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Bone marrow aspirate showed diffuse infiltration by a population of monomorphic cells with scant cytoplasm, markedly increased nuclear-to-cytoplasmic ratio, and numerous indistinct nucleoli. Bone marrow biopsy confirmed extensive marrow infiltration by a malignant neoplasm with strong and diffuse expression of synaptophysin by immunohistochemistry, consistent with metastases from Merkel Cell carcinoma., (© 2024 The Authors. International Journal of Laboratory Hematology published by John Wiley & Sons Ltd.)

Myelodysplastic neoplasms (MDS) with ring sideroblasts (RS) are diagnosed via bone marrow aspiration in the presence of either (i) ≥15% RS or (ii) 5-14% RS and an SF3B1 mutation. In the MEDALIST trial and in an interim analysis of the COMMANDS trial, lower-risk MDS-RS patients had decreased transfusion dependency with luspatercept treatment. A total of 6817 patients with suspected hematologic malignancies underwent molecular testing using a next-generation-sequencing-based genetic assay and 395 MDS patients, seen at our centre from 1 January 2018 to 31 May 2023, were reviewed. Of these, we identified 39 evaluable patients as having lower-risk MDS with SF3B1 mutations: there were 20 (51.3%) males and 19 (48.7%) females, with a median age of 77 years (range of 57 to 92). Nineteen (48.7%) patients had an isolated SF3B1 mutation with a mean variant allele frequency of 35.2% +/- 8.1%, ranging from 7.4% to 46.0%. There were 29 (74.4%) patients with ≥15% RS, 6 (15.4%) with 5 to 14% RS, one (2.6%) with 1% RS, and 3 (7.7%) with no RS. Our study suggests that a quarter of patients would be missed based on the morphologic criterion of only using RS greater than 15% and supports the revised 2022 definitions of the World Health Organization (WHO) and International Consensus Classification (ICC), which shift toward molecularly defined subtypes of MDS and appropriate testing.

Graft versus host disease is a rare but deadly complication of solid organ transplant. Clinical features of graft-versus-host-disease are non-specific, which may lead to delayed diagnosis as more common conditions including infections or drug reactions are considered. We describe a 54-year-old male patient who underwent liver transplantation for alcohol use disorder-related cirrhosis and developed acute graft-versus-host disease. Initial clinical presentation included dermatitis, bone marrow failure and enteritis. Results of skin biopsy and cytogenetic studies were consistent with liver transplant-associated acute graft-versus-host disease. The importance of this case is to highlight to transplant physicians and surgeons the challenges of diagnosing graft-versus-host-disease. In our case, pre-existing partnerships among the liver and hematopoietic stem cell transplant teams, transfusion medicine specialists, critical care specialists and facilitated timely communication relevant to confirming graft-versus-host disease. We propose an algorithm to assist in the workup of suspected graft-versus-host disease. Because this condition is characterized by high mortality, a high index of suspicion is imperative for prompt diagnosis and optimal management of the donor-recipient immune interaction when patients present with classic clinical features.

Background: Idiopathic pulmonary fibrosis (IPF) is associated with increased expression of cyclin-dependent kinase inhibitors such as p16 and p21, and subsequent induction of cell cycle arrest, cellular senescence, and pro-fibrotic gene expression. We sought to link p16-expression with a diagnosis of IPF or other fibrotic interstitial lung diseases (ILDs), radiographic pattern, senescent foci-specific gene expression, antifibrotic therapy response, and lung transplant (LTx)-free survival., Methods: Eighty-six cases of fibrosing ILD were identified with surgical lung biopsy. Immunohistochemistry for p16 was performed on sections with the most active fibrosis. p16-positive foci (loose collection of p16-positive fibroblasts with overlying p16-positive epithelium) were identified on digital slides and quantified. Cases were scored as p16-low (≤ 2.1 foci per 100 mm 2 ) or p16-high (> 2.1 foci per 100 mm 2 ). Twenty-four areas including senescent foci, fibrotic and normal areas were characterized using in situ RNA expression analysis with digital spatial profiling (DSP) in selected cases., Results: The presence of p16-positive foci was specific for the diagnosis of IPF, where 50% of cases expressed any level of p16 and 26% were p16-high. There was no relationship between radiographic pattern and p16 expression. However, there was increased expression of cyclin-dependent kinase inhibitors, collagens and matrix remodeling genes within p16-positive foci, and cases with high p16 expression had shorter LTx-free survival. On the other hand, antifibrotic therapy was significantly protective. DSP demonstrated that fibroblastic foci exhibit transcriptional features clearly distinct from that of normal-looking and even fibrotic areas., Conclusions: We demonstrated the potential clinical applicability of a standardized quantification of p16-positive fibroblastic foci. This method identifies an IPF phenotype associated with foci-specific upregulation of senescence-associated and matrix remodeling gene expression. While these patients have reduced LTx-free survival, good response to antifibrotic therapies was observed in those who were treated., (© 2022. The Author(s).)

