Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.

BACKGROUND: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation. METHODS: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments. RESULTS: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P=0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P=0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; Pinteraction=0.009). CONCLUSIONS: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings.

Predictors of OSA following adenotonsillectomy in children with trisomy 21.

OBJECTIVES: Given that 30%-50% of children with trisomy 21 have persistent obstructive sleep apnoea (OSA) after adenotonsillectomy, we evaluated whether demographic, clinical and polysomnographic factors predicted persistent OSA and OSA severity after adenotonsillectomy. DESIGN: Retrospective study. SETTING: Secondary care hospital. PARTICIPANTS: Retrospective review of 32 children with the diagnosis of trisomy 21 and OSA by polysomnography who underwent adenotonsillectomy, from January 2010 to December 2018. MAIN OUTCOME AND MEASURE: Non-parametric analysis was used to compare pre- and postoperative factors, and regression was used to model persistent OSA and OSA severity. RESULTS: Thirty-two children were included (17 males, median age 10.00 ± 8.00 years, median body mass index z-score 0.89 ± 1.25). Overall, adenotonsillectomy resulted in a significant improvement in median obstructive apnoea-hypopnoea index (oAHI) from 7.5 ± 8.95 to 4.40 ± 4.38 events per hour (P < .001) and in median OSA-18 score from 85.00 ± 12.00 to 61.00 ± 37.75 (P < .001). Persistent OSA was found in 56.25% of the children. Univariate regression suggests that postoperative OSA-18 score was associated with persistent OSA after adenotonsillectomy. Preoperative oAHI, preoperative oxygen desaturation index, pre- and postoperative OSA-18 scores correlated with OSA severity after adenotonsillectomy. However, in a multivariate model only the postoperative OSA-18 score correlated with OSA severity after adenotonsillectomy. CONCLUSIONS: Although adenotonsillectomy results in a significant improvement of OSA in children with trisomy 21, more than half of the children had persistent OSA. The postoperative OSA-18 score was associated both with persistent OSA and OSA severity after adenotonsillectomy.

The prognostic value of NRF2 in breast cancer patients: a systematic review with meta-analysis.

PURPOSE: Nuclear factor E2-related factor 2 (NRF2) is a transcription factor that plays a major role in the regulation of intracellular antioxidant response. The effect of NRF2 overexpression in many malignancies is still unclear and recent meta-analysis correlated NRF2 overexpression with poor prognosis in a variety of human cancers. However, the effect of NRF2 overexpression in breast cancer is still unclear. Thus, the main goal of this work was to clarify the role of NRF2 expression in survival and relapse of breast cancer patients by performing a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, followed by a meta-analysis. METHODS: The electronic search was conducted in PubMed, Scopus, SciELO, Web of Science and Embase between November of 2017 and September of 2018. To be included, studies should evaluate NRF2 expression in breast cancer tissue, through immunohistochemistry and/or mRNA and had to report one or more of the following outcomes: overall survival (OS), disease-free survival (DFS), mean survival and median survival. RESULTS: For the meta-analysis, seven studies were included and NRF2 expression was correlated with OS and DFS. It was observed that compared to patients with low NRF2 expression, patients with NRF2 overexpression had poorer OS with a hazard ratio of 1.82 (95% CI 1.32-2.50; p value < 0.0001), and poorer DFS, with a hazard ratio of 1.79 (95% CI 1.07-3.01; p value = 0.03). CONCLUSIONS: These results suggest that tumours that overexpress NRF2 have a worse clinical outcome. Thus, NRF2 expression could be a marker for the prognostic of breast cancer patients and, in the future, it would be pertinent to focus on improving treatment efficacy for patients with NRF2 overexpression.

Prognosis of hormone-dependent breast cancer seems to be influenced by KEAP1, NRF2 and GSTM1 genetic polymorphisms.

