Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study.

BACKGROUND: CARTITUDE-1 aimed to assess the safety and clinical activity of ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T-cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma with poor prognosis. METHODS: This single-arm, open-label, phase 1b/2 study done at 16 centres in the USA enrolled patients aged 18 years or older with a diagnosis of multiple myeloma and an Eastern Cooperative Oncology Group performance status score of 0 or 1, who received 3 or more previous lines of therapy or were double-refractory to a proteasome inhibitor and an immunomodulatory drug, and had received a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. A single cilta-cel infusion (target dose 0·75 × 106 CAR-positive viable T cells per kg) was administered 5-7 days after start of lymphodepletion. The primary endpoints were safety and confirmation of the recommended phase 2 dose (phase 1b), and overall response rate (phase 2) in all patients who received treatment. Key secondary endpoints were duration of response and progression-free survival. This trial is registered with ClinicalTrials.gov, NCT03548207. FINDINGS: Between July 16, 2018, and Oct 7, 2019, 113 patients were enrolled. 97 patients (29 in phase 1b and 68 in phase 2) received a cilta-cel infusion at the recommended phase 2 dose of 0·75 × 106 CAR-positive viable T cells per kg. As of the Sept 1, 2020 clinical cutoff, median follow-up was 12·4 months (IQR 10·6-15·2). 97 patients with a median of six previous therapies received cilta-cel. Overall response rate was 97% (95% CI 91·2-99·4; 94 of 97 patients); 65 (67%) achieved stringent complete response; time to first response was 1 month (IQR 0·9-1·0). Responses deepened over time. Median duration of response was not reached (95% CI 15·9-not estimable), neither was progression-free survival (16·8-not estimable). The 12-month progression-free rate was 77% (95% CI 66·0-84·3) and overall survival rate was 89% (80·2-93·5). Haematological adverse events were common; grade 3-4 haematological adverse events were neutropenia (92 [95%] of 97 patients), anaemia (66 [68%]), leukopenia (59 [61%]), thrombocytopenia (58 [60%]), and lymphopenia (48 [50%]). Cytokine release syndrome occurred in 92 (95%) of 97 patients (4% were grade 3 or 4); with median time to onset of 7·0 days (IQR 5-8) and median duration of 4·0 days (IQR 3-6). Cytokine release syndrome resolved in all except one with grade 5 cytokine release syndrome and haemophagocytic lymphohistiocytosis. CAR T-cell neurotoxicity occurred in 20 (21%) patients (9% were grade 3 or 4). 14 deaths occurred in the study; six due to treatment-related adverse events, five due to progressive disease, and three due to treatment-unrelated adverse events. INTERPRETATION: A single cilta-cel infusion at the target dose of 0·75 × 106 CAR-positive viable T cells per kg led to early, deep, and durable responses in heavily pretreated patients with multiple myeloma with a manageable safety profile. The data from this study formed the basis for recent regulatory submissions. FUNDING: Janssen Research & Development and Legend Biotech.

Overall survival results of AGO-OVAR16: A phase 3 study of maintenance pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced ovarian cancer.

OBJECTIVE: The AGO-OVAR16 study was designed to test the efficacy, safety, and tolerability of pazopanib maintenance after first-line chemotherapy in patients with newly diagnosed advanced ovarian cancer (AOC). METHODS: Nine hundred and forty patients with histologically confirmed AOC, International Federation of Gynecology and Obstetrics (FIGO) stage II-IV, were randomized in a 1:1 ratio to receive either 800 mg pazopanib once daily or placebo for up to 24 months, unless there was disease progression, toxicity, withdrawal of consent, or death. The primary endpoint (investigator-assessed progression-free survival [PFS]) was met and previously reported. The results of final analyses of overall survival (OS) are reported here. RESULTS: A third OS interim analysis showed futility and led to study closure and a final OS analysis after last patient last visit. At the time of the final OS analysis, 494 (89.7% of the planned 551) events had occurred. No difference was observed in OS between pazopanib and placebo. The hazard ratio (HR) was 0.960 (95% confidence interval [CI]: 0.805-1.145), and the median OS from randomization was 59.1 months in pazopanib and 64.0 months in placebo arms. For the East Asian patients, similar to the first three interim OS analyses, a numerical negative trend was observed favoring placebo (HR, 1.332; 95% CI: 0.863-2.054). Exploratory analyses showed a trend for a longer time to first subsequent anti-cancer therapy or death with pazopanib over placebo (HR, 0.829; 95% CI: 0.713-0.965), with a median estimate of 19.0 and 14.5 months, respectively. No new safety signals were observed. CONCLUSION: Although pazopanib prolonged PFS, this was not associated with improvement in median OS. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov: NCT00866697.

