Rationale and protocol paper for the Asia Pacific Network for inherited eye diseases.

PURPOSE: There are major gaps in our knowledge of hereditary ocular conditions in the Asia-Pacific population, which comprises approximately 60% of the world's population. Therefore, a concerted regional effort is urgently needed to close this critical knowledge gap and apply precision medicine technology to improve the quality of lives of these patients in the Asia-Pacific region. DESIGN: Multi-national, multi-center collaborative network. METHODS: The Research Standing Committee of the Asia-Pacific Academy of Ophthalmology and the Asia-Pacific Society of Eye Genetics fostered this research collaboration, which brings together renowned institutions and experts for inherited eye diseases in the Asia-Pacific region. The immediate priority of the network will be inherited retinal diseases (IRDs), where there is a lack of detailed characterization of these conditions and in the number of established registries. RESULTS: The network comprises 55 members from 35 centers, spanning 12 countries and regions, including Australia, China, India, Indonesia, Japan, South Korea, Malaysia, Nepal, Philippines, Singapore, Taiwan, and Thailand. The steering committee comprises ophthalmologists with experience in consortia for eye diseases in the Asia-Pacific region, leading ophthalmologists and vision scientists in the field of IRDs internationally, and ophthalmic geneticists. CONCLUSIONS: The Asia Pacific Inherited Eye Disease (APIED) network aims to (1) improve genotyping capabilities and expertise to increase early and accurate genetic diagnosis of IRDs, (2) harmonise deep phenotyping practices and utilization of ontological terms, and (3) establish high-quality, multi-user, federated disease registries that will facilitate patient care, genetic counseling, and research of IRDs regionally and internationally.

Effect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosis.

BACKGROUND: Consistent evidence supports the involvement of genetic and environmental factors, and their interactions, in the etiology of psychosis. First-episode psychosis (FEP) comprises a group of disorders that show great clinical and long-term outcome heterogeneity, and the extent to which genetic, familial and environmental factors account for predicting the long-term outcome in FEP patients remains scarcely known. METHODS: The SEGPEPs is an inception cohort study of 243 first-admission patients with FEP who were followed-up for a mean of 20.9 years. FEP patients were thoroughly evaluated by standardized instruments, with 164 patients providing DNA. Aggregate scores estimated in large populations for polygenic risk score (PRS-Sz), exposome risk score (ERS-Sz) and familial load score for schizophrenia (FLS-Sz) were ascertained. Long-term functioning was assessed by means of the Social and Occupational Functioning Assessment Scale (SOFAS). The relative excess risk due to interaction (RERI) was used as a standard method to estimate the effect of interaction of risk factors. RESULTS: Our results showed that a high FLS-Sz gave greater explanatory capacity for long-term outcome, followed by the ERS-Sz and then the PRS-Sz. The PRS-Sz did not discriminate significantly between recovered and non-recovered FEP patients in the long term. No significant interaction between the PRS-Sz, ERS-Sz or FLS-Sz regarding the long-term functioning of FEP patients was found. CONCLUSIONS: Our results support an additive model of familial antecedents of schizophrenia, environmental risk factors and polygenic risk factors as contributors to a poor long-term functional outcome for FEP patients.

Estado nutricional, obesidad y eventos en pacientes con fibrilación auricular / Nutrition status, obesity and outcomes in patients with atrial fibrillation

Introducción y objetivos Se ha descrito un efecto protector paradójico de la obesidad en pacientes con fibrilación auricular (FA) cuya mecanismo no está claro. El objetivo de este estudio fue determinar el impacto del estado nutricional y el índice de masa corporal (IMC) en el pronóstico de los pacientes con FA. Métodos Se realizó un estudio de cohortes retrospectivo de pacientes con FA entre 2014 y 2017 de una única área sanitaria en España. La escala CONUT se utilizó para evaluar el estado nutricional. La asociación del IMC y escala CONUT con la mortalidad se analizó por regresión de Cox. La asociación con eventos embólicos y hemorrágicos se evaluó mediante análisis de riesgos competitivos. Resultados Entre los 14.849 pacientes, se observó sobrepeso y obesidad en 42,6% y 46,0%, respectivamente, mientras que malnutrición en 34,3%. Durante un seguimiento medio de 4,4 años, 3.335 pacientes murieron, 984 pacientes sufrieron un evento embólico y 1.317 una hemorragia. El IMC se asoció inversamente con la mortalidad, embolias y hemorragias en el análisis univariado; sin embargo, esta asociación se perdió después del ajuste por edad, sexo, comorbilidades y escala CONUT (HR para el combinado de eventos 0,98; IC95%, 0,95-1,01; p=0,719). Por el contrario, la escala CONUT si se asoció con la mortalidad, la embolia y la hemorragia (HR = 1,15; IC95%, 1,14-1,17; p<0,001). Conclusiones El IMC no fue un predictor independiente de eventos en pacientes con FA, a diferencia del estado nutricional, que mostró una fuerte asociación con la mortalidad, la embolia y la hemorragia (AU)

