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.

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.

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.

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.

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.

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.

[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.

Fecal incontinence and radiation dose on anal sphincter in patients with locally advanced rectal cancer (LARC) treated with preoperative chemoradiotherapy: a retrospective, single-institutional study.

BACKGROUND: The objective of the study is to determine the correlations among the variables of dose and the sphincter function (SF) in patients with locally advanced rectal cancer treated with preoperative capecitabine/radiotherapy followed by low anterior resection (LAR) + TME. METHODS: We retrospectively reviewed 92 consecutive patients with LARC treated at our center with LAR from 2006 and more than 2 years free from disease. We re-contoured the anal sphincters (AS) of patients with the help of the radiologist. SF was assessed with the Wexner scale (0-20 points, being punctuation inversely proportional to annal sphincter functionality). All questionnaires were filled out between January 2010 and December 2012. Dosimetric parameters that have been studied include V 20, V 30, V 40, V 50, mean dose (D mean), minimum dose (D min), D 90 (dose received by 90% of the sphincter) and D 98. STATISTICAL ANALYSIS: The correlations among the variables of dose and SF were studied by the Spearman correlation coefficient. Differences in SF relating to maximum doses to the sphincter were assessed by the Mann-Whitney test. RESULTS: Mean Wexner score was 5.5 points higher in those patients with V 20 > 0 compared to those for which V 20 = 0 (p = 0.008). In a multivariate regression model, results suggest that the effect of V 20 on poor anal sphincter control is independent of the effect of distance, with an adjusted OR of 3.42. CONCLUSIONS: In order to improve the SF in rectal cancer treated with preoperative radiotherapy/capecitabine followed by conservative surgery, the maximum radiation dose to the AS should be limited, when possible, to <20 Gy.

Missing patients in "Major Trauma Registry" of Navarre: incidence and pattern.

BACKGROUND: Trauma registries (TR) collect information about trauma patients according to inclusion criteria, and it helps to establish protocols to improve care. However, all TR deal with incompleteness. The aim of this study is to assess the number of patients not included despite fulfilling inclusion criteria in our regional TR and identifying the predictors for being missing. METHODS: The sample was randomly selected. Two months of each year from 2010 to 2014 (5 years) were selected, and medical files of all patients attended in the emergency department room during those months were studied. Patients who were already correctly included in the TR were assigned to the 'included' group, and patients who should have been but were not to the 'missing' group. The multivariable logistic regression analysis was performed to identify predictors for being missed from the TR. RESULTS: Of a total of 200, 79 (40 % approximately) were identified as missing. We defined the characteristic profiles of missing patients and found that the hospital RTS and the number of injuries are independent predictors to be missing in our trauma registry, with an adjusted odds ratio of 1844 [95 % (1092-3114) and 0.574 (95 % CI 0.428-0.770)], respectively. CONCLUSIONS: Overall, 40 % of the patients who met the inclusion criteria of the TR were not included in the registry. Our results can be generalized to other trauma records based on Utstein style, because we think probably that this fact is also happening in other databases.

Insomnia in patients admitted to psychiatric hospital departments / Insomnio en pacientes que ingresan en unidades de hospitalización psiquiátricas.

Background. The aim of this study is to estimate the prevalence of insomnia in patients requiring admittance to short-stay hospital psychiatric units. Methodology. A descriptive observational study was designed with the participation of 16 units for brief adult psychiatric hospitalization in Spain. The Athens Insomnia Scale was the instrument used. Results. Four hundred and twenty-five patients were included, with an average value on the global score of the Athens Insomnia Scale of 8.56 (SD: 5.78). The item that obtained the highest average score concerned the presence of waking up during the night, followed by that concerning the time needed to fall asleep. The estimated prevalence of insomnia is 53% (CI 95%). Conclusions. Insomnia is a problem with a high prevalence in psychiatric hospitalization units. The greatest difficulties are found in inducing sleep and staying asleep.

Sex and age differences in the achievement of control targets in patients with type 2 diabetes: results from a population-based study in a South European region.

BACKGROUND: We aimed to determine the degree to which control targets of glycaemia and cardiovascular risk factors were achieved among patients with type 2 diabetes and to investigate sex- and age-related differences in this population. METHODS: This cross-sectional, population-based study was conducted in Spain. Glycated hemoglobin (HbA1c), blood pressure, LDL-c, HDL-c, triglycerides, BMI, and smoking history were obtained from electronic clinical primary care records (n = 32,638 cases). The proportions of patients who met control targets were determined according to sex and age groups. Comparisons between groups were conducted with t-tests for continuous variables, tests for trends in proportions for categorical and ordinal variables, and Pearson's chi-square tests and binary logistic regression models for categorical variables. RESULTS: The overall proportions of patients with type 2 diabetes who met the target objectives for HbA1c (<7 %, 53 mmol/mol), blood pressure (130/80 mmHg), and LDL-cholesterol (100 mg/dl) were 60, 40 and 41 %, respectively. Women were less likely than men to meet the control targets of HbA1c (59 vs 61 %), LDL (35 vs 45 %), and HDL (58 vs 78 %). Patients under 65 years of age presented poorer control than older age groups. Only a minority of patients with type 2 diabetes met the composite target objectives for glycemic control, blood pressure, and LDL. CONCLUSIONS: There are differential gaps in the control results of female patients and younger patients, which should prompt improvements in case management and care. There is room for further improvement in the cardiometabolic control of patients with type 2 diabetes.

