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Background: In a previous paper, we have demonstrated that: (1) local injection of corticosteroids for carpal tunnel syndrome (CTS) is as effective as decompressive surgery, at 1-year follow-up; and (2) surgery has an additional benefit in the 2-year follow-up. In this study, we assess the long-term outcomes of both therapies in an observational extension of the patients originally enrolled in our randomized clinical trial. Methods: Patients were included in an open, randomized clinical trial, comparing injections versus surgery in CTS. After the end of the clinical trial, patients received the treatment prescribed by their general practitioner or specialist. Therapeutic failure was defined as the need of any new therapeutic intervention on the involved wrist. Comparison between groups was made using Cox multiple regression analysis. Estimation of the accumulated incidence of new therapeutic failure was made considering the withdrawal as a competitive risk (Gooley’s test). Results: Of 163 randomized wrists at the beginning of the study, only 148 were available at the final follow-up. The mean follow-up was 6.3 and the median was 5.9 years. In the long-term follow-up, the accumulated incidence of therapeutic failure in the surgery group was 11.6% versus 41.8% in the injection group. The Cox multiple regression analysis showed a risk of failure associated with injection group of 4.5 (95% confidence interval [CI], 2.1-9.8; P < .0001). Conclusions: In long-term follow-up, surgery seems more effective than local corticosteroid injections in primary CTS. Nonetheless, about 58% of the patients in the injection group will not need further therapeutic interventions during the follow-up.

Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Resumen Objetivo: Revisar la utilidad pronostica de la radiografia de torax en la seleccion de pacientes con sospecha de infeccion por SARS-CoV-2. Material y metodos: Estudio observacional, descriptivo y transversal, realizado en 978 pacientes con sospecha de infeccion por SARS-CoV-2 a los que se les hizo una radiografia de torax en el servicio de urgencias de un hospital terciario, en marzo de 2020. Se analizaron variables demograficas, clinicas y pronosticas por separado en pacientes con RT-PCR (reaccion en cadena de la polimerasa por transcriptasa inversa) hecha (grupo 1, n = 535) o no hecha por baja sospecha clinica (grupo 2, n = 443). Resultados: En el grupo 1 se observo una prevalencia de SARS-CoV-2 del 70,4%. La radiografia mostro una sensibilidad del 62,8%. En el grupo 2, la radiografia fue negativa en el 97,5%, corroborando la baja sospecha clinica, y fueron dados de alta;de ellos, el 5,6% volvio a consultar con formas leves de la enfermedad. En el grupo 1 no se observaron diferencias estadisticamente significativas en el porcentaje de radiografias de torax patologicas entre los pacientes ingresados en plantas hospitalarias (68,3%) y los ingresados en la unidad de cuidados intensivos (72,9%), (p = 0,22). Conclusion: En situacion de pandemia, los pacientes con baja sospecha clinica y radiografia negativa pueden ser dados de alta con baja probabilidad de volver a consultar o de desarrollar formas graves de la enfermedad. En los pacientes con SARS-CoV-2 positivo, la radiografia de torax inicial no tiene utilidad pronostica. Objective: To review the prognostic usefulness of chest X-rays in selecting patients with suspected SARS-CoV-2 infection. Material and methods: This cross-sectional descriptive observational study analyzed 978 patients with suspected SARS-CoV-2 infections who underwent chest X-ray examinations in the emergency department of a tertiary hospital in March 2020. We separately analyzed demographic, clinical, and prognostic variables in two groups of patients: those in whom reverse-transcriptase polymerase chain reaction (RT-PCR) was done (n=535) and those in whom RT-PCR was not done because of low clinical suspicion (n=443). Results: In the group of patients with RT-PCR, the prevalence of SARS-CoV-2 was 70.4%, and the sensitivity of chest X-rays was 62.8%. In the group of patients without RT-PCR, chest X-rays were negative in 97.5%, corroborating the low clinical suspicion;these patients were discharged, and 5.6% of them reconsulted with mild forms of the disease. In the group of patients with RT-PCR, we observed no statistically significant differences in the percentage of pathologic chest X-rays between patients hospitalized in the ICU (72.9%) and in those hospitalized in other wards (68.3%) (p=0.22). Conclusion: In the context of the pandemic, patients with low clinical suspicion and negative chest X-rays can be discharged with a low probability of reconsultation or of developing severe COVID19. In patients with RT-PCR positive for SARS-CoV-2, chest X-rays have no prognostic usefulness.

Background In comatose patients receiving oro-tracheal intubation for mechanical ventilation (MV), the risk of aspiration is increased. Aspiration can lead to chemical pneumonitis (inflammatory reaction to the gastric contents), or aspiration pneumonia (infection caused by inhalation of microorganisms). Distinguishing between the two types is challenging. We tested the interest of using a decisional algorithm based on procalcitonin (PCT) values to guide initiation and discontinuation of antibiotic therapies in intubated patients. Methods The PROPASPI (PROcalcitonin Pneumonia/pneumonitis Associated with ASPIration) trial is a multicenter, prospective, randomized, controlled, single-blind, superiority study comparing two strategies: (1) an intervention group where threshold PCT values were used to guide initiation and discontinuation of antibiotics (PCT group); and (2) a control group, where antibiotic therapy was managed at the physician’s discretion. Patients aged 18 years or over, intubated for coma (Glasgow score ≤ 8), with MV initiated within 48 h after admission, were eligible. The primary endpoint was the duration of antibiotic treatment during the first 15 days after admission to the ICU. Results From 24/2/2015 to 28/8/2019, 1712 patients were intubated for coma in the 5 participating centers, of whom 166 were included in the study. Data from 159 were available for intention-to-treat analysis: 81 in the PCT group, and 78 in the control group. Overall, 67 patients (43%) received antibiotics in the intensive care unit (ICU); there was no significant difference between groups (37 (46%) vs 30 (40%) for PCT vs control, p = 0.432). The mean duration of antibiotic treatment during the first 15 days in the ICU was 2.7 ± 3.8 days; there was no significant difference between groups (3.0 ± 4.1 days vs 2.3 ± 3.4 days for PCT vs control, p = 0.311). The mean number of days under MV was significantly higher in the PCT group (3.7 ± 3.6 days) than in controls (2.7 ± 2.5 days, p = 0.033). The duration of ICU stay was also significantly longer in the PCT group: 6.4 ± 6.5 days vs 4.6 ± 3.5 days in the control group (p = 0.043). After adjustment for SAPS II score, the difference in length of stay and duration of mechanical ventilation between groups was no longer significant. Conclusion The use of PCT values to guide therapy, in comparison to the use of clinical, biological (apart from PCT) and radiological criteria, does not modify exposure to antibiotics in patients intubated for coma. Trial registration Clinicaltrials.gov Identifier NCT02862314.

BACKGROUND: Visual vertigo (VV), triggered by environmental or dynamic visual stimuli and repetitive visual patterns, can affect daily life activities. The Visual Vertigo Analogue Scale (VVAS) is a valid and reliable self-administered questionnaire to assess VV, which has been culturally adapted to the Argentine population but has not been validated. OBJECTIVE: To validate the Argentine version of VVAS (VVAS-A) by confirming its psychometric properties in patients with vestibular disorders. METHODS: Vestibular patients (n = 82) completed the VVAS-A and the Dizziness Handicap Inventory Argentine version (DHI-A) during their initial visit and one week later. The VVAS-A's internal consistency, test retest reliability, ceiling and floor effects, and construct validity were determined. Test-retest data (n = 71) was used to calculate reliability using the intraclass correlation coefficient (ICC 2.1). RESULTS: A ceiling effect was observed in 12 patients (14.6%). Internal consistency was acceptable (Cronbach’s alpha: 0.91). The reliability was r = 0.764 [CI 95%: 0.7 –0.86]). Correlations were observed between the VVAS-A and the total DHI-A score (rho = 0.571), the DHI-A physical subscale (rho: 0.578), and DHI-A functional and emotional subscales of the DHI-A (rho: 0.537 and 0.387, respectively). CONCLUSION: The VVA-A is a valid, reliable tool to evaluate VV in patients with vestibular disorders.

