Keratose Self-Cross-Linked Wound Dressing for Iron Sequestration in Chronic Wounds.

Chronic wound diseases affect a large part of the world population, and therefore, novel treatments are becoming fundamental. People with chronic wounds show high iron and protease levels due to genetic disorders or other comorbidities. Since it was demonstrated that iron plays an important role in chronic wounds, being responsible for oxidative processes (ROS generation), while metalloproteinases prevent wound healing by literally "eating" the growing skin, it is crucial to design an appropriate wound dressing. In this paper, a novel bioactive dressing for binding iron in chronic wounds has been produced. Wool-derived keratose wound dressing in the form of films has been prepared by casting an aqueous solution of keratoses. These films are water-soluble; therefore, in order to increase their stability, they have been made insoluble through a thermal cross-link treatment. Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analyzer (TGA) analyses clarified the structure and the properties of the keratose wound dressing films. The capability of this new biomaterial in iron sequestration has been investigated by testing the adsorption of Fe3+ by inductively coupled plasma-optical emission spectrometry (ICP-OES). The results suggest that the keratose cross-linked films can adsorb a large amount of iron (about 85% of the average amount usually present in chronic wounds) following pseudo-second-order kinetics and an intraparticle diffusion model, thus opening new perspectives in chronic wound care. Furthermore, the QSAR Toolbox was applied for conducting in silico tests and for predicting the chemical behavior of the C-Ker-film. All of the data suggest that the keratose bioactive dressing can significantly contribute to wound healing by mechanisms such as iron depletion, acting as a radical scavenger, diminishing the proteolytic damage, acting as a substrate in place of skin, and, finally, promoting tissue regeneration.

International Union of Angiology consensus document on vascular compression syndromes.

Vascular compression syndromes (VCS) are rare diseases, but they may cause significant symptoms interfering with the quality of life (QoL) of patients who are often in their younger age. Given their infrequent occurrence, multiform clinical and anatomical presentation, and absence of dedicated guidelines from scientific societies, further knowledge of these conditions is required to investigate and treat them using modern imaging and surgical (open or endovascular) techniques. This consensus document will focus on known VCS, affecting the arterial and venous system. The position paper, written by members of International Union of Angiology (IUA) Youth Committee and senior experts, will show an overview of pathophysiology, diagnostic, and therapeutical approaches for patients with VCS. Furthermore, this document will provide also unresolved issues that require more research that need to be addressed in the future.

Randomized controlled trial on occupational graduated compression clinical and cost-effectiveness.

BACKGROUND: Subjects exposed to occupational standing are at risk of developing chronic venous disease. Graduated compression stockings (GCS) counteract venous hypertension. Aim of the present investigation was to assess GCS clinical and cost effectiveness in prolonged standing up workers. METHODS: Randomized controlled trial involving 75 healthy healthcare professionals working in 6 hours standing up shifts without or with GCS (group A and B, respectively). Outcome measures were performed before and after the shift, at baseline (T0), at 1 (T1), 6 (T6) and 12 (T12) months and included lower limb volume, air plethysmography (APG), quality of life, and dedicated cost-effectiveness questionnaires. RESULTS: Seventy-two subjects completed the data collection. Leg volume increased in group A and decreased in B at all assessment points (T0, 1, 6, 12) (P<0.0001). Venous filling index did not change within the 12 months, but, after every shift, its value was lower in B compared to A (P<0.0001). At 12 months, VVSymQ worsened in A and improved in B (P<0.0001) and CIVIQ significantly worsened in A (P<0.0001), while in B it significantly improved (P<0.0001). Perceived disability was higher in A at 12 months (P<0.001) and the cost calculation revealed a saving of 1510 euro per year in B. CONCLUSIONS: GCS counteracted occupational oedema and positively influenced venous filling index, while improving vein specific quality of life measurements in addition to cost savings.

Cerebral Outflow Discrepancies in Recurrent Benign Paroxysmal Positional Vertigo: Focus on Ultrasonographic Examination.

