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Exudative retinal detachment (ERD) is a rare complication that occurring in 1% of patients with preeclampsia, its incidence is increased when it is associated with HELLP syndrome. Preeclampsia is defined by the development of arterial hypertension and proteinuira occurs after 20 weeks of gestation until postpartum. HELLP syndrome (low platelets, hemolysis and elevated liver enzymes) is a severe form of preeclampsia. ERD in preeclampsia is related to choroidal ischaemia, in the vast majority of the cases associated with hypertensive retinopathy. However, it has been proposed that the combination of hypertension with a microangiopathic hemolysis, hipercoagulability and hypoalbuminemia are the main factors contributing to the development of ERD. Its treatment includes a rapid resolution of labor to reverse ocular manifestations and prevent visual sequels. We describe the case of a pregnant woman with atypical preeclampsia who, in the postpartum of a cesarean, presented an ERD concomitantly with a HELLP syndrome.

A 68 year-old male was referred for assessment of an amelanotic lesion in the right eye (RE) that was associated with a gradual loss of visual acuity (VA), of 2 months onset, as the main symptom. It was noted in his medical history, that 6 years ago, he had prostate cancer treated with prostatectomy, lymphadenectomy, and coadjuvant local radiotherapy (RT). He was asymptomatic until 6 months ago, when a metastasis was discovered in the left femur, which was treated with radiotherapy. There were no findings of interest in the left eye (LE). His AV was very low in his RE, and in the eye fundus examination a mass without pigment was observed in the posterior pole with an adjacent exudative retinal detachment. Due to his personal history and results of the complementary tests such as ultrasound and magnetic resonance, the most likely diagnostic option was metastasis of prostate carcinoma, subsequently being confirmed with the histopathology results. Despite 4 cycles of chemotherapy, the patient did not show any clinical or radiological response, worsening until his death 3 months later.

Intravenous drug users (IDUs) with hepatitis C virus (HCV)/human immunodeficiency virus (HIV)-coinfection are recognised as a high-risk, vulnerable group.Between February 2015 and April 2018, a single-centre, non-interventional cohort study was conducted in an outpatient setting, to evaluate the sustained virologic response (SVR12) and assess treatment uptake models. The study included 385 former or recent IDUs divided into two groups: A-without use of opioid substitution treatment (OST) and B-patients taking opioid substitution; patients in group B received OST and self-administered therapy (B1) or OST and therapy under DOT (B2). Patients were characterised by demographic and clinical features and compared for treatment response. Correlations between SVR12 and independent variables were determined by logistic regression.Patients were mostly males (88.3%) with a mean age of 46 ± 5 years and HCV genotype 1a (63.7%). Approximately 28% were treatment-experienced and 84.9% received sofosbuvir/ledipasvir. The mean CD4IDU with HCV/HIV coinfection, including individuals on self-administration of HCV therapy and opioid substitution treatments or in DOT programmes, are no longer considered a difficult-to-treat group, as they achieve high rates of SVR12.

Meningiomas are the most common primary intracranial tumors, but meningioma metastases are rare. Accordingly, the clinical workup, diagnostic testing, and molecular classification of metastatic meningioma is incompletely understood. Here, we present a case report of multiply recurrent meningioma complicated by liver metastasis. We discuss the patient presentation, imaging findings, and conventional histopathologic characterization of both the intracranial lesion and the metastatic focus. Further, we perform multiplatform molecular profiling, comprised of DNA methylation arrays and RNA-sequencing, of six stereotactically-guided samples from the intracranial meningioma and a single ultrasound-guided liver metastasis biopsy. Our results show that DNA methylation clusters distinguish the liver metastasis from the intracranial meningioma samples, and identify a small focus of hepatocyte contamination with the liver biopsy. Nonetheless, DNA methylation-based classification accurately identifies the liver metastasis as a meningioma with high confidence. We also find that clustering of RNA-sequencing results distinguishes the liver metastasis from the intracranial meningiomas samples, but that differential gene expression classification is confounded by hepatocyte-specific gene expression programs in the liver metastasis. In sum, this case report sheds light on the comparative biology of intracranial and metastatic meningioma. Furthermore, our results support methylation-based classification as a robust method of diagnosing metastatic lesions, underscore the broad utility of DNA methylation array profiling in diagnostic pathology, and caution against the routine use of bulk RNA-sequencing for identifying tumor signatures in heterogeneous metastatic lesions.

The manuscript presented herein documents the findings of filaria nematodes in 5 keel-billed toucans, and one emerald toucanet, originated from 2 private aviaries in Mexico City during two years. The birds displayed ruffled feathers, depression, inability to perch, convulsions, and sudden death. Furthermore, thickened wall of the aortic and brachiocephalic arteries, with connective tissue proliferation and chondroid metaplasia were observed. Molecular characterization matched Filarioidea sp (Nematoda: Spirurida: Filarioidea). To the authors’ knowledge, this is the first documented report of filariae Filarioidea sp. causing mortality in ramphastids in Mexico. This manuscript may contribute to expand current knowledge of filariasis and the health risks and livability of wild birds., Graphical abstract Image 1, Highlights • Filaria nematodes causes aortic and brachiocephalic lesions in ramphastids. • The phylogenetic analyzes of the nematode show high similarity to Filarioidea sp. • Filariae Filarioidea sp. can cause mortality in keel-billed toucan and emerald toucanet. • This is the first report of Filarioidea sp. causing mortality in ramphastids in Mexico.

We present the case of a 17-year-old male patient with a history of cocaine use who consulted for chest pain and dyspnoea. A pneumomediastinum is defined as the irruption of air in the mediastinal space, and is associated with different causes, including addiction to inhaled drugs. It occurs in people with predisposing factors and the presence of precipitating factors such as consumption of inhaled drugs. X-ray and computed tomography of the thorax are very useful tools in guiding the diagnosis. The low incidence of this pathology represents a difficult diagnosis for the doctor, although in some characteristic work environments a high level of suspicion is necessary.

[Abstract] Background and objectives: Cardiovascular risk estimation in people over 70 years of age is problematic. Most scores have been created based on cohorts of middle-aged people, with an underrepresentation of older adults. The predictive power of classical cardiovascular risk factors declines with age. The aim of this work is to develop a specific score for estimating cardiovascular risk among the elderly population in Spain. Methods: This work is a population-based cohort established in 1995. Setting: Three geographical areas of Spain (Madrid, Ávila, and Lugo). Participants: 3,729 people older than 64 years with no cardiovascular diseases (CVD) at baseline. Measurements: Suspected fatal and nonfatal CVD (both coronary heart disease and stroke) were investigated annually and confirmed using the WHO-MONICA criteria. All participants were followed-up on until occurrence of a first CVD event, until death, or until December 31, 2015. Results: Age was the strongest predictor of CVD at 10 years in both men and women. In men, variables associated with CVD were high blood pressure treatment (HR: 1.35; 95% CI: 1.067-1.710), diabetes (HR: 1.359; 95% CI: 0.997-1.852), and smoking (HR: 1.207; 95% CI: 0.945-1.541) and in women, the variables were smoking (HR: 1.881; 95% CI: 1.356-2.609) and diabetes (HR: 1.285; 95% CI: 0.967-1.707). Total cholesterol did not increase the risk of CVD in men or women. However, total cholesterol levels >200 mg/dL were inversely associated with 10-year risk of CVD in men and women. Conclusions: In elderly Spanish men, total CVD at 10 years is significantly increased by age, diabetes, and antihypertensive treatment and in elderly Spanish women by diabetes and smoking. Total cholesterol levels did not increase the risk of CVD, particularly in males. [Resumen] Antecedentes y objetivos. La estimación del riesgo cardiovascular en personas mayores de 70 años es problemática. La mayoría de las escalas se han creado basándose en cohortes de personas de mediana edad, con una representación insuficiente de los adultos de más edad. El poder predictivo de los factores de riesgo cardiovascular clásicos disminuye con la edad. El objetivo de este estudio es desarrollar una escala específica para estimar el riesgo cardiovascular de la población anciana española. Métodos. Este estudio se realizó en una cohorte poblacional establecida en 1995. Marco: tres zonas geográficas de España (Madrid, Ávila y Lugo). Participantes: 3.729 personas mayores de 64 años sin enfermedades cardiovasculares (ECV) al inicio del seguimiento. Mediciones: Se investigaron anualmente las sospechas de ECV mortal y no mortal (cardiopatía coronaria e ictus) y se confirmaron usando los criterios del proyecto MONICA de la OMS. Se siguió a todos los participantes hasta que apareció el primer episodio de ECV, hasta su muerte o hasta el 31 de diciembre de 2015. Resultados. La edad fue el factor predictivo más potente de ECV a los 10 años en ambos sexos. Las variables asociadas con ECV en los varones fueron el tratamiento de la hipertensión arterial (HR: 1,35; IC al 95%: 1,067−1,710), la diabetes (HR: 1,359; IC al 95%: 0,997−1,852) y el tabaquismo (HR: 1,207; IC al 95%: 0,945−1,541) y en las mujeres, el tabaquismo (HR: 1,881; IC al 95%: 1,356−2,609) y la diabetes (HR: 1,285; IC al 95%: 0,967−1,707). El colesterol-total no aumentó el riesgo de ECV, ni en varones ni en mujeres. Sin embargo, las concentraciones de colesterol total > 200 mg/dL se asociaron inversamente al riesgo de ECV a los 10 años, tanto en varones como en mujeres. Conclusiones. La ECV total a los 10 años aumenta significativamente en los varones españoles de edad avanzada con la edad, la diabetes y el tratamiento antihipertensivo y en las mujeres con la diabetes y el tabaquismo. Los niveles de colesterol total no aumentaron el riesgo de ECV, sobre todo en los varones. Instituto de Salud Carlos III; FIS 93/012 Instituto de Salud Carlos III; FIS 96/1993 Instituto de Salud Carlos III; FIS 02/0896 Ministerio de Economía y Competitividad (España); PB/255-Co4