Resumen Introduccion El objetivo principal de nuestro estudio es valorar la seguridad y la eficacia de la colecistostomia percutanea para el tratamiento de la colecistitis aguda determinando la incidencia de efectos adversos que presentan los pacientes sometidos a este procedimiento. Material y metodo Estudio observacional con inclusion consecutiva de todos los pacientes con diagnostico de colecistitis aguda durante 10 anos. La variable principal estudiada ha sido la morbilidad (efectos adversos) recogida de forma prospectiva. Seguimiento minimo de un ano de los pacientes sometidos a colecistostomia percutanea. Resultados De 1.223 pacientes ingresados por colecistitis aguda, 66 pacientes han precisado colecistostomia percutanea. El 21% de estos han presentado algun efecto adverso, con un total de 22 efectos adversos. Tan solo 5 de estos efectos, presentados por 5 pacientes (7,6%), han podido ser atribuidos al propio drenaje vesicular. La mortalidad asociada a la tecnica es del 1,5%. Tras la colecistostomia un tercio de los pacientes (22 pacientes) han sido sometidos a colecistectomia. Se ha realizado intervencion quirurgica urgente por fracaso del tratamiento percutaneo en 2 pacientes, y diferida en otros 2 pacientes por recidiva del proceso inflamatorio. El resto de los pacientes colecistectomizados han sido intervenidos de forma programada pudiendose llevar a cabo el procedimiento de forma laparoscopica en 16 pacientes (72,7%). Conclusion Consideramos la colecistostomia percutanea como tecnica segura y eficaz por relacionarse con una baja incidencia de morbimortalidad, debiendose considerar como alternativa puente o definitiva en aquellos pacientes no tributarios de colecistectomia urgente tras fracaso del tratamiento conservador con antibiotico.

One of the most effective ways to improve quality of life in dementia is by exposing people to meaningful activities. The study of engagement is crucial to identify which activities are significant for persons with dementia and customize them. Previous work has mainly focused on developing assessment tools and the only available model of engagement for people with dementia focused on factors influencing engagement or influenced by engagement. This article focuses on the internal functioning of engagement and presents the development and testing of a model specifying the components of engagement, their measures, and the relationships they entertain. We collected behavioral and physiological data while participants with dementia (N = 14) were involved in six sessions of play, three of game-based cognitive stimulation and three of robot-based free play. We tested the concurrent validity of the measures employed to gauge engagement and ran factorial analysis and Structural Equation Modeling to determine whether the components of engagement and their relationships were those hypothesized. The model we constructed, which we call the ENGAGE-DEM, achieved excellent goodness of fit and can be considered a scaffold to the development of affective computing frameworks for measuring engagement online and offline, especially in HCI and HRI.

Resumen Objetivo Analizar la eficacia, adherencia, satisfaccion del paciente, seguridad, farmacodinamica y costo-efectividad del metotrexato (MTX) parenteral en pacientes con enfermedades reumaticas. Metodos Se llevo a cabo una revision sistematica basada en una estrategia de busqueda en Medline, Embase y Cochrane Library (inicio-06/2019). Se identificaron estudios que incluyeran pacientes adultos con enfermedades reumaticas en tratamiento con MTX parenteral y que analizaran datos de eficacia, adherencia, satisfaccion, seguridad, farmacocinetica o costo-efectividad. En cuanto a los disenos se permitieron revisiones sistematicas, ensayos clinicos o estudios observacionales, incluyendo transversales y estudios con muestras pequenas si eran estudios de farmacocinetica. Resultados De 4.160 articulos identificados, se incluyeron finalmente 80. El MTX parenteral parece util de manera general y en especial en aquellos pacientes con respuesta insuficiente a MTX oral. La via parenteral no parece aumentar la tasa ni la gravedad de los eventos adversos con respecto a la oral y podria reducir costes en aquellos pacientes con respuesta inadecuada a MTX oral. La adherencia y satisfaccion se ven favorecidas por programas de entrenamiento en la via parenteral. Los resultados en enfermedades reumaticas distintas a la artritis reumatoide (AR) son muy escasos y no permiten obtener datos concluyentes. Conclusiones El MTX por via parenteral podria ser una alternativa al uso de MTX oral, por su perfil de eficacia, seguridad, adherencia, satisfaccion y resultados farmaco-economicos, especialmente en pacientes con AR.

Graphical abstract, Introduction Impairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia. Methods COVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits. Results In total, 313, aged 61.12 ± 12.26 years, out of 481 included patients were available. The proportion of patients with DLCO

A 45-year-old female presented to hospital with confusion and visual disturbances. She had undergone a liver transplant 3 years prior for cirrhosis secondary to primary biliary cholangitis. Computed tomography and magnetic resonance imaging of the brain showed features consistent with posterior reversible encephalopathy syndrome. Her medications included tacrolimus, sirolimus, and prednisone. She reported smoking 4 grams of cannabis per day. Following cessation of tacrolimus, the patient’s encephalopathy and visual disturbances resolved. To our knowledge, this case represents the longest time elapsed from liver transplantation to the development of tacrolimus-associated posterior reversible encephalopathy syndrome in the literature. This case highlights the potential danger of cannabis use in transplant recipients who are on immunosuppressants such as tacrolimus. Clinicians should have a high index of suspicion for posterior reversible encephalopathy syndrome in post-transplant patients presenting with altered mental status, even years after liver transplantation, and be familiar with potential interactions between cannabis and immunosuppressants.

The number of people with dementia worldwide is estimated at 50 million by 2018 and continues to rise mainly due to increasing aging and population growth. Clinical impact of current interventions remains modest and all efforts aimed at the identification of new therapeutic approaches are therefore critical. Previously, we showed that JM-20, a dihydropyridine-benzodiazepine hybrid molecule, protected memory processes against scopolamine-induced cholinergic dysfunction. In order to gain further insight into the therapeutic potential of JM-20 on cognitive decline and Alzheimer's disease (AD) pathology, here we evaluated its neuroprotective effects after chronic aluminum chloride (AlCl3) administration to rats and assessed possible alterations in several types of episodic memory and associated pathological mechanisms. Oral administration of aluminum to rodents recapitulates several neuropathological alterations and cognitive impairment, being considered a convenient tool for testing the efficacy of new therapies for dementia. We used behavioral tasks to test spatial, emotional- associative and novel object recognition memory, as well as molecular, enzymatic and histological assays to evaluate selected biochemical parameters. Our study revealed that JM-20 prevented memory decline alongside the inhibition of AlCl3 -induced oxidative stress, increased AChE activity, TNF-α and pro-apoptotic proteins (like Bax, caspase-3, and 8) levels. JM-20 also protected against neuronal damage in the hippocampus and prefrontal cortex. Our findings expanded our understanding of the ability of JM-20 to preserve memory in rats under neurotoxic conditions and confirm its potential capacity to counteract cognitive impairment and etiological factors of AD by breaking the progression of key steps associated with neurodegeneration.

