Continued Positive Job Search Experience for New Pathologists Seeking First Employment During the COVID-19 Pandemic (2020-2022).

CONTEXT.­: As pathologists retire and leave the field, it is critical to accurately capture employment trends for new-in-practice pathologists. There is always interest in the job market for newly graduated pathology trainees and prospective pathology trainees, but it is unclear how the COVID-19 pandemic may have affected the job search experience. OBJECTIVE.­: To provide an update on trends gleaned from a survey of pathology graduates' job search experiences during the COVID-19 pandemic. DESIGN.­: We analyzed data from an annual job search survey sent by the College of American Pathologists Graduate Medical Education Committee between 2020 and 2022 to College of American Pathologists junior members and fellows in practice 3 years or less actively looking for a nonfellowship position. Various indicators of the job search experience were compared year to year and with the data previously published 2017 to 2019 and 2012 to 2016. RESULTS.­: Analysis revealed continued positive trends between the 2020 to 2022 data and the data from 2017 to 2019 and 2012 to 2016. This includes continued ease in finding positions, continued availability of jobs in the subspecialty of choice, continued satisfaction with the positions accepted, and, notably, higher starting salaries. CONCLUSIONS.­: Despite the many challenges of the COVID-19 pandemic, job market trends for newly graduated pathology trainees continue to be favorable with respect to multiple indicators compared with 2 prior periods, 2017 to 2019 and 2012 to 2016.

Leadership perspectives on osteopathic medical school applicants to pathology residency training.

The number of graduating allopathic (MD) medical students matching into pathology has declined in recent years, while the number of osteopathic (DO) medical students has increased modestly, given the rapid expansion of osteopathic medical schools. Nonscholarly publications and materials on the internet often perpetuate negative perceptions of osteopathic physicians. Anecdotally, perspectives exist that some pathology residency programs are not DO-friendly; however, the reasons and how widespread an effect this might be are unclear. Our survey queried pathology chairs and residency program directors about their perceptions of osteopathic applicants and their knowledge of osteopathic medical school/training in general. This study utilized two similar, parallel surveys of pathology chairs and residency program directors with general questions structured around the perceptions and knowledge of both allopathic and osteopathic physicians, their medical training, and the consideration of osteopathic applicants to pathology residency. Pathology residency leaders acknowledge some negative perceptions of osteopathic physicians in the medical profession, the news, and social media. They also have some knowledge and perception gaps regarding osteopathic training and applicants, although experience with training osteopathic physicians as residents has been equivalent to that with allopathic physicians, and consideration appears to be fairly equal for osteopathic applicants. Even though negative perceptions of osteopathic physicians persist in news and social media, our surveys demonstrate that the leadership of pathology residency programs does not hold the same degree of bias and that DOs perform well in allopathic pathology residency programs without evidence of inferior outcomes.

The next phase in patient safety education: Towards a standardized, tools-based pathology patient safety curriculum: A call to action from the Association of Pathology Chairs' Residency Program Directors Section Training Residents in Patient Safety Workgroup.

Patient safety education is a mandated Common Program Requirement of the Accreditation Council for Graduate Medical Education and for the Royal College of Physicians and Surgeons of Canada in all medical residency and fellowship programs. Although many hospitals and healthcare environments have general patient safety education tools for trainees, few to none focus on the unique training milieu of pathologists, including a mix of highly automated and manual error-prone processes, frequent multiplicity of events, and lack of direct patient relationships for error disclosure. We established a national Association of Pathology Chairs-Program Directors Section Workgroup focused on patient safety education for pathology trainees entitled Training Residents in Patient Safety (TRIPS). TRIPS included diverse representatives from across the United States, as well as representatives from pathology organizations including the American Board of Pathology, the American Society for Clinical Pathology, the United States and Canadian Academy of Pathology, the College of American Pathologists, and the Society to Improve Diagnosis in Medicine. Objectives of the workgroup included developing a standardized patient safety curriculum, designing teaching and assessment tools, and refining them with pilot sites. Here we report the establishment of TRIPS as well as data from national needs assessment of Program Directors across the country, who confirmed the need for a standardized patient safety curriculum.

Entrustable Professional Activities in Hematopathology Pathology Fellowship Training: Consensus Design and Proposal.

