Myocardial Calcification: An Unusual Complication of Remote Trauma With Coidentified Amyloidosis.

We present the heart of a 38-year-old man with paraplegia due to a remote traumatic spinal cord injury. In the 20 years following his injury, he experienced chronic decubitus ulcers, osteomyelitis, neurogenic bladder, malnutrition, and urinary tract infections. He was admitted to the hospital with septic shock secondary to multiple decubitus ulcers and osteomyelitis and expired after a two-month hospitalization. At autopsy, there was marked replacement of left ventricle and interventricular septal myocardium by gritty, firm, yellow-white tissue. Microscopic examination demonstrated a remote infarct with marked dystrophic calcification and unexpected amyloid deposition. This example demonstrates the extraordinary extent to which dystrophic calcifications can replace myocardium and highlights multiple potential etiologies of myocardial calcifications. Of note, this is the first report documenting myocardial calcification as a complication of remote, non-iatrogenic trauma. The role of the amyloidosis in the development of calcification is unclear, but a contributory effect cannot be excluded.

Thoracic Aortic Aneurysm and Dissection: Review and Recommendations for Evaluation.

ABSTRACT: Aortic dissection and rupture (collectively termed "sudden aortic death") are commonly encountered by forensic pathologists, with an estimated incidence at autopsy between 0.6% and 7.7%. Despite this, there is no standard of practice for the evaluation of sudden aortic death at autopsy.Recent studies have shown 20% of patients with thoracic aortic aneurysm or dissection (TAAD) have an identifiable genetic syndrome, and 19% will have an affected first-degree relative. The past 2 decades have seen identification of new culprit genes and syndromes, which can have subtle or nonexistent external phenotypes. A high index of suspicion is warranted to identify possible hereditary TAAD (H-TAAD), allowing family members to obtain screening to avoid catastrophic vascular events. Forensic pathologists need broad knowledge of the spectrum of H-TAAD and awareness of the relative significance of hypertension, pregnancy, substance use, and microscopic changes of aortic architecture.This article reviews the common subtypes of H-TAAD, including Marfan syndrome, vascular Ehlers-Danlos, Loeys-Dietz, and familial thoracic aortic aneurysm and dissection. Recommendations for the evaluation of sudden aortic death at autopsy are presented, including (1) performance of a complete autopsy, (2) documentation of aortic circumference and valve morphology, (3) notifying family of the need for screening, and (4) preservation of a sample for potential genetic testing.

Atrial Endocardial Unipolar Voltage Mapping for Detection of Viable Intramural Myocardium: A Proof-of-Concept Study.

BACKGROUND: Endocardial bipolar voltage amplitude is largely derived from endocardial and subendocardial wall layers. This may result in situations of low bipolar voltage amplitude despite the presence of mid-myocardial including epicardial (ie, intramural-epicardial) viable myocardium. This study examined the utility of endocardial unipolar voltage mapping for detection of viable intramural-epicardial atrial myocardium. METHODS: In 15 swine, an atrial intercaval ablation line with an intentional gap was created. Animals survived for 6 to 8 weeks before electroanatomical mapping followed by sacrifice. Gaps were determined by the presence of electrical conduction and classified based on the histopathologiclly layer(s) of viable myocardium into the following: (1) transmural, (2) endocardial, and (3) intramural-epicardial. Voltage data from healthy, scar, and gap points were exported into excel. The sensitivity and specificity of bipolar and unipolar voltage amplitude to detect intramural-epicardial gaps were compared using receiver operating characteristic analysis. RESULTS: In 9 of 15 (60%) swine, a focal ablation gap was detected in the intercaval line, while in the remainder 6 of 15 (40%), the line was complete without gaps. Gaps were classified into transmural (n=3), endocardial (n=3), or intramural-epicardial (n=3). Intramural-epicardial gaps were characterized by very low bipolar voltage amplitude that was similar to areas with transmural scar (P=0.91). In comparison, unipolar voltage amplitude in intramural-epicardial gaps was significantly higher compared to transmural scar (P<0.001). Unipolar voltage amplitude had higher sensitivity (93% versus 14%, respectively) and similar specificity (95% versus 98%, respectively) to bipolar voltage for detection of intramural-epicardial gaps. CONCLUSIONS: Atrial unipolar voltage mapping may be a useful technique for identifying viable intramural-epicardial myocardium in patients with endocardial scar.

