Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage.

BACKGROUND: Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. METHODS: We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. RESULTS: A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. CONCLUSIONS: Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).

Systematic review and meta-analysis on the association between chronic low back pain and cognitive function.

This study aimed to identify and assess the evidence on the association between idiopathic chronic low back pain (LBP) and cognitive function in individuals with LBP. A secondary aim was to explore whether changes in cognitive function are associated with pain characteristics and psychological factors (eg, catastrophizing and fear of movement). Eleven studies were included in this systematic review, and four meta-analyses were conducted. Low to very low-quality evidence suggests impaired cognitive function in individuals with LBP compared to asymptomatic controls for problem solving (k = 5; d = 0.33; CI = 0.16-0.50; z = 3.85 p = 0.0001), speed of information processing (k = 5; d = 0.44; CI = 0.22-0.65; z = 4.02 p < 0.0001), working memory (k = 6; d = 0.50; CI = 0.34-0.66; z = 6.09 p < 0.0001), and delayed memory (k = 3; d = 0.34; CI = 0.07-0.6, z = 2.49 p = 0.02). The association between LBP intensity and psychological factors and cognitive function was inconclusive. More studies are needed to explore these associations and improve evidence in this field. The results of this study suggest that cognitive aspects should be considered during the rehabilitation process of patients with LBP and raise further questions, including whether individuals with LBP are at a greater risk of developing dementia or whether targeting cognitive function will increase the probability of success of LBP treatment. These questions should, also, be considered in future studies.

Interchangeability of two versions of the Montreal Cognitive Assessment for the longitudinal evaluation of patients with breast cancer.

PURPOSE: The cognitive performance of patients with breast cancer (BCa) may be affected by cancer and its treatments. The Montreal Cognitive Assessment (MoCA) is a widely used cognitive impairment screening tool, but practice effects must be considered for longitudinal assessments. Since learning effects could be overcome through the alternate use of two versions of the MoCA, we aimed to explore their interchangeability by comparing their overall, and domain- and task-specific, scores among patients with BCa. METHODS: BCa patients from the NEON-BC cohort were evaluated with the MoCA, version 7.1, after diagnosis and after 1 year. At the 3-year follow-up (n = 422), the 7.1 and 7.3 versions were applied at the beginning and at the end (approximately 1 h later) of this evaluation, respectively. Agreements between versions, regarding total, sub-domain, and task scores, were assessed using Bland-Altman plots and intraclass correlation coefficients (ICC). RESULTS: The mean total scores were not statistically different between versions and the ICC was 0.890. The Bland-Altman limits of agreement were - 3.70 to 3.88. For women with midrange scores, total scores were significantly higher in version 7.1. There were significant differences in the percentage of correct answers in 7 out of 12 tasks, being the highest for the copy of a geometric figure (more than twofold higher with version 7.3). In version 7.1, the language and memory domains presented higher scores and lower visuospatial ability. CONCLUSION: Despite similar overall scores being obtained with the two versions of the MoCA, there were item-specific differences that may compromise their interchangeable use.

Healthcare, Clinical Factors and Rehabilitation Predicting Quality of Life in First-time Stroke Patients: A 12-month Longitudinal Study.

OBJECTIVES: One of the long-term rehabilitation goals in stroke survivors is to achieve the best health-related quality of life (HRQoL). This study analyzes the evolution of HRQoL one-year post-stroke to establish the main pre-stroke, clinical, health care and rehabilitation predictors. MATERIALS AND METHODS: This study uses patient-level data from a one-year single-center prospective cohort study of first stroke patients, assessed at baseline, 3, 6 and 12 months. A generalized linear model with a linear response determined independent predictors of HRQol with EQ-5D-3L and SF-6D. The model included age, gender, scholarity, monthly income, residence, occupation, National Institute of Health Stroke Scale (NIHSS), Modified Rankin Scale (mRS), Barthel Index (BI), Mini-Mental State Examination (MMSE), length of stay, door-to-neurological examination time, access, frequency, and satisfaction with rehabilitation care. RESULTS: A total of 391 acute stroke patients, with a mean disability of 3.7 and severity of 11.7 participated. A decline of HRQoL was observed from baseline to the first three months in both indexes, with an increase in HRQoL at 3 months until 12 months. Scores were significantly lower compared to corresponding population norms throughout follow-up, mostly affected by stroke severity, disability, rehabilitation access and frequency. Higher HRQoL was associated with lower mRS, NIHSS, age, length of stay, and with higher BI, MMSE, scholarity, occupation, and rehabilitation care. CONCLUSION: Clinical measures and rehabilitation care were the strongest HRQoL predictors of stroke survivors regardless of severity levels. These findings may contribute to the development of future health policies that focus on post-stroke recovery.

