Multidisciplinary clinical guidelines in proactive monitoring, early diagnosis, and effective management of trastuzumab deruxtecan (T-DXd)-induced interstitial lung disease (ILD) in breast cancer patients.

Trastuzumab deruxtecan (T-DXd), a human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugate (ADC), has altered the treatment landscape in breast cancer (BC), irrespective of the HR-receptor status. The use of the agent is increasing, despite the finding that exposure to T-DXd increases the risk of interstitial lung disease (ILD), particularly in BC patients. Although T-DXd-related ILD can be potentially severe and life-threatening, most low-grade cases can be treated safely using a multidisciplinary approach comprising early and accurate diagnosis, effective management, close monitoring, and the prompt administration of steroids. Additionally, increasing patients' education on ILD symptoms ensures close attention and enables prompt reporting, enhancing patient outcomes. It is recommended that predictive biomarkers are assessed in patients with risk factors for developing ILD. Currently, diagnostic criteria comprise newly identified pulmonary opacities, the relation of symptom onset to medication initiation, and the exclusion of other causes of ILD. The general condition of patients is weakened during the management of ILD (BC progression and corticosteroid treatment). Consequently, BC chemotherapy might be attenuated. This highlights the importance of preventing (high-grade) ILD, especially since its use is expanded. Identifying high-risk patients, diagnosing, and customizing treatment is, however, challenging and additional information on patient selection is often not fully clarified. In this paper, we provide updated multidisciplinary clinical guidance for patient selection, proactive monitoring, early diagnosis, and effectively management of T-DXd-induced ILD in HER2-positive BC patients. We describe the risk factors for developing ILD, patients' characteristics of ILD, and the histopathological and radiographic characteristics of ILD, including real-world clinical practice reports. These recommendations provide a structured step-by-step approach for managing each suspected BC-related ILD grade.

Pulmonary transit time as a marker of diastolic dysfunction in Takotsubo syndrome.

AIM: To evaluate the pulmonary transit time (PTT) and its derived parameters using cardiac magnetic resonance imaging (CMRI) as markers of diastolic dysfunction in Takotsubo syndrome (TS) and its relationship with transthoracic echocardiography and CMRI parameters. MATERIALS AND METHODS: Twenty-two patients with TS, who exhibited diastolic dysfunction as assessed by transthoracic echocardiography, were enrolled retrospectively and the PTT, pulmonary transit time index (PTTI), and pulmonary blood volume index (PBVI) were evaluated using first-pass CMRI. PTT was calculated as the number of cardiac cycles required for a bolus of contrast agent to move from the right ventricle (RV) to the left ventricle (LV), whereas PTTI represents the PTT interval corrected for the heart rate. Finally, PBVI was calculated as the product of PTTI, and RV stroke volume indexed for body surface area. Normal references of PTT, PTTI, and PBVI were evaluated in a cohort of 20 age- and sex-matched healthy controls. RESULTS: Compared with healthy subjects, TS patients showed significantly higher PTT, PTTI, and PBVI (p=0.0001, p=0.0001, and p=0.002, respectively). Using multivariable logistic regression, PBVI provided the best differentiation between TS and controls (AUC 0.84). PBVI was significantly associated with the index of diastolic dysfunction and left atrial strain parameters. In addition, PBVI demonstrated a significant correlation with global T2 mapping (r=0,520, p=0,019). CONCLUSION: PTT and the derived parameters, as assessed using first-pass CMRI, are potential tools for assessing LV diastolic dysfunction in patients with TS.

Impact of COVID-19 on the Lifestyle of Students of Taibah University, Madinah.