Histologic and Immunohistochemical Features of Antemortem Thrombus Compared to Postmortem Clot: Updating the Definition of Lines of Zahn.

CONTEXT.­: Distinguishing true antemortem thrombus (AMT) from artifactual postmortem clot (PMC) can occasionally be challenging at autopsy. Lines of Zahn are cited as pathognomonic of AMT, but review of literature reveals heterogeneous definitions of the term. Neutrophil karyorrhexis and CD61 immunohistochemistry can also be used to define AMT, but there has been no systematic study determining the specificity of these features. OBJECTIVE.­: To identify features that distinguish AMT from PMC, and to clarify the definition of lines of Zahn. DESIGN.­: PMC from the heart was collected in 50 hospital autopsies. Fifty arterial and 50 venous surgical thrombectomy specimens were reviewed for comparison. The microscopic features with hematoxylin-eosin staining, phosphotungstic acid-hematoxylin (PTAH) staining, and CD61 immunohistochemistry were documented. RESULTS.­: Thin curvilinear strands of fibrin and clumps of fibrin were frequently observed in both AMT and PMC. Thick bands of nested platelets wrapped in fibrin were nearly exclusive to AMT. Neutrophil karyorrhexis was readily apparent on low power in AMT but was seen in 40 of 50 PMCs (80%) only sparsely on high-power examination. Bone marrow elements were identified in 38 of 50 PMCs (76%). CD61 staining showed a geographic pattern in AMT and a speckled pattern in PMC. PTAH staining confirmed features seen with hematoxylin-eosin. CONCLUSIONS.­: Thin curvilinear strands of fibrin are found in both AMT and PMC and can be misinterpreted as lines of Zahn. We define lines of Zahn as thick bands formed by nested platelets wrapped in fibrin. Diffuse neutrophil karyorrhexis is common in AMT; in contrast, bone marrow elements are often seen in PMC.

Effect of Pulsed-Field and Radiofrequency Ablation on Heterogeneous Ventricular Scar in a Swine Model of Healed Myocardial Infarction.

BACKGROUND: Pulsed-field ablation (PFA) is a nonthermal energy with higher selectivity to myocardial tissue in comparison to radiofrequency ablation (RFA). We compared the effects of PFA and RFA on heterogeneous ventricular scar in a swine model of healed infarction. METHODS: In 9 swine, myocardial infarction was created by balloon occlusion of the left anterior descending artery. After a survival period of 8 to 10 weeks, ablation with PFA or RFA was performed at infarct border zones identified by abnormal electrograms. In the PFA group (4 swine), ablation was performed with a lattice catheter (Sphere-9, Affera, Inc). In the RFA group (5 swine), ablation was performed using a 3.5-mm tip catheter (Thermocool ST-SF; Biosense Webster). To further investigate the effect of RFA on temperature development in scar tissue, intramyocardial temperature was measured in healthy and infarcted myocardium using an ex vivo bath model. RESULTS: A total of 11 PFA and 15 RFA lesions were created at infarct border zones with heterogeneous scar. PFA produced uniform and well-demarcated lesions exhibiting irreversible injury characterized by cardiomyocyte death, contraction bands, and lymphocytic infiltration. This effect of PFA extended from the subendocardium through collagen and fat to the epicardial layers. In contrast, the effect of RFA is less uniform and largely limited to the subendocardium with minimal effect on viable myocardium deeper to separating layers of collagen and fat. PFA produced deeper and more transmural lesions (6.4 [interquartile range, 5.5-7.5) versus 5.4 [interquartile range, 4.8-5.9]), 72% versus 30%, respectively; P≤0.02 for each comparison). The limited effect of RFA on viable myocardium at deeper infarct layers was related to a lower intramyocardial maximal temperature compared with healthy myocardium (P=0.01). CONCLUSIONS: PFA may be advantageous for ablation in ventricular scar, producing lesions that unlike RFA are not limited to the subendocardium, but also eliminate viable myocardium separated from the catheter by collagen and fat.

Incremental Utility of 3D Printing to Guide the Surgical Management of Apical Aneurysm.

