Cardiac genetic test yields and genotype-phenotype correlations from large cohort investigated by medical examiner's office.

BACKGROUND: Few reports describe the yield of postmortem genetic testing from medical examiners' offices or correlate genetic test results with autopsy-confirmed phenotypes from a large cohort. OBJECTIVES: To report results from cardiomyopathy- and cardiac arrhythmia-associated genetic testing in conjunction with autopsy findings of cases investigated at the United States' largest medical examiner office. METHODS: Postmortem cases tested from 2015 to 2022 with a cardiomyopathy- and cardiac arrhythmia-associated gene panel were reviewed. American College of Medical Genetics and Genomics/Association for Molecular Pathology guidelines were used to classify variant pathogenicity. Correlations of pathogenic/likely pathogenic variants (P/LPVs) with cardiac pathology were evaluated. RESULTS: The cohort included 1107 decedents of diverse ages and ethnicities. P/LPVs were detected in 87 (7.9%) cases, with 73 and 14 variants in cardiomyopathy and cardiac arrhythmia genes, respectively. Variants of uncertain significance were detected in 437 (39.5%) cases. The diagnostic yield (percentage of P/LPV) in decedents with cardiomyopathy (26.1%) was significantly higher than those without (P<.0001). The diagnostic yield was significantly lower in infants (0.7%) than older age groups (ranging from 1 to 74 years old, 5.7%-25.9%), which had no statistical difference between their yields. The diagnostic yields by cardiac autopsy findings were 54.0% for hypertrophic cardiomyopathy, 47.1% for arrhythmogenic cardiomyopathy, 20.0% for myocardial fibrosis, 19.0% for dilated cardiomyopathy, and 11.3% for myocarditis. Most P/LPVs were in MYBPC3, TTN, PKP2, SCN5A, MYH7, and FLNC. Ten P/LPVs were novel. CONCLUSIONS: Our results support the importance of performing postmortem genetic testing on decedents of all ages with cardiomyopathy, cardiac lesions insufficient to diagnosis a specific cardiomyopathy (e.g., myocardial fibrosis), and myocarditis. Combined postmortem cardiac examination and genetic analysis are advantageous in accurately determining the underlying cause of death and informing effective clinical care of family members.

Pathology and Monkeypox virus Localization in Tissues From Immunocompromised Patients With Severe or Fatal Mpox.

BACKGROUND: Pathology and Monkeypox virus (MPXV) tissue tropism in severe and fatal human mpox is not thoroughly described but can help elucidate the disease pathogenesis and the role of coinfections in immunocompromised patients. METHODS: We analyzed biopsy and autopsy tissues from 22 patients with severe or fatal outcomes to characterize pathology and viral antigen and DNA distribution in tissues by immunohistochemistry and in situ hybridization. Tissue-based testing for coinfections was also performed. RESULTS: Mucocutaneous lesions showed necrotizing and proliferative epithelial changes. Deceased patients with autopsy tissues evaluated had digestive tract lesions, and half had systemic tissue necrosis with thrombotic vasculopathy in lymphoid tissues, lung, or other solid organs. Half also had bronchopneumonia, and one-third had acute lung injury. All cases had MPXV antigen and DNA detected in tissues. Coinfections were identified in 5 of 16 (31%) biopsy and 4 of 6 (67%) autopsy cases. CONCLUSIONS: Severe mpox in immunocompromised patients is characterized by extensive viral infection of tissues and viremic dissemination that can progress despite available therapeutics. Digestive tract and lung involvement are common and associated with prominent histopathological and clinical manifestations. Coinfections may complicate mpox diagnosis and treatment. Significant viral DNA (likely correlating to infectious virus) in tissues necessitates enhanced biosafety measures in healthcare and autopsy settings.

Association of Preventive Care Attitudes and Beliefs with Colorectal Cancer Screening History among African American Patients of Community Health Centers.