Introduction and objectives A paradoxical protective effect of obesity has been previously reported in patients with atrial fibrillation (AF). The aim of this study was to determine the impact of nutritional status and body mass index (BMI) on the prognosis of AF patients. Methods We conducted a retrospective population-based cohort study of patients with AF from 2014 to 2017 from a single health area in Spain. The CONUT score was used to assess nutritional status. Cox regression models were used to estimate the association of BMI and CONUT score with mortality. The association with embolism and bleeding was assessed by a competing risk analysis. Results Among 14 849 AF patients, overweight and obesity were observed in 42.6% and 46.0%, respectively, while malnutrition was observed in 34.3%. During a mean follow-up of 4.4 years, 3335 patients died, 984 patients had a stroke or systemic embolism, and 1317 had a major bleeding event. On univariate analysis, BMI was inversely associated with mortality, embolism, and bleeding; however, this association was lost after adjustment by age, sex, comorbidities, and CONUT score (HR for composite endpoint, 0.98; 95%CI, 0.95-1.01; P=.719). Neither obesity nor overweight were predictors of mortality, embolism, and bleeding events. In contrast, nutritional status—assessed by the CONUT score—was associated with mortality, embolism and bleeding after multivariate analysis (HR for composite endpoint, 1.15; 95%CI, 1.14-1.17; P<.001). Conclusion BMI was not an independent predictor of events in patients with AF in contrast to nutritional status, which showed a strong association with mortality, embolism, and bleeding (AU)

Remote ischaemic conditioning: defining critical criteria for success-report from the 11th Hatter Cardiovascular Workshop.

The Hatter Cardiovascular Institute biennial workshop, originally scheduled for April 2020 but postponed for 2 years due to the Covid pandemic, was organised to debate and discuss the future of Remote Ischaemic Conditioning (RIC). This evolved from the large multicentre CONDI-2-ERIC-PPCI outcome study which demonstrated no additional benefit when using RIC in the setting of ST-elevation myocardial infarction (STEMI). The workshop discussed how conditioning has led to a significant and fundamental understanding of the mechanisms preventing cell death following ischaemia and reperfusion, and the key target cyto-protective pathways recruited by protective interventions, such as RIC. However, the obvious need to translate this protection to the clinical setting has not materialised largely due to the disconnect between preclinical and clinical studies. Discussion points included how to adapt preclinical animal studies to mirror the patient presenting with an acute myocardial infarction, as well as how to refine patient selection in clinical studies to account for co-morbidities and ongoing therapy. These latter scenarios can modify cytoprotective signalling and need to be taken into account to allow for a more robust outcome when powered appropriately. The workshop also discussed the potential for RIC in other disease settings including ischaemic stroke, cardio-oncology and COVID-19. The workshop, therefore, put forward specific classifications which could help identify so-called responders vs. non-responders in both the preclinical and clinical settings.

Análisis de la atención al infarto con elevación del segmento ST en España. Resultados del Registro de Código Infarto de la ACI-SEC / Analysis of the management of ST-segment elevation myocardial infarction in Spain. Results from the ACI-SEC Infarction Code Registry

Introducción y objetivos Las redes de Código Infarto deben garantizar una atención al infarto agudo de miocardio con elevación del segmento ST con buenos resultados clínicos y dentro de los parámetros de tiempo recomendados. No hay información contemporánea sobre el funcionamiento de estas redes en España. El objetivo es analizar las características clínicas de los pacientes atendidos, el tiempo hasta la reperfusión, las características de la intervención realizada y la mortalidad a 30 días. Métodos Registro prospectivo, observacional y multicéntrico de pacientes los consecutivos atendidos en 17 redes de Código Infarto en España (83 centros con Código Infarto) entre el 1 de abril y el 30 de junio de 2019. Resultados Se atendió a 5.401 pacientes (media de edad, 64±13 años; el 76,9% varones), de los que 4.366 (80,8%) sufrieron un infarto con elevación del ST. De estos, se trató al 87,5% con angioplastia primaria, al 4,4% con fibrinolisis y al 8,1% sin reperfusión. En los casos tratados con angioplastia primaria, el tiempo entre el inicio de los síntomas y la reperfusión fue 193 [135-315] min y el tiempo entre el primer contacto médico y la reperfusión, 107 [80-146] min. La mortalidad total a 30 días por infarto agudo de miocardio con elevación del ST fue del 7,9%, mientras que entre los pacientes tratados con angioplastia primaria fue del 6,8%. Conclusiones Se trató con angioplastia primaria a la inmensa mayoría de los pacientes con infarto agudo de miocardio con elevación del ST, y en más de la mitad de los casos el tiempo desde el primer contacto médico hasta la reperfusión fue <120 min. La mortalidad a 30 días fue relativamente baja (AU)

Introduction and objectives ST-segment elevation myocardial infarction (STEMI) networks should guarantee STEMI care with good clinical results and within the recommended time parameters. There is no contemporary information on the performance of these networks in Spain. The objective of this study was to analyze the clinical characteristics of patients, times to reperfusion, characteristics of the intervention performed, and 30-day mortality. Methods Prospective, observational, multicenter registry of consecutive patients treated in 17 STEMI networks in Spain (83 centers with the Infarction Code), between April 1 and June 30, 2019. Results A total of 5401 patients were attended (mean age, 64±13 years; 76.9% male), of which 4366 (80.8%) had confirmed STEMI. Of these, 87.5% were treated with primary angioplasty, 4.4% with fibrinolysis, and 8.1% did not receive reperfusion. In patients treated with primary angioplasty, the time between symptom onset and reperfusion was 193 [135-315] minutes and the time between first medical contact and reperfusion was 107 [80-146] minutes. Overall 30-day mortality due to STEMI was 7.9%, while mortality in patients treated with primary angioplasty was 6.8%. Conclusions Most patients with STEMI were treated with primary angioplasty. In more than half of the patients, the time from first medical contact to reperfusion was <120 minutes. Mortality at 30 days was relatively low (AU)

