Search

Cutaneous T cell lymphoma (CTCL) is a potentially fatal clonal malignancy of T cells primarily affecting the skin. The most common form of CTCL, mycosis fungoides, can be difficult to diagnose, resulting in treatment delay. We performed single-cell and spatial transcriptomics analysis of skin from patients with mycosis fungoides-type CTCL and an integrated comparative analysis with human skin cell atlas datasets from healthy and inflamed skin. We revealed the co-optation of T helper 2 (T H 2) cell-immune gene programs by malignant CTCL cells and modeling of the tumor microenvironment to support their survival. We identified MHC-II + fibroblasts and dendritic cells that can maintain T H 2 cell-like tumor cells. CTCL tumor cells are spatially associated with B cells, forming tertiary lymphoid structure-like aggregates. Finally, we validated the enrichment of B cells in CTCL and its association with disease progression across three independent patient cohorts. Our findings provide diagnostic aids, potential biomarkers for disease staging and therapeutic strategies for CTCL., Competing Interests: Competing interests: In the past 3 years, S.A.T. has received remuneration for scientific advisory board membership from Sanofi, GlaxoSmithKline, Foresite Labs and Qiagen. She is a co-founder of and holds equity in Transition Bio and Ensocell. From 8 January 2024, she has been a part-time employee of GlaxoSmithKline. The remaining authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Trichomonas vaginalis (TV) is the etiological agent of the common non-viral sexually transmitted infection (STI), trichomoniasis. TV can inherently harbour Mycoplasma hominis and Trichomonas vaginalis virus (TVV) species. Endosymbiosis of TV with M. hominis and TVV may contribute to metronidazole resistance in this pathogen. This study determined the prevalence of TVVs across clinical isolates of TV, as well as the symbiosis between TV, TVV, and M. hominis in relation to metronidazole resistance., Methodology: Twenty-one clinical isolates of TV were analysed in this study. The isolates were subjected to drug susceptibility assays using varying concentrations of metronidazole. Nucleic acids (RNA and DNA) were extracted from the isolates for molecular assays. The presence of intracellular M. hominis was determined by 16S rRNA polymerase chain reaction (PCR) with specific primers. The presence of the individual TVVs was determined by PCR using gene specific primers with template cDNA., Results: The prevalence of TVV and M. hominis were 76% (16/21) and 86% (18/21), respectively. No significant associations were observed between the presence of TVV and clinical symptoms. A significant association was noted between the coinfection of TVV4 and M. hominis (p = 0.014). The presence of any TVV was significantly associated with metronidazole susceptibility patterns (p = 0.012). No significant associations were noted between the coinfection of endosymbionts and metronidazole resistance., Conclusions: The information obtained displays the ability of TV to form an endosymbiotic relationship with several microorganisms, simultaneously. Based on these findings, both endosymbionts pose no significant influence on metronidazole resistance., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Rowen Govender, Nonkululeko Mabaso, Nathlee S Abbai.)

Despite perinatal damage to the cerebellum being one of the highest risk factors for later being diagnosed with autism spectrum disorder (ASD), it is not yet clear how the cerebellum might influence the development of cerebral cortex and whether this co-developmental process is distinct between neurotypical and ASD children. Leveraging a large structural brain MRI dataset of neurotypical children and those diagnosed with ASD, we examined whether structural variation in cerebellar tissue across individuals was correlated with neocortical variation during development, including the thalamus as a coupling factor. We found that the thalamus plays a distinct role in moderating cerebro-cerebellar structural coordination in ASD. Notably, structural coupling between cerebellum, thalamus, and neocortex was strongest in younger childhood and waned by early adolescence, mirroring a previously undescribed trajectory of behavioral development between ASD and neurotypical children. Complementary functional connectivity analyses likewise revealed atypical connectivity between cerebellum and neocortex in ASD. This relationship was particularly prominent in a model of cerebellar structure predicting functional connectivity, where ASD and neurotypical children showed divergent patterns. Interestingly, these functional-structural relationships became more prominent with age, while structural effects were most prominent earlier in childhood, and showed significant lateralization. This pattern may suggest a developmental sequence where early uncoordinated structural growth amongst regions is followed by increasingly atypical functional synchronization. These findings provide multimodal evidence in the living brain for a cerebellar diaschisis model of autism, where both increased cerebellar-cerebral structural coupling and altered functional connectivity in cerebro-cerebellar pathways contribute to the ontogeny of this neurodevelopmental disorder., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