Purpose: The Clinician Investigator Trainee Association of Canada/ Association des cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) recently published the first survey to assess factors contributing to trainee satisfaction. One key finding is that increased level of mentorship strongly correlates with overall satisfaction; however, while 98% of respondents reported mentorship as important to success, more than 60% expressed some dissatisfaction with the mentorship received. To help address this discrepancy, we reviewed mentorship in academic medicine, focusing on clinician-investigator trainees, and distilled a set of recommendations for mentors, mentees and institutions., Source: OVID and manual curation based on the search terms 'mentorship' AND 'education, medical and research' identified 198 articles. Two authours independently reviewed both titles and abstracts and narrowed them down to 75 articles, based on relevance to mentorship in academic medicine. Consensus resulted in the selection of 19 articles for detailed review. Principal findings and Conclusion: Mentorship is beneficial at each training stage and is associated with greater research productivity, career retention and promotion. Nevertheless, more rigorous studies are needed, especially regarding cost-effectiveness. Studies have identified the characteristics of good mentors, including the ability to ensure open communication, ability to maintain confidentiality and ability to ensure that there is no mentor-mentee competition. Similarly, the characteristics of good mentees have been identified as the ability to take ownership of a project and the ability to build a network or team of mentors. The literature has also identified the actions that institutions can take to facilitate mentorship, which include mentor training and recognizing mentorship through awards.

The 2013 joint Canadian Society of Clinician Investigators (CSCI)-Clinical Investigator Trainee Association of Canada/Association des cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) annual general meeting(AGM) was held in Ottawa, September 2013. The symposium focused on "Applications of the 'omics' to Clinical Practice", with presentations from Drs. William T. Gibson (University of British Columbia), Julie Ho (University of Manitoba) and David Hwang (University of Toronto), discussing topics of genome, proteome and the microbiome, respectively. Other highlights from the 2013 AGM include presentations by Dr. Salim Yusuf (McMaster University, 2013 CSCI-RCPSC Henry Friesen Award winner), Dr. Gary Lewis (University of Toronto, 2013 CSCI Distinguished Scientist Award winner) and Dr. Michael Taylor (University of Toronto, 2013 Joe Doupe Award winner). The CSCI/CITAC/Friends of CIHR Joint Symposium consisted of presentations from Drs. John Bell (University of Ottawa), Dan Drucker (University of Toronto) and Heather J. Dean (University of Manitoba). Finally, the meeting ended with the presentation "The Power of an Idea to Bring Ideas to Power" by Dr. Harvey V. Fineberg (President, U.S. Institute of Medicine), the winner of the 2013 Henry Friesen International Prize. Also presented at the conference was research by clinician investigator (CI) trainees from across Canada; ie., those enrolled in MD/MSc, MD/PhD or Clinician Investigator Program(CIP) programs. Canadian trainees' research extended beyond the pillar of biomedical research, covering the spectrum between basic and clinical research, with a focus on the causes of significant morbidity and mortality for Canadians, including cancers, infectious diseases and other maladies. It is this research that we have summarized in this review.

There is an increasing demand of functional foods in developed countries. Yogurt plays an important role in the management of blood pressure. Several bioactive peptides isolated from Allium sativum or fish collagen have shown antihypertensive activity. Thus, in the present study the effects of A. sativum and/or Fish Collagen (FC) on proteolysis and ACE inhibitory activity in yogurt (0, 7 and 14 day) and cheese (0, 14 and 28 day) were investigated. Proteolytic activities were the highest on day 7 of refrigerated storage in A. sativum-FC-yogurt (337.0 +/- 5.3 microg g(-1)) followed by FC-yogurt (275.3 +/- 2.0 microg g(-1)), A. sativum-yogurt (245.8 +/- 4.2 microg g(-1)) and plain-yogurt (40.4 +/- 1.2 microg g(-1)). On the other hand, proteolytic activities in cheese ripening were the highest (p < 0.05) on day 14 of storage for plain and A. sativum-cheeses (411.4 +/- 4.3 and 528.7 +/- 1.6 microg g(-1), respectively). However, the presence of FC increased the proteolysis to the highest level on day 28 of storage for FC- and A. sativum-FC cheeses (641.2 +/- 0.1 and 1128.4 +/- 4.5 microg g(-1), respectively). In addition, plain- and A. sativum-yogurts with or without FC showed maximal inhibition of ACE on day 7 of storage. Fresh plain- and A. sativum-cheeses showed ACE inhibition (72.3 +/- 7.8 and 50.4 +/- 1.6 % respectively), the presence of FC in both type of cheeses reduced the ACE inhibition to 62.9 +/- 0.8 and 44.5 +/- 5.0%, respectively. However, refrigerated storage increased ACE inhibition in cheeses (p < 0.05 on day 28) in the presence of FC more than in the absence. In conclusion, the presence of FC in A. sativum-yogurt or cheese enhanced the proteolytic activity. Thus, it has potential in the development of an effective dietary strategy for hypertension associated cardiovascular diseases.