Neuro-COVID frequency and short-term outcome in the Northern Portuguese population.

BACKGROUND AND PURPOSE: COVID-19-related acute neurological phenotypes are being increasingly recognised, with neurological complications reported in more than 30% of hospitalised patients. However, multicentric studies providing a population-based perspective are lacking. METHODS: We conducted a retrospective multicentric study at five hospitals in Northern Portugal, representing 45.1% of all hospitalised patients in this region, between 1 March and 30 June 2020. RESULTS: Among 1261 hospitalised COVID-19 patients, 457 (36.2%) presented neurological manifestations, corresponding to a rate of 357 per 1000 in the North Region. Patients with neurologic manifestations were younger (68.0 vs. 71.2 years, p = 0.002), and the most frequent neurological symptoms were headache (13.4%), delirium (10.1%), and impairment of consciousness (9.7%). Acute well-defined central nervous system (CNS) involvement was found in 19.1% of patients, corresponding to a rate of 217 per 1000 hospitalised patients in the whole region. Assuming that all patients with severe neurological events were hospitalised, we extrapolated our results to all COVID-19 patients in the region, estimating that 116 will have a severe neurological event, corresponding to a rate of nine per 1000 (95% CI = 7-11). Overall case fatality in patients presenting neurological manifestations was 19.8%, increasing to 32.6% among those with acute well-defined CNS involvement. CONCLUSIONS: We characterised the population of hospitalised COVID-19 patients in Northern Portugal and found that neurological symptoms are common and associated with a high degree of disability at discharge. CNS involvement with criteria for in-hospital admission was observed in a significant proportion of patients. This knowledge provides the tools for adequate health planning and for improving COVID-19 multidisciplinary patient care.

A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1, Mapping to SCA37, Causes Spinocerebellar Ataxia.

Advances in human genetics in recent years have largely been driven by next-generation sequencing (NGS); however, the discovery of disease-related gene mutations has been biased toward the exome because the large and very repetitive regions that characterize the non-coding genome remain difficult to reach by that technology. For autosomal-dominant spinocerebellar ataxias (SCAs), 28 genes have been identified, but only five SCAs originate from non-coding mutations. Over half of SCA-affected families, however, remain without a genetic diagnosis. We used genome-wide linkage analysis, NGS, and repeat analysis to identify an (ATTTC)n insertion in a polymorphic ATTTT repeat in DAB1 in chromosomal region 1p32.2 as the cause of autosomal-dominant SCA; this region has been previously linked to SCA37. The non-pathogenic and pathogenic alleles have the configurations [(ATTTT)7-400] and [(ATTTT)60-79(ATTTC)31-75(ATTTT)58-90], respectively. (ATTTC)n insertions are present on a distinct haplotype and show an inverse correlation between size and age of onset. In the DAB1-oriented strand, (ATTTC)n is located in 5' UTR introns of cerebellar-specific transcripts arising mostly during human fetal brain development from the usage of alternative promoters, but it is maintained in the adult cerebellum. Overexpression of the transfected (ATTTC)58 insertion, but not (ATTTT)n, leads to abnormal nuclear RNA accumulation. Zebrafish embryos injected with RNA of the (AUUUC)58 insertion, but not (AUUUU)n, showed lethal developmental malformations. Together, these results establish an unstable repeat insertion in DAB1 as a cause of cerebellar degeneration; on the basis of the genetic and phenotypic evidence, we propose this mutation as the molecular basis for SCA37.

Tracking cognitive impairment in multiple sclerosis using the Brain on Track test: a validation study.

