To do this, physician scientists may need to lead clinical research teams composed of individuals from diverse training backgrounds.

Purpose: This study aimed to screen hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC)-related feature ribonucleic acids (RNAs) and to establish a prognostic model.Methods: The transcriptome expression data of HBV-associated HCC were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus database. Differential RNAs between HBV-associated HCC and normal controls were identified by a meta-analysis of TCGA, GSE55092 and GSE121248. Weighted gene co-expression network analysis was performed to identify key RNAs and modules. A prognostic score model was established using TCGA as a training set by Cox regression analysis and was validated in E-TABM-36 dataset. Additionally, independent prognostic clinical factors were screened, and the function of lncRNAs waspredicted through Gene Set Enrichment Analysis.Results: A total of 710 consistent differential RNAs between HBV-associated HCC and normal controls were obtained, including five lncRNAs and 705 mRNAs. An optimized combination of six differential RNAs (DSCR4, DBH, ECM1, GDAP1, MATR3 and RFC4) was selected and a prognostic score model was constructed. Kaplan-Meier analysis demonstrated that the prognosis of the high-risk and low-risk groups separated by this model was significantly different in the training set and the validation set. Gene Set Enrichment Analysis showed that the co-expression genes of DSCR4 were significantly correlated with neuroactive ligand receptor interactionpathway.Conclusion: A prognostic model based on DSCR4, DBH, ECM1, GDAP1, MATR3 and RFC4 was developed that can accurately predict the prognosis of patients with HBV-associated HCC. These genes, as well as histologic grade, may serve as independent prognostic factors in HBV-associated HCC.

I hope you’re taking care and found some time to relax this summer. A new semester may mean a big transition—some folks are starting their graduate studies, re-entering clerkship, starting residency or entering a fellowship. For some, there will be little or no change at all; but just a continuation of one of the many phases of the physician-scientist training pathway. Whatever stage you’re at, the Clinical Investigator Trainee Association of Canada (CITAC) community is here to support and advocate for you!

Purpose: The use of intravenous immunoglobulins (IVIG) has increased significantly in the last decade causing challenges for blood suppliers to respond to the demand. Indications for which IVIG infusion should be given to critically ill children remain unclear. The objective of this study is to characterize the epidemiology of IVIG use in this population.Methods: We performed a single-center retrospective cohort study of all patients aged between 3 days and 18 years who received at least one IVIG infusion while hospitalized in the pediatric intensive care unit of the Centre hospitalier universitaire (CHU) Sainte-Justine, Montréal Quebec (Canada) between January 1, 2013 and December 31, 2018.Results: One hundred and seventy-two patients received a total of 342 IVIG infusions over the study period. Most common indications for IVIG infusions were staphylococcal or streptococcal toxic shock syndrome (n=53/342, 15.5%), immunoglobulin replacement in chylothorax (n=37/342, 10.9%), prophylaxis following bone marrow transplantation (n=31/342, 9.1%), myocarditis (n=25/342, 7.3%) and post-solid organ transplant complications (n=21/342, 6.1%). The median dose of IVIG per infusion was 0.95 g/kg (IQR 0.5-1.0) and median number of IVIG infusions per patient was one (IQR: 1-2). Seventy-nine percent of IVIG infusions given were administrated for off-label indications with regards to Health Canada recommendations.Conclusion: This study identified the most common indications for IVIG infusion in critically ill children in a tertiary care pediatric intensive care unit. Given the costs, the known adverse events associated with IVIG and the pressure that blood suppliers are facing to meet the demands, clinical trials are needed to evaluate the efficacy and safety of IVIG in conditions where use is significant.

In this issue, Ryan Kirkpatrick and Gordon Boyd speculated on the reasons for the dwindling number of physician scientists in Canada. To help stimulate discussion on this important issue, Clinical and Investigative Medicine invited two distinguished scientists to present their views on this issue.

Purpose: Infliximab (INX) has been approved for treating Crohn disease (CD) for many years, showing promis-ing efficacy in the clinic. However, the efficacy of the drug and the prognosis of CD vary significantly with dif-ferent locations of disease pathology. This study evaluated the efficacy of INX and prognosis in CD in different locations of disease pathology using systematic meta-analysis.

Methods: We used "Infliximab OR Remicade OR Avakine OR Inflectra OR Renflexis OR Remsima OR IgG1k monoclonal antibody" AND "Crohn's disease OR IBD OR inflammatory bowel disease" as search strategies for searching in PubMed, Wanfang and Embase. A systematic meta-analysis for overall proportions was used to analyze the data.

Results: Twelve studies involving 1,978 patients were included. The results confirmed that treatment with INX led to high clinical remission rates (82%, 95% CI: 64%-92%) and low relapse rates (4%, 95% CI: 2%-9%) in patients with CD. Our results also indicated that use of INX in patients with colon only (L2) CD led to lower clinical remission rates, and use of INX in patients with ileum and colon (L3) CD led to higher relapse rates.

Conclusion: Our findings show different remission rates depending on location of the disease and may be useful for clinicians' choice of therapeutics.