There has been considerable financial investment by the for-profit cannabis industry to conduct research on cannabis in Canada. Similar to peer industry counterparts such as the pharmaceutical, alcohol, tobacco, and food industries, there is evidence that for-profit cannabis companies are financially sponsoring research programs and researchers as well as non-financially, such as donating products. However, a large body of research has established that researchers' financial relationships with industries may influence research agendas, outcomes, lead to conflicts of interest, and bias the evidence base. Within a complex, emerging context of legalization, there is limited information on how cannabis researchers negotiate their relationships with the for-profit cannabis industry in Canada. Following a qualitative phenomenological methodology informed by moral experience for bioethics research, we conducted 38 semi-structured interviews with academic researchers, peer researchers, and clinicians with relevant perspectives about Canadian cannabis companies' research activities. We used a codebook approach to thematic analysis which generated three central themes: Navigating Systemic Barriers to Conduct Research; Impressions and Influences; and Guiding Principles for an Ethical Research Process. Our findings suggest that Canadian cannabis researchers tend to be morally ambivalent about cannabis industry sponsorship of research: they are motivated to conduct high quality research and generate evidence for population health benefit, yet they have concerns over the potential for research agenda bias created by these relationships which could be harmful to population health. Participants spoke how they relied heavily on personal values and individual strategies (transparency, value alignment, arms-length association, independence) to determine how they manage cannabis industry relationships. Our findings highlight how the issue of industry-academic relationships is a structural problem, thus individual-level solutions without attention to the relationship itself will only deepen ethical worries about industry-sponsored research., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Coronary artery bypass grafting (CABG) has significantly reduced the morbidity and mortality of patients suffering from ischemic heart disease over its six decades of practice. In recent years, minimally invasive techniques have been increasingly described and utilized, with the promise of providing patients with the same standard of care without the need for the traditional full sternotomy, and in select cases without cardiopulmonary bypass, and thus providing improved recovery metrics. The present systematic review and meta-analysis sought to determine the outcomes of all patients receiving robotic-assisted CABG in an Atlantic patient demographic., Methods: The methods for this systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Four databases were searched, using appropriate search terminology. Meta-analysis using proportions or means, as appropriate, were applied, and were presented as per routine practice. Kaplan-Meier curves were digitized and aggregated using previously reported, validated techniques. Quality assessment and risk of bias of each study were assessed systematically. Patient populations were subcategorized as per established technical definitions., Results: Thirty-five studies were identified through the literature search, with three studies having subgroupings appropriate for separate analysis (yielding 42 data points maximally). A total of 9,078 patients (69% male), with a mean age of 62.3 years, were identified across the study period. On actuarial assessment, survival at yearly assessment from 1-, 2-, 3-, 4- and 5-yearly intervals was determined to be 95%, 94%, 92%, 90%, and 88%, respectively., Conclusions: The present systematic review and meta-analysis demonstrated that short-term mortality, operative time, and admission [intensive care unit (ICU) and overall length of stay] outcomes were encouraging in the Atlantic demographic. Freedom from long-term mortality assessment of a smaller cohort showed encouraging results. A major caveat to the present analysis is the high degree of heterogeneity in the reporting of data. Analysis of future randomized controlled trials will be vital in establishing these procedures as commonplace., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Sacituzumab Govitecan (SG) is an antibody-drug conjugate (ADC) comprised of an anti-Trop-2 IgG1 molecule conjugated to SN-38, the active metabolite of irinotecan, via a pH-sensitive hydrolysable linker. As a result of recent Canadian funding for SG in advanced hormone receptor (HR)-positive breast cancer and triple-negative breast cancer (TNBC), experience with using SG and managing adverse events (AEs) has grown. This review presents a summary of evidence and adverse event recommendations derived from Canadian experience, with SG use in metastatic TNBC for extrapolation and guidance in all indicated settings. SG is dosed at 10 mg/kg on day 1 and day 8 of a 21-day cycle. Compared to treatment of physicians' choice (TPC) the phase III ASCENT and TROPiCS-02 studies demonstrated favorable survival data in unresectable locally advanced or metastatic TNBC and HR-positive HER2 negative metastatic breast cancer, respectively. The most common AEs were neutropenia, diarrhea, nausea, fatigue, alopecia, and anemia. This review outlines AE management recommendations for SG based on clinical trial protocols and Canadian guidelines, incorporating treatment delay, dose reductions, and the use of prophylactic and supportive medications.

