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INTRODUCTION: Data on pathological changes in COVID-19 are scarce. The aim of this study was to describe the histopathological and virological findings of postmortem biopsies, and the existing clinical correlations, in people who died of COVID-19. MATERIALS AND METHODS: We performed postmortem needle core biopsies of the chest in 11 people who died of COVID-19 pneumonia. Tissue examination was done by light microscopy and real-time polymerase chain reaction (RTPCR). RESULTS: The age of the patients were between 61 to 94 years. Of the 11 postmortem chest biopsies, lung tissue was obtained in 8, myocardium tissue in 7, and liver tissue in 5. Histologically of lung, the main findings pertaining to the lung were diffuse alveolar damage in proliferative phase (n = 4, 50%), diffuse alveolar damage in exudative and proliferative phase (n = 3, 37.5%), diffuse alveolar damage in exudative (n=1; 12.5%) and acute pneumonia (n = 2, 25%). Necrotising pneumonia, acute fibrinous and organising pneumonia, and neutrophils were detected in one sample each (12.5%). Another case presented myocarditis. RT-PCR showed RNA of SARS-CoV-2 in 7 of the 8 lung samples (87.5%), 2 of the 7 myocardial tissue samples (28.6%), and 1 of the 5 liver tissue samples (20%). CONCLUSION: The postmortem examinations show diffuse alveolar damage, as well as acute or necrotising pneumonia. RT-PCR of SARS-CoV-2 was positive in most lung samples.

OBJECTIVE: There is early evidence about Valproic acid (VPA) antiviral effect. Our aim was to investigate the incidence and severity of SARS-CoV-2 infection in VPA users as compared with the general population. MATERIAL AND METHODS: A case-control study nested within a cohort, carried out between March 1 and December 17, 2020. Retrospectively, we identified confirmed SARS-CoV-2 infection patients exposed to VPA in our health department (defined as case). We ascertained VPA regimen (all the time (AT)(292 days) or at least 20% of the study period (notAT)(=58 days) and if VPA levels were in therapeutic range (ATR) (50-100 mcg/mL) in the last 24 months. We calculated the cumulative incidence of SARS-CoV-2 infection and hospital admission in the cases, comparing it with the general unexposed VPA population (controls). RESULTS: During the study period, 6183 PCR+ were detected among 281035 inhabitants, of these, 746 were hospitalized. 691 patients were on VPA notAT and 628 (90.1%) AT. The indication for VPA use was epilepsy in 54.9%. The incidence of PCR+ was 1.736 % (OR 0.785 (95%CI 0.443-1.390) and 1.910 % (OR 0.865 (95%CI 0.488-1.533), on VPA notAT and VPA AT patients, respectively vs. 2.201% in people without VPA regimen. Those patients with VPA ATR had a lower risk of PCR + (OR 0.233 (95%CI 0.057-0.951) notAT; OR 0.218 (95%CI 0.053-0.890) AT). Hospital admission incidence was lower in patient on VPA (OR was 0.543 (95% CI 0.076 to 3.871). CONCLUSION: Patients with VPA within the therapeutic range had a reduction of SARS-Cov-2 infection incidence greater than 75%. There is a downward trend in the risk of COVID-19 admission by SARS-CoV-2 in patients on VPA therapy. These ?ndings warrant further investigation.

To evaluate the effectiveness of an integrated emergency department (ED)/hospital at home (HH) medical care model in mild COVID-19 pneumonia and evaluate baseline predictors of major outcomes and potential savings. Retrospective cohort study with patients evaluated for COVID-19 pneumonia in the ED, from March 3 to April 30, 2020. All of them were discharged home and controlled by HH. The main outcomes were ED revisit and the need for deferred hospital admission (protocol failure). Outcome predictors were analyzed by simple logistic regression model (OR; 95% CI). Potential savings of this medical care model were estimated. Of the 377 patients attended in the ED, 109 were identified as having mild pneumonia and were included in the ED/HH medical care model. Median age was 50.0 years, 52.3% were males and 57.8% had Charlson index = 1. The median HH stay was 8 (IQR 3.7-11) days. COVID-19-related ED revisit was 19.2% (n = 21) within 6 days (IQR 3-12.5) after discharge from ED. Overall protocol failure (deferred hospital admission) was 6.4% (n = 7), without ICU admission. The ED/HH model provided potential cost savings of 77% compared to traditional stay, due to the costs of home care entails 23% of the expenses generated by a conventional hospital stay. 789 days of hospital stay were avoided by HH, rather than hospital admission. An innovative ED/HH model for selected patients with mild COVID-19 pneumonia is feasible, safe and effective. Less than 6.5% of patients requiring deferred hospital admission and potential savings were generated due to hospitalization.