Diseño y justificación del estudio clínico aleatorizado BA-SCAD (bloqueadores beta y agentes antiplaquetarios en pacientes con disección arterial coronaria espontánea) / Rationale and design of the BA-SCAD (Beta-blockers and Antiplatelet agents in patients with Spontaneous Coronary Artery Dissection) randomized clinical trial

Introducción y objetivos: La disección coronaria espontánea (DCE) es una causa rara de síndrome coronario agudo. La mayor parte de los pacientes con DCE son tratados empíricamente con bloqueadores beta (BB) y antiagregantes plaquetarios (AP). El estudio BA-SCAD (bloqueadores beta y agentes antiplaquetarios en pacientes con disección coronaria espontánea) es un ensayo clínico académico, pragmático, diseñado con metodología PROBE (prospective randomized open blinded endpoint), con el patrocinio de la Sociedad Española de Cardiología, para conocer la eficacia del tratamiento farmacológico en pacientes con DCE. Métodos: Mediante un diseño factorial 2 × 2, se aleatorizará a 600 pacientes (1:1/1:1) a: a) BB (sí/no) y b) tratamiento con AP «corto» (1 mes) frente a tratamiento antiagregante plaquetario doble y «prolongado» (12 meses). Se aleatorizará a BB (sí/no) solo a los pacientes con fracción de eyección del ventrículo izquierdo conservada, ya que a los pacientes con fracción de eyección reducida se los tratará con BB de acuerdo con las guías actuales. De modo similar, se aleatorizará al estrato de AP solo a los pacientes en tratamiento conservador (sin revascularización), ya que los que requieran intervención coronaria recibirán tratamiento antiagregante plaquetario doble durante 1 año. El objetivo primario de valoración incluye muerte, infarto de miocardio, accidente cerebrovascular, revascularización coronaria, DCE recurrente y hospitalización no planeada por síndrome coronario agudo o insuficiencia cardiaca al año de seguimiento. El objetivo de seguridad es la hemorragia. Todos los pacientes serán seguidos anualmente. Se desarrollará un programa exhaustivo de subestudios adicionales (clínicos, de imagen, de revascularización, de biomarcadores, inflamatorios, inmunológicos, farmacogenéticos y genéticos) para garantizar una visión completa de esta entidad tan especial y compleja (AU)

introduction y objectives: Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome. Most patients are empirically treated with beta-blockers and antiplatelet drugs. The Beta-blockers and Antiplatelet agents in patients with Spontaneous Coronary Artery Dissection (BA-SCAD) is an academic, pragmatic, prospective, randomized, open-label, blinded-endpoint clinical trial, performed under the auspices of the Spanish Society of Cardiology, to assess the efficacy of pharmacological therapy in patients with SCAD. Methods: Using a 2 x 2 factorial design, 600 patients will be randomized (1:1/1:1) to: a) beta-blockers (yes/no) and b) “short” (1 month) vs “prolonged” (12 months) antiplatelet therapy. Only patients with preserved left ventricular ejection fraction will be randomized to beta-blockers (yes/no) because patients with reduced left ventricular ejection fraction will receive beta-blockers according to current guidelines. Similarly, only conservatively managed patients (ie, no coronary intervention) will be randomized to the antiplatelet stratum, as patients requiring coronary interventions will receive 1-year dual antiplatelet therapy. The primary efficacy endpoint includes a composite of death, myocardial infarction, stroke, coronary revascularization, recurrent SCAD, and unplanned hospitalization for acute coronary syndrome or heart failure at 1 year. The primary safety endpoint will be bleeding. All patients will be clinically followed up yearly. A comprehensive set of additional substudies (clinical, imaging, revascularization, biomarkers, inflammatory, immunologic, pharmacogenetics, and genetic) will be conducted to ensure a holistic view of this unique and challenging clinical entity.Conclusions: The results of the BA-SCAD randomized clinical trial will advance our knowledge in the treatment of patients with SCAD (AU)

Regional analysis of inflammation and contractile function in reperfused acute myocardial infarction by in vivo 19F cardiovascular magnetic resonance in pigs.

Inflammatory cell infiltration is central to healing after acute myocardial infarction (AMI). The relation of regional inflammation to edema, infarct size (IS), microvascular obstruction (MVO), intramyocardial hemorrhage (IMH), and regional and global LV function is not clear. Here we noninvasively characterized regional inflammation and contractile function in reperfused AMI in pigs using fluorine (19F) cardiovascular magnetic resonance (CMR). Adult anesthetized pigs underwent left anterior descending coronary artery instrumentation with either 90 min occlusion (n = 17) or without occlusion (sham, n = 5). After 3 days, in surviving animals a perfluorooctyl bromide nanoemulsion was infused intravenously to label monocytes/macrophages. At day 6, in vivo 1H-CMR was performed with cine, T2 and T2* weighted imaging, T2 and T1 mapping, perfusion and late gadolinium enhancement followed by 19F-CMR. Pigs were sacrificed for subsequent ex vivo scans and histology. Edema extent was 35 ± 8% and IS was 22 ± 6% of LV mass. Six of ten surviving AMI animals displayed both MVO and IMH (3.3 ± 1.6% and 1.9 ± 0.8% of LV mass). The 19F signal, reflecting the presence and density of monocytes/macrophages, was consistently smaller than edema volume or IS and not apparent in remote areas. The 19F signal-to-noise ratio (SNR) > 8 in the infarct border zone was associated with impaired remote systolic wall thickening. A whole heart value of 19F integral (19F SNR × milliliter) > 200 was related to initial LV remodeling independently of edema, IS, MVO, and IMH. Thus, 19F-CMR quantitatively characterizes regional inflammation after AMI and its relation to edema, IS, MVO, IMH and regional and global LV function and remodeling.

