Moncton Hospital

The introduction of immune checkpoint inhibitors (ICI) as first-line therapy in the treatment of non-small cell lung cancer has dramatically improved response rates. However, more than half of NSCLC patients receiving ICI fail to have a durable response to treatment and therefore the identification of circulating biomarkers to improve patient stratification is required. Cytokines and chemokines are critical mediators of immune responses, affecting tumor progression and immune evasion mechanisms. Thus, profiling circulating cytokines is particularly important, as these signaling molecules may provide valuable insights into predicting response and resistance to ICI. Twenty-four circulating chemokines and cytokines were profiled in NSCLC patient plasma collected either prior to treatment or while on-treatment with anti-PD1 therapy and correlated to treatment response as well as to progression-free survival (PFS) and overall survival (OS). Sex-disparities in correlations of cytokines to response and survival was analyzed. Regardless of sex, baseline levels of CCL5/RANTES were associated with anti-PD1 treatment response, while CXCL5 was associated with response in males and CXCL10 was elevated in female responders to anti-PD1 treatment. VEGF and CD40L were associated with short PFS and OS, while CCL5 and CXCL5 were correlated to longer PFS and OS. Sex disparities in baseline cytokine levels were also observed. CCL5 was significantly correlated to PFS and OS in females but not males, and CXCL10 was found to be predictive of longer OS in females only. VEGF was found to be a better predictor of response t to anti-PD1 in females, while CXCL12 was found to be associated with short PFS and OS in males but not females. Uniform Manifold Approximation and Projection (UMAP) dimension reduction method and k-means clustering analysis identified a cluster of male patients with short PFS characterized by elevated baseline levels of VEGF, CCL4, CCL5, CCL20, and CXCL2. Plasma cytokine levels can be useful biomarkers for predicting response to anti-PD1 therapy in NSCLC patients. However, the data presented in this study demonstrate that sex needs to be considered as an important variable in biomarker studies in immuno-oncology due to sex disparities in correlations of cytokines to anti-PD1 treatment response.

Parkinson's disease (PD) is the second most common neurodegenerative disease following Alzheimer's disease. Nearly 30 causative genes have been identified for PD and related disorders. However, most of these genes were identified in European-derived families, and little is known about their role in Latin American populations. Our goal was to assess the spectrum and frequency of pathogenic variants in known PD genes in familial PD patients from Latin America. We selected 335 PD patients with a family history of PD from the Latin American Research Consortium on the Genetics of PD. We capture-sequenced the coding regions of 26 genes related to neurodegenerative parkinsonism. Of the 335 PD patients, 324 had sufficient sequencing coverage to be analyzed. We identified pathogenic variants in 41 individuals (12.7%) in FBXO7, GCH1, LRRK2, PARK7, PINK1, PLA2G6, PRKN, SNCA, and TARDBP, GBA1 risk variants in 25 individuals (7.7%), and variants of uncertain significance in another 24 individuals (7.4%) in ATP13A2, ATP1A3, DNAJC13, DNAJC6, GBA1, LRKK2, PINK1, VPS13C, and VPS35. Of the 70 unique variants identified, 19 were more frequent in Latin Americans than in any other population. This is the first screening of known PD genes in a large cohort of patients with familial PD from Latin America. There were substantial differences in the spectrum of variants observed in comparison to previous findings from PD families of European origin. Our data provide further evidence that differences exist between the genetic architecture of PD in Latinos and European-derived populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Single-agent regorafenib is approved in Canada for metastatic colorectal cancer (mCRC) patients who have failed previous lines of therapy. Identifying prognostic biomarkers is key to optimizing therapeutic strategies for these patients. In this clinical study (NCT01949194), we evaluated the safety and efficacy of single-agent regorafenib as a second-line therapy for mCRC patients who received it after failing first-line therapy with an oxaliplatin or irinotecan regimen with or without bevacizumab. Using various omics approaches, we also investigated putative biomarkers of response and resistance to regorafenib in metastatic lesions and blood samples in the same cohort. Overall, the safety profile of regorafenib seemed similar to the CORRECT trial, where regorafenib was administered as ≥ 2 lines of therapy. While the mutational landscape showed typical mutation rates for the top five driver genes (APC, KRAS, BRAF, PIK3CA, and TP53), KRAS mutations were enriched in intrinsically resistant lesions. Additional exploration of genomic-phenotype associations revealed several biomarker candidates linked to unfavorable prognoses in patients with mCRC using various approaches, including pathway analysis, cfDNA profiling, and copy number analysis. However, further research endeavors are necessary to validate the potential utility of these promising genes in understanding patients’ responses to regorafenib treatment.