Studies are needed to identify useful biomarkers to assess the severity and prognosis of COVID-19 disease, caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus. Here, we examine the levels of various plasma species of the SARS-CoV-2 host receptor, the angiotensin-converting enzyme 2 (ACE2), in patients at different phases of the infection. Human plasma ACE2 species were characterized by immunoprecipitation and western blotting employing antibodies against the ectodomain and the C-terminal domain, using a recombinant human ACE2 protein as control. In addition, changes in the cleaved and full-length ACE2 species were also examined in serum samples derived from humanized K18-hACE2 mice challenged with a lethal dose of SARS-CoV-2. ACE2 immunoreactivity was present in human plasma as several molecular mass species that probably comprise truncated (70 and 75 kDa) and full-length forms (95, 100, 130, and 170 kDa). COVID-19 patients in the acute phase of infection (n = 46) had significantly decreased levels of ACE2 full-length species, while a truncated 70-kDa form was marginally higher compared with non-disease controls (n = 26). Levels of ACE2 full-length species were in the normal range in patients after a recovery period with an interval of 58-70 days (n = 29), while the 70-kDa species decreased. Levels of the truncated ACE2 species served to discriminate between individuals infected by SARS-CoV-2 and those infected with influenza A virus (n = 17). In conclusion, specific plasma ACE2 species are altered in patients with COVID-19 and these changes normalize during the recovery phase. Alterations in ACE2 species following SARS-CoV-2 infection warrant further investigation regarding their potential usefulness as biomarkers for the disease process and to asses efficacy during vaccination.

OBJECTIVES: To describe the clinical characteristics and predictors of major outcomes in patients treated with tocilizumab (TCZ) for severe COVID-19 pneumonia. PATIENTS AND METHODS: Case series of all sequential patients with severe COVID-19 pneumonia treated with TCZ at an Academic Spanish hospital (March 12 - May 2, 2020). Clinical outcomes: death, length of hospital stay. An early clinical response to TCZ (48-72 h after the administration) was assessed by variations in respiratory function markers, Brescia COVID Respiratory Severity Scale (BCRSS), inflammatory parameters, and patients' and physicians' opinion. Associations were tested by multiple logistic regression. RESULTS: From a cohort of 236 patients, 77 patients treated with TCZ were included (median age 62 years (IQR 53.0-72.0), 64.9% were males), 42.9% had Charlson index =3; hypertension (41.6%), obesity (34.7%), and diabetes (20.8%). Median follow-up was 83.0 days (78.0-86.5), no patient was readmitted. ICU admission was required for 42 (54.5%), invasive mechanical ventilation in 38 (49.4%) and 10 patients died (12.9% global, 23.8% at ICU admitted). After multivariate adjustment, TCZ response by BCRSS (OR 0.03 (0.01-0.68), p = 0.028), and Charlson index (OR 3.54 (1.20-10.44), p = 0.022) has been identified as independent factors associated with mortality. Median of hospital stay was 16.0 days (11.0-23.0); BCRSS, physician subjective and D-dimer response were associated with shorter hospitalization stay. CONCLUSIONS: In a Mediterranean cohort, use of tocilizumab for severe COVID-19 show 12.9% of mortality. Early TCZ-response by BCRSS and low comorbidity were associated with increased survival. Early TCZ-response was related to shorter median hospital stay.