A 24-year-old man presented with a nonischemic cardiomyopathy of unknown etiology, apical aneurysm, and a secondary mitral regurgitation. Computer tomography-derived 3-dimensional model of the patient's heart was an essential step in guiding the surgical management for an optimal outcome. (Level of Difficulty: Advanced.).

Association Between Atrial Uptake on Cardiac Scintigraphy With Technetium-99m-Pyrophosphate Labeled Bone-Seeking Tracers and Atrial Fibrillation.

BACKGROUND: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized disease, in which atrial fibrillation (AF) has been shown to be prevalent. Cardiac scintigraphy with technetium-99m-pyrophosphate (99mTc-PyP) labeled bone-seeking tracers is used to noninvasively make the diagnosis of ATTR-CA, based on ventricular myocardial uptake. Assessment of atrial wall uptake (AU) on 99mTc-PyP is currently not used in the clinical setting Methods: We analyzed a cohort of patients referred for 99mTc-PyP scan at a tertiary center to explore AU and associations between any and incident AF, ATTR-CA, and all-cause mortality. RESULTS: Among 580 patients included, 296 patients (51%) had a diagnosis of AF; 164 patients (28%) had scans consistent with ATTR-CA while 117 patients (20%) had AU. Of 117 patients with AU, 107 (91%) had any AF. In contrast, of 463 patients without AU 191(41%) had any AF. Of those with AU, 59/117(50%) patients had a 99mTc-PyP diagnosis of ATTR-CA while 58/117(50%) patients did not have such a diagnosis (P=1.00). Patients with AU had significantly more any AF (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), independent of ATTR-CA diagnosis and sex. On multivariable Cox proportional hazards analyses adjusting for age, AU, ATTR-CA diagnosis, sex, smoking, hypertension, diabetes, left ventricular ejection fraction, and coronary artery disease, both age (HR, 1.03 [95% CI, 1.02-1.04]; P<0.0001) and AU (HR, 2.68 [95% CI, 2.11-3.41]; P<0.0001) were independently associated with the development of any AF. Freedom from incident AF at 1-year was significantly lower in patients with AU, both in patients with and without ATTR-CA respectively (HR, 2.27 [95% CI, 1.37-3.78]; P<0.0001 versus HR, 2.21 [95% CI, 1.46-3.34]; P<0.0001). CONCLUSIONS: In a consecutive cohort of patients undergoing 99mTc-PyP scans, 20% had AU, which was statistically associated with any AF, independently of ATTR-CA diagnosis and sex. AU was associated with significantly lower freedom from incident AF at 1-year. Overlooking AU on 99mTc-PyP scans could potentially miss an earlier disease manifestation, or an additional risk factor for any/incident AF.

A Clinico-Pathologic Approach to the Differential Diagnosis of Pericardial Tumors.

PURPOSE OF REVIEW: Tumors of the pericardium are rare, but a wide variety of congenital, infectious, inflammatory, and neoplastic processes have been reported. Pericardial tumors can be categorized as non-neoplastic or neoplastic. Neoplastic lesions can be further divided into benign or malignant, with malignancies being either primary or secondary (metastatic). Clinical, radiographic, and pathologic features of the most common entities are discussed. RECENT FINDINGS: Metastatic neoplasms involving the heart and pericardium are far more common than primary pericardial neoplasms. Of primary pericardial malignancies, mesothelioma is the most common; notably, cytology of effusion fluid is relatively insensitive to the diagnosis. The prognosis for most malignancies of the pericardium, primary or secondary, is poor. Increasingly, clinically recognized diseases that involve the pericardium include Erdheim-Chester and IgG4-related disease. This article provides a comprehensive review of the most recent literature to develop a structured framework to the differential diagnosis of pericardial tumors.

Development of sacral/buttock retiform purpura as an ominous presenting sign of COVID-19 and clinical and histopathologic evolution during severe disease course.

