Cardiovascular collapse and McConnell's sign as early manifestations of leucostasis.

A man in his late 70s with chronic myelomonocytic leukaemia presented for evaluation of acute leukaemic transformation and initiation of cytoreductive therapy after being found to have asymptomatic hyperleucocytosis. Within 24 hours, the patient developed vasopressor-refractory shock, severe lactic acidosis and multiorgan failure. Serial echocardiographic assessments revealed interval enlargement of the right ventricle with development of the McConnell's sign, and abdominal CT showed diffuse bowel wall thickening, likely due to ischaemia. CT angiography excluded pulmonary embolism or occlusion of intra-abdominal arteries. Despite aggressive care, the patient died from cardiovascular collapse within 8 hours of the onset of hypotension. An autopsy revealed extensive infiltration of early myeloid cells in pulmonary, myocardial, hepatic and intestinal microvasculature. This case illustrates different mechanisms by which leucostasis causes acute cardiovascular collapse and stresses the emergent nature of this diagnosis.

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Here, near-infrared auto-photoacoustic (NIRAPA) imaging is shown to detect plaque components and, when combined with ultrasound imaging, to differentiate stable and vulnerable plaque. In an ex vivo study of photoacoustic imaging of excised plaque from 25 patients, 88.2% sensitivity and 71.4% specificity were achieved using a clinically-relevant protocol. In order to determine the origin of the NIRAPA signal, immunohistochemistry, spatial transcriptomics and spatial proteomics were co-registered with imaging and applied to adjacent plaque sections. The highest NIRAPA signal was spatially correlated with bilirubin and associated blood-based residue and with the cytoplasmic contents of inflammatory macrophages bearing CD74, HLA-DR, CD14 and CD163 markers. In summary, we establish the potential to apply the NIRAPA-ultrasound imaging combination to detect vulnerable carotid plaque and a methodology for fusing molecular imaging with spatial transcriptomic and proteomic methods.

Combined near infrared photoacoustic imaging and ultrasound detects vulnerable atherosclerotic plaque.

Atherosclerosis is an inflammatory process resulting in the deposition of cholesterol and cellular debris, narrowing of the vessel lumen and clot formation. Characterization of the morphology and vulnerability of the lesion is essential for effective clinical management. Photoacoustic imaging has sufficient penetration and sensitivity to map and characterize human atherosclerotic plaque. Here, near infrared photoacoustic imaging is shown to detect plaque components and, when combined with ultrasound imaging, to differentiate stable and vulnerable plaque. In an ex vivo study of photoacoustic imaging of excised plaque from 25 patients, 88.2% sensitivity and 71.4% specificity were achieved using a clinically-relevant protocol. In order to determine the origin of the near-infrared auto-photoacoustic (NIRAPA) signal, immunohistochemistry, spatial transcriptomics and proteomics were applied to adjacent sections of the plaque. The highest NIRAPA signal was spatially correlated with bilirubin and associated blood-based residue and inflammatory macrophages bearing CD74, HLA-DR, CD14 and CD163 markers. In summary, we establish the potential to apply the NIRAPA-ultrasound imaging combination to detect vulnerable carotid plaque.

In vivo visualization and molecular targeting of the cardiac conduction system.

Accidental injury to the cardiac conduction system (CCS), a network of specialized cells embedded within the heart and indistinguishable from the surrounding heart muscle tissue, is a major complication in cardiac surgeries. Here, we addressed this unmet need by engineering targeted antibody-dye conjugates directed against the CCS, allowing for the visualization of the CCS in vivo following a single intravenous injection in mice. These optical imaging tools showed high sensitivity, specificity, and resolution, with no adverse effects on CCS function. Further, with the goal of creating a viable prototype for human use, we generated a fully human monoclonal Fab that similarly targets the CCS with high specificity. We demonstrate that, when conjugated to an alternative cargo, this Fab can also be used to modulate CCS biology in vivo, providing a proof of principle for targeted cardiac therapeutics. Finally, in performing differential gene expression analyses of the entire murine CCS at single-cell resolution, we uncovered and validated a suite of additional cell surface markers that can be used to molecularly target the distinct subcomponents of the CCS, each prone to distinct life-threatening arrhythmias. These findings lay the foundation for translational approaches targeting the CCS for visualization and therapy in cardiothoracic surgery, cardiac imaging, and arrhythmia management.

Educational Case: Pneumoconiosis.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Educational Case: Tetralogy of Fallot and a Review of the Most Common Forms of Congenital Heart Disease.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Educational Case: Primary Osteosarcoma.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Educational Case: Symptomatic but Unruptured Abdominal Aortic Aneurysm.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.

