Bovine somatotropin increases the pregnancy rate in fixed-time artificial insemination in beef cattle.

This study evaluated the effect of bovine somatotropin (bST) on pregnancy rate (PR) and size of the dominant follicle (DF) on the day of intravaginal progesterone (P4) removal in protocols for fixed-time artificial insemination (FTAI). Bos indicus (Nellore) females (n = 392) were distributed into three groups. The control group (CG; n = 92) received an intravaginal P4 device + estradiol benzoate on day (d)0; prostaglandin F2α on d7 (first application); removal of P4 + estradiol cypionate (EC) + PGF2α (second application) + ultrasound (US) of the DF on d9; the FTAI was performed on d11; and pregnancy diagnosis (PD) was performed on d45. The bST group (bSTG; n = 142) underwent the same protocol as the CG, except that the animals received 125 mg of bST on d7. The equine chorionic gonadotropin (eCG) group (eCGG; n = 158) underwent the same protocol as the CG, except that the animals received 300 IU of eCG on d9. The PRs of the bSTG, eCGG, and CG were 48%, 48%, and 35%, respectively (p < .05); the bSTG and eCGG showed greater PRs, with follicles 6-7.9 mm (p < .05) and 8-8.9 mm in diameter, respectively. The bSTG exhibited a greater dimension of the DF on d9 of the protocol (p < .05). The eCGG had higher PRs with a body condition score (BCS) of 2.5, and the bSTG had a BCS of 3.0 (p < .05). It was concluded that bST increased PR, bST showed better performance in smaller DF and larger follicular diameter on d9 of the protocol, eCG acted better on animals with lower BCSs, and bST can be used in FTAI.

Short Telomere Syndrome presenting with pulmonary fibrosis, liver cirrhosis and hepatopulmonary syndrome: a case report.

BACKGROUND: Idiopathic pulmonary fibrosis is thought to result from aberrant post-injury activation of epithelial cells leading to fibroblast proliferation and activation. A number of genetic aetiologies have been implicated in this disease process, including, among others, the short telomere syndromes. Short telomere syndromes follow an autosomal dominant pattern of inheritance resulting in shortened telomere length, which consequently leads to accelerated cell death. Organs with rapid cell turnover are most affected. CASE PRESENTATION: We describe a case of a 53-year-old man with a chief complaint of cough and dyspnea on exertion. His presentation was otherwise significant for features of accelerated aging, including a history of osteoporosis and early greying, and a family history of pulmonary fibrosis in his father. Pulmonary function testing revealed a restrictive pattern with severely reduced diffusion capacity and high resolution CT of the chest showed diffuse lung disease with mild fibrosis, in pattern suggesting an alternative diagnosis to IPF. Biopsy of the lung was in keeping with chronic fibrosing interstitial pneumonia. Imaging of the abdomen showed splenomegaly, hepatic cirrhosis and portal hypertension. Transthoracic contrast echocardiogram showed intrapulmonary shunting consistent with hepatopulmonary syndrome. Given the constellation of early aging, idiopathic pulmonary fibrosis, cryptogenic cirrhosis and a family history of pulmonary fibrosis in this patient, the Short Telomere Syndrome was suspected. Peripheral blood was sent for Flow-cytometry FISH, which demonstrated granulocyte telomere length below the 10th percentile for the patient's age, consistent with a diagnosis of Short Telomere Syndrome in this clinical context. Targeted genetic testing of mutations known to be associated with short telomere was negative though it was acknowledged that the full spectrum of disease-causing mutations remains unknown. Given the extensive fibrosis on biopsy and his progressive hypoxemia he was treated with mycophenolate and prednisone. Ultimately, he developed progressive respiratory failure and underwent double lung and concurrent liver transplant 18 months after the initial diagnosis was made. CONCLUSIONS: Short Telomere Syndrome is a rare cause of end stage organ disease and testing lacks sensitivity making diagnosis challenging. Organ transplant is still the mainstay of treatment. Nevertheless, disease identification is important because of implications for family member screening and the possibility of future treatment options.

Influence of tropical, subtropical, and temperate climate conditions on seminal redox status and sperm quality parameters in breeding bulls.

