Humoral efficacy of the third SARS-CoV-2 vaccine dose in Multiple Sclerosis subjects undergoing different disease-modifying therapies.

BACKGROUND: It remains unclear how vaccine doses and combinations of vaccination and infection affect the magnitude and quality of immune responses, particularly against novel SARS-CoV-2 variants in subjects with immune-related disorders, such as people with multiple sclerosis (pwMS). Several studies have evaluated the duration of anti-SARS-CoV-2 immune protection in healthy individuals; however clinical data suggest an attenuated short-term humoral response to SARS-CoV-2 vaccines in pwMS receiving disease-modifying therapies (DMTs). METHODS: In this prospective study, we evaluated the humoral response to the third (3rd) BNT162b2 vaccine (booster) dose in a monocentric cohort of pwMS undergoing eight different DMTs, all without previous SARS-CoV-2 infection. Quantitative determination of SARS-CoV-2 IgG Spike titre was carried out by anti-SARS-CoV-2 S assay in 65 pwMS and 9 healthy controls, all without previous SARS-CoV-2 infection. Moreover, these measurements were also compared to their relative levels at 21 days (T1) and ∼6 months (T2) after the second (2nd) vaccination. RESULTS: We observed that the humoral response to the booster dose in Interferon ß-1a-, Dimethyl fumarate- and Teriflunomide-treated pwMS is comparable to healthy controls, while increased in Cladribine-treated pwMS. Additionally, the 3rd dose elicits a seroconversion in the 100% of pwMS under Fingolimod and in the 65% of those under Ocrelizumab. Moreover, multivariate regression analysis showed that treatment with Interferon ß-1a, Dimethyl fumarate and Cladribine positively associates with an increased humoral response. CONCLUSIONS: Taken together this evidence strongly indicates the importance of the booster dose to enhance SARS-CoV-2-specific immunity especially in immunocompromised subjects, such as pwMS under DMTs.

GAD65 autoimmunity after treatment with nivolumab: a multifocal presentation.

INTRODUCTION: Neurological disorders are considered rare complications of immune-checkpoint inhibitor. CASE DESCRIPTION: We report a 63-year-old man with recurrence of melanoma who presented epilepsy, limbic encephalitis, cerebellar ataxia, and stiff person syndrome soon after treatment with nivolumab, an immune-checkpoint inhibitor. On autoimmune screening, serum and CSF GAD65 were detected. Significant response to steroids and intravenous immunoglobulins were observed, but cancer recurred after nivolumab discontinuation in parallel with epileptic seizure and worsening of cognitive impairment and the patient died. DISCUSSION: This case expands the spectrum of GAD65-associated conditions induced by immune-checkpoint inhibitor and underlines treatment complexity when both neurological complications and tumour recurrence occur.

Anti-MOG-associated demyelinating disorders: two sides of the same coin.

BACKGROUND: Anti-myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) are new emerging diseases with heterogeneous course, treatment, response, and prognosis. CASE REPORT: We herein present 2 cases with antibodies to MOG, one with a cerebellar/brainstem monophasic syndrome which partially improved after treatment, and the other with an optic neuritis onset then relapsed with cortical encephalitis and presented a subsequent complete recovery. We further discuss elements possibly associated with disease heterogeneity and influencing treatment choices. CONCLUSIONS: MOGAD is an extremely variable disease which can relapse and accumulate disability over time. An early diagnosis and correct timely treatment is fundamental to improve clinical outcome.

Brain Radionecrosis After Adjuvant Radiation Therapy for a Primary Intracerebral Undifferentiated Sarcoma.