Safety of pazopanib and sunitinib in treatment-naive patients with metastatic renal cell carcinoma: Asian versus non-Asian subgroup analysis of the COMPARZ trial.

BACKGROUND: The international, phase 3 COMPARZ study demonstrated that pazopanib and sunitinib have comparable efficacy as first-line therapy in patients with advanced renal cell carcinoma, but that safety and quality-of-life profiles favor pazopanib. Our report analyzed pazopanib and sunitinib safety in Asian and non-Asian subpopulations. METHODS: Patients were randomized 1:1 to receive pazopanib 800 mg once daily (continuous dosing) or sunitinib 50 mg once daily in 6-week cycles (4 weeks on, 2 weeks off). RESULTS: Safety population was composed of 363 Asian patients and 703 non-Asian patients. Asian patients had similar duration of exposure to either drug compared with non-Asian patients, although Asian patients had a higher frequency of dose modifications. Overall, hematologic toxicities, cytopenias, increased AST/ALT, and palmar-plantar erythrodysesthesia (PPE) were more prevalent in Asian patients, whereas gastrointestinal toxicities were more prevalent in non-Asian patients. Among Asian patients, hematologic adverse events and most non-hematologic AEs were more common in sunitinib-treated versus pazopanib-treated patients. Among Asian patients, the most common grade 3/4 AEs with pazopanib were hypertension (grade 3, 22%) and alanine aminotransferase increased (grade 3, 12%; grade 4, 1%); the most common grade 3/4 AEs with sunitinib were thrombocytopenia/platelet count decreased (grade 3, 36%; grade 4, 10%), neutropenia/neutrophil count decreased (grade 3, 24%; grade 4, 3%) hypertension (grade 3, 20%), and PPE (grade 3, 15%). CONCLUSIONS: A distinct pattern and severity of adverse events was observed in Asians when compared with non-Asians with both pazopanib and sunitinib. However, the two drugs were well tolerated in both subpopulations. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00720941 , Registered July 22, 2008 ClinicalTrials.gov, NCT01147822 , Registered June 22, 2010.

Randomized Phase III Trial of Adjuvant Pazopanib Versus Placebo After Nephrectomy in Patients With Localized or Locally Advanced Renal Cell Carcinoma.

Purpose This phase III trial evaluated the efficacy and safety of pazopanib versus placebo in patients with locally advanced renal cell carcinoma (RCC) at high risk for relapse after nephrectomy. Patients and Methods A total of 1,538 patients with resected pT2 (high grade) or ≥ pT3, including N1, clear cell RCC were randomly assigned to pazopanib or placebo for 1 year; 403 patients received a starting dose of 800 mg or placebo. To address toxicity attrition, the 800-mg starting dose was lowered to 600 mg, and the primary end point analysis was changed to disease-free survival (DFS) for pazopanib 600 mg versus placebo (n = 1,135). Primary analysis was performed after 350 DFS events in the intent-to-treat (ITT) pazopanib 600 mg group (ITT600mg), and DFS follow-up analysis was performed 12 months later. Secondary end point analyses included DFS with ITT pazopanib 800 mg (ITT800mg) and safety. Results The primary analysis results of DFS ITT600mg favored pazopanib but did not show a significant improvement over placebo (hazard ratio [HR], 0.86; 95% CI, 0.70 to 1.06; P = .165). The secondary analysis of DFS in ITT800mg (n = 403) yielded an HR of 0.69 (95% CI, 0.51 to 0.94). Follow-up analysis in ITT600mg yielded an HR of 0.94 (95% CI, 0.77 to 1.14). Increased ALT and AST were common adverse events leading to treatment discontinuation in the pazopanib 600 mg (ALT, 16%; AST, 5%) and 800 mg (ALT, 18%; AST, 7%) groups. Conclusion The results of the primary DFS analysis of pazopanib 600 mg showed no benefit over placebo in the adjuvant setting.

Genetic and epigenetic fine mapping of causal autoimmune disease variants.

