Characteristics of Lambl excrescences of aortic and pulmonary valves in healthy hearts.

Lambl excrescences (LEs) were initially described in the mid-1800s during autopsies of human hearts, and their significance and biology have been debated ever since. LEs are typically found on aortic and pulmonary valve (semilunar) cusps. There is debate concerning whether LEs are a significant cause of thromboembolic events, or whether they are harmless growths. However, there have not been many reports discussing LEs, and fewer still have examined the prevalence and characteristics of LEs in healthy human hearts. Those who have examined LE prevalence have reported a very high incidence of LEs (85-90%). Herein, we examine LE prevalence and characteristics (size, location, number) in 403 healthy human hearts across all age groups. We find that the prevalence of LEs in healthy hearts is far lower than previously reported.

Characteristics of aortic and pulmonary valve cusp fenestrations in healthy hearts.

Fenestrations in semilunar valves of human hearts have been incidentally described during autopsies since the 1800s, and were thought to be a degenerative process of the valve cusps. Due to the nature of autopsy, prior literature has primarily examined these fenestrations in pathologic hearts, and has implicated them in leading to valve insufficiency, regurgitation, and cusp rupture. More recent studies have predicted an increase in fenestration prevalence in the rapidly aging United States and have warned of a potential increase in fenestration-related valvular pathology. Herein, we analyze fenestration prevalence in 403 healthy human hearts and report findings that differ from these prior reports, and emphasize that fenestrations may not necessarily portend significant valvular dysfunction.

Cardiac hemangioma mimicking a neuroendocrine tumor on 68 Ga Dotatate PET/CT.

Cardiac hemangioma is a rare, benign primary tumor characterized by endothelial proliferation. While reports of cardiac hemangiomas demonstrating 18 F FDG avidity and other forms of hemangiomas showing 68 Ga Dotatate avidity have been published, we present a rare case of primary cardiac hemangioma demonstrating 68 Ga Dotatate avidity, mimicking a primary neuroendocrine tumor.

Extracorporeal membrane oxygenation in the forensic setting: A series of 19 forensic cases.

Extracorporeal membrane oxygenation (ECMO) employs vascular cannulation and a gas exchange circuit to provide support to patients with severely compromised cardiopulmonary function. ECMO is often the last intervention taken before death and thus presents a unique challenge to medical examiners. This study describes the characteristics of decedents on ECMO at the time of death, including clinical indications, types of circuit configurations, causes and manners of death, gross findings at autopsy, and therapeutic complications. Files of a regional medical examiner office within an academic medical center were searched for the period between 2013 and 2019. Nineteen cases were identified with a median age of 36 years. The circumstances surrounding the initial presentation included: sudden death, trauma, substance abuse, homicide, therapeutic complication, work-related injury, drowning, and hypothermia. The underlying causes of death included injury-related, as well as respiratory and cardiac-related natural diseases. The time spent on ECMO varied from less than 1 h to 10 months. Complications encountered due to ECMO included cannulation site bleeding, pneumohemopericardium, retroperitoneal hematoma, limb ischemia, clotting, and cannula dislodgement. The patient population likely to receive ECMO has significant overlap with death circumstances likely to be reported to the medical examiner. As ECMO therapy has become increasingly available, it is of importance for medical examiners and death investigators to be familiar with the procedure as well as its limitations. Familiarity with ECMO and its sequelae allows for the proper documentation of postmortem findings and fosters an informed determination of the cause and manner of death.

COVID-19-Associated Nonocclusive Fibrin Microthrombi in the Heart.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resultant clinical presentation, coronavirus disease 2019 (COVID-19), is an emergent cause of mortality worldwide. Cardiac complications secondary to this infection are common; however, the underlying mechanisms of such remain unclear. A detailed cardiac evaluation of a series of individuals with COVID-19 undergoing postmortem evaluation is provided, with 4 aims: (1) describe the pathological spectrum of the myocardium; (2) compare with an alternate viral illness; (3) investigate angiotensin-converting enzyme 2 expression; and (4) provide the first description of the cardiac findings in patients with cleared infection. METHODS: Study cases were identified from institutional files and included COVID-19 (n=15: 12 active, 3 cleared), influenza A/B (n=6), and nonvirally mediated deaths (n=6). Salient information was abstracted from the medical record. Light microscopic findings were recorded. An angiotensin-converting enzyme 2 immunohistochemical H-score was compared across cases. Viral detection encompassed SARS-CoV-2 immunohistochemistry, ultrastructural examination, and droplet digital polymerase chain reaction. RESULTS: Male sex was more common in the COVID-19 group (P=0.05). Nonocclusive fibrin microthrombi (without ischemic injury) were identified in 16 cases (12 COVID-19, 2 influenza, and 2 controls) and were more common in the active COVID-19 cohort (P=0.006). Four active COVID-19 cases showed focal myocarditis, whereas 1 case of cleared COVID-19 showed extensive disease. Arteriolar angiotensin-converting enzyme 2 endothelial expression was lower in COVID-19 cases than in controls (P=0.004). Angiotensin-converting enzyme 2 myocardial expression did not differ by disease category, sex, age, or number of patient comorbidities (P=0.69, P=1.00, P=0.46, P=0.65, respectively). SARS-CoV-2 immunohistochemistry showed nonspecific staining, whereas ultrastructural examination and droplet digital polymerase chain reaction were negative for viral presence. Four patients (26.7%) with COVID-19 had underlying cardiac amyloidosis. Cases with cleared infection had variable presentations. CONCLUSIONS: This detailed histopathologic, immunohistochemical, ultrastructural, and molecular cardiac series showed no definitive evidence of direct myocardial infection. COVID-19 cases frequently have cardiac fibrin microthrombi, without universal acute ischemic injury. Moreover, myocarditis is present in 33.3% of patients with active and cleared COVID-19 but is usually limited in extent. Histological features of resolved infection are variable. Cardiac amyloidosis may be an additional risk factor for severe disease.

