Utility of CDC Screening Guidelines and Autopsy Findings in Identifying Decedents Who Die of SARS-CoV-2 Infection.

ABSTRACT: We assess the utility of a Centers for Disease Control and Prevention (CDC) guidelines-based coronavirus disease 2019 (COVID-19) screening checklist for postmortem severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surveillance, detailing the relationship between the histologic findings at autopsy and attribution of death to COVID-19.SARS-CoV-2 nasopharyngeal swabs were collected at the time of autopsy in all "checklist-positive" decedents. Additional "checklist-negative" decedents were randomly tested daily. Lung slides were blindly reviewed by 3 pathologists, assessing for the presence of diffuse alveolar damage (DAD) and other findings. Sixteen decedents had positive postmortem SARS-CoV-2 nasopharyngeal swabs and underwent complete autopsies. Seven decedents had positive screening checklists. Of these, 4 had DAD and 1 had COVID-19-associated thromboembolic disease. Of the 9 decedents with negative screening checklists, 2 had DAD, but only 1 was attributed to COVID-19; the other was likely drug related. Acute bronchopneumonia was the second most common finding, and aspiration was the likely etiology in cases without concomitant DAD. COVID-19-related DAD was identified more commonly in decedents who screened positive by CDC checklist, but false-negatives did occur. Medical examiner offices should maintain a low threshold for random testing of decedents even when COVID-19 is not suspected.

Intraplacental Gestational Neoplasms: A Review of Clinically Relevant Diagnostically Challenging Lesions.

CONTEXT.­: Case studies reporting intraplacental choriocarcinoma (IPC) and intraplacental "chorangiocarcinoma" have recently increased, with IPC also represented in molecular analyses of gestational trophoblastic neoplasms. OBJECTIVE.­: To provide an overview of 2 intraplacental neoplastic lesions that can have a significant impact on both mother and fetus/infant, focusing on diagnostic characteristics, and ancillary and molecular tools that support diagnosis, determine prognosis, and further elucidate the nature of these lesions. DATA SOURCES.­: Data were compiled from a PubMed literature review that included diagnostic and additional keywords within the scope of study for gestational choriocarcinoma in general. Illustrative cases were retrieved from the pathology archives at Michigan Medicine, including the consultation files of the author. CONCLUSIONS.­: Intraplacental gestational tumors exist along the spectrum of benign (chorangioma) to aggressive malignant (choriocarcinoma) neoplasms with a high potential for metastasis. Although most gestational choriocarcinomas follow complete hydatidiform mole, 20% to 25% occur in association with normal intrauterine gestations, including rare cases in which they are detected within the placenta (IPC). IPCs range from asymptomatic to widely metastatic, with metastases possible even when only microscopic IPCs are present. A second, even less common lesion, variably called "chorangiocarcinoma" and chorangioma with atypical trophoblast proliferation, is also reviewed. The incidence of these lesions is likely to be underestimated. Heightened suspicion and more liberal placental sampling, particularly when specific clinical features are present, may result in higher detection. Enhanced detection to provide the earliest intervention for both mother and infant may improve prognosis, particularly for asymptomatic disease that may later present with metastasis.

Second opinion for pulmonary and pleural cytology is valuable for patient care.

INTRODUCTION: Thoracic cytology can be challenging due to limited procured material or overlapping morphology between benign and malignant entities. In such cases, expert consultation might be sought. This study aimed to characterize all pulmonary and pleural cytology consult cases submitted to our practice and provide recommendations on approaching difficult cases. MATERIALS AND METHODS: All thoracic (pulmonary and pleural) cytology cases submitted for expert consultation to the University of Michigan (MLabs) from 2013 to mid-2022 were reviewed. Cases where cytology was only part of a hematopathology or surgical pathology consult were excluded. Patient demographics, specimen location, procedure performed, referring diagnosis, and our diagnoses were recorded for each case. Diagnoses were categorized according to the Papanicolaou Society of Cytopathology recommendations for pulmonary and effusion cytology. Discordant diagnoses were stratified as major or minor. Data was analyzed using chi-square analysis and logistic models. RESULTS: We received 784 thoracic cytology consult cases, including 530 exfoliative samples and 307 fine-needle aspirations. The most common anatomic locations sampled were the bronchial wall (n = 194, 23%), lung nodule (n = 322, 38%), and pleura (n = 296, 35%). 413 cases had a diagnostic discrepancy (48.3%), with 274 (66%) minor and 139 (34%) major discrepancies. By location, pleural effusion specimens had the highest probability of a discrepant diagnosis (P = 0.003). By specimen type, fine-needle aspiration samples were significantly more likely to have a discrepant diagnosis (P = 0.06). CONCLUSION: Nearly half of the thoracic cytology cases submitted for expert second opinion had diagnostic discrepancies. Consequently, consulting a tertiary medical care center with cytopathology expertise for challenging thoracic cytology diagnoses is beneficial.

Complete genome sequence of Microbacterium paraoxydans phage Damascus.

Phage Damascus was isolated from soil in northwestern Wisconsin using Microbacterium paraoxydans as the host. The Damascus genome is 56,477 bp with 3' single-stranded overhangs and 56.5% G+C content. Damascus was assigned to cluster EL and shares 42.6%-91.7% gene content with the three other phages in this cluster.

