COVID-19 Pathology in the Lung, Kidney, Heart and Brain: The Different Roles of T-Cells, Macrophages, and Microthrombosis.

Here, we aim to describe COVID-19 pathology across different tissues to clarify the disease's pathophysiology. Lungs, kidneys, hearts, and brains from nine COVID-19 autopsies were compared by using antibodies against SARS-CoV-2, macrophages-microglia, T-lymphocytes, B-lymphocytes, and activated platelets. Alzheimer's Disease pathology was also assessed. PCR techniques were used to verify the presence of viral RNA. COVID-19 cases had a short clinical course (0-32 days) and their mean age was 77.4 y/o. Hypoxic changes and inflammatory infiltrates were present across all tissues. The lymphocytic component in the lungs and kidneys was predominant over that of other tissues (p < 0.001), with a significantly greater presence of T-lymphocytes in the lungs (p = 0.020), which showed the greatest presence of viral antigens. The heart showed scant SARS-CoV-2 traces in the endothelium-endocardium, foci of activated macrophages, and rare lymphocytes. The brain showed scarce SARS-CoV-2 traces, prominent microglial activation, and rare lymphocytes. The pons exhibited the highest microglial activation (p = 0.017). Microthrombosis was significantly higher in COVID-19 lungs (p = 0.023) compared with controls. The most characteristic pathological features of COVID-19 were an abundance of T-lymphocytes and microthrombosis in the lung and relevant microglial hyperactivation in the brainstem. This study suggests that the long-term sequelae of COVID-19 derive from persistent inflammation, rather than persistent viral replication.

Drug Abuse-Related Neuroinflammation in Human Postmortem Brains: An Immunohistochemical Approach.

The aim of the study was to investigate blood-brain barrier alterations, neuroinflammation, and glial responses in drug abusers. Five immunohistochemical markers (CD3, zonula occludens-1 [ZO-1], intracellular adhesion molecule 1 [ICAM-1], vascular cell adhesion molecule [VCAM-1], and glial fibrillary acidic protein [GFAP]) were assessed on postmortem brain samples collected from drug abusers who died from acute intoxication of cocaine, heroin, or a combination of both, compared with controls. CD3 and ICAM-1 immunopositivity were significantly stronger in drug abusers than in controls. VCAM-1 immunopositivity was similar across drug abuser and control groups. In heroin abusers, significantly lower ZO-1 immunopositivity was observed relative to controls. GFAP positivity did not show significant differences between groups, but its distribution within the brain did differ. Both cocaine and heroin abuse promoted neuroinflammation, increasing expression of ICAM-1 and recruiting CD3+ lymphocytes. Heroin affected the molecular integrity of tight junctions, as reflected by reduced ZO-1 expression. The outcomes of the present study are, overall, consistent with prior available evidence, which is almost exclusively from studies conducted in vitro or in animal models. These findings provide important information about the downstream consequences of neuroinflammation in drug abusers and may help to inform the development of potential therapeutic targets.

Pre and post operative radiation protection in Ru-106 brachytherapy ophthalmic plaque surgery and related material shielding properties.

Pre and post-operative exposure levels of medical staff and people from public in intra-operative Ru-106 ophthalmic brachytherapy are reported, together with attenuation properties of selected shielding materials. In particular radiation exposure of workers during plaque transportation and during medical assistance of implanted plaque patient was measured. Taking into account dose rates and considering standard assistance procedure of hospitalized patients, the exposure of medical staff and people of the public were evaluated for a given workload. In order to provide tools to optimize radiation protection, considering social and economic aspects due to possible hospital discharge or hospital stay, the attenuation properties of common shielding materials (lead, concrete, red brick, PMMA and gypsum) were measured, considering both narrow and broad beam setups. The eye was simulated using a water equivalent phantom and plaque was fixed on it. All measurements were performed with calibrated survey meters. Results were compared with numerical simulation of bremsstrahlung X-ray radiation spectra emitted from patient eye. Exposure levels measured at 1 m distance in front of the implanted eye are 0.05 µSv/h/MBq, at 10 cm from patient head, 0.44 µSv/h/MBq (plaque side), 0.4 µSv/h/MBq (front), 0.25 µSv/h/MBq (lateral, opposed to plaque), 0.2 µSv/h/MBq (back). Average exposure levels, under conservative assumptions, for medical staff is 17 µSv/patient and less than 23 µSv/patient for careers and comforters. TVLs in lead and concrete are about 1.6 cm and 11.5 cm respectively.