Trends in Pathology Graduate Medical Education Programs and Positions, 2001 to 2017.

The US medical workforce is facing an impending physician shortage. This shortage holds special concern for pathologists, as many senior practitioners are set to retire in the coming years. Indeed, studies indicate a "pathologist gap" may grow through 2030. As such, it is important to understand current and future trends in US pathology. One key factor is graduate medical education. In this study, we analyzed data from the Accreditation Council of Graduate Medical Education, to determine the change in pathology graduate medical education programs and positions, from 2001 to 2017. We found that pathology programs and positions have increased since the 2001 to 2002 academic year, even after adjusting for population growth. However, this increase is much lower than that of total graduate medical education. Furthermore, many pathology subspecialties have declined in population-adjusted levels. Other subspecialties, such as selective pathology, have grown disproportionately. Our findings may be valuable for understanding the state of US pathology, now and in the future. They imply that more resources-or technological innovations-may be needed for specific pathology programs, in hopes of closing the pathologist gap for both this specialty and its subspecialties.

Mock gynecologic cytology proficiency testing as a milestone assessment tool for anatomic pathology residents.

INTRODUCTION: One of the major aims of the Next Accreditation System is to move toward an outcomes-based evaluation system where each accredited medical residency program must demonstrate that its residents are competent in performing the essential tasks necessary for clinical practice. Because all pathologists who sign-out or screen Papanicolaou (Pap) tests are required to pass an annual 10-slide gynecologic cytology proficiency test (PT), we developed mock PT modules as a tool for assessing competency. MATERIALS AND METHODS: In 2007, we introduced mock proficiency testing with 3 distinct modules, each consisting of 3 10-slide test sets (10 ThinPrep, 10 SurePath, and 10 conventional Pap slides). Each module was administered at 3 different time points. We evaluated the following parameters: (1) performance differences between Pap preparations; (2) performance over time; (3) performance before and after initiation of one-on-one teaching sessions with cytotechnologists in 2009; and (4) quality of test slides. RESULTS: Residents showed improvement over time, and overall scores did not differ significantly among ThinPrep, SurePath, and conventional slide sets. The average score for the first test set was significantly higher for residents who received formal training by a cytotechnologist than for those who did not. Overall, 16 of 90 slides were misclassified by 40% or more of residents, half of which exhibited glandular abnormalities. CONCLUSIONS: The objective assessment provided by mock PT is a useful tool for both faculty and residents.

Thrombotic thrombocytopenic purpura in a child with systemic lupus erythematosus.

We report a child with thrombotic thrombocytopenic purpura (TTP) secondary to systemic lupus erythematosus. The diagnosis was confirmed by low ADAMTS13 activity (<5%) along with the presence of a low titer inhibitor. Her clinical course was complicated by systemic lupus erythematosus, immunosuppressant therapy, and septic shock. She responded to plasma exchange and ADAMTS13 activity levels recovered. This case illustrates the heterogeneity of TTP and the difficulty of making a diagnosis of TTP. ADAMTS13 activity assay can be useful in the differential diagnosis of diseases with clinical features of thrombotic microangiopathy in pediatric patients. However, treatment needs to be decided carefully case-by-case.

Diagnostic challenges in native valve fungal endocarditis producing a massive septic pulmonary embolus.

Diagnosis and treatment of Candida albicans endocarditis can be difficult. We report a case of this rare condition in which a patient on oral fluconazole presented with septic pulmonary emboli without initial echocardiographic evidence of vegetation. Rapid attainment of a tissue diagnosis, along with combined medical surgical treatment proved to be effective for this patient.

Neuroblastoma of unknown primary site with periorbital bone metastasis in a child.

Neuroblastoma is the second most common solid tumor in children. Most tumors arise in the adrenal glands or paravertebral region. Rarely, patients present with metastatic disease but no primary site can be found despite extensive imaging. We report here a patient with a large periorbital bone metastasis and bone marrow involvement but with no known primary site.

Screening for and treatment of polycystic ovary syndrome in teenagers.

Polycystic ovary syndrome (PCOS) usually arises during puberty and is marked by hyperinsulinemia and hyperandrogenism. Adolescents with PCOS are at an increased risk of developing health problems later on in life such as type 2 diabetes, cardiovascular disease, and infertility. Furthermore, the physical signs of PCOS can be detrimental to a teenage girl's self-image. Early diagnosis and treatment of PCOS in adolescents are essential in ensuring adulthood health and restoring self-esteem. Treatments for an adolescent with PCOS include diet and exercise, metformin, and oral contraceptive pills. Each of these options has been shown to be effective in improving certain aspects of PCOS, and probably the best treatment plan involves some combination of them.