Ultrastructural findings of lung injury due to Vaccine-induced Immune Thrombotic Thrombo- cytopenia (VITT) following COVID-19 vaccination: a scanning electron microscopic study.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare new syndrome occurring after the ChAdOx1 nCoV-19 vaccine immunization. Patients with VITT are characterized by a variable clinical presentation, likewise also the outcome of these patients is very variable. Here we report the lung ultrastructural findings in the course of VITT of a 58-year-old male patient. Alveoli were mainly dilated, irregular in shape, and occupied by a reticular network of fibrin, while interalveolar septa appeared thickened. The proliferation of small capillaries gave rise to plexiform structures and pulmonary capillary hemangiomatosis-like features. Near the alveoli occupied by a dense fibrin network, the medium-sized arteries showed a modified wall and an intraluminal thrombus. This scenario looks quite similar to that found during COVID-19, where the lungs suffer from the attack of the antigen-antibodies complexes and the virus respectively. In both diseases, the final outcome is a severe inflammation, activation of the haemostatic system and fibrinolysis.

Thrombotic sinusoiditis and local diffuse intrasinusoidal coagulation in the liver of subjects affected by COVID-19: the evidence from histology and scanning electron microscopy.

OBJECTIVE: Liver injury has been reported in patients with COVID-19. This condition is characterized by severe outcome and could be related with the ability of SARS-CoV-2 to activate cytotoxic T cells. The purpose of this study is to show the histological and scanning electron microscopy features of liver involvement in COVID-19 to characterize the liver changes caused by the activation of multiple molecular pathways following this infection. PATIENTS AND METHODS: Liver biopsies from 4 patients (3 post-mortems and 1 in vivo) with COVID-19 were analyzed with histology and by scanning electron microscopy. RESULTS: The liver changes showed significant heterogeneity. The first case showed ground glass hepatocytes and scattered fibrin aggregates in the sinusoidal lumen. The second evidenced intra-sinusoidal thrombi. The third was characterized by sinusoidal dilatation, atrophy of hepatocytes, Disse's spaces dilatation and intra-sinusoidal aggregates of fibrin and red blood cells. The fourth case exhibited diffuse fibrin aggregates in the dilated Disse spaces and microthrombi in the sinusoidal lumen. CONCLUSIONS: In COVID-19-related liver injury, a large spectrum of pathological changes was observed. The most peculiar features were very mild inflammation, intra-sinusoidal changes, including sinusoidal dilatation, thrombotic sinusoiditis and diffuse intra-sinusoidal fibrin deposition. These findings suggested that a thrombotic sinusoiditis followed by a local diffuse intra-vascular (intra-sinusoidal) coagulation could be the typical features of the SARS-CoV-2-related liver injury.

Vaccine-induced severe thrombotic thrombocytopenia following COVID-19 vaccination: a report of an autoptic case and review of the literature.

OBJECTIVE: Vaccine-induced immune thrombocytopenia (VITT) is a new syndrome occurring primarily in healthy young adults, with a female predominance, after receiving the first dose of ChAdOx1 nCoV-19 vaccine. We describe VITT syndrome characterized by severe thrombosis and thrombocytopenia found in our patient, with fatal outcome. CASE REPORT: A 58-year-old man, after 13 days from the first administration of ChAdOx1 nCoV-19 vaccine (AstraZeneca), presented with abdominal pain, diarrhea and vomitus. Laboratory tests revealed a severe thrombocytopenia, low fibrinogen serum levels and marked increase of D-dimer serum levels. The patient quickly developed a multiple organ failure, till death, three days after the hospital admission. RESULTS: At histology, in the lungs, interalveolar septa appeared thickened with microthrombi in the capillaries and veins. Interalveolar septa appeared thickened and showed vascular proliferation. Thrombi were detected in the capillaries of glomerular tufts. In the hearth, thrombi were observed in veins and capillaries. In the liver, voluminous fibrin thrombi were diffusely observed in the branches of the portal vein. Microthrombi were also found in the vasa vasorum of the wall of abdominal aorta. In the brain, microthrombi were observed in the capillaries of the choroid plexuses. Diffuse hemorrhagic necrosis was observed in the intestinal wall with marked congestion of the venous vessels. CONCLUSIONS: In our patient, the majority of data necessary for a VITT final diagnosis were present: thrombocytopenia and thrombosis in pulmonary, portal, hepatic, renal and mesenteric veins, associated with a marked increase of D-dimer serum levels. The finding of cerebral thrombosis in choroid plexuses, is a new finding in VITT. These features are suggestive for a very aggressive form of VITT.