Background The coronavirus disease 2019 (COVID-19) lockdown affected the daily habits of people around the world. Many countries have contributed to restricting its transmission by ensuing a quarantine, including Saudi Arabia, by shutting down educational facilities. Therefore, the system adapted to those changes, and people were required to stay home for work and education. Objectives This study aimed to explore the effect of the lockdown and house confinement during the COVID-19 pandemic on the important aspects of lifestyle, such as body weight, dietary habits, sleeping patterns, stress levels, screen time, and physical activity among students of Taibah University in Madinah, Saudi Arabia. Methods A cross-sectional study was carried out by a self-administered online questionnaire that was quoted from a Palestinian study. Then was translated from English to Arabic. In total, 528 Taibah University students were eligible to participate. It addressed food-related behavior (types of foods consumed) and lifestyle behavior (physical activity, sleep quality, and screen time). Results Study participants aged from 17 to 30 years, males and females. Mainly non-infected COVID-19 persons previously (54.4%). Participants showed an increase in body weight, intake of fried food, intake of sweets, sleep hours, screen time, and physical activity during lockdown. The most reported sources of stress during lockdown were staying at home all day (62.3%) and distance learning (44.9%). Conclusion The COVID-19 lockdown and the closure of universities have led to many changes in the everyday routine of university students, leading to changes in their lifestyle behaviors.

Adherence to Levothyroxine Treatment Among Patients With Hypothyroidism in Madinah, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Hypothyroidism is one of the most prevalent chronic diseases worldwide. The key factor for a good clinical outcome for hypothyroidism is medication adherence, as the mainstay treatment of hypothyroidism is lifelong hormonal replacement therapy, Levothyroxine (LT4). Poor adherence to LT4 is not only linked to great healthcare costs but also to significant economic burdens. OBJECTIVES: The aim of this study is to assess the medication adherence of patients on LT4 treatment in the Madinah region and its association with socio-demographic characteristics, participants' experience with hypothyroidism and taking LT4, and Morisky Medication Adherence Scale 8-Item (MMAS-8). METHODOLOGY: A cross-sectional study was conducted on 420 hypothyroidism patients on LT4 for at least three months in the Madinah region using a self-administered electronic form. The variables in the questionnaire included socio-demographic characteristics, participants' experience with hypothyroidism and taking LT4, and MMAS-8. RESULTS: This study included a total of 420 patients with 81% being females, 52.1% aged 40 years and above, and 91% living in Madinah City. The study shows an overall poor adherence rate toward taking LT4, where the vast majority, 66.7% of the participants, had a low adherence level toward taking LT4, 23.3% had a moderate adherence level, and only 10% had a high adherence level. Results of the multivariate logistic regression showed that the following factors predicted a higher rate of a high level of adherence toward taking levothyroxine, being 50-59 years old, being 60 years or older, and following up regularly in the clinic. CONCLUSION: Patients with hypothyroidism showed low adherence to LT4.

MR Imaging of Carotid Artery Atherosclerosis: Updated Evidence on High-Risk Plaque Features and Emerging Trends.

MR imaging is well-established as the criterion standard for carotid artery atherosclerosis imaging. The capability of MR imaging to differentiate numerous plaque components has been demonstrated, including those features that are associated with a high risk of sudden changes, thrombosis, or embolization. The field of carotid plaque MR imaging is constantly evolving, with continued insight into the imaging appearance and implications of various vulnerable plaque characteristics. This article will review the most up-to-date knowledge of these high-risk plaque features on MR imaging and will delve into 2 major emerging topics: the role of vulnerable plaques in cryptogenic strokes and the potential use of MR imaging to modify carotid endarterectomy treatment guidelines.

The human carotid atherosclerotic plaque: an observational review of histological scoring systems.