Genome-wide association studies have identified loci underlying human diseases, but the causal nucleotide changes and mechanisms remain largely unknown. Here we developed a fine-mapping algorithm to identify candidate causal variants for 21 autoimmune diseases from genotyping data. We integrated these predictions with transcription and cis-regulatory element annotations, derived by mapping RNA and chromatin in primary immune cells, including resting and stimulated CD4(+) T-cell subsets, regulatory T cells, CD8(+) T cells, B cells, and monocytes. We find that ∼90% of causal variants are non-coding, with ∼60% mapping to immune-cell enhancers, many of which gain histone acetylation and transcribe enhancer-associated RNA upon immune stimulation. Causal variants tend to occur near binding sites for master regulators of immune differentiation and stimulus-dependent gene activation, but only 10-20% directly alter recognizable transcription factor binding motifs. Rather, most non-coding risk variants, including those that alter gene expression, affect non-canonical sequence determinants not well-explained by current gene regulatory models.

[Results of the cooperative study of Spanish peritoneal dialysis registries: analysis of 12 years of follow-up]. / Resultados del trabajo cooperativo de los registros españoles de diálisis peritoneal: análisis de 12 años de seguimiento.

INTRODUCTION AND OBJECTIVES: There is currently no registry that gives a complete and overall view of the peritoneal dialysis (PD) situation in Spain. However, a report on PD in Spain was developed for various conferences and meetings over several years from data provided by each registry in the autonomous communities and regions. The main objective of this study is to analyse this data in aggregate and comparatively to obtain a representative sample of the Spanish population on PD in recent years, in order that analysis and results in terms of demographic data, penetration of the technique, geographical differences, incidence and prevalence, technical aspects, intermediate indicators, comorbidity, and outcomes such as patient and technique survival may be extrapolated to the whole country. DESIGN, MATERIAL AND METHOD: Observational cohort study of autonomous PD registries, covering the largest possible percentage of the adult Spanish population (over 14 years of age) on PD, at least in the last decade (1999-2010), and in the largest possible geographical area in which we were able to recruit. A precise data collection strategy was followed for each regional registry. Once the information was received and clarified, they were added as aggregate data for statistical study. RESULTS: The regional registries that participated represent a total geographical area that encompasses 32,853,251 inhabitants over 14 years of age, 84% of the total Spanish population older than that age. The mean annual rate of incidents per million inhabitants (ppm) was variable (between 17.81 ppm in Andalusia and 29.90 ppm in the Basque Country), with a discrete and permanent increase in the overall PD incidence in Spain being observed in recent years. The mean annual prevalence per million population (ppm) was very heterogeneous (from 42 to 99 ppm). A mean progressive increase in the use of automated peritoneal dialysis (APD) was observed. The peritonitis rate was approximately one episode every 25-30 months/patient, with a slight decrease being observed in recent years. The causes of discontinuing PD were distributed fairly evenly between communities; almost a third was due to patient death (mean 28%), a third was due to renal transplantation (mean 39%) and a third was due to transfer to haemodialysis (technique failure: mean 32%). The main comorbidities were cardiovascular disease (30.2%) and diabetes mellitus (24.2%). The overall accumulated mean survival was 92.2%, 82.8%, 74.2%, 64.8% and 57% after one, two, three, four and five years respectively. There was significantly and independently worse survival for older patients and those with cardiovascular disease, patients with diabetes mellitus, those on continuous ambulatory peritoneal dialysis (vs. APD), those who started PD before 2004 (analysed in Andalusia and Catalonia), and patients with lower residual renal function at the start of PD (analysed in the Levante registry). Similarly, the technique survival has improved, showing a mean figure above 50% after 5 years. CONCLUSIONS: The incidence and prevalence of PD in Spain are growing moderately and in a generalised manner and continue to maintain an irregular distribution by autonomous community. Both patient and technique survival were greater than 50% after 5 years, with an improvement being observed in recent years, and are comparable to countries with better results in this treatment.

Prenatal diagnosis of a female fetus with ring chromosome 9, 46,XX,r(9)(p24q34), and a de novo interstitial 9p deletion.