Colorectal cancer (CRC) is the third most common cancer and third leading cause of cancer-related death among African Americans in the United States. However, when detected early, CRC is treatable and survival rates are high. CRC health disparities for African Americans compared with other groups may be due in part to lower screening adherence and later stage diagnosis. The objective of this research phase was to test predictors of ever having received CRC screening (i.e., self-report of lifetime receipt of CRC screening) using survey measures in the domains of healthcare communication, trust in doctors, CRC perceived susceptibility, CRC worry, negative cancer beliefs, CRC screening self-efficacy, and cultural constructs for CRC screening in a sample of African American community health center patients. The study recruited 115 African American patients between the ages of 45 to 64 years old from community health centers in north Florida to complete the baseline survey. Our results show significant differences in CRC screening history by age, marital status, level of mistrust of healthcare providers, and level of empowerment toward cancer screening. To increase CRC screening in this population, the study findings suggest development of intervention programs that focus on priority populations of younger, unmarried African Americans, especially given the current trend of early onset CRC. Moreover, survival rates are lower for unmarried and younger African Americans relative to older and married individuals. Such interventions should also aim to increase trust in healthcare providers and increase empowerment for CRC screening decision making to increase screening participation.

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.

Associations of Content and Context of Communication with Prostate-Specific Antigen Testing.

There is limited research about the content and context of communication on prostate-specific antigen (PSA) testing among men in the state of Florida. The purpose of this study is to understand how the content communication (discussion of advantages and disadvantages of PSA testing between provider and patient; provider recommendations of PSA testing) and the context of communication (continuity of care denoted by the presence of a personal doctor) influence PSA testing. Data were drawn from the Florida Behavioral Risk Factor Surveillance System. Receipt of PSA testing was the primary outcome. Multiple logistic regression analyses were used to adjust for sociodemographic, clinical, healthcare access, and lifestyle characteristics when associating the content and context of communication with PSA testing. Discussions were classified into four mutually exclusive categories: discussions of advantages and disadvantages, only advantages, only disadvantages, and no discussion. The most significant predictors for PSA testing included physician recommendation, discussions including advantages, older age, non-smoking, and having a personal doctor. Individualized PSA screening may be a pathway to reducing racial disparities in screening for prostate cancer (PCa) and, by extension, lower incidence and mortality rates. Developing a bill to create an Office of Men's Health at Health & Human Services is recommended.

The Eyes Have It: How Critical are Ophthalmic Findings to the Diagnosis of Pediatric Abusive Head Trauma?

Pediatric abusive head trauma (AHT), still colloquially known as shaken baby syndrome, is a leading cause of morbidity and mortality among infants. Controversy has grown surrounding this diagnosis, and the specificity of the clinical findings-subdural hemorrhage, cerebral edema, and retinal hemorrhages-has been challenged. A literature search of peer reviewed publications on PubMed pertaining to the history, clinical, and pathologic features of AHT was conducted using the terms "shaken baby syndrome," "non-accidental trauma," "abusive head trauma," "inflicted traumatic brain injury," "shaken impact syndrome," and "whiplash shaken infant syndrome." Focus was placed on articles discussing ophthalmic findings in AHT. Retinal hemorrhages-particularly those that are too numerous to count, occurring in all layers of the retina (preretinal, intraretinal, subretinal), covering the peripheral pole and extending to the ora serrata, and accompanied by retinoschisis and other ocular/periocular hemorrhages-are highly suggestive of AHT, particularly in the absence of otherwise explained massive accidental trauma. Although the diagnosis has grown in controversy in recent years, AHT has well-documented clinical and pathologic findings across a large number of studies.

Patient-facing communication for cytopathologists: A framework for disclosing diagnostic error.

Medical errors are a major source of harm to patients. Regulatory bodies mandate and patient safety experts advocate the disclosure of medical errors to patients to promote transparency and to create accountability for improving health care processes. Although pathologists regularly report errors-either to pathology or clinical colleagues or via internal safety reporting systems-few pathologists directly disclose those errors to patients. Yet many pathologists are interested in participating in the direct disclosure of medical errors to patients and may even be mandated to do so. When surveyed on why they do not directly disclose errors to patients, pathologists commonly cite a lack of confidence and a lack of training. Another barrier cited is the lack of a preexisting relationship between the pathologist and the patient. With respect to this last barrier, cytopathologists have a distinct advantage over surgical or clinical pathologists, as many cytopathologists regularly interact with and develop a rapport with patients when they are performing fine-needle aspiration (FNA) procedures. To improve the safety culture in pathology, direct error disclosure practices must be developed, supported, and strengthened. It is critical for cytopathologists to be comfortable with disclosing errors to patients. Being comfortable with disclosing an error, however, requires training, practice, and advance reflection. Using a practical, case-based format centered around FNA examples, this article addresses how to disclose a medical error to a patient. It provides a framework, heuristic principles, and structured conversation systems and talking points to guide the inexperienced pathologist to find his or her voice in a challenging disclosure conversation.