Introduction: A variety of procedures for the endoscopic surgical treatment of symptomatic benign prostatic hyperplasia (BPH) refractory to medical therapy have existed for decades. The present study examined trends in surgeon compensation for these treatments within Canada., Methods: The physician fee schedule for BPH surgery across 10 Canadian provinces for the years 2010 and 2023 were obtained. A descriptive study examined first the provincial reimbursement for transurethral resection of prostate (TURP) and laser ablative/enucleation surgery; second, the difference in TURP reimbursement between 2010 and 2023; and third, the annual change in TURP reimbursement juxtaposed with the annual change in the provincial Consumer Price Index (CPI) and annual salary for the working population aged 35-44., Results: Seven of 10 Canadian provinces reimburse laser BPH surgery equally to TURP. The average provincial TURP reimbursement is $545, ranging from $451 in Ontario to $688 in Saskatchewan. Since 2010, TURP reimbursement has varied by province from a 0% net change in Ontario to an increase of 21% in Nova Scotia. Reimbursement for TURP has increased at a slower pace than the local CPI, and for half of the provinces at a slower pace than the annual salary for people aged 35-44., Conclusions: The compensation model for endoscopic BPH surgery does not have a unified structure in Canada that is consistent across provinces, nor does it keep up with inflation, possibly impacting future recruitment, increasing geographic disparities, and most importantly, limiting the adoption of new BPH therapies.

The escalating antibiotic resistance rates in Neisseria gonorrhoeae ( N. gonorrhoeae ) are now a grave concern. There is a critical need for alternative treatment options for infection since N. gonorrhoeae has developed resistance to multiple antibiotics used for treatment. In this study, plant nanoemulsions from Ocimum tenuiflorum , Moringa oleifera , and Azadirachta indica were tested for their antimicrobial properties against N. gonorrhoeae. The study also assessed the toxicity of these plant nanoemulsions using human erythrocytes. The plants were sourced from the Botanical Gardens in Durban, South Africa. Nanoemulsions were produced from the dried plants using established methods. The nanoemulsion-based plant extracts were tested against laboratory (World Health Organization (WHO) strains) and clinical isolates of N. gonorrhoeae using the disk diffusion method. All six isolates had zones of inhibition for the 1000  μ M concentration for all three nanoemulsion-based plant extracts. No zones of inhibition were observed for 100  μ M, 10  μ M, and 1  μ M nanoemulsion concentrations for five of the isolates. Isolate G176 had zones of inhibition at 1000  μ M and 100  μ M concentrations for the nanoemulsions of Ocimum tenuiflorum . Both the WHO strains had zones of inhibition appearing at the 1000  μ M concentration. For the WHO Y strain, zones of inhibition for both 1000  μ M and 100  μ M concentrations were observed for the nanoemulsions of Ocimum tenuiflorum and Azadirachta indica . According to the analysis, there was 0% haemolytic activity observed which suggests the nontoxic nature of the extracts. This study showed that the nanoemulsion and plant mix may potentially be used as a safer alternative to treat gonorrhoea., Competing Interests: The authors declare that they have no conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Deshanta Naicker et al.)

Introduction: The COVID-19 pandemic positioned healthcare systems in North America at the epicentre of the crisis, placing inordinate stress on clinicians. Concurrently, discussions about structural racism, social justice and health inequities permeated the field of medicine, and society more broadly. The confluence of these phenomena required rapid action from continuing professional development (CPD) leaders to respond to emerging needs and challenges., Methods: In this qualitative study, researchers conducted 23 virtual semistructured interviews with CPD leaders in Canada and the USA. Interview audiorecordings were transcribed, deidentified and thematically analysed., Results: This study revealed that the CPD leaders attributed the pandemic as illuminating and exacerbating problems related to clinician wellness; equity, diversity and inclusion; and health inequities already prevalent in the healthcare system and within CPD. Analysis generated two themes: (1) From heroes to humans: the shifting view of clinicians and (2) Melding of crises: an opportunity for systemic change in CPD., Discussion: The COVID-19 pandemic increased recognition of burn-out and health inequities creating momentum in the field to prioritise and restrategise to address these converging public health crises. There is an urgent need for CPD to move beyond mere discourse on these topics towards holistic and sustainable actionable measures., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The onset of the COVID-19 pandemic catalysed a monumental shift in the field of continuing professional development (CPD). Prior to this, the majority of CPD group-learning activities were offered in-person. However, the pandemic forced the field to quickly pivot towards more novel methods of learning and teaching in view of social distancing regulations. The purpose of this study was to obtain the perspectives of CPD leaders on the impact of the pandemic to elucidate trends, innovations, and potential future directions in the field., Methods: Semi-structured interviews were conducted between April-September 2022 with 23 CPD leaders from Canada and the USA. Interviews were audio-recorded, transcribed, and de-identified. A thematic analysis approach was used to analyse the data and generate themes., Results: Participants characterised COVID-19 as compelling widespread change in the field of CPD. From the interviews, researchers generated six themes pertaining to the impact of the pandemic on CPD: (1) necessity is the mother of innovation, (2) the paradox of flexibility and accessibility, (3) we're not going to unring the bell, (4) reimagining design and delivery, (5) creating an evaluative culture, and (6) a lifeline in times of turmoil., Conclusion: This qualitative study discusses the impact of the pandemic on the field of CPD and leaders' vision for the future. Despite innumerable challenges, the pandemic created opportunities to reform design and delivery. Our findings indicate a necessity to maintain an innovative culture to best support learners, to improve the healthcare system, and to prepare for future emergencies., (© 2024. The Author(s).)