Gender dysphoria (GD) in childhood and adolescence is a complex condition where early detection and comprehensive treatment are essential to improve quality of life, decrease mental comorbidity, and improve GD. In this position statement, the Working Group on Gender Identity and Sexual Development of the Spanish Society of Endocrinology and Nutrition (GIDSEEN), consisting of specialists in Endocrinology, Psychology, Psychiatry, Pediatrics and Sociology, sets out recommendations for evaluation and treatment of GD in children and adolescents. Interdisciplinary management of GD should be carried out at specialized units (UTIGs), considering that any clinical intervention should follow the principles of scientific rigor, experience, ethical and deontological principles, and the necessary caution in front of chronic, aggressive, and irreversible treatments. (C) 2015 SEEN. Published by Elsevier Espana, S.L.U. All rights reserved.

INTRODUCTION AND OBJECTIVE: The ability to predict recurrence of pituitary adenoma (PA) after surgery may be helpful to determine follow-up frequency and the need for adjuvant treatment. The purpose of this study was to assess the prognostic capacity of pituitary tumor transforming gene (PTTG), insulin-like growth factor 1 receptor (IGF1R), and Ki-67. MATERIALS AND METHODS: In this retrospective study, the normalized copy number (NCN) of PTIG and IGF1R mRNA was measured using RT-PCR, and the Ki-67 index was measured by immunohistochemistry in 46 PA samples. Clinical data, histological subtype, and radiographic characteristics were collected to assess associations between variables and tumor behavior. Progression of tumor remnants and its association to markers was also studied in 14 patients with no adjuvant treatment after surgery followed up for 46±36 months. RESULTS: Extrasellar tumors had a lower PTTG expression as compared to sellar tumors (0.065 [1st-3rd quartile: 0.000-0.089] NCN vs. 0.135 [0.105-0.159] NCN, p=0.04). IGF1R expression changed depending on histological subtype (p=0.014), and was greater in tumor with remnant growth greater than 20% during follow-up (10.69±3.84 NCN vs. 5.44±3.55 NCN, p=0.014). CONCLUSIONS: Our results suggest that the IGF1R is a more helpful molecular marker than PTTG in PA management. Ki-67 showed no association to tumor behavior. However, the potential of these markers should be established in future studies with standardized methods and on larger samples.

Transsexual patients can only be diagnosed and treated at functional gender identity Units with provision of high quality care, development of clinical practice guidelines, and interdisciplinary working groups. The therapeutic process has three mainstays: initial psychological diagnostic evaluation and psychotherapy, endocrinological evaluation and hormone therapy, and sex reassignment surgery. Cross-sex hormone therapy is essential for the anatomical and psychological transition process in duly selected patients. Hormones help optimize real-life sex identity, improve quality of life, and limit psychiatric co-morbidities often associated to lack of treatment. Development of this clinical practice guideline addresses the need for implementing a coordinated action protocol for comprehensive health care for transgender people in the National Health System.

BACKGROUND: The measurement of human chorionic gonadotropin (hCG) in cerebrospinal fluid (CSF) is useful for the differential diagnosis of suprasellar lesions. However, the concentrations that prove diagnostic for neurohypophyseal germinoma have not been well defined. In addition, the immunoassays used for such measurements are the same as those applied in serum, and few studies have been performed regarding the validation of such techniques in CSF. The present study aims to apply the Elecsys(®) hCG + ß immunoassay from Roche Diagnostics to measure hCG in CSF, as a useful tool in the diagnosis of neurohypophyseal germinomas in children and young adults. METHODS: Validation of the immunoassay involved calculation of the functional sensitivity and reference values for hCG in CSF in 35 controls in the absence of pregnancy, trophoblastic disease or tumour pathology. For the clinical application study, three patients diagnosed with neurohypophyseal germinoma have been reviewed. RESULTS: The functional sensitivity obtained was 0.4 IU/L. The reference values for hCG in CSF ranged from undetectable values to 0.7 IU/L. The hCG concentrations in CSF in the three studied patients, with confirmed diagnosis of neurohypophyseal germinoma, were 21.1, 32.6 and 23 IU/L, respectively. CONCLUSIONS: The Elecsys® hCG + ß immunoassay from Roche Diagnostics can be used to detect hCG in CSF with high precision. According to our results, CSF-hCG concentrations that exceed the established reference interval (undetectable values to 0.7 IU/L) in the presence of suprasellar lesions and hypophyseal stalk thickening must be considered pathological, establishing the need to exclude the presence of germinoma.