BACKGROUND: The accurate and regular monitoring cognitive performance in multiple sclerosis (MS) patients is critical to develop new prevention and management strategies for cognitive impairment (CI). The Brain on Track (BoT) test is a self-administered web-based tool developed for cognitive screening and monitoring. The objective of this study was to validate the use of the BoT in MS, by assessing its ability to distinguish between MS patients and matched controls, as well as detect CI among MS patients, by analysing its correlation with standard cognitive tests and its reliability and learning effects in repeatable use. METHODS: The BoT was applied in 30 patients with MS consecutively selected and 30 age- and education-matched controls, first in a hospital clinic, under supervision, and then 1 week later from home. After these first two trials, MS patients repeated the test from home every 4 weeks for 3 months. A standard neuropsychological battery was also applied to MS patients at baseline. RESULTS: The Cronbach's alpha was 0.89. Test scores were significantly different between MS patients and controls (Cohen's d = 0.87; p < 0.01). Among MS patients, scores were significantly lower in those with CI documented in the standard neuropsychological battery than in their cognitively preserved counterparts (Cohen's d = 2.0; p < 0.001). The BoT scores presented a good correlation with standard neuropsychological tests, particularly for information processing speed. Regarding test-retest reliability, 10/11 subtests presented two-way mixed single intraclass consistency correlation coefficients > 0.70. CONCLUSION: The BoT showed good neuropsychological parameters in MS patients, endorsing the use of self-administered computerized tests in this setting.

Correction to: Tracking cognitive impairment in multiple sclerosis using the Brain on Track test: a validation study.

The above article was published online with an error in author name's affiliations. Affiliation 8 has to be added to Maria Pia Amato and has to be deleted from Vitor Tedim.

Persistent trigeminal artery in a patient with posterior circulation stroke treated with rt-PA: case report.

BACKGROUND: A persistent trigeminal artery (PTA) is a non-involuted embryonic vessel that connects the cavernous part of the internal carotid artery with the posterior circulation. In the adult it is associated with multiple pathological conditions including trigeminal neuralgia, ophthalmoplegia, hypopituitarism, intracavernous fistula, brain aneurysms and posterior circulation strokes. The latter may occur through steal phenomena or thrombosis in the anterior circulation. PTA associated vertebrobasilar hypoplasia has yet to be associated to TIA like events, however, in the reported case, that seems to be the case with reported vertigo being probably linked to vertebrobasilar insufficiency. CASE REPORT: We present a case of an 82-year-old man with sudden onset neurological deficits, including left hemiparesis with crural predominance, vertical nystagmus, right internuclear ophthalmoplegia, dysarthria and dysmetria on the left arm. CT angiography disclosed basilar artery hypoplasia in the proximal two thirds and a persistent trigeminal artery. He was diagnosed with acute ischemic stroke. He was submitted to rt-PA with partial reversion of deficits. CONCLUSION: The ischemic events related to PTA remain a rare cause of stroke with specific pathophysiological mechanisms and implications. They may occur through steal phenomena or thrombosis in the anterior circulation. Upon literature review, in the described case both mechanisms seem possible, however the transient episodes of vertigo could have been the first sign of vertebrobasilar insufficiency.

Mechanical Thrombectomy in Acute Ischemic Stroke: Initial Single-Center Experience and Comparison with Randomized Controlled Trials.

BACKGROUND: Until recently, intravenous thrombolysis was the only reperfusion therapy with proven efficacy in patients with acute ischemic stroke. However, this treatment option has low recanalization rates in large-vessel occlusions. The search for additional treatments continued until 5 randomized trials (MR CLEAN, ESCAPE, EXTEND-IA, SWIFT PRIME, and REVASCAT) revealed the superiority of mechanical thrombectomy for anterior circulation large-vessel occlusion. After 1 year of performing thrombectomy with stent retrievers in our tertiary hospital, we intended to answer the question: is it possible to achieve similar results in a "real-world" setting? METHODS: We analyzed data from our prospective observational registry, compared it with the trials aforementioned, and concluded that the answer is affirmative. RESULTS: Our study population of 77 patients, with a mean age of 68,2 years and 48,1% men, is comparable with these trials in much of selection criteria, baseline characteristics, and rate of previous intravenous thrombolysis (72,7%). Recovery of functional independence at 90 days was achieved in almost two thirds of patients, similarly to the referred trials. We devoted special emphasis on fast recanalization, keeping a simple image selection protocol (based on non-enhanced and computed tomography angiography) and not waiting for clinical response to thrombolysis in patients eligible for mechanical thrombectomy. We emphasize a successful recanalization rate of 87% and only 2,6% symptomatic intracranial hemorrhage. CONCLUSION: In summary, mechanical thrombectomy seems to be a safe and effective treatment option in a "real-world" scenario, with results similar to those of the recent randomized controlled trials.

Alteration of ganglioside biosynthesis responsible for complex hereditary spastic paraplegia.