Influence of Glutathione S-transferase Mu1 (GSTM1) has long been studied in breast cancer and GSTM1 null genotype was correlated with breast cancer risk. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a transcription factor that forms a complex with Kelch-like ECH-associated protein-1 (KEAP1). Recent studies have demonstrated that expression of these proteins is deregulated in several malignancies. Thus, in the present study we aim to distinguish GSTM1 heterozygous from wild type genotype in breast cancer patients and evaluate the presence and clinical significance of NRF2 and KEAP1 polymorphisms, alone or in association, with breast cancer prognosis, in cases confirmed to have GSTM1-present genotype. Study population consisted in 52 patients with breast cancer. Genomic DNA was extracted, GSTM1 was genotyped through multiplex PCR and gene dose was evaluated through real-time PCR. All cases were sequenced, through Sanger sequencing, for specific regions of NRF2 and KEAP1. Genotyping and clinicopathological data were correlated and statistical analysis was performed. GSTM1 wild type was identified in 1 case and 26 cases were identified as heterozygous, these data were correlated with Human Epidermal growth factor Receptor 2 (HER2) status (p value = 0.017). We also verified that most cancers diagnosed at younger ages had the presence of KEAP1 and/or NRF2 polymorphisms. The association of GSTM1 heterozygous genotype with rs1048290 and rs35652124 seems to be associated with HER2+ (p < 0.05). Our results suggest that GSTM1 * 1/0 genotype and the cumulative presence of at least one allele mutated in KEAP1 and/or NRF2 polymorphisms might be associated with worse prognosis for breast cancer patients.

Gender Disparities in the Academic Performance of Neurology Residents in Portugal.

Implicit bias has been linked to gender disparities in medical careers, impacting not only access to leadership positions but also early career opportunities. We aimed to evaluate if there were differences in the assessment of Neurology residents according to gender. We collected publicly available grades and rankings of two major evaluations that residents are submitted to, one at the beginning and another at the end of the neurology residency program, the National Board Exam and neurology examination, respectively. The National Board Examination is a multiple-choice gender-blinded evaluation, while the neurology examination is an oral gender-unblinded evaluation. We found that 36.5% of women and 21.6% of men were in the first quartile of the National Board Examination ranking, which reflects a similar representation among top classifications when assessed through a gender-blinded examination. On the other hand, the percentage of men who were in the top classification of NE, a gender-unblinded evaluation, was more than twice as high compared to women (37.8% vs 18.3%, p < 0.05). The findings of the present study may imply that there could be a disparity in women's career progression among neurology residents in Portugal, although the recruitment seems balanced between genders.

HBV and VZV seroprotection loss in MS patients under DMT.

BACKGROUND: Strategies recommended to decrease the risk of infection associated with the use of multiple sclerosis disease-modifying treatments include screening and immunization against common viral infections such as varicella-zoster (VZV) and hepatitis B (HBV). However, the data concerning the durability of those vaccine responses and the need for re-test is scarce. OBJECTIVES: We aimed to evaluate HBV and VZV seroprotection loss in MS patients under DMT. METHODS: We conducted a cohort study including patients with basal seroprotective titers against HBV/VZV viruses and a subsequent serology performed at least 3 months apart. We evaluated predictors of seroprotection loss through a binary regression. RESULTS: HBV seroprotection loss occurred in one-fifth of patients in a median interval of 21.3 months. Anti-CD20 treatment (OR 8.559 95%CI 3.467- 21.130, p < 000.1), age at last serology higher or equal to 55 years (OR 7.506, 95% CI 2.473-22.786, p < 0.001) and basal HBsAb titer (OR 0.992, 95%CI 0.987 -0.996, p=0.001) increase the risk of seroprotection loss. VZV seroprotection loss occurred rarely in a median interval of 21.3 months. We could not identify any factor associated with an increased risk of VZV seroprotection loss. CONCLUSIONS: Anti-CD20 drugs are associated with a loss of seroprotection against HBV in a short-interval follow-up.

Swallowing evaluation in patients who underwent Partial CO2 LASER Epiglottectomy for Sleep Apnea treatment.

