Medico legal aspects on neuromonitoring in thyroid surgery: informed consent on malpractice claims.

AIM: The purpose of this paper is to provide a forensic profile framework of neuromonitoring in thyroid surgery, regarding the information given to the patient and its classification as part of professional liability in the event of recurrent injury. METHOD: Evaluation and reflections on the required behaviour of the surgeon on providing details on the operation before the informed consent is given and to outline the possible legal implications regarding professional liability as a result of recurrent injury. In particular, if it is an obligation to inform the patient about using this method and if it is possible for the surgeon to freely choose whether to employ this method, which is still burdened by a certain percentage of error and for that reason it cannot be defined a "standard of care". RESULTS: To recognize neuromonitoring the role of standard of care in surgery of the thyroid means attribute a role of method able to avoid the surgeon to cause iatrogenic damage to the laryngeal nerve. For the foregoing reasons that is not true, determining false positives and false negatives, and this can be a double edged sword for the surgeon. CONCLUSIONS: Although the progress in the field of thyroid surgery made in the last decade, currently there is no scientific reassuring evidence to completely avoid the possibility of producing an iatrogenic lesion of the laryngeal nerve. Information given to the patient prior to surgery should respect the requirements of completeness, freedom and honesty in order to allow the patient to self-determination.

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.

Immunohistochemical findings in the lungs of COVID-19 subjects: evidence of surfactant dysregulation.

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is characterized by quantitative and qualitative changes in surfactant composition, leading to surfactant dysregulation with alveolar collapse and acute respiratory hypoxic failure. Recently, surfactant has been hypothesized to play a relevant role in COVID-19, representing a strong defender against SARS-CoV-2 infection. The aim of our work was the study of immunohistochemical surfactant expression in the lungs of patients died following SARS-CoV-2 ARDS, in order to shed light on a possible therapeutic surfactant administration. PATIENTS AND METHODS: We investigated four patients who died due to ARDS following SARS-COV-2 infection and four patients submitted to lung biopsy, in the absence of SARS-CoV-2 infection. In all 8 cases, lung specimens were immunostained with anti-surfactant protein A (SP-A) and B (SP-B). RESULTS: In control subjects, reactivity for SP-B was restricted to type II alveolar cells. Immunostaining for SP-A was observed on the surface of alveolar spaces. In the COVID-19 positive lungs, immunoreactivity for SP-B was similar to that observed in control lungs; SP-A was strongly expressed along the alveolar wall. Moreover, dense aggregates of SP-A positive material were observed in the alveolar spaces. CONCLUSIONS: Our immunohistochemical data show the dysregulation of surfactant production in COVID-19 patients, particularly regarding SP-A expression. The increased presence of SP-A in condensed masses inside alveolar spaces could invalidate the therapeutic efficacy of the treatment with exogenous surfactant.

Aortic vulnerability to COVID-19: is the microvasculature of vasa vasorum a key factor? A case report and a review of the literature.

Arterial thromboembolic complications reported in patients with COVID-19 infection suggested that SARS-CoV-2 can trigger atherosclerotic plaque vulnerability. While endothelial cells in healthy subjects protect against thrombus formation, after injury they show prothrombotic activity. In addition, it has been hypothesized that "cytokine storm" might stimulate the production of neo-platelets triggering an abnormal "immunothrombosis" responsible for the hypercoagulable state induced in COVID-19 patients. The aim of this study is to report a case of severe COVID-19 infection characterized by the occurrence of microthrombosis in the vasa vasorum of the aorta. A 67-year-old male patient, in good health status and without comorbidities, who underwent a severe COVID-19 infection with fatal outcome, showed scattered aortic atherosclerotic plaques, characterized by multiple occlusive micro-thromboses in the vasa vasorum, spread out lymphocytic infiltrates and foci of endotheliitis and endothelial detachment. This case report confirms the previously described thrombotic involvement of vasa vasorum in COVID-19. The occurrence of the synchronous damage involving both the lumen surface (endothelial dysfunction, endotheliitis and endothelial detachment) and the adventitia (inflammation and occlusive thrombosis of vasa vasorum) could be the key points related to the fatal outcome of the SARS-CoV-2 patients. In our opinion, vasa vasorum thrombosis may thus initiate an atherogenic process that could be characterized by a much more rapid development.