This study evaluated the effect of climate change on andrological parameters of beef bulls raised under tropical, subtropical, and temperate conditions. Bull ejaculates were collected to evaluate seminal quality parameters, sperm membrane integrity, and redox status (SOD; GPx; GSH; GRx; CARB; DCF; and SOD/GPx ratio). Bulls located in the temperate region showed a higher sperm motility rate and percentage of viable sperm (P < 0.05). When evaluating regions independently, we observed a lower GPx activity from animals in the tropical region (P < 0.05). In contrast, we found that SOD and GRx activities, GSH content, and CARB oxidative levels were higher in the tropical region, while oxidation values of DCF were lower (P < 0.05). Braford bulls showed higher CARB and DCF levels (1.23 ± 0.61 nmol/mg and 1453.60 ± 828.63 nmol/mg, respectively) compared to Hereford bulls (1.00 ± 0.43 nmol/mg and 1138.70 ± 423.24 nmol/mg, respectively) in the temperate region. However, Nellore bulls showed higher DCF levels (650.50 ± 401.53 nmol/mg) than Braford bulls (409.40 ± 286.97 nmol/mg). In addition, the SOD/GPx ratio was lower in Braford (12.44 ± 7.64 U/mg) compared to Nellore bulls in tropical conditions (87.25 ± 2.83 U/mg). A positive correlation was found in temperate conditions between DCF levels, SOD, and GRx activities (0.51, 0.58; P < 0.01, respectively), as well as in subtropical conditions between DCF levels and GRx activity (0.53; P < 0.01). A negative correlation between the temperature-humidity index and CARB content was found in subtropical and tropical regions (-0.44; P < 0.01). We concluded that Braford breeds showed lower seminal motility, DCF contents and SOD/GPx ratios compared to Nellore bulls in tropical climate conditions. Finally, in temperate environmental conditions, Braford bulls also showed lower seminal motility but higher levels of CARB and DCF contents compared to Hereford bulls. Therefore, the existence of climatic differences between the temperate and tropical regions evaluated affected Braford bulls' seminal motility and seminal redox homeostasis.

Impact of a 1-day urodynamic course on knowledge, perceptions, and attitudes of urology residents.

AIMS: No evidence-informed educational curriculum is available for designing urodynamics (UDS) courses. We evaluated the learning outcomes of a short-lasting urodynamic course for urology residents. METHODS: Urology residents of postgraduate years 4 and 5 (n = 13 and n = 1316, respectively) attended a 1-day urodynamic course. Learning objectives included patient preparation, indication and technique, terminology, trace interpretation, and impact on patient management. Instructional methods consisted of short lectures (3 h) and case-based discussions (7.5 h). Learners' reactions, modifications of perceptions and attitudes, and acquisition of knowledge and skills were assessed by three written tests with a single group, pretest, posttest 1, and posttest 2 design. Tests were conducted precourse, 1 week after, and 4 months after the course. RESULTS: All participants felt more confident in several urodynamic competencies after the course, including patient preparation, urodynamic indication and technique, terminology, trace interpretation, and impact for patient management. These perceptions remained unchanged after 4 months. Most became stricter in the indication of UDS, including 20 (87.0%) at posttest 1 and 8 (66.7%) at posttest 2. The mean number of correct answers in the knowledge evaluation was 52.2% versus 61.4% versus 56.7%, respectively at pretest, posttest 1, and posttest 2; p = 0.535). All participants rated the course as very useful or useful in both posttest evaluations. CONCLUSIONS: Our study demonstrates that a 1-day urodynamic course can promote lasting improvements in self-reported perceptions, attitudes, and urodynamic-related competencies of urology residents. Further studies using evidence-informed educational principles are needed to determine the effect of specific educational interventions on urodynamic competencies in different contexts.

The Hydroalcoholic Extract of Leaves of Mandevilla moricandiana Induces NO-Mediated Vascular Relaxation.