Resovist enhanced MR imaging of the liver: does quantitative assessment help in focal lesion classification and characterization?

PURPOSE: To improve characterization of focal liver lesions by a prospective quantitative analysis of percentage signal intensity change, in dynamic and late phases after slow (0.5 mL/s) Resovist administration. MATERIALS AND METHODS: Seventy-three patients were submitted on clinical indication to MR examination with Resovist. Signal intensity of 92 detected focal lesions (5-80 mm) were measured with regions of interest and normalized to paravertebral muscle in arterial, portal, equilibrium and T1/T2 late phases, by two observers in conference. Five values of percentage variations per patient were obtained and statistically evaluated. RESULTS: The enhancement obtained on dynamic study is more suitable in hemangiomas and focal nodular hyperplasias than in adenomas and hepatocellular carcinomas. To discriminate benign versus malignant lesions on late-phase-T2-weighted images, a cutoff = -26%, allowed sensitivity and specificity values of 97.4% and 97.7%, respectively. Area under the receiver operating characteristic (ROC) curve was 0.99. To differentiate hemangioma versus all other focal liver lesions, on late-phase-T1-weighted images, a cutoff = +40% permitted sensitivity and specificity values of 90.5% and 98.0%, respectively. Area under the ROC curve was 0.98. CONCLUSION: Late phase quantitative evaluation after slow Resovist administration, allows to differentiate malignant from benign hepatic masses and hemangiomas from all the others focal liver lesions, on T2-/T1-weighted acquisitions, respectively. J

Transient hepatic attenuation differences and focal liver lesions: sump effect due to primary arterial hyperperfusion.

OBJECTIVE: To analyze at computed tomography (CT) examination the "sump effect," a particular type of transient hepatic attenuation differences, related primarily to an increase in arterial flow without any accompanying decrease in portal flow. METHODS: We retrospectively evaluated all biphasic upper abdomen CT examinations (1283 in 807 patients) performed from the year 2003 to the year 2006 and selected and organized those with at least 1 transient hepatic attenuation differences. Of these, we enrolled patients with lobar/multisegmental arterializations surrounding focal lesion(s), without CT portal hypoperfusion signs, in the study group. We assessed histology, number, site, diameter, and volume of causing focal lesion(s); site, extension, and attenuation of arterial area; greater visibility of feeding artery branches ipsilateral to causal focal lesion; and presence of aberrant left hepatic artery. Thirty patients with normal liver represented the control group. RESULTS: Fifteen of the 99 patients with transient hepatic attenuation differences presented with sump effect. In our series, this phenomenon was always related to hypervascular inflammatory and benign lesion(s) with overall average diameter of 8 +/- 4 cm inscribed in arterial area. Attenuation of arterial enhanced areas were significantly higher than the contralateral parenchyma and control patients' parenchyma, with frequent hypertrophy of ipsilateral arterial feeding branches and/or aberrant left hepatic artery visibility. CONCLUSIONS: Siphonage seems to be primary hyperperfusion area determined by arterial bed enlargement, induced by inscribed large hypervascular inflammatory/benign lesion(s).

Performance of Doppler ultrasound in the prediction of severe portal hypertension in hepatitis C virus-related chronic liver disease.

