The impact of music, play, and pet therapies in managing pain and anxiety in paediatric patients in hospital: a rapid systematic review.

Background: Hospitalized children face pain and anxiety associated with the environment and procedures. Objective: This review aimed to assess the impact of music, play, pet and art therapies on pain and anxiety in hospitalized paediatric patients. RCTs assessing the impact of music, play, pet, and/or art therapies on pain and/or anxiety in hospitalized paediatric patients were eligible. Methods: Database searching and citation screening was completed to identify studies. A narrative synthesis was used to summarize study findings and certainty of evidence was assessed using GRADE. Of the 761 documents identified, 29 were included spanning music (n = 15), play (n = 12), and pet (n = 3) therapies. Results: A high certainty of evidence supported play in reducing pain and moderate certainty for music and pet. A moderate certainty of evidence supported music and play in reducing anxiety. Conclusion: Complementary therapies utilized alongside conventional medical treatment may mitigate pain and anxiety in hospitalized paediatric patients.

Anti-oppressive pedagogy in medical education: A qualitative study of trainees and faculty.

PURPOSE: Despite the proliferation of interest in health equity and justice in medical education, there is limited research into the practical implementation of pedagogical approaches that align with anti-oppressive practices. This study sought to explore how to integrate anti-oppressive pedagogy into medical education. METHODS: Using constructivist grounded theory, the authors conducted 19 semi-structured interviews with a continuum of medical education stakeholders including learners and faculty in a Canadian context between June and August 2021. Transcripts were iteratively analysed using constant comparative analysis. RESULTS: Findings suggest that existing approaches to anti-oppressive pedagogy in medical education are misaligned with the perceived values, priorities, pace, biomedical focus and hierarchical nature of medical education, and medical practice. Although some learners are motivated to advance anti-oppressive teaching, their motivations are often related to their personal experiences of oppression. Participants suggested that transformative and structural changes are required to effectively integrate anti-oppressive pedagogy into medical education. Suggestions included a shift to community-based learning while ensuring adequate compensation for educators and addressing resistance at individual and institutional levels. CONCLUSION: Anti-oppressive pedagogy does not presently align with existing medical education practices. Effectively integrating anti-oppressive approaches will require individual and institutional reflection on the values and assumptions that underpin the field before progress can be made in a meaningful and sustainable way.

Significance of p53 and presence of differentiated vulvar intra-epithelial neoplasia (dVIN) at resection margin in early stage human papillomavirus-independent vulvar squamous cell carcinoma.

OBJECTIVE: Vulvar squamous cell carcinoma and in situ lesions can be stratified by human papillomavirus (HPV) and TP53 status into prognostic risk groups using p16 and p53 immunohistochemistry. We assessed the significance of vulvar squamous cell carcinoma resection margin positivity for either differentiated vulvar intra-epithelial neoplasia (dVIN) or abnormal p53 immunohistochemistry, and other pathologic variables, in a cohort of patients with HPV-independent (HPV-I) p53 abnormal (p53abn) vulvar squamous cell carcinomas. METHODS: Patients with stage I-II HPV-I p53abn vulvar squamous cell carcinoma with negative invasive margins who did not receive adjuvant radiation from a single institution were included. Tumors underwent margin reassessment using p53 immunohistochemistry. Cases were segregated into (1) morphologic dVIN at margin; or (2) abnormal p53 immunohistochemistry staining at margin without morphologic dVIN (p53abn immunohistochemistry); or (3) margins negative by morphology and p53 immunohistochemistry. Clinicopathologic/outcome data were collected. RESULTS: A total of 51 patients were evaluated: (1) 12 with dVIN on margin; (2) 12 with p53abn immunohistochemistry on margin without morphologic dVIN; and (3) 27 with margins negative for morphologic dVIN and p53abn immunohistochemistry. The recurrence rate for patients with dVIN or p53abn immunohistochemistry on the margin was equally high at 75% each, compared with 33% with margins negative for morphologic dVIN and p53abn immunohistochemistry (p=0.009). On multivariate analysis, positive in situ margins maintained an association with disease recurrence (p=0.03) whereas invasive margin distance (radial and deep), lymphovascular invasion, and tumor size did not. CONCLUSIONS: Patients with stage I-II HPV-I vulvar squamous cell carcinoma with margins positive for either dVIN or p53abn immunohistochemistry without morphologic dVIN showed increased disease recurrence, regardless of invasive margin distance. These findings show that p53 immunohistochemistry is a useful adjunct for evaluating margin status in HPV-I vulvar squamous cell carcinoma and may support repeat excision for positive in situ margins (dVIN or p53abn immunohistochemistry).