The peculiar electrophysiological properties of the sinoatrial node and the cardiac conduction system are key components of the normal physiology of cardiac impulse generation and propagation. Multiple genes and transcription factors and metabolic proteins are involved in their development and regulation. In this review, we have summarized the genetic underlying causes, key clinical findings, and the latest available clinical evidence. We will discuss clinical diagnosis and management of the genetic conditions associated with conduction disorders that are more prevalent in clinical practice, for this reason, very rare genetic diseases presenting sinus node or cardiac conduction system abnormalities are not discussed. Sin financiación No data JCR 2021 0.422 SJR (2021) Q3, 200/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEM

This study aimed to analyze the benefits of a lower-limb fast-velocity concentric resistance training on rate of force development, mobility, and quality of life in people with Multiple Sclerosis. A randomized controlled trial was conducted in 30 people with Multiple Sclerosis, who were randomly assigned to either an experimental (n=18) or a control (n=12) group. The experimental group carried out 10-weeks of fast-velocity concentric resistance training, while the control group did not perform any intervention. Early and late rate of force development during knee extension in both legs, sit-to-stand and Timed Up and Go tests and quality life questionnaire were evaluated before and after intervention. The training program evoked an increase in early rate of force development in experimental group (0–30; Rightleg: 63.9%, p

Objectives To determine how the COVID-19 lockdown influenced the lifestyle, eating behavior, use of substances, mental health, and weight in patients who had undergone bariatric surgery (BS) and explore the self-perception of one’s own health and fears related to COVID-19. Methods We performed a cross-sectional exploratory study in obesity patients who had undergone BS surgery > 1 year previously in a university hospital. Assessment was performed 40 days after initiating lockdown and included 2 periods: from April 24 until May 8 and during the initial de-escalation period: from May 9 until 22, 2020. A structured telephone interview and an online survey were administered. Results One hundred eighty-eight patients were interviewed; 156 also responded to the online survey (77% females, mean age 53.46 ± 10.48 years, mean follow-up 5.71 ± 4.30 years). Dietary habits were affected in 72% of the participants, with 15% reporting better diet planning; 83.5% reported having more sedentary behaviors; 27% and 36% showed depression and anxiety, respectively; and 45% of participants reported bad sleep quality. In relation to changes in the use of any substance, the use increased in the majority of patients who were previously users. Self-perception of one’s own health and fears related to COVID-19 were only moderate. Finally, emotional eating and time since BS were statistically significant risk factors for predicting weight gain. Conclusions Lockdown during COVID-19 pandemic negatively influenced the lifestyle, mental health, substance use, and weight in BS patients. These alterations were somewhat similar to those observed in the general population but more severe and with important clinical implications. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s11695-021-05792-1.

The case is presented on a young Honduran female with no medical history of note, who presented with multiple areas of exudative retinal detachment (RD), and a best-corrected visual acuity of 1.3logMAR in both eyes. She was diagnosed with incomplete Vogt-Koyanagi-Harada syndrome, and treated early with a combination of intravenous therapy with 1g of prednisolone per day for 3 days, as recommended by published evidence, as well as mycophenolate mofetil (2g per day). During the corticosteroids tapering, there was a recurrence of exudative retinal detachments, and megadoses of 1g of intravenous corticosteroids per day were reintroduced for 6 days until the complete resolution of the fluid of the exudative RD, and cyclosporine (100mg per day), subtenon triamcinolone (40mg/mL), and intravitreal ranibizumab once a month in the both eyes were added to the treatment, with a great control of choroidal inflammation that resulted in the remission of symptoms and signs.

Resumen Objetivo Evaluar el uso de la terapia con beneficio cardiovascular en pacientes con DM tipo 2 previo al ingreso en servicios de medicina interna. Metodos Estudio transversal en un dia de los pacientes con DM tipo 2 hospitalizados en servicios de medicina interna. Se recogieron variables demograficas y antropometricas, datos de laboratorio y utilizacion de farmacos antihiperglucemiantes. La variable desenlace fue la proporcion y los determinantes de uso de inhibidores del cotransportador sodio-glucosa 2 (iSGLT2) y de agonistas del receptor del peptido similar al glucagon tipo 1 (AR-GLP1). Resultados Se incluyeron 928 pacientes pertenecientes a 74 hospitales. La edad media fue 78,9 anos (DE: 10,86), un 50% varones. Un total de 557 (60%) presentaba cardiopatia isquemica, 189 (20,4%) enfermedad cerebrovascular, 293 (31,6%) insuficiencia cardiaca, 274 (29,5%) enfermedad renal cronica y 129 (13,9%) enfermedad arterial periferica. Los antihiperglucemiantes utilizados previo al ingreso fueron: sulfonilureas (5.7%), biguanidas (49.1%), inhibidores de la alfa-glucosidasa (0,2%), pioglitazona (0%), iDPP4 (39%), iSGLT2 (5,8%), AR-GLP1 (2,6%) y analogos de insulina basal (24%). La edad mayor de 75 anos fue el factor determinante principal para no utilizar iSGLT2 (OR ajustada 0,28; intervalo de confianza al 95%: 0,10-0,74; p = 0,039) o AR-GLP1 (OR ajustada 0,09; intervalo de confianza al 95%: 0,02-0,46; p = 0,006). Discusion Una gran proporcion de pacientes ancianos con DM tipo 2 de muy alto riesgo cardiovascular no recibe terapia antihiperglucemiante con farmacos de probado beneficio cardiovascular. El tratamiento mas frecuentemente utilizado fue metformina e iDPP4. Existe un margen de mejora en el tratamiento en esta poblacion de muy alto riesgo.

Resumen Introduccion y objetivos La laringectomia total (LT) es uno de los tratamientos disponibles en los carcinomas de laringe localmente avanzados o como rescate ante el fracaso de la preservacion de organo, logrando altas tasas de supervivencia y escasas complicaciones. El objetivo de nuestro trabajo es analizar los resultados oncologicos obtenidos, comparandolos con la literatura actual y analizando sus complicaciones y supervivencia. Metodos Se incluyeron 62 pacientes con carcinoma primario de laringe tratados mediante LT primaria o de rescate entre los anos 2003 y 2019. Analizamos las caracteristicas demograficas, clinicas y anatomopatologicas, el estadio tumoral, los tratamientos complementarios, las complicaciones postoperatorias, las recidivas locorregionales, las metastasis y las causas de muerte. Resultados Los pacientes tenian una edad media de 64 anos, el 90,3% eran hombres, el 96,8% eran fumadores y el 43,5% tenian pluripatologia. El 82,3% tenian un estadio localmente avanzado. Al 71% se les realizo LT primarias y al 29% de rescate. Al 59,6% se les practico vaciamiento cervical asociado. El 30,6% tenian invasion linfovascular, el 30,6% invasion perineural y el 14,5% afectacion de margenes. Durante el seguimiento, el 17,7% presentaron una recidiva locorregional y el 11,3% metastasis a distancia. En cuanto a tratamientos complementarios, el 56,4% de los pacientes recibieron tratamiento adyuvante. La incidencia de hemorragia fue del 11,3%, la de infeccion del 14,5% y la de fistula faringocutanea del 21%. Hubo significacion estadistica entre la fistula y la hemorragia (p = 0,000) y entre la fistula y la infeccion (p = 0,000). No se encontraron diferencias estadisticamente significativas entre los factores estudiados de la LT primaria y de rescate. La supervivencia global fue a los 3 anos del 92% y los 5 anos del 88%, encontrando significacion estadistica con el estadio localmente avanzado (p = 0,038), los T4 (p = 0,026), la invasion linfovascular (p = 0,019) y la afectacion de mas de 3 ganglios linfaticos en la anatomia patologica (p = 0,005). En el analisis multivariante la unica variable que mostro una relacion significativa fue la invasion linfovascular (p = 0,026). Conclusiones Aunque la preservacion de organo es un objetivo primordial, la LT sigue siendo un tratamiento referente en los carcinomas localmente avanzados y como rescate ante el fracaso de la terapia medica o la cirugia parcial.