Balance entre el efecto de los eventos embólicos frente a los hemorrágicos en la mortalidad de los pacientes ancianos con fibrilación auricular / Trade-off between the effects of embolic versus bleeding events on mortality in elderly patients with atrial fibrillation

Introducción y objetivos: La toma de decisiones clínicas sobre la anticoagulación de pacientes ancianos con fibrilación auricular (FA) requiere que se considere no solo la incidencia de eventos embólicos y hemorrágicos, sino también el riesgo de muerte tras esos efectos adversos. Nuestro objetivo es analizar el balance con respecto a la mortalidad entre los eventos embólicos y hemorrágicos en pacientes ancianos con FA. Métodos: Se analizó a todos los pacientes de 75 o más años de un área de salud española diagnosticados de FA entre 2014 y 2017 (n=9.365). El riesgo de muerte se estimó utilizando modelos de Cox que incluyeron los episodios embólicos y hemorrágicos como variables dependientes del tiempo. Resultados: Durante una mediana de seguimiento de 4,0 años, los eventos se asociaron con mayor mortalidad, tanto los embólicos (HR=2,39; IC95%, 2,12-2,69) como los hemorrágicos (HR=1,79; IC95%, 1,64-1,96). El riesgo de muerte fue un 33% mayor después de una embolia que después de una hemorragia (rRR=1,33; IC95%, 1,15-1,55), aunque con accidente isquémico transitorio el riesgo fue menor que con hemorragia (rRR=0,79; IC95%, 0,63-0,99). La mortalidad tras una hemorragia intracraneal fue similar que tras una embolia mayor (RR=1,00; IC95%, 0,75-1,29). Conclusiones: En los pacientes de edad avanzada con FA, los eventos embólicos parecen estar asociados con una mayor mortalidad que las hemorragias extracraneales, salvo los accidentes isquémicos transitorios. Con hemorragia intracraneal, el riesgo de muerte es similar al de una embolia mayor (AU)

Introduction and objectives: Clinical decision-making on anticoagulation in elderly patients with atrial fibrillation (AF) requires clinicians to consider not only the incidence of embolic and bleeding events, but also the risk of death following these adverse events. We aimed to analyze the trade-off between embolic and bleeding events with respect to mortality in elderly patients with AF. Methods: The study cohort comprised all patients aged ≥ 75 years from a Spanish health area diagnosed with AF between 2014 and 2017 (n=9365). The risk of death was investigated using Cox proportional hazards models, including embolic and bleeding events as time-dependent binary indicators. Results: During a median follow-up of 4.0 years, both embolic and bleeding events were associated with a higher risk of death (adjusted HR, 2.39; 95%CI, 2.12-2.69; and adjusted HR, 1.79; 95%CI, 1.64-1.96, respectively). The relative risk of death was 33% higher following an embolism than following a bleeding event (rRR, 1.33; 95%CI, 1.15-1.55), although for transient ischemic attack the risk was lower than for bleeding (rRR, 0.79; 95%CI, 0.63-0.99). The risk of death associated with intracranial hemorrhage was similar to that of major embolisms (RR, 1.00; 95%CI, 0.75-1.29). Conclusions: In elderly AF patients, embolic events appeared to be associated with a higher risk of mortality than extracranial bleeding, except for transient ischemic attacks, which have a better prognosis. For ICH, the mortality risk was similar to that of major embolism (AU)

Transcultural adaptation and validation of the Spanish-language version of ACTIVLIM in adults with inherited myopathies using the Rasch model.

INTRODUCTION: ACTIVLIM is an instrument for the measurement of activity limitations in patients with neuromuscular disorders. The aim of this study is to establish a transcultural adaptation and psychometric validation of the Spanish-language version of ACTIVLIM in a sample of Spanish patients with inherited myopathies. PATIENTS AND METHOD: A Spanish-language version of ACTIVLIM was developed using the translation/back translation method. The questionnaire was administered to 135 patients with inherited myopathies. The psychometric properties of the questionnaire were assessed using the Rasch model. Floor and ceiling effects were estimated. Unidimensionality was evaluated with a principal component analysis of the residuals of the model, and using infit and outfit statistics. We estimated reliability with the person separation reliability index and invariance with differential item functioning. External construct validity was tested through correlation with the Brooke scale, the Vignos scale, the Functional Independence Measure scale, and floor-to-stand time. Test-retest reliability was evaluated with the intraclass correlation coefficient and differential item functioning. RESULTS: The psychometric analysis of the Spanish-language version of ACTIVLIM demonstrated that floor effect was absent, although a modest ceiling effect was identified. The instrument displayed unidimensionality, good internal consistency, external construct validity, and good test-retest reliability. CONCLUSION: The Spanish-language version of ACTIVLIM is a valid and reliable measurement instrument for assessing activity limitations in patients with inherited myopathies.