Multiple Immune-Suppressive Mechanisms in Fibrolamellar Carcinoma.

Fibrolamellar carcinoma (FLC) is a rare type of liver cancer that affects adolescents and young adults. The most effective treatment for FLC is surgical resection, but no standardized systemic therapy exists for patients with recurrent or unresectable FLC. As a first step to understand the immune microenvironment of FLC, we investigated targetable immune-checkpoint pathways, PD-1, PD-L1, B7-H3, IDO-1, and LAG3, in relation to CD8+ cytotoxic T-lymphocyte density. Thirty-two FLC tumor specimens were analyzed using IHC staining for PD-L1, CD8, PD-1, IDO, LAG3, and B7-H3. Sixty-three percent of FLC cases demonstrated membranous PD-L1 expression on tumor cells, and almost 70% of cases demonstrated PD-L1+ tumor-infiltrating lymphocytes and tumor-associated macrophages (TIL/TAM). Myeloid-derived cells appeared to be a major component of PD-L1+ tumor-infiltrating immune cells. Forty percent of the cases showed B7-H3 expression in the tumor zone, with 91% cases showing B7-H3 expression in TILs and TAMs. IDO and PD-1 expression was highest in the tumor interface zone. B7-H3 or IDO expression on tumor cells significantly correlated with higher CD8+ T-cell density. In conclusion, a high proportion of FLC cases showed robust expression of PD-1, PD-L1, B7-H3, and IDO in an adaptive immune-resistance pattern. Our findings provide further basis for targeting these different immune-checkpoint axes in FLC.

Effective fetch and relative exposure index maps for the Laurentian Great Lakes.

Wind exposure is a key physical driver of coastal systems in aquatic environments influencing circulation and wave dynamics. A measure of wind exposure is fetch, the distance over which wind can travel across open water. In large lake systems, such as the Laurentian Great Lakes, estimating fetch has proven to be difficult due to their vast size and complex topobathymetry. Here we describe the development of two spatially discrete indicators of exposure to provide a more accurate indicator of the influence of wind exposure in the nearshore of the Laurentian Great Lakes. We summarized wind data from offshore buoys and used existing tools to calculate effective fetch and a relative exposure index (effective fetch scaled by mean wind speed) at a 30-m grid cell resolution. We validated these models by comparing our exposure maps to the U.S. Army Corps of Engineers Wave Information Studies models and found general agreement. These exposure maps are available for public download for the years 2004-2014.

Epidemiology of vestibular evoked myogenic potentials: Data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To evaluate whether age-related changes in vestibular evoked myogenic potentials (VEMPs) differ by demographic and cardiovascular risk groups. METHODS: Participants in the Baltimore Longitudinal Study of Aging underwent cervical and ocular VEMP testing. VEMP latency, amplitude, asymmetry ratios, and prevalence of absent responses were compared across demographic and cardiovascular risk groups. RESULTS: In 257 participants (mean age 72.9, 57% female), ocular VEMP (oVEMP) n10 latency increased by 0.12ms/decade while amplitude decreased by 2.9µV/decade. Black participants had better oVEMP function (shorter latency, increased amplitude, and decreased odds of absent responses) relative to white participants. In 250 participants (mean age 72.6, 54% female), EMG-corrected cervical VEMP (cVEMP) amplitude decreased by 0.14µV/decade and p13 latency was 0.38ms longer in males. The odds of absent responses were significantly higher in individuals age ⩾80 for oVEMPs, and age ⩾70 for cVEMPs. Cardiovascular risk factors had no association with VEMP parameters. CONCLUSIONS: We confirmed age-related declines in otolith function, and observed a protective effect of black race on oVEMP latency and amplitude. SIGNIFICANCE: These results illustrate how measures of otolith function change with age in community-dwelling adults. Further investigations are needed to ascertain whether better otolith function in blacks might contribute to a lower risk of mobility disability and falls.