Background. People with multiple sclerosis (MS) suffer from symptoms related to neural control, such as reduced central activation, lower muscle activity, and accentuated spasticity. A forced 9-week home confinement related to COVID-19 in Spain may have worsened these symptoms. However, no study has demonstrated the impact of home confinement on neuromuscular mechanisms in the MS population. This study was aimed at analyzing the effects of a 9-week home confinement on central activation, muscle activity, contractile function, and spasticity in MS patients. Methods. Eighteen participants were enrolled in the study. Left and right knee extensor maximum voluntary isometric contraction (MVIC), maximal neural drive via peak surface electromyography (EMG) of the vastus lateralis, central activation ratio (CAR), and muscle contractile function via electrical stimulation of the knee extensor muscles, as well as spasticity using the pendulum test, were measured immediately before and after home confinement. Results. Seventeen participants completed the study. CAR significantly decreased after lockdown ( ES = 1.271 , p < 0.001 ). Regarding spasticity, there was a trend to decrease in the number of oscillations ( ES = 0.511 , p = 0.059 ) and a significant decrease in the duration of oscillations ( ES = 0.568 , p = 0.038 ). Furthermore, in the left leg, there was a significant decrease in the first swing excursion ( ES = 0.612 , p = 0.027 ) and in the relaxation index ( ES = 0.992 , p = 0.001 ). Muscle contractile properties, MVIC, and EMG variables were not modified after confinement. Conclusions. The results suggest that a home confinement period of 9 weeks may lead to an increase in lower limb spasticity and a greater deficit in voluntary activation of the knee extensors.

Purpose Individuals with obesity frequently regain weigh after endoscopic bariatric therapies (EBT) unless they adhere to healthy habits. The objective was to create and validate a short, self-administered questionnaire (EMOVE) to assess healthy dietary and physical activity (PA) habits’ adherence to be used in clinical practice. Materials and Methods In this prospective, unicentric study, 463 patients completed the short, Spanish EMOVE questionnaire, to be validated following the Medical Outcome Trust Criteria. Conceptual and measurement model, reliability (internal consistency and test–retest [subgroup of 93 patients]), construct validity, responsiveness, interpretability, and burden were evaluated. Patients enrolled from January 2017 through August 2018 and auto-filled the EMOVE at baseline and at 3, 6, and 12 months. Results Patients submitted to intragastric ballon for 6 and 12 months or POSE were 82.7% women with a mean age of 42.7 years, and a mean BMI of 37.1 kg/m2. Four factors were extracted with exploratory factor analysis related to intake frequency, portions and proportions, time and place of eating, and physical activity. EMOVE showed adequate internal consistency (α = 0.73), very good test–retest (r = 0.91, CI: 0.86–0.94; p r = 0.24, CI: 0.11–0.37, p r = 0.44, CI 0.30–0.58; p p p Conclusion The EMOVE is a useful tool in Spanish language to easily assess the level of adherence to healthy dietary and PA habits to be used routinely in clinical practice. Graphical abstract

Background COVID-19 severely impacted older adults and long-term care facility (LTCF) residents. Our primary aim was to describe differences in clinical and epidemiological variables, in-hospital management, and outcomes between LTCF residents and community-dwelling older adults hospitalized with COVID-19. The secondary aim was to identify risk factors for mortality due to COVID-19 in hospitalized LTCF residents. Methods This is a cross-sectional analysis within a retrospective cohort of hospitalized patients ≥75 years with confirmed COVID-19 admitted to 160 Spanish hospitals. Differences between groups and factors associated with mortality among LTCF residents were assessed through comparisons and logistic regression analysis. Results Of 6 189 patients ≥75 years, 1 185 (19.1%) were LTCF residents and 4 548 (73.5%) were community-dwelling. LTCF residents were older (median: 87.4 vs 82.1 years), mostly female (61.6% vs 43.2%), had more severe functional dependence (47.0% vs 7.8%), more comorbidities (Charlson Comorbidity Index: 6 vs 5), had dementia more often (59.1% vs 14.4%), and had shorter duration of symptoms (median: 3 vs 6 days) than community-dwelling patients (all, p < .001). Mortality risk factors in LTCF residents were severe functional dependence (adjusted odds ratios [aOR]: 1.79; 95% confidence interval [CI]: 1.13–2.83; p = .012), dyspnea (1.66; 1.16–2.39; p = .004), SatO2 < 94% (1.73; 1.27–2.37; p = .001), temperature ≥ 37.8°C (1.62; 1.11–2.38; p = .013); qSOFA index ≥ 2 (1.62; 1.11–2.38; p = .013), bilateral infiltrates (1.98; 1.24–2.98; p < .001), and high C-reactive protein (1.005; 1.003–1.007; p < .001). In-hospital mortality was initially higher among LTCF residents (43.3% vs 39.7%), but lower after adjusting for sex, age, functional dependence, and comorbidities (aOR: 0.74, 95%CI: 0.62–0.87; p < .001). Conclusion Basal functional status and COVID-19 severity are risk factors of mortality in LTCF residents. The lower adjusted mortality rate in LTCF residents may be explained by earlier identification, treatment, and hospitalization for COVID-19.

BACKGROUND A growing body of work shows that children with developmental language disorder (DLD) perform poorly on statistical word learning (SWL) tasks, consistent with the predictions of the Procedural Deficit Hypothesis that predicts that procedural memory is impaired in DLD. To date, however, SWL performance has not been compared across linguistically heterogeneous populations of children with DLD. AIMS To compare SWL performance in a group of age, sex and non-verbal IQ-matched Catalan-Spanish and English-speaking children with and without DLD. METHODS & PROCEDURES Two cohorts of children: (1) 35 Catalan-Spanish-speaking children with DLD (Mage = 8;7 years) and 35 age/sex-matched typical developing (TD) children (Mage = 8;9 years), and (2) 24 English-speaking children with DLD (Mage = 9;1 years) and 19 age/sex matched TD controls (Mage = 8;9 years) completed the tone version of a SWL task from Evans et al. (2009). Children listened to a tone language in which transitional probabilities within tone words were higher than those between words. OUTCOMES & RESULTS For both Catalan-Spanish and English cohorts, overall performance for the children with DLD was poorer than that of the TD controls regardless of the child's native language. Item analysis revealed that children with DLD had difficulty tracking statistical information and using transitional probability to discover tone word boundaries within the input. For both the Catalan-Spanish and English-speaking children, SWL accounted for a significant amount of unique variance in Receptive and Expressive vocabulary. Likelihood ratio analysis revealed that for both Catalan-Spanish and English cohorts, children having performance ≤ 45% on the SWL task had an extremely high degree of likelihood of having DLD. The analysis also revealed that for the Catalan-Spanish and English-speaking children, scores of ≥ 75% and ≥ 70%, respectively, were highly likelihood to be children with normal language abilities. CONCLUSIONS & IMPLICATIONS The findings add to a pattern suggesting that SWL is a mechanism that children rely on to acquire vocabulary. The results also suggest that SWL deficits, in particular when combined with other measures, may be a reliable diagnostic indicator for children with DLD regardless of the child's native language, and whether or not the child is bilingual or monolingual. WHAT THIS PAPER ADDS What is already known on the subject Although there is some disagreement, a small but growing body of work suggests that deficits in procedural memory, as measured either by motor sequencing (Serial Reaction Time-SRT) or SWL tasks, may be part of the deficit profile of children with DLD. To date, studies have not examined SWL across linguistically heterogeneous populations of children with DLD to determine if it is a unique clinical marker of the disorder. What this paper adds to existing knowledge The results show that children with DLD, regardless of their native language, or whether the child is bi- or monolingual, have difficulties on SWL tasks, and that these deficits are linked to severity of the language disorder. Taken together, these results indicate that procedural memory deficits may be a core feature of DLD. This suggests that statistical-learning tasks using tone stimuli can also advance our understanding of statistical-learning abilities in children with DLD more globally. What are the potential or actual clinical implications of this work? The current study shows that statistical-learning tasks using tone stimuli can be used in conjunction with standardized assessment measures to differentiate children with DLD from children with typical language ability.