This prospective pilot study aimed to evaluate whether cerebral inflow and outflow abnormalities assessed by ultrasonographic examination could be associated with recurrent benign paroxysmal positional vertigo (BPPV). Twenty-four patients with recurrent BPPV, affected by at least two episodes, and diagnosed according to American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria, evaluated at our University Hospital, between 1 February 2020 and 30 November 2021, have been included. At the ultrasonographic examination, 22 of 24 patients (92%) reported one or more alterations of the extracranial venous circulation, among those considered for the diagnosis of chronic cerebrospinal venous insufficiency (CCSVI), although none of the studied patients were found to have alterations in the arterial circulation. The present study confirms the presence of alterations of the extracranial venous circulation in recurrent BPPV; these anomalies (such as stenosis, blockages or regurgitation of flow, or abnormal valves, as per the CCSVI) could cause a disruption in the venous inner ear drainage, hampering the inner ear microcirculation and then possibly causing recurrent otolith detachment.

Overcoming Challenges and Innovations in Orthopedic Prosthesis Design: An Interdisciplinary Perspective.

Recent advances in the orthopedic prostheses design have significantly improved the quality of life for individuals with orthopedic disabilities. However, there are still critical challenges that need to be addressed to further enhance the functionality of orthopedic prostheses improving biocompatibility to promote better integration with natural tissues, enhancing durability to withstand the demands of daily use, and improving sensory feedback for better control of movement are the most pressing issues. To address these challenges, promising emerging solutions such as smart prosthetics, 3D printing, regenerative medicine, and artificial intelligence have been developed. These innovative technologies hold the potential to significantly enhance the functionality of orthopedic prostheses. Realizing the full potential of these next-generation orthopedic prostheses requires addressing several critical factors. These include interdisciplinary collaboration between experts in orthopedics, materials science, biology, and engineering, increased investment in research and development, standardization of components to ensure quality and reliability, and improved access to prosthetics. A comprehensive review of these challenges and considerations for future orthopedic prosthesis design is s provided in this paper addressing the further advances to the field. By addressing these issues, we can continue to improve the lives of individuals with orthopedic disabilities and further enhance the field of orthopedic prosthetics.

Styloid Jugular Nutcracker: The Possible Role of the Styloid Process Spatial Orientation-A Preliminary Morphometric Computed Study.

Styloid Jugular Nutcracker (SJN, also known as Eagle Jugular Syndrome EJS) derives from a jugular stenosis caused by an abnormal styloid process, compressing the vessel in its superior portion (J3) against the C1 anterior arch. It could be considered a venous vascular variant of Eagle Syndrome (ES). Main clinical features of this ES variant are headache, pulsatile tinnitus and dizziness, possibly related to venous hypertension and impaired cerebral parenchyma drainage. In our opinion, conceptually, it is not the absolute length of the styloid bone that defines its abnormality, but its spatial direction. An elongated bone pointing outward far away from the midline could not compress the vein; vice versa, a short styloid process tightly adherent to the cervical spine could be pathological. To prove this hypothesis, we developed a semi-automatic software that processes CT-Angio images, giving quantitative information about distance and direction of the styloid process in three-dimensional space. We compared eight patients with SJN to a sample of healthy subjects homogeneous for sex and age. Our results suggest that SJN patients have a more vertically directed styloid, and this feature is more important than the absolute distance between the two bony structures. More studies are needed to expand our sample, including patients with the classic and carotid variants of Eagle Syndrome.

COVID-19 induced aorto duodenal fistula following evar in the so called "negative" patient.

OBJECTIVES: Since October 2019, SARS-CoV-2 pandemic represents a challenge for the international healthcare system and for the treatment and survival of patients. We normally focus on symptomatic patients, and symptoms can range from the respiratory to the gastrointestinal system. In addition, we consider patients without fever and respiratory symptoms, with both a negative RT nasopharyngeal swab and lung CT, as a "Covid-19 negative patient." In this article, we present a so called Covid-19 "negative" patient, with an unsuspected vascular clinical onset of the viral infection. METHODS: An 80 y.o. man, who previously underwent endovascular aortic repair for an infrarenal abdominal aortic aneurysm, presented to our department with an atypical presentation of an aorto-enteric fistula during the pandemic. While in hospital, weekly nasopharyngeal swab tests were always negative for SARS-CoV-2. However, the absence of aortic endograft complications, the gross anatomy of duodenal ischemic injury, and the recent history of the patient who lived the last months in Bergamo, the Italian city with the highest number of COVID-19 deaths, lead the senior Author to suspect an occult SARS-CoV-2 infection. The patient underwent to resection of the fourth portion of the duodenum and the first jejunal loop, with subsequent duodenum-jejunal latero-lateral anastomosis and the direct suture of the aortic wall. The intestinal specimen was investigated as suspected SARS-CoV-2 bowel infection by the means of immune-histochemistry (IHC). An ileum sample obtained in the pre-COVID-19 era was used as a control tissue. RESULTS: The histological analysis of the bowel revealed sustained wall ischemia and liponecrosis of the duodenal wall, with intramural blood vessels thrombosis. Blood vessel endotheliitis and neo-angiogenesis were also observed. Finally, the IHC was strongly positive for SARS-CoV-2 RNA and for HLA-G presence, with a particular concentration both in blood vessels and in the intestinal villi. The control tissue sample was not positive for both SARS-CoV-2 and HLA-G. CONCLUSIONS: Coronavirus pandemic continues to be an international challenge and more studies and trials must be done to learn its pathogenesis and its complications. As for thromboembolic events caused by SARS-COV-2, vascular surgeons are involved in treatment and prevention of the complications of this syndrome and must be ready with general surgeons to investigate atypical and particular cases such as the one discussed in this article.