OBJECTIVE: The atherosclerotic plaque is a complex dynamic pathological lesion of the arterial wall, characterized by multiple elementary lesions of different diagnostic and prognostic significance. Fibrous cap thickness, lipid necrotic core dimension, inflammation, intra-plaque hemorrhage (IPH), plaque neovascularization and endothelial dysfunction (erosions) are generally considered the most relevant morphological details of plaque morphology. In this review, the most relevant features able to discriminate between stable and vulnerable plaques at histological level are discussed. SUBJECTS AND METHODS: Retrospectively, we have evaluated the laboratory results from one hundred old histological samples from patients treated with carotid endarterectomy. These results were analyzed to assess elementary lesions that characterize stable and unstable plaques. RESULTS: A thin fibrous cap (<65 micron), loss of smooth muscle cells, collagen depletion, a large lipid-rich necrotic core, infiltrating macrophages, IPH and intra-plaque vascularization are identified as the most important risk factors associated with plaque rupture. CONCLUSIONS: Immunohistochemistry for smooth muscle actin (smooth muscle cell marker) and for CD68 (marker of monocytes/macrophages) and glycophorin (marker of red blood cells) are suggested as useful tools for an in deep characterization of any carotid plaque and for distinguishing plaque phenotypes at histology. Since patients with a carotid vulnerable plaque are at higher risk of developing vulnerable plaques in other arteries as well, the definition of the vulnerability index is underlined, in order to stratify patients at higher risk for undergoing cardiovascular events.

Symptoms, Mechanisms, and Treatments of Video Game Addiction.

Video game addiction is defined as the steady and repetitive use of the Internet to play games frequently with different gamers, potentially leading to negative consequences in many aspects of life. As recent technological development has given easy access to gaming on many devices, video game addiction has become a serious public health issue with increased prevalence. Many studies have shown that video game addiction leads to changes in the brain that are similar to those that occur in substance addiction and gambling. Evidence has also shown that there is an association between video game addiction and depression, as well as other psychological and social problems. In light of these issues, our review article aims to increase awareness of video game addiction in society. The main objectives of this review are as follows: to describe the mechanism of addiction, to consider whether video game addiction is a real addiction, and to highlight the signs and symptoms of addiction. In addition, we identify the consequences of video game addiction and possible treatments for addicts. The information was extracted from high-quality research papers and reliable websites like PubMed and ScienceDirect.

Nonstenotic Carotid Plaques and Embolic Stroke of Undetermined Source: A Multimodality Review.

Symptomatic nonstenotic carotid artery disease has been increasingly recognized as a thromboembolic source in patients who would otherwise be classified as having embolic stroke of undetermined source. Evidence suggests that certain plaque features seen on sonography, CT, and MR imaging in nonstenotic carotid artery disease may predispose to recurrent stroke in patients with embolic stroke of undetermined source. We performed a focused literature review to further study plaque features in the context of embolic stroke of undetermined source and to determine which plaque features may be associated with ipsilateral ischemic events in such patients. Plaque thickness as seen on both ultrasound and CT appears to have a consistent association with ipsilateral stroke in patients with embolic stroke of undetermined source across multiple studies. Intraplaque hemorrhage as seen on MR imaging is now understood to have a strong association with ipsilateral stroke in patients with embolic stroke of undetermined source. Continued study of various plaque features as seen on different modalities is warranted to uncover other potential associations.

Survey of the American Society of Neuroradiology Membership on the Use and Value of Extracranial Carotid Vessel Wall MRI.

BACKGROUND AND PURPOSE: Extracranial vessel wall MRI (EC-VWI) contributes to vasculopathy characterization. This survey study investigated EC-VWI adoption by American Society of Neuroradiology (ASNR) members and indications and barriers to implementation. MATERIALS AND METHODS: The ASNR Vessel Wall Imaging Study Group survey on EC-VWI use, frequency, applications, MR imaging systems and field strength used, protocol development approaches, vendor engagement, reasons for not using EC-VWI, ordering provider interest, and impact on clinical care was distributed to the ASNR membership between April 2, 2019, to August 30, 2019. RESULTS: There were 532 responses; 79 were excluded due to minimal, incomplete response and 42 due to redundant institutional responses, leaving 411 responses. Twenty-six percent indicated that their institution performed EC-VWI, with 66.3% performing it ≤1-2 times per month, most frequently on 3T MR imaging, with most using combined 3D and 2D protocols. Protocols most commonly included pre- and postcontrast T1-weighted imaging, TOF-MRA, and contrast-enhanced MRA. Inflammatory vasculopathy (63.3%), plaque vulnerability assessments (61.1%), intraplaque hemorrhage (61.1%), and dissection-detection/characterization (51.1%) were the most frequent applications. For those not performing EC-VWI, the reasons were a lack of ordering provider interest (63.9%), lack of radiologist time/interest (47.5%) or technical support (41.4%) for protocol development, and limited interpretation experience (44.9%) and knowledge of clinical applications (43.7%). Reasons given by 46.9% were that no providers approached radiology with interest in EC-VWI. If barriers were overcome, 51.1% of those not performing EC-VWI indicated they would perform it, and 40.6% were unsure; 48.6% did not think that EC-VWI had impacted patient management at their institution. CONCLUSIONS: Only 26% of neuroradiology groups performed EC-VWI, most commonly due to limited clinician interest. Improved provider and radiologist education, protocols, processing techniques, technical support, and validation trials could increase adoption.