Pseudomonas species may appear strikingly filamentous in tissue sections: an important consideration for surgical pathologists and a reminder of the utility of modified silver impregnation methods.

Although tissue culture is the gold standard for diagnosing infection, histologic examination of surgically resected tissue can be a critical component in the diagnosis of tissue infection. The goal of this brief report is to alert surgical pathologists that Pseudomonas species can appear strikingly filamentous histologically and may somewhat mimic the appearance of filamentous bacteria, such Actinomyces or Nocardia, or thin fungal hyphae. A secondary aim is to raise awareness that Pseudomonas can sometimes only be identified histologically through the use of a modified silver impregnation method (Steiner stain). Five cases of filamentous Pseudomonas were encountered in three different surgical pathology subspecialities (ophthalmic pathology, cardiovascular pathology, and dermatopathology) over a 1-year period. All cases were of formalin-fixed, paraffin-embedded tissue, stained using hematoxylin & eosin (H&E) and multiple histochemical stains. Four cases grew Pseudomonas aeruginosa in culture and, in the fifth case, a nonaeruginosa species was detected using polymerase chain reaction-based methods. The markedly filamentous-appearing Pseudomonas organisms were identified in five different tissue sites: vascular graft, enucleation (whole eye) specimen, scleral biopsy, soft-tissue excision, and skin punch biopsy. In one of the five cases the organisms were seen on H&E, and in only two of the five were the organisms seen on Brown-Hopps stain. In all five cases, the organisms were identified on Steiner stain. It is therefore important to recognize that Pseudomonas can appear markedly filamentous, Pseudomonas or other bacterial infection is suspected, the surgical pathologist would be advised to employ the Steiner stain to most consistently detect the organisms.

Pathology trainees rarely report safety incidents: A review of 13,722 safety reports and a call to action.

Reporting and understanding patient safety incidents is a cornerstone of improving patient care quality and safety. The Accreditation Council for Graduate Medical Education specifically mandates that physician trainee education include participation in the recognition, reporting, and root cause analysis of patient safety incidents. Studies on safety event reporting, however, have consistently shown that attending physicians submit few safety reports, and trainees submit even fewer. We undertook a study to assess the rate at which pathology trainees report patient safety events relative to the rates at which trainees in other medical specialties do. We performed a retrospective analysis of 13,722 safety reports submitted to our medium-sized Academic Medical Center's incident reporting system. We then analyzed those reported by trainees (residents and fellows), and then further drilled down on the subset of trainee-reported safety events reported by pathology trainees. Despite accounting for over 5% of all types of trainees at the enterprise level, pathology trainees accounted for only 0.5% of all trainee safety reports. Our findings represent a call to action for pathology training programs to engage their residents and fellows in quality and safety initiatives, to understand and remove barriers to safety event reporting for vulnerable populations such as trainees, and to empower trainees to confidently report safety risks as valued frontline care providers.

Towards high reliability in national pathology education: Evaluating the United States and Canadian Academy of Pathology educational product.

The United States and Canadian Academy of Pathology (USCAP) leadership undertook a high level, global review of educational product outcomes data using high reliability organization (HRO) principles: preoccupation with failure; reluctance to simplify; sensitivity to operations; commitment to resilience; and deference to expertise. HRO principles have long been applied to fields such as aviation, nuclear power, and more recently to healthcare, yet they are rarely applied to the field that underpins these-and many other-complex systems: education. While errors in education are less calamitous than in air travel or healthcare delivery, USCAP's educational products impact over 15,000 learners a year, and thus have important implications for the future practice of pathology. Here we report USCAP's experiences using HRO principles to evaluate our keystone educational product, the "USCAP Short Course." Following this novel method of data review, USCAP leadership was able to better understand diverse learner needs based on practice venue, training level, and course topic. Unexpected lessons included the identification of specifically challenging educational topics, such as molecular pathology, and a need to focus more resources on emerging fields such as quality and patient safety. The results allow USCAP to assess educational product performance using HRO tools, and provide strong data-driven decision support for future national pathology education strategy.

Role of time from transplantation to biopsy in histologic ABMR: A single center report.