The Effect of Active Stretching Training in Patients with Chronic Venous Insufficiency Monitored by Raster-Stereography.

(1) Background: Musculoskeletal disorders can be associated with advanced clinical stages of chronic venous insufficiency (CVI). The aim of the study is to investigate the effect of active stretching (AS) training on lower limb venous function and quality of life in patients affected by CVI. (2) Methods: A prospective two-armed pilot randomized controlled was conducted. Twenty (20) CVI patients were randomly assigned to an AS training or to a control group (C) who did not receive any exercise indication. At baseline and after three months all the participants were tested for leg volumetry (LV), air plethysmography (APG), and quality of life (QoL) measured by a disease specific validated questionnaire (VVSymQ), ankle range of motion (ROM), and postural deformities using an optoelectronic body posture machine. (3) Results: At the end of the training in the AS group a significant leg volume reduction was detected (from 2340 ± 239 mL to 2239 ± 237 mL (4.3%); p < 0.0001), whereas in the C group no significant volume changes were found. The ejection fraction rate (EF%) increased significantly from 49.3 ± 9.3 to 61.1 ± 14.5, p < 0.005. A moderate-strong linear correlation with EF% and ankle ROM variation was found (R2 = 0.6790; p < 0.0034). Several postural outcomes such as pelvic tilt, pelvic torsion, and lordotic angle significantly improved in the AS group (p < 0.01, p < 0.04, p < 0.01 respectively). (4) Conclusion: The AS training impacts on the APG parameters related to the musculoskeletal pump efficiency, opening a further possibility in the management of CVI patients by means of an appropriate adapted physical exercise program.

The Effect of Submaximal Exercise on Jugular Venous Pulse Assessed by a Wearable Cervical Plethysmography System.

The jugular venous pulse (JVP) is a one of the crucial parameters of efficient cardiovascular function. Nowadays, limited data are available regarding the response of JVP to exercise because of its complex and/or invasive assessment procedure. The aim of the present work is to test the feasibility of a non-invasive JVP plethysmography system to monitor different submaximal exercise condition. Twenty (20) healthy subjects (13M/7F mean age 25 ± 3, BMI 21 ± 2) underwent cervical strain-gauge plethysmography, acquired synchronously with the electrocardiogram, while they were carrying out different activities: stand supine, upright, and during the execution of aerobic exercise (2 km walking test) and leg-press machine exercise (submaximal 6 RM test). Peaks a and x of the JVP waveform were investigated since they reflect the volume of cardiac filling. To this aim, the Δax parameter was introduced, representing the amplitude differences between a and x peaks. Significant differences in the values of a, x, and Δax were found between static and exercise conditions (p < 0.0001, p < 0.0001, p < 0.0001), respectively. Particularly, the Δax value for the leg press was approximately three times higher than the supine, and during walking was even nine times higher. The exercise monitoring by means of the novel JVP plethysmography system is feasible during submaximal exercise, and it provides additional parameters on cardiac filling and cerebral venous drainage to the widely used heartbeat rate value.

Micropatterned Neurovascular Interface to Mimic the Blood-Brain Barrier's Neurophysiology and Micromechanical Function: A BBB-on-CHIP Model.

