RESUMEN
BACKGROUND: The combination of highly localized impedance (LI) and contact force (CF) may improve tissue characterization and lesion prediction during radiofrequency (RF) pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). OBJECTIVE: We report the outcomes of our acute and long-term clinical evaluation of CF-LI-guided PVI in consecutive AF ablation cases from an international multicenter clinical setting. METHODS: Three hundred twenty-four consecutive patients from 20 European centers undergoing RF catheter ablation with the Stablepoint™ catheter were enrolled in the CHARISMA registry. Of these, 275 had a minimum follow-up of 1 year and were included in the primary analysis. RESULTS: The mean procedure duration was 115 ± 47 min, and the mean fluoroscopy time was 9.9 ± 6 min. At the end of the procedures, all PVs had been successfully isolated in all study patients. Minor complications were reported in 12 patients (4.4%). At 1 year, 36 (13.1%) patients had had an AF recurrence, and freedom from antiarrhythmic drugs and AF recurrence was achieved in 228 (82.9%) patients. The recurrence rate was higher in patients with persistent AF (21/116, 18.1%) than in those with paroxysmal AF (15/159, 9.4%; p = 0.0459). On multivariate logistic analysis adjusted for baseline confounders, only time > 6 months from first diagnosis of AF to ablation (HR = 2.93, 95%CI 1.03 to 8.36, p = 0.0459) was independently associated with recurrences. CONCLUSION: An ablation strategy for PVI guided by CF-LI technology proved safe and effective and resulted in a low recurrence rate of AF over 1-year follow-up, irrespective of the underlying AF type. CLINICAL TRIAL REGISTRATION: Catheter Ablation of Arrhythmias with a High-Density Mapping System in Real-World Practice. (CHARISMA). URL: http://clinicaltrials.gov/ Identifier: NCT03793998.
RESUMEN
INTRODUCTION: Recently, a new cryoballoon (CB) technology (POLARx; Boston Scientific) has come onto the market. Preliminary data have shown that its acute safety and efficacy are similar to those of the first-generation CB. The aim of this study was to assess the medium-term outcome of pulmonary vein isolation (PVI) with the POLARxTM CB in a large multicenter registry. METHODS: We prospectively collected data on 125 consecutive patients with paroxysmal atrial fibrillation (AF) who underwent PVI by means of a novel CB system. Two cases of transient phrenic nerve palsy occurred, with full recovery in the 48h post procedure; no major procedure-related adverse events were reported. During the 90-day blanking period, 4 (3.2%) patients experienced an early recurrence. After the blanking period, over a mean follow-up of 411 ± 62 days, 19 patients (15.2%) suffered an AF/atrial tachycardia (AT) recurrence. The 1-year freedom from AF/AT recurrence was 86.4% (n = 17): 10 (8%) patients had an AF recurrence, 6 (4.8%) had an AT occurrence and 1 (0.8%) suffered both events. Patients with AF/AT recurrences had both a shorter deflation time and total deflation time. Moreover, CB ablations with measured TTI < 90 s and TTI < 60 s were more frequent in patients without AF/AT recurrence (88.5% and 77.4%, respectively) than in those who experienced at least one AF/AT recurrence (67.5% and 55.0%, p = .001 and p = .005, respectively). CONCLUSION: The novel POLARx cryo-balloon system is safe and effective for PV isolation, displaying a 1-year freedom from atrial arrhythmia recurrence of 86.4%, which is in line to that reported with AFA-Pro CB or RF ablation. CLINICAL TRIAL REGISTRATION: Catheter Ablation of Arrhythmias with a High-Density Mapping System in Real-World Practice (CHARISMA). URL: http://clinicaltrials.gov/ Identifier: NCT03793998. Registration date: January 4, 2019.
Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Criocirugía , Venas Pulmonares , Humanos , Venas Pulmonares/cirugía , Resultado del Tratamiento , Criocirugía/métodos , Italia/epidemiología , Sistema de Registros , Ablación por Catéter/métodos , RecurrenciaRESUMEN
Background: Highly localized impedance (LI) measurements during atrial fibrillation (AF) ablation have the potential to act as a reliable predictor of the durability of the lesions created. Objective: We aimed to collect data on the procedural parameters affecting LI-guided ablation in a large multicenter registry. Methods: A total of 212 consecutive patients enrolled in the CHARISMA registry and undergoing their first pulmonary vein (PV) isolation for paroxysmal and persistent AF were included. Results: In all, 13,891 radiofrequency (RF) applications of ≥3â s duration were assessed. The first-pass PV isolation rate was 93.3%. A total of 80 PV gaps were detected. At successful ablation spots, baseline LI and absolute LI drop were larger than at PV gap spots (161.4 ± 19â Ω vs. 153.0 ± 13â Ω, p < 0.0001 for baseline LI; 22.1 ± 9â Ω vs. 14.4 ± 5â Ω, p < 0.0001 for LI drop). On the basis of Receiver operating characteristic curve analysis, the ideal LI drop, which predicted successful ablation, was >21â Ω at anterior sites and >18â Ω at posterior sites. There was a non-linear association between the magnitude of LI drop and contact-force (CF) (r = 0.14, 95% CI: 0.13-0.16, p < 0.0001) whereas both CF and LI drop were inversely related with delivery time (DT) (-0.22, -0.23 to -0.20, p < 0.0001 for CF; -0.27, -0.29 to -0.26, p < 0.0001 for LI drop). Conclusion: An LI drop >21â Ω at anterior sites and >18â Ω at posterior sites predicts successful ablation. A higher CF was associated with an increased likelihood of ideal LI drop. The combination of good CF and adequate LI drop allows a significant reduction in RF DT. Clinical trial registration: http://clinicaltrials.gov/, identifier: NCT03793998.
