[Reversible cerebral vasoconstriction syndrome. Recurrence of thunderclap headaches after treatment with corticosteroids]. / Síndrome de vasoconstricción cerebral reversible. Recurrencia de cefaleas en trueno tras tratamiento con corticoides.

INTRODUCTION: Reversible cerebral vasoconstriction syndrome is a clinicoradiological entity with a self-limiting course that manifests with recurrent episodes of thunderclap headache, and is associated with certain triggers. Recurrence is very rare, and the pathophysiology is thought to be related to altered autoregulation of the cerebrovascular tone. We present a clinical case that raises questions about possible recurrences and triggers. CASE REPORT: A 44-year-old woman with a history of multiple sclerosis treated with interferon beta-1b who had four episodes of thunderclap headache while resting, after completing a course of corticosteroids due to a flare-up of optic neuritis. Three years earlier, the patient had presented several episodes of explosive-onset headache during a self-limited period of one month, only occurring during sexual intercourse. In the year prior to our assessment, she had suffered three thunderclap headaches with similar characteristics, but they were triggered only by intense physical exercise. She had not consulted a physician about these events. A cranial computed tomography scan was performed after the administration of contrast media and a cerebral arteriography, which were consistent with cerebral vasoconstriction syndrome, and its reversibility was confirmed three months later. CONCLUSIONS: Reversible cerebral vasoconstriction syndrome shares a phenotypic expression with primary exertion headaches. It is associated with drugs with vasoactive effects, including interferons, and corticosteroids are associated with a worse prognosis, and such their administration should be avoided.

TITLE: Síndrome de vasoconstricción cerebral reversible. Recurrencia de cefaleas en trueno tras tratamiento con corticoides.Introducción. El síndrome de vasoconstricción cerebral reversible es una entidad clinicorradiológica de curso autolimitado que se manifiesta con episodios de cefalea en trueno recurrentes y que se asocia a determinados desencadenantes. La recidiva es muy poco frecuente y la fisiopatología se cree que está en relación con la alteración de la autorregulación del tono vascular cerebral. Presentamos un caso clínico que plantea cuestiones sobre posibles recurrencias y desencadenantes. Caso clínico. Mujer de 44 años con antecedente de esclerosis múltiple en tratamiento con interferón beta-1b que consultó por cuatro episodios de cefalea en trueno en reposo, tras finalizar un ciclo de corticoides por un brote de neuritis óptica. Tres años antes, la paciente había presentado varios episodios de cefalea de inicio explosivo durante un período autolimitado de un mes, únicamente producidos en el contexto de relaciones sexuales. El año previo a nuestra valoración padeció en tres ocasiones cefalea en trueno de características similares, pero exclusivamente desencadenadas con el ejercicio físico intenso. No había consultado por estos eventos. Se realizó una tomografía computarizada craneal tras la administración de contraste y una arteriografía cerebral, que fueron compatibles con síndrome de vasoconstricción cerebral, y se confirmó su reversibilidad tres meses después. Conclusiones. El síndrome de vasoconstricción cerebral reversible comparte expresión fenotípica con el grupo de cefaleas primarias por esfuerzo físico. Se asocia a fármacos con efectos vasoactivos, entre los que se encuentran los interferones, y los corticoides se asocian a un peor pronóstico, por lo que es importante evitar su administración.

Kinetics and toxicity of nanoplastics in ex vivo exposed human whole blood as a model to understand their impact on human health.

The ubiquitous presence of nanoplastics (NPLs) in the environment is considered of great health concern. Due to their size, NPLs can cross both the intestinal and pulmonary barriers and, consequently, their presence in the blood compartment is expected. Understanding the interactions between NPLs and human blood components is required. In this study, to simulate more adequate real exposure conditions, the whole blood of healthy donors was exposed to five different NPLs: three polystyrene NPLs of approximately 50 nm (aminated PS-NH2, carboxylated PS-COOH, and pristine PS- forms), together with two true-to-life NPLs from polyethylene terephthalate (PET) and polylactic acid (PLA) of about 150 nm. Internalization was determined in white blood cells (WBCs) by confocal microscopy, once the different main cell subtypes (monocytes, polymorphonucleated cells, and lymphocytes) were sorted by flow cytometry. Intracellular reactive oxygen species (iROS) induction was determined in WBCs and cytokine release in plasma. In addition, hemolysis, coagulation, and platelet activation were also determined. Results showed a differential uptake between WBC subtypes, with monocytes showing a higher internalization. Regarding iROS, lymphocytes were those with higher levels, which was observed for different NPLs. Changes in cytokine release were also detected, with higher effects observed after PLA- and PS-NH2-NPL exposure. Hemolysis induction was observed after PS- and PS-COOH-NPL exposure, but no effects on platelet functionality were observed after any of the treatments. To our knowledge, this is the first study comprehensively evaluating the bloodstream kinetics and toxicity of NPL from different polymeric types on human whole blood, considering the role played by the cell subtype and the NPLs physicochemical characteristics in the effects observed after the exposures.

