Multi-omics Characterization of Response to PD-1 Inhibitors in Advanced Melanoma.

Immunotherapy improves the survival of patients with advanced melanoma, 40% of whom become long-term responders. However, not all patients respond to immunotherapy. Further knowledge of the processes involved in the response and resistance to immunotherapy is still needed. In this study, clinical paraffin samples from fifty-two advanced melanoma patients treated with anti-PD-1 inhibitors were assessed via high-throughput proteomics and RNA-seq. The obtained proteomics and transcriptomics data were analyzed using multi-omics network analyses based on probabilistic graphical models to identify those biological processes involved in the response to immunotherapy. Additionally, proteins related to overall survival were studied. The activity of the node formed by the proteins involved in protein processing in the endoplasmic reticulum and antigen presentation machinery was higher in responders compared to non-responders; the activity of the immune and inflammatory response node was also higher in those with complete or partial responses. A predictor for overall survival based on two proteins (AMBP and PDSM5) was defined. In summary, the response to anti-PD-1 therapy in advanced melanoma is related to protein processing in the endoplasmic reticulum, and also to genes involved in the immune and inflammatory responses. Finally, a two-protein predictor can define survival in advanced disease. The molecular characterization of the mechanisms involved in the response and resistance to immunotherapy in melanoma leads the way to establishing therapeutic alternatives for patients who will not respond to this treatment.

Evaluation of the better operative outcome software tool to predict cataract surgical outcome in the early postoperative follow-up.

BACKGROUND: Cataracts are the world's leading cause of avoidable blindness. In low-income countries, there are high rates of poor follow-up, which makes it very difficult to monitor surgical outcomes. To address this issue, the Better Operative Outcome Software Tool (BOOST Cataract app) predicts outcome on the first postoperative day and provides specific advice to improve outcomes. The aim of the study is to evaluate the ability of the BOOST Cataract app to categorise surgical outcomes and to analyse the possible factors that contribute to its performance. This was a prospective observational study performed at the General Hospital of Hospitalet of Llobregat. RESULTS: A total of 126 cataracts were included. Patients had a mean [SD] age of 75.8 [12.19] years, and 52% were females. Manual small-incision cataract surgery was involved in 57% and phacoemulsification in 43%. Thirty-eight percent of eyes presented significant corneal oedema on day 1. The BOOST Cataract app succeeded in categorising the final outcome in 65.6% of the eyes and in 93,4% of the eyes with good outcome.The agreement between the BOOST and UDVA outcomes was 0.353 (p< .000). The level of agreement improved to 0.619 (p< .000) in eyes with clear corneas. Success obtained by BOOST for both types of surgery was not statistically different. Eyes that obtained a good outcome on day one after surgery and eyes with clear cornea had 37 times higher odds (95% CI 6.66, 212.83) and 12 times higher odds (95% CI 3.13, 47.66) of being correctly categorised by the BOOST Cataract app than eyes that obtained a suboptimal (moderate and poor) outcome and eyes with corneal oedema on day 1. CONCLUSIONS: The BOOST Cataract app is an e-Health tool designed to address issues of measuring quality in low- and middle-income settings. Although its reliability is limited to eyes that obtain a good outcome and with clear corneas on day 1, the use of the tool on a regular basis facilitates monitoring and reporting outcomes when clinical data collection is challenging due to low postoperative follow-up rates.

[Assessment model for evaluating the preparedness plan for COVID-19 in a tertiary care hospital]. / Modelo de evaluación del plan de respuesta frente a la pandemia de COVID-19 en un hospital de tercer nivel.

BACKGROUND AND PURPOSE: During the first wave of the epidemic caused by SARS-CoV-2, hospitals have come under significant pressure. This scenario of uncertainty, low scientific evidence, and insufficient resources, has generated significant variability in practice between different health organisations. In this context, it is proposed to develop a standards-based model for the evaluation of the preparedness and response system against COVID-19 in a tertiary hospital. MATERIALS AND METHODS: The study, carried out at the University Hospital of Vall d'Hebron in Barcelona (Spain), was designed in two phases: 1) development of the standards-based model, by means of a narrative review of the literature, analysis of plans and protocols implemented in the hospital, a review process by expert professionals from the centre, and plan of action, and 2) validation of usability and usefulness of the model through self-assessment and hospital audit. RESULTS: The model contains 208 standards distributed into nine criteria: leadership and strategy; prevention and infection control; management of professionals and skills; public areas; healthcare areas; areas of support for diagnosis and treatment; logistics, technology and works; communication and patient care; and information and research systems. The evaluation achieved 85.2% compliance, with 42 areas for improvement and 96 good practices identified. CONCLUSIONS: Implementing a standards-based model is a useful tool to identify areas for improvement and good practices in COVID-19 preparedness and response plans in a hospital. In the current context, it is recommended to repeat this methodology in other non-hospital and public health settings.