OBJECTIVE: To evaluate swallowing in patients who underwent CO2 LASER Partial Epiglottectomy (CO2-LPE) for Obstructive Sleep Apnea Syndrome and to assess the risk of aspiration with this technique. MATERIAL & METHODS: Chart review of adult patients who underwent CO2-LPE between 2016 and 2020, in a secondary care hospital. Patients underwent surgery for OSAS, in accordance to Drug Induced Sleep Endoscopy findings and an objective swallowing evaluation was done at least 6 months after surgery. Eating Assessment Tool (EAT-10) questionnaire was applied and Volume-Viscosity Swallow Test (V-VST) and Fiberoptic Endoscopic Evaluation of Swallowing (FEES) were performed. Dysphagia was classified according to Dysphagia Outcome Severity Scale (DOSS). RESULTS: Eight patients were included in the study. The mean time between surgery and the swallowing evaluation was 50 (±13,2) months. Only 3 patients presented ≥ 3 points on EAT-10 questionnaire. Two patients presented signs of decreased efficacy of swallowing (piecemeal deglutition) but none had a decrease in safety, according to V-VST. Although 50% of the patients presented some pharyngeal residue on FEES, it was classified as trace to mild in most of the cases. No evidence of penetration or aspiration was identified (DOSS ≥ 6 in all patients). CONCLUSION: The CO2-LPE is a potential treatment for OSAS patients with epiglottic collapse and no evidence of swallowing safety compromise was found.

Unilateral vocal fold paralysis as a port complication.

Unilateral vocal fold paralysis (UVFP) is a frequent finding in otorhinolaryngology practice, but its occurrence as a port complication was very rarely described in English Literature. The authors report a 55-year-old woman with a pancreatic adenocarcinoma who presented a left vocal fold paralysis that occurred concurrently with a venous thrombosis of the left subclavian vein, where a totally implantable venous-access had been previously placed. Although the patient's oncologic disease, that could mislead to a neoplastic cause of the UVFP, the authors came across with an unusual etiology and to their best knowledge, it is the first case of irreversible UVFP associated with onsite thrombosis of the vessel where a port was implanted. The objective of this article is to present and discuss this rare case of UVFP secondary to a port complication and to review the main mechanisms of iatrogenic vocal fold paralysis related to these devices.

Thymoma and myasthenia gravis - an observational study at a tertiary center.

INTRODUCTION: Acquired Myasthenia Gravis (MG) is a rare autoimmune neurological disorder characterized by fluctu- ating paresis of the skeletal muscle due to pathogenic antibodies against the acetylcholine receptor or other elements of the neuromuscular plaque. There is a close relation between MG and thymoma. We aimed to characterize a population of patients with Myasthenia Gravis associated thymoma (MGAT). METHODS: Retrospective and longitudinal study in all patients with MGAT observed at a tertiary center between 2009 and 2020. We assessed epidemiological, clinical, laboratory and therapeutic features of both MG and thymoma. RESULTS: We found 18 patients with an average age of 53 ± 16.2, 13 of them females. Most patients (n=15) presented the generalized MG form. Most frequent Masaoka staging was II (n=7). Regarding the WHO histopathological classification of thymoma, most patients (n=11) presented with type B2 or B3. Thirteen patients underwent extended thymectomy (12 by median sternotomy and 1 by VATS). Of the remaining 5 patients, 4 of them underwent a CT scan guided biopsy, and 1 patient did not accept further work-up. Seven patients were classified as R0 for surgical resection margins and only one of them had recurrence of thymoma. Besides surgery, oncological treatment included radiotherapy and chemotherapy. Five patients expe- rienced a myasthenic crisis during the course of the disease. Three deaths occurred in the studied population. CONCLUSIONS: This study helped to pinpoint important aspects concerning therapeutic orientation of MGAT patients, such as the clinical impact of thymectomy in the course of MGAT, the oncological prognostic value of surgical resection mar- gins, and the importance of preoperative intravenous immunoglobulin. Management of MGAT patients is only possible with a multidisciplinary approach.

Influence of Estrogenic Metabolic Pathway Genes Polymorphisms on Postmenopausal Breast Cancer Risk.

