Lithium salts as a treatment for COVID-19: Pre-clinical outcomes.

INTRODUCTION: Identifying effective drugs for Coronavirus disease 2019 (COVID-19) is urgently needed. An efficient approach is to evaluate whether existing approved drugs have anti-SARS-CoV-2 effects. The antiviral properties of lithium salts have been studied for many years. Their anti-inflammatory and immune-potentiating effects result from the inhibition of glycogen synthase kinase-3. AIMS: To obtain pre-clinical evidence on the safety and therapeutic effects of lithium salts in the treatment of COVID-19. RESULTS: Six different concentrations of lithium, ranging 2-12 mmol/L, were evaluated. Lithium inhibited the replication of SARS-CoV-2 virus in a dose-dependent manner with an IC50 value of 4 mmol/L. Lithium-treated wells showed a significantly higher percentage of monolayer conservation than viral control, particularly at concentrations higher than 6 mmol/L, verified through microscopic observation, the neutral red assay, and the determination of N protein in the supernatants of treated wells. Hamsters treated with lithium showed less intense disease with fewer signs. No lithium-related mortality or overt signs of toxicity were observed during the experiment. A trend of decreasing viral load in nasopharyngeal swabs and lungs was observed in treated hamsters compared to controls. CONCLUSIONS: These results provide pre-clinical evidence of the antiviral and immunotherapeutic effects of lithium against SARS-CoV-2, which supports an advance to clinical trials on COVID-19's patients.

Cirugías de afirmación de género en mujeres trans: resultados estéticos, sexuales y urinarios de una serie inicial de vaginoplastias / Gender affirmation surgeries in transgender women: Aesthetic, sexual, and urinary results of an initial series of vaginoplasties

Introducción y objetivos: La disforia de género se asocia a elevada comorbilidad de salud mental, como depresión y suicidio. Las «cirugías de afirmación de género» mejoran la sexualidad y el bienestar psicosocial. El objetivo de la vaginoplastia es que los genitales se asemejen en forma y función a una vagina con una profundidad de al menos 11cm y un clítoris sensible. Además, la uretra debe acortarse y permitir la micción en posición sentada. Nuestro objetivo es describir los resultados estéticos, sexuales y urinarios.Pacientes y métodoEstudio retrospectivo de todas las pacientes operadas de genitoplastia feminizante en el Hospital Sótero del Río entre 2018 y 2019 que cumplían requisitos de WPATH. Se evaluaron dimensiones vaginales, sensibilidad del neoclítoris, conformidad estética y sexual de la neovagina, cuestionarios Índice de Función Sexual Femenina (FSFI) y la Escala de Autoimagen Genital Femenina (FGSIS), IPSS-QoL, uroflujometría y residuo posmiccional.ResultadosSe identificaron 10 mujeres operadas de genioplastia feminizante. La profundidad promedio neovaginal fue de 14,2cm. No hubo lesión rectal ni reoperación. Hubo 100% de sensibilidad del neoclítoris y 88% de conformidad con el ancho neovaginal. La FGSIS promedió 25,4 puntos y el FSFI promedió 16 puntos. El IPSS fue de 6,7 puntos, el Qmax promedio fue de 22ml/s y el residuo posmiccional promedio fue de 22ml. No hubo estenosis del neomeato.ConclusionesLa genitoplastia feminizante es una cirugía compleja, exigente y no completamente estandarizada. Sin embargo, es un procedimiento relativamente seguro que logra adecuados resultados estéticos, sexuales y urinarios. (AU)