Expression of L1 Cell Adhesion Molecule (L1CAM) in extracellular vesicles in the human spinal cord during development.

OBJECTIVE: L1  cell adhesion molecule (L1CAM) is a glycoprotein characterized by three components: an extracellular region, a transmembrane segment, and a cytoplasmic tail. L1CAM is expressed in multiple human cells, including neurons. The neural cell adhesion molecule L1 has been implicated in a variety of neurologic processes, including neuritogenesis and cerebellar cell migration. The presence of L1CAM on the surface of nerve cells allows the adhesion of neurons among them. Furthermore, when it is bound to itself or to other proteins, L1-CAM induces signals inside the cell. The aim of this work was to study L1CAM expression in the human spinal cord during development, at different gestational ages, through immunohistochemistry. MATERIALS AND METHODS: Immunohistochemical analysis for L1CAM was performed in five human spinal cord samples, including three embryos and two fetuses of different gestational ages, ranging from 8 to 12 weeks. RESULTS: L1CAM expression was detected in all 5 spinal cords examined in this study. The adhesion molecule was found in the vast majority of cells. The highest levels of immunoreactivity for L1CAM were detected at the periphery of the developing organs, in the spinal cord zones occupied by sensory and motor fibers. In the alar and basal columns, immunoreactivity for L1CAM was characterized by a reticular pattern, being mainly expressed in axons. Strong reactivity of L1CAM was also found in extracellular vesicles. This extracellular localization might indicate the ability of L1CAM to mediate the transduction of extracellular signals that support axon outgrowth. CONCLUSIONS: The high reactivity of L1cam in the axons of developing neurons in the fetal spinal cord confirms previous studies on the ability of L1CAM to promote axon sprouting and branching in the developing nervous system. In this work, a new actor is reported to have a role in the complex field of human spinal cord development: L1CAM, whose expression is highly found in the developing neuronal and glial precursors.

Interindividual variability in L1CAM expression in the human kidney during development: are there implications for fetal programming of kidney diseases presenting in adulthood?

OBJECTIVE: L1 cell adhesion molecule (L1CAM) is a member of the immunoglobulin superfamily of cell adhesion molecules. The present study investigated the expression of L1CAM during the development in the fetal human kidney at different gestational ages, to reach a better knowledge on the role of L1CAM in renal morphogenesis. MATERIALS AND METHODS: The immunohistochemical analysis for L1CAM was performed in 24 fetal kidneys of different gestational ages, ranging from 10 to 38 weeks. L1CAM expression was observed in all 24 kidneys examined. RESULTS: Immunoreactivity for L1CAM was restricted to the collecting tubules, of the developing fetal kidneys. Moreover, L1CAM was detected in the ureteric bud tips, near the subcapsular metanephric mesenchymal stem/progenitor cells. L1CAM was also expressed in the collecting tubules undergoing fusion with the distal tubules of the developing nephrons. L1CAM was mainly expressed along the cell membrane. In fetal kidneys in which the renal pelvis was observed, epithelial cells of the renal pelvis showed strong membranous reactivity for L1CAM. CONCLUSIONS: Our study shows that L1CAM is expressed in all stages of human kidney nephrogenesis, being restricted to the renal structures derived from the ureteric bud. The expression of L1CAM in the cells of the ureteric bud tips suggests a major role for this adhesion molecule in the induction of metanephric mesenchymal cells to undergo mesenchymal-to-epithelial transition and differentiation into new nephrons. The interindividual variability in L1CAM expression observed in this study might be related to different levels of nephrogenesis, suggesting L1CAM involvement in the fetal programming of adult kidney diseases.