Càncer de pulmó; Fumar; Diferències entre sexes Cancer de pulmón; Fumar; Diferencias entre sexos Lung neoplasms; Smoking; Sex Factors Background: Lung cancer causes approximately 25% of all cancer deaths. Despite its relevance, few studies have analyzed differences by sex at the time of diagnosis in terms of symptoms, stage, age or smoking status. We aim to assess if there are differences between men and women on these characteristics at diagnosis. Methods: We analyzed the Thoracic Tumour Registry (TTR), sponsored by the Spanish Lung Cancer Group using a case-series design. This is a nationwide registry of lung cancer cases which started recruitment in 2016. For each case included, clinicians fulfilled an electronic record registering demographic data, symptoms, exposure to lung cancer risk factors, and treatment received in detail. We compared men and women using descriptive statistics. Results: A total of 13,590 participants took part in this study, 25.6% women. Women were 4 years younger than men (64 vs. 69), and men had smoked more frequently. Adenocarcinoma was the most frequent histological type in both sexes. Stage IV at diagnosis was 50.8% in women compared to 43.6% in men. Weight loss/anorexia/asthenia was the most frequent symptom in both sexes and there were no differences in the number of symptoms at diagnosis. There were no relevant differences in the frequency or number of symptoms by sex when non-small cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) were analyzed separately. Smoking status did not appear to cause different lung cancer presentation in men compared to women. Conclusions: There seems to be no differences in lung cancer characteristics by sex at the time at diagnosis on stage, specific symptoms or number of symptoms. This research received funding from the Spanish Lung Cancer Group

Introduction: The disease SARS-CoV-2, named COVID-19, was officially declared a pandemic by the World Health Organization on March 11th, 2020. SARS-CoV-2 contains a single-stranded, positive-sense RNA genome surrounded by an extracellular membrane containing a series of spike glycoproteins resembling a crown. Neuropsychiatric manifestations are common during viral pandemics but are not effectively addressed. Case Report: We report the case of a man, 42 years old, who after the infection by SARS-COV2, presented dysnomy, cognitive easing and errors in motor processing. Results and Discussion: Studies have shown the neuroinvasive capability of SARS-COV2, resulting in neurological complications. Common neurological symptoms are headache, dizziness, anosmia, dysgeusia, mental confusion, and muscle weakening, progressing toward severe complications like cerebrovascular disease, seizures, muscle pain, and Guillain-Barre syndrome. The patient in the present case, about seven days after the initial infection, began to have difficulties in naming basic objects and "cognitive" slowness in the performance of basic and instrumental activities of daily life, especially those that required mutual tasks and that required concentration. Patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. Neuroinvasive capacities and neuroinflammatory events that may lead to the same short- and long-term neuropathologies that SARS-CoV had shown in human and animal models. The presence of dementia, minimal cognitive impairment and problems with motor planning and execution has been described. Conclusion: A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations, Background There is a lack of useful diagnostic tools to identify EGFR mutated NSCLC patients with long-term survival. This study develops a prognostic model using real world data to assist clinicians to predict survival beyond 24 months. Methods EGFR mutated stage IIIB and IV NSCLC patients diagnosed between January 2009 and December 2017 included in the Spanish Lung Cancer Group (SLCG) thoracic tumor registry. Long-term survival was defined as being alive 24 months after diagnosis. A multivariable prognostic model was carried out using binary logistic regression and internal validation through bootstrapping. A nomogram was developed to facilitate the interpretation and applicability of the model. Results 505 of the 961 EGFR mutated patients identified in the registry were included, with a median survival of 27.73 months. Factors associated with overall survival longer than 24 months were: being a woman (OR 1.78); absence of the exon 20 insertion mutation (OR 2.77); functional status (ECOG 0–1) (OR 4.92); absence of central nervous system metastases (OR 2.22), absence of liver metastases (OR 1.90) or adrenal involvement (OR 2.35) and low number of metastatic sites (OR 1.22). The model had a good internal validation with a calibration slope equal to 0.781 and discrimination (optimism corrected C-index 0.680). Conclusions Survival greater than 24 months can be predicted from six pre-treatment clinicopathological variables. The model has a good discrimination ability. We hypothesized that this model could help the selection of the best treatment sequence in EGFR mutation NSCLC patients.

Background Patient limitations guide selection of heart failure therapies, for which indications often specify New York Heart Association Class. Objectives To determine the extent of patient‐reported limitations during daily activities and compare to New York Heart Association class assigned by providers during the same visit, and to left ventricular ejection fraction (LVEF) group. Methods and Results While waiting for their appointment, 948 patients on return visits to an ambulatory HF clinic completed a written questionnaire assessing specific activity limitations, which were compared to physician‐assigned NYHA class during the same visit. Patient‐reported limitation to perform daily activity ranged from 25% for bathing to 61% for yardwork or housework and 71% for jogging or hurrying. Most patients who did not report limitations to perform daily life activities were correctly classified as NYHA I by the physicians (76%), but 12% of the 376 patients classified as NYHA I reported limitations to showering or bathing and 73% reported limitations while doing yardwork or house work. Limitation to walking was reported by 172 patients (50%) classified as class II. Limitations to walking one block were most common in patients with LVEF ≥40% compared to patients with LVEF

INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is one of the cancers with worst prognosis due to the intense desmoplastic reaction that occurs in this disease, which hinders the action of therapeutic agents and contributes to cancer progression. A possible way to develop new strategies for PDAC diagnosis and therapy is the study of the abnormal components of the tumor stroma. However, new receptors capable of detecting these components are needed. MATERIALS AND METHODS Two types of molecular receptors, monoclonal antibodies and aptamers, were developed in parallel targeting an extracellular matrix protein with potential as a PDAC marker. Antibodies were generated using mice of the DBA/1J strain, while aptamers were obtained by means of an in vitro selection method called SELEX. The analytical characteristics of the developed receptors were studied by ELISA-like assays, as well as cytochemistry on positive and negative cell lines for the protein of interest. RESULTS A total of 44 potential aptamers were identified. After a first bioinformatic screening, 9 candidates were chosen for evaluating their binding affinity in vitro. Two of them showed dissociation constants in the nanomolar range. One of the aptamers also showed specific staining of cells positive for the marker protein, as did one of the generated antibody clones. CONCLUSIONS The newly developed receptors have shown a great potential in the study of PDAC. However, their diagnostic and therapeutic usefulness requires a more in-depth evaluation, currently in progress. ACKNOWLEDGEMENTS This research was funded by the Spanish Government (RTI-2018-095756-B-I00) and Principado de Asturias Government (IDI2018-000217), co-financed by FEDER funds. R.L.G. thanks the Spanish Government for a predoctoral FPU fellowship (FPU16/05670).