The pathogenesis of pituitary tumours is far to be understood. Pituitary transforming tumour gene (PTTG), a gen that induces aneuploidy, genetic instability, cellular proliferation and to stimulate angiogenesis, has been involved in neoplasic transformation and shown overexpressed in many neoplasm as lung, breast, endometrium, thyroid and colon malignant tumours. On the other hand, PTTG has been inconsistently studied in pituitary tumours. The majority of studies have been performed in animals and there is a great variability in the methods used in its determination. The goal of this review is to resume the role of PTTG in tumourogenesis and critically to revise the studies published in humans in order to advance in the knowledge of the pathogenesis of pituitary adenomas and to find clinical useful predictors of the behavior of these tumours.

OBJECTIVES: To determine the prevalence of erectile dysfunction in a cohort of HIV-infected men in a stable clinical state, the effect of exposure to antiretroviral therapy on sexual dysfunction and to identify the risk factors. DESIGN: This is a cross-sectional, observational study. METHODS: HIV-infected men without hepatitis C virus coinfection were included if they were antiretroviral therapy-naive (naive group), on current treatment with an enhanced protease inhibitor (protease inhibitor group) or on current treatment with two to three nucleoside reverse transcriptase inhibitors along with one nonnucleoside reverse transcriptase inhibitor and never having received treatment with protease inhibitor (nonnucleoside reverse transcriptase inhibitor group). Erectile dysfunction was defined as an ejection fraction of 25 or less (International Index of Erectile Function-15). RESULTS: Ninety patients were included, with an age of 42 +/- 8.2 years and CD4 cell count of 465 cells/microl [P25-75 361-676]: 18.9% in Centers for Disease Control and Prevention class C and 72.2% with undetectable viral load. Seventy-six patients (84.4%) were receiving antiretroviral therapy, 39 (43.3%) in the protease inhibitor group. The prevalence of lipodystrophy was 31.5%. Forty-seven (53.4%) patients had an erectile dysfunction. Multivariate logistic regression analysis confirmed that there was an independent association between the patients' age (per decade; odds ratio 2.2, 95% confidence interval 1.04-4.5, P = 0.04) and greater duration of exposure to protease inhibitor (per year; odds ratio 1.6, 95% confidence interval 1.12-2.4, P = 0.01). Older age, depression and lipodystrophy, combined with the duration of exposure to protease inhibitor, determined a lower score on various sexual dysfunction domains (P < 0.05). CONCLUSION: There is a high prevalence of erectile dysfunction in HIV-infected men, with age and the duration of exposure to protease inhibitor being the only identifiable risk factors.

INTRODUCTION: Hypogonadism is common in human immunodeficiency virus (HIV)-infected men; the high concentration of sex hormone binding globulin (SHBG) in this population, induces a "false increase" in total testosterone (TT) values. AIMS: To validate the determination of TT and measured free testosterone (FT [radioimmunoassay {RIA}]) for hypogonadism diagnosis in an HIV-infected population using calculated free testosterone (CFT) as reference method; and also to determine the prevalence and identify the risks factors of hypogonadism. METHODS: Cross-sectional, observational study. Ninety HIV-infected males (42 ± 8.2 years), not HCV coinfected, antiretroviral therapy (ART)-naive (14 patients), on current ART with enhanced protease inhibitor (PI) (39 patients), or patients on PI-naive ART (NN) (37 patients). MAIN OUTCOME MEASURES: CFT was calculated by determining TT, SHBG, and albumin (Vermeulen's formula); hypogonadism was defined as CFT