Background Type I autoimmune pancreatitis (AIP) and IgG4-related sclerosing cholangitis (IgG4-SC) belong to the IgG4-related disease (IgG4-RD) spectrum. Both entities respond to glucocorticoids, but iatrogenic toxicity associated with prolonged steroid therapy and relapse represent relevant clinical concerns in the long-term. Rituximab is increasingly used as an effective alternative strategy to induce remission but data regarding the safety and efficacy of B-cell depletion therapy for pancreato-biliary involvement of IgG4-RD are limited. We performed a systematic review and meta-analysis to estimate the rate of remission, flare, and adverse events (AEs) occurring in pancreato-biliary IgG4-RD following rituximab treatment. Methods The MEDLINE, SCOPUS, and EMBASE databases were searched from inception to December 2020 to identify studies reporting the outcomes of IgG4-related pancreato-biliary disease after treatment with rituximab. Studies involving ≥2 patients were selected. In case of duplicated studies, the most recent or the one with the biggest N were chosen. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Pooled effects were calculated using a random-effect model and expressed in terms of pooled remission, relapse, and AEs rates. Results Seven cohort studies met inclusion criteria and 101 patients were included. Reasons for rituximab administration were new disease onset (18.5%), disease flare after glucocorticoids (63.5%), and glucocorticoids intolerance (17.9%). The median follow-up time was 19 months. The pooled rate of complete response at 6 months was 88.9% (95%CI 80.5–93.9) with no heterogeneity (I2 = 0%). The pooled estimate of relapse rate was 21% (95%CI 10.5–40.3) with moderate heterogeneity (I2 = 51%). A higher rate of relapse (35.9%, 95%CI 17.3–60.1) was reported in studies including patients with multiorgan involvement (OOI). The median time to relapse was 10 months. The pooled estimate of rituximab-related AEs was 25% (95%CI 8.8–53) with substantial heterogeneity (I2 = 73.6%). No publication bias was observed. Conclusion Treatment of IgG4-related pancreato-biliary disease with rituximab is associated with high remission rate, a higher relapse rate in the presence of OOI, and limited AEs. Randomized controlled trials with adequate power are needed to confirm these findings.

Background: Clinical factors associated with vitiligo in patients receiving anti–programmed cell death-1 (PD-1) remain unknown. Objective: To better characterize the occurrence of vitiligo in patients receiving anti–PD-1. Methods: The present single-center ambispective cohort study included patients with melanoma treated with anti–PD-1. Progression-free survival, overall survival, and objective tumor response were compared between patients with and those without vitiligo using Kaplan-Meier curves and the log-rank test. Demographic and clinical factors associated with vitiligo were evaluated using multivariate logistic regression. Results: Of the 457 patients included in the study, vitiligo developed in 85 patients. The clinical presentation of vitiligo consisted of the presence of ovalar and multiple flecked white macules, mainly located on chronic sun-exposed areas. The presence of vitiligo was associated with a significant improvement in overall survival and progression-free survival (P

Adenoid cystic carcinoma of the breast (ACCB) is a rare triple negative tumor (TNT) with an excellent prognosis in most cases. Three different histologic types are recognized: classic ACCB, solid basaloid ACCB (SB-ACCB), and ACCB with high-grade transformation. A majority of these tumors show characteristic molecular and immunohistochemical (IHC) features, with fusion of MYB and NFIB genes and overexpression of MYB, respectively. Basaloid carcinomas of the breast (BCB) are infrequently described. They resemble SB-ACCB and TNT of no special type (TNT-NST). We have studied the clinicopathological features of 17 ACCB and 9 BCB, investigating the expression of MYB by IHC and the rearrangements of MYB by fluorescence in situ hybridization (FISH). MYB was expressed by IHC in 15 ACCB and in 3 BCB. MYB FISH detected rearrangements in 11 ACCB and in 2 BCB. After a mean follow-up of 90 months, with a range of 12-204 months, 2 patients with ACCB with high-grade transformation and 1 patient with BCB developed metastases and died of disease. In summary, most ACCB have a good prognosis, but tumors with adverse histopathological features may metastasize. BCB may overlap with ACCB and TNT-NST, and their prognosis should be further studied.

Background In recent decades, increasing longevity (among other factors) has fostered a rise in Parkinson's disease incidence. Although not exhaustively studied in this devastating disease, the impact of sex represents a critical variable in Parkinson’s disease as epidemiological and clinical features differ between males and females. Methods To study sex bias in Parkinson’s disease, we conducted a systematic review to select sex-labeled transcriptomic data from three relevant brain tissues: the frontal cortex, the striatum, and the substantia nigra. We performed differential expression analysis on each study chosen. Then we summarized the individual differential expression results with three tissue-specific meta-analyses and a global all-tissues meta-analysis. Finally, results from the meta-analysis were functionally characterized using different functional profiling approaches. Results The tissue-specific meta-analyses linked Parkinson’s disease to the enhanced expression of MED31 in the female frontal cortex and the dysregulation of 237 genes in the substantia nigra. The global meta-analysis detected 15 genes with sex-differential patterns in Parkinson’s disease, which participate in mitochondrial function, oxidative stress, neuronal degeneration, and cell death. Furthermore, functional analyses identified pathways, protein–protein interaction networks, and transcription factors that differed by sex. While male patients exhibited changes in oxidative stress based on metal ions, inflammation, and angiogenesis, female patients exhibited dysfunctions in mitochondrial and lysosomal activity, antigen processing and presentation functions, and glutamic and purine metabolism. All results generated during this study are readily available by accessing an open web resource (http://bioinfo.cipf.es/metafun-pd/) for consultation and reuse in further studies. Conclusions Our in silico approach has highlighted sex-based differential mechanisms in typical Parkinson Disease hallmarks (inflammation, mitochondrial dysfunction, and oxidative stress). Additionally, we have identified specific genes and transcription factors for male and female Parkinson Disease patients that represent potential candidates as biomarkers to diagnosis.

CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89). We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome. Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed antitumor activity in estrogen receptor-positive non-basal-like breast cancer patient-derived xenografts, independently of PIK3CA, ESR1 or RB1 mutation, also in drug de-escalation experiments or omitting endocrine therapy. Our results offer insights into predicting primary/acquired resistance to CDK4/6 inhibitors and post-progression therapeutic strategies. This study has been supported by the Susan G. Komen Foundation (CCR15330331) and by the Catalan Agency AGAUR (2017 SGR 540) [to V.S.]. V.S. received funds from the Instituto de Salud Carlos III: grants PI13/01714, CP14/00228, MV15/00041, CPII19/00033 and PI20/00892. M.P. received a Juan de la Cierva Grant from the Ministerio de Economía y Competitividad (FJCI-2015-25412), L.Mo. a grant from FI-AGAUR (2019 FI_B 01199), F.B-M. a grant from the Fundación Científica Asociación Española Contra el Cáncer (AECC_Postdoctoral17-1062) and M.S-G, a Marie Slodowska-Curie Innovative Training Networks PhD fellowship (H2020-MSCA-ITN-2015_675392). This work was supported by Breast Cancer Research Foundation (BCRF-19-08), Instituto de Salud Carlos III Project Reference number AC15/00062 and the EC under the framework of the ERA-NET TRANSCAN-2 initiative co-financed by FEDER, Instituto de Salud Carlos III (CB16/12/00449 and PI19/01181) and Asociación Española Contra el Cáncer (to J.A.). R.B.C. laboratory is supported by Breast Cancer Now (grant numbers: MAN-Q1 and MAN-Q2), NIHR Manchester Biomedical Research Centre (IS-BRC-1215-20007) and EdiREX Horizon 2020 grant No.731105. The xenograft program in the C.C. laboratory is supported by Cancer Research UK and also received funding from an EU H2020 Network of Excellence (EuroCAN). This work has been supported by NIH grants P30 CA008748 and RO1CA190642-01, the CDMRP grant BC171535P1, and the Breast Cancer Research Foundation [to M.S.]. A.P. received funds from Instituto de Salud Carlos III—PI16/00904 and PI19/01846, Breast Cancer Now—2018NOVPCC1294, Breast Cancer Research Foundation-AACR Career Development Awards for Translational Breast Cancer Research 19-20-26-PRAT, Fundació La Marató TV3 201935-30, the European Union’s Horizon 2020 research and innovation program H2020-SC1-BHC-2018-2020. IRB Barcelona is a recipient of a Severo Ochoa Centre of Excellence Award from the Spanish Ministry of Economy and Competitiveness (MINECO; Government of Spain) and is supported by CERCA (Generalitat de Catalunya). C. S. Verma reports grants from MSD International and grants from Ipsen outside the submitted work.