Hereditary spastic paraplegias (HSPs) form a heterogeneous group of neurological disorders. A whole-genome linkage mapping effort was made with three HSP-affected families from Spain, Portugal, and Tunisia and it allowed us to reduce the SPG26 locus interval from 34 to 9 Mb. Subsequently, a targeted capture was made to sequence the entire exome of affected individuals from these three families, as well as from two additional autosomal-recessive HSP-affected families of German and Brazilian origins. Five homozygous truncating (n = 3) and missense (n = 2) mutations were identified in B4GALNT1. After this finding, we analyzed the entire coding region of this gene in 65 additional cases, and three mutations were identified in two subjects. All mutated cases presented an early-onset spastic paraplegia, with frequent intellectual disability, cerebellar ataxia, and peripheral neuropathy as well as cortical atrophy and white matter hyperintensities on brain imaging. B4GALNT1 encodes ß-1,4-N-acetyl-galactosaminyl transferase 1 (B4GALNT1), involved in ganglioside biosynthesis. These findings confirm the increasing interest of lipid metabolism in HSPs. Interestingly, although the catabolism of gangliosides is implicated in a variety of neurological diseases, SPG26 is only the second human disease involving defects of their biosynthesis.

Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum.

Autosomal recessive hereditary spastic paraplegia (ARHSP) with thin corpus callosum (TCC) is a common and clinically distinct form of familial spastic paraplegia that is linked to the SPG11 locus on chromosome 15 in most affected families. We analyzed 12 ARHSP-TCC families, refined the SPG11 candidate interval and identified ten mutations in a previously unidentified gene expressed ubiquitously in the nervous system but most prominently in the cerebellum, cerebral cortex, hippocampus and pineal gland. The mutations were either nonsense or insertions and deletions leading to a frameshift, suggesting a loss-of-function mechanism. The identification of the function of the gene will provide insight into the mechanisms leading to the degeneration of the corticospinal tract and other brain structures in this frequent form of ARHSP.

Web-based cognitive training: patient adherence and intensity of treatment in an outpatient memory clinic.

BACKGROUND: Cognitive training has been playing an increasing role in the treatment of patients with cognitive deficits. This type of intervention, namely its intensity, can be optimized by incorporating information technology-based systems. OBJECTIVE: The intent of the study was to determine the treatment intensity and patient adherence to home-based cognitive training strategies (Web-based cognitive training). METHODS: A cohort of 45 patients with neurologic and psychiatric diseases attending an outpatient memory clinic (average age 50.7 years, SD 17.0; average education 7.8 years, SD 4.9) was followed over 18 months. Participants were challenged to use a Web-based cognitive training system, "COGWEB", on a daily basis, and fulfilled at least four weeks of training supervised remotely. Additionally, 11 patients attended face-to-face sessions. RESULTS: The average duration of continuous cognitive training was 18.8 weeks (SD 18.9). Each patient performed on average 363.5 minutes/week (SD 136.6). At 6-month follow-up, 82.8% complied with their treatment plan. The average proportion of complete weeks was 0.75 (SD 0.22). Patients with dementia trained more intensively (444.6 minutes/week), followed by patients with static brain lesion (414.5 minutes/week; P=.01). The group that held face-to-face sessions performed more training overall (481.4 vs 366.9 minutes/week), achieving a stronger expression and statistical significance in the last week of training (652.6 versus 354.9 minutes/week, P=.027). CONCLUSIONS: Overall, the weekly training intensity was high. Patients with dementia and static lesions performed more cognitive training. Face-to-face sessions were associated with higher intensities. The combination of classical methods with information technology systems seems to ensure greater training intensity.

Stroke rehabilitation pathways during the first year: A cost-effectiveness analysis from a cohort of 460 individuals.