Association between saccular function and gait speed: data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To investigate whether otolith function (saccular and utricular) is associated with walking performance. STUDY DESIGN: Cross-sectional analysis of observational data collected in the Baltimore Longitudinal Study of Aging. SETTING: National Institute on Aging Intramural Research Program Clinical Research Unit at Harbor Hospital, Baltimore, Maryland. PATIENTS: Community-dwelling participants. INTERVENTION(S): Cervical and ocular vestibular evoked myogenic potentials (VEMPs) were used to assess saccular and utricular function, respectively. MAIN OUTCOME MEASURE(S): Cervical and ocular VEMP latency and amplitude responses and usual, rapid, and narrow (20 cm) gait speed assessed over a 6-m course. RESULTS: In 314 participants (mean age, 73.1 yr; range, 26-96 yr), cervical VEMP amplitude mediated the association between age and gait speed-particularly narrow walk speed-in both men and women. Cervical VEMP latency had an independent association with gait speed in age-, height-, and weight-adjusted analyses, although the direction of the association differed by sex. Greater cervical VEMP latency was associated with slower usual, rapid, and narrow gait speed in women but faster rapid gait speed in men. Neither the amplitude nor latency of ocular VEMP was associated with gait speed in men or women. CONCLUSION: These findings suggest that age-related slowing of gait speed is in part mediated by the decreased magnitude of saccular response associated with age. The sex-related differential association between saccular response latency and gait speed requires further study.

Epidemiology of vestibulo-ocular reflex function: data from the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To determine age-related changes in vestibulo-ocular reflex (VOR) function in community-dwelling adults, and evaluate these for associations with demographic characteristics and cardiovascular risk factors. STUDY DESIGN: Cross-sectional analysis within the Baltimore Longitudinal Study of Aging (BLSA), a longitudinal prospective cohort study. SETTING: Vestibular testing laboratory within an acute care teaching hospital. PATIENTS: Community-dwelling adults enrolled in the BLSA. INTERVENTION(S): Horizontal VOR gain measurement using video head-impulse testing and visual acuity testing. MAIN OUTCOME MEASURE(S): VOR gain was calculated as the ratio of eye velocity to head velocity. Demographic and cardiovascular risk factor data were collected through study questionnaires. RESULTS: One hundred nine subjects were analyzed with mean age (SD) 69.9 years (14.2), with a range from 26 to 92 years. VOR gain remained stable from age 26 to 79 after which it significantly declined at a rate of 0.012/year (p = 0.033) in adjusted analyses. Individuals aged 80 years or older had a nearly 8-fold increased odds of VOR gain less than 0.80 relative to those aged less than 80 years in multivariate models (prevalence of 13.2% vs. 2.8%; OR 7.79, 95% CI: 1.04-58.38). Otherwise, VOR gain did not differ significantly across demographic or cardiovascular risk groups. CONCLUSION: We report age-related decline in VOR function in individuals aged 80 years and older. Further analyses are in progress to establish the significance of these VOR abnormalities to functional and mobility outcomes in older individuals.

Late stage erythroid precursor production is impaired in mice with chronic inflammation.

BACKGROUND: We and others have shown previously that over-expression of hepcidin antimicrobial peptide, independently of inflammation, induces several features of anemia of inflammation and chronic disease, including hypoferremia, sequestration of iron stores and iron-restricted erythropoiesis. Because the iron-restricted erythropoiesis evident in hepcidin transgenic mice differs from the normocytic, normochromic anemia most often observed in anemia of inflammation, we tested the hypothesis that chronic inflammation may contribute additional features to anemia of inflammation which continue to impair erythropoiesis following the acute phase of inflammation in which hepcidin is active. DESIGN AND METHODS: We compared erythropoiesis and iron handling in mice with turpentine-induced sterile abscesses with erythropoiesis and iron handling in hepcidin transgenic mice. We compared erythrocyte indices, expression of genes in the hepcidin regulatory pathway, tissue iron distribution, expression of heme and iron transport genes in splenic macrophages, the phenotype of erythroid maturation and chloromethyl dichlorodihydrofluorescein diacetate, acetyl ester fluorescence. RESULTS: Mice with sterile abscesses exhibited an intense, acute inflammatory phase followed by a mild to moderate chronic inflammatory phase. We found that erythrocytes in mice with sterile abscesses were normocytic and normochromic in contrast to those in hepcidin transgenic mice. We also observed that although hypoferremia resolved in the late phases of inflammation, erythropoiesis remained suppressed, with evidence of inefficient maturation of erythroid precursors in the bone marrow of mice with sterile abscesses. Finally, we observed increased oxidative stress in erythroid progenitors and circulating erythrocytes of mice with sterile abscesses which was not evident in hepcidin transgenic mice. CONCLUSIONS: Our results suggest that chronic inflammation inhibits late stages of erythroid production in the turpentine-induced sterile abscess model and induces features of impaired erythropoiesis which are distinct from those in hepcidin transgenic mice.