Ring chromosomes are circular structures formed as a result of breaks in the chromosome arms and the fusion of the proximal broken ends with a loss of distal material, or by fusion of dysfunctional telomeres without any loss. The mechanism underlying this process has not yet been sufficiently explained. Commonly, rings occur as acquired genetic abnormalities; however, sometimes they are found as constitutional aberrations with a prevalence of around 1:50,000 live births. Here, we present a new case of r(9) in a female fetus with intrauterine growth retardation and slight craniofacial dysmorphisms. Both parents had a normal phenotype. Amniotic fluid karyotype showed r(9)(p24q34). An array CGH revealed 3 deletion segments: a ring chromosome with a 2.57-Mb deletion at 9pterp24.2 (chr9:163,131-2,729,722), a 2.60-Mb deletion at 9q34.3qter (chr9:138,523,302-141,122,055), and also a 0.15-Mb interstitial deletion at 9p24.1 (chr9:5,090,443-5,235,765). These deletions overlap with proposed regions for the 9p24.3 deletion and Kleefstra syndrome. Segregation analysis revealed a maternal origin of the rearranged chromosome. We conclude that both the ring chromosome and the interstitial deletion occurred de novo. This last deletion has not been reported before. Prenatal array CGH, combined with fine mapping of breakpoints contributes to the assessment of genotype-phenotype correlations.

Advancing in the management of chronic kidney disease: the results of implementing a quick resolution consultation.

BACKGROUND: Currently, chronic kidney disease (CKD) is understood as global important public health problem, a situation that requires a new approach. OBJECTIVES: To show the results obtained after implementing a quick resolution consultation for CKD management. METHODS: Results were analysed during 6 month time period. RESULTS: A total of 9.61% of received proposals were referred to primary care without in-person visits. In addition, 28.05% of patients were initially evaluated through high resolution clinics and 62.33% were directly referred to other clinics. From the initial 28.05% mentioned, once evaluated, treatment adjusted and informed about the disease, 70% were referred over to primary care for monitoring and the remaining 30% were given specialist appointments. As a consequence, 70.65% of patients were selected for monitoring by nephrology from all proposals received, and 29.35% for primary care monitoring. We observed a significant decrease in the delay until the first medical appointment. CONCLUSIONS: Quick resolution consultations demonstrated to be an efficient tool for CKD management. Its implementation allowed both low consumption of health care resources, selected patients with high risk of progressive cardiovascular disease for long term monitoring, and offered not only an initial evaluation and adjustment of treatment with information provided to those who would be monitored by primary care, but also diminished primary care delays significantly.

Avanzando en el manejo de la enfermedad renal crónica: resultados de la implantación de una consulta de rápida resolución / Advancing in the management of chronic kidney disease: the results of implementing a quick resolution consultation

Antecedentes: La enfermedad renal crónica (ERC) se entiende actualmente como un importante problema de salud pública global, que requiere una nueva aproximación. Objetivos: Mostrar los resultados de la implantación de una consulta de rápida resolución para el manejo de la ERC. Métodos: Se han analizado de manera retrospectiva los resultados obtenidos durante un período de seis meses, entre septiembre de 2011 y febrero de 2012. Las variables estudiadas han sido la edad de los pacientes, el origen de las propuestas, la causa de las remisiones, el destino inicial dado a estas y el destino final de los pacientes. Resultados: Un 9,61 % de las propuestas recibidas se ha remitido a Atención Primaria sin consulta presencial. Un 28,05 % de los pacientes han sido evaluados inicialmente en la consulta de alta resolución y un 62,33 % se ha citado directamente para el resto de las consultas. Del 28,05 % inicial, tras el proceso de evaluación, ajuste e información acerca de la enfermedad un 70 % ha sido remitido nuevamente a Primaria para seguimiento, y el otro 30 % se ha citado para su seguimiento en consultas. Por tanto, del total de propuestas se ha seleccionado un 70,65 % de pacientes para seguimiento por Nefrología y un 29,35 % para seguimiento por Atención Primaria. Por otro lado, se ha disminuido la demora para primeras visitas a menos de la mitad. Conclusiones: La consulta de alta resolución se ha mostrado como un instrumento eficiente en el manejo de la ERC. Su implantación ha permitido, consumiendo un mínimo de los recursos asistenciales, seleccionar para seguimiento a largo plazo a aquellos pacientes de mayor riesgo de progresión y cardiovascular pero ofreciendo también una evaluación inicial, ajuste de tratamiento e información a los que serán seguidos por Atención Primaria, y disminuir la demora en primeras visitas de manera significativa (AU)