Resumo Fundamento O exame físico permite a avaliação prognóstica de pacientes com insuficiência cardíaca (IC) descompensada, porém não é suficientemente confiável e depende da experiência clínica do profissional. Considerando as respostas hemodinâmicas a situações do tipo “luta ou fuga” tais como a admissão no serviço de emergência, foi proposto o índice hemodinâmico agudo (IHA), calculado a partir da frequência cardíaca e pressão de pulso. Objetivo avaliar a capacidade prognóstica intra-hospitalar do IHA na IC descompensada. Métodos estudo prospectivo, multicêntrico e observacional baseado no registro BREATHE, incluindo dados de hospitais públicos e privados no Brasil. Foram utilizadas análises ROC (Receiver Operating Characteristic), de estatística c e de regressão multivariada, assim como o critério de informação de Akaike, para testar a capacidade prognóstica do IHA. O valor-p < 0,05 foi considerado estatisticamente significativo. Resultados Foram analisados dados de 463 pacientes com IC com fração de ejeção reduzida a partir do registro BREATHE. A mortalidade intra-hospitalar foi de 9%. A mediana do IHA foi considerada o valor de corte (4 mmHg⋅bpm). Um baixo IHA (≤ 4 mmHg⋅bpm) foi encontrado em 80% dos pacientes falecidos. O risco de mortalidade intra-hospitalar em pacientes com baixo IHA foi 2,5 vezes maior que aquele para pacientes com IHA > 4 mmHg⋅bpm. O IHA foi capaz de predizer independentemente a mortalidade intra-hospitalar na IC aguda descompensada [sensibilidade: 0,786; especificidade: 0,429; AUC (área sob a curva): 0,607 (0,540-0,674), p = 0,010] mesmo depois dos ajustes para comorbidades e uso de medicamentos [razão de chances (RC): 0,061 (0,007-0,114), p = 0,025]. Conclusões O IHA é capaz de predizer independentemente a mortalidade intra-hospitalar na IC aguda descompensada. Esse índice simples e realizado à beira do leito pode se mostrar útil em serviços de emergência. (Arq Bras Cardiol. 2021; 116(1):77-86) Abstract Background The physical examination enables prognostic evaluation of patients with decompensated heart failure (HF), but lacks reliability and relies on the professional’s clinical experience. Considering hemodynamic responses to “fight or flight” situations, such as the moment of admission to the emergency room, we proposed the calculation of the acute hemodynamic index (AHI) from values of heart rate and pulse pressure. Objective To evaluate the in-hospital prognostic ability of AHI in decompensated HF. Methods A prospective, multicenter, registry-based observational study including data from the BREATHE registry, with information from public and private hospitals in Brazil. The prognostic ability of the AHI was tested by receiver-operating characteristic (ROC) analyses, C-statistics, Akaike’s information criteria, and multivariate regression analyses. p-values < 0.05 were considered statistically significant. Results We analyzed data from 463 patients with heart failure with low ejection fraction. In-hospital mortality was 9%. The median AHI value was used as cut-off (4 mmHg⋅bpm). A low AHI (≤ 4 mmHg⋅bpm) was found in 80% of deceased patients. The risk of in-hospital mortality in patients with low AHI was 2.5 times that in patients with AHI > 4 mmHg⋅bpm. AHI independently predicted in-hospital mortality in acute decompensated HF (sensitivity: 0.786; specificity: 0.429; AUC: 0.607 [0.540–0.674]; p = 0.010) even after adjusting for comorbidities and medication use [OR: 0.061 (0.007–0.114); p = 0.025). Conclusions The AHI independently predicts in-hospital mortality in acute decompensated HF. This simple bed-side index could be useful in an emergency setting. (Arq Bras Cardiol. 2021; 116(1):77-86)

Mesothelioma is a rare and aggressive tumour with dismal prognosis arising in the pleura and associated with asbestos exposure. Its incidence is on the rise worldwide. In selected patients with early-stage MPM, a maximal surgical cytoreduction in combination with additional antitumour treatment may be considered in selected patients assessed by a multidisciplinary tumor board. In patients with unresectable or advanced MPM, chemotherapy with platinum plus pemetrexed is the standard of care. Currently, no standard salvage therapy has been approved yet, but second-line chemotherapy with vinorelbine or gemcitabine is commonly used. Novel therapeutic approaches based on dual immunotherapy or chemotherapy plus immunotherapy demonstrated promising survival benefit and will probably be incorporated in the future., E. Nadal thanks the support of Health Institute Carlos III-FEDER (ISCIII) [PI14/01109 and PI18/00920].

BackgroundIn contrast with the setting of acute myocardial infarction, there are limited data regarding the impact of diabetes mellitus on clinical outcomes in contemporary cohorts of patients with chronic coronary syndromes. We aimed to investigate the prevalence and prognostic impact of diabetes according to geographical regions and ethnicity.Methods and resultsCLARIFY is an observational registry of patients with chronic coronary syndromes, enrolled across 45 countries in Europe, Asia, America, Middle East, Australia, and Africa in 2009–2010, and followed up yearly for 5 years. Chronic coronary syndromes were defined by ≥1 of the following criteria: prior myocardial infarction, evidence of coronary stenosis >50%, proven symptomatic myocardial ischaemia, or prior revascularization procedure.Among 32 694 patients, 9502 (29%) had diabetes, with a regional prevalence ranging from below 20% in Northern Europe to ∼60% in the Gulf countries. In a multivariable-adjusted Cox proportional hazards model, diabetes was associated with increased risks for the primary outcome (cardiovascular death, myocardial infarction, or stroke) with an adjusted hazard ratio of 1.28 (95% confidence interval 1.18, 1.39) and for all secondary outcomes (all-cause and cardiovascular mortality, myocardial infarction, stroke, heart failure, and coronary revascularization). Differences on outcomes according to geography and ethnicity were modest.ConclusionIn patients with chronic coronary syndromes, diabetes is independently associated with mortality and cardiovascular events, including heart failure, which is not accounted by demographics, prior medical history, left ventricular ejection fraction, or use of secondary prevention medication. This is observed across multiple geographic regions and ethnicities, despite marked disparities in the prevalence of diabetes.ClinicalTrials identifierISRCTN43070564

Background Small-cell lung cancer (SCLC) is an aggressive disease with high metastatic potential and poor prognosis. Due to its low prevalence, epidemiological and clinical information of SCLC patients retrieved from lung cancer registries is scarce. Patients and methods This was an observational multicenter study that enrolled patients with lung cancer and thoracic tumors, recruited from August 2016 to January 2020 at 50 Spanish hospitals. Demographic and clinical data, treatment patterns and survival of SCLC patients included in the Thoracic Tumor Registry (TTR) were analyzed. Results With a total of 956 cases, the age of 64.7 ± 9.1 years, 78.6% were men, 60.6% smokers, and ECOG PS 0, 1 or ≥ 2 in 23.1%, 53.0% and 23.8% of cases, respectively. Twenty percent of patients had brain metastases at the diagnosis. First-line chemotherapy (CT), mainly carboplatin or cisplatin plus etoposide was administered to >90% of patients. In total, 36.0% and 13.8% of patients received a second and third line of CT, respectively. Median overall survival was 9.5 months (95% CI 8.8–10.2 months), with an estimated rate of 70.3% (95% CI 67.2–73.4%), 38.9% (95% CI 35.4–42.4%), and 14.8% (95% CI 11.8–17.8%) at 6, 12 and 24 months respectively. Median progression-free survival was 6.3 months. Higher mortality and progression rates were significantly associated with male sex, older age, smoking habit, and ECOG PS 1–2. Long-term survival (> 2 years) was confirmed in 6.6% of patients, showing a positive correlation with better ECOG PS, poor smoking and absence of certain metastases at diagnosis. Conclusion This study provides an updated overview of the clinical situation and treatment landscape of ES-SCLC in Spain. Our results might assist oncologists to improve current clinical practice towards a better prognosis for these patients.