A hybrid blood-brain barrier (BBB)-on-chip cell culture device is proposed in this study by integrating microcontact printing and perfusion co-culture to facilitate the study of BBB function under high biological fidelity. This is achieved by crosslinking brain extracellular matrix (ECM) proteins to the transwell membrane at the luminal surface and adapting inlet-outlet perfusion on the porous transwell wall. While investigating the anatomical hallmarks of the BBB, tight junction proteins revealed tortuous zonula occludens (ZO-1), and claudin expressions with increased interdigitation in the presence of astrocytes were recorded. Enhanced adherent junctions were also observed. This junctional phenotype reflects in-vivo-like features related to the jamming of cell borders to prevent paracellular transport. Biochemical regulation of BBB function by astrocytes was noted by the transient intracellular calcium effluxes induced into endothelial cells. Geometry-force control of astrocyte-endothelial cell interactions was studied utilizing traction force microscopy (TFM) with fluorescent beads incorporated into a micropatterned polyacrylamide gel (PAG). We observed the directionality and enhanced magnitude in the traction forces in the presence of astrocytes. In the future, we envisage studying transendothelial electrical resistance (TEER) and the effect of chemomechanical stimulations on drug/ligand permeability and transport. The BBB-on-chip model presented in this proposal should serve as an in vitro surrogate to recapitulate the complexities of the native BBB cellular milieus.

Investigation of the Associations between a Nanomaterial's Microrheology and Toxicology.

With the advent of Nanotechnology, the use of nanomaterials in consumer products is increasing on a daily basis, due to which a deep understanding and proper investigation regarding their safety and risk assessment should be a major priority. To date, there is no investigation regarding the microrheological properties of nanomaterials (NMs) in biological media. In our study, we utilized in silico models to select the suitable NMs based on their physicochemical properties such as solubility and lipophilicity. Then, we established a new method based on dynamic light scattering (DLS) microrheology to get the mean square displacement (MSD) and viscoelastic property of two model NMs that are dendrimers and cerium dioxide nanoparticles in Dulbecco's Modified Eagle Medium (DMEM) complete media at three different concentrations for both NMs. Subsequently, we established the cytotoxicological profiling using water-soluble tetrazolium salt-1 (WST-1) and a reactive oxygen species (ROS) assay. To take one step forward, we further looked into the tight junction properties of the cells using immunostaining with Zonula occluden-1 (ZO-1) antibodies and found that the tight junction function or transepithelial resistance (TEER) was affected in response to the microrheology and cytotoxicity. The quantitative polymerase chain reaction (q-PCR) results in the gene expression of ZO-1 after the 24 h treatment with NPs further validates the findings of immunostaining results. This new method that we established will be a reference point for other NM studies which are used in our day-to-day consumer products.

Vaccine-induced immune thrombotic thrombocytopenia with atypical vein thrombosis: Implications for clinical practice.

OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a new and rare syndrome resulting from the largest vaccination campaign against SARS-CoV-2 in the history of mankind. The aim of this review is to clarify underlying mechanisms, pathology, diagnosis, and therapy, with the related clinical implications. METHODS: We performed a comprehensive literature review in order to collect the clinical and treatment data about patients suffering from VITT. PubMed, Ovid Medline, Ovid EMBASE, Scopus, and Web of Science were screened regarding patients who developed VITT. Last search was launched on June 30th 2021. RESULTS: Abdominal and/or neurological symptoms develop between 5 and 20 days after vaccine administration and do not involve the lower extremities. VITT is suspected if the platelet count is lower than 100.000/mm3 and D-dimer is higher than the age-adjusted range. Medical treatment is mainly based on intravenous immunoglobulins, corticosteroids, and anticoagulant drugs with a short plasma half-life, but the complete avoidance of low molecular weight heparin is recommended. Endovascular treatment and/or decompressive craniectomy might be an option in a minority of cases. CONCLUSION: Due to widespread vaccination concerns, the vascular specialist and phlebologist are increasingly consulted to prevent or diagnose VITT. The latter has peculiar and completely different localizations, symptoms, and treatment compared to the common pictures of venous thrombosis.

Structured pain-free exercise progressively improves ankle-brachial index and walking ability in patients with claudication and compressible arteries: an observational study.