Scanning electron microscopy of lung disease due to COVID-19 - a case report and a review of the literature.

OBJECTIVE: The ongoing Coronavirus pandemic (COVID-19) showed similar characteristics with the severe acute respiratory syndrome (SARS). In the most compromised cases, COVID-19 infection leads to death due to severe respiratory complications. COVID-19-related acute respiratory distress syndrome (ARDS) is the primary cause of death in these patients. In the present study, we show an ultrastructural analysis on the lungs of a patient affected by COVID-19. PATIENTS AND METHODS: Lung specimens obtained at autopsy from a 63-years old patient affected by COVID-19 were fixed in 1% paraformaldehyde. Slices of 300 µm thickness were dehydrated and dried by Critical Point Drying in CO2. Slices were covered with a conductive gold film approximately 30 nm thick and observed at a Zeiss Sigma 300 SEM FEG in the secondary electron (SE) and backscattered electron (BSE) modes. As case control a lung biopsy from a 60-year-old man was considered. RESULTS: At low power in all COVID-19 lung specimens severe changes in the pulmonary architecture were found, due to the collapse of air spaces. Moreover, alveolar cavities were covered by large membranes. At high power, alveolar membranes showed a fibrillar structure, suggestive of a loose network of fibrin. It has been also found that intra-alveolar red blood cells were frequently present in the alveolar spaces, surrounded by a reticular fibrin network, suggestive for fibrin-hemorrhagic alveolitis. Alveolar changes were constantly associated with pathological features related to the pulmonary vessels. Vascular changes were prominent, including endothelial damage and thrombosis of large pulmonary vessels. Fibrinous microthrombi were frequently detected in the inter-alveolar septal capillaries. In addition, it has been frequently detected capillary proliferation in the alveolar septa with finding suggestive for intussusceptive neo-angiogenesis. CONCLUSIONS: In conclusion, our electron microscopy analysis showed that COVID-19-related lung disease is characterized by a substantial architectural distortion, with the interactions between alveolar and vascular changes. Intra-alveolar hyaline membranes are associated with macro- and micro-thrombotic angiopathy, ending with capillary proliferation. The new blood vessel formation originates from the septa and extends into the surrounding parenchyma. Our findings confirm previous reports on the specificity of the multiple and complex morphological pattern typical, and apparently specific, of COVID-19-related lung disease.

[Stress and work-related injuries]. / Stress e infortuni sul lavoro.

OBJECTIVE: The aim of this study was to evaluate in scientific literature the more frequent work injuries among the occupational categories examined (construction workers, healthcare workers, night workers and shift work, drivers) and to identify occupational stressors that increase the risk of injury. MATERIALS AND METHODS: The research was conducted through review of the scientific literature between 1990 and 2014. Two hundred articles were found of which 42 selected in the following categories: construction workers, healthcare workers, shift workers, lorry drivers. RESULTS: The movement of machinery and working at height are due to injury for building sector and they were positively correlated with physical (r = 0,206) and mental (r = 0,254) stress. In health workers the injuries are more frequently bruises and sprains (50%). Studies showed a higher rate of injury in a group of shift workers compared to a control group on a rota basis (p <0.0001). Road accidents for drivers represent the most frequent cause of injury of which 13% comes from falling asleep, while 31% from distractions (OR = 3.16; CI = 1:22 to 8:24). CONCLUSIONS: Nurses have frequent injuries due to bruises, lumbago, punctures with needles and surgical wounds. Construction workers often suffer serious injury derived from falls at height, handling machinery. For workers on a rota basis, injuries are often related to lack of sleep. Road accidents in drivers are the most common injuries. A synergistic action finalized to promote health and safety organization, to ensure a work environment more secure, is advisable.

Occupational exposure to urban stressors and effects on atrial natriuretic peptide: preliminary results.