OBJECTIVE Tumors compressing the trigeminal nerve can cause facial pain, numbness, or paresthesias. Limited data exist describing how these symptoms change after resection and what factors predict symptom improvement. The objective of this study was to report trigeminal pain and sensory outcomes after tumor resection and identify factors predicting postoperative symptom improvement. METHODS This retrospective study included patients with tumors causing facial pain, numbness, or paresthesias who underwent resection. Trigeminal schwannomas were excluded. Logistic regression, recursive partitioning, and time-to-event analyses were used to report outcomes and identify variables associated with facial sensory outcomes. RESULTS Eighty-six patients met inclusion criteria, and the median follow-up was 3.1 years; 63 patients (73%) had meningiomas and 23 (27%) had vestibular schwannomas (VSs). Meningioma patients presented with pain, numbness, and paresthesias in 56%, 76%, and 25% of cases, respectively, compared with 9%, 91%, and 39%, respectively, for patients with VS. Most meningioma patients had symptoms for less than 1 year (60%), whereas the majority of VS patients had symptoms for 1–5 years (59%). The median meningioma and VS diameters were 3.0 and 3.4 cm, respectively. For patients with meningiomas, gross-total resection (GTR) was achieved in 27% of patients, near-total resection (NTR) in 29%, and subtotal resection (STR) in 44%. For patients with VS, GTR was achieved in 9%, NTR in 30%, and STR in 61%. Pain improved immediately after tumor resection in 81% of patients and in 92% of patients by 6 weeks. Paresthesias improved immediately in 80% of patients, increasing to 84% by 6 weeks. Numbness improved more slowly, with 52% of patients improving immediately, increasing to 79% by 2 years. Pain recurred in 22% of patients with meningiomas and 0% of patients with VSs. After resection, the Barrow Neurological Institute (BNI) facial pain intensity score improved in 73% of patients. The tumor diameter significantly predicted improvement in BNI score (OR 0.47/cm larger, 95% CI 0.22–0.99; p = 0.047). Complete decompression of the trigeminal nerve was associated with qualitative improvement in pain (p = 0.037) and decreased pain recurrence (OR 0.08, 95% CI 0.01–0.67; p = 0.024). CONCLUSIONS Most patients with facial sensory symptoms caused by meningiomas or VSs experienced improvement after resection. Surgery led to immediate and sustained improvement in pain and paresthesias, whereas numbness was slower to improve. Patients with smaller tumors and complete decompression of the trigeminal nerve were more likely to experience improvement in facial pain.

Background Lung cancer is currently the leading cause of cancer death. Despite its high incidence and mortality, there are few studies describing its symptoms at diagnosis broken down by tumour stage and tobacco use. Accordingly, this study was proposed to describe the frequency of the most common symptoms of non-small cell lung cancer and small cell lung cancer (SCLC) at diagnosis, with a breakdown by stage and tobacco use. Patients and methods Cases were collected from the Spanish Thoracic Tumour Registry, a nationwide registry sponsored by the Spanish Lung Cancer Group. More than 50 hospitals recruited histologically confirmed lung cancer cases and information was gathered through personal interview plus data contained in the electronic clinical record. There were no data available on the lag between the appearance of the first symptoms and diagnosis of lung cancer. Results A total of 9876 patients (74% male, median age 64 years) were recruited from 2016 to 2019. Of these, 12.5% presented with SCLC. Stage IV was the most frequent stage at diagnosis (46.6%), and the most frequent symptom was cough (33.9%), followed by dyspnoea (26.7%). No symptom was present in 59% of patients diagnosed in stage I; 40% of stage I patients presented with at least one symptom, while 27.7% of patients in stage IV had no symptoms at diagnosis. Cough was the most frequent symptom in SCLC (40.6%), followed by dyspnoea (34.3%). The number of symptoms was similar across the respective smoking categories in SCLC, and differences between the symptoms analysed did not exceed 7% in any case. Conclusion The absence of the most frequent symptoms (ie, cough, pain, dyspnoea) should not lead to a decision to rule out the presence of lung cancer. A relevant percentage of stage IV patients displayed no symptoms at diagnosis.

Background: COVID-19 pandemic has drastically changed the management of patients with cancer;however, limited data exists regarding which pre-conditions affect the course of COVID-19 infection Here, we sought to assess the clinical features and outcomes of COVID-19 infection in a large cohort of patients with cancer Methods: We conducted a multicenter retrospective cohort study of patients with cancer diagnosed with SARS-CoV-2 infection by RT-PCR/Ag detection (n=274) or CT-scan (N=13) between 7/March and 30/April across 12 international centers Clinical, pathological and biological data were collected Primary endpoints were 30-day mortality rate and the rate of severe acute respiratory failure (SARF), defined by oxygen requirements >15 L/min Descriptive statistics were used Results: 287 patients were enrolled with a median follow-up of 23 days [95%CI 22-26] Median age was 69 (range 35-98), 52% were male, 49% had hypertension and 23% had cardiovascular disease As per cancer characteristics, 68% had active disease, 52% advanced stage and 79% had a baseline ECOG PS ≤1 Most frequent cancer-types were: 26% thoracic, 21% gastrointestinal, 19% breast and 15% genitourinary Most patients (61%) were under systemic therapy, including chemotherapy (51%), endocrine therapy (23%) and immunotherapy (19%) At COVID-19 diagnosis, 44% of patients had moderate/severe symptoms such as fever (70%), cough (54%) and dyspnea (48%) The majority of patients (90%) required in-patient management and the median hospital stay duration was 10 days (range 1-52);8% of patients required intermediate or intensive care unit admission Patients received treatment with: hydroxychloroquine (81%), azithromycin (61%), antiviral therapy (38%) and immunomodulatory drugs (14%) Finally, the overall mortality rate was 27% and the rate of SARF was 26% In patients admitted to intermediate/intensive care units, the mortality and SARF rates were 45% and 73%, respectively Mortality rate according to ECOG PS before COVID-19 was 20% in PS≤1 and 51% in PS>2 (p

Background: Smoking is the leading cause of cancer worldwide Active smoking alters the inflammatory environment of the respiratory epithelium, increasing the production of potent pro-inflammatory cytokines that promote the recruitment of macrophages and neutrophils, leading to lung damage We hypothesize that smoking-induced inflammation can impact on COVID-19 infection severity and mortality related to the proinflammatory cascade Methods: Multicenter retrospective cohort of cancer patients (pts) with COVID-19 infection diagnosed by PCR/Ag detection (n=274) and CT-scan (N=13) in Mar-Apr/20r in 12 centers Clinical and biological data were collected Smoker was defined as active tobacco consumption and heavy smoker as >30 pack-year (PY) Primary endpoints were 30-day mortality rate and the rate of severe acute respiratory failure (SARF), defined by oxygen requirements >15 L/min Results: A total of 287 pts were enrolled: 25 (9%) were active smokers, 127 (47%) were former and 116 (43%) never smoker Among active smokers: 73% were heavy smokers, median age was 62y, 60% were male and median body mass index was 22 Regarding their comorbidities: 25% had hypertension, 8% cardiovascular disease, 28% chronic obstructive pulmonary disease and 24% diabetes Thoracic tumors were the most common (52%), 72% had advanced disease and 56% were under systemic therapy 92% of active smokers required hospitalization, 68% developed pneumonia and 58% required oxygen Only 4% were escalated to the intensive care unit Active smokers received treatment with hydroxychloroquine (91%), azithromycin (61%), antiviral therapy (33%) and steroids (29%) Only 4% received immunomodulatory drugs SARF was the most common complication (25%) and no thromboembolic events were observed A pro-inflammatory status was observed at COVID-19 diagnosis in active smokers, e g median of absolute neutrophil count was 6 35 (vs 5 4), mean ferritin was 1269 (vs 991) and D-Dimer was 2422 (vs 1816);but with no significant differences Overall mortality rate was 27% Mortality rate was higher in active smokers (40% vs 24% in non-smokers;p=0 08) Conclusions: Active smoking might be associated with severe COVID-19 infection and early death in cancer patients Smoking induced-inflammation should be further explored Legal entity responsible for the study: Aleix Prat Funding: Has not received any funding Disclosure: E Auclin: Travel/Accommodation/Expenses: Mundifarma;Speaker Bureau/Expert testimony: Sanofi Genzime S Pilotto: Speaker Bureau/Expert testimony: Astra-Zeneca;Speaker Bureau/Expert testimony: Boehringer Ingelheim;Speaker Bureau/Expert testimony: Eli-Lilly;Speaker Bureau/Expert testimony: BMS A Prat: Honoraria (institution), Speaker Bureau/Expert testimony: Roche;Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer;Honoraria (institution), Advisory/Consultancy, Speaker Bureau/Expert testimony: Novartis;Amgen;Speaker Bureau/Expert testimony: BMS;Honoraria (institution), Speaker Bureau/Expert testimony: Daiichi Sankyo;Nanostring;Advisory/Consultancy: Puma;Oncolytics Biotech;MSD;Honoraria (institution), Advisory/Consultancy: Lilly;Boehringer;Sysmex Europa GmbH;Medican Scientia inno Research;Celgene;Astellas;Officer/Board of Directors: Breast International Group;Solti's Foundation;Actitud frente al cancer foundation L Mezquita: Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bristol-Meyers Squibb;Speaker Bureau/Expert testimony: Tecnofarma;Honoraria (institution), Speaker Bureau/Expert testimony: Astrazeneca;Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche;Research grant/Funding (self): Boehringer Intelligence All other authors have declared no conflicts of interest