Background: Numerous authors were interested in investigating and identifying the quality indicators for assessing clinical care in HIV and AIDS management.Most of these indicators were established in developed countries settings.Nevertheless, an appropriate fundamental core set of quality indicators for assessing clinical care in HIV and AIDS management for low and middle-income countries' settings is crucial.This study aims to identify existing quality indicators for monitoring and evaluating HIV and AIDS clinical care and propose a fundamental set of quality indicators, considering indicators' local usefulness and relevance.Methods: The authors used CINAHL, PubMed, Google Scholar, and Cochrane database, along with the official websites of organizations dedicated to HIV and AIDS care, aiming to identify relevant articles and information about HIV and AIDS clinical care quality indicators.All studies only based on services set and/or patient insight were excluded, as well as articles without available full text.Each study was assessed using the appropriate Critical Appraisal Skills Programme.(CASP) checklist.The GRADE methodology was applied to rate the quality of evidence.Results: A total of 180 studies were identified through this study; among them, 20 were selected as relevant studies, and 88 AIDS AIDS clinical care quality indicators were retrieved.These quality indicators were distributed in domains as follows: Functional organizational structure (9), initial evaluation and diagnosis (14), screening for opportunistic diseases (17), prevention (7), immunization (5), HIV monitoring (20), and therapy (16).Conclusions: In summary, developing a core set of quality indicators for assessing AIDS AIDS clinical care is important in promoting high-quality healthcare services.It can help to standardize the evaluation of care quality, promote transparency and accountability, and identify areas where improvements are needed.However, careful consideration must be given to ensure that the indicators chosen are relevant, feasible, and reliable.

BackgroundRecent studies have demonstrated the effectiveness of nirmatrelvir-ritonavir in reducing the risk of progression to severe disease among outpatients with mild to moderate coronavirus disease 2019 (COVID-19); however, data are limited regarding the use and role of nirmatrelvir-ritonavir among hospitalized patients. This study describes the use and outcomes of nirmatrelvir-ritonavir among adults hospitalized with COVID-19 in a sentinel network of Canadian acute care hospitals during the Omicron variant phase of the pandemic.MethodsThe Canadian Nosocomial Infection Surveillance Program conducts surveillance of hospitalized patients with COVID-19 in acute care hospitals across Canada. Demographic, clinical, treatment and 30-day outcome data were collected by chart review by trained infection control professionals using standardized questionnaires.ResultsFrom January 1 to December 31, 2022, 13% (n=490/3,731) of adult patients (18 years of age and older) hospitalized with COVID-19 in 40 acute care hospitals received nirmatrelvir-ritonavir either at admission or during hospitalization. Most inpatients who received nirmatrelvir-ritonavir, 79% of whom were fully vaccinated, had at least one pre-existing comorbidity (97%) and were of advanced age (median=79 years). Few were admitted to an intensive care unit (2.3%) and among the 490 nirmatrelvir-ritonavir treated inpatients, there were 13 (2.7%) deaths attributable to COVID-19.ConclusionThese findings from a large sentinel network of Canadian acute-care hospitals suggest that nirmatrelvir-ritonavir is being used to treat adult COVID-19 patients at admission who are at risk of progression to severe disease or those who acquired COVID-19 in hospital. Additional research on the efficacy and indications for nirmatrelvir-ritonavir use in hospitalized patients is warranted to inform future policies and guidelines.

In 2017, our tertiary hospital-based imaging practice transitioned from score-based peer review to the peer learning methodology for learning and improvement. In our subspecialized practice, peer learning submissions are reviewed by domain experts, who then provide feedback to individual radiologists, curate cases for group learning sessions, and develop associated improvement initiatives. In this paper, we share lessons learned from our abdominal imaging peer learning submissions with the assumption that trends in our practice likely mimic others', and hope that other practices can avoid future errors and elevate the level of the quality of their own performance. Adoption of a nonjudgmental and efficient method to share peer "learning opportunities" and "great calls" has increased participation in this activity and increased transparency into our practice, thus allowing for visualization of trends in performance. Peer learning allows us to bring our own individual knowledge and practices together for group review in a collegial and safe environment. We learn from each other and decide how to improve together.

Therapeutic hypothermia (TH) is the gold-standard treatment for moderate and severe neonatal encephalopathy (NE). Care during TH has implications for long-term outcomes. Outcome variability exists among neonatal intensive care units (NICUs) in Canada, but care variations are not understood well. This study examines variations in care practices for neonates with NE treated with TH in NICUs across Canada. A non-anonymous, web-based questionnaire was emailed to tertiary NICUs in Canada providing TH for NE to assess care practices during the first days of life and neurodevelopmental follow-up. Ninety-two percent (24/26) responded. Centres followed national guidelines regarding the use of the modified Sarnat score to assess the initial severity of NE, the need to initiate TH within the first 6 h of birth, and the importance of follow-up. However, other practices varied, including ventilation mode, definition/treatment of hypotension, routine echocardiography, use of sedation, use of electroencephalogram (EEG), MRI timing, placental analysis, and follow-up duration. NICUs across Canada follow available national guidelines, but variations exist in practices for managing NE during TH. Development and implementation of a consensus-based care bundle for neonates during TH may reduce practice variability and improve outcomes. This survey describes the current HIE care practices and variation among tertiary centres in Canada. Variations exist in the care of neonates with NE treated with TH in NICUs across Canada. This paper Identifies areas of variation that are not discussed in detail in the national guidelines and will help to set up quality improvement initiatives. Elucidating the variation in care practices calls for the creation and implementation of a national, consensus-based care bundle, with the objective to improve the outcomes of these critically ill neonates.