RATIONALE AND OBJECTIVE: The treatment of active moderate-severe Graves' ophthalmopathy (GO) is based on the administration of highdose intravenous glucocorticoids. The present study compares the efficacy and safety of 2 different intravenous methylprednisolone (MTPiv) dosing regimens. MATERIAL AND METHODS: We carry a retrospective descriptive study with sequential sampling of 24 patients (83% females) presenting moderatesevere GO (EUGOGO criteria) and receiving treatment in our center between January 2006 and June 2008. We use 2 dosing regimens: regimen A (12 weeks): 6 doses of 0.5g/week followed by 6 doses of 0.25 g/week, for a cumulative dose of 4.5 g of MTPiv (n=13); and regimen B (16 weeks): 4 cycles of 15 mg/kg, followed by 4 cycles of 7.5mg/kg, for a cumulative dose of 90 mg/kg (range, 4.9-7.4 g) (n=11). Comparisons were made for safety (fasting glucose, cytolysis-cholestasis enzymes, lipid profile) and efficacy data (clinical improvement and recurrence). RESULTS: Mild-moderate liver cytolysis was recorded in four patients, one with associated moderate cholestasis and another with hyperglycemia, leading to treatment suspension - with no differences between the 2 treatment regimens. Percentage clinical improvement with regimen A was 92% (CI, 65-94%) versus 100% with regimen B (CI, 74-100%). The recurrence rate was 43% with regimen A and 63% with regimen B (p>0.05). None of the variables examined in the univariate logistic regression study were associated to a lesser treatment response or increased risk of recurrence of GO. CONCLUSIONS: The treatment of GO with MTPiv is safe and effective, with a lower recurrence rate when using dosing regimen A.

HIV-associated hypogonadism is known to be a prevalent endocrine disorder, with a multifactorial etiology. Low testosterone levels are associated with decreased muscle mass, exercise capacity loss, erectile dysfunction, cognitive impairment, depression and decreased quality of life. In the same way, hypogonadism in HIV-infected men is associated with decreased muscle mass quantity and function, changes in corporal fat mass distribution and quantity, secretion of adipocytokines and endothelial dysfunction. This combined effect renders the entire body less sensitive to insulin, promoting development of atherosclerosis and glucose metabolism disorders. The clinical presentation is non-specific and hypogonadism screening scales are not useful in this population. Diagnostic procedures must include determination of free testosterone (FTc) in any HIV-infected men at the time of first HIV diagnosis and periodically, because of the clinical implications and the absence of specific predictive disease factors. Substitutive hormonal treatment must be offered only for HIV-infected men with FTc under reference levels and when reversible causes have been ruled out. Metabolic impact of hypogonadism suggests the incorporation of low testosterone levels to the list of cardiovascular risk factor in HIV-infected men.

Parathyroid carcinoma (PC) is an uncommon disease affecting 0.5-5% of all patients with primary hyperparathyroidism. PC is characterized by the association of severe symptoms of hypercalcemia, high serum calcium and parathyroid hormone (PTH) concentrations and a palpable neck mass. Definitive diagnosis can only be made by histological study after surgery. We report the case of a 77-year-old man admitted to our hospital due to pulmonary embolism and hypercalcemia. The patient was initially diagnosed with primary hyperparathyroidism, but displayed the atypical clinical features described above. Due to clinical suspicion of PC, a surgical procedure was carried out. Diagnosis of parathyroid carcinoma was confirmed by histopathologic study.

Clinically silent corticotroph adenomas are rare. The clinical course of these tumors varies: while some have an insidious course, others behave aggressively, especially during tumoral recurrence. Given the absence of clinical and biochemical features of hypercortisolism, the definitive diagnosis is histological.