ACTIVLIM: adaptación transcultural al castellano y validación en adultos con miopatías hereditarias utilizando el modelo Rasch / Transcultural adaptation and validation of the Spanish-language version of ACTIVLIM in adults with inherited myopathies using the Rasch model

Introducción: ACTIVLIM es un instrumento de medición de la limitación funcional en pacientes con enfermedades neuromusculares. El objetivo de este estudio es la adaptación transcultural y la validación psicométrica de la versión en castellano del ACTIVLIM en una muestra española de pacientes con miopatías hereditarias.Pacientes y métodoSe elaboró una versión en castellano del cuestionario ACTIVLM mediante el método de traducción-retrotraducción. El cuestionario obtenido fue cumplimentado por 135 pacientes con miopatías hereditarias. Las propiedades psicométricas del mismo fueron evaluadas mediante el modelo Rasch. Se valoró la adecuación del rango mediante la estimación de efectos techo y suelo; la unidimensionalidad mediante análisis de componentes principales de los residuales del modelo y estadísticos infit y outfit; la fiabilidad mediante el índice de fiabilidad asociado al índice de separación y la invarianza mediante la estimación del funcionamiento diferencial. Asimismo, la validez de constructo se evaluó estimando la correlación con las escalas de Brooke, de Vignos, la medida de independencia funcional y el tiempo de Gowers, y la fiabilidad test-retest mediante el índice de correlación intraclase y con el plot del funcionamiento diferencial del ítem.ResultadosEl análisis psicométrico de la versión en castellano del ACTIVLIM demostró ausencia de efecto suelo y moderado efecto techo, unidimensionalidad, una buena consistencia interna, validez externa de constructo y buena fiabilidad test-retest.ConclusiónLa versión en castellano del ACTIVLIM es un instrumento de medición válido y fiable para evaluar las limitaciones en la actividad en pacientes con miopatías hereditarias. (AU)

Introduction: ACTIVLIM is an instrument for the measurement of activity limitations in patients with neuromuscular disorders. The aim of this study is to establish a transcultural adaptation and psychometric validation of the Spanish-language version of ACTIVLIM in a sample of Spanish patients with inherited myopathies.Patients and methodA Spanish-language version of ACTIVLIM was developed using the translation/back translation method. The questionnaire was administered to 135 patients with inherited myopathies. The psychometric properties of the questionnaire were assessed using the Rasch model. Floor and ceiling effects were estimated. Unidimensionality was evaluated with a principal component analysis of the residuals of the model, and using infit and outfit statistics. We estimated reliability with the person separation reliability index and invariance with differential item functioning. External construct validity was tested through correlation with the Brooke scale, the Vignos scale, the Functional Independence Measure scale, and floor-to-stand time. Test-retest reliability was evaluated with the intraclass correlation coefficient and differential item functioning.ResultsThe psychometric analysis of the Spanish-language version of ACTIVLIM demonstrated that floor effect was absent, although a modest ceiling effect was identified. The instrument displayed unidimensionality, good internal consistency, external construct validity, and good test-retest reliability.ConclusionThe Spanish-language version of ACTIVLIM is a valid and reliable measurement nstrument for assessing activity limitations in patients with inherited myopathies. (AU)

Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study.

BACKGROUND: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. PATIENTS AND METHODS: We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA-IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. RESULTS: The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799-1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458-1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690-1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. CONCLUSION: We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. CLINICAL TRIALS IDENTIFIER: NCT04037124.

Vaginal fertility-sparing surgery and laparoscopic sentinel lymph node detection in early cervical cancer. Retrospective study with 15 years of follow-up.

OBJECTIVE: The aim of this study was to evaluate the oncological outcomes of vaginal fertility-sparing surgery plus laparoscopic sentinel lymph node biopsy in patients with early cervical cancer over a 15-years period. PATIENTS AND METHODS: From March 2005 to April 2018, 38 patients diagnosed with early stage cervical cancer underwent vaginal fertility-sparing surgery at the Hospital Clínic, Barcelona, Spain. Patients with FIGO stage IA1 with lymphovascular space invasion and stage IA2 underwent simple trachelectomy and patients with stage IB1 underwent radical vaginal trachelectomy. All cases underwent laparoscopic sentinel lymph node biopsy. In the first 19 cases, laparoscopic bilateral pelvic lymphadenectomy was completed immediately after sentinel lymph node biopsy. Clinical and oncological follow-up data were collected. RESULTS: The median age at diagnosis was 33.5 years (range 22-44). Simple trachelectomy was performed in seven cases (18.4%) and vaginal radical trachelectomy in 31 (81.6%). Nineteen patients were exclusively treated with laparoscopic sentinel lymph node biopsy and 19 with sentinel lymph node biopsy plus laparoscopic bilateral pelvic lymphadenectomy. There were no significant differences between the two lymph node assessment groups regarding histology and tumour size. The median follow-up was 73 months (range 1-160 months). There were 4 recurrences (3 patients with IB1 and 1 with IA2). Two occurred in the sentinel lymph node biopsy group and 2 in the sentinel lymph node biopsy plus laparoscopic bilateral pelvic lymphadenectomy group. All the recurrences were diagnosed in patients with adenocarcinoma and in 3 patients without lymphovascular space invasion. CONCLUSION: Vaginal fertility-sparing surgery combined with laparoscopic sentinel lymph node biopsy seems to be a safe oncological procedure in selected patients with early stage cervical cancer. Further studies are needed to clarify the role of sentinel lymph node biopsy in fertility- sparing surgery in cervical cancer. Adenocarcinoma histology seems to be an important risk factor for recurrence.

[Long-term effects of a mindfulness and self-compassion program with Primary Healthcare professionals]. / Persistencia a largo plazo de los efectos de un programa de mindfulness y autocompasión en profesionales sanitarios de Atención Primaria.