Natural products extracted from plants represent a valuable source of new bioactive substances. Many studies describe the potential of plant products for the treatment of cardiovascular diseases. Species of the Mandevilla genus have been studied for their biological activities, mainly as antioxidant, anti-inflammatory, and vasorelaxant. However, the phytochemical and pharmacological profiles of Mandevilla moricandiana have not been investigated yet. The aim of this study was to evaluate the vasodilator effect of the hydroalcoholic extract of the leaves of M. moricandiana, as well as its chemical profile. Chemical analysis and quantification of major compounds were performed by HPLC analysis. Total flavonoid content was quantified based on rutin equivalents, and major compounds were identified based on HPLC-DAD-MS analysis. M. moricandiana leaf extract-induced vasodilation was investigated in rat aortic rings precontracted with phenylephrine. The total flavonoids were quantified as 3.25 ± 0.11 % w/w of the hydroalcoholic leaf extract, and HPLC-DAD-MS allowed for the identification of luteolin and quercetin glycosides. The maximal relaxant effect of the hydroalcoholic leaf extract was 86.07 ± 1.68 % at a concentration of 30 µg/mL (p < 0.05; n = 6). The concentration of hydroalcoholic extract of the leaves of M. moricandiana necessary to reduce phenylephrine-induced contractions of the endothelium-intact aorta by 50 % was 0.82 ± 0.10 µg/mL. M. moricandiana leaf extract-induced vasodilation was abolished in aortas pretreated with NG-nitro-L-arginine methyl ester and 1H-[1,2,4]oxadiazolo-[4,3-α]quinoxalin-1-one. In addition, diphenhydramine partially inhibited the effect of the hydroalcoholic extract of the leaves of M. moricandiana. Thus, M. moricandiana-induced relaxation depends on the endothelium and on the activation of the nitric oxide/cyclic GMP pathway, with the involvement of endothelial histamine H1 receptors. Luteolin and quercetin glycosides seem to contribute to the extract activity.

Aerogenous metastases: a potential game changer in the diagnosis and management of primary lung adenocarcinoma.

OBJECTIVE: The purposes of this article are to summarize the relevant literature on aerogenous metastasis, explain the putative pathogenetic mechanism of aerogenous spread, present the characteristic imaging and pathologic features, and review the importance of aerogenous spread to staging and clinical management. CONCLUSION: Cumulative evidence suggests that aerogenous spread may exist and is underrecognized. Imaging features are helpful in differentiating possible aerogenous spread of tumor from hematogenous and lymphatic metastases and from synchronous primary tumors. The putative occurrence of intrapulmonary aerogenous metastasis of lung cancer has staging, management, and prognostic implications.

Noninfectious pulmonary complications after hematopoietic stem cell transplantation: practical approach to imaging diagnosis.

Hematopoietic stem cell transplantation (HSCT) is a widely available treatment for a variety of malignant and nonmalignant disorders. The treatment outcome is affected by the type of transplant and is limited by complications secondary to immunosuppression and treatment-related toxicity. Pulmonary complications are very common and follow a predictable timeline that reflects the immunologic status of the patient in the peritransplant period. Until recently, pulmonary complications were largely attributed to infectious causes. However, advances in diagnosis and treatment have led to a shift, and noninfectious complications have emerged as a major cause of morbidity and mortality in this population. With the increasing number of centers that perform HSCT, knowledge of posttransplant noninfectious pulmonary complications has become increasingly relevant. The basic principles of and indications for HSCT are described, and a timeline for the clinical, radiologic, and pathologic manifestations of noninfectious pulmonary complications is presented. Emphasis is given to high-resolution computed tomographic findings and the role of imaging in management of complications. A practical approach is provided to guide imaging interpretation and diagnosis of noninfectious pulmonary complications after HSCT.

Acute Dyspnea With an Infiltrative Tracheal Mass.

CASE PRESENTATION: A 48-year-old woman presented to the ED with a nonproductive cough, shortness of breath, and stridor. She was otherwise healthy and had never used tobacco. The patient was mildly tachycardic but otherwise hemodynamically stable, afebrile, and saturating well on room air. She did not display any signs of increased work of breathing at rest. Although auscultation of her thorax indicated good air entry bilaterally without any adventitious sounds, stridor was elicited with forced expiration.

Competence By Design: a transformational national model of time-variable competency-based postgraduate medical education.

Postgraduate medical education is an essential societal enterprise that prepares highly skilled physicians for the health workforce. In recent years, PGME systems have been criticized worldwide for problems with variable graduate abilities, concerns about patient safety, and issues with teaching and assessment methods. In response, competency based medical education approaches, with an emphasis on graduate outcomes, have been proposed as the direction for 21st century health profession education. However, there are few published models of large-scale implementation of these approaches. We describe the rationale and design for a national, time-variable competency-based multi-specialty system for postgraduate medical education called Competence by Design. Fourteen innovations were bundled to create this new system, using the Van Melle Core Components of competency based medical education as the basis for the transformation. The successful execution of this transformational training system shows competency based medical education can be implemented at scale. The lessons learned in the early implementation of Competence by Design can inform competency based medical education innovation efforts across professions worldwide.