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.

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.

1 alpha(OH) vitamin D3 increases plasma aluminum in hemodialized patients taking AI(OH)3.

1 alpha(OH) vitamin D3 at the dose of 6 micrograms per week was given for 4 weeks to 16 stable patients on chronic hemodialysis with a low dialysate aluminum while taking a constant dose of Al(OH)3. A significant increase of their plasma aluminum was observed from 1.2 +/- .25 mumol/l before 1 alpha(OH)D3 to 1.7 +/- .35 during the second fortnight of 1 alpha(OH)D3 administration and this increase surprisingly was maintained at 1.71 +/- .3 up to 6 weeks after 1 alpha(OH)D3 discontinuation. Increases in plasma calcium and decreases in plasma PTH were observed during 1 alpha(OH)D3 administration and these changes were correlated to the changes in plasma aluminum. It is concluded that the increase in plasma aluminum observed with 1 alpha(OH)D3 and after its discontinuation is either due to body aluminum burden redistribution or to increased aluminum intestinal absorption whatever the mechanism is, this effect should lead to close monitoring of plasma aluminum in uremic patients taking 1 alpha OH vitamin D3.

Indirect clinical evidence that 1 alpha OH vitamin D3 increases the intestinal absorption of aluminum.

In a previous study we showed that 1 alpha OH vitamin D3 [1 alpha (OH)3] given to 16 hemodialyzed patients taking Al(OH)3 at a constant dose increased their plasma concentrations of aluminum [Demontis et al. 1986]. In order to choose between 2 possible mechanisms explaining this increase (increased intestinal absorption or decreased tissue storage of aluminum), we gave, in the present study, 1 alpha (OH)3 the same dose (6 micrograms per week) for the same period (4 weeks) to 15 stable hemodialyzed patients after their Al(OH)3 had been discontinued for 6 weeks. Under Al(OH)3 treatment they had a mean plasma aluminum (2.33 +/- 2.36 mumol/l) which was not significantly different from that of the patients in our former study (1.23 +/- 0.25 mumol/l). After Al(OH)3 discontinuation, plasma aluminum (measured by inductively coupled plasma emission spectrometry) decreased significantly as early as the 2nd week of the control period (1.39 mumol/l). The decrease was maintained at a plateau throughout the 5 weeks of the control period (1.38 mumol/l), the 4 weeks of 1 alpha OH vitamin (vit) D3 administration (1.40 mumol/l) and the 8 weeks of the post 1 alpha (OH)3 period (1.22 mumol/l). Plasma calcium and phosphate concentrations increased significantly with 1 alpha (OH)3 and decreased thereafter whereas plasma PTH concentrations decreased during 1 alpha (OH)2 D3 and increased after its discontinuation suggesting biological activity of 1 alpha (OH)3. Since 1 alpha (OH)3 increases plasma aluminum in hemodialyzed patients only when they are simultaneously taking Al(OH)3, it is suggested that this increase is explained by an increase of intestinal absorption of aluminum and not by a tissue redistribution of aluminum.

[Nodular regenerative hyperplasia associated with primary antiphospholipid syndrome]. / Hyperplasie nodulaire régénérative associée à un syndrome primaire des antiphospholipides.

Nodular regenerative hyperplasia of the liver is characterized by diffuse nodularity of the hepatic parenchyma without fibrotic septa. It may be related to venous or arterial obstruction in the portal tract. We report a case of primary antiphospholipid syndrome associated with nodular regenerative hyperplasia in a 45-year old woman. The patient had an ischemic stroke, associated with an acute arterial ischemia of the left leg. She had high titers of serum anticardiolipin antibodies. Nodular regenerative hyperplasia of the liver was histologically confirmed and was associated with anicteric cholestasis. This case provides additional evidence that a thrombotic mechanism may play a role in the pathogenesis of nodular regenerative hyperplasia of the liver.

[Hepatitis C epidemiology at a general hospital center. Management and natural history as a function of the manner of identification]. / Epidémiologie de l'hépatite C dans un centre hospitalier général. Prise en charge et histoire naturelle en fonction du mode de découverte.