De-escalating axillary management after neoadjuvant chemotherapy in breast cancer: The ratio of positive sentinel lymph nodes matters.

BACKGROUND: De-escalation of axillary surgery in breast cancer (BC) patients diminishes sequelae without compromising cancer outcomes. Surgical management of the axilla is challenging after neoadjuvant treatment. We aimed to identify the factors associated with residual axillary disease amenable to lymphadenectomy in patients with positive sentinel lymph node biopsy (SLNB). METHODS: We conducted a retrospective observational study in Hospital 12 de Octubre (Spain). We included BC patients with positive SLNB who underwent axillary dissection after neoadjuvant chemotherapy. Univariate and multivariate logistic regression models were performed to identify independent predictors of residual axillary disease. We estimated the ratio of positive nodes in SLNB and assessed the diagnostic validity of this ratio in relation to residual axillary disease. RESULTS: We included 103 patients in the study. Residual axillary disease was identified in 54 patients (52.4%). Clinically node positive status at diagnosis (OR = 18.3, 95%CI: 4.0-83.6) and a ratio of positive nodes in SLNB ≥0.5 (OR = 6.5, 95%CI 41.7-23.7) were associated with residual axillary disease. The sensitivity and negative predictive value of a ratio of positive nodes in SLNB ≥0.5 were 87% (95%CI 75.1%-94.6%) and 75% (95%CI 55.1%-89.3%), respectively. CONCLUSIONS: In our study, for patients with positive SLNB after neoadjuvant chemotherapy, stage N+ at diagnosis and a ratio of positive nodes in SLNB ≥0.5 were independent risk factors of positive residual axillary disease. This ratio is a feasible measure with a good diagnostic validity for residual axillary disease and could be used as a guiding factor in the surgical management of these patients.

Single nucleotide polymorphisms in ADAM17, IL23R and SLCO1C1 genes protect against infliximab failure in adults with Crohn's disease.

BACKGROUND: To predict primary failure of infliximab (IFX) therapy in Crohn's disease (CD) and to identify patients who maintain long-term effectiveness to IFX is currently not feasible. Some genetic variations are proposed as potential biomarkers. AIM: We assessed a set of single nucleotide polymorphisms (SNPs) in genes related to the IFX mechanism of action and the presence of HLA-DQA1 * 05 allele on the primary response and long-term durability in CD patients. METHODS: A multi-centre cross-sectional study of IFX-exposed adult patients with CD was undertaken. Treatment persistence and time to failure were co-primary endpoints. DNA from the 131 patients was genotyped. Association between SNPs and clinical variables with IFX persistence was assessed. RESULTS: Failure to IFX was documented in 65 (49.6%) out of 131 patients. IFX persistence was associated either with carrying the TT genotype in ADAM17 rs10929587 (ORa=0.2; 95%CI=0.1-0.8; p = 0.021), or the CC genotype in SLCO1C1 rs3794271 (ORa=0.2; 95%CI=0.1-0.7; p = 0.008), according to multivariate logistic regression. In contrast, previous bowel resection increased the risk of IFX failure (ORa=2.8; 95%CI=1.1-7.3; p = 0.025). Cox regression analysis confirmed these findings and also identified IL23R rs10489629-TT (HRa 0.41; 95%CI=0.22-0.75; p = 0.004) and concomitant immunosuppressants (HRa 0.46; 95%CI=0.27-0.77; p = 0.003) as protection from IFX failure. However, no association between HLA-DQA1 * 05 allele and persistence of IFX therapy was found, with similar failure rates among carriers and non-carriers (52.8% vs. 47.4%, respectively; p = 0.544). CONCLUSIONS: SNPs rs10929587-TT in ADAM17, rs10489629-TT in IL23R and rs3794271-CC in SLCO1C1, together with no previous bowel surgery and concomitant immunosuppression, were identified as protection from failure to IFX.