Assessing limits of detection in qualitative methods: A simple implementation of logistic regression in a web-based R Shiny application environment and its potential in toxicology and doping control.

The estimation of limits of detection (LOD) for solely qualitative methods in analytical chemistry may prove challenging because all the approaches with which chemists are familiar require some type of numeric data input. The best model to describe the binary response in these methods (detected/not detected) is a logistic model; however, these models are not easily handled by most of the laboratories and generally demand expensive statistical software packages. In this work, the advantages of applying this approach are discussed and its implementation using commercial spreadsheet software is demonstrated. A free online application based on the R environment using shinyapps was developed and its application was validated and discussed with a dataset of 57 different target compounds analyzed in urine according to the requirements of the World Anti-Doping Agency (WADA). This tool allows free, extremely quick, and easy determinations of LOD in qualitative analyses as well as the determination of the probabilities of detection in any given concentration.

Oncogenic viral DNA related to human breast cancer found on cattle milk and meat.

Bovine leukemia virus (BLV) is a major cause of lymphoma in cattle and has been recently correlated to breast cancer in humans. How and whether BLV might reach humans remains unknown but it could be through cattle-derived milk and meat. Here our aim was to investigate whether BLV DNA could be found in fresh milk and raw meat destined to human consumption and whether anti-BLV antibodies could be detected in human blood at the same geographical region. Milk (n = 36) and meat (n = 54) samples were collected from cows knowingly seropositive or negative to BLV and evaluated by nested PCR targeting BLV tax gene. Human serum samples (n = 900) were tested by ELISA to detect anti-BLV antibodies. BLV DNA was detected in 39 % of the milk samples and in 32 % of meat samples from BLV positive cows. Anti-BLV antibodies were found in 4.1 % of the human serum samples. Our data further supports the hypothesis that BLV might cause a zoonotic infection and indicate that milk and meat from BLV-infected cattle might be considered a potential source of infection to humans.

Benign Metastasizing Leiomyoma in the Lung Presenting in a Phyllodes-Like Pattern Mimicking a Biphasic Tumor: A Case Report.

Primary biphasic tumors of the lung are rare. Lung lesions with a biphasic pattern are far more commonly primary or metastatic soft tissue tumors with entrapped native respiratory epithelium, giving the false impression of a biphasic tumor. We report a case of bilateral benign metastasizing leiomyomas in a 69-year-old female where the tumor cells diffusely entrapped native respiratory glands in a phyllodes-like pattern. The radiographic characteristics and histologic appearance were not immediately diagnostic and covered a wide differential. Reaching the final diagnosis required the use of immunohistochemical studies as well as correlation with the patient's history and radiographic findings. To the best of our knowledge, this is the first report of pulmonary benign metastasizing leiomyoma presenting in a phyllodes-like pattern. This case illustrates the importance of considering entrapment of native lung epithelium in the differential diagnosis of biphasic-appearing lung tumors.

Neuroendocrine differentiation distinguishes basaloid variant of lung squamous cell carcinoma.

BACKGROUND: Neuroendocrine (NE) differentiation is widely studied in non-small cell lung carcinomas (NSCLC) however, its significance remains unclear in basaloid squamous cell carcinomas (B-SqCC). This study aims to assess the extent of NE differentiation in B-SqCC and characterize the underlying molecular process. METHODS: This study evaluated resected B-SqCC, small cell lung cancer (SCLC) and poorly differentiated SqCC (PD-SqCC) from 2005 to 2020 at the Ottawa Hospital. Samples were subject to pathological review, immunohistochemistry (IHC) and survival analysis. Gene expression analysis was performed on B-SqCC samples exhibiting NE+ and NE- regions (paired samples) to identify differentially expressed genes (DEGs). These DEGs were subsequently validated in unpaired B-SqCC and TCGA samples. RESULTS: B-SqCC cases were more likely to exhibit nuclear molding, resetting and peripheral palisading than PD-SqCC. B-SqCC were also more likely to demonstrate NE differentiation compared to PD-SqCC (p = 0.006). Pure basaloid squamous cell carcinoma (PB-SqCC) experienced poorer disease-free survival (HR = 3.12, p = 0.043) adjusted for stage. Molecular characterization of paired B-SqCC samples demonstrated DEGs implicated in NOTCH signaling, SCLC and pulmonary neuroendocrine differentiation. Hierarchical clustering using discovered DEGs in unpaired B-SqCC samples distinguished tumors based on NE status (p = 0.048). Likewise, clustering The Cancer Genome Atlas (TCGA) samples with DEGs distinguished B-SqCC from SqCC samples (p = 0.0094). CONCLUSION: This study provides IHC and molecular evidence of significant NE-differentiation in B-SqCC and demonstrates their aggressive clinical behavior. These findings suggest that B-SqCC are biologically distinct from SqCC and share characteristics with SCLC.