Background: Currently, chronic kidney disease (CKD) is understood as global important public health problem, a situation which requires a new approach. Objectives: To show the results obtained after implementing a quick resolution consultation for CKD management. Methods: Results were analysed during 6 month time period. Results: A total of 9.61% of received proposals were referred to primary care without in-person visits. In addition, 28.05% of patients were initially evaluated through high resolution consults and 62.33% were directly referred to other consults. From the initial 28.05% mentioned, once evaluated, treatment adjusted and informed about the disease, 70% were referred over to primary care for monitoring and the remaining 30% were given specialist appointments. As a consequence, 70.65% of patients were selected for monitoring by nephrology from all proposals received, and 29.35% for primary care monitoring. We observed a significant decrease in the delay until the first medical appointment. Conclusions: Quick resolution consultations demonstrated to be an efficient tool for CKD management. Its implementation allowed both low consumption of health care resources, selected patients with high risk of progression cardiovascular disease for long term monitoring, and offered not only an initial evaluation and adjustment of treatment with information provided to those who would be monitored by primary care, but also diminished primary care delays significantly (AU)

C/EBPα and DEK coordinately regulate myeloid differentiation.

The transcription factor C/EBPα is a critical mediator of myeloid differentiation and is often functionally impaired in acute myeloid leukemia. Recent studies have suggested that oncogenic FLT3 activity disrupts wild-type C/EBPα function via phosphorylation on serine 21 (S21). Despite the apparent role of pS21 as a negative regulator of C/EBPα transcription activity, the mechanism by which phosphorylation tips the balance between transcriptionally competent and inhibited forms remains unresolved. In the present study, we used immuno-affinity purification combined with quantitative mass spectrometry to delineate the proteins associated with C/EBPα on chromatin. We identified DEK, a protein with genetic links to leukemia, as a member of the C/EBPα complexes, and demonstrate that this association is disrupted by S21 phosphorylation. We confirmed that DEK is recruited specifically to chromatin with C/EBPα to enhance GCSFR3 promoter activation. In addition, we demonstrated that genetic depletion of DEK reduces the ability of C/EBPα to drive the expression of granulocytic target genes in vitro and disrupts G-CSF-mediated granulocytic differentiation of fresh human BM-derived CD34(+) cells. Our data suggest that C/EBPα and DEK coordinately activate myeloid gene expression and that S21 phosphorylation on wild-type C/EBPα mediates protein interactions that regulate the differentiation capacity of hematopoietic progenitors.

Paragonimiasis y afectaciones pulmonar, neurológica y hepática: presentación de caso / Pulmonary, neurological and hepatic compromise in paragonimiasis: case report

La paragonimiasis es una infección parasitaria, con manifestaciones principalmente pulmonares; sin embargo, debido a la migración errática del parásito, puede afectar otros órganos. Esta enfermedad es endémica en el sureste asiático, aunque también se han descrito casos en otras regiones tropicales y subtropicales. En este artículo se reporta un caso de un paciente indígena con manifestaciones pulmonares por paragonimiasis y, además, alteraciones neurológicas y hepáticas.

Online nanoflow multidimensional fractionation for high efficiency phosphopeptide analysis.

Despite intense, continued interest in global analyses of signaling cascades through mass spectrometry-based studies, the large-scale, systematic production of phosphoproteomics data has been hampered in-part by inefficient fractionation strategies subsequent to phosphopeptide enrichment. Here we explore two novel multidimensional fractionation strategies for analysis of phosphopeptides. In the first technique we utilize aliphatic ion pairing agents to improve retention of phosphopeptides at high pH in the first dimension of a two-dimensional RP-RP. The second approach is based on the addition of strong anion exchange as the second dimension in a three-dimensional reversed phase (RP)-strong anion exchange (SAX)-RP configuration. Both techniques provide for automated, online data acquisition, with the 3-D platform providing the highest performance both in terms of separation peak capacity and the number of unique phosphopeptide sequences identified per µg of cell lysate consumed. Our integrated RP-SAX-RP platform provides several analytical figures of merit, including: (1) orthogonal separation mechanisms in each dimension; (2) high separation peak capacity (3) efficient retention of singly- and multiply-phosphorylated peptides; (4) compatibility with automated, online LC-MS analysis. We demonstrate the reproducibility of RP-SAX-RP and apply it to the analysis of phosphopeptides derived from multiple biological contexts, including an in vitro model of acute myeloid leukemia in addition to primary polyclonal CD8(+) T-cells activated in vivo through bacterial infection and then purified from a single mouse.