Clinical landscape of LAG-3-targeted therapy.

Lymphocyte-activated gene 3 (LAG-3) is a cell surface inhibitory receptor and a key regulator of immune homeostasis with multiple biological activities related to T-cell functions. LAG-3 is considered a next-generation immune checkpoint of clinical importance, right next to programmed cell death protein 1 (PD-1) and cytotoxic T-cell lymphocyte antigen-4 (CTLA-4). Indeed, it is the third inhibitory receptor to be exploited in human anticancer immunotherapies. Several LAG-3-antagonistic immunotherapies are being evaluated at various stages of preclinical and clinical development. In addition, combination therapies blocking LAG-3 together with other immune checkpoints are also being evaluated at preclinical and clinical levels. Indeed, the co-blockade of LAG-3 with PD-1 is demonstrating encouraging results. A new generation of bispecific PD-1/LAG-3-blocking agents have also shown strong capacities to specifically target PD-1+ LAG-3+ highly dysfunctional T cells and enhance their proliferation and effector activities. Here we identify and classify preclinical and clinical trials conducted involving LAG-3 as a target through an extensive bibliographic research. The current understanding of LAG-3 clinical applications is summarized, and most of the publically available data up to date regarding LAG-3-targeted therapy preclinical and clinical research and development are reviewed and discussed.

Efficacy and safety of onabotulinumtoxin A injection in male patients with detrusor overactivity after stress urinary incontinence surgery.

INTRODUCTION AND OBJECTIVE: The use of onabotulinumtoxin A (BoNT-A) injection in male patients with detrusor overactivity (DO) after stress urinary incontinence (SUI) surgery has been scarcely described. Our aim was to assess results of this treatment in this specific population. MATERIALS AND METHODS: Retrospective analysis of men with previous SUI surgery who had been treated with a first injection of 100 U BoNT-A because of DO since 2010 in our department. Treatment response was assessed with the Treatment Benefit Scale: 1) greatly improved; 2) improved; 3) not changed; 4) worsened after treatment (Treatment Benefit Scale 1 or 2: treatment response). Complications were classified according to the Clavien-Dindo classification. Treatment continuation was considered present if, at the last visit, patients had received a BoNT-A injection within the preceding 12 months. Pre- and post-treatment urodynamic variables were compared. RESULTS: Eighteen patients were included, median age 71.1 (59.1-83.5) years. Twelve (66.7%) patients reported response to treatment. Two (11.1%) complications were detected: urinary retention requiring clean intermittent catheterization (Clavien-Dindo 2). No complications related to previous SUI surgery were detected. Fifteen (83.3%) patients had a follow-up >12 months (median follow-up 57 [15-89] months) and all of them had discontinued treatment at the end of follow-up. Urodynamic studies showed significant improvement in terms of DO and bladder compliance. CONCLUSION: Although most men with DO after SUI surgery respond to intradetrusor BoNT-A injection, all of them discontinue treatment due to personal reasons. It is a safe procedure, with urinary retention requiring clean intermittent catheterization being the most frequent complication.

Perception of the validity of the Migraine Disability Assessment questionnaire in a population of patients with chronic migraine.

OBJECTIVES: The Migraine Disability Assessment (MIDAS) questionnaire is the most frequently used instrument for assessing the level of disability in studies into migraine. This study aims to determine the level of completion of the questionnaire, assess the ease of use, and understand patients' subjective perception of the questionnaire's actual ability to measure disability. MATERIAL AND METHODS: We performed a prospective study of a sample of 78 patients with chronic migraine, determining their level of education and employment status. In a baseline visit, patients were trained to properly complete the questionnaire. At 3 months, we determined the total score and level of completion. Patients also completed a survey measuring ease of use of the questionnaire and patients' perception of whether the score accurately reflected their disability. RESULTS: Only 46% of patients fully completed the questionnaire. Sixty-nine percent reported finding it difficult to complete (this was influenced by patient's employment status but not by educational level). Sixty-two percent of respondents believed that the questionnaire did not fully reflect their own perception of their disability. CONCLUSIONS: Although the validity and consistence of the MIDAS questionnaire are well documented, a high percentage of the study population reported finding it difficult to complete; many patients also considered that the questionnaire did not accurately reflect their disability. Understanding patients' opinions of the suitability of questionnaires used in consultation is crucial to improving completion.