BACKGROUND: Allograft biopsies with lesions of Antibody-Mediated Rejection (ABMR) with Microvascular Inflammation (MVI) have shown heterogeneous etiologies and outcomes. METHODS: To examine factors associated with outcomes in biopsies that meet histologic ABMR criteria, we retrospectively evaluated for-cause biopsies at our center between 2011 and 2017. We included biopsies that met the diagnosis of ABMR by histology, along with simultaneous evaluation for anti-Human Leukocyte Antigen (HLA) donor-specific antibodies (DSA). We evaluated death-censored graft loss (DCGL) and used a principal component analysis (PCA) approach to identify key predictors of outcomes. RESULTS: Out of the histologic ABMR cohort (n = 118), 70 were DSA-positive ABMR, while 48 had no DSA. DSA(+)ABMR were younger and more often female recipients. DSA(+)ABMR occurred significantly later post-transplant than DSA(-)ABMR suggesting time-dependence. DSA(+)ABMR had higher inflammatory scores (i,t), chronicity scores (ci, ct) and tended to have higher MVI scores. Immunodominance of DQ-DSA in DSA(+)ABMR was associated with higher i+t scores. Clinical/histologic factors significantly associated with DCGL after biopsy were inputted into the PCA. Principal component-1 (PC-1), which contributed 34.8% of the variance, significantly correlated with time from transplantation to biopsy, ci/ct scores and DCGL. In the PCA analyses, i, t scores, DQ-DSA, and creatinine at biopsy retained significant correlations with GL-associated PCs. CONCLUSIONS: Time from transplantation to biopsy plays a major role in the prognosis of biopsies with histologic ABMR and MVI, likely due to ongoing chronic allograft injury over time.

Prioritizing Patient Safety and Minimizing Waste: Institutional Review of Cases and a Proposed Process for Designing a Surgical Pathology Gross-Only Examination Policy.

OBJECTIVES: Gross-only examination policies vary widely across pathology departments. Several studies-particularly a College of American Pathologists' Q-Probes study-have looked at the variations in gross-only policies, and even more studies have addressed the (in)appropriateness of certain specimen types for gross-only examination. Few, if any, studies have tackled the important task of how to revise and safely implement a new gross-only examination protocol, especially in collaboration with clinical colleagues. METHODS: We reviewed the grossing protocols from three anatomic pathology centers to identify common gross-only specimen types. We compiled an inclusive list of any specimen types that appeared on one or more centers' lists. We performed a retrospective review of the gross and microscopic diagnoses for those specimen types to determine if any diagnoses of significance would have been missed had that specimen been processed as a gross-only. RESULTS: We reviewed 940 cases among 13 specimen types. For 7 specimen types, the gross diagnoses provided equivalent information to the microscopic diagnoses. For 6 specimen types, microscopic diagnoses provided clinically meaningful information beyond what was captured in the gross diagnoses. CONCLUSIONS: To improve the value of care provided, pathology departments should conduct internal reviews and consider transitioning specimen types to gross-only when safe.

Vasculopathy and Increased Vascular Congestion in Fatal COVID-19 and Acute Respiratory Distress Syndrome.

Rationale: The leading cause of death in coronavirus disease 2019 (COVID-19) is severe pneumonia, with many patients developing acute respiratory distress syndrome (ARDS) and diffuse alveolar damage (DAD). Whether DAD in fatal COVID-19 is distinct from other causes of DAD remains unknown. Objective: To compare lung parenchymal and vascular alterations between patients with fatal COVID-19 pneumonia and other DAD-causing etiologies using a multidimensional approach. Methods: This autopsy cohort consisted of consecutive patients with COVID-19 pneumonia (n = 20) and with respiratory failure and histologic DAD (n = 21; non-COVID-19 viral and nonviral etiologies). Premortem chest computed tomography (CT) scans were evaluated for vascular changes. Postmortem lung tissues were compared using histopathological and computational analyses. Machine-learning-derived morphometric analysis of the microvasculature was performed, with a random forest classifier quantifying vascular congestion (CVasc) in different microscopic compartments. Respiratory mechanics and gas-exchange parameters were evaluated longitudinally in patients with ARDS. Measurements and Main Results: In premortem CT, patients with COVID-19 showed more dilated vasculature when all lung segments were evaluated (P = 0.001) compared with controls with DAD. Histopathology revealed vasculopathic changes, including hemangiomatosis-like changes (P = 0.043), thromboemboli (P = 0.0038), pulmonary infarcts (P = 0.047), and perivascular inflammation (P < 0.001). Generalized estimating equations revealed significant regional differences in the lung microarchitecture among all DAD-causing entities. COVID-19 showed a larger overall CVasc range (P = 0.002). Alveolar-septal congestion was associated with a significantly shorter time to death from symptom onset (P = 0.03), length of hospital stay (P = 0.02), and increased ventilatory ratio [an estimate for pulmonary dead space fraction (Vd); p = 0.043] in all cases of ARDS. Conclusions: Severe COVID-19 pneumonia is characterized by significant vasculopathy and aberrant alveolar-septal congestion. Our findings also highlight the role that vascular alterations may play in Vd and clinical outcomes in ARDS in general.