The role of fetal programming in human carcinogenesis - May the Barker hypothesis explain interindividual variability in susceptibility to cancer insurgence and progression?

The growing incidence of cancers is pushing oncologists to find out new explanations other than the somatic mutation theory, based on the accumulation of DNA mutations. In particular, the embryo-fetal exposure to an increasing number of environmental factors during gestation might represent a trigger able to influence the susceptibility of the newborn to develop cancer later in life. This idea agrees with the fetal programming theory, also known as the Barker hypothesis. Here the role of insulin-like growth factors, thymosin beta-4, and epigenome are discussed as mediators of cancer in prenatal human development. The role of epigenetic factors that during gestation increase the predisposition to develop cancer and the similarities in the gene expression (like MMP9, OPN, TP53 and CDKN2A) between embryonic development and cancer are key factors. Likewise, maternal obesity might be able to re-program embryo-fetal development with long-term changes, including an increased risk to develop neuroblastoma and acute leukemia. Birth weight alone and birth weight corrected for gestational age are proposed as important variables capable of predicting the vulnerability to develop cancers. According to the findings here reported, we hypothesize that cancer prevention should start during gestation by improving the quality of maternal diet. In conclusion, the Barker hypothesis should be applied to cancer as well. Therefore, the identification of the epigenetic factors of cancer appears mandatory, so that the cancer prevention might start in the womb before birth.

Survey of the American Society of Neuroradiology Membership on the Use and Value of Intracranial Vessel Wall MRI.

BACKGROUND AND PURPOSE: Intracranial vessel wall MR imaging is an emerging technique for intracranial vasculopathy assessment. Our aim was to investigate intracranial vessel wall MR imaging use by the American Society of Neuroradiology (ASNR) members at their home institutions, including indications and barriers to implementation. MATERIALS AND METHODS: The ASNR Vessel Wall Imaging Study Group survey on vessel wall MR imaging use, frequency, applications, MR imaging systems and field strength used, protocol development approaches, vendor engagement, reasons for not using vessel wall MR imaging, ordering-provider interest, and impact on clinical care, was distributed to the ASNR membership between April 2 and August 30, 2019. RESULTS: There were 532 responses; 79 were excluded due to nonresponse and 42 due to redundant institutional responses, leaving 411 responses. Fifty-two percent indicated that their institution performs vessel wall MR imaging, with 71.5% performed at least 1-2 times/month, most frequently on 3T MR imaging, and 87.7% using 3D sequences. Protocols most commonly included were T1-weighted pre- and postcontrast and TOF-MRA; 60.6% had limited contributions from vendors or were still in protocol development. Vasculopathy differentiation (94.4%), cryptogenic stroke (41.3%), aneurysm (38.0%), and atherosclerosis (37.6%) evaluation were the most common indications. For those not performing vessel wall MR imaging, interpretation (53.1%) or technical (46.4%) expertise, knowledge of applications (50.5%), or limitations of clinician (56.7%) or radiologist (49.0%) interest were the most common reasons. If technical/expertise obstacles were overcome, 56.4% of those not performing vessel wall MR imaging indicated that they would perform it. Ordering providers most frequently inquiring about vessel wall MR imaging were from stroke neurology (56.5%) and neurosurgery (25.1%), while 34.3% indicated that no providers had inquired. CONCLUSIONS: More than 50% of neuroradiology groups use vessel wall MR imaging for intracranial vasculopathy characterization and differentiation, emphasizing the need for additional technical and educational support, especially as clinical vessel wall MR imaging implementation continues to grow.