Retiform purpura has been described as a relatively frequent cutaneous finding in patients with coronavirus disease 2019 (COVID-19). The etiology is hypothesized to be related to thrombotic vasculopathy based on lesional biopsy specimen findings, but the pathogenesis of the vasculopathy is not completely understood. Here, we present a case of a retiform purpuric patch on the sacrum/buttocks in a hospitalized patient prior to subsequent diagnosis of COVID-19 and an eventual fatal disease course. Two lesional biopsy specimens at different time points in the disease course revealed thrombotic vasculopathy, despite therapeutic anticoagulation. Detailed histopathologic evaluation using immunohistochemical markers suggest the etiology of the vasculopathy involves both persistent complement activation and platelet aggregation, which possibly promote ongoing thrombus formation. This case highlights that sacral/buttock retiform purpuric patches may be a presenting sign of infection with SARS-CoV-2 virus and may represent an ominous sign supporting a future severe disease course. In addition, biopsy specimen findings at separate time points demonstrate that cutaneous vasculopathy may persist despite adequate systemic anticoagulation, possibly due to the combination of persistent complement and platelet activation. Finally, occlusive thrombi in sacral/buttock retiform purpuric patches may contribute to future ulceration and significant cutaneous morbidity in patients who survive COVID-19.

Homicide by Unspecified Means: Cleveland 2008 to 2019.

ABSTRACT: The diagnosis homicide by unspecified means (HUM) is used to categorize deaths occurring under suspicious or criminal circumstances, but a specific cause of death cannot be identified. In 2010, Matshes and Lew (Am J Forensic Med Pathol. 2010;31(2):174-177) presented a HUM cases series, from which they derived 5 diagnostic criteria; however, the accuracy of these criteria has not been assessed.To identify a validation cohort, Cuyahoga County Medical Examiner's Office records were searched from 2008 to 2019 for cases certified as HUM. Thirteen cases were identified; on review, all cases fulfilled criteria 1, 4, and 5. Only 1 case had a potential anatomic cause of death identified (criterion 2).However, in 3 cases, toxicologic analyses could not be conducted because of skeletonization; in 2 cases, the decedents tested positive for cocaine/benzoylecgonine but were found in proximity to other victims for whom a specific violent cause of death was determined. By strict reading of criterion 3, these cases would have been excluded from the diagnosis of HUM. Perpetrators confessed to homicide in 7 cases, including the 5 cases that failed the toxicologic criterion. The 2010 diagnostic criteria are a reasonable foundation for the determination of HUM; modification of criterion 3 would provide improved flexibility based on clinical judgment.

Autopsy Service Death Certificate Review.

CONTEXT.­: Despite the importance of accurate death statistics for epidemiologic studies and public health initiatives, there remains a high frequency of errors in death certification. This deficiency can be addressed by the hospital autopsy service. OBJECTIVES.­: To improve the quality and accuracy of death certificates issued in the hospital and improve resident and clinician education by initiating a death certificate review process, performed by pathology residents while on their hospital autopsy rotation. DESIGN.­: A resident reviewed all death certificates issued in the hospital daily through the state electronic death certificate filing system and correlated with the decedent's medical record. When errors were found, the resident filed an amended death certificate with the state. If applicable, the Office of the Medical Examiner was contacted to investigate. The original certifying physician was then contacted via email with an explanation for the amendment. RESULTS.­: In 12 months, 590 death certificates were issued by the hospital. Eighty-eight of 590 (15%) were amended. Of those 88 amended, 41 (47%) were missing an underlying cause of death, 7 (8%) had an inaccurate cause of death, 41 (47%) failed to include relevant contributory causes of death, and 17 (19%) had major typographic errors. Of 88, 24 (27%) fell under the Office of the Medical Examiner's jurisdiction and were reported with a subsequent change in the manner of death in 23 of 88 cases (26%). CONCLUSIONS.­: Death certificate review by the autopsy service improves the accuracy of death certification, impacts resident and clinician education, and serves as quality assurance for both the hospital and the state.

Aspergillosis myocarditis in the immunocompromised host.

Invasive cardiac aspergillosis has been rarely described in immunocompromised patients. This disease is difficult to diagnose by conventional laboratory, microbiologic, and imaging techniques, and is often recognized only post-mortem. The authors present the case of a 60-year-old woman admitted with an exacerbation of eosinophilic granulomatosis with polyangitiis (EGPA) who subsequently died from Aspergillus myocarditis, and compare the patient's case to prior literature. This serves as an up-to-date literature review on the topic of invasive cardiac aspergillosis.