BACKGROUND: Primary intracranial sarcomas of the central nervous system are rare tumors. They mainly arise from intracranial mesenchymal tissue present in the meninges and can occur at any age. Sometimes osteosarcoma can involve the skull rather than long body bones. In this latter case it is the more common subtype. Surgery, when possible, is a mandatory option often associated with radiation therapy (RT) and chemotherapy. Brain radionecrosis (BRN) is commonly observed due to the growing use of radiosurgery and higher cumulative doses of radiation therapy. The combination of perfusion magnetic resonance imaging and 18fluoro-deoxy-glucose positron emission tomography can help to differentiate tumor progression from radiation injury. Steroids, anticoagulants, and bevacizumab usually control BRN. However, BRN can also have an unfavorable course. CASE DESCRIPTION: Here, we present a case of a 60-year-old male who underwent surgery for a brain tumor. The examination showed a primary undifferentiated high-grade sarcoma. Adjuvant RT was given with a total dose of 60 Gy. Six months later, the patient underwent a second surgery that revealed a BRN progressing despite different pharmacologic attempts. CONCLUSIONS: Primary intracranial sarcomas of the central nervous system are less prevalent among older adults with respect to the younger population. The use of RT alone or combined with chemotherapy is aimed at prolonging survival. However, it is not clearly defined if adjuvant treatments affect this parameter in older patients. RT should be carefully discussed owing to its potential severe neurologic toxicity. Indeed, a BRN can have a significant impact on quality of life and lead to death in certain cases.

Early Detection of Deep Venous Thrombosis in Trauma Patients.

Background This study was performed to determine whether trauma patients are at an increased risk of developing deep venous thrombosis (DVT) within the first 48 hours of hospitalization. Materials and methods A retrospective review was performed using a prospectively maintained database of patients admitted to a trauma center during a five-year time period. Patients hospitalized for greater than 48 hours who received a screening venous duplex for DVT were included in the study. Results There were 1067 venous duplex scans obtained, 689 (64.5%) within the first 48 hours of admission (early DVT group), 378 (35.4%) after the first 48 hours (late DVT group). Only 142 (13.2%) patients had a positive duplex scan for DVT, 55 (early group), 87 (late group). Comorbid conditions of congestive heart failure (P = 0.02), pelvic fractures (P = 0.04), and a lower initial systolic blood pressure on presentation (p = 0.04) were associated with early DVT. Head trauma (P < 0.01), mechanical ventilation (P < 0.001), and transfusion of blood products (P < 0.001), were predictors of DVT in the late group. Conclusions Trauma patients are at an increased risk of developing venous thrombosis early in the hospital course due to comorbidities associated with trauma. Whereas, venous thrombosis in trauma patients diagnosed after the first 48 hours of hospitalization appears to be associated with prolonged patient immobility.

Survival after endovascular therapy in patients with ruptured thoracic aortic diseases: Results from the Global Registry for Endovascular Aortic Treatment Registry.

OBJECTIVE: The Global Registry for Endovascular Aortic Treatment is a prospective observational multicenter cohort registry of all Gore aortic endografts for a variety of aortic pathologies. The purpose of this study was to evaluate the outcome of the Conformable GORE TAG Thoracic Endoprosthesis and GORE TAG Thoracic Endoprosthesis devices for ruptured thoracic aortic syndromes. METHODS: Between December 2010 and October 2016, a total of 5018 patients were enrolled from 114 international sites in this registry. The database was queried for patients with at least one of the following pathologies: descending thoracic aortic aneurysm with rupture, thoracoabdominal aortic aneurysm rupture, descending aortic dissection rupture, and aortic arch aneurysm rupture. Patient demographics, operative details, and clinical outcomes were analyzed. RESULTS: A total of 40 patients were treated with a ruptured thoracic aortic disease (62.5% male; mean age, 67.5 ± 14.1 years). Nineteen patients were treated for descending thoracic aneurysm rupture, 9 for thoracoabdominal aneurysm rupture, 7 for descending aortic dissection rupture, and 5 for aortic arch aneurysm rupture. Technical success was achieved in 40 of 40 patients (100%). There were no intraoperative mortalities and no conversions to an open procedure. A total of 12 patients (30.0%) required intervention for involvement of at least one aortic branch vessel (4 covered, 5 surgically debranched, 1 stented, and 6 chimney technique). The 30-day mortality was four patients (10.0%). Early reintervention (≤30 days) was required in seven patients (17.5%), five of which were device related. There was a total of five endoleaks and all five required a reintervention. The median follow-up duration was 14.7 months (range, 1-57 months). Freedom from device-related intervention at 1 year was 87.1% (95% confidence interval, [CI], 0.716-0.944), at 2 years was 81.3% (95% CI 0.607-0.917) and at 3 years was 73.1% (95% CI, 0.47-0.878). Freedom from all-cause mortality at 1 year was 65.0% (95% CI, 0.474-0.780), at 2 years was 61.2% (95% CI, 0.431-0.751), and at 3 years was 56.1% (95% CI, 0.369-0.715). CONCLUSIONS: The Conformable GORE TAG Thoracic Endoprosthesis and GORE TAG Thoracic Endoprosthesis thoracic endografts provide an effective treatment for ruptured thoracic aortic diseases. Adjunctive coverage or revascularization of an aortic branch vessel may be necessary. Longer follow-up and larger studies are needed to determine durability of these repairs.