OBJECTIVES: To study the epidemiological characteristics of patients with chronic hepatitis C virus followed in a primary referral hospital and the clinical influence of "systematic screening" defined as the screening of patients without symptoms and with known risk factors of hepatitis C (past transfusion, past or present intravenous drug use, haemodialysis) on the natural history and treatment of chronic hepatitis C virus. METHODS: The files of 311 consecutive patients who screened positive for anti-hepatitis C virus and were seen at the primary referral hospital, Creil, from January 1992 to February 1996, were analyzed. RESULTS: Patients who underwent "systematic screening" were younger with a shorter duration of infection. They were more often intravenous drug addicts and had lower alanine aminotransferase activity and Knodell scores than patients who underwent screening during "a diagnostic procedure", because of symptoms and/or abnormal liver biochemistry. Increased age at contamination and alcohol consumption of more than 40 g per day was associated with an increased risk of cirrhosis while patients who underwent "systematic screening" had a lower risk of cirrhosis and higher survival rate. Interferon therapy was attempted less often in anti-hepatitis C virus positive patients from "systematic screening" programs. CONCLUSIONS: Anti-hepatitis C virus positive patients from "systematic screening" programs had a benign disease and were rarely treated with interferon compared to anti-hepatitis C virus positive patients diagnosed during a "diagnostic procedure".

[Acute renal insufficiency caused by observed a combination of enalapril, furosemide and flurbiprofen in a patient with retroperitoneal fibrosis]. / Insuffisance rénale aiguë observée sous association énalapril, furosémide et flurbiprofène chez un malade ayant une fibrose rétropéritonéale.

The case of vasomotor parenchymal acute renal failure is reported in a patient a few days after the initiation of treatment by Enalapril which is a new converting enzyme inhibitor. No renal artery stenosis could be demonstrated, which is in contrast with the numerous cases reported up to now. However the helping roles of an incomplete obstruction by a peri-aneurysmal retroperitoneal sclerosis, of prolonged anterior treatment with flurbiprofen and of simultaneous administration of furosemide may be discussed.

Intraoperative recurrent laryngeal nerve monitoring in thyroid surgery: is it really useful?

AIM: The aim of this study was to evaluate the ability of intraoperative recurrent laryngeal nerve monitoring to predict the postoperative functional outcome and the potential role of this technique in reducing the postoperative nerve palsy rate. MATERIALS AND METHODS: Between June 2007 and December 2011, 1693 consecutive patients who underwent thyroidectomy by a single surgical team were evaluated. We compared patients who have had a neuromonitoring and patients who have undergone surgery with the only visualization. Patients in which NIM was not utilized (Group A) were 942 against the others 751 (group B). RESULTS: In group A there were 28 recurrent laryngeal nerve injuries (2.97%) of which 21 were transients (2.22%) and 7 were permanents (0.74%). In group B there were 20 recurrent laryngeal nerve injuries (2.66%) of which 14 (1.86%) transients and 6 (0.8%) permanents. Differences between the two groups were not statistically significative. CONCLUSIONS: The technique of intraoperative neuromonitoring in thyroid surgery is safe and reliable in excluding postoperative recurrent laryngeal nerve palsy; it has high accuracy, specificity, sensitivity and negative predictive value. Neuromonitoring is useful to identify the recurrent laryngeal nerve and it can be a useful adjunctive technique for reassuring surgeons of the functional integrity of the nerve but it does not decrease the incidence of injuries compared with visualization alone. Its application can be particularly recommended for high-risk thyroidectomies.

[Diagnosis of Fabry disease: usefulness of the clinical investigation]. / Le diagnostic de la maladie de Fabry: intérêt de l'enquête clinique.

Fabry disease, an X-linked lysosomal storage disorder due to alpha-galactosidase A deficiency, leads to an accumulation of globotriaosylceramide resulting in a multisystemic disorder. The initial manifestations of the disease are not specific, leading to a delayed diagnosis. We report a patient in whom the diagnosis was obtained by family screening and the confrontation of clinical signs. We also present a 4 year follow-up under enzyme replacement therapy (agalsidase ß, 1 mg/kg/14 days).