BACKGROUND: Stroke burden challenges global health, and social and economic policies. Although stroke recovery encompasses a wide range of care, including in-hospital, outpatient, and community-based rehabilitation, there are no published cost-effectiveness studies of integrated post-stroke pathways. OBJECTIVE: To determine the most cost-effective rehabilitation pathway during the first 12 months after a first-ever stroke. METHODS: A cohort of people in the acute phase of a first stroke was followed after hospital discharge; 51 % women, mean (SD) age 74.4 (12.9) years, mean National Institute of Health Stroke Scale score 11.7 (8.5) points, and mode modified Rankin Scale score 3 points. We developed a decision tree model of 9 sequences of rehabilitation care organised in 3 stages (3, 6 and 12 months) through a combination of public, semi-public and private entities, considering both the individual and healthcare service perspectives. Health outcomes were expressed as quality-adjusted life years (QALY) over a 1-year time horizon. Costs included healthcare, social care, and productivity losses. Sensitivity analyses were conducted on model input values. RESULTS: From the individual perspective, pathway 3 (Short-term Inpatient Unit ¼ Community Clinic) was the most cost-effective, followed by pathway 1 (Rehabilitation Centre ¼ Community Clinic). From the healthcare service perspective, pathway 3 was the most cost-effective followed by pathway 7 (Outpatient Hospital ¼ Private Clinic). All other pathways were considered strongly dominated and excluded from the analysis. The total 1-year mean cost ranged between €12104 and €23024 from the individual's perspective and between €10992 and €31319 from the healthcare service perspective. CONCLUSION: Assuming a willingness-to-pay threshold of one times the national gross domestic product (€20633/QALY), pathway 3 (Short-term Inpatient Unit ¼ Community Clinic) was the most cost-effective strategy from both the individual and healthcare service perspectives. Rehabilitation pathway data contribute to the development of a future integrated care system adapted to different stroke profiles.

Adherence to the Mediterranean Diet, Sodium and Potassium Intake in People at a High Risk of Dementia.

Adequate sodium and potassium intake, along with adherence to the Mediterranean diet (MedDiet), are key factors for preventing hypertension and cerebrovascular diseases. However, data on the consumption of these nutrients within the MedDiet are scarce. This cross-sectional study aims to assess the association between MedDiet adherence and sodium/potassium intake in the MIND-Matosinhos randomized controlled trial, targeting Portuguese adults at a high risk of dementia. Good adherence to the MedDiet was defined using the Portuguese Mediterranean Diet Adherence Screener questionnaire (≥10 points), and both sodium/potassium intakes were estimated from 24-hour urine collections. The association between MedDiet adherence and these nutrients' intake (dichotomized by the median) was quantified by calculating odds ratios (OR) and respective 95% confidence intervals (95% CI) using a logistic regression. A total of 169 individuals (60.9% female; median age: 70 years; range: 36-85 years) were included. Good adherence to the MedDiet was observed among 18.3% of the sample. After adjusting for sex, age, education and using antihypertensive drugs, good MedDiet adherence was associated with higher sodium (OR = 3.11; 95% CI: 1.27-7.65) and potassium intake (OR = 9.74; 95% CI: 3.14-30.26). Increased adherence to the MedDiet may contribute to a higher potassium intake but seems to have limited effects on the adequacy of sodium levels.

Validation of a web-based self-administered test for cognitive assessment in a Swedish geriatric setting.

Computerized cognitive tests have the potential to cost-effectively detect and monitor cognitive impairments and thereby facilitate treatment for these conditions. However, relatively few of these tests have been validated in a variety of populations. Brain on Track, a self-administered web-based test, has previously been shown to have a good ability to differentiate between healthy individuals and patients with cognitive impairment in Portuguese populations. The objective of this study was to validate the differential ability and evaluate the usability of Brain on Track in a Swedish memory clinic setting. Brain on Track was administered to 30 patients with mild cognitive impairment/mild dementia and 30 healthy controls, all scheduled to perform the test from home after one week and after three months. To evaluate the usability, the patient group was interviewed after completion of the testing phase. Patients scored lower than healthy controls at both the first (median score 42.4 vs 54.1, p<0.001) and the second test (median score 42.3 vs 55.0, p<0.001). The test-retest intra-class correlation was 0.87. A multiple logistic regression model accounting for effects of age, gender and education rendered an ability of Brain on Track to differentiate between the groups with an area under the receiver operation characteristics curve of 0.90 for the first and 0.88 for the second test. In the subjective evaluation, nine patients left positive comments, nine were negative whereas five left mixed comments regarding the test experience. Sixty percent of patients had received help from relatives to log on to the platform. In conclusion, Brain on Track performed well in differentiating healthy controls from patients with cognitive impairment and showed a high test-retest reliability, on par with results from previous studies. However, the substantial proportion of patients needing help to log in could to some extent limit an independent use of the platform.

Association between sociodemographic and clinical features, health behaviors, and health literacy of patients with prostate cancer and prostate cancer prognostic stage.