Purpose We investigated experiences of families who provide consent for research on behalf of a loved-one hospitalized in intensive care (ICU). Methods Multicentre, qualitative, descriptive study using semi-directive interviews in 3 ICUs. Eligible relatives were aged >18 years, and had provided informed consent for a clinical trial on behalf of a patient hospitalized in ICU. Interviews were conducted from 06/2018 to 06/2019 by a qualified sociologist, recorded and transcribed. Results Fifteen relatives were interviewed; average age 50.3 ± 15 years. All emphasized their interest in clinical research, seeing it as a duty. Involving their loved-one in research allowed them to find meaning in the events. Participants underlined that trust in caregivers and communication are determinant. The strict regulation of research was perceived as a guarantee of safety. Participants felt they lacked the intellectual capacity and knowledge to question explanations. The greatest fear was not that they might incur a risk for the patient, but rather, that they might deprive the patient of a chance at a cure. Conclusion Acceptance of research opportunities by relatives on behalf of decisionally-incapacitated patients is underpinned by trust in the physicians and the legislative framework. Communication and the quality of information provided by the caregivers are key.

Objective To evaluate the feasibility of using the Sentinella® portable gamma-camera for the diagnosis of brain death (BD). Design A prospective, observational feasibility study was carried out. Setting Intensive Care Unit of a third level hospital. Patients Consecutive recording was made of the adults diagnosed with brain death based on clinical criteria following admission to the Intensive Care Unit in the period from January to December 2017. Interventions The procedure was performed at the patient bedside with the intravenous administration of technetium 99 metastable hexamethylpropylene amine oxime. The absence of perfusion in the cerebral hemispheres and brainstem was described as a pattern consistent with BD. The diagnosis was correlated to the transcranial Doppler and/or electroencephalographic findings. Results A total of 66.1% of the patients were men with an average age of 60 years [IQR: 51–72]. The most frequent causes resulting in BD were hemorrhagic stroke (48.2%, n = 27), followed by traumatic brain injury (30.4%, n = 17), ischemic stroke (10.7%, n = 6) and post-cardiac arrest anoxic encephalopathy (7.1%, n = 4). A clinical diagnosis of BD was made in all cases, and the portable gamma-camera confirmed the diagnosis in 100% of the patients with a pattern characterized by the absence of brain perfusion. In addition, the results were compared with the transcranial Doppler findings in 46 patients, confirming the presence of diastolic reverberation and/or systolic peaks. The electroencephalographic tracing was obtained in 10 cases, with the appearance of electrical silence, due to the absence of an acoustic window in the transcranial Doppler study. Conclusions A portable gamma-camera could be a useful and feasible tool for the diagnosis of BD.

Resumen Objetivo Evaluar la factibilidad del empleo de la minigammacamara portatil Sentinella®, para el diagnostico de muerte encefalica (ME). Diseno Estudio observacional, prospectivo, de factibilidad. Ambito Unidad de cuidados intensivos de un hospital de tercer nivel. Pacientes Desde enero a diciembre de 2017 se registraron de forma consecutiva los pacientes mayores de edad que tras su ingreso en unidad de cuidados intensivos fueron diagnosticados de ME segun criterios clinicos. Intervenciones El procedimiento se realizo a la cabecera del paciente tras la administracion intravenosa de tecnecio 99 metaestable-hexametil-propilen-amino-oxima. La ausencia de perfusion a nivel de hemisferios cerebrales y fosa posterior se describia como patron compatible con ME. Se correlaciono el diagnostico con doppler transcraneal y/o electroencefalograma. Resultados Cincuenta y seis pacientes presentaron exploracion fisica compatible con ME. Un 66,1% fueron hombres con una mediana de edad de 60 (RIQ: 51-72) anos. La causa mas frecuente que precipito la ME fue el ictus hemorragico en el 48,2% (27) seguido por traumatismo craneoencefalico grave en el 30,4% (17), ictus isquemico en el 10,7% (6) y encefalopatia anoxica tras parada cardiorrespiratoria en el 7,1% (4). En todos los casos se realizo el diagnostico clinico de ME y posteriormente una gammagrafia portatil que confirmo dicho diagnostico en el 100% de los pacientes. Se contrasto el resultado con doppler transcraneal en 46 de ellos que confirmaba la presencia de reverberacion diastolica y/o picos sistolicos. En 10 casos se registro el electroencefalograma, con aparicion de silencio electrico, debido a la ausencia de ventana acustica en el doppler transcraneal. Conclusiones El uso de minigammacamara portatil puede resultar una herramienta util y factible para el diagnostico de ME.

BACKGROUND: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. METHODS: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. RESULTS: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of ≥1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged ≥65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. LIMITATIONS: . Cross-sectional survey, preponderance of non-representative participants. CONCLUSIONS: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics. ispartof: JOURNAL OF AFFECTIVE DISORDERS vol:299 pages:393-407 ispartof: location:Netherlands status: published

BACKGROUND: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. METHODS: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www.coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via non-probability/snowball and representative sampling and assessed via self-rating and parental rating. Non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co-primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. RESULTS: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COH-FIT project, with representative samples from eleven countries. LIMITATIONS: Cross-sectional and anonymous design. CONCLUSIONS: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on children's, adolescents' and families', mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth. ispartof: JOURNAL OF AFFECTIVE DISORDERS vol:299 pages:367-376 ispartof: location:Netherlands status: published