Are we overtreating stage I triple-negative breast cancer in Ontario? A population-based retrospective epidemiological analysis using the ICES database.

Triple-negative breast cancer (TNBC) is associated with inferior outcomes. The use of adjuvant chemotherapy is the mainstay of treatment, and its efficacy was demonstrated to be correlated with tumor size. Different guidelines exist regarding chemotherapy in early-stage TNBC. This study uses ICES database to examine the outcomes of the use of adjuvant chemotherapy in stage I TNBC in Ontario stratified by tumor size. Records of TNBC patients diagnosed in 2012 to 2014 were collected from ICES database. Stage I patients were analyzed by tumor size: T1a (≤ 0.5 cm), T1b (> 0.5 cm and ≤ 1.0 cm), and T1c (> 1.0 cm and ≤ 2.0 cm). Kaplan-Meier curves, log-rank test statistic, and Cox's proportional hazard regression were used to compare differences in overall survival (OS) between chemotherapy and no-chemotherapy groups. Of 610 patients, 183 had tumor sizes ≤ 1 cm, representing stages T1aN0M0 and T1bN0M0, and 427 had tumors > 1 cm to 2 cm, representing stage T1cN0M0. Patients with tumors ≤ 1 cm who received chemotherapy did not have a significant difference in OS compared to the no-chemotherapy group (p = 0.41, hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.021-2.5). However, patients with tumor sizes > 1 cm to 2 cm who received chemotherapy demonstrated significantly better OS compared to those without (p = 0.023, HR = 0.40, 95% CI 0.16-0.86). Patients with TNBC stage T1cN0M0 should receive adjuvant chemotherapy. For TNBC tumors ≤ 1 cm, avoidance of chemotherapy can be considered. Prospective research should further investigate the efficacy of chemotherapy in TNBC stages T1a-bN0M0.Trial Registration University of Windsor REB#16-119.

Molecular subtypes of clear cell carcinoma of the endometrium: Opportunities for prognostic and predictive stratification.

OBJECTIVE: Our aim was to characterize the pathological, molecular and clinical outcomes of clear cell carcinoma of the endometrium (CCC). METHODS: CCC underwent ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification identifying four molecular subtypes: i) 'POLEmut' for ECs with pathogenic POLE mutations, ii) 'MMRd', if there is loss of mismatch repair proteins by immunohistochemistry (IHC), iii) 'p53wt' or iv) 'p53abn' based on p53 IHC staining. Clinicopathologic parameters, immune markers (CD3, CD8, CD79a, CD138, PD-1), ER, L1CAM, and outcomes were assessed. RESULTS: 52 CCCs were classified, including 1 (2%) POLEmut, 5 (10%) MMRd, 28 (54%) p53wt and 18 (35%) p53abn. Women with p53abn and p53wt CCCs were older than women with MMRd and POLEmut subtypes. p53wt CCC were distinct from typical p53wt endometrioid carcinomas; more likely to arise in older, thinner women, with advanced stage disease, LVSI and lymph node involvement, and a higher proportion ER negative, L1CAM overexpressing tumors with markedly worse outcomes. High levels of immune infiltrates (TILhigh) were observed in 75% of the CCC cohort. L1CAM overexpression was highest within p53abn and p53wt subtypes of CCC. CONCLUSION: CCC is a heterogeneous disease encompassing all four molecular subtypes and a wide range of clinical outcomes. Outcomes of patients with POLEmut, MMRd and p53abn CCC are not distinguishable from those of other patients with these respective subtypes of EC; p53wt CCC, however, differ from endometrioid p53wt EC in clinical, pathological, molecular features and outcomes. Thus, p53wt CCC of endometrium appear to be a distinct clinicopathological entity within the larger group of p53wt ECs.