Introduction and objectives: Gender dysphoria is associated with mental health comorbidity, such as depression and suicide. “Gender affirming surgeries” improve sexuality and psychosocial well-being. The goal of vaginoplasty is for the genitalia to resemble in form and function to a biological vagina with a depth of at least 11 cm and a sensitive clitoris. In addition, the urethra must be shortened and allow voiding in a sitting position. Our objective is to describe the aesthetic, sexual and urinary results.Patients and methodRetrospective study of all patients undergoing feminizing genitoplasty, at Hospital Sótero del Río between 2018 and 2019, that met WPATH requirements. Vaginal dimensions, neo-clitoral sensitivity, aesthetic and sexual satisfaction of the neovagina, questionnaires Female Sexual Function Index (FSFI) and the Female Genital Self-Image Scale (FGSIS), IPSS-QoL, uroflowmetry and post-void residue were evaluated.Results10 women who underwent feminizing genitoplasty were identified. The neovaginal depth average was 14.2 cm. There was no rectal injury or reoperation. There was 100% of Neoclitoris sensitivity and 88% satisfaction with the neovaginal width.The FGSIS averaged 25.4 points and the FSFI averaged 16 points. The IPSS was 6.7 points, the average Qmax was 22 ml/s and post-void residual volume average was 22 ml. There was no neomeatal stenosis.ConclusionsFeminizing Genitoplasty is a complex, demanding and not completely standardized surgery. However, it is a relatively safe procedure that achieves adequate aesthetic, sexual and urinary results. (AU)

Global and local sensitivity analysis to improve the understanding of physically-based urban wash-off models from high-resolution laboratory experiments.

Physically-based urban wash-off models are a promising means of studying the transport of finer suspended solids and their associated pollutants during rain events, considering spatial and temporal heterogeneities. This study contributes to the understanding of these models through an in-depth sensitivity analysis to provide the necessary information to simplify the model and deal with parameter identifiability. First, based on twelve tailored high-resolution experiments, the accurate measurement of input variables was used to study the parameters of the Hairsine-Rose sediment transport model through a global sensitivity analysis. Using Standardized Regression Coefficients (SRC) and Extended Fourier Amplitude Sensitivity Test (EFAST) methods, the analysis showed that both the total washed-off mass and the TSS peaks concentration are highly sensitive to the critical mass, which considers the reduction in the detachment of particles when the sediment available decreases and is scattered over the surface. In addition, the rain- and flow-driven detachment parameters were presented as key for smaller and larger sediment particles, respectively. Then, those uncertainties that are associated in field studies with the determination of the model input variables were also considered by conducting a local sensitivity analysis. The initial load of sediment and the mean grain size were seen to be the most important variables, thus underlining the need for very accurate measurements here. Moreover, a precise definition of Harsine-Rose parameters is also necessary to achieve reliable results in order to work on treatment and management techniques to minimize the impact of urban surface contaminants on urban environments.

Neutropenia management and granulocyte colony-stimulating factor use in patients with solid tumours receiving myelotoxic chemotherapy--findings from clinical practice.

PURPOSE: Clinical practice adherence to current guidelines that recommend primary prophylaxis (PP) with granulocyte colony-stimulating factors (G-CSFs) for patients at high (≥20 %) overall risk of febrile neutropenia (FN) was evaluated. METHODS: Adult patients with breast cancer, non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), or ovarian cancer were enrolled if myelotoxic chemotherapy was planned, and they had an investigator-assessed overall FN risk ≥20 %. The primary outcome was FN incidence. RESULTS: In total, 1,347 patients were analysed (breast cancer, n = 829; NSCLC, n = 224; SCLC, n = 137; ovarian cancer, n = 157). Patients with breast cancer exhibited fewer individual FN risk factors than patients with other cancers and were far more likely to have received a high-FN-risk chemotherapy regimen. However, a substantial proportion of all patients (45-80 % across tumour types) did not receive G-CSF PP in alignment with investigator risk assessment and guideline recommendations. FN occurred in 127 patients overall (9 %, 95% confidence interval (CI) 8-11 %), and incidence was higher in SCLC (15 %) than other tumour types (8 % in ovarian and NSCLC, 9 % in breast cancer). A post hoc analysis of G-CSF use indicated that G-CSF prophylaxis was not given within the recommended timeframe after chemotherapy (within 1-3 days) or was not continued across all cycles in 39 % of patients. CONCLUSIONS: FN risk assessment was predominantly based on clinical judgement and individual risk factors, and guidelines regarding G-CSF PP for patients at high FN risk were not consistently followed. Improved education of physicians may enable more fully informed neutropenia management in patients with solid tumours.