Summary Background Etrolizumab is a gut-targeted, anti-β7 integrin, monoclonal antibody. In an earlier phase 2 induction study, etrolizumab significantly improved clinical remission compared with placebo in patients with moderately to severely active ulcerative colitis. We aimed to evaluate the efficacy and safety of etrolizumab in patients with moderately to severely active ulcerative colitis who had been previously treated with anti-tumour necrosis factor (TNF) agents. Methods HICKORY was a multicentre, phase 3, double-blind, placebo-controlled study in adult (18–80 years) patients with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6–12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) previously treated with TNF inhibitors. Patients were recruited from 184 treatment centres across 24 countries in North America, South America, Europe, Asia, Oceania, and the Middle East. Patients needed to have an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. In cohort 1, patients received open-label etrolizumab 105 mg every 4 weeks for a 14-week induction period. In cohort 2, patients were randomly assigned (4:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks for the 14-week induction phase. Patients in either cohort achieving clinical response to etrolizumab induction were eligible for the maintenance phase, in which they were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg or placebo every 4 weeks through to week 66. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants (induction randomisation only), baseline disease activity, week 14 MCS remission status (maintenance randomisation only), and induction cohort (maintenance randomisation only). All patients and study site personnel were masked to treatment assignment. Primary endpoints were remission (Mayo Clinic total score [MCS] ≤2, with individual subscores of ≤1 and a rectal bleeding subscore of 0) at week 14, and remission at week 66 among patients with a clinical response (MCS with ≥3-point decrease and ≥30% reduction from baseline, plus ≥1 point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) at week 14. Efficacy was analysed using a modified intent-to-treat population. Safety analyses included all patients who received at least one dose of study drug during the induction phase. This study is registered at ClinicalTrials.gov , NCT02100696 . Findings HICKORY was conducted from May 21, 2014, to April 16, 2020, during which time 1081 patients were screened, and 609 deemed eligible for inclusion. 130 patients were included in cohort 1. In cohort 2,479 patients were randomly assigned to the induction phase (etrolizumab n=384, placebo n=95). 232 patients were randomly assigned to the maintenance phase (etrolizumab to etrolizumab n=117, etrolizumab to placebo n=115). At week 14, 71 (18·5%) of 384 patients in the etrolizumab group and six (6·3%) of 95 patients in the placebo group achieved the primary induction endpoint of remission (p=0·0033). No significant difference between etrolizumab and placebo was observed for the primary maintenance endpoint of remission at week 66 among patients with a clinical response at week 14 (27 [24·1%] of 112 vs 23 [20·2%] of 114; p=0·50). Four patients in the etrolizumab group reported treatment-related adverse events leading to treatment discontinuation. The proportion of patients reporting at least adverse event was similar between treatment groups for induction (etrolizumab 253 [66%] of 384; placebo 63 [66%] of 95) and maintenance (etrolizumab to etrolizumab 98 [88%] of 112; etrolizumab to placebo 97 [85%] of 114). The most common adverse event in both groups was ulcerative colitis flare. Most adverse events were mild or moderate. During induction, the most common serious adverse event was ulcerative colitis flare (etrolizumab ten [3%] of 384; placebo: two [2%] of 95). During maintenance, the most common serious adverse event in the etrolizumab to etrolizumab group was appendicitis (two [2%] of 112) and the most common serious adverse events in the etrolizumab to placebo group were ulcerative colitis flare (two [2%] of 114) and anaemia (two [2%] of 114). Interpretation HICKORY demonstrated that a significantly higher proportion of patients with moderately to severely active ulcerative colitis who had been previously treated with anti-TNF agent were able to achieve remission at week 14 when treated with etrolizumab compared with placebo; however, there was no significant difference between groups in remission at week 66 among patients with a clinical response at week 14. Funding F Hoffmann-La Roche.

Purpose The aim of this study was to determine the prevalence of distress and unmet supportive care needs in post-treatment colorectal cancer (CRC) survivors. Also, to explore the association between both variables and to identify potential associated sociodemographic and cancer-related risk factors. Methods A cross-sectional study of 200 CRC survivors who at least 1 month before had completed the primary treatment for CRC was conducted. The Brief Symptom Inventory-18 (BSI-18) and the Spanish version of Cancer Survivors’ Unmet Needs (S-CaSUN) were used. Results One in five CRC survivors showed clinical distress and 86% expressed at least one unmet need. Distress was positively associated with the prevalence of needs in all domains. All comprehensive care and information needs were expressed by at least 20% of survivors and some by more than 50%. Other needs also mentioned by 20% of survivors were financial support, ongoing case manager, and concerns about cancer recurrence. The risk factors associated were lower socioeconomic status, younger age, and a primary treatment that includes more than surgery. Conclusions The findings highlight the relevance of extending psychosocial care beyond the CRC primary medical treatment. A person-centered approach that addresses informational, emotional, social, and physical needs can increase satisfaction with care and also prevent psychological morbidity in CRC survivors.

Leptin is a hormone primarily produced by the adipose tissue in proportion to the size of fat stores, with a primary function in the control of lipid reserves. Besides adipose tissue, leptin is also produced by other tissues, such as the stomach, placenta, and mammary gland. Altogether, leptin exerts a broad spectrum of short, medium, and long-term regulatory actions at the central and peripheral levels, including metabolic programming effects that condition the proper development and function of the adipose organ, which are relevant for its main role in energy homeostasis. Comprehending how leptin regulates adipose tissue may provide important clues to understand the pathophysiology of obesity and related diseases, such as type 2 diabetes, as well as its prevention and treatment. This review focuses on the physiological and long-lasting regulatory effects of leptin on adipose tissue, the mechanisms and pathways involved, its main outcomes on whole-body physiological homeostasis, and its consequences on chronic diseases.

© 2021 The Authors. Published by American Chemical Society, The frequency of brain disease has increased significantly in the past years. After diagnosis, therapeutic options are usually limited, which demands the development of innovative therapeutic strategies. The use of antibody−drug conjugates (ADCs) is promising but highly limited by the existence of the blood−brain barrier (BBB). To overcome the impermeability of this barrier, antibody fragments can be engineered and conjugated to BBB peptide shuttles (BBBpS), which are capable of brain penetration. Herein, we linked the highly efficient BBBpS, PepH3, to the IgG fragment crystallizable (Fc) domain using the streamlined expressed protein ligation (SEPL) method. With this strategy, we obtained an Fc-PepH3 scaffold that can carry different payloads. Fc-PepH3 was shown to be nontoxic, capable of crossing an in vitro cellular BBB model, and able to bind to the neonatal Fc receptor (FcRn), which is responsible for antibody long half-life (t1/2). Overall, we demonstrated the potential of Fc-PepH3 as a versatile platform readily adaptable to diverse drugs of therapeutic value to treat different brain conditions., We acknowledge the Portuguese Funding Agency, Fundação para a Ciência e a Tecnologia, FCT IP (Grant Nos. PD/BD/128281/2017, PTDC/BIA-BQM/5027/2020, and DL 57/2016/CP1451/CT0023), and “la Caixa” Banking Foundation (ID 100010434), under the agreement LCF/PR/HR17/5215001.

To evaluate the benefits of aerobic training (AT) programs on cardiorespiratory fitness, functional capacity, balance, and fatigue in individuals with multiple sclerosis (MS) and to identify the optimal dosage of AT programs for individuals with MS via a systematic review with meta-analysis.Two electronic databases were searched until March 2020 (PubMed-Medline and Web of Science).Studies examining the effect of AT program on cardiorespiratory fitness, functional capacity, balance, and fatigue were included.After applying the inclusion and exclusion criteria, we included 43 studies. A total sample of 1070 individuals with MS (AT group, n=680; control group, n=390) were analyzed.The AT group demonstrated a significant increase in cardiorespiratory fitness (standardized mean difference [SMD], 0.29; P=.002), functional capacity (timed Up and Go Test: SMD, -1.14; P.001; gait speed: SMD, -1.19; P.001; walking endurance: SMD, 0.46; P.001), and balance (SMD, 3.49; P.001) after training. Fatigue perception also decreased (SMD, -0.45; P.001). However, no significant differences were observed when compared with the control group in either cardiorespiratory fitness (SMD, 0.14; P=.19) or fatigue perception. Nevertheless, we observed significant differences between the AT and control groups in balance (P=.02), gait speed (P=.02), and walking endurance (P=.03), favoring the participants who performed AT. Regarding the subgroup analysis, no significant differences were observed between subgroups in any of the variables studied except for gait speed, for which a greater increase in posttraining was observed when the AT program applied the continuous method (χAerobic training improves gait speed, walking endurance, and balance. Cardiorespiratory fitness and fatigue perception also improved after AT, but we found no differences with the control group. In addition, subgroup analysis suggested that training using continuous and walking methods could optimize gait speed.