Hematopathology fellowship education has grown in complexity as patient-centered treatment plans have come to depend on integration of clinical, morphologic, immunophenotypic, molecular, and cytogenetic variables. This complexity is in competition with the need for timely hematopathology care with stewardship of patient, laboratory, and societal resources. Accreditation Council for Graduate Medical Education Milestones provide a guidance document for hematopathology training, but fellows and their educators are in need of a simple framework that allows assessment and feedback of growth toward independent hematopathology practice. Entrustable professional activities provide one such framework, and herein, we provide proposed Hematopathology Fellowship Entrustable Professional Activities based on review of pertinent guidelines and literature, with multiple rounds of expert and stakeholder input utilizing a modified mini-Delphi approach. Ten core entrustable professional activities deemed essential for graduating hematopathology fellows were developed together with skills and knowledge statements, example scenarios, and corresponding Accreditation Council for Graduate Medical Education Milestones. Application of these entrustable professional activities in program design, fellow evaluation, and decisions regarding level of supervision is discussed with consideration of benefits and barriers to implementation. These entrustable professional activities may be used by hematopathology fellowship directors and faculty to provide fellows with timely constructive feedback, determine entrustment decisions, provide the Clinical Competency Committee with granular data to support Milestone evaluations, and provide insight into areas of potential improvement in fellowship training. Fellows will benefit from a clear roadmap to independent hematopathology practice with concrete and timely feedback.

Surface Proteomics Reveals CD72 as a Target for In Vitro-Evolved Nanobody-Based CAR-T Cells in KMT2A/MLL1-Rearranged B-ALL.

Alternative strategies are needed for patients with B-cell malignancy relapsing after CD19-targeted immunotherapy. Here, cell surface proteomics revealed CD72 as an optimal target for poor-prognosis KMT2A/MLL1-rearranged (MLLr) B-cell acute lymphoblastic leukemia (B-ALL), which we further found to be expressed in other B-cell malignancies. Using a recently described, fully in vitro system, we selected synthetic CD72-specific nanobodies, incorporated them into chimeric antigen receptors (CAR), and demonstrated robust activity against B-cell malignancy models, including CD19 loss. Taking advantage of the role of CD72 in inhibiting B-cell receptor signaling, we found that SHIP1 inhibition increased CD72 surface density. We establish that CD72-nanobody CAR-T cells are a promising therapy for MLLr B-ALL. SIGNIFICANCE: Patients with MLLr B-ALL have poor prognoses despite recent immunotherapy advances. Here, surface proteomics identifies CD72 as being enriched on MLLr B-ALL but also widely expressed across B-cell cancers. We show that a recently described, fully in vitro nanobody platform generates binders highly active in CAR-T cells and demonstrate its broad applicability for immunotherapy development.This article is highlighted in the In This Issue feature, p. 1861.

Molecular assessment of pretransplant chemotherapy in the treatment of juvenile myelomonocytic leukemia.

BACKGROUND: Despite the intensity of hematopoietic stem cell transplantation (HCT), relapse remains the most common cause of death in juvenile myelomonocytic leukemia (JMML). In contrast to other leukemias where therapy is used to reduce leukemic burden prior to transplant, many patients with JMML proceed directly to HCT with active disease. The objective of this study was to elucidate whether pre-HCT therapy has an effect on the molecular burden of disease and how this affects outcome post-HCT. PROCEDURE: Twenty-one patients with JMML who received pre-HCT therapy and were transplanted at UCSF were analyzed in this study. The mutant allele frequency of the driver mutation was assessed before and after pre-HCT therapy, using custom amplicon next-generation sequencing. RESULTS: Of the 21 patients, seven patients (33%) responded to therapy with a significant reduction in their mutant allele frequency and were classified as molecular responders. Six of these patients received moderate-intensity chemotherapy, one patient received only azacitidine. The 5-year progression-free survival after HCT of molecular responders was 100% versus 61% for nonresponders (P = .12). Survival of molecular nonresponders was not improved by use of high-intensity conditioning, but patients were salvaged if they experienced severe graft versus host disease. There were no baseline clinical characteristics that were associated with response to pre-HCT therapy. CONCLUSIONS: Despite the myelodysplastic nature of JMML, patients treated with pre-HCT therapy can achieve molecular remissions. These patients experienced a trend toward improved outcomes post-HCT. Importantly, molecular testing can be helpful to distinguish between responders and nonresponders and should become an integral part of clinical care.

Efficacy of an Intensive, Ultrasound-Guided Fine-Needle Aspiration Biopsy Training Workshop in Tanzania.

