Younger age is associated with cardiovascular pathological phenotype of severe COVID-19 at autopsy.

Introduction: COVID-19 affects patients of all ages. There are few autopsy studies focusing on the younger population. We assessed an autopsy cohort aiming to understand how age influences pathological outcomes in fatal COVID-19. Methods: This study included autopsied patients, aged 6 months to 83 years, with confirmed COVID-19 in 2020-2021. We collected tissue samples from deceased patients using a minimally invasive autopsy protocol and assessed pathological data following a systematic approach. Results: Eighty-six patients were included, with a median age of 55 years (IQR 32.3-66.0). We showed that age was significantly lower in patients with acute heart ischemia (p = 0.004), myocarditis (p = 0.03) and lung angiomatosis (p < 0.001), and significantly higher in patients with exudative diffuse alveolar damage (p = 0.02), proliferative diffuse alveolar damage (p < 0.001), lung squamous metaplasia (p = 0.003) and lung viral atypia (p = 0.03), compared to patients without those findings. We stratified patients by their age and showed that cardiovascular findings were more prevalent in children and young adults. We performed principal component analysis and cluster of pathological variables, and showed that cardiovascular variables clustered and covariated together, and separated from pulmonary variables. Conclusion: We showed that age modulates pathological outcomes in fatal COVID-19. Younger age is associated with cardiovascular abnormalities and older age with pulmonary findings.

Perivascular clusters of Th2 cells and M2 macrophages in allergic contact dermatitis to methylchloroisothiazolinone and methylisothiazolinone.

BACKGROUND: Methylisothiazolinone (MI) and Methylchloroisothiazolinone (MCI) are among the most common skin sensitizers, yet the immunological events that occur during MCI/MI allergic contact dermatitis (ACD) are still poorly understood. OBJECTIVES: To analyse dendrocytes, macrophage subtypes and T cells in skin during the elicitation phase of MCI/MI ACD. METHODS: Thirteen patients with positive patch test reactions to MCI/MI (ACD group) and 11 individuals with negative patch test results were selected. Skin biopsies were only performed at 48 hours of patch testing. Immunohistochemistry was conducted to assess T cells, dendrocytes (Factor XIIIa), M1 (p-Stat1, CD68) and M2 (c-Maf, CD163) macrophages. Transcriptional analyses were performed for cytokines and related factors, and further compared to atopic dermatitis samples (n=4). Immunofluorescence assays addressed T cells location, along with IL-4 or IL-13, within the skin. RESULTS: MCI/MI elicited dermal dendrocytes and macrophages, pronouncedly the M2 subtype. T cells, majorly CD4+ T cells, accumulated in the perivascular areas. Similarly, abundant IL-4 protein was detected in these areas. There was an upregulation of IL-4 and IL-13 mRNA expression, a mild increase in IFNG mRNA levels and a down-regulation of RORC in the ACD group. Immunofluorescence revealed dermal clusters of T cells co-localized with IL-4. CONCLUSIONS: M2 macrophages and Th2 cells participate in the immunopathogenesis of MCI/MI ACD. Dermal dendrocytes and M2 macrophages may assist the formation of CD4+ T cells perivascular clusters. These findings render a mechanistic insight into the MCI/MI reaction. Further analysis at different timepoints of patch testing is required to fully comprehend this ACD kinetics.

Evidence of bone marrow downregulation in brain-dead rats.

Experimental findings support the evidence of a persistent leucopenia triggered by brain death (BD). This study aimed to investigate leucocyte behaviour in bone marrow and blood after BD in rats. BD was induced using intracranial balloon catheter inflation. Sham-operated (SH) rats were trepanned only. Thereafter bone marrow cells were harvested every six hours from the femoral cavity and used for total and differential counts. They were analysed further by flow cytometry to characterize lymphocyte subsets, granulocyte adhesion molecules expression and apoptosis/necrosis [annexin V/propidium iodide (PI) protocol]. BD rats exhibited a reduction in bone marrow cells due to a reduction in lymphocytes (40%) and segmented cells (45%). Bone marrow lymphocyte subsets were similar in BD and SH rats (CD3, P = 0.1; CD4, P = 0.4; CD3/CD4, P = 0.4; CD5, P = 0.4, CD3/CD5, P = 0.2; CD8, P = 0.8). Expression of L-selectin and beta2 -integrins on granulocytes did not differ (CD11a, P = 0.9; CD11b/c, P = 0.7; CD62L, P = 0.1). There were no differences in the percentage of apoptosis and necrosis (Annexin V, P = 0.73; PI, P = 0.21; Annexin V/PI, P = 0.29). In conclusion, data presented suggest that the downregulation of the bone marrow is triggered by brain death itself, and it is not related to changes in lymphocyte subsets, granulocyte adhesion molecules expression or apoptosis and necrosis.

Periprostatic innervation: New issues based on segmental analysis of 10 human cadaver pelvic blocs.

BACKGROUND: The exact paths of periprostatic nerves have been under debate over the last decades. In the present study, the topographic distribution of nerves around the prostate and their relative distances from the prostatic capsule were analyzed in male cadaver visceral blocs. METHODS: The pelvic organs from ten fresh male cadavers were removed and serial sectioned en bloc for histological investigation. The macroslices was divided into four sectors. Each sector was centrally covered with a raster dividing each sector in three subsectors numbered clockwise. The prostatic capsule was identified, and distances of 2.5 and 5 mm from the prostate were demarked with lines. We quantified the number of nerve fibers present in each subsector of each slide and recorded their position relative to the prostatic capsule. RESULTS: In general, the topographic analysis revealed that the majority of nerves were identified in sectors 4 through 9, corresponding to the posterolateral and posterior surfaces of the prostate gland. At the prostate base, the majority of nerves were found at the posterolateral and posterior surfaces of the gland. Within the mid-region of the prostate, the same topographic distribution pattern was observed, but the nerve fibers were closer to the prostatic capsule. At the apical region, the percentage of nerve fibers identified in the anterior region was higher, despite their major concetration in the posterior surface. The nerves identified at the apex were mainly located up to 2.5 mm from the prostate. This proximity to the prostate was specifically observed in the anterolateral and anterior sectors. In the craniocaudal sense, the percentage of nerves identified between 2.5 and 5 mm from the prostatic capsule remained constant. CONCLUSIONS: A significant number of nerve fibers were present in the anterior and anterolateral positions, especially at the apex. The anterior nerves were closer to the prostate. This proximity suggests that the anterior nerves may participate in local physiology and that the cavernous nerves are probably formed by the posterior nerve fibers. It is likely that the safe distance of 2.5 mm from all surfaces of the prostate may be related to cavernous fiber preservation.