Changes in Surgical Pathology Case Volume and Amendment Rates During the COVID-19 Pandemic.

OBJECTIVES: Surgical pathology volume decreased during the peak of the coronavirus disease 2019 (COVID-19) pandemic. We looked at the 4 months with the greatest reduction in surgical pathology volume during the COVID-19 pandemic and compared them with those same months in 2019 to determine changes in specimen volume. We compared the amendment rates during those periods and types of amendments issued (identification [ID], report defect [RD], diagnostic information [DI]). METHODS: All pathology reports between March to June 2019 and March to June 2020 were extracted from the pathology information system. All amendments issued were extracted over the same period and then subclassified by two pathologists. RESULTS: There was a 52.1% reduction in surgical pathology volume between the 4-month periods in 2019 and 2020 (P = .04). The amendment rate was 0.9% in 2019 compared with 1.4% in 2020, representing a 65.5% increase in amendments overall. There was a 53.3% reduction in amendments issued for ID, a 3.8% reduction in RD, and a 23.2% increase in amendments issued for DI. The change in amendments was not statistically significant. CONCLUSIONS: These findings suggest that a reduction in workload would not improve error rates. The circumstances of the pandemic highlight the many factors contributing to error rates in surgical pathology.

Assessing the effectiveness of a community health advisor plus screen to save educational intervention on stool-based testing adherence in an African American safety net clinic population: study protocol for a randomized pragmatic trial.

BACKGROUND: Colorectal cancer (CRC) is the second most deadly cancer affecting US adults and is also one of the most treatable cancers when detected at an earlier clinical stage of disease through screening. CRC health disparities experienced by African Americans are due in part to the later stage of diagnosis, suggesting the importance of improving African Americans' CRC screening participation. The national Screen to Save (S2S) initiative employs a community health educator to deliver CRC screening education which can be tailored for specific populations, and such approaches have increased CRC screening rates in disadvantaged and racial/ethnic minority populations. METHODS/DESIGN: In this trial emphasizing stool-based CRC screening, focus groups informed the development of an adapted S2S video and brochure tailored for African Americans and identified preferred motivational text messages for a multicomponent community health advisor (CHA) intervention. A CHA hired from the community was trained to deliver a 6-week CRC educational intervention consisting of an initial face-to-face meeting followed by 5 weeks of calls and texts. Interested eligible persons are enrolled primarily through recruitment by two partnering community health centers (CHCs) and secondarily through various outreach channels and, after consenting and completing a baseline survey, are randomly assigned to one of two study arms. The CHCs are blinded to study arm assignment. Intervention arm participants receive the brochure and CHA intervention while participants assigned to the control group receive only the brochure. All participants receive a stool-based CRC screening test from their health center, and the primary outcome is the completion of the screening test at 12 months. Secondary objectives are to estimate the effect of the intervention on mediating factors, explore the effect of moderating factors, and perform a cost-effectiveness analysis of the CHA intervention. DISCUSSION: The TUNE-UP study will enhance understanding about CRC screening in African Americans obtaining primary health care through CHCs and is one of the very few studies to examine a CHA intervention in this context. A better understanding of the mechanisms by which the intervention affects patient beliefs and behaviors will help focus future research while the exploratory cost-effectiveness analysis will inform CHCs' decision-making about implementing a CHA program to increase screening and reduce cancer health disparities. TRIAL REGISTRATION: ClinicalTrials.gov NCT04304001 . Registered on March 11, 2020.