Resumen Objetivos: Evaluar la prevalencia de calcificación vascular y fracturas vertebrales en una cohorte de pacientes sometidos a trasplante renal, y su asociación con mortalidad por todas las causas y disfunción del injerto, así como la relación con parámetros bioquímicos del metabolismo óseo y mineral. Material y métodos: Estudio prospectivo, observaciónal, unicéntrico, en el que se incluyeron 405 pacientes sometidos a trasplante renal, con recogida de parámetros clínicos, bioquímicos, epidemiológicos y de calcificación vascular radiológica y fracturas vertebrales mediante radiografía simple en el momento del trasplante, con un seguimiento mínimo de dos años, evaluando mortalidad cardiovascular y por todas las causas y descenso del filtrado glomerular. Se dispuso además de 39 estudios de densitometría ósea realizados en los meses previos al trasplante. Resultados: La supervivencia de los pacientes fue significativamente menor en el grupo de pacientes con calcificación vascular (131±1,5 meses sin calcificación frente a 110±3,5 meses con calcificación vascular, p

Background Approximately 43% of Spanish men report experiencing premature ejaculation (PE) at some point in their lives and 12.1% suffer from erectile dysfunction (ED), of whom only 16.5% have seen a doctor. Despite this, ED and PE remain undiagnosed among a supposedly healthy segment of the population. Aim To assess the general knowledge of a representative population of healthy Spanish males of the symptoms, treatment, and expectations related to ED and PE. Methods This was a descriptive study based on an online questionnaire in which 2,515 males aged 25–75 years with no history of ED and/or PE presented their perception of aspects related to symptoms, diagnosis, treatment, and expectations in ED and PE. Main Outcome Measures The study provided an evaluation of the knowledge, attitude, and underdiagnosis of ED and/or PE in healthy males and the approach taken by urology specialists and other disciplines. Results The survey was completed by 2,515 healthy males, including over 80% of those who had completed secondary or higher education. 60% of the sample had never seen a urologist and 59% and 62% of the participating men responded correctly to the statements about PE and ED, respectively. Their lack of knowledge of the therapeutic alternatives was clear (74% and 76% of the panel were unaware of the existence of effective treatments for ED and PE, respectively). Despite the initiative shown by some participants in seeking information about each condition (10.3% for ED; 16.7% for PE), only 4.7% of them had been questioned about ED by a medical practitioner (1.9% for PE). The underdiagnosis rate stood at 3.5% for ED (5.6% participants >65 years) and at about 10% for PE. Clinical Implications These results will represent a point of departure for establishing some recommendations to improve the detection and treatment of these disorders. Strengths & Limitations This is the first study of its kind in Spain to analyze the underdiagnosis of ED and/or PE inferred from data reported by a population of healthy males. Screening for ED was performed with a validated questionnaire. However, the rest of the research was conducted using adaptations of validated questionnaires or a self-designed questionnaire based on and in consultation with a group of experienced andrologists. Conclusion People need to have greater knowledge of both the conditions and the related false myths to make sure that they are familiar with the existence of drug treatments and socio-sanitary interventions. Primary care physicians and urologists should also be more proactive in routine visits in order to achieve better management of ED and PE.

Background:TNF inhibitors (TNFi) represent an extraordinary advance in the management of Rheumatoid Arthritis (RA). Despite their benefits, there is a percentage of patients (20–40%) that do not achieve clinical improvement. Therefore, it is necessary to search for new and easily accessible biomarkers predictive of therapeutic response that might guide precision medicine.Objectives:1. To explore changes in the molecular profile of RA patients following TNFi therapy in serum samples. 2. To search for new and reliable biomarkers predictive of TNFi response, based on clinical and molecular profiles of RA patients, by using machine learning algorithms.Methods:In a prospective multicenter study, 79 RA patients undergoing TNFi and 29 healthy donors (HD) were enrolled. Twenty-two RA patients were further included as a validation cohort. Serum samples were obtained before and after 6 months of treatment, and therapeutic efficacy was evaluated. Patients’ response was determined following EULAR response criteria. Serum inflammatory profile was analyzed by a multiplex immunoassay, along with oxidative and NETotic profiles, evaluated by commercial kits. A circulating miRNA array was also performed by next-generation sequencing. Clustering analysis was carried out to identify groups of patients with distinctive molecular signatures. Then, clinical and molecular changes induced by TNFi were delineated after 6 months of therapy. Finally, integrative clinical and molecular signatures as predictors of response were assessed at baseline by supervised machine learning methods, using regularized logistic regressions.Results:Inflammatory, oxidative stress and NETosis-derived biomolecules were found altered in RA patients versus HD, closely interconnected and associated with several deregulated miRNAs. This altered molecular profile at baseline allowed the unsupervised division of three clusters of RA patients with distinctive clinical phenotypes, further linked to TNFi effectiveness. Cluster 1 included RA patients with low levels of pro-inflammatory cytokines, associated with a medium-low disease activity score and good clinical response. Clusters 2-3 comprised patients with high levels of pro-inflammatory cytokines, associated with a high disease activity and a non-response rate of 30%.After 6 months of therapy the molecular profile found altered in RA patients was reversed in responder patients, who achieved a molecular phenotype similar to HDs. However, non-responder patients’ molecular profile remained significantly deregulated, including alterations in inflammatory mediators (IL-6, L-8, TNFα, VEGF, IL-1RA, IL-5, IL-15, GMCSF, GCSF, FGFb), oxidative stress markers (LPO) and NETosis-derived products (Elastase), along with specific miRNAs (miR-199a-5p). These molecular changes further correlated with changes in disease activity score. Machine-learning algorithms identified clinical (Creatinine, IgM, Vitamin D, Swollen Joints, C4, Disease Duration and Tryglicerides) and molecular (Nucleosomes, IL-10, miR-106a-5p, IL-13, IL-12p70, IL-15 and LPO) signatures as potential predictors of response to TNFi treatment with high accuracy. Furthermore, the integration of both features in a combined model increased the predictive value of these signatures (AUC: 0.91). These results were further confirmed in an independent validation cohort.Conclusion:1. RA patients display distinctive altered molecular profiles directly linked to their clinical status and associated with TNFi effectiveness. 2. Clinical response was associated with a specific modulation of the inflammatory profile, the reestablishment of the altered oxidative status, the reduction of NETosis and the reversion of related altered miRNAs. 3. The integrative analysis of the clinical and molecular profiles using machine learning allows the identification of novel signatures as potential predictors of therapeutic response to TNFi therapy.Disclosure of Interests:None declared

COVID-19 pandemic has dramatically impacted the health national systems, interfering with the access to standard care of other illnesses. However, the real impact of COVID-19 crisis on the cancer care remains unknown. We assessed the access to invasive procedures and critically ill patient units (intensive and intermediate care) in patients with lung cancer hospitalized during pandemic period (during-Covid) compared to the same period in 2019 (before-Covid).