Quantifying Macrophages and Hemosiderin in Pediatric Dura Mater.

Determining the age of a subdural hematoma at autopsy is of great interest for medicolegal purposes. The appearance of pigment-laden macrophages is often referenced as evidence that the subdural hematoma is 3-4 days old. However, understanding the significance of macrophages and hemosiderin requires understanding the histology of infant dura. Samples of grossly unremarkable dura taken from 17 pediatric autopsies were identified and histologically confirmed to lack subdural neomembrane. CD68 immunostaining and Prussian blue staining was performed. The CD68-positive cells per high-power field were quantified, and the presence of iron-containing cells was recorded. CD68-positive cells were present in all cases, even in the dural border layer. Iron-containing cells were identified in 59% of cases, and in the dural border layer in 29%. Therefore, CD68-positive and iron-containing cells can be present in pediatric dura without neomembrane or macroscopic subdural hemorrhage, and this requires consideration when estimating the age of a subdural hematoma.

Fatal Rotavirus Infection in a 4-Year-Old with Unsuspected Autoimmune Adrenal Insufficiency.

The diagnosis of adrenal insufficiency is often delayed, as the presenting symptoms of fatigue, abdominal pain, and anorexia are vague and nonspecific. However, timely diagnosis and treatment with replacement steroids are needed to prevent fatal adrenal crisis. While the most common cause of primary adrenal insufficiency in childhood is congenital adrenal hyperplasia, a significant minority (13-23%) is caused by autoimmune destruction of the gland. We present a case of a 4-year-old, previously healthy child who had a one-day history of nausea and vomiting, and was found unresponsive by her caretaker. Despite emergency rescue and transport to the hospital, she was pronounced dead. At autopsy, the adrenal glands were atrophied. Histologic examination revealed lymphocytic infiltration of the adrenal glands consistent with autoimmune adrenal insufficiency. Fecal viral antigen testing was positive for rotavirus. The cause of death was determined to be adrenal crisis in the setting of rotavirus gastroenteritis due to adrenal insufficiency (Addison disease).

Analysis of MT-45, a Novel Synthetic Opioid, in Human Whole Blood by LC-MS-MS and its Identification in a Drug-Related Death.

MT-45 (1-cyclohexyl-4-(1,2-diphenylethyl)piperazine) is just one of the many novel psychoactive substances (NPS) to have reached the recreational drug market in the twenty-first century; it is however, one of the first designer opioids to achieve some degree of popularity, in a market currently dominated by synthetic cannabinoids and designer stimulants. A single fatality involving MT-45 and etizolam is described. A method for the quantitation of MT-45 in whole blood using liquid chromatography-tandem mass spectrometry was developed and validated. The linear range was determined to be 1.0-100 ng/mL with a detection limit of 1.0 ng/mL, and the method met the requirements for acceptable linearity, precision and accuracy. After analyzing the sample on dilution and by standard addition, the concentration of MT-45 in the decedent's blood was determined to be 520 ng/mL, consistent with other concentrations of MT-45 reported in drug-related fatalities. Etizolam was present at a concentration of 35 ng/mL. This case illustrates the importance of considering non-traditional drugs in unexplained apparent drug-related deaths.

A Retrospective Study of Blade Wound Characteristics in Suicide and Homicide.

The distinction between self-inflicted blade wounds and blade wounds inflicted by another can be difficult in situations where there is little available history or context. We reviewed homicides and suicides in the past 10 years at the Vermont Office of the Chief Medical Examiner to define the characteristics of homicidal and suicidal blade wounds. All homicides and suicides involving blade wounds, not just those in which blade wounds were the cause of death, were included. Information regarding victim demographics, location and type of injuries, toxicology, and evidence of suicidality was gathered. Blade wounds were the cause of death in 85.7% of homicides but only in 36% of suicides. Hanging and gunshot wounds were the cause of death in 28% and 24% of suicides, respectively. Multiple stab wounds were found in 10% of homicides and in 0% of suicides, whereas multiple incised wounds were found in 60% of suicides and only 10% of homicides. However, several unusual instances of suicide were found, including suicides with clothing damage or bone or cartilage injury from blade wounds. No characteristics of blade wounds were definitive for homicide or suicide. History and circumstances of the scene are thus crucial in determining the manner of death.