Optimizing the delivery of genetic and advanced diagnostic testing in the province of Ontario: challenges and implications for laboratory technology assessment and management in decentralized healthcare systems.

AIMS: The Canadian province of Ontario provides full coverage for its residents (pop.14.8 M) for hospital-based diagnostic testing. Historical governance of the healthcare system and a legacy scheme of health technology assessment (HTA) and financing has led to a suboptimal approach of adopting advanced diagnostic technology (i.e. protein expression, cytogenetic, and molecular/genetic) for guiding therapeutic decisions. The aim of this research is to explore systemic barriers and provide guidance to improve patient and care provider experiences by reducing delays and inequity of access to testing, while benefitting laboratory innovators and maximizing system efficiency. MATERIALS AND METHODS: A mixed-methods approach including literature review, semi-structured interviews, and a multi-stakeholder forum involving patient representatives (n = 1), laboratory leaders (n = 6), physicians (n = 5), Ministry personnel (n = 4), administrators (n = 3), extra-provincial experts, and researchers (n = 7), as well as pharmaceutical (n = 5) and diagnostic companies (n = 2). The forum considered evidence of good practices in adoption, implementation, and financing laboratory services and identified barriers as well as feasible options for improving advanced diagnostic testing in Ontario. RESULTS: Overarching challenges identified included: barriers to define what is needed; need for a clear approach to adoption; and the need for more oversight and coordination. Recommendations to address these included a shift to an anticipatory system of test adoption, creating a fit-for-purpose system of health technology management that consolidates existing evaluation processes, and modernizing the governance and financing of testing so that it is managed at a care-delivery level. CONCLUSIONS: The proposals for change in Ontario highlight the role that HTA, governance, and financing of health technology play along the continuum of a health technology life cycle within a healthcare system where decision-making is highly decentralized. Resource availability and capacity were not a concern - instead, solutions require higher levels of coordination and system integration along with innovative approaches to HTA.

Histologic and Genotypic Characterization of Lung Cancer in the Inuit Population of the Eastern Canadian Arctic.

Inuit are the Indigenous Arctic peoples and residents of the Canadian territory of Nunavut who have the highest global rate of lung cancer. Given lung cancer's mortality, histological and genomic characterization was undertaken to better understand the disease biology. We retrospectively studied all Inuit cases from Nunavut's Qikiqtani (Baffin) region, referred to the Ottawa Hospital Cancer Center between 2001 and 2011. Demographics were compiled from medical records and tumor samples underwent pathologic/histologic confirmation. Tumors were analyzed by next generation sequencing (NGS) with a cancer hotspot mutation panel. Of 98 patients, the median age was 66 years and 61% were male. Tobacco use was reported in 87%, and 69% had a history of lung disease (tuberculosis or other). Histological types were: non-small cell lung carcinoma (NSCLC), 81%; small cell lung carcinoma, 16%. Squamous cell carcinoma (SCC) represented 65% of NSCLC. NGS on 55 samples demonstrated mutation rates similar to public lung cancer datasets. In SCC, the STK11 F354L mutation was observed at higher frequency than previously reported. This is the first study to characterize the histologic/genomic profiles of lung cancer in this population. A high incidence of SCC, and an elevated rate of STK11 mutations distinguishes this group from the North American population.

Aerogenous Metastasis and Spread Through the Air Spaces - Distinct Entities or Spectrum of the Same Process?

Clinicopathological and imaging studies indicate that metastatic spread of cancer cells through the airways may occur in primary lung cancer. The term aerogenous metastasis was been proposed years before the concept of spread through the airspaces (STAS) was introduced in the current World Health Organization classification. The pathogenesis of STAS has not been fully elucidated. The current definition of STAS is controversial and limited to early stage adenocarcinomas. In this article, existing knowledge on the pathogenesis, histology, imaging findings, and clinical and prognostic significance of these 2 entities is presented.

Dyspnea, focal wheeze, and a slow growing endobronchial tumor.