Overland flow computations in urban and industrial catchments from direct precipitation data using a two-dimensional shallow water model.

This paper presents the experimental validation and the application to a real industrial catchment of a two-dimensional depth-averaged shallow water model used for the computation of rainfall-runoff transformation from direct precipitation data. Instead of using the common approach in flood inundation modelling, which consists in computing the water depth and velocity fields given the water discharge, in this study the rainfall intensity is imposed directly in the model, the surface runoff being generated automatically. The model considers infiltration losses simultaneously with flow simulation. Gullies are also included in the model, although the coupling between the surface runoff and the sewer network is not considered. Experimental validation of the model is presented in several simplified laboratory configurations of urban catchments, in which the surface runoff has been measured for different hyetographs. The application to a real industrial catchment includes a sewer network flow component, which is solved with the SWMM model. The numerical predictions of the discharge hydrograph generated by a 12 hours storm event are compared with field measurements, providing encouraging results.

Adult stem cells applied to tissue engineering and regenerative medicine.

Regeneration takes place in the body at a moment or another throughout life. Bone, cartilage, and tendons (the key components of the structure and articulation in the body) have a limited capacity for self-repair and, after traumatic injury or disease, the regenerative power of adult tissue is often insufficient. When organs or tissues are irreparably damaged, they may be replaced by an artificial device or by a donor organ. However, the number of available donor organs is considerably limited. Generation of tissue-engineered replacement organs by extracting stem cells from the patient, growing them and modifying them in clinical conditions after re-introduction in the body represents an ideal source for corrective treatment. Mesenchymal stem cells (MSCs) are the multipotential progenitors that give rise to skeletal cells, vascular smooth muscle cells, muscle (skeletal and cardiac muscle), adipocytes (fat tissue) and hematopoietic (blood)-supportive stromal cells. MSCs are found in multiple connective tissues, in adult bone marrow, skeletal muscles and fat pads. The wide representation in adult tissues may be related to the existence of a circulating blood pool or that MSCs are associated to the vascular system.

Heart metastases and superior vena cava syndrome.

Superior vena cava syndrome (SVCS) may be due to a tumour infiltrating the right atrium. We present two patients with SVCS. The first one was secondary to solitary atrial metastases of rectal adenocarcinoma and benefited from palliative chemotherapy. The second patient had a disseminated large cell B-cell lymphoma with rapid clinical complete response, but she eventually died after relapse.

Heart metastases and superior vena cava síndrome

Superior vena cava syndrome (SVCS) may be due to a tumour infiltrating the right atrium. We present two patients with SVCS. The first one was secondary to solitary atrial metastases of rectal adenocarcinoma and benefited from palliative chemotherapy. The second patient had a disseminated large cell B-cell lymphoma with rapid clinical complete response, but she eventually died after relapse (AU)

Protocolo para diagnóstico y tratamiento de sarcomas de tejidos blandos del hospital de Basurto / Protocol for diagnosis and treatment of soft tissue sarcomas at the hospital of Basurto

La preservación de la función en el tratamiento de los sarcomas de tejidos blandos (STB) se consigue por medio de resecciones marginales, reconstrucción de tejidos blandos y terapia adyuvante sin que ello implique un aumento en las tasas de recidiva local, de metástasis o de mortalidad; exigen un abordaje multidisciplinario por lo que es necesario coordinar, bajo la forma de Comisión, a los diferentes especialistas que intervienen en las fases diagnóstica y terapéutica. Este es un artículo de revisión del diagnóstico y tratamiento de los sarcomas de tejidos blandos con motivo de la presentación del protocolo establecido en el Hospital de Basurto (Bilbao, España), vigente desde febrero de 2001 que intenta asegurar que los pacientes se beneficien de un tratamiento óptimo (AU)