Background Inflammatory Bowel Disease patients (IBD) are in a higher risk of colorectal cancer (CRC) than the general population. Studies show that surveillance with chromoendoscopy (CE) is useful for prevention as it detects a higher number of dysplastic lesions, allowing their endoscopic resection and therefore preventing CRC. We aimed to assess our endoscopic results in IBD patients with previous diagnose of dysplasia. Methods We performed a retrospective data collection from IBD patients who have had dysplastic lesions in screening chromoendoscopy, performed in our hospital from January 2013 to June 2019. Demographic and clinical data at basal time were collected, as well as endoscopic and histological findings in basal chromoendoscopy and in the first follow-up Results 353 chromoendoscopies were performed in our Endoscopy Unit in this period and 50 patients showed dysplastic lesions. 14 (28%) of them had already had dysplasia in previous colonoscopies, which were performed with white light and aleatory biopsies. Basal characteristics are shown in the following table. In the initial chromoendoscopy, an average of 2.57 dysplastic lesions with an average size of 7.59 mm was detected. 70.8% were flat lesions (0-IIa/0-IIb Paris classification) and 53% were located distal to the splenic flexure. 85.7% were tubular adenomas low-grade dysplasia (LGD), 2 cases of high-grade dysplasia (HGD), one serrated polyp and one adenocarcinoma. Twenty-nine follow-up chromoendoscopy have been performed and new dysplasia lesions were found in 41.37% (average of 1.86 lesions, median 8 mm). 55.6% of the lesions were tubular adenomas LGD and 11.1% serrated adenomas LGD. Our analysis shows that patients with new lesions in the second chromoendoscopy had had worse bowel preparation on the first one (7.5 vs. 8.9, p = 0,006). We also found that these patients with new lesions had more flat lesions than sessile ones (70.6% Paris IIa, 23.5% IIb, 5.9% Is, p < 0,005). Conclusion Surveillance with chromoendoscopy in IBD patients with previous dysplastic lesions detects new dysplasia in 28% of them and LGD is the most frequent histology. In our sample, finding flat lesions or worse bowel cleaning in the first chromoendoscopy predicts having a higher number of lesions on the follow-up.

The fragile X mental retardation protein (FMRP) is an RNA-binding protein involved in translational regulation of mRNAs that play key roles in synaptic morphology and plasticity. The functional absence of FMRP causes the fragile X syndrome (FXS), the most common form of inherited intellectual disability and the most common monogenic cause of autism. No effective treatment is available for FXS. We recently identified the Phosphodiesterase 2A (Pde2a) mRNA as a prominent target of FMRP. PDE2A enzymatic activity is increased in the brain of Fmr1-KO mice, a recognized model of FXS, leading to decreased levels of cAMP and cGMP. Here, we pharmacologically inhibited PDE2A in Fmr1-KO mice and observed a rescue both of the maturity of dendritic spines and of the exaggerated hippocampal mGluR-dependent long-term depression. Remarkably, PDE2A blockade rescued the social and communicative deficits of both mouse and rat Fmr1-KO animals. Importantly, chronic inhibition of PDE2A in newborn Fmr1-KO mice followed by a washout interval, resulted in the rescue of the altered social behavior observed in adolescent mice. Altogether, these results reveal the key role of PDE2A in the physiopathology of FXS and suggest that its pharmacological inhibition represents a novel therapeutic approach for FXS.

Objectives: This study, developed within the Innovative Medicines Initiative Joint Undertaking project PRECISESADS framework, aimed at functionally characterize the monocyte subsets in RA patients, and analyze their involvement in the increased CV risk associated with RA. Methods: The frequencies of monocyte subpopulations in the peripheral blood of 140 RA patients and 145 healthy donors (HDs) included in the PRECISESADS study were determined by flow cytometry. A second cohort of 50 RA patients and 30 HDs was included, of which CD14+ and CD16+ monocyte subpopulations were isolated using immuno-magnetic selection. Their transcriptomic profiles (mRNA and microRNA), proinflammatory patterns and activated pathways were evaluated and related to clinical features and CV risk. Mechanistic in vitro analyses were further performed. Results: CD14++CD16+ intermediate monocytes were extended in both cohorts of RA patients. Their increased frequency was associated with the positivity for autoantibodies, disease duration, inflammation, endothelial dysfunction and the presence of atheroma plaques, as well as with the CV risk score. CD14+ and CD16+ monocyte subsets showed distinctive and specific mRNA and microRNA profiles, along with specific intracellular signaling activation, indicating different functionalities. Moreover, that specific molecular profiles were interrelated and associated to atherosclerosis development and increased CV risk in RA patients. In vitro, RA serum promoted differentiation of CD14+CD16- to CD14++CD16+ monocytes. Co-culture with RA-isolated monocyte subsets induced differential activation of endothelial cells. Conclusions: Our overall data suggest that the generation of inflammatory monocytes is associated to the autoimmune/inflammatory response that mediates RA. These monocyte subsets, -which display specific and distinctive molecular signatures- might promote endothelial dysfunction and in turn, the progression of atherosclerosis through a finely regulated process driving CVD development in RA. ispartof: FRONTIERS IN IMMUNOLOGY vol:10 ispartof: location:Switzerland status: published

Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Programa de P?s-Gradua??o em Epidemiologia e Vigil?ncia em Sa?de. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Universidade Federal do Par?. N?cleo de Medicina Tropical. Bel?m, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Minist?rio da Sa?de. Secretaria de Vigil?ncia em Sa?de. Instituto Evandro Chagas. Laborat?rio de Rotav?rus. Ananindeua, PA, Brasil. Immunosuppressive therapy causes severe impairment of host defense and diarrhea is a frequent complication in renal transplant recipients. This study aimed to describe the occurrence of Rotavirus A (RVA) and Human Bocavirus (HBoV) in fecal samples of immunosuppressed patients submitted to renal transplantation during posttransplant follow?up. A longitudinal study was carried out involving a 25?patient cohort, selected for kidney transplantation. A total of 126 fecal samples were collected between May 2014 and May 2016. Molecular techniques were used to detect and characterize circulating RVA and HBoV genotypes and statistical analysis were applied to verify the association between epidemiological and clinical characteristics. The prevalence of RVA and HBoV was 24% (6/25) and 40% (10/25), respectively. Among RVA and HBoV positive cases, the majority was female; did not conduct water treatment nor had adequate sewage facilities. The most detected genotypes were RVA G3 (62.5%) and HBoV?3 (95%). Phylogenetic analysis of HBoV strains indicated that studied samples were similar to those found in Asian and American countries. The present study point out the circulation of these viral agents among immunosuppressed individuals and these findings will enable the construction of new knowledge and care perspectives on the cause of diarrhea in this population.

Summary Cerebellar phaeohyphomycosis was diagnosed in an 8-year-old neutered male domestic cat. Gross lesions were limited to the cerebellum, which had a focally extensive dark brown–black, soft, irregular area affecting the cortex and white matter of the left hemisphere and extending to the reticular formation. Microscopically, multifocal pyogranulomatous meningoencephalitis with intralesional pigmented fungal hyphae effaced the cerebellar grey and white matter. Fungal hyphae were 3–6 μm in diameter, septate and non-dichotomously branched, with parallel, thin and slightly bulbous walls. Polymerase chain reaction for the internal transcribed spacer 1–2 ribosomal RNA genes was performed on tissue samples from formalin-fixed and paraffin wax-embedded sections of cerebellum. Nucleotide sequence analysis of the amplified fragment identified the fungal agent as Cladosporium cladosporioides. This is the first confirmed report of cerebellar phaeohyphomycosis attributable to C. cladosporioides-complex in a domestic cat.

Current antifungal drugs present poor effectiveness and there is no available vaccine for fungal infections. Thus, novel strategies to treat or prevent invasive mycosis, such as cryptococcosis, are highly desirable. One strategy is the use of immunomodulators of polysaccharide nature isolated from mushrooms. The purpose of the present work was to evaluate the immunostimulatory activity of β-(1,3)-glucan-containing exopolysaccharides (EPS) from the edible mushrooms Auricularia auricula in phagocytes and mice infected with Cryptococcus neoformans. EPS triggered macrophages and dendritic cell activation upon binding to Dectin-1, a pattern recognition receptor of the C-type lectin receptor family. Engagement of Dectin-1 culminated in pro-inflammatory cytokine production and cell maturation via its canonical Syk-dependent pathway signaling. Furthermore, upon EPS treatment, M2-like phenotype macrophages, known to support intracellular survival and replication of C. neoformans, repolarize to M1 macrophage pattern associated with enhanced production of the microbicidal molecule nitric oxide that results in efficient killing of C. neoformans. Treatment with EPS also upregulated transcript levels of genes encoding products associated with host protection against C. neoformans and Dectin-1 mediated signaling in macrophages. Finally, orally administrated β-glucan-containing EPS from A. auricular enhanced the survival of mice infected with C. neoformans. In conclusion, the results demonstrate that EPS from A. auricula exert immunostimulatory activity in phagocytes and induce host protection against C. neoformans, suggesting that polysaccharides from this mushroom may be promising as an adjuvant for vaccines or antifungal therapy.