Objetivos: Determinar aquellos factores pronósticos que mejor puedan prever el resultado de una intervención nutricional vía enteral y evaluar la calidad asistencial de una unidad de nutrición. Ámbito y sujetos: Pacientes que precisaron nutrición enteral en régimen de ingreso hospitalario, en un centro de 3.er nivel. Intervenciones: Estudio observacional, prospectivo, en el que se incluyeron 160 pacientes mediante muestreo consecutivo, durante un período de seguimiento de 6 meses. Se determinó: patología de base, grado de incapacidad, valoración nutricional, tipo de nutrición enteral, complicaciones, cuidados de enfermería y evolución clínica de los pacientes. Resultados: Se diagnosticó desnutrición calórica y protéica graves en el 48,4 y 52,9% de los pacientes; el grado de estrés fue moderado en el 52,2% y grave en el 36,5%. En el 88,2% de los pacientes la variación de los parámetros protéicos fueron de igual o mejor, con un incremento en las concentraciones de albúmina de 0,26 g/dl y prealbúmina de 2,4 mg/dl (p < 0,05). El análisis multivariante, ajustado por la albúmina plasmática al ingreso mostró que, además de este parámetro bioquímico, el grado de estrés grave, el nivel de consciencia disminuido, y el empeoramiento en la variación protéica durante el ingreso, son factores pronósticos independientes de mortalidad en el transcurso de una intervención nutricional enteral en el paciente hospitalizado (p < 0,05). Conclusiones: El nivel de consciencia, grado de desnutrición calórica, grado de estrés, concentraciones de albúmina plasmática y la variación de los parámetros proteicos durante el soporte nutricional, son factores pronósticos independientes del resultado de una inter-vención nutricional. El desarrollo de sistemas de monitorización global de la actividad y calidad asistencial de las Unidades de Nutrición, son básicos para mejorar la eficiencia del soporte nutricional vía enteral en el ámbito intrahospitalario, avanzar en el cuidado de los pacientes y favorecer el desarrollo de la terapia nutricional. Objective: To determine the prognostic factors that may best for see the outcome of an enteral nutritional intervention and to assess the assistance quality of a nutrition unit. Setting and subjects: Patients that required enteral nutrition during hospital admission at a third level center. Interventions: observational prospective study in which 160 patients were included by means of consecutive sampling, for a 6-months follow-up period. Underlying pathology, disability degree, nutritional assessment, type of enteral nutrition, complications, nursing care, and clinical course of patients were determined. Results: severe caloric and protein hyponutrition was diagnosed in 48.4 and 52.9% of patients; stress degree was moderate in 52.2% and severe in 36.5%. In 88.2% of patients variation of protein parameters was unchanged or improved, with a 0.26 g/dL increase in albumin levels and 2.4 m/dL in prealbumin (p < 0.05). Multivariate analysis adjusted for plasma albumin at admission showed that besides this biochemical parameter, a severe stress degree, a decreased alertness level, and worsening of protein variation during admission are independent prognostic mortality factors during an enteral nutritional intervention in the hospitalized patient (p < 0.05). Conclusions: alertness level, degree of caloric hyponutrition, stress degree, plasma albumin levels, and variation of protein parameters during nutritional support are independent prognostic factors for the nutritional intervention outcomes. The development of global monitoring systems of assistance activity and quality of Nutrition Units is paramount in order to improve the efficiency of enteral nutritional support at the hospital setting, to advance in patients care and promote the development of nutritional therapy.

Objetivos: Determinar aquellos factores pronósticos que mejor puedan prever el resultado de una intervención nutricional vía enteral y evaluar la calidad asistencial de una unidad de nutrición. Ámbito y sujetos: Pacientes que precisaron nutrición enteral en régimen de ingreso hospitalario, en un centro de 3.er nivel. Intervenciones: Estudio observacional, prospectivo, en el que se incluyeron 160 pacientes mediante muestreo consecutivo, durante un período de seguimiento de 6 meses. Se determinó: patología de base, grado de incapacidad, valoración nutricional, tipo de nutrición enteral, complicaciones, cuidados de enfermería y evolución clínica de los pacientes. Resultados: Se diagnosticó desnutrición calórica y protéica graves en el 48,4 y 52,9% de los pacientes; el grado de estrés fue moderado en el 52,2% y grave en el 36,5%. En el 88,2% de los pacientes la variación de los parámetros protéicos fueron de igual o mejor, con un incremento en las concentraciones de albúmina de 0,26 g/dl y prealbúmina de 2,4 mg/dl (p < 0,05). El análisis multivariante, ajustado por la albúmina plasmática al ingreso mostró que, además de este parámetro bioquímico, el grado de estrés grave, el nivel de consciencia disminuido, y el empeoramiento en la variación protéica durante el ingreso, son factores pronósticos independientes de mortalidad en el transcurso de una intervención nutricional enteral en el paciente hospitalizado (p < 0,05). Conclusiones: El nivel de consciencia, grado de desnutrición calórica, grado de estrés, concentraciones de albúmina plasmática y la variación de los parámetros proteicos durante el soporte nutricional, son factores pronósticos independientes del resultado de una inter-vención nutricional. El desarrollo de sistemas de monitorización global de la actividad y calidad asistencial de las Unidades de Nutrición, son básicos para mejorar la eficiencia del soporte nutricional vía enteral en el ámbito intrahospitalario, avanzar en el cuidado de los pacientes y favorecer el desarrollo de la terapia nutricional.