The preservation of the function in the treatment of Soft Tissue Sarcomas (STS) has been achieved by means of marginal resections, reconstruction of soft tissues and adjuvant therapy without it implies an increase in the rates of local relapse, metastasis or mortality. It demands a multidisciplinary orientation for what is necessary to coordinate, under the form of Commission, the different specialists that take part in the diagnostic and therapeutic phases. This is a review article of the diagnosis and treatment of soft tissues sarcomas because of the protocol presentation settled down in the Hospital of Basurto (Bilbao, España), effective from February of 2001, that tries to assure patient’s benefit with optimal care (AU)

Informe de la actividad del comité de tumores de partes blandas del hospital de Basurto / Report of the activity of the soft tissue tumors committee of the hospital of Basurto

La captación, registro y seguimiento de los pacientes que padecen un tumor de partes blandas es un proceso necesario para asegurar que el paciente es tratado, para coordinar, de una forma completa y sin demoras las fases diagnóstica y terapéutica, y para valorar los resultados de los protocolos aplicados. Entre febrero de 2001 y julio de 2002 fueron presentados 106 pacientes en el Comité de Tumores de Partes Blandas (CTPB) del Hospital de Basurto (Bilbao, España). En esta publicación hacemos un informe descriptivo de la actividad de nuestro Comité y de su funcionamiento (AU)

The reception, registration and follow-up of patients that suffer from a soft tissue tumour are a necessary process to assure adecuate treatment of those patients, to coordinate, in a comprehensive way and without delays, the diagnostic and therapeutic steps and to evaluate the results of the applied protocols. Between February 2001 and July 2002, 106 patients were visited at the Soft Tissue Tumours Committee of the Hospital de Basurto (Bilbao, Espa- ña). In this publication we make a description of the patients included in our protocol and a comment on the way of working of the Committee (AU)

Tabaco, lactancia y sibilantes en los primeros tres años / Tobacco, infant feeding, and wheezing in the first three years of life

Antecedentes: Las enfermedades del tracto respiratorio inferior con sibilantes son frecuentes y problemáticas en los niños pequeños. Los únicos factores de riesgo evitables son la exposición al tabaco y el tipo de lactancia. Objetivo: Medir la influencia de esos factores de riesgo evitables sobre el riesgo de aparición de sibilantes en los primeros 3 años de vida. Métodos Estudio poblacional, con todos los niños nacidos entre enero de 1998 y noviembre de 2002, y atendidos desde el nacimiento en un centro de salud de Palencia. Precozmente tras el nacimiento, se recogió información sobre historia familiar, gestación, parto y hábito de fumar. La pauta de alimentación se identificó en visitas mensuales. Un pediatra identificó los episodios de sibilantes en los primeros 3 años. Resultados: Se incluyeron 234 niños, y 43 de ellos tuvieron al menos un episodio de sibilantes. Tras ajustar por sexo, historia familiar de alergia, tener hermanos mayores, edad materna y mes de nacimiento, no hubo asociación de la aparición de sibilantes con la lactancia materna exclusiva 3 meses (razón de riesgos [HR] = 0,83; intervalo de confianza del 95 por ciento [IC 95 por ciento], 0,42-1,64), ni con la exposición al tabaco sólo tras el nacimiento (HR = 1,2; IC 95 por ciento, 0,45-2,34). La exposición al tabaco durante la gestación se asociaba a mayor riesgo de sibilantes: HR = 2,54 (IC 95 por ciento, 1,18-5,48).Conclusiones La exposición prenatal al tabaco es el principal factor de riesgo modificable para la aparición de sibilantes en los primeros 3 años (AU)

[Tobacco, infant feeding, and wheezing in the first three years of life]. / Tabaco, lactancia y sibilantes en los primeros tres años.