SEOM Clinical Guideline for gastrointestinal sarcomas (GIST) (2016).

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract, and this disease has served as a paradigmatic model for successful rational development of targeted therapies. The introduction of tyrosine kinase inhibitors with activity against KIT/PDGFRA in both localized and advanced stages has remarkably improved the survival in a disease formerly deemed resistant to all systemic therapies. The Spanish Society of Medical Oncology (SEOM) guidelines provide a multidisciplinary and updated consensus for the diagnosis and treatment of GIST patients. We strongly encourage that the managing of these patients should be performed within multidisciplinary teams in reference centers.

Evaluación de la técnica de análisis domiciliario de glucemia capilar entre la población con diabetes de siete comunidades autónomas de España / Evaluation of the home blood glucose self-monitoring technique among the population with diabetes in seven Spanish regions

Introducción. Son conocidas la importancia y la trascendencia de la técnica de glucemia capilar, que puede mejorar el control metabólico de las personas con diabetes mellitus (DM). Objetivos. Conocer y evaluar la realización correcta de la técnica de glucemia capilar entre la población con DM y comparar, si existe, correlacion entre esta técnica y la frecuencia de autoanálisis con el grado de control glucémico de la enfermedad. Materiales y método. Estudio multicéntrico, aleatorizado y sistemático en el que se incluyó a personas con DM de siete comunidades autónomas de España, que realizaron análisis domiciliarios de glucemia capilar entre el 1 de enero y el 30 de septiembre de 2010. Resultados. Se analizaron los datos de 455 pacientes con una distribución por zona geográfica y sexo (53%, mujeres; 47%, varones). En cuanto a la evaluación sobre la técnica de glucemia capilar y glucómetros utilizados, un 87% reutiliza las lancetas (40%, más de 10 veces). El 42% no realiza rotación en zonas de punción. Sólo el 58% refiere lavado previo de manos y el 13% utiliza antisépticos, mayoritariamente alcohol. Un 20% no tiene un criterio claro de cuándo y para qué hacerse autoanálisis y un 60% no modifica su tratamiento tras los resultados. El 89% de los pacientes del estudio presentaba un dispositivo para la punción capilar sucio y/o roto. El 60% de los glucómetros requería algún tipo de codificación previa, y en 20 de ellos era incorrecta; el 26% no tenía mensajes de alerta y un 4% presentaba tiras caducadas. Un 9% de la muestra no tenía hemoglobina glucosilada (HbA1C) registrada (83% eran pacientes con DM tipo 2) y el 70% de las registradas era superior al 7%. Conclusiones. Los resultados obtenidos en nuestro estudio muestran la necesidad no sólo de enseñar la realización correcta de la técnica de autoanálisis, sino también que los profesionales la evalúen de forma periódica, así como revisar los glucómetros, los dispositivos de punción capilar y las zonas de punción de los dedos. Teniendo en cuenta que la tasa de reutilización de lancetas encontrada es muy elevada, cabe reflexionar sobre la bioseguridad de los pacientes que realizan esta práctica. En cuanto a los sistemas utilizados, se ha observado un conocimiento escaso de ellos sobre cuestiones tan importantes como codificación, caducidad de tiras, mensajes de alerta, entre otros, unas especificaciones que son importantes y que pueden alterar el resultado real y, por tanto, la toma de decisiones. Un número importante de pacientes presentaba un mal control metabólico, que coincidía con otras series publicadas y, a pesar de las recomendaciones actuales propuestas por las sociedades científicas, no se realizaron las modificaciones indicadas por ellas en relación con la frecuencia tanto de HbA1C, como de autoanálisis(AU)