BACKGROUND: The effectiveness of mindfulness and self-compassion-based interventions (MSCI) on emotional fatigue and stress in Primary Healthcare (PHC) professionals has been demonstrated in the short term. The aims of this work were to assess whether these effects persist after two years, and if the observed results differ between those who practiced mindfulness regularly during the follow-up (meditators) and those who did not. METHODS: Prospective study - pre-post and two years after performing an MSCI that was offered to all PHC professionals in Navarra, with group sessions of 2.5 hours / week for 8 weeks. Attending at least 75% of the sessions and practicing at home for 45 minutes a day were mandatory. At the three moments of the study, questionnaires were distributed to measure levels of mindfulness (FFMQ), self-compassion (SCS), perceived stress (PSQ) and burnout (MBI). At the end of the follow-up period, participants were asked if they were meditators and the time they dedicated to this weekly. RESULTS: Forty-eight professionals were enrolled and 41 (83% women) met the inclusion criteria, without loss to follow-up. Mean scores in mindfulness, self-compassion and perceived stress significantly improved after the intervention and in the long term (p <0.001), without observing differences in the level of burnout. The group of meditators achieved a greater long-term improvement in self-compassion (3.6 points vs. 1.6). CONCLUSIONS: The effectiveness of an MSCI persists two years later regardless of meditator status, although there is a significant improvement in self-compassion in the meditators.

Persistencia a largo plazo de los efectos de un programa de mindfulness y autocompasión en profesionales sanitarios de Atención Primaria / Long-term effects of a mindfulness and self-compassion program with Primary Healthcare professionals

INTRODUCCIÓN: La efectividad de las intervenciones basadas en mindfulness (IBM) y autocompasión sobre el cansancio emocional y el estrés en profesionales sanitarios de Atención Primaria (AP) ha sido demostrada a corto plazo. Los objetivos de este trabajo fueron valorar si esos efectos persisten a los dos años, y si los resultados encontrados difieren entre quienes practicaron mindfulness habitualmente durante ese tiempo (meditadores) y los que no. MATERIAL Y MÉTODOS: Estudio prospectivo antes-después y a los dos años de realizar una IBM ofertado a todos los profesionales sanitarios de AP de Navarra, con sesiones grupales de 2,5 horas/semana durante 8 semanas. Se requería asistir al menos al 75% de las sesiones y practicar en casa 45 minutos diarios. En los tres momentos se pasaron cuestionarios para medir los niveles de mind-fulness (FFMQ), autocompasión (SCS), estrés percibido (PSQ) y burnout (MBI). A los dos años tras la intervención se les preguntó si practicaban habitualmente mind-fulness y el tiempo semanal dedicado a ello. RESULTADOS: Aceptaron 48 profesionales y 41 (83% mujeres) cumplieron los criterios de inclusión, sin pérdidas en el seguimiento. Las puntuaciones medias en mind-fulness, autocompasión y estrés percibido mejoraron significativamente tras la intervención y a largo plazo (p < 0,001), sin obtenerse diferencias en el nivel de burnout. La mejoría a largo plazo en autocompasión fue mayor en el grupo que meditó regularmente (3,6 puntos vs 1,6). CONCLUSIONES: La efectividad de una IBM persiste a los dos años de la intervención independientemente de si se practicó meditación o no, aunque la autocompasión mejoró significativamente más en los meditadores

BACKGROUND: The effectiveness of mindfulness and self-compassion-based interventions (MSCI) on emotional fatigue and stress in Primary Healthcare (PHC) professionals has been demonstrated in the short term. The aims of this work were to assess whether these effects persist after two years, and if the observed results differ between those who practiced mindfulness regularly during the follow-up (meditators) and those who did not. METHODS: Prospective study - pre-post and two years after performing an MSCI that was offered to all PHC professionals in Navarra, with group sessions of 2.5 hours / week for 8 weeks. Attending at least 75% of the sessions and practicing at home for 45 minutes a day were mandatory. At the three moments of the study, questionnaires were distributed to measure levels of mindfulness (FFMQ), self-compassion (SCS), perceived stress (PSQ) and burnout (MBI). At the end of the follow-up period, participants were asked if they were meditators and the time they dedicated to this weekly. RESULTS: Forty-eight professionals were enrolled and 41 (83% women) met the inclusion criteria, without loss to follow-up. Mean scores in mindfulness, self-compassion and perceived stress significantly improved after the intervention and in the long term (p <0.001), without observing differences in the level of burnout. The group of meditators achieved a greater long-term improvement in self-compassion (3.6 points vs. 1.6). CONCLUSIONS: The effectiveness of an MSCI persists two years later regardless of meditator status, although there is a significant improvement in self-compassion in the meditators

Pathology findings and clinical outcomes after risk reduction salpingo-oophorectomy in BRCA mutation carriers: a multicenter Spanish study