Peripheral blood mononuclear cells (PBMC) are widely used as a biomarker source in nutrition/obesity studies because they reflect gene expression profiles of internal tissues. In this pilot proof-of-concept study we analysed in humans if, as we previously suggested in rodents, PBMC could be a surrogate tissue to study overweight/obesity impact on lipid metabolism. Pre-selected key lipid metabolism genes based in our previous preclinical studies were analysed in PBMC of normoglycemic normal-weight (NW), and overweight-obese (OW-OB) subjects before and after a 6-month weight-loss plan. PBMC mRNA levels of CPT1A, FASN and SREBP-1c increased in the OW-OB group, according with what described in liver and adipose tissue of humans with obesity. This altered expression pattern was related to increased adiposity and early signs of metabolic impairment. Greater weight loss and/or metabolic improvement as result of the intervention was related to lower CPT1A, FASN and SREBP-1c gene expression in an adjusted linear mixed-effects regression analysis, although no gene expression recovery was observed when considering mean comparisons. Thus, human PBMC reflect lipid metabolism expression profile of energy homeostatic tissues, and early obesity-related alterations in metabolic at-risk subjects. Further studies are needed to understand PBMC usefulness for analysis of metabolic recovery in weigh management programs.

PRC2-mediated epigenetic function involves the interaction with long non-coding RNAs (lncRNAs). Although the identity of some of these RNAs has been elucidated in the context of developmental programs, their counterparts in postmitotic adult tissue homeostasis remain uncharacterized. To this aim, we used terminally differentiated postmitotic skeletal muscle cells in which oxidative stress induces the dynamic activation of PRC2-Ezh1 through Embryonic Ectoderm Develpment (EED) shuttling to the nucleus. We identify lncRNA Malat-1 as a necessary partner for PRC2-Ezh1-dependent response to oxidative stress. We show that in this pathway, PRC2-EZH1 dynamic assembly, and in turn stress induced skeletal muscle targeted genes repression, depends specifically on Malat-1. Our study reports about PRC2–RNA interactions in the physiological context of adaptive oxidative stress response and identifies the first lncRNA involved in PRC2-Ezh1 function.

The gut microbiota is increasingly recognized as an important regulator of host immunity and brain health. The aging process yields dramatic alterations in the microbiota, which is linked to poorer health and frailty in elderly populations. However, there is limited evidence for a mechanistic role of the gut microbiota in brain health and neuroimmunity during aging processes. Therefore, we conducted fecal microbiota transplantation from either young (3–4 months) or old (19–20 months) donor mice into aged recipient mice (19–20 months). Transplant of a microbiota from young donors reversed aging-associated differences in peripheral and brain immunity, as well as the hippocampal metabolome and transcriptome of aging recipient mice. Finally, the young donor-derived microbiota attenuated selective age-associated impairments in cognitive behavior when transplanted into an aged host. Our results reveal that the microbiome may be a suitable therapeutic target to promote healthy aging. The gut microbiome can change with age and influence aging-related diseases systemically, including in the brain. The authors show that rejuvenation of the gut microbiome by fecal microbiota transplantation from young mice reverses aging-induced deficits in the hippocampal immune system, metabolome and transcriptome, and rescues selective cognitive deficits.

11 pags., 6 figs., 5 tabs., Multidrug resistance against conventional antibiotics poses an important threat to human health. In this context, antimicrobial peptides (AMPs) have been extensively studied for their antibacterial activity and promising results have been shown so far. However, AMPs tend to be rather vulnerable to protease degradation, which offsets their therapeutic appeal. Here, we demonstrate how replacing functional residues in the antimicrobial region of human RNase 3 - also named eosinophil cationic protein - by non-natural amino acids increases stability in human serum. These changes were also shown to reduce the hemolytic effect of the peptides in general terms, whereas the antimicrobial activity was reasonably preserved. Digestion profiles enabled us to design new peptides with superior stability and lower toxicity that could become relevant candidates to reach clinical stages., This work was supported by the Spanish Ministerio de Ciencia, Innovacion y Universidades: SAF2015-72518-EXP, SAF2017- ́ 82158-R and RYC-2012-09999 to M.T.; CTQ2017-84371-P to M.A.J.; AGL2014-52395-C2; AGL2017-84097-C2-2-R to D.A. and PID2019-106123GB-I00 to E.B. Additional financial support from the European Society for Clinical Microbiology and Infectious Disease, ESCMID 2016, to M.T., the Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya, 2019 LLAV 00029 to M.T. and 2016 PROD 00060 to E.B. The “Marí a de Maeztu” Program for Units of Excellence in R&D from the Spanish Ministry of Innovation and Competitiveness (MINECO) for work at Pompeu Fabra University (D.A.) is acknowledged. This work was supported, in part, by the European Regional Development Fund ‘A Way to Achieve Europe’ [Spanish Network for Research in Infectious Diseases (Grant No. RD16/0016/0003)]. D.S. and B.C.-A. are recipients of pre-doctoral FPI scholarships (PRE2018-083243 and BES-2015-073383, respectively) from the Spanish Ministerio de Ciencia, Innovacion y Universidades.

STUDY OBJECTIVES: To analyze differences in mandibular cortical width (MCW) among children diagnosed with obstructive sleep apnea (OSA) or at high- or low-risk for OSA. METHODS: A total of 161 children were assessed: 60 children with polysomnographically diagnosed OSA, 56 children presenting symptoms suggestive of high-risk for OSA, and 45 children at low risk for OSA. Children at high- and low-risk for OSA were evaluated through the Pediatric Sleep Questionnaire. MCW was calculated using ImageJ software from panoramic radiograph images available from all participants. Differences between MCW measurements in the 3 groups were evaluated using analysis of covariance and Bonferroni post-hoc tests, with age as a covariate. The association between MCW and specific cephalometric variables was assessed through regression analysis. RESULTS: The participants’ mean age was 9.6 ± 3.1 years (59% male and 41% female). The mean body mass index z-score was 0.62 ± 1.3. The polysomnographically diagnosed OSA group presented smaller MCW than the group at low-risk for OSA (mean difference = –0.385 mm, P = .001), but no difference with the group at high-risk for OSA (polysomnographically diagnosed OSA vs high-risk OSA: P = .085). In addition, the MCW in the group at high-risk for the OSA was significantly smaller than the group at low-risk for the OSA (mean difference = –0.301 mm, P = .014). The cephalometric variables (Sella-Nasion-A point angle (SNA) and Frankfort - Mandibular Plane angle (FMA)) explained only 8% of the variance in MCW. CONCLUSIONS: Reductions in MCW appear to be present among children with OSA or those at high-risk for OSA, suggesting potential interactions between mandibular bone development and/or homeostasis and pediatric OSA. CITATION: Fernandes Fagundes NC, d’Apuzzo F, Perillo L, et al. Potential impact of pediatric obstructive sleep apnea on mandibular cortical width dimensions. J Clin Sleep Med. 2021;17(8):1627–1634

Background We identified a global chemical pattern of volatile organic compounds in exhaled breath capable of discriminating between COVID-19 patients and controls (without infection) using an electronic nose. Methods The study focused on 42 SARS-CoV-2 RT-qPCR positive subjects as well as 42 negative subjects. Principal component analysis indicated a separation of the study groups and provides a cumulative percentage of explanation of the variation of 98.3%. Results The canonical analysis of principal coordinates model shows a separation by the first canonical axis CAP1 (r2 = 0.939 and 95.23% of correct classification rate), the cut-off point of 0.0089; 100% sensitivity (CI 95%:91.5–100%) and 97.6% specificity (CI 95%:87.4–99.9%). The predictive model usefulness was tested on 30 open population subjects without prior knowledge of SARS-CoV-2 RT-qPCR status. Of these 3 subjects exhibited COVID-19 suggestive breath profiles, all asymptomatic at the time, two of which were later shown to be SARS-CoV-2 RT-qPCR positive. An additional subject had a borderline breath profile and SARS-CoV-2 RT-qPCR positive. The remaining 27 subjects exhibited healthy breath profiles as well as SARS-CoV-2 RT-qPCR test results. Conclusions In all, the use of olfactory technologies in communities with high transmission rates as well as in resource-limited settings where targeted sampling is not viable represents a practical COVID-19 screening approach capable of promptly identifying COVID-19 suspect patients and providing useful epidemiological information to guide community health strategies in the context of COVID-19.