Background. The importance and significance of the blood glucose self monitoring technique on improving the quality of life in people with diabetes is well known. Objectives. To determine and evaluate the correct performance of the blood glucose self-monitoring technique among the diabetes mellitus population and to compare this technique and the blood glucose self-monitoring frequency with the degree of glycaemic control of the disease. Material and methods. It is a multicentre, randomised and systematic study in which a population with diabetes mellitus from seven Spanish Regions who performed home blood glucose self-monitoring tests between January 1st and September 30th 2010 were included. Results. Data from 455 patients were analyzed with an equal distribution regarding geographic area and gender (53% females, 47% males). Related to the evaluation of the blood glucose self monitoring technique and the glucose meters used for this purpose, 87% re-used the lancets (40% more than 10 times). 42% did not rotate puncture areas. Only 58% mentioned a previous hand-washing and 13% used antiseptics, mainly alcohol. Some patients (20%) had no clear idea about when and for what purpose they performed the blood glucose self-monitoring test and 60% did not modify the treatment according to the results. Most of the study patients (89 %) had a dirty and/or broken capillary puncture device. The majority (60%) of the glucose meters required some kind of previous coding, which was not correct in 20 of them; 26% did not have alert messages and 4% had expired test strips. Nine per cent of the sample had not recorded any HbA1C (83% were DM2 patients) and 70% of those recorded were > 7%. Conclusions. According to the results of our study, it is shown that not teaching the correct use of the blood glucose self-monitoring technique is needed, but it must also be evaluated periodically by the professionals. Both the glucose meters and capillary puncture devices also need to be reviewed, taking into account the very high re-use rate of the lancets found. We must think carefully about the biosecurity of the patients who perform this technique. Regarding the used devices, a lack of knowledge about them is shown as regards important issues such as coding, test strips expiry date and alert messages among others. These are very important as they are able to alter the true results, and therefore the decission making process. A high number of patients had poor metabolic control, which is in agreemnt other published series and, despite the current recommendations proposed by the Scientific Societies, the modifications suggested related to the frequency of both HbA1C and blood glucose self-monitoring were not performed(AU)

Phase II study of capecitabine as palliative treatment for patients with recurrent and metastatic squamous head and neck cancer after previous platinum-based treatment.

BACKGROUND: Platinum-based therapy (PBT) is the standard therapy for recurrent and/or metastatic head and neck cancer (HNC), but the incidence of recurrence remains high. This study evaluates the efficacy and tolerability of capecitabine as palliative monotherapy for recurrent HNC previously treated with PBT. METHODS: Patients aged 18-75 years, with Eastern Cooperative Oncology Group performance status 0-2, squamous HNC with locoregional and/or metastatic recurrence previously treated with PBT and adequate organ functions, were included. Capecitabine (1.250 mg m(-2) BID) was administered on days 1-14 every 21 days for at least two cycles. RESULTS: A total of 40 male patients with a median age of 58 years were analysed. All patients received a median number of four cycles of capecitabine (range: 1-9) and the median relative dose intensity was 91%. Seven patients were not evaluable for response. Overall response rate was 24.2%. Median time to progression and overall survival were 4.8 and 7.3 months, respectively. Haematological adverse events (AEs) grade 3/4 were reported in six patients. Most common grade 3/4 non-haematological AEs were asthenia (12.5%), palmar-plantar eritrodisestesia (10%), mucositis (10%), dysphagia (10%) and diarrhoea (7.5%). CONCLUSIONS: Capecitabine seems to be an active, feasible and well-tolerated mode of palliative treatment for advanced HNC patients who have previously received PBT schedules.

[Vertebral osteomyelitis caused by Streptococcus agalactiae in healthy adults. Description of 2 new cases]. / Osteomielitis vertebral por Streptococcus agalactiae en adultos sanos: descripción de 2 nuevos casos.

The importance of Streptococcus agalactiae as a pathogen in nonpregnant adults has been widely recognized in recent years, especially in the elderly or immunocompromised patients. Two cases of vertebral osteomyelitis caused by S. agalactiae in young patients with no known underlying diseases or predisposing factor to infection are reported. A systematic review of the literature (MEDLINE, 1976-May 2008) was performed, 10 cases previously reported in the literature of vertebral osteomyelitis due to S. agalactiae being found in adults under 65 years of age with no predisposing risk factors for infection, most of which have been reported over the last 10 years. We believe that this microbial etiology should be considered in patients of any age and immunological status. Other factors, other than increasing the number of patients with chronic diseases, explaining the increased rate of S. agalactiae infections in adults need to be studied.