BACKGROUND: Fine-needle aspiration biopsy (FNAB) is a minimally invasive, cost-effective diagnostic tool that can be used in low-resource settings. However, adequacy and accuracy of FNAB is highly dependent on the skills of the operator and requires specialized training. Poor technique can preclude definitive diagnoses because of insufficient quality or quantity of FNAB samples. We evaluated the efficacy of an intensive training experience in Tanzania on improving ultrasound-guided FNAB techniques. METHODS: A 2-day workshop offered didactic lectures, demonstrations, and hands-on practicum on fundamentals of ultrasound imaging and FNAB technique. A prospective interventional study design was used with pre- and postintervention surveys and assessments to measure the effect of the workshop on specific skills related to slide smearing and ultrasound-guidance among participants. RESULTS: Twenty-six pathologists and radiologists, including trainees in each specialty, participated in the workshop. Pre- and postworkshop assessments demonstrated that most participants improved significantly in nearly all technical skills for slide smearing and ultrasound-guided FNAB. After the workshop, most participants demonstrated substantial improvements in ability to prepare the ultrasound equipment, measure the lesion in three dimensions by ultrasound, target lesions in one pass using both parallel and perpendicular approaches, and prepare high-quality aspirate smears. CONCLUSION: An in-country 2-day workshop in Tanzania was efficacious in transferring basic skills in FNAB smear preparation and ultrasound-guided FNAB, resulting in skills enhancement among participating pathologists and radiologists. Although mastery of skills was not the goal of this short workshop, participants demonstrated proficiency in most technical elements after workshop completion, and the workshop generated interest among select participants to pursue additional intensive training in cytopathology.

Investigation of the Fate and Dynamics of Extracellular Polymeric Substances (EPS) during Sludge-Based Photogranulation under Hydrostatic Conditions.

Oxygenic photogranules have received increasing interest due to their ability to treat wastewater without aeration and recover wastewater's chemical energy and solar energy. It has been reported that these photogranules can be produced under both hydrostatic and hydrodynamic conditions, and enrichment of filamentous cyanobacteria is required for this photogranulation to occur. Despite the critical role extracellular polymeric substances (EPS) play in granulation, EPS in photogranulation is yet virtually unknown. Here, we present the fate and dynamics of different fractions of EPS in sludge-based photogranulation under hydrostatic conditions. The study shows that during the transformation of activated sludge into a photogranular biomass, sludge's base-extractable proteins selectively degrade. Strong correlations between base-extracted proteins and the growth of chlorophyll a and chlorophyll a/ b ratio suggest that the bioavailability of this organic nitrogen is linked with selection and enrichment of filamentous cyanobacteria under hydrostatic conditions. The results of soluble and sonication-extractable EPS and microscopy also show that the growth of filamentous cyanobacteria required large amounts of polysaccharide-based EPS for their motility and maintenance. With findings on the progression of photogranulation, the fate and dynamics of EPS, and microscopy on microstructures associated with EPS, we discuss potential mechanisms of photogranulation occurring under hydrostatic conditions.

Cytology cases of the week: an educational tool that improves trainee exposure to cytology.

INTRODUCTION: The Accreditation Council for Graduate Medical Education requires residents to examine 1500 cytology specimens by the end of residency. Cytology cases of the week (COWs) were instituted in 2010-2011 in an effort to increase trainee exposure to cytology. MATERIALS AND METHODS: Images of 2 to 5 cases with basic clinical information are sent to residents weekly. Residents have 1 week to respond by e-mail; after which, correct answers are e-mailed. Cytology resident in-service examination (RISE) scores were used to assess the effectiveness of COWs. Additionally, a feedback survey was distributed to trainees to determine the perception of COWs as a teaching tool. RESULTS: An unpaired two-sided t test showed residents who participated in COWs scored 15.4% higher on the RISE than residents who participated minimally or not at all over the 5-year period (P < 0.05). In 2014-2015 and 2015-2016, when COWs were minimally and not at all offered, we saw a significant decrease in average cytology RISE scores compared with prior years when COWs were offered (P < 0.05). There was no correlation between percentage of correctly submitted answers for COWs and RISE scores. The vast majority (83%) of trainees reported participating in COWs for self-study, and the majority (86%) felt participation in COWs increased their cytology knowledge. Major reasons for not participating included technical challenges and time limitations. CONCLUSIONS: COWs are an effective educational tool that increase resident fund of knowledge in cytology. Residents who participate in COWs perform higher on the RISE, regardless of percentage of correctly submitted answers.

The importance of filamentous cyanobacteria in the development of oxygenic photogranules.