Efficacy and safety of onabotulinumtoxin A injection in male patients with detrusor overactivity after stress urinary incontinence surgery. / Eficacia y seguridad de la inyección de onabotulinumtoxin A en pacientes varones con hiperactividad del detrusor tras la cirugía para incontinencia urinaria de esfuerzo.

INTRODUCTION AND OBJECTIVE: The use of onabotulinumtoxin A (BoNT-A) injection in male patients with detrusor overactivity (DO) after stress urinary incontinence (SUI) surgery has been scarcely described. Our aim was to assess results of this treatment in this specific population. MATERIALS AND METHODS: Retrospective analysis of men with previous SUI surgery who had been treated with a first injection of 100U BoNT-A because of DO since 2010 in our department. Treatment response was assessed with the Treatment Benefit Scale: 1) greatly improved; 2) improved; 3) not changed; 4) worsened after treatment (Treatment Benefit Scale 1 or 2: treatment response). Complications were classified according to the Clavien-Dindo classification. Treatment continuation was considered present if, at the last visit, patients had received a BoNT-A injection within the preceding 12 months. Pre- and post-treatment urodynamic variables were compared. RESULTS: Eighteen patients were included, median age 71.1 (59.1-83.5) years. Twelve (66.7%) patients reported response to treatment. Two (11.1%) complications were detected: urinary retention requiring clean intermittent catheterization (Clavien-Dindo 2). No complications related to previous SUI surgery were detected. Fifteen (83.3%) patients had a follow-up>12 months (median follow-up 57 [15-89] months) and all of them had discontinued treatment at the end of follow-up. Urodynamic studies showed significant improvement in terms of DO and bladder compliance. CONCLUSION: Although most men with DO after SUI surgery respond to intradetrusor BoNT-A injection, all of them discontinue treatment due to personal reasons. It is a safe procedure, with urinary retention requiring clean intermittent catheterization being the most frequent complication.

Úlcera duodenal benigna con penetración en cabeza de páncreas, con obstrucción de la vía biliar / Benign duodenal ulcer penetrating into pancreas, with obstruction of common bile duct

Resumen Objetivo: Reportamos un caso clínico con presentación atípica de una úlcera duodenal benigna que simula el cuadro clínico y radiológico de una neoplasia de páncreas. Materiales y Método: Presentamos el caso de un varón de 83 años que debuta con un cuadro clínico de astenia e ictericia mucocutánea. En estudio de imagen se identifica una masa en cabeza pancreática. En estudio endoscópico se observa úlcera duodenal benigna penetrada a cabeza de páncreas que condiciona obstrucción de vía biliar. Discusión y Conclusiones: El manejo de estos pacientes suele ser quirúrgico porque desarrollan un deterioro asociado a sepsis o perforación. Si la situación clínica lo permite se puede intentar un tratamiento conservador. En nuestro caso el paciente precisó un mes de hospitalización con antibioticoterapia intravenosa de amplio espectro, reposo alimentario, nutrición parenteral y tratamiento con inhibidores de la bomba de protones (IBP) para la resolución del cuadro. La penetración o fistulización a la cabeza del páncreas es una complicación grave e infrecuente de la enfermedad ulcerosa péptica. Su manejo puede ser conservador en casos seleccionados donde no exista perforación de la úlcera a la cavidad peritoneal, ni exista deterioro séptico ni hemodinámico.

Aim: To report an atypical presentation of a benign duodenal ulcer that simulates pancreatic neoplasia. Materials and Method: A case of a 83 years old male patient with astenia and jaundice due to a benign duodenal ulcer penetrating into the pancreas with obstruction of common bile duct. Imagining study identified a pancreatic head mass. The patient required one month admission, receiving broad-spectrum antibiotics, parenteral nutrition and intravenous proton pump inhibitors. Discussion and Conclusion: Due to frequent complications associated to this condition, such as haemodynamic failure, sepsis or free peritoneal perforation, surgery is the main treatment. However, in mild cases, as in our patient, conservative management can be considered. Penetration or fistulization to the head of the pancreas is a rare and serious complication of peptic ulcer disease. Its management can be conservative in selected cases where there is no perforation of the ulcer into the peritoneal cavity, nor septic or hemodynamic deterioration.