Osteomielitis vertebral por Streptococcus agalactiae en adultos sanos: descripción de 2 nuevos casos / Vertebral osteomyelitis caused by Streptococcus agalactiae in healthy adults. Description of 2 new cases

La importancia de Streptococcus agalactiae como patógeno en adultos fuera del período gestacional ha quedado bien demostrada en los últimos años, afectando a pacientes de edad avanzada o con inmunodepresión. Se describen 2 casos de osteomielitis vertebral por S. agalactiae en pacientes jóvenes sin enfermedad de base conocida ni factor predisponente de infección. Se realiza una revisión sistemática de la literatura (MEDLINE, 1976-Mayo 2008), encontrando 10 casos previamente publicados de osteomielitis vertebral por S. agalactiae en adultos menores de 65 años y sin ningún factor predisponente de infección, la mayoría publicados en los últimos 10 años. Consideramos que esta etiología microbiana debe ser tenida en cuenta en pacientes de cualquier edad y estado inmunológico. Otros factores, distintos al aumento del número de pacientes con enfermedades crónicas, que expliquen el incremento en la incidencia de las infecciones por S. agalactiae en adultos deben ser estudiados (AU)

The importance of Streptococcus agalactiae as a The importance of Streptococcus agalactiae as a pathogen in nonpregnant adults has been widely recognized in recent years, especially in the elderly or immunocompromised patients. Two cases of vertebral osteomyelitis caused by S. agalactiae in young patients with no known underlying diseases or predisposing factor to infection are reported. A systematic review of the literature (MEDLINE, 1976-May 2008) was performed, 10 cases previously reported in the literature of vertebral osteomyelitis due to S. agalactiae being found in adults under 65 years of age with no predisposing risk factors for infection, most of which have been reported over the last 10 years. We believe that this microbial etiology should be considered in patients of any age and immunological status. Other factors, other than increasing the number of patients with chronic diseases, explaining the increased rate of S. agalactiae infections in adults need to be studied (AU)

Influence of metyrapone treatment during pregnancy on the development and maturation of brain monoaminergic systems in the rat.

AIM: This study examines the effect of reducing the corticosterone levels of gestating rat dams on the postnatal development and maturation of monoaminergic systems in their offspring's brains. METHODS: Metyrapone, an inhibitor of CORT synthesis, was administered to pregnant rats from E0 to E17 of gestation. Monoamine concentrations were determined in male and female offspring at postnatal days (PN) 23 and 90 in the hippocampus, hypothalamus and striatum. RESULTS: Reducing maternal corticosterone (mCORT) during gestation led to alterations in dopamine and serotonin levels in all three brain areas studied at PN 23. Alterations persisted until at least PN 90 in the serotonergic systems; the dopamine content of the hippocampus also remained modified. Reduced mCORT during gestation also led to alterations in the development and maturation of the hypothalamic noradrenergic systems. Sexually dimorphic responses were observed in all these monoaminergic systems at different times. CONCLUSION: These results suggest that while they are still developing, brain monoaminergic systems are particularly sensitive to epigenetic influences. An adequate foetal level of CORT is required for the normal ontogeny of brain monoaminergic systems. The present data also provide that during the critical period of brain development, maternal CORT plays an important role in the sexual differentiation of monoaminergic systems, with particular influence on brain serotonergic neurones.

The foreign language cocktail party problem: Energetic and informational masking effects in non-native speech perception.

Studies comparing native and non-native listener performance on speech perception tasks can distinguish the roles of general auditory and language-independent processes from those involving prior knowledge of a given language. Previous experiments have demonstrated a performance disparity between native and non-native listeners on tasks involving sentence processing in noise. However, the effects of energetic and informational masking have not been explicitly distinguished. Here, English and Spanish listener groups identified keywords in English sentences in quiet and masked by either stationary noise or a competing utterance, conditions known to produce predominantly energetic and informational masking, respectively. In the stationary noise conditions, non-native talkers suffered more from increasing levels of noise for two of the three keywords scored. In the competing talker condition, the performance differential also increased with masker level. A computer model of energetic masking in the competing talker condition ruled out the possibility that the native advantage could be explained wholly by energetic masking. Both groups drew equal benefit from differences in mean F0 between target and masker, suggesting that processes which make use of this cue do not engage language-specific knowledge.

Effect of masker type on native and non-native consonant perception in noise.

Spoken communication in a non-native language is especially difficult in the presence of noise. This study compared English and Spanish listeners' perceptions of English intervocalic consonants as a function of masker type. Three maskers (stationary noise, multitalker babble, and competing speech) provided varying amounts of energetic and informational masking. Competing English and Spanish speech maskers were used to examine the effect of masker language. Non-native performance fell short of that of native listeners in quiet, but a larger performance differential was found for all masking conditions. Both groups performed better in competing speech than in stationary noise, and both suffered most in babble. Since babble is a less effective energetic masker than stationary noise, these results suggest that non-native listeners are more adversely affected by both energetic and informational masking. A strong correlation was found between non-native performance in quiet and degree of deterioration in noise, suggesting that non-native phonetic category learning can be fragile. A small effect of language background was evident: English listeners performed better when the competing speech was Spanish.