BACKGROUND: Wheezing lower respiratory tract diseases are frequent and troublesome in young children. However, the only avoidable risk factors for them are tobacco smoke exposure and feeding practices. OBJECTIVE: To measure the influence of these avoidable factors on the risk of wheeze in the first 3 years of life. METHODS: We performed a population study including all the children born between January 1998 and November 2002 who were attended in the same primary health center in Palencia (Spain) from birth. Information on family history, pregnancy, delivery, and smoking was obtained soon after birth. Feeding practices were recorded on monthly visits. Wheezing episodes in the first 3 years of life were identified by a pediatrician. RESULTS: Two hundred thirty-four children were included and 43 had at least one episode of wheezing. The results were adjusted by sex, prematurity, a family history of allergy, having older siblings, maternal age, and month of birth. No association was found between wheezing and exclusive breast feeding for 3 months (hazard ratio [HR] 5 0.83, 95 % CI: 0.42-1.64), or with postnatal exposure to tobacco smoke (HR 5 1.2, 95 % CI: 0.45-2.34). Tobacco smoke exposure during pregnancy was associated with a higher risk of wheezing: HR 5 2.54 (95 % CI: 1.18-5.48). CONCLUSIONS: Prenatal exposure to tobacco smoke is the main modifiable risk factor for wheezing diseases in the first 3 years of life.

High-dose mitoxantrone and cyclophosphamide without stem cell support in patients with high-risk and advanced breast carcinoma: a Phase II multicentric trial.

BACKGROUND: Currently employed high-dose regimens for patients with breast carcinoma consist mainly of single-cycle combinations of alkylating agents. In a previous Phase I trial, the authors developed a tandem high-dose combination of two cycles of mitoxantrone and cyclophosphamide for the treatment of patients with metastatic breast carcinoma (MBC) and high-risk breast carcinoma (HRBC). Treatment was delivered with granulocyte-colony stimulating factor (G-CSF) but without stem cell support to avoid potential tumor cell reinfusion. The objective was to validate the safety and obtain preliminary efficacy assessment of this combination in a Phase II trial. METHODS: Fifty-three patients were included: 27 patients with MBC and 26 patients with HRBC. After standard induction treatment, patients received two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 separated by a 4-week interval. Patients received G-CSF and ciprofloxacin until hematologic recovery. Follow-up was performed in an outpatient setting. RESULTS: One hundred one of 106 projected cycles (95%) were delivered. The mean dose intensities achieved were mitoxantrone 5.8 mg/m2 per week and cyclophosphamide 933 mg/m2 per week. Infection developed in 46% of the cycles, and platelet transfusions were required in 42%. Nonhematologic toxicity was mainly Grade 3 emesis. There were no toxic deaths. In 17 evaluable patients with MBC, 13 patients (77%) had response improvements, including 7 complete responses (41%). CONCLUSIONS: Treatment with two cycles of mitoxantrone 25 mg/m2 and cyclophosphamide 4000 mg/m2 with G-CSF but without stem cell support was well tolerated. The dose intensities achieved approach those obtained with conventional high-dose therapy. This combination warrants further investigation as an alternative to conventional high-dose regimens.

Tratamiento domiciliario del cáncer avanzado de células renales basado en Interlukina-2 / Interleukin-2-based home therapy in advanced renal cell cancer

Propósito: Determinar la eficacia clínica y toxicidad de la interleukina 2 (rIL-2) administrada por vía subcutánea (s.c) y de forma ambulatoria en pacientes con carcinoma de células renales avanzado (ARCC). Material y métodos: Veintitrés pacientes consecutivos sin tratamiento previo con diagnóstico histológico de ARCC y enfermedad progresiva fueron incluidos en el estudio. La rlL-2 fue administrada por vías a una dosis de 18 millones 3 veces por semana o 9 millones 4 veces a la semana. Resultados: Veintitrés pacientes fueron evaluables pura toxicidad. Solo 2 pacientes toleraron la dosis de 18 millones 3 veces a la semana. Doce pacientes experimentaron fiebre con el tratamiento. Síntomas gripales severos fueron recogidos en 11 pacientes y chica de dolor/celulitis en la zona de la inyección fue referido por 6 pacientes. Dieciocho pacientes desarrollaron una leucocitosis reversible pero no se observó toxicidad hematológica o clínica de permeación vascular. Ningún paciente de 21 considerados evaluables para actividad respondió al tratamiento, 15 tuvieron una enfermedad estable y 6 una enfermedad progresiva. La mediana de tiempo a la progresión y supervivencia global fue de 12 semanas (intervalo de confianza al 95porciento; 2-38 semanas) y 42 semanas (10-75 semanas) respectivamente. Conclusiones: La dosis administrada a las dosis y esquema antes mencionadas no ha demostrado eficacia terapéutica en los pacientes con ARCC ocasionando una moderada a severa toxicidad no hematológica (AU)