PURPOSE: The aim of this pilot study is to evaluate whether occupational exposure to low doses of pollutants present in the air of the city selected for the study could cause alterations in the concentration of atrial natriuretic peptide (ANP) in workers from the Municipal Police with outdoor tasks, compared to those with indoor tasks. METHODS: A total of 208 non-smoking male and female subjects were enrolled and divided on the basis of whether their tasks were mainly outdoors or indoors. The dosage of plasma ANP was carried out on all workers included in the study. Differences between means and frequencies were compared using student's t-test for unpaired data and chi-square test with Yates' correction, and they were considered significant when the p value was <0.05. RESULTS: Even after the subdivision of the total sample on the basis of sex, mean plasma levels of ANP were higher but not statistically significant in traffic police compared with controls. CONCLUSIONS: The preliminary results suggest that further studies should be conducted before the influence of urban pollution on ANP could be confirmed or rejected.

Work related etiology of amyotrophic lateral sclerosis (ALS): a meta-analysis.

BACKGROUND: The aim of this meta-analysis was to evaluate the association between ALS and occupational exposure to physical (ELF-EMF) and chemicals (solvents, heavy metals and pesticides) agents. METHODS: We considered articles published from 1980 up to April 2013; in total, 750 publications were evaluated. The studies had to satisfy the following criteria: 1) cohort or case-control studies; 2) the presence of individual exposures; 3) clinical diagnosis of sporadic ALS or sporadic ALS on the death certificate. We followed the evaluation of quality in two steps. The first step classified studies according to a rating system based on a mix of criteria developed by scientific organizations, especially developed for studies of risk factors for ALS. The ratings obtained range from I (highest) to V (lowest). The data on risk factors derived from studies with Armon ratings of I, II, and III can reach levels of evidence A (established risk factor), B (likely risk factor), or C (possible risk factor). The second step evaluated the exposure and a score from 1 to 4 was assigned to each item; an exposure with a score of 3 or 4 was considered sufficient. Different analyses were performed on ALS and exposure to metals, solvents, pesticides and electromagnetic fields. In our study the heterogeneity was assessed both by χ2-based Q-tests and through the index of inconsistency I² while the measure RR/OR and CI of 95% to estimate the relationship between ALS and the various considered risk factors was employed. RESULTS: The association between exposure to pesticides and ALS as a whole is weak and not significant. With regard to the results of individual studies the following critical synthesis can be reported: 1) the selected studies showed a low level of association between ALS and electromagnetic fields; 2) as regards the solvents, the association with ALS in some studies is combined with a slightly increased risk, particularly in women, and in others a slight but significant linear association is observed; 3) for the metals, in some cases there was a stronger association in women than in men; for individual metals, there was an association especially with chromium and lead; 4) lastly, with regard to the products of agricultural pesticides in general, there was an association with ALS in men but not in women, with a dose-response relationship. CONCLUSIONS: The lack of statistically significant association between occupational exposure and ALS is mainly due to the methodological diversity of the studies and the lack of prospective studies at the workplace.

Workers of the printing industry and hepatic damage.

BACKGROUND: Typesetting industry is still the primary instrument of communication, despite the development of new technological systems. This study focuses on the analysis of the hepatic effects induced by the use of some organic solvents employed in the printing industry. METHODS: We studied a group of 194 workers: 93 exposed and 101 not exposed. The level of the exposure to chemical pollutants were assessed through the environmental monitoring of blood concentrations and the analysis of airborne substances. The health survey was performed through the collection of the medical history and the use of hepatic tests, which were evaluated by calculating Mean, Standard Deviation, Student's t-test and X² test with Yates Correction, to investigate statistically significant differences in some hepatic parameters: AST, ALT, ALP, GGT, fractional and total bilirubin. The environmental data sometimes exceeded the TLV-TWA. RESULTS: The clinical evaluation of the hepatic parameters showed statistically significant differences as to the hematic concentrations of AST, ALT, GGT. CONCLUSIONS: The results we obtained support the hypothesis of a risk among the printing industrial workers attributable to the hepatotoxic solvents. This risk seems to be related to the use of a mixture of solvents, although at low doses, and the analysis of the results obtained confirms the validity of the investigation for the health screening protocol adopted in order to identify subjects and/or population at risk of hepatotoxicity.

Urinary hydroxypyrene and estradiol in an occupationally exposed "outdoor" population.

BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs) are widely present in the air pollution. The urinary hydroxypyrene (1-HOPu) is considered the main biological biomarker currently available to measure the exposure to PAH. It is supposed responsible of an increase of estradiol levels in males. Aim of this study is to verify whether there is a relation between 1-HOPu and plasmatic estradiol in non-smoker male workers. METHODS: The study was conducted on a sample of 122 non-smoker policemen in a large Italian city; we monitored their levels of 1-HOPu and the values of estradiol. The sample was divided into three groups according to the levels of urinary hydroxypyrene. The indices of correlation (r) and multiple linear regression (ß), between levels of 1-HOPu and estradiol were calculated. It was also calculated the student's t-test among the groups to check the differences. RESULTS: We found statistically significant correlations and multivariate linear regressions between 1-HOPu and estradiol in the total sample and in group III (levels of 1-HOPu above the 75th percentile). The average levels of estradiol in group III was statistically and significantly higher than in the group I (levels of 1-HOPu below the 25th percentile) and group II (levels 1-HOPu between 25th and the 75th percentile). CONCLUSIONS: 1-HOPu in non-smoker male workers is related with an increase of plasmatic estradiol. We believe that PAHs, of which 1-HOPu is the main biomarker, can interact with the hypothalamic-pituitary axis. The preliminary results suggest that the topic needs further research on male and female as well.

[Urban individual exposure to cadmium and baroreceptor response to posture]. / Esposizione ad inquinanti urbani e riflessi barocettivi posturali.

OBJECTIVE: Outdoor workers are daily exposed to urban pollutants. The aim of the study is to evaluate the relationship between the values of environmental monitoring collected by personal dosimetries and changes in blood pressure due to posture in outdoor workers. MATERIALS AND METHODS: 32 subjects of both sexes were enrolled in the study, we evaluated the values of environmental monitoring of breathable dust, nickel, arsenic, cadmium, lead, benzene, toluene, xylene and 16 PAHs. Blood pressure in supine and standing positions was measured in all subjects. RESULTS: The multiple linear regression analysis showed a significant reduction of orthostatic response of diastolic blood pressure in non-smoking outdoor workers occupationally exposed to cadmium. CONCLUSIONS: The results of our study let us to believe that exposure to low doses of urban polluted cadmium may affect the response of diastolic blood pressure to orthostatism, as per a paraphysiological condition of sympathetic down-regulation.

Professional exposure to anaesthetic gases in health workers: estimate of some hepatic and renal tests.

OBJECTIVES: The aim of this study is to estimate whether the occupational exposure to low dose of anaesthetic gases could cause alterations of haematochemical hepatic and renal parameters in the health workers of a city hospital. MATERIALS AND METHODS: After excluding the main confounding factors, 154 exposed subjects and 98 not exposed controls were included in the study. The exposed subjects were divided in more exposed (group 1: n.54) and less exposed (group 2: n.100). Each worker included in this study underwent the CBC test (Complete Blood Count test). The differences between means were compared using the Student T test for unpaired data and considered significant when the p value was < 0.05. RESULTS: The mean values of serum albumin, alpha 1, alpha 2, beta and gamma globulins were significantly decreased in health workers of both groups compared to controls. The mean values of serum creatinine and gamma-GT were significantly higher in health workers of group 2 compared to controls. CONCLUSIONS: The obtained results suggest that occupational exposure to low dose of anaesthetic gases could influence haematochemical hepatic and renal parameters in exposed health workers.

Professional exposure to ionizing radiations in health workers and white blood cells.

BACKGROUND: The aim of this study is to estimate if low dose of occupational exposure to ionizing radiations can cause alterations of plasma concentrations of total white blood cells, lymphocytes, monocytes and granulocytes (eosinophils, basophils, neutrophils), in the health workers of a big hospital. METHODS: 266 non smokers subjects of both sexes (133 health workers and 133 controls) were included in this study, compared on the basis of sex, age and working seniority. The complete blood count (CBC) was performed in all included workers. RESULTS: The differences between the mean values were compared using Student T-test for unpaired data. The frequencies of the single variables were compared using Chi (2) test with Yates correction. The differences were considered significant when the P values were < 0.05. The mean values and the distribution of the mean values of total white blood cell were significantly decreased in health workers of both sexes compared to controls. The average values of granulocytes neutrophils were significantly low in female health workers compared to female controls. CONCLUSIONS: The obtained results suggest that low dose of occupational exposure to ionizing radiations is able to influence some lines of the hematopoietic system in exposed workers.