[Alzemon: a prospective follow-up study of eslicarbazepine acetate monotherapy in patients with newly diagnosed epilepsy]. / Alzemon: estudio de seguimiento prospectivo del acetato de eslicarbacepina en monoterapia en pacientes con epilepsia de diagnóstico reciente.

INTRODUCTION: Eslicarbazepine acetate is a novel sodium channel blocker for use in the treatment of focal onset seizures. Prospective studies on its effectiveness in monotherapy in patients with newly diagnosed partial epilepsy in routine clinical practice are scarce. AIM: To evaluate the effectiveness of eslicarbazepine as initial monotherapy in patients with newly diagnosed partial epilepsy in routine clinical practice. PATIENTS AND METHODS: A prospective, multicentre, post-authorisation study. Patients with newly diagnosed partial epilepsy aged 18 years or older without previous treatment were included. The efficacy variables were: percentage of seizure-free patients, responders and reduction in monthly frequency of seizures. The safety variables analyse the 12-month retention rate and the occurrence of adverse effects. RESULTS: Fifty-three patients were included. The retention rate was 77.4%. At the end of the observation period, 83% of patients were seizure-free and 92.5% had reduced their baseline frequency by 50% or more. In addition, 68% of the patients reported some adverse effect and 7.5% of them dropped out of the study for this reason. The effectiveness analysis of the subgroup of patients aged 65 years or more showed no differences with respect to the overall population. CONCLUSION: Eslicarbazepine monotherapy in patients with newly diagnosed partial epilepsy, both in the general population and in the population over 65 years old, is effective and safe in routine clinical practice.

TITLE: Alzemon: estudio de seguimiento prospectivo del acetato de eslicarbacepina en monoterapia en pacientes con epilepsia de diagnóstico reciente.Introducción. El acetato de eslicarbacepina es un nuevo bloqueante de los canales de sodio en el tratamiento de las crisis de inicio focal. Los estudios prospectivos sobre su efectividad en monoterapia en pacientes con epilepsia parcial de reciente diagnóstico en la práctica clínica habitual son escasos. Objetivo. Evaluar la efectividad de la eslicarbacepina en monoterapia de inicio en pacientes con epilepsia parcial de reciente diagnóstico en la práctica clínica habitual. Pacientes y métodos. Estudio postautorización prospectivo y multicéntrico. Se incluyó a pacientes con epilepsia parcial de reciente diagnóstico de 18 años o más sin tratamiento previo. Las variables de eficacia fueron: porcentaje de pacientes libres de crisis, respondedores y reducción en la frecuencia mensual de crisis. Las variables de seguridad analizan la tasa de retención a los 12 meses y la aparición de efectos adversos. Resultados. Se incluyó a 53 pacientes. La tasa de retención fue del 77,4%. Al final del período de observación, el 83% de los pacientes se encontraba libre de crisis y el 92,5% había reducido en un 50% o más su frecuencia basal. El 68% de los pacientes notificó algún efecto adverso y el 7,5% de ellos abandonó el estudio por este motivo. El análisis de efectividad del subgrupo de 65 años o más no mostró diferencias respecto a la población global. Conclusión. La eslicarbacepina en monoterapia en pacientes con epilepsia parcial de reciente diagnóstico, tanto en la población general como en la población de más de 65 años, es eficaz y segura en la práctica clínica habitual.

Geographically distant isolates of the persistent southern tomato virus (STV) show very low genetic diversity in the putative coat protein gene.

Southern tomato virus (STV) from genus Amalgavirus (Family Amalgaviridae) is a persistent virus infecting tomato crops worldwide. Information on genetic diversity and evolutionary mechanisms for plant persistent viruses are very scarce in comparison with plant acute viruses. In this work, the putative coat protein gene of worldwide STV isolates was analyzed showing very low nucleotide diversity (< 0.0100). Phylogenetic analysis separated STV isolates into two clades, but no correlation was found between genetic and geographic distances. Also, no recombination events among STV isolates were detected. Comparison of synonymous and nonsynonymous substitutions indicated negative selection at the amino acid level.

Procedure to build a signal transfer set, independent of the target analytes, between a portable fluorimeter based on light-emitting diodes and a master fluorimeter.