PURPOSE: To evaluate the correlation between hepatic vein pressure gradient measurement and Doppler ultrasonography (DUS) in patients with chronic liver disease (CLD). PATIENTS AND METHODS: Sixty-six patients with fibrotic to cirrhotic hepatitis C virus-related CLD, were consecutively included upon referral to our haemodynamic laboratory. Superior mesenteric artery pulsatility index (SMA-PI), right interlobar renal and intraparenchymal splenic artery resistance indices, were determined, followed by hepatic venous pressure gradient (HVPG) measurement. RESULTS: A correlation was found between HVPG and intraparenchymal splenic artery resistance index (SA-RI) (r=0.50, P<0.0001), SMA-PI (r=-0,48, P<0.0001), right interlobar renal artery resistance index (RRA-RI) (r=0.51, P<0.0001) in the whole patient population. However, dividing patients according to the presence/absence of severe portal hypertension (i.e. HVPG > or =12 mmHg), a correlation between HVPG and intraparenchymal SA-RI (r=0.70, P<0.0001), SMA-PI (r=-0.49, P=0.02), RRA-RI (r=0.66, P=0.0002) was observed only for HVPG values <12 mmHg. HVPG but not DUS correlated with the presence of esophageal varices (P<0.0001). CONCLUSIONS: Superior mesenteric artery pulsatility index, intraparenchymal splenic and right interlobar renal artery resistance indices do not adequately predict severe portal hypertension.

Subcortical damage and cortical functional changes in men and women with Fabry disease: a multifaceted MR study.

PURPOSE: To prospectively compare brain magnetic resonance (MR) imaging and hydrogen 1 (1H) MR spectroscopy findings and to use functional MR imaging to explore the patterns of brain activation in men and women with Fabry disease (FD). MATERIALS AND METHODS: Eight men and eight women with FD (mean age, 38.8 years +/- 13.9 [standard deviation]) with absent or mild neurologic deficit and 16 healthy control subjects (eight men and eight women; mean age, 42.7 years +/- 15.3) gave informed consent to participate in the study, which was approved by the local ethical committee. Patients and control subjects underwent MR imaging, 1H MR spectroscopy of the frontal cortex and subcortical white matter, and functional MR imaging during repetitive flexion-extension of the last four fingers of the right hand. Extent of cerebral white matter damage was rated on fluid-attenuated inversion recovery MR images by using a visual score. Areas of activation were identified by using statistical parametric mapping software and the adoption of a height threshold of P < .001 (uncorrected) and an extent threshold of P < .05 (corrected). RESULTS: Men and women with FD showed a similar distribution of cerebral white matter changes, lacunar and cortical infarcts, small hemorrhages, and vertebrobasilar dolichoectasia. No significant (P > .05) difference was observed between patients with FD and control subjects for concentration of N-acetylaspartate, creatine, and choline. During the motor task, patients showed recruitment of additional cortical areas in comparison with control subjects. Increased activation of the contralateral sensorimotor area correlated (P = .002) with extent of white matter damage. CONCLUSION: Subcortical ischemic changes in men and women with FD are similar and are associated with increased recruitment of the sensorimotor network during a simple motor task, which might limit the functional effect of the white matter small-vessel disease.

Risk-benefit analysis of X-ray exposure associated with lung cancer screening in the Italung-CT trial.

OBJECTIVE: Prior analyses of X-ray exposures in lung cancer screening with CT considered the basic acquisition technique in single-detector scanners and the effects of a lifetime screening regimen, whereas the potential benefit in terms of lives saved was not addressed. MATERIALS AND METHODS: We determined the total-body effective dose of different acquisition techniques for one single-detector and one MDCT scanner and made projections about the cumulative radiation exposure to smokers undergoing four annual CT examinations on the same scanners in the Italung-CT Trial. Combining these data with estimates of radiation-induced fatal cancer and of the benefit of screening, we calculated the risk-benefit ratio for participants in the trial, ex-smokers, and never-smokers. RESULTS: The cumulative effective doses per 1,000 subjects were 3.3 Sv using an MDCT scanner and 5.8 or 7.1 Sv using a single-detector scanner. Potential fatal cancers associated with radiation exposure were 0.11 per 1,000 subjects for MDCT scanners and 0.20 or 0.24 for single-detector scanners, which is about 10-100 times lower than the number of expected lives saved by screening assuming a 20-30% lung cancer-specific mortality reduction in current smokers. They were, however, of similar magnitude to the lives saved by screening in never-smokers and former smokers assuming a 10% efficacy of screening. CONCLUSION: MDCT is associated with lower radiation doses than single-detector CT technology. The risk of radiation dose in the Italung-CT Trial is compensated for by the expected benefit. CT screening for lung cancer should not be offered to never-smokers, whereas its recommendation in former smokers is debatable.