Microorganisms often respond to their environment by growing as densely packed communities in biofilms, flocs or granules. One major advantage of life in these aggregates is the retention of its community in an ecosystem despite flowing water. We describe here a novel type of granule dominated by filamentous and motile cyanobacteria of the order Oscillatoriales. These bacteria form a mat-like photoactive outer layer around an otherwise unconsolidated core. The spatial organization of the phototrophic layer resembles microbial mats growing on sediments but is spherical. We describe the production of these oxygenic photogranules under static batch conditions, as well as in turbulently mixed bioreactors. Photogranulation defies typically postulated requirements for granulation in biotechnology, i.e., the need for hydrodynamic shear and selective washout. Photogranulation as described here is a robust phenomenon with respect to inoculum characteristics and environmental parameters like carbon sources. A bioprocess using oxygenic photogranules is an attractive candidate for energy-positive wastewater treatment as it biologically couples CO2 and O2 fluxes. As a result, the external supply of oxygen may become obsolete and otherwise released CO2 is fixed by photosynthesis for the production of an organic-rich biofeedstock as a renewable energy source.

The role of inorganic nitrogen in successful formation of granular biofilms for wastewater treatment that support cyanobacteria and bacteria.

Recently, the use of phototrophs for wastewater treatment has been revisited because of new approaches to separate them from effluent streams. One manifestation uses oxygenic photogranules (OPGs) which are dense, easily-settleable granular biofilms of cyanobacteria, which surrounding populations of heterotrophs, autotrophs, and microalgae. OPGs can remove COD and nitrogenous compounds without external aeration. To better grow and maintain biomass in the proposed wastewater process, this study seeks to understand the factors that contribute to successful granulation. Availability of initial inorganic nitrogen, particularly ammonium, was associated with successful cultivation of OPGs. In the first days of granulation, a decrease in ammonium coupled with an increase in a cyanobacterial-specific 16S rRNA gene, may suggest that ammonium was assimilated in cyanobacteria offering a competitive environment for growth. Though both successful and unsuccessful OPG formation demonstrated a shift from non-phototrophic bacterial dominated communities on day 0 to cyanobacterial dominated communities on day 42, the successful community had a greater relative abundance (46%) of OTUs associated with genera Oscillatoria and Geitlernema than the unsuccessful community (27%), supporting that filamentous cyanobacteria are essential for successful OPG formation. A greater concentration of chlorophyll b in the unsuccessful OPG formation suggested a greater abundance of algal species. This study offers indicators of granulation success, notably availability of inorganic nitrogen and chlorophyll a and b concentrations for monitoring the health and growth of biomass for a potential OPG process.

Statistical Literacy Among Academic Pathologists: A Survey Study to Gauge Knowledge of Frequently Used Statistical Tests Among Trainees and Faculty.

CONTEXT: -Statistical literacy can be defined as understanding the statistical tests and terminology needed for the design, analysis, and conclusions of original research or laboratory testing. Little is known about the statistical literacy of clinical or anatomic pathologists. OBJECTIVE: -To determine the statistical methods most commonly used in pathology studies from the literature and to assess familiarity and knowledge level of these statistical tests by pathology residents and practicing pathologists. DESIGN: -The most frequently used statistical methods were determined by a review of 1100 research articles published in 11 pathology journals during 2015. Familiarity with statistical methods was determined by a survey of pathology trainees and practicing pathologists at 9 academic institutions in which pathologists were asked to rate their knowledge of the methods identified by the focused review of the literature. RESULTS: -We identified 18 statistical tests that appear frequently in published pathology studies. On average, pathologists reported a knowledge level between "no knowledge" and "basic knowledge" of most statistical tests. Knowledge of tests was higher for more frequently used tests. Greater statistical knowledge was associated with a focus on clinical pathology versus anatomic pathology, having had a statistics course, having an advanced degree other than an MD degree, and publishing research. Statistical knowledge was not associated with length of pathology practice. CONCLUSIONS: -An audit of pathology literature reveals that knowledge of about 12 statistical tests would be sufficient to provide statistical literacy for pathologists. On average, most pathologists report they can interpret commonly used tests but are unable to perform them. Most pathologists indicated that they would benefit from additional statistical training.

Visceral leishmaniasis-associated hemophagocytic lymphohistiocytosis in a traveler returning from a pilgrimage to the Camino de Santiago.

We report the case of a 73-year-old American traveler who presented with 3 weeks of fatigue, fevers, chills, and pancytopenia. Clinical and laboratory findings were consistent with hemophagocytic lymphohystiocytosis (HLH) and bone marrow biopsy revealed amastigotes consistent with visceral leishmaniasis. The range of endemic visceral leishmaniasis transmission now extends into northern Spain and travelers to this region should use personal protective measures against sand fly exposure.