[Background] Lung cancer remains a leading cause of cancer incidence and mortality worldwide. Although Spain contributes to global statistics related to cancer, it is difficult to discern aspects linked to clinical presentation of the disease or molecular testing. The Thoracic Tumor Registry (TTR) was created with the aim of filling this gap., [Methods] Observational cohort multicenter study performed in Spain, including patients with lung cancer or other types of thoracic tumors undergoing active treatment or palliative care only. Enrollment took place between August 2016 and December 2018. The evaluation included a review of demographic, epidemiological, clinical and molecular data., [Results] A total of 6,600 patients diagnosed with non-small cell lung cancer (NSCLC) were recruited at 56 Spanish hospitals. The mean age at diagnosis was 64 years. The majority of patients (80%) presented with advanced disease, being adenocarcinoma the most frequent histological type. Up to 86% of patients were current- or ex-smokers, with men starting to smoke earlier than women (average age 17.9 vs. 19.2 years). Sixty-seven percent of patients underwent some type of molecular testing. Mutations in EGFR and KRAS genes were found in 18% and 28% of patients, respectively., [Conclusions] Our findings suggest that the TTR study accurately describes the clinical reality of lung cancer in Spain, including useful information on smoking status as well as molecular profiling and tumor histology, and can therefore be used to drive improvements in health care. Social and political pressure to reduce tobacco consumption among the population should be reinforced, particularly among youth., This work was supported by Grupo Español de Cáncer de Pulmón (GECP), Novartis, Lilly and Merck Sharp & Dohme (MSD).

Objectives:To analyze survival, causes of death, and risk factors associated with mortality in a cohort of patients with Systemic Sclerosis (SSc) at a single centerMethods:We performed a retrospective observational study of a cohort of patients with SSc undergoing follow-up during 2012 and until August 2020. We used the Kaplan-Meier method to estimate survival from onset of symptoms and multivariate Cox regression analysis to obtain independent risk factors associated with mortalityResults:The study population included 85 patients (women, 85.8%; mean age at diagnosis, 64.4 ± 12.7 years). A total of 19 patients (22.6%) died (table 1). Of these 11 (57.9%) died of a cause related to the disease itself (interstitial lung disease [ILD], 5 (26.3%); pulmonary hypertension, 2 (10.5%); or a combination of both, 3 (15.8%). The main cause of non–SSc-related death was cancer (21.1%). Survival rates at 5, 10, and 20 years were 98%, 92%, and 75%, respectively. Survival was statistically significantly poorer for the absence of ACA, the presence of antitopoisomerase I antibodies, proximal skin thickening, pulmonary hypertension, ILD, cancer and the diffuse subtype. The multivariate analysis performed to determine which factors were independently associated with mortality confirmed that older age at diagnosis of the disease, lower FVC in spirometry at diagnosis of ILD, and proximal skin thickening were associated with greater mortalityTable 1.Clinical and immunological characteristics of patients who died and patients who livedDead(n=19)Alive(n=66)p-valueFemale sex, n (%)17 (89.5)55 (83.3)0.594Age at diagnosis (years), mean (SD)56.9 (13.7)50.4 (13.6)0.076Time since diagnosis (years), mean (SD)11.6 (7.3)14.2 (9.2)0.215lcSSc, n (%)6 (33.3)50 (75.7)< 0.001dcSSc, n (%)12 (66.7)10 (15.1)< 0.001Digital ulcers, n (%)9 (47.4)33 (50)0.748Calcinosis, n (%)1 (5.3)16 (24.2)0.061Telangiectasias, n (%)15 (78.9)56 (84.8)0.184ILD, n (%)15 (78.9)32 (48.5)0.021 FEV1 at diagnosis of ILD, mean (SD)78.3 (19.3)78.7 (17.7)0.955 FVC at diagnosis of ILD, mean (SD)65.2 (13.1)78.1 (20.7)0.043 DLCO at diagnosis of ILD, mean (SD)56.9 (17.5)63.9 (16.7)0.301Pulmonary hypertension, n (%)11 (57.9)14 (21.9)0.002 sPAP (mmHg), mean (SD)49.2 (24.7)30.2 (8.2)0.009Gastrointestinal involvement, n (%)13 (68.4)30 (45.4)0.125Cardiac involvement, n (%)3 (15.8)11 (16.7)0.907Muscle involvement, n (%)1 (5.3)2 (3.03)0.851Arthritis or arthralgia, n (%)5 (26.3)23 (34.8)0.436Renal crisis, n (%)02 (3.03)Cancer, n (%)5 (26.3)2 (3.03)0.001Positive ACA, n (%)5 (26.3)35 (53.03)0.034Positive ATA, n (%)10 (52.6)9 (13.6)< 0.001Abbreviations: ILD: diffuse interstitial lung disease, SSc: systemic sclerosis, FEV1: forced expiratory volume in the first second, FVC: forced vital capacity, DLCO: diffusing capacity for carbon monoxide, sPAP: systolic pulmonary artery pressure, ACA: anticentromere antibody, ATA: antitopoisomerase I antibody.Conclusion:Survival at 10 years was greater than 90% in the study cohort. The main causes of death were ILD, pulmonary hypertension and cancer. The main factors associated with mortality were proximal skin thickening, older age at diagnosis, and lower forced vital capacityDisclosure of Interests:None declared

Background:Patients diagnosed with Rheumatoid Arthritis (RA) have an increased risk of comorbidities and secondary mortality, in a large extent due to cardiovascular events.Objectives:To identify the frequency of comorbidity, mortality and variables related to its increase in a cohort of patients with rheumatoid arthritis established (RAE).Methods:Controlled cross-sectional observational study of a cohort of 188 patients with RAE a 10 year follow-up (5 years if not complete this period).Results:62.8% were women, mean age of patients at the time of inclusion was high 73.3 (+/-13.8) years and mean duration of disease was 12,8 (+/-6,99) years. Regarding CV risk factors, 26.6% smoked, 60.6% hypertension and 52.1 % diabetic. Regarding comorbidities, the most frequent were serious infections (45.2%), CVD (35.1%), Osteoporosis (31.9%), Depression (31.9%) and Kidney disease (26.6%). During follow-up, an improvement was observed inflammatory parameters and activity levels (p Conclusion:-The incidence of comorbidities in our cohort is similar to that described in the literature.-Relationship between mortality and CVD and severe infection is demonstrated.-The mortality rate observed is higher than that described in the literature, which be influenced by the advanced age of the patients in the cohort and high time evolution of RA.References:[1]Lee YK, Ahn GY, Lee J, Shin JM, Lee TH, Park DJ, Song YJ, Kim MK, Bae SC. Excess mortality persists in patients with rheumatoid arthritis. Int J Rheum Dis. 2021 Jan 19. doi: 10.1111/1756-185X.14058. Epub ahead of print. PMID: 33463890.[2]Mikuls, T. R. (2003). Co-morbidity in rheumatoid arthritis. Best Practice & Research Clinical Rheumatology, 17(5), 729-752.[3]Naz, S. M., & Symmons, D. P. M. (2007). Mortality in established rheumatoid arthritis. Best Practice & Research Clinical Rheumatology, 21(5), 871-883.Table 1.Student’s t test for paired data.VariablesBasal10 yearPDAS285,25 (15,08)2,89 (1,06)0,036VAS38,61 (36,45)26,93 (24,97)HAQ1,04 (0,79)0,88 (0,87)NSTJC4,96 (5,38)1,40 (2,57)SJC3,55 (3,69)0,72 (2,11)ESR (mm/h)31,47 (21,19)25,86 (18,47)CRP (mg/L)15,24 (16,13)9,41 (21,02)0,001Hemoglobin (mg/dL)13,44 (7,92)13,52 (7,64)NSGlucose (mg/dL)102,26(35,97)103,83 (37, 98)NSCholesterol (mg/dL)203,56 (46,11)195,65 (38,12)0,042LDL (mg/dL)123,91 (40,69)119,58 (33,89)NSHDL (mg/dL)56,73 (19,07)54,84 (20,38)NSTriglycerides (mg/dL)110,85 (60,77)113,44 (55,61)NSTable 2.Logistic regression model. Hosmer-Lemeshow Chi square 9.035 Gl 7 p 0.25. Likelihood ratio test Chi square 64.658 Gl 5 p VariableUnivariate analysisOR (IC 95%)pMultiivariate analysisFINAL MODELOOR (IC 95%)PDyslipidemia1,02 (0,47-2,23)0,965HT4,73 (1,79-12,48)0,002DM1,42 (0,59-3,44)0,438CV disease11,25 (4,45-28,44)< 0,00112,33 (3.89-39,04)< 0,001Hyperuricemia3,27 (1,39-7,65)0,006Thyroid disease0,56 (0,15-2,11)0,393Interstitial lung disease2,48 (0,77-7,99)0,1277,37 (1,48-36,84)0,015Osteoporosis2,38 (1,07-5,29)0,033Renal disease8,25 (3,41-19,97)< 0,0014,14 (1,34-12,80)0,014Depressión0,32 (0,12-0,84)0,0210,20 (0,06-0,74)0,015Solyd CA1,12 (0,44-2,87)0,809Hematologic CA0,999Amyloidosis2,65 (0,16-43,52)0,496Severe infecction6,22 (2,53-15,29)< 0,0015,59 (1,66-18,79)0,005COVID-19 infection1,31 (0,12-14,91)0,828Disclosure of Interests:None declared