We describe a case of an otherwise healthy woman who presented with nonspecific respiratory symptoms, but was found to have recurrent focal findings on chest radiograph. Her CT scan showed an endobronchial lesion with distal bronchiectasis which was ultimately diagnosed as a mucoepidermoid carcinoma. In this report we discuss the clinical, radiographic, bronchoscopic and pathologic findings of rarely seen endobronchial mucoepidermoid tumors.

How to Design and Foster Thoracic Oncology Multidisciplinary Cancer Conferences.

In this chapter, the authors review and discuss the literature on multidisciplinary cancer conferences (MCCs, aka tumor boards), clarifying the terminology, showing the evolution of the field, and providing an evidence-based perspective on positive outcomes, best practices, factors influencing the quality of MCCs, evaluation tools to assess the quality of MCCs, and quality improvement interventions for MCCs. The authors then discuss some perspectives from their MCC and initiatives that they undertook to improve the work of their team and the care that they provide to patients in the area of thoracic oncology.

Recognition of Hematopoietic Stem Cell Transplantation and Cellular Therapy Expertise to Promote Care Accessibility: A Formally Credentialed Area of Focused Competence in Canada.

Hematopoietic stem cell transplantation (HSCT) and cellular therapy (CT) exploit the therapeutic potential of manipulated or unmanipulated hematopoietic cells to treat diseases. While initially dedicated to the treatment of hematologic malignancies and disorders, the use of these therapies in several diseases and cancers is currently under investigation. Indications are currently booming. In the midst of this expansion, both the American Society for Transplantation and Cellular Therapy (ASTCT) and the European Society for Blood and Marrow Transplantation (EBMT) have highlighted the global shortage of hematologists adequately trained in this field of high expertise. This shortage in transplant physicians and cellular therapists can significantly impact patients' access to cell-based therapy. To address this unmet need and attract aspiring hematologists to the field of cellular therapy, as well as to standardize training, anticipating this trend, a Canadian national task force aiming to develop a structured academic program in HSCT and CT was created. Workshops were organized to identify and establish the fundamentals of the practice in HSCT and CT. These workshops followed a rigorous process in developing the competency-based training program established by the Royal College. The program begins with the development of the main tasks associated with the practice of the discipline and the evidence that trainees must provide to demonstrate that they can perform these tasks independently (the competence portfolio). It continues with the development of training requirements that summarize the knowledge, skills, and aptitudes required to perform these tasks, followed by specific exposure during training (milestones) essential to demonstrate the acquisition of these skills. HSCT and CT together is now formally recognized as an Area of Focused Competence (AFC) by the Royal College of Physicians and Surgeons of Canada, a national organization that provides oversight of the medical education of specialists in Canada. AFCs are areas of specialty medicine that address a legitimate societal and patient population need previously unmet by the system of primary and subspecialty disciplines. The AFC designation for HSCT and CT provides a standardized curriculum, training experience, and accreditation process to attract young hematologists and promote expertise and quality care to meet the needs of both patients and society. A critical number of highly qualified hematologists will ensure continuing expansion of accessibility to HSCT and CT.

Teaching and assessing intra-operative consultations in competency-based medical education: development of a workplace-based assessment instrument.

Competency-based medical education (CBME) is being implemented worldwide. In CMBE, residency training is designed around competencies required for unsupervised practice and use entrustable professional activities (EPAs) as workplace "units of assessment". Well-designed workplace-based assessment (WBA) tools are required to document competence of trainees in authentic clinical environments. In this study, we developed a WBA instrument to assess residents' performance of intra-operative pathology consultations and conducted a validity investigation. The entrustment-aligned pathology assessment instrument for intra-operative consultations (EPA-IC) was developed through a national iterative consultation and used clinical supervisors to assess residents' performance at an anatomical pathology program. Psychometric analyses and focus groups were conducted to explore the sources of evidence using modern validity theory: content, response process, internal structure, relations to other variables, and consequences of assessment. The content was considered appropriate, the assessment was feasible and acceptable by residents and supervisors, and it had a positive educational impact by improving performance of intra-operative consultations and feedback to learners. The results had low reliability, which seemed to be related to assessment biases, and supervisors were reluctant to fully entrust trainees due to cultural issues. With CBME implementation, new workplace-based assessment tools are needed in pathology. In this study, we showcased the development of the first instrument for assessing resident's performance of a prototypical entrustable professional activity in pathology using modern education principles and validity theory.