Estrogen metabolism plays an important role in tumor initiation and development. Lifetime exposure to high estrogens levels and deregulation of enzymes involved in estrogen biosynthetic and metabolic pathway are considered risk factors for breast cancer. The present study aimed to evaluate the impact of mutations acquisition during the lifetime in low penetrance genes that codify enzymes responsible for estrogen detoxification. Genotype analysis of GSTM1 and GSTT1 null polymorphisms, CYP1B1 Val432Leu and MTHFR C677T polymorphisms was performed in 157 samples of women with hormone-dependent breast cancer and correlated with the age at diagnosis. The majority of patients with GSTT1 null genotype and with both GSTM1 and GSTT1 null genotypes were 50 years old or more at the diagnosis (p-value = 0.021 and 0.018, respectively). Older women with GSTM1 null genotype were also carriers of the CYP1B1Val allele (p-value = 0.012). As well, GSTT1 null and CYP1B1Val genotypes were correlated with diagnosis at later ages (p-value = 0.022). Similar results were found associating MTHFR C677T and GSTT1 null polymorphism (p-value = 0.034). Our results suggest that estrogen metabolic pathway polymorphisms constitute a factor to be considered simultaneously with models for breast cancer risk assessment.

Influence of Face Masks on the Use of Contact Lenses.

BACKGROUND: The COVID-19 epidemic is largely controlled by the use of face masks. The use of a face mask has been indicated as a strong cause of dry eye, although it is not yet described in the literature. This study aims to compare the impact of the use of masks on the visual quality of patients. The symptoms in the human eye intensified during the pandemic versus the symptoms before the pandemic, in a Portuguese population. METHODS: A fifteen-question questionnaire was conducted to find out what changes occurred in the use of soft contact lenses during the pandemic in relation to the use of masks. Statistical analysis was performed with SPSS 27.0 software (SPSS Inc., Chicago, IL, USA). RESULTS: The use of contact lenses decreased compared with before the pandemic (p < 0.001). The number of hours of wear decreased significantly compared with before the pandemic (p < 0.001). The sensation of dry eyes was found to be worse in those using monthly replacement contact lenses (p = 0.034), and the need to remove contact lenses was more frequent in women (p = 0.026) after using a mask. CONCLUSIONS: Mask use increases dry eye symptoms in contact lens wearers, negatively impacting visual quality.

Auditory Brainstem Response in Preterm Infants in the Neonatal Intensive Care Unit.

OBJECTIVE: To analyze auditory brainstem response (ABR) findings of preterm and term infants in the neonatal intensive care unit (NICU) with perinatal problems. STUDY DESIGN: Case series with chart review. SETTING: Secondary care hospital. METHODS: Analysis consisted of a consecutive series of 101 infants (69 preterm and 32 term) admitted in the NICU of Hospital Fernando Fonseca between 2016 and 2018 with perinatal problems who underwent an ABR evaluation. RESULTS: The major perinatal problems identified were hyperbilirubinemia, intravenous gentamicin >5 days, mechanical ventilation >5 days, congenital cytomegalovirus infection, meningitis, and periventricular hemorrhage. Gentamicin use significantly increased the absolute latency of wave I in preterm infants (95% CI, 0.01-0.37; P = .037). Mechanical ventilation significantly decreased the latency of wave V and intervals I-V and III-V in preterm infants (95% CI, -0.35 to -0.22; P = .026; 95% CI, -0.33 to -0.00; P = .001; 95% CI, -0.46 to 0.12; P = .049). Congenital cytomegalovirus significantly decreased interval III-V in preterm infants (95% CI, -0.36 to -0.01; P = .042).Multivariate analysis revealed that gentamicin use, lower gestational age, and lower birth weight predicted an increased ABR threshold in preterm infants (95% CI, 1.64-15.31; P = .016; 95% CI -1.72 to -0.09; P = .030; 95% CI, -14.55 to -0.63; P = .033). ABR measurements in term infants were not significantly altered, with the exception of an increased latency of wave III with a lower gestational age (95% CI, -0.49 to -0.01; P = .038). CONCLUSIONS: These findings suggest that perinatal problems in the NICU significantly impair the ABR threshold and the auditory pathway maturational process in preterm but not term infants.