Competing Interests: We declare no competing interests.

Background: Recovery Colleges (RCs) are mental health and well-being education centres where people come together and learn skills that support their wellness. Co-production, co-learning and transformative education are fundamental to RCs. People with lived experience are recognized as experts who partner with health professionals in the design and actualization of educational programming. The pandemic has changed how RCs operate by necessitating a shift from in-person to virtual offerings. Given the relational ethos of RCs, it is important to explore how the experiences of RC members and communities were impacted during this time. To date, there has been limited scholarship on this topic., Methods: In this exploratory phase of a larger project, we used participatory action research to interview people who were accessing, volunteering and/or working in RCs across Canada. Semi-structured interviews were conducted with twenty-nine individuals who provided insights on what is important to them about RC programming., Results: Our study was conducted amid the COVID-19 pandemic. Accordingly, participants elucidated how their involvement in RCs was impacted by pandemic related restrictions. The results of this study demonstrate that RC programming is most effective when it: (1) is inclusive; (2) has a "good vibe"; and (3) equips people to live a fuller life., Conclusions: The pandemic, despite its challenges, has yielded insights into a possible evolution of the RC model that transcends the pandemic-context. In a time of great uncertainty, RCs served as safe spaces where people could redefine, pursue, maintain or recover wellness on their own terms., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference of the human YS from 3 to 8 postconception weeks by integrating single-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis, we highlight roles in metabolism, coagulation, vascular development, and hematopoietic regulation. We reconstructed the emergence and decline of YS hematopoietic stem and progenitor cells from hemogenic endothelium and revealed a YS-specific accelerated route to macrophage production that seeds developing organs. The multiorgan functions of the YS are superseded as intraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancy proceeds.

Background: Recovery Colleges (RCs) are education-based centres providing information, networking, and skills development for managing mental health, well-being, and daily living. A central principle is co-creation involving people with lived experience of mental health/illness and/or addictions (MHA). Identified gaps are RCs evaluations and information about whether such evaluations are co-created., Aims: We describe a co-created scoping review of how RCs are evaluated in the published and grey literature. Also assessed were: the frameworks, designs, and analyses used; the themes/outcomes reported; the trustworthiness of the evidence; and whether the evaluations are co-created., Methods: We followed Arksey and O'Malley's methodology with one important modification: "Consultation" was re-conceptualised as "co-creator engagement" and was the first, foundational step rather than the last, optional one., Results: Seventy-nine percent of the 43 included evaluations were peer-reviewed, 21% grey literature. These evaluations represented 33 RCs located in the UK (58%), Australia (15%), Canada (9%), Ireland (9%), the USA (6%), and Italy (3%)., Conclusion: Our findings depict a developing field that is exploring a mix of evaluative approaches. However, few evaluations appeared to be co-created. Although most studies referenced co-design/co-production, few described how much or how meaningfully people with lived experience were involved in the evaluation.