In patients with peripheral artery disease (PAD), supervised exercise at near-moderate pain improves walking ability but not ankle-brachial index (ABI) values. In a retrospective observational study, we determined vascular and functional effects of a 6-month structured pain-free exercise program in patients with claudication and compressible vessels. Four-hundred and fifty-nine consecutive patients were studied. Segmental limb pressures were measured and ABI calculated during circa-monthly hospital visits. The 6-min (6MWD) and the pain-free walking distance (PFWD) during the 6-min walking test were determined. Two daily 8-min sessions of slow-moderate in-home walking at increasing metronome-paced speed were prescribed. After excluding patients with unmeasurable ABI or incompletion of the program, 239 patients were studied. Safe and satisfactory (88%) execution of the prescribed training sessions was reported. During the visits, bilateral ABI improved (+ 0.07; p < 0.001) as well as the segmental pressures in the more impaired limb, with changes already significant after 5 weeks of slow walking. Both systolic and diastolic blood pressure decreased overtime (F = 46.52; p < 0.001; F = 5.52; p < 0.001, respectively). 6MWD and PFWD improved (41[0‒73]m p < 0.001 and 107[42‒190]m p < 0.001, respectively) with associated decrease of walking heart rate (F = 15.91; p < 0.001) and Physiological Cost Index (F = 235.93; p < 0.001). The variations of most parameters at different visits correlated to the training load calculated. In a regression model, the PFWD variations directly correlated with rate sessions completed, training load and ABI change and inversely with the baseline value (R2 = 0.27; p < 0.001). In the PAD population studied, moderate pain-free exercise improved ABI with associated progressive functional and cardiovascular changes occurring regardless of subjects characteristics.

Patient specific Polymethyl methacrylate customised cranioplasty using 3D printed silicone moulds: Technical note.

INTRODUCTION: Cranioplasty after decompressive craniectomy can be performed with several techniques and materials. With the common use of 3D printing, custom cranioplasty can be produced at affordable cost. Aim of this technical note is to describe our technique for producing patient specific Polymethyl methacrylate (PMMA) cranioplasty using 3D printed silicone moulds. MATERIALS AND METHODS: We enrolled seven patients from January 2020 to June 2021 who required surgery for cranioplasty. The 3D printing was used to produce silicone moulds for defining the exact shape of the PMMA cranioplasty, according to the CT scan of the patient. RESULTS: We performed seven procedures. The mean time of the surgery was 80 min. All cranioplasties perfectly matched the patient specific anatomy. No complications occurred. CONCLUSIONS: Using 3D printed patient specific silicone moulds and PMMA resulted to be effective, with affordable costs and ensuring a good cosmetic result.

Physical fitness changes induced by thermal aquatic standardized exercise in chronic venous disease patients.

BACKGROUND: Lack of physical activity represents a risk factor for both cardiovascular and chronic venous diseases (CVD), nevertheless a specific exercise protocol for CVD patient is still missing. This investigation was aimed to assess the impact of a standardized exercise protocol in a thermal water environment on physical fitness and quality-of-life (QoL) in CVD patients. METHODS: Sixteen (16) CVD patients performed 5 standardized exercise sessions in a thermal water pool. Before starting the exercise protocol, the cohort filled International Physical Activity Questionnaire (IPAQ) to determine their physical activity level. At baseline and at the end of the exercise program, leg volume, QoL, musculoskeletal and cardiovascular physical fitness were assessed by means of water plethysmography, validated questionnaire and functional test, blood pressure and heart rate at rest were also reported. RESULTS: All the patients were categorized as physically inactive: average activity time 235.6 (155.2) MET-minutes per week. At the end of the study, a significant leg volume reduction was found (-16%; p < .002). Significant improvement in lower limb strength (p < .0001), endurance (p < .006), rapidity and balance (p < .05) together with decrease in resting heart rate (-1.8%, p < .0001) and systolic blood pressure (-1.1%, p < .04) were reported, significant improvement in bodily pain (p < .0005) and social function (p < .002) QoL items were observed. CONCLUSIONS: The proposed exercise protocol in thermal aquatic environment demonstrated to be an effective treatment modality improving both cardiovascular and musculoskeletal outcomes and QoL in sedentary CVD patients. Aquatic environment investigations require proper analysis of the various factors involved, in a standardized and reproducible way. The herein report can be a reference for further studies on different health related conditions.

A New Insight in Nonaneurysmal Subarachnoid Hemorrhage: The Potential Role of the Internal Jugular Veins.