Background:Systemic sclerosis (SSc) is a chronic autoimmune disease that carries significant mortality. Despite diagnostic and therapeutic advances in recent years, there is still a significant percentage of patients who do not present a complete clinical response, with the associated increase in morbidity and mortality. Specifically, pulmonary disease is frequent and entails a poor prognosis, with interstitial lung disease (ILD) and pulmonary hypertension (PAH) being the two most important complications, the first and second cause of mortality, respectively.Objectives:To evaluate the prevalence of ILD and/or PAH in patients affected by SSc and to determine the factors associated with ILD.Methods:Cross-sectional observational study of 102 patients diagnosed with SSc (Limited, Diffuse, SSc without scleroderma or Pre-scleroderma), treated between 1975 and 2020 at the Reina Sofia University Hospital in Cordoba. A descriptive study of the cohort was carried out and factors independently associated with ILD were evaluated using a multiple logistic regression model.Results:102 patients were included, 87.3% of these were female with an average age of 50.8 (14) years. There were 20 deaths (19.8%), from which 55% died because of SSc and the main reason was ILD and/or PAH. Respiratory complications (as ILD or as PAH) were present in 59 patients (57.8%), of whom 52 were diagnosed with ILD (90.4% with a pattern of non-specific interstitial pneumonia) and 25 PAH, whose mean pulmonary artery systolic pressure was 47.16 (18.54) mmHg. Anti-topoisomerase I antibodies were positive in 34.6% of patients who developed ILD, while anticentromere antibodies were more frequent in SSc without interstitial lung disease (80%). Independent factors associated with ILD were type of SSc, proximal skin involvement, anticentromere antibodies, current treatment with corticoids and the death.Conclusion:Just over half of the patients with SSc have lung disease (as ILD or as PAH). The main risk factors associated with ILD are proximal skin involvement and treatment with glucocorticoids, probably in the context of more severe forms that require more treatment. Anticentromere antibodies are more prevalent in patients with Limited SSc and their expression decreases the risk of developing ILD in these patients.References:[1]Orlandi M, Barsotti S, Lepri G, et al. Clin Exp Rheumatol 2018 Jul-Aug; 36 Suppl 113: 3-23[2]Hao Y, Hudson M, Baron M, et al. Arthritis Rheumatol. 2017;69(5):1067-1077.[3]Furue M, Mitoma C, Mitoma H, et al. Immunol Res. 2017 Aug; 65: 790-7.[4]Nihtyanova SI, Schreiber BE, Ong VH, et al. Arthritis Rheumatol. 2014 Jun; 66: 1625-35.Disclosure of Interests:None declared.

Objectives:To analyze the effect of disease-modifying antirheumatic drugs (DMARDs) and identify risk factors associated with disease progression and mortality in patients with rheumatoid arthritis associated with interstitial lung disease (RA-ILD).Methods:We performed a multicenter, prospective, observational study of patients with RA-ILD receiving DMARDs between 2015 and 2020. The patients were assessed using high-resolution computed tomography and pulmonary function tests at baseline and at 60 months. The main outcome measure at 60 months was worsening of FVC >10% or DLCO >15% and radiological progression or death. We recorded demographic and clinical characteristics, lung function, and the incidence of adverse events. A Cox regression analysis was performed to identify factors associated with worsening of ILD.Results:After 60 months, lung disease had stabilized in 66 patients (56.9%), improved in 9 (7.8%), and worsened in 23 (19.8%). Eighteen patients (15.5%) died, with a mean survival of 71.8 (1.9) months. Baseline characteristics of 116 with RA-ILD treated with DMARDs is in table 1.The Cox multivariate analysis revealed the independent predictors of worsening of RA-ILD to be usual interstitial pneumonia (HR, 2.6 [95%CI, 1.0-6.7]), forced vital capacity (%) (HR, 3.8 [95%CI, 1.5-6.7]), anticitrullinated protein antibody titers (HR, 2.8 [95%CI, 1.1-6.8]), smoking (HR, 2.5 [95%CI, 1.1-6.2]), and treatment with abatacept, tocilizumab, or rituximab (HR, 0.4 [95%CI, 0.2-0.8]). During follow-up, 79 patients (68%) experienced an adverse event, mostly infection (61%).Conclusion:Lung function is stable in most patients with RA-ILD receiving treatment with DMARDs, although one third of patients die. Identifying factors of worsening in RA-ILD is important for clinical management.Table 1.Baseline characteristics of 116 with RA-ILD treated with DMARDsVariableTotal=116Epidemiological characteristicsFemale sex, n (%)63 (54.3)Age, years, mean (SD)68.3 (9.9)Clinical and analytical characteristicsCurrent smokerNonsmoker, n (%)57 (49.1)Smoker, n (%)23 (19.8)Exsmoker, n (%)36 (31.0)Time since diagnosis of RA, months, median (p25-p75)148.5 (71.5-217.8)Diagnostic delay, months, median (p25-p75)8.5 (4.9-16.8)Time since diagnosis of ILD, months, median (p25-p75)27.5 (9.8-60.0)Positive rheumatoid factor (>10), n (%)111 (95.7)Positive ACPA titer (>20), n (%)100 (86.2)Erosive disease, n (%)76 (65.5)Treatment Synthetic DMARD100 (86.2) Methotrexate, n (%)51 (44.0) Leflunomide, n (%)30 (25.9) Sulfasalazine, n (%)9 (7.8) Hydroxychloroquine, n (%)21 (18.1)Biologic DMARD50 (43.1) Infliximab, n (%)1 (0.9) Etanercept, n (%)6 (5.2) Adalimumab, n (%)3 (2.6) Golimumab, n (%)3 (2.6) Certolizumab, n (%)3 (2.6) Tocilizumab, n (%)6 (5.2) Abatacept, n (%)15 (12.9) Rituximab, n (%)13 (11.2) Immunosuppressants11 (9.5) Mycophenolate, n (%)7 (6.0) Azathioprine, n (%)4 (3.4) Antifibrotic agents, nintedanib, n (%)1 (0.9) Baseline corticosteroids, n (%)69 (60.0) Dose of baseline corticosteroids, median (p25-p75)5.0 (0.0-7.5)Abbreviations. RA: rheumatoid arthritis; ILD: interstitial lung disease; ACPA: anticyclic citrullinated protein antibody; DMARD: disease-modifying antirheumatic drug; SD: standard deviation.Acknowledgements:Grant for Medical Researchers of the “Fundación Española de Reumatología” 2019. declare.Disclosure of Interests:None declared