Background: The COVID-19 pandemic has disrupted medical care, increased isolation, and exacerbated anxiety in breast cancer patients. Since March 2020, Breastcancer.org experienced a sustained surge in requested pandemic-related information and support. To characterize the pandemic-related experiences of breast cancer patients, we surveyed the Breastcancer.org Community early in the COVID-19 era., Methods: Breastcancer.org Community members were invited to complete an online questionnaire regarding their experience during the pandemic. Self-reported data on demographics, comorbidities, care disruptions, anxiety, coping ability, telemedicine use, and satisfaction with care were collected. Results were analyzed using Stata 16.0 (Stata Corp., Inc)., Results: Included were 568 current and previous breast cancer patients, primarily with U.S. residence. Overall, 43.8% reported at least one comorbidity associated with severe COVID-19 illness and 61.9% experienced care delays. Moderate to extreme anxiety about contracting COVID-19 was reported by 36.5%, increasing with number of comorbidities (33.0% vs. 55.4%, p = 0.021), current breast cancer diagnosis (30.4% vs. 42.5%, p = 0.011), and poorer coping ability (15.5% vs. 53.9%, p < 0.0001). Moderate to extreme anxiety about cancer care disruptions was reported by 29.1%, increasing with current breast cancer diagnosis (19.1% vs. 38.9%, p < 0.0001), actual delayed care (18.9% vs. 35.3%, p < 0.0001), and poorer coping ability (13.1% vs. 57.7%, p < 0.0001). Most utilized telehealth and found it helpful, but also expressed increased anxiety and subjectively expressed that these were less preferable., Conclusion: Early in the COVID-19 pandemic, anxiety was reported by a large proportion of breast cancer patients, with increased prevalence in those with risk factors. Attention to mental health is critical, as emotional distress not only harms quality of life but may also compromise outcomes., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Aim: To compare evening and overnight hypoglycemia risk after late afternoon exercise with a nonexercise control day in adults with type 1 diabetes using automated insulin delivery (AID). Methods: Thirty adults with type 1 diabetes using AID (Minimed 670G) performed in random order 40 min high intensity interval aerobic exercise (HIE), resistance (RE), and moderate intensity aerobic exercise (MIE) exercise each separated by >1 week. The closed-loop set-point was temporarily increased 2 h pre-exercise and a snack eaten if plasma glucose was ≤126 mg/dL pre-exercise. Exercise commenced at ∼16:00. A standardized meal was eaten at ∼20:40. Hypoglycemic events were defined as a continuous glucose monitor (CGM) reading <70 mg/dL for ≥15 min. Four-hour postevening meal and overnight (00:00-06:00) CGM metrics for exercise were compared with the prior nonexercise day. Results: There was no severe hypoglycemia. Between 00:00 and 06:00, the proportion of nights with hypoglycemia did not differ postexercise versus control for HIE (18% vs. 11%; P  = 0.688), RE (4% vs. 14%; P  = 0.375), and MIE (7% vs. 14%; P  = 0.625). Time in range (TIR) (70-180 mg/dL), >75% for all nights, did not differ between exercise conditions and control. Hypoglycemia episodes postmeal after exercise versus control did not differ for HIE (22% vs. 7%; P  = 0.219) and MIE (10% vs. 14%; P  > 0.999), but were greater post-RE (39% vs. 10%; P  = 0.012). Conclusions: Overnight TIR was excellent with AID without increased hypoglycemia postexercise between 00:00 and 06:00 compared with nonexercise days. In contrast, hypoglycemia risk was increased after the first meal post-RE, suggesting the importance of greater vigilance and specific guidelines for meal-time dosing, particularly with vigorous RE. ACTRN12618000905268.

Context: Patients with mutations in thyroid hormone transporter MCT8 have developmental delay and chronic thyrotoxicosis associated with being underweight and having cardiovascular dysfunction., Objective: Our previous trial showed improvement of key clinical and biochemical features during 1-year treatment with the T3 analogue Triac, but long-term follow-up data are needed., Methods: In this real-life retrospective cohort study, we investigated the efficacy of Triac in MCT8-deficient patients in 33 sites. The primary endpoint was change in serum T3 concentrations from baseline to last available measurement. Secondary endpoints were changes in other thyroid parameters, anthropometric parameters, heart rate, and biochemical markers of thyroid hormone action., Results: From October 15, 2014 to January 1, 2021, 67 patients (median baseline age 4.6 years; range, 0.5-66) were treated up to 6 years (median 2.2 years; range, 0.2-6.2). Mean T3 concentrations decreased from 4.58 (SD 1.11) to 1.66 (0.69) nmol/L (mean decrease 2.92 nmol/L; 95% CI, 2.61-3.23; P < 0.0001; target 1.4-2.5 nmol/L). Body-weight-for-age exceeded that of untreated historical controls (mean difference 0.72 SD; 95% CI, 0.36-1.09; P = 0.0002). Heart-rate-for-age decreased (mean difference 0.64 SD; 95% CI, 0.29-0.98; P = 0.0005). SHBG concentrations decreased from 245 (99) to 209 (92) nmol/L (mean decrease 36 nmol/L; 95% CI, 16-57; P = 0.0008). Mean creatinine concentrations increased from 32 (11) to 39 (13) µmol/L (mean increase 7 µmol/L; 95% CI, 6-9; P < 0.0001). Mean creatine kinase concentrations did not significantly change. No drug-related severe adverse events were reported., Conclusions: Key features were sustainably alleviated in patients with MCT8 deficiency across all ages, highlighting the real-life potential of Triac for MCT8 deficiency., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)