Investigating Cortisol in a STEM Classroom: The Association Between Cortisol and Academic Performance.

Science, technology, engineering, and mathematics (STEM) education can be stressful, but uncertainty exists about (a) whether stressful academic settings elevate cortisol, particularly among students from underrepresented racial/ethnic groups, and (b) whether cortisol responses are associated with academic performance. In four classes around the first exam in a gateway college STEM course, we investigated participants' (N = 271) cortisol levels as a function of race/ethnicity and tested whether cortisol responses predicted students' performance. Regardless of race/ethnicity, students' cortisol, on average, declined from the beginning to the end of each class and across the four classes. Among underrepresented minority (URM) students, higher cortisol responses predicted better performance and a lower likelihood of dropping the course. Among non-URM students, there were no such associations. For URM students, lower cortisol responses may have indicated disengagement, whereas higher cortisol responses may have indicated striving. The implication of cortisol responses can depend on how members of a group experience an environment.

Cl-Amidine Improves Survival and Attenuates Kidney Injury in a Rabbit Model of Endotoxic Shock.

Objective: Sepsis causes millions of deaths on a global scale annually. Activation of peptidylarginine deiminase (PAD) enzymes in sepsis causes citrullination of histones, which results in neutrophil extracellular trap formation and sepsis progression. This study evaluates pan-PAD inhibitor, Cl-amidine, in a model of lipopolysaccharide (LPS)-induced endotoxic shock in rabbits. We hypothesized that Cl-amidine would improve survival and attenuate kidney injury. Methods: In the survival model, rabbits were injected injected intravenously with 1 mg/kg of LPS, and then randomly assigned either to receive dimethyl sulfoxide (DMSO; 1 mcL/g) or Cl-amidine (10 mg/kg diluted in 1 mcL/g DMSO). They were then monitored for 14 days to evaluate survival. In the non-survival experiment, the same insult and treatment were administered, however; the animals were euthanized 12 hours after LPS injection for kidney harvest. Acute kidney injury (AKI) scoring was performed by a histopathologist who was blinded to the group assignment. Serial blood samples were also collected and compared. Results: Rabbits that received Cl-amidine had a higher survival (72%) compared with the rabbits that received DMSO (14%; p < 0.05). Cl-amidine-treated rabbits had lower (p < 0.05) histopathologic AKI scores, as well as plasma creatinine and blood urea nitrogen (BUN) levels 12 hours after insult. Conclusions: Pan-PAD inhibitor Cl-amidine improves survival and attenuates kidney injury in LPS-induced endotoxic shock in rabbits.

Comparative analysis of isoform-specific and non-selective histone deacetylase inhibitors in attenuating the intestinal damage after hemorrhagic shock.

BACKGROUND: Isoform-specific histone deacetylase inhibitors (HDACIs) MC1568 and ACY1083 are comparable to the non-selective HDACI valproic acid (VPA) in improving survival in rodents undergoing lethal hemorrhage. However, the organ-specific properties of isoform-specific HDACIs have not been fully evaluated. Also, whether they can act synergistically is not known. We hypothesized that isoform-specific HDACIs are superior to VPA in attenuating intestinal injury and act synergistically when coadministered. METHODS: Sprague Dawley rats were hemorrhaged (40% of total blood volume) and randomized to receive (n=4 per group) (1) MC1568 (5 mg/kg), (2) ACY1083 (30 mg/kg), (3) MC1568+ACY1083 (combination: 5 mg/kg + 30 mg/kg, respectively), (4) VPA (250 mg/kg), or (5) normal saline (NS; vehicle; 250 µL). Animals were observed for 3 hours, after which blood samples were collected and samples of the ileum were harvested. Expression of interleukin 1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and cytokine-induced neutrophil chemoattractant 1 (CINC-1) was assessed in the tissues using enzyme-linked immunosorbent assay. Intestinal cleaved caspase 3 (c-caspase 3) levels were assessed as a marker of apoptosis, and histologic sections of the ileum were examined for signs of bowel injury. Levels of IL-1ß and TNF-α were also measured in the serum as global markers of inflammation. RESULTS: Treatments with MC1568, ACY1083, MC1568+ACY1083, and VPA were associated with decreased IL-1ß levels in the intestine and serum compared with NS. IL-1ß and TNF-α levels were significantly lower in the ACY1083 group compared with the VPA group. CINC-1 levels were significantly lower in the isoform-specific HDACI groups compared with the NS; however, no significant differences were seen with VPA. All treatment groups had a lower expression of intestinal c-caspase 3 compared with NS. Furthermore, MC1568 and ACY1083 groups had lower apoptosis compared with the VPA group. Bowel injury scores were significantly lower in the isoform-specific HDACI groups compared with the NS group; however, the attenuation in the VPA-treated animals did not reach statistical significance. DISCUSSION: Isoform-specific HDACIs provide superior intestinal protection compared with VPA in a rodent model of hemorrhagic shock. LEVEL OF EVIDENCE: Preclinical study.

The practice of gastroenterology: evolution versus intelligent design.

This article describes the economic pressures threatening the traditional practice of gastroenterology and suggests steps by which gastroenterology practices can adapt and adopt a collaborative model that can position the practice for success in a changing environment.