BACKGROUND: Causes of the nonaneurysmal subarachnoid hemorrhage (na-SAH) are still debated. Many studies confirmed the possible involvement of the intracranial venous system, in particular variants of the basal vein of Rosenthal. STUDY OBJECT: The aim of this study is to investigate the role of extracranial venous system, in particular the jugular drainage, in the na-SAH pathophysiology. MATERIALS AND METHODS: This is a multicenter retrospective study including patients suffering from na-SAH who were radiologically screened to exclude vascular malformations. The course of the internal jugular veins was evaluated to reveal any stenosis (caliber reduction >80%). Particular attention was paid at the passage between the styloid process and the arch of C1 to detect possible compression. As a control group, we enrolled patients who underwent CT angiograms and/or cerebral DSAs in the past 2 years. RESULTS: We included 194 patients. The na-SAH group consisted of 94 patients, whereas the control group consisted of 100 patients. Fifty patients of the control group underwent a CT angiography for an ischemic cerebrovascular disease or trauma and 50 patients for an SAH due to a ruptured aneurysm. A significant jugular stenosis was found in 49 (52.1%) patients in the na-SAH group and in 18 (18%) patients in the control group. At univariate and multivariate analysis, the difference was statistically significant (p < 0.0001). CONCLUSIONS: This is the first study investigating the correlation between jugular stenosis and the occurrence of na-SAH. The impaired venous outflow due to reduced venous caliber could result in an engorgement of the upstream intracranial veins with transient hypertensive phases facilitating ruptures. Further larger prospective studies are necessary to confirm these data.

Bowel ischemia as onset of COVID-19 in otherwise asymptomatic patients with persistently negative swab.

BACKGROUND: Asymptomatic patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) can develop hypercoagulable conditions and acute vascular events. The objective of this study is to determine whether SARS-CoV-2 was present in resected specimens from patients with acute bowel ischemia, but asymptomatic for Coronavirus Disease 2019 (COVID-19) and with persistently real-time polymerase chain reaction negative pharyngeal swab. METHODS: Three consecutive patients presented severe abdominal symptoms due to extensive ischemia and necrosis of the bowel, with co-existent thrombosis of abdominal blood vessels. None had the usual manifestations of COVID-19, and repeated pharyngeal swabs tested negative. They underwent emergency surgery with intestinal resection. Immunohistochemical testing for SARS-CoV-2 on resected tissue was performed. RESULTS: All tested samples were strongly positive for SARS-CoV-2. CONCLUSIONS: This is the first case report in which patients with severe intestinal symptoms presented a marked SARS-CoV-2 positivity in the resected tissues, without any usual clinical manifestations of COVID-19. These results suggest that the patients might be infected with SARS-CoV-2 presenting acute abdominal distress but without respiratory or constitutional symptoms.

Autopsy Findings and Causality Relationship between Death and COVID-19 Vaccination: A Systematic Review.

The current challenge worldwide is the administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Considering that the COVID-19 vaccination represents the best possibility to resolve this pandemic, this systematic review aims to clarify the major aspects of fatal adverse effects related to COVID-19 vaccines, with the goal of advancing our knowledge, supporting decisions, or suggesting changes in policies at local, regional, and global levels. Moreover, this review aims to provide key recommendations to improve awareness of vaccine safety. All studies published up to 2 December 2021 were searched using the following keywords: "COVID-19 Vaccine", "SARS-CoV-2 Vaccine", "COVID-19 Vaccination", "SARS-CoV-2 Vaccination", and "Autopsy" or "Post-mortem". We included 17 papers published with fatal cases with post-mortem investigations. A total of 38 cases were analyzed: 22 cases were related to ChAdOx1 nCoV-19 administration, 10 cases to BNT162b2, 4 cases to mRNA-1273, and 2 cases to Ad26.COV2.S. Based on these data, autopsy is very useful to define the main characteristics of the so-called vaccine-induced immune thrombotic thrombocytopenia (VITT) after ChAdOx1 nCoV-19 vaccination: recurrent findings were intracranial hemorrhage and diffused microthrombi located in multiple areas. Moreover, it is fundamental to provide evidence about myocarditis related to the BNT162B2 vaccine. Finally, based on the discussed data, we suggest several key recommendations to improve awareness of vaccine safety.