[Utility of cardiac event recorders in diagnosing arrhythmic etiology of palpitations in patients without structural heart disease]. / Utilidad de un grabador de acontecimientos en el diagnóstico de la etiología arrítmica de las palpitaciones en pacientes sin cardiopatía estructural.

OBJECTIVE: To determine the diagnostic yield of transtelephonic event monitors for identifying the reason for palpitations in patients with no structural heart disease. PATIENTS AND METHOD: For 20 months we enrolled all patients reporting palpitations in whom heart disease had been ruled out by medical history, physical examination, ECG and transthoracic echocardiography. All patients underwent 24 h Holter monitoring, which did not provide diagnostic information. Later, a Cardiotest 4DM transtelephonic event monitor was provided to each patient for a mean of 15 3 days. We used SPSS V 10 for statistical analysis. RESULTS: Two hundred twenty-seven consecutive patients were enrolled. Mean age was 45 3 years (range 12-85); 167 were females (74%). Two hundred twelve of the 227 patients (93.3%) experienced palpitations while wearing the device, and 210 (92.5%) used the monitor correctly, recording the cardiac rhythm during palpitations. Fifteen patients (6.6%) had no palpitations during the days of study. In 125 (55%) the Cardiotest 4DM correctly recorded and transmitted arrhythmia that justified the patients' reference to palpitations. In 35 (15.4%) significant arrhythmia was detected: paroxysmal supraventricular tachycardia in 21, atrial fibrillation in 9, atrial flutter in 5, runs of ventricular extrasystoles in 4 and right outflow tract ventricular tachycardia in 1. Sinus rhythm was recorded during palpitations in 85 patients (37%), and arrhythmia as the cause could be ruled out. CONCLUSIONS: Cardiotest 4DM identifies arrhythmia in a very high proportion of patients with palpitations and no structural heart disease.

Utilidad de un grabador de acontecimientos en el diagnóstico de la etiología arrítmica de las palpitaciones en pacientes sin cardiopatía estructural / Utility of Cardiac Event Recorders in Diagnosing Arrhythmic Etiology of Palpitations in Patients without Structural Heart Disease

Introducción y objetivos. El objetivo del presente trabajo es determinar cuál es el rendimiento de la utilización del grabador de acontecimientos en el diagnóstico de la etiología de las palpitaciones como síntoma en pacientes sin cardiopatía estructural. Pacientes y método. Durante 20 meses se han incluido en el estudio a todos los pacientes que consultaban por palpitaciones y en los que se descartaba mediante historia clínica, exploración, ECG y ecocardiografía la existencia de cardiopatía estructural. A todos se les realizó un Holter de 24 h que no resultó diagnóstico. Posteriormente se les proporció un registrador de acontecimientos Cardiotest 4DM® durante una media de 15 ñ 3 días. Utilizamos el paquete estadístico SPSS V.10.Resultados. Se incluyeron en el estudio 227 pacientes consecutivos. La edad media fue de 45 ñ 3 años (rango, 12-85 años) y 167 eran mujeres (74 por ciento). Un total de 212 de los 227 pacientes incluidos (93,3 por ciento) tuvieron palpitaciones durante los 15 días que dispusieron del monitor, y 210 (92,5 por ciento) utilizaron correctamente el monitor, grabando el ritmo cardíaco coexistente con dichas palpitaciones. Quince pacientes (6,6 por ciento) no tuvieron palpitaciones durante los días de estudio. En 125 (55 por ciento) el Cardiotest 4DM® grabó y transmitió por vía transtelefónica correctamente arritmias que justificaban las palpitaciones referidas por los pacientes. En 35 pacientes (15,4 por ciento) se detectaron arritmias significativas: 21 taquicardias paroxísticas supraventriculares, 9 fibrilaciones auriculares, 5 aleteos auriculares, 4 tripletes de extrasístoles ventriculares y una taquicardia ventricular de tracto de salida de ventrículo derecho. En 85 pacientes (37 por ciento), durante las palpitaciones no se detectó arritmia alguna que las justificara, excluyendo así las arritmias como etiología de la misma. Conclusiones. El Cardiotest 4DM® permite identificar arritmias en una proporción muy elevada de pacientes con palpitaciones y sin cardiopatía estructural conocida (AU)