Epidemiology of Lower Extremity Deep Venous Thrombosis in Critically Ill Adolescents.

OBJECTIVE: To determine the epidemiology of lower extremity deep venous thrombosis (DVT) in critically ill adolescents, which currently is unclear. STUDY DESIGN: We performed a multicenter, prospective, cohort study. Adolescents aged 13-17 years who were admitted to 6 pediatric intensive care units and were anticipated to receive cardiopulmonary support for at least 48 hours were eligible, unless they were admitted with DVT or pulmonary embolism or were receiving or anticipated to receive therapeutic anticoagulation. While patients were in the unit, serial sonograms of the lower extremities were performed, then centrally adjudicated. Bayesian statistics were used to leverage the similarities between adults and adolescents. RESULTS: A total of 88 adolescents were enrolled, from whom 184 lower extremity sonograms were performed. Of these, 9 adolescents developed DVT, with 1 having bilateral DVT. The frequency of DVT was 12.4% (95% credible interval: 6.1%, 20.1%), which ranged from 6.3% to 19.8% with a variability of 41.0% across units. All cases of DVT occurred in adolescents who received invasive mechanical ventilation (frequency: 16.5%; 95% credible interval 8.1%, 26.6%). DVT was associated with femoral central venous catheterization (OR 15.44; 95% credible interval 1.62, 69.05) and severe illness (OR for every 0.1 increase in risk of mortality 3.11; 95% credible interval 1.19, 6.85). DVT appears to be associated with prolonged days on support. CONCLUSIONS: Our findings highlight the similarities and differences in the epidemiology of DVT between adults and adolescents. They support the conduct and inform the design of a trial of pharmacologic prophylaxis in critically ill adolescents.

Balloon angioplasty for symptomatic inferior vena cava aneurysm.

Aneurysms of the inferior vena cava (IVC) are uncommon. Symptomatic patients usually present with thrombosis and venous obstruction. Classification is based on location and the presence or absence of congenital IVC interruption. Treatment options include observation, open surgical resection, and endovascular modalities, of which coil embolization and stent graft placement have previously been described. We report the case of a patient with a 5.0-cm infrarenal IVC aneurysm and associated congenital stenosis who successfully underwent balloon angioplasty. Whereas management should be determined on an individual basis, balloon angioplasty is a plausible treatment for IVC aneurysms in the setting of congenital stenosis.

Gliomatosis cerebri: a review of 296 cases from the ANOCEF database and the literature.

Gliomatosis cerebri (GC) is a rare disease, defined as a diffuse neoplastic glial cell infiltration of the brain. Diagnosis and management of GC are difficult. This study analyzed 296 individual cases (90 patients followed through the ANOCEF network, and 206 cases from the literature), aged 1 month to 85 years (median 42), sex ratio=1.31. Median survival was 14.5 months. It was higher for patients younger than 42 years (17 months vs. 13 months), with performance status>or=80 (27 months vs. 9 months), low grade gliomatosis (grade 2=20 months, grade 3=11.5 months, grade 4=8.5 months), oligodendroglial subtype (36 months compared to 14 months for mixed GC and 11 months for astrocytic GC). Male population was younger (median 39 years vs. 45), had a higher incidence of oligodendroglial GC (22% vs. 13%), which may explain their better prognosis (median survival 17 months vs. 11.5 months) than female population. Despite a high rate of stabilization, the impact on survival of whole brain radiotherapy, which carries the risk of severe toxicity, is still unclear. Up-front chemotherapy benefit to some patients and may be preferred to whole brain radiotherapy. However, the many bias of such retrospective heterogeneous data claim for multicentric clinical trials in this rare disease.