Objective: To determine the incidence of serous tubal intraepithelial carcinoma (STIC) after risk reduction salpingo-oophorectomy(RRSO), and to describe oncological outcomes after RRSO. Materials and methods: BRCA pathogenic mutation carriers who had undergone an RRSO were evaluated in this retrospective multicenter observational study. Patients were only included when fallopian tubes were analyzed following the protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Surgeries were performed between June 2010 and April 2017 at eight Spanish hospitals.Results: A total of 359 patients met the inclusion criteria. STIC was diagnosed in 3 (0.8%) patients; one of them underwent surgical staging due to positive peritoneal washing, with absence of disease at the final pathology report. None of the three patients received adjuvant chemotherapy and were free of disease at last follow-up. Fallopian tube and ovarian carcinoma were diagnosed in 5 (1.4%) and 1 (0.3%), respectively. At a median (range) follow-up time of 29 (3-92) months, five patients had a newly diagnosed breast cancer. Other types of cancer, which were diagnosed during the follow-up time, included: serous primary peritoneal carcinoma (n = 1), serous endometrial carcinoma (n = 1), colon (n = 1), pancreas (n = 1), jaw (n = 1), and lymphoma (n = 1). Seven patients died due to different types of cancer: breast (n = 4), pancreas (n = 1), jaw (n = 1), and colon (n = 1). Conclusion: The incidence of STIC after RRSO in BRCA mutation carriers is low (0.8%) and it presents an excellent oncological outcome. Patients after RRSO, however, run the risk to develop other types of cancer during follow-up and should be properly advised before the prophylactic surgery

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Pathology findings and clinical outcomes after risk reduction salpingo-oophorectomy in BRCA mutation carriers: a multicenter Spanish study.

OBJECTIVE: To determine the incidence of serous tubal intraepithelial carcinoma (STIC) after risk reduction salpingo-oophorectomy(RRSO), and to describe oncological outcomes after RRSO. MATERIALS AND METHODS: BRCA pathogenic mutation carriers who had undergone an RRSO were evaluated in this retrospective multicenter observational study. Patients were only included when fallopian tubes were analyzed following the protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Surgeries were performed between June 2010 and April 2017 at eight Spanish hospitals. RESULTS: A total of 359 patients met the inclusion criteria. STIC was diagnosed in 3 (0.8%) patients; one of them underwent surgical staging due to positive peritoneal washing, with absence of disease at the final pathology report. None of the three patients received adjuvant chemotherapy and were free of disease at last follow-up. Fallopian tube and ovarian carcinoma were diagnosed in 5 (1.4%) and 1 (0.3%), respectively. At a median (range) follow-up time of 29 (3-92) months, five patients had a newly diagnosed breast cancer. Other types of cancer, which were diagnosed during the follow-up time, included: serous primary peritoneal carcinoma (n = 1), serous endometrial carcinoma (n = 1), colon (n = 1), pancreas (n = 1), jaw (n = 1), and lymphoma (n = 1). Seven patients died due to different types of cancer: breast (n = 4), pancreas (n = 1), jaw (n = 1), and colon (n = 1). CONCLUSION: The incidence of STIC after RRSO in BRCA mutation carriers is low (0.8%) and it presents an excellent oncological outcome. Patients after RRSO, however, run the risk to develop other types of cancer during follow-up and should be properly advised before the prophylactic surgery.

Incidencia de diabetes tipo 1 en Navarra (2009-2016): mayor en la zona sur de la comunidad / Incidence of type 1 diabetes in Navarre (2009-2016): higher in the southern regions of the autonomous community

Fundamento: Las variaciones geográficas y estacionales en la incidencia de diabetes tipo 1 (DM1) son útiles para intentar conocer la etiopatogenia de la enfermedad. El objetivo de este estudio consiste en conocer los datos de incidencia de DM1 en Navarra durante el período 2009-2016, su distribución geográfica y su variación en cuanto a la estación del año en la que tiene lugar tanto el nacimiento como el diagnóstico de las personas afectadas. Métodos: Estudio prospectivo, con una fuente primaria y tres secundarias. La exhaustividad del registro se evaluó mediante el método de captura-recaptura y fue del 96,08%. La estimación de las tasas e intervalos de confianza al 95% por zonas y estaciones al debut se realizó asumiendo una distribución subyacente de Poisson. La influencia independiente de las variables edad al debut, sexo, zonas y estaciones del año, se estudió mediante la regresión de Poisson. Para la comparación de la incidencia interregional, los valores obtenidos se ajustaron por el método de estandarización indirecta. Resultados: Se detectaron 428 casos (incidencia= 8,36/100.000 habitantes-año; IC95%: 7,58-9,19). La enfermedad predomina en hombres (63%). La incidencia en menores de 15 años fue mayor que en los adultos (21,54; IC95%: 18,43-25,02 vs. 5,94; IC95%: 5,23-6,71; p<0,001). Se observa mayor incidencia en las cuatro regiones del sur de la Comunidad Foral, y en invierno y primavera como estaciones al debut. No hay diferencias en la estación al nacimiento. Conclusión: Navarra mantiene una alta incidencia de DM1 en la infancia que va disminuyendo progresivamente con la edad. Se detectan diferencias por sexo, edad, zona geográfica y estación al diagnóstico (AU)

Background: Geographical and seasonal variations of type 1 diabetes (T1D) are useful for establishing the key ethiopathogenic factors of the disease. The present work seeks to analyze the incidence rates of T1D in Navarre for the 2009-2016 period, its geographical distribution and seasonal variations in birth and diagnosis in affected persons. Methods: Prospective study with one primary and three secondary sources. The completeness of the registry, determined using the capture-recapture method, was 96.08%. The confidence intervals of zone and onset season incidence rates were determined assuming an underlying Poisson distribution. Adjusted effect of onset age, sex, onset season and geographical area over changes in incidence rates were analyzed using a Poisson regression model. Comparison among areas was carried out after the corresponding adjustments of incidence by the indirect standardization method. Results: Four hundred and twenty-eight new cases were detected (incidence= 8.36/100,000 inhabitants per year, CI95%: 7.58-9.19). The disease is predominant in males (63% of patients). The incidence in children under 15 years was higher than in adults (21.54, CI95%: 18.43-25.02 vs. 5.94, CI95%: 5.23-6.71; p<0.001). Incidence was highest in the four southern regions of Navarre, most of the cases being in winter and spring. No differences were found regarding birth season over incidence. Conclusion: Navarre maintains a high T1D incidence in childhood that decreases progressively with age. Sex, age group, geographical zone and onset season are independently associated with the incidence rates observed in the study (AU)

[Incidence of type 1 diabetes in Navarre (2009-2016): higher in the southern regions of the autonomous community]. / Incidencia de diabetes tipo 1 en Navarra (2009-2016): mayor en la zona sur de la comunidad.