Drug-Induced Sleep Endoscopy in Pediatric Obstructive Sleep Apnea.

OBJECTIVE: To describe drug-induced sleep endoscopy (DISE) findings in children with obstructive sleep apnea and to differentiate them between surgically naïve children and children who had adenotonsillectomy performed. STUDY DESIGN: Retrospective case series with chart review. SETTING: Secondary care hospital. SUBJECTS AND METHODS: A cohort of 56 children with the diagnosis of obstructive sleep apnea was submitted to DISE and subsequent upper airway surgery: 23 were surgically naïve, and 33 had persistent obstructive sleep apnea after adenotonsillectomy. Comparisons between groups were calculated with chi-square test and Student's t test. Simple linear regression was used to model polysomnographic indices. RESULTS: In surgically naïve children, the most common sites of obstruction were the adenoids (78.2%) and the lateral pharyngeal walls/tonsils (82.6%). In children with persistent obstructive sleep apnea after adenotonsillectomy, the most common sites of obstruction were the adenoids (54.5%), followed by the supraglottis (48.5%) and the tongue base (45.5%). No correlation was found between obstructive apnea-hypopnea index and DISE findings. Simple linear regression revealed that the degree of obstruction at the tongue base (ß = -0.73; 95% CI, -1.22 to -0.25; P = .004) and the presence of multilevel obstruction (ß = -1.75; 95% CI, -3.20 to -0.30; P = .02) predicted saturation nadir in children with persistent obstructive sleep apnea after adenotonsillectomy. CONCLUSION: DISE findings differed between surgically naïve children and children with persistent obstructive sleep apnea after adenotonsillectomy. Increased obstruction at the level of the tongue base and the presence of multilevel obstruction predicted a lower saturation nadir in children with persistent obstructive sleep apnea after adenotonsillectomy.

5-Hydrazinylethylidenepyrimidines effective against multidrug-resistant Acinetobacter baumannii: Synthesis and in vitro biological evaluation of antibacterial, radical scavenging and cytotoxic activities.

Acinetobacter baumannii has emerged as an important nosocomial pathogen in recent years, with infectious outbreaks caused by multidrug-resistant strains increasing worldwide. Thus, new antibacterial treatments for multidrug-resistant A. baumannii strains are needed. In this work, a series of 5-hydrazinylethylidenepyrimidines were synthesized and in vitro evaluated against two multidrug-resistant A. baumannii strains (AcB 13/10 and AcB 73/10). Minimum inhibitory concentration results demonstrated that generally the compounds in study presented values in a low micromolar range. In the determination of in vitro bacterial growth at 24 h, it was observed that the pyrimidines 3a and 3c, with an unsubstituted hydrazinylphenyl, have bacteriostatic activity in both multidrug-resistant A. baumannii strains, with a concentration-dependent action. In general, an additive effect occurred in the combination of these compounds with gentamicin, rifampicin and polymyxin B, for both strains. Furthermore, all 5-hydrazinylethylidenepyrimidines under study presented a good 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, generally low xanthine oxidase inhibition and low cytotoxicity in normal human dermal fibroblasts as well as potential favorable drug-likeness properties. Thus, these molecules can be considered attractive for the future development of antibacterial agents against multidrug-resistant A. baumannii.

Extensive upper respiratory tract sarcoidosis.

Sarcoidosis is a chronic granulomatous disease of unknown aetiology. It can affect any part of the organism, although the lung is the most frequently affected organ. Upper airway involvement is rare, particularly if isolated. Sarcoidosis is a diagnosis of exclusion, established by histological evidence of non-caseating granulomas and the absence of other granulomatous diseases. The authors report a case of a man with sarcoidosis manifesting as a chronic inflammatory stenotic condition of the upper respiratory tract and trachea.