Strong ACE-2 expression in the choroidal vessels: do high choroid plexuses serve as a gateway for SARS-CoV-2 infection on the human brain?

OBJECTIVE: Previous studies have confirmed the key mechanism by which SARS-CoV-2 enters human cells. It is well established that ACE2 is the receptor that can mark the beginning of the infection. In light of this, the organs that express higher levels of ACE2 are generally considered at higher risk, while those with lower levels should be somehow more protected. This - if related to the scarcity of ace2-expressing cells in the brain - seems to contrast with the presence of a variety of neurological symptoms that follow infection with ace2.  The aim of this work was to analyze ACE2 expression in the human brain, focusing on the choroid plexuses. PATIENTS AND METHODS: Twenty brain samples were obtained at autopsy from ten human fetuses and from ten adult subjects. All samples were selected to contain the choroid plexus. Specimens were fixed in 10% formalin, routinely processed and paraffin embedded. 5-micron sections were stained with Hematoxylin and Eosin (H&E) and immunostained with a commercial anti-human ACE2 rabbit monoclonal antibody at 1:100 dilution. RESULTS: We analyzed 20 samples by immunohistochemistry, and we noted that, as far as fetal samples are concerned, a strong reactivity for ACE2 was detected in the myxoid stroma of the choroid plexuses and in the endothelial cells in fetuses. The complete absence of the ACE2 marker was detected in epithelial cells, neurons and glial cells of the cerebral cortex, both in fetuses and in adults. Whereas a  strong but selective reactivity for ACE2 was also detected in adult choroid plexuses, mainly localized in the endothelial cells of the choroid capillaries. CONCLUSIONS: Our study shows a strong expression of ACE in the fetal and adult brain choroid plexuses. This new histopathological finding may clarify the susceptibility of the human brain to SARS-COV-2 infection. Our data indicate the choroid plexus as the entry gate of virus for in the human brain; therefore, the entrance of SARS-CoV-2 into the cerebrospinal fluid through the choroid plexuses might represent the mechanism utilized by this coronavirus to cause direct injury to brain cells.

Reassessing the Carotid Artery Plaque "Rim Sign" on CTA: A New Analysis with Histopathologic Confirmation.

BACKGROUND AND PURPOSE: The CTA "rim sign" has been proposed as an imaging marker of intraplaque hemorrhage in carotid plaques. This study sought to investigate such findings using histopathologic confirmation. MATERIALS AND METHODS: Included patients had CTA neck imaging <1 year before carotid endarterectomy. On imaging, luminal stenosis and the presence of adventitial (<2-mm peripheral) and "bulky" (≥2-mm) calcifications, total plaque thickness, soft-tissue plaque thickness, calcification thickness, and the presence of ulcerations were assessed. The rim sign was defined as the presence of adventitial calcifications with internal soft-tissue plaque of ≥2 mm in maximum thickness. Carotid endarterectomy specimens were assessed for both the presence and the proportional makeup of lipid material, intraplaque hemorrhage, and calcification. RESULTS: Sixty-seven patients were included. Twenty-three (34.3%) were women; the average age was 70.4 years. Thirty-eight (57.7%) plaques had a rim sign on imaging, with strong interobserver agreement (κ = 0.85). A lipid core was present in 64 (95.5%) plaques (average, 22.2% proportion of plaque composition); intraplaque hemorrhage was present in 52 (77.6%), making up, on average, 13.7% of the plaque composition. The rim sign was not associated with the presence of intraplaque hemorrhage (P = .11); however, it was associated with a greater proportion of intraplaque hemorrhage in a plaque (P = .049). The sensitivity and specificity of the rim sign for intraplaque hemorrhage were 61.5% and 60.0%, respectively. CONCLUSIONS: The rim sign is not associated with the presence of intraplaque hemorrhage on histology. However, it is associated with a higher proportion of hemorrhage within a plaque and therefore may be a biomarker of more severe intraplaque hemorrhage, if present.