A phase II trial of cyclophosphamide, epirubicin and vinorelbine in the treatment of advanced breast cancer.

BACKGROUND: Vinorelbine (Navelbin; N) has proven to be active in patients with advanced breast cancer (ABC) and cyclophosphamide (C) and epirubicin (Epiadriamycin: E) are still among the main cytostatic agents against this tumor. On this basis was carried out a study to determine the activity and toxicity of the combination of these three agents (CEN). PATIENTS AND METHOD: From April 1996 to March 1998, 59 patients with ABC were recruited of whom 56 were found eligible and evaluable for toxicity and 55 for activity. The treatment regimen was C: 400 mg/m2, E: 30 mg/m2 and N: 25 mg/m2 administered intravenously on days 1 and 8 of a 28-day cycle. RESULTS: The median number of cycles administered was 6 (range: 1-16). The most common hematological toxicity was grade (G) 3 and 4 neutropenia occurring in 36% of patients, associated with fever in 7% of them. Grade 3-4 thrombocytopenia and anemia occurred in 5% and 7%, respectively. Other G2-G3 non hematologic toxicities were: N/vomiting in 34%, alopecia in 73% and mucositis in 11% of patients. An objective response was achieved in 28 of 56 patients (50%) (95% confidence interval (CI): 37-63%): complete response (CR) in 9%, partial response (PR) in 41%. The median duration of response, time to progression and overall survival time was 54, 47 and 90 weeks, respectively. CONCLUSION: The CEN combination at these doses and treatment schedule appears to have acceptable tolerability but there is no apparent improvement in therapeutic efficacy when compared to other regimens used as first line treatment in ABC.

[Risk factors in the elderly. A study of 143 patients]. / Factores de riesgo en ancianos. Estudio de 143 pacientes.

UNLABELLED: Growing old is a process of natural diminish with decrease of biological answer to extrinsic and intrinsic factors and a bigger risk of presenting cardiovascular and metabolic processes. The aim of this study has been to analyse the incidence of cardiovascular factors in an aged population from Almería. PATIENTS AND METHODS: The group is by 172 patients (29 gave up); average global age 72.6 +/- 6.1 (85 women and 58 men). In all cases history and a whole clinic exam have been undertaken; general analytical study (glucose, creatinine, hepatic function cholesterol, HDL-c, LDL-c, trigliceride fibrinogen, microalbuminuria, etc.); blood pressure. STATISTICS: T Students, varianza analysis, Kolmogorov-Smirnov test. RESULTS: With regard to overweight, this was bigger in women (32.1 +/- 4.8 Kg/m2) in relation to men (27.9 +/- 4 Kg/m2). The most frequent risk factor has been hypertension (50.3%) followed by over weight-obesity (46.8%) and hypercholesterolemia (45.4%), only 11.2% did not present any risk factor; shile three factors appeared in 29.5%. Hypertension patients have more risk factors (increase of cholesterol and triglicerids, obesity, diabetes) than normotensive old patients; also diabetic patients have a bigger cardiovascular and lipid risk than non diabetic patients. The ingestion of estatinas or fibrates improves the lipid profile of old patients. In summarizing, conventional therapy can improve the cardiologic and metabolic situation, decreasing so the morbidity and mortality of old patients.