9th Hatter Biannual Meeting: position document on ischaemia/reperfusion injury, conditioning and the ten commandments of cardioprotection.

In the 30 years since the original description of ischaemic preconditioning, understanding of the pathophysiology of ischaemia/reperfusion injury and concepts of cardioprotection have been revolutionised. In the same period of time, management of patients with coronary artery disease has also been transformed: coronary artery and valve surgery are now deemed routine with generally excellent outcomes, and the management of acute coronary syndromes has seen decade on decade reductions in cardiovascular mortality. Nonetheless, despite these improvements, cardiovascular disease and ischaemic heart disease in particular, remain the leading cause of death and a significant cause of long-term morbidity (with a concomitant increase in the incidence of heart failure) worldwide. The need for effective cardioprotective strategies has never been so pressing. However, despite unequivocal evidence of the existence of ischaemia/reperfusion in animal models providing a robust rationale for study in man, recent phase 3 clinical trials studying a variety of cardioprotective strategies in cardiac surgery and acute ST-elevation myocardial infarction have provided mixed results. The investigators meeting at the Hatter Cardiovascular Institute workshop describe the challenge of translating strong pre-clinical data into effective clinical intervention strategies in patients in whom effective medical therapy is already altering the pathophysiology of ischaemia/reperfusion injury-and lay out a clearly defined framework for future basic and clinical research to improve the chances of successful translation of strong pre-clinical interventions in man.

Randomized comparison of three transducer orientation approaches for ultrasound guided internal jugular venous cannulation.

BACKGROUND: Ultrasound-guided internal jugular venous access increases the rate of successful cannulation and reduces the incidence of complications, compared with the landmark technique. Three transducer orientation approaches have been proposed for this procedure: short-axis (SAX), long-axis (LAX) and oblique-axis (OAX). Our goal was to assess and compare the performance of these approaches. METHODS: A prospective randomized clinical trial was conducted in one teaching hospital. Patients aged 18 yr or above, who were undergoing ultrasound-guided internal jugular cannulation, were randomly assigned to one of three intervention groups: SAX, LAX and OAX group. The main outcome measure was successful cannulation on first needle pass. Incidence of mechanical complications was also registered. Restricted randomization was computer-generated. RESULTS: In total, 220 patients were analysed (SAX n=73, LAX n=75, OAX n=72). Cannulation was successful on first needle pass in 51 (69.9%) SAX patients, 39 (52%) LAX patients and 53 (73.6%) OAX patients. First needle pass failure was higher in the LAX group than in the OAX group (adjusted OR 3.7, 95% CI 1.71-8.0, P=0.002). A higher mechanical complication rate was observed in the SAX group (15.1%) than in the OAX (6.9%) and LAX (4%) groups (P=0.047). CONCLUSIONS: As OAX showed a higher first needle pass success rate than LAX and a lower mechanical complications rate than SAX, we recommend it as the standard approach when performing ultrasound-guided internal jugular venous access. Further clinical studies are needed to confirm this conclusion. CLINICAL TRIAL REGISTRATION: NCT 01966354.

Erratum:Quality of life in long-term premenopausal early-stage breast cancer survivors from Spain. Effects of surgery and time since surgery.

In this article published in Volume 21, issue 5, the authors' names were incorrectly stated in the Pubmed abstract as: "Ignacio Arraras J(1), Juan Illarramendi J, de la Cruz S, Asin G, Manterola A, Ibanez B, Salgado E, Cambra K, Zarandona U, Angel Dominguez M, Vera R.". The correct authors' names are: "Arraras JI(1), Illarramendi JJ, de la Cruz S, Asin G, Manterola A, Ibanez B, Salgado E, Cambra K, Zarandona U, Dominguez MA, Vera R.". This error appeared only in the PubMed database and not in the print form of the Journal.

EPB41L3, TSP-1 and RASSF2 as new clinically relevant prognostic biomarkers in diffuse gliomas.

Hypermethylation of tumor suppressor genes is one of the hallmarks in the progression of brain tumors. Our objectives were to analyze the presence of the hypermethylation of EPB41L3, RASSF2 and TSP-1 genes in 132 diffuse gliomas (astrocytic and oligodendroglial tumors) and in 10 cases of normal brain, and to establish their association with the patients' clinicopathological characteristics. Gene hypermethylation was analyzed by methylation-specific-PCR and confirmed by pyrosequencing (for EPB41L3 and TSP-1) and bisulfite-sequencing (for RASSF2). EPB41L3, RASSF2 and TSP-1 genes were hypermethylated only in tumors (29%, 10.6%, and 50%, respectively), confirming their cancer-specific role. Treatment of cells with the DNA-demethylating-agent 5-aza-2'-deoxycytidine restores their transcription, as confirmed by quantitative-reverse-transcription-PCR and immunofluorescence. Immunohistochemistry for EPB41L3, RASSF2 and TSP-1 was performed to analyze protein expression; p53, ki-67, and CD31 expression and 1p/19q co-deletion were considered to better characterize the tumors. EPB41L3 and TSP-1 hypermethylation was associated with worse (p = 0.047) and better (p = 0.037) prognosis, respectively. This observation was confirmed after adjusting the results for age and tumor grade, the role of TSP-1 being most pronounced in oligodendrogliomas (p = 0.001). We conclude that EPB41L3, RASSF2 and TSP-1 genes are involved in the pathogenesis of diffuse gliomas, and that EPB41L3 and TSP-1 hypermethylation are of prognostic significance.