Impact Analysis of Different CT Configurations of Carotid Artery Plaque Calcifications on Cerebrovascular Events.

BACKGROUND AND PURPOSE: CT is considered the standard reference both for quantification and characterization of carotid artery calcifications. Our aim was to investigate the relationship among different types of calcium configurations detected with CT within the plaque with a novel classification and to investigate the prevalence of cerebrovascular events. MATERIALS AND METHODS: Seven hundred ninety patients (men = 332; mean age, 69.7 [SD, 13] years; 508 symptomatic for cerebrovascular symptoms and 282 asymptomatic) who underwent computed tomography of the carotid arteries were retrospectively included in this institutional review board-approved study. The plaque was classified into 6 types according to the different types of calcium configurations as the following: type 1, complete absence of calcification within the plaque; type 2, intimal or superficial calcifications; type 3, deep or bulky calcifications; type 4, adventitial calcifications with internal soft plaque of <2 mm thickness; type 5, mixed patterns with intimal and bulky calcifications; and type 6, positive rim sign. RESULTS: The highest prevalence of cerebrovascular events was observed for type 6, for which 89 of the 99 cases were symptomatic. Type 6 plaque had the highest degree of correlation with TIA, stroke, symptoms, and ipsilateral infarct for both sides with a higher prevalence in younger patients. The frequency of symptoms observed by configuration type significantly differed between right and left plaques, with symptoms observed more frequently in type 6 calcification on the right side (50/53; 94%) than on the left side (39/46; 85%, P < .001). CONCLUSIONS: We propose a novel carotid artery plaque configuration classification that is associated with the prevalence of cerebrovascular events. If confirmed in longitudinal analysis, this classification could be used to stratify the risk of occurrence of ischemic events.

Corpus callosum volumetrics and clinical progression in early multiple sclerosis.

OBJECTIVE: Corpus callosum (CC) is commonly affected in multiple sclerosis (MS), with known association between CC atrophy and MS clinical activity. In this study, we assessed the association of callosal atrophy, lesions volume and residual CC volume with the clinical disability of early MS patients. SUBJECTS AND METHODS: Thirteen MS subjects (9 female, mean age 36.9 years), studied with magnetic resonance imaging (MRI) were selected. MRI scans were performed at baseline (T0), at 6 (T1), 12 (T2), and 24 months (T3) from baseline. CC was segmented into three sections (genu, body, and splenium); callosal boundaries were outlined and all CC lesions were manually traced. Normal CC and CC lesion volumes were measured using a semiautomatic software. RESULTS: From January 2014 to December 2016, all selected patients had confluent lesions on MRI at T3 with a significant increase in the size of confluent lesions compared to baseline (p=0.0007). At T1, a significant increase in the size of confluent (p=0.02) and single lesions located in the callosal body (p=0.04) was detected in patients with EDSS ≥1.5. Also, CC residual volume (CCR) rather than the whole CC volume (CCV) significantly correlated (p=0.03) with the clinical progression of MS in the whole cohort. CONCLUSIONS: In early MS patients with higher EDSS at baseline, a significant increase in confluent CC lesions size is evident, particularly in the callosal body. Also, median CCR is significantly associated with MS progression in the whole MS group, regardless of initial EDSS. Given their significant association with disability, we encourage measuring CC body lesions and residual CC size for therapeutic decisions and prognostic planning in early MS.

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.

Acute embolisms in multiple arterial districts following Ad26.COV2-S vaccine.

A case of multiple arterial thrombosis/embolisms in a 74-year-old Caucasian man with no other cardiovascular risk factors who received Ad26.COV2-S vaccine 16 days before is reported. The unusual presentation required a longer diagnostic workup. The clinical manifestations and the therapy-specific response suggest an unusual presentation of Vaccine-induced immune thrombotic thrombocytopenia (VITT).