BACKGROUND: Geographical and seasonal variations of type 1 diabetes (T1D) are useful for establishing the key ethio-pathogenic factors of the disease. The present work seeks to analyze the incidence rates of T1D in Navarre for the 2009-2016 period, its geographical distribution and seasonal variations in birth and diagnosis in affected persons. METHODS: Prospective study with one primary and three secondary sources. The completeness of the registry, determined using the capture-recapture method, was 96.08%. The confidence intervals of zone and onset season incidence rates were determined assuming an underlying Poisson distribution. Adjusted effect of onset age, sex, onset season and geographical area over changes in incidence rates were analyzed using a Poisson regression model. Comparison among areas was carried out after the corresponding adjustments of incidence by the indirect standardization method. RESULTS: Four hundred and twenty-eight new cases were detected (incidence= 8.36/100,000 inhabitants per year, CI95%: 7.58-9.19). The disease is predominant in males (63% of patients). The incidence in children under 15 years was higher than in adults (21.54, CI95%: 18.43-25.02 vs. 5.94, CI95%: 5.23-6.71; p<0.001). Incidence was highest in the four southern regions of Navarre, most of the cases being in winter and spring. No differences were found regarding birth season over incidence. CONCLUSION: Navarre maintains a high T1D incidence in childhood that decreases progressively with age. Sex, age group, geographical zone and onset season are independently associated with the incidence rates observed in the study.

[A comparative study of three systems for quantifying the spike and wave index in patients with continuous spikes and waves during slow sleep]. / Estudio comparativo entre tres sistemas de cuantificacion del indice de punta-onda en pacientes con punta-onda continua del sueño lento.

INTRODUCTION: Continuous spikes and waves during slow sleep (CSWS) is an epileptic encephalopathy of childhood with a pattern of epileptiform discharges during sleep, which, if prolonged over time, produce severe neuropsychological impairment. Quantification of the paroxysms by means of a spike and wave index (SWI) > 85% establishes a presumptive diagnosis and allows early therapy to be started to prevent such impairment. AIMS: To compare the results of the classic method for calculating the SWI against two proposals that optimise the relation between the analysis time employed and the diagnostic sensitivity. PATIENTS AND METHODS: The nocturnal electroencephalographic registers of 17 patients with CSWS were studied. Two observers calculated the SWI with the classic method, as well as with two other methods, M2 and M3, first in the active phase and then in the remission phase. The time required by each method, the individual SWI values and the agreement between methods and observers were compared. RESULTS: With M3 two of the patients failed to reach the cut-off point of SWI > 85%. Agreement in the active phase of CSWS after M2 and M3 was 0.762 and 0.704, respectively, while in the remission phase it was 0.951 and 0.830. Inter-observer agreement exceeded 0.905 in all cases. CONCLUSIONS: The two abbreviated methods can be used in both the active and the remission phases, with a substantial reduction in the analysis time that is needed. Our results support the current tendency to consider SWI > 60% as suggestive of CSWS. Method M2 yields results that are closer to those of the classic method than those of M3.

TITLE: Estudio comparativo entre tres sistemas de cuantificacion del indice de punta-onda en pacientes con punta-onda continua del sueño lento.Introduccion. La punta-onda continua del sueño lento (POCS) es una encefalopatia epileptiforme infantil con un patron de descargas epileptiformes durante el sueño que, prolongadas en el tiempo, producen un grave deterioro neuropsicologico. La cuantificacion de los paroxismos mediante el indice de punta-onda (SWI) > 85% establece un diagnostico de sospecha y permite iniciar una terapia precoz que puede evitar dicho deterioro. Objetivos. Comparar los resultados del metodo clasico de calculo del SWI con dos propuestas que optimicen la relacion entre el tiempo de analisis empleado y la sensibilidad diagnostica. Pacientes y metodos. Se estudiaron los registros electroencefalograficos nocturnos de 17 pacientes con POCS. Dos observadores calcularon el SWI con el metodo clasico, asi como con otros dos metodos, M2 y M3, primero en la fase activa y posteriormente en la fase de remision de la POCS. Se comparo el tiempo consumido por cada metodo, los valores individuales de SWI y la concordancia entre metodos y observadores. Resultados. Con el M3 dos pacientes no alcanzaron el corte del SWI > 85%. La concordancia en la fase activa de la POCS tras el M2 y el M3 fue de 0,762 y 0,704, respectivamente, mientras que en la fase de remision fue de 0,951 y 0,830. La concordancia entre observadores supero el 0,905 en todos los casos. Conclusiones. Los dos metodos abreviados se pueden utilizar tanto en la fase activa de la POCS como en la fase de remision, con una sustancial reduccion del tiempo de analisis empleado. Nuestros resultados apoyan la tendencia actual de considerar el SWI > 60% como sugestivo de POCS. El metodo M2 arroja resultados mas cercanos a los del metodo clasico que los de M3.