The need of performing "in situ" analytical determinations together with the availability of high-power deep UV-LEDs have led to the use of fluorescence spectroscopy. However, it is necessary to register excitation-emission matrices (EEM) to obtain three-way data which can be decomposed using parallel factor analysis for enabling the unequivocal identification of the analytes. In this context, the feasibility of transferring EEM between a portable fluorimeter based on LEDs and a master fluorimeter based on a xenon source has been recently reported without losing analytical quality. To build the transfer function, the signals of the same N samples must be recorded in the portable and in the master fluorimeter. In literature, these samples always contained the target analytes so the EEM signal transfer methodology is very limited in practice. Therefore, the challenge is to search for a set of samples whose EEM enable to perform the signal transfer without previously knowing the target analytes. The aim of this work is the design of a procedure to build N mixtures of P fluorophores so the N EEM would be optimal for the signal transfer. Five criteria have been defined a priori to identify the quality of a transfer set made up of N EEM. Then, a procedure has been designed to obtain the n mixtures of the P fluorophores "in silico" using the Pareto front of the optimal solutions and a desirability function to choose the desired N EEM. The procedure has been used to find five mixtures of the three chosen fluorophores for the signal transfer (coumarin 120, DL-Tyrosine and DL-Tryptophan) which are chemically different from the analytes of interest (enrofloxacin and flumequine) and are contained in a different matrix. These two analytes are antibiotics which have maximum residue limits set in the EU legislation in force. The correlation coefficients between the experimental reference spectra and the PARAFAC spectral loadings of the data registered with the master fluorimeter were greater than or equal to 0.999 in all cases. On the other hand, the correlation coefficients obtained with the portable fluorimeter ranged from 0.900 to 0.950 once the procedure was applied to the two antibiotics. Therefore, the unequivocal identification of the analytes was ensured.

Reversible Homonymous Inferior Quadrantanopia in a Nonketotic Hyperglycemic Patient.

Homonymous hemianopia is frequently associated with retrochiasmal lesions. Vascular etiology is the most common and usually evident on magnetic resonance imaging. When the results of neuroimaging are normal, there are other etiologies that we should consider, like nonketotic hyperglycemia (NKH). We report a 62-year-old female diabetic patient with headache, colour vision and sudden homonymous inferior quadrantanopia and elevated blood sugar levels with normal pH. The neuroimaging was normal and the visual lost improved after the correction of the hyperglycemia. NKH should be considered in patients with sudden and transient hemianopia and normal neuroimaging.

Prognostic utility of electrocardiograms in patients with hypertension older than 65 years. The PAFRES study. / Utilidad pronóstica del electrocardiograma en pacientes hipertensos mayores de 65 años. Estudio FAPRES.

OBJECTIVE: Left ventricular hypertrophy is the most common marker of target organ damage in arterial hypertension. Electrocardiograms are typically performed to identify left ventricular hypertrophy. The aim of this study was to analyse the prognostic utility of other electrocardiographic abnormalities in patients with arterial hypertension, beyond ventricular hypertrophy. MATERIALS AND METHODS: The study included 1003 patients older than 65years with arterial hypertension. We recorded risk factors, previous cardiovascular history and medical treatment and analysed various electrocardiographic abnormalities including the Sokolow-Lyon index, the Cornell index, ventricular overload and branch blocks. The study conducted a 2-year follow-up, recording the major cardiovascular events (mortality, myocardial infarction, stroke and hospitalisation for heart failure). RESULTS: The study population's mean age was 72.9±5.8years, 47.5% of whom were men. During the follow-up, 13.9% of the patients experienced a major cardiovascular event. These patients were older, more often smokers and engaged in less physical exercise, without presenting differences in the antihypertensive therapy or blood pressure control. The ventricular overload pattern (HR: 1.93; 95%CI: 1.160-3.196; P=.011) and the complete left bundle branch block (HR: 2.27; 95%CI: 1.040-4.956; P=.040) behaved as independent electrocardiographic predictors of major cardiovascular events; however, left ventricular hypertrophy using the Sokolow and/or Cornell index did not behave as such. CONCLUSIONS: For patients with hypertension, the presence in the baseline electrocardiogram of complete left bundle branch block or a pattern of ventricular overload identifies a population at increased cardiovascular risk.