Patient characteristics may influence access and acceptance of Prostate Specific Antigen test, and therefore, the timing of prostate cancer (PCa) diagnosis. A group of 361 patients from a cohort (n = 451) diagnosed with PCa in 2018-2020 at the Portuguese Institute of Oncology of Porto was evaluated before treatment, using a structured interview, the Medical Term Recognition Test, and the EORTC Quality of Life Questionnaire QLQ-PR25. PCa prognostic stages (I, II, III, IV) were attributed according to the American Joint Committee on Cancer eighth edition. Multinomial logistic regression was used to compute the odds ratio and 95% confidence interval (OR [95% CI]), considering PCa stage II, the most frequent, as reference. Older age (OR = 4.21 [2.24-7.93]), living outside the Porto Metropolitan Area while having low income (OR = 6.25 [1.53-25.62]), and erectile dysfunction (OR = 2.22 [0.99-4.99]) were associated with stage III, while urination during the night (OR = 3.02 [1.42-6.41]) was associated with stage IV. Urine leakage was less frequent in stage III (OR = 0.23 [0.08-0.68]), and living with a partner (OR = 0.41 [0.19-0.88]) and family history of cancer (OR = 0.25 [0.07-0.86]) in stage IV. Health literacy was not associated with PCa stage but lower education was less frequent in stage I (OR = 0.27 [0.11-0.69]). Patient sociodemographic and clinical characteristics should be considered as targets to improve PCa early detection and prognosis.

Pulmonary embolism versus pulmonary vasculitis in Hughes-Stovin syndrome: Characteristic computed tomography pulmonary angiographic findings and diagnostic and therapeutic implications. HSS International Study Group.

BACKGROUND AND AIM: Hughes-Stovin syndrome (HSS) is a rare systemic vasculitis with widespread venous/arterial thrombosis and pulmonary vasculitis. Distinguishing between pulmonary embolism (PE) and in-situ thrombosis in the early stages of HSS is challenging. The aim of the study is to compare clinical, laboratory, and computed tomography pulmonary angiography (CTPA) characteristics in patients diagnosed with PE versus those with HSS. METHODS: This retrospective study included 40 HSS patients with complete CTPA studies available, previously published by the HSS study group, and 50 patients diagnosed with PE from a single center. Demographics, clinical and laboratory findings, vascular thrombotic events, were compared between both groups. The CTPA findings were reviewed, with emphasis on the distribution, adherence to the mural wall, pulmonary infarction, ground glass opacification, and intra-alveolar hemorrhage. Pulmonary artery aneurysms (PAAs) in HSS were assessed and classified. RESULTS: The mean age of HSS patients was 35 ± 12.3 years, in PE 58.4 ± 17 (p < 0.0001). Among PE 39(78 %) had co-morbidities, among HSS none. In contrast to PE, in HSS both major venous and arterial thrombotic events are seen.. Various patterns of PAAs were observed in the HSS group, which were entirely absent in PE. Parenchymal hemorrhage was also more frequent in HSS compared to PE (P < 0.001). CONCLUSION: Major vascular thrombosis with arterial aneurysms formation are characteristic of HSS. PE typically appear loosely-adherent and mobile whereas "in-situ thrombosis" seen in HSS is tightly-adherent to the mural wall. Mural wall enhancement and PAAs are distinctive pulmonary findings in HSS. The latter findings have significant therapeutic ramifications.

Predictors of Hospitalization in Breakthrough COVID-19 among Fully Vaccinated Individuals with Immune-Mediated Rheumatic Diseases: Data from SAFER-Study.

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune-mediated rheumatic disease (IMRD) patients are scarce. This study describes breakthrough COVID-19 occurring in IMRD patients participating in the SAFER-study, a Brazilian multicentric cohort evaluating the safety, effectiveness, and immunogenicity of SARS-CoV-2 vaccines in patients with autoimmune diseases. A descriptive analysis of the population and a binary logistic regression model were performed to evaluate the predictors of COVID-19-related hospitalization. A p-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with a mean (SD) age of 40.23 (13.19) years. The patients received two (19%), three (70%), or four (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n = 150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n = 112) was with BNT162b2 (40%) or ChAdOx1 (26%). The COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84; CI: 1.9-18.5; p = 0.002) and treatment with corticosteroids (OR: 2.94; CI: 1.02-8.49; p = 0.0043) were associated with higher odds of hospitalization, while increasing the number of vaccine doses was protective (OR: 0.37; CI: 0.15-0.9; p = 0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favor of booster vaccination in IMRD patients.