The association between increasing levels of O-GlcNAc and galectins in the liver tissue of hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus).

Post-translational glycosylation of proteins with O-linked ß-N-acetylglucosamine (O-GlcNAcylation) and changes of galectin expression profiles are essential in many cellular stress responses. We examine this regulation in the liver tissue of hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus) representing a biological model of hypometabolism and physiological stress resistance. The tissue levels of O-GlcNAcylated proteins as well as galectin-1 and galectin-3 proteins detected by immunodot blot assay were significantly lower by 4.6-5.4-, 2.2-2.3- and 2.5-2.9-fold, respectively, in the non-hibernating summer squirrels compared with those in winter, whether hibernating or aroused. However, there were no differences in the expression of genes encoding enzymes involved in O-GlcNAc cycle (O-GlcNAc transferase and O-GlcNAcase) and such galectins as LGALS1, LGALS2, LGALS3, LGALS4 and LGALS9. Only the expression of LGALS8 gene in the liver tissue was significantly decreased by 37.6 ± 0.1% in hibernating ground squirrels relative to summer animals. Considering that the expression of a proven genetic biomarker ELOVL6 encoding ELOVL fatty acid elongase 6 was readily upregulated in non-hibernating animals by 11.3-32.9-fold, marginal differential changes in the expression of galectin genes cannot be classified as biomarkers of hibernation. Thus, this study provides evidence that hibernation in Ictidomys tridecemlineatus is associated with increasing O-GlcNAcylation of liver proteins and suggests that the contribution of galectins deserves further studies at the protein level.

Molecular classification defines outcomes and opportunities in young women with endometrial carcinoma.

OBJECTIVE: Approximately 15% of endometrial carcinomas (ECs) arise in young women who may wish to avoid surgical menopause and/or preserve fertility. Our aim was to evaluate the prognostic significance of Proactive Molecular risk classifier for Endometrial Carcinoma (ProMisE) in young (<50 yo) women with EC. METHODS: ProMisE was applied to a retrospective cohort of women with ECs <50 yo at diagnosis, and associations between the four ProMisE molecular subtypes (MMR deficient (MMRd), POLE mutated (POLE), p53 wild type (p53wt), and p53 abnormal (p53abn)) and clinicopathological parameters, including outcomes, were assessed. RESULTS: Of 257 ECs, there were 48 (19%) MMRd, 34 (13%) POLE, 164 (64%) p53wt and 11 (4%) p53abn. ProMisE subtypes were associated with differences in all measured clinicopathological parameters except for presence of synchronous ovarian tumours and fertility. Age at diagnosis was youngest and BMI highest in women with p53wt ECs. MMRd and p53abn tumours were more likely to be advanced stage (III/IV), high-risk (ESMO), and receive chemotherapy. ProMisE subtypes were strongly associated with outcomes (overall, disease-specific, and progression-free survival (p < 0.0001 for all)). Advanced stage, grade, LVSI, myometrial invasion and ESMO risk groups showed associations with some but not all survival parameters. ProMisE maintained a strong association with OS and DSS on multivariable analysis. CONCLUSIONS: ProMisE molecular classification is prognostic in young women with EC, enabling early stratification and risk assignment to direct care. Further studies can assess response to therapy, fertility, and cancer-related outcomes within the framework of molecular subtype.