RESUMEN
Introduction: Unrecognized incomplete pulmonary vein (PV) isolation during the index procedure, can be a major cause of clinical recurrences of atrial fibrillation (AF) after cryoballoon (CB) ablation. We aimed to characterize the extension of the lesions produced by CB ablation and to assess the value of using an ultra-high resolution electroanatomic mapping (UHDM) system to detect incomplete CB lesions. Materials and methods: Twenty-nine consecutive patients from the CHARISMA registry undergoing AF ablation at four Italian centers were prospectively evaluated. The Rhythmia™ mapping system and the Orion™ (Boston Scientific) mapping catheter were used to systematically map the left atrium and PVs before and after cryoablation. Results: A total of 116 PVs were targeted and isolated. Quantitative assessment of the lesions revealed a significant reduction of the antral surface area of the PV, resulting in an ablated area of 5.7 ± 0.7 cm2 and 5.1 ± 0.8 cm2 for the left PV pair and right PV pair, respectively (p = 0.0068). The mean posterior wall (PW) area was 22.9 ± 2 cm2 and, following PV isolation, 44.8 ± 6% of the PW area was ablated. After CB ablation, complete isolation of each PV was documented by the POLARMap™ catheter in all patients. By contrast, confirmatory UHDM and the Lumipoint™ tool unveiled PV signals in 1 out of 114 of the PVs (0.9%). Over 30-day follow-up, no major procedure-related adverse events were reported. After a mean follow-up of 333 days, 89.7% of patients were free from arrhythmia recurrence. Conclusion: The lesion extension achieved by the new CB ablation system involved the PV antrum, with less than 50% of the PW remaining untouched. The new system, with short tip and circular mapping catheter, failed to achieve PV isolation in only 0.9% of all PVs treated. Clinical trial registration: [http://clinicaltrials.gov/], identifier [NCT03793998].
RESUMEN
PURPOSE: Highly localized impedance (LI) measurements during atrial fibrillation (AF) ablation have emerged as a viable real-time indicator of tissue characteristics and the consequent durability of the lesions created. We investigated the impact of catheter-tissue contact force (CF) on LI behavior during pulmonary vein isolation (PVI). METHODS: Forty-five consecutive patients of the CHARISMA registry undergoing de novo AF radiofrequency (RF) catheter ablation with a novel open-irrigated-tip catheter endowed with CF and LI measurement capabilities (Stablepoint™ catheter, Boston Scientific) were included. RESULTS: A total of 2895 point-by-point RF applications were analyzed (RF delivery time (DT) = 8.7±4s, CF = 13 ±±8 g, LI drop = 23 ±±7 Ω). All PVs were successfully isolated in an overall procedure time of 118 ±±34 min (fluoroscopy time = 13 ±±8 min). The magnitude of LI drop weakly correlated with CF (r = 0.13, 95% confidence interval (CI): 0.09 to 0.16, p < 0.0001), whereas both CF and LI drop inversely correlated with DT (r = -0.26, 95%CI: -0.29 to -0.22, p < 0.0001 for CF; r = -0.36, 95%CI: -0.39 to -0.33, p < 0.0001 for LI). For each 10 g of CF, LI drop markedly increased from 22.4 ± 7 Ω to 24.0 ± 8 Ω at 5 to 25 g CF intervals (5-14 g of CF vs 15-24 g of CF, p < 0.0001), whereas it showed smooth transition over 25 g (24.8 ± 7Ω at ≥ 25 g CF intervals, p = 0.0606 vs 15-24 g of CF). No major complications occurred during the procedures or within 30 days. CONCLUSIONS: CF significantly affects LI drop and probable consequent lesion formation during RF PVI. The benefit of higher contact (> 25 g) between the catheter and the tissue appears to have less impact on LI drop. TRIAL REGISTRATION: Catheter Ablation of Arrhythmias With High Density Mapping System in the Real World Practice (CHARISMA). URL: http://clinicaltrials.gov/ Identifier: NCT03793998.
Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Impedancia Eléctrica , Humanos , Venas Pulmonares/cirugía , Sistema de Registros , Resultado del TratamientoRESUMEN
OBJECTIVES: The aim of the study was to confirm the value of the VALID-cardiac resynchronization therapy (CRT) risk score in predicting outcome and to assess its association with clinical response (CR) in an unselected real-world CRT population. METHODS AND RESULTS: The present analysis comprised all consecutive CRT patients (pts) enrolled in the CRT-MORE registry from 2011 to 2013. Pts were stratified into five groups (quintiles 1-5) according to the VALID-CRT risk predictor index applied to the CRT-MORE population. In the analysis of clinical outcome, adverse events comprised death from any cause and non-fatal heart failure (HF) events requiring hospitalization. CR at 12-month follow-up was also assessed. We enrolled 905 pts. During a median follow-up of 1005 [627-1361] days, 134 patients died, and 79 had at least one HF hospitalization. At 12 months, 69% of pts displayed an improvement in their CR. The mean VALID-CRT risk score derived from the CRT-MOdular Registry (MORE) population was 0.317, ranging from -0.419 in Q1 to 2.59 in Q5. The risk-stratification algorithm was able to predict total mortality after CRT (survival ranging from 93%-Q1 to 77%-Q5; hazards ratio [HR] = 1.42, 95% confidence interval [CI]: 1.25-1.61, P < .0001), and HF hospitalization (ranging from 95% to 90%; HR = 1.24, 95% CI: 1.06-1.45, P = .009). CR was significantly lower in pts with a high-to-very high risk profile (Q4-5) than in pts with a low-to-intermediate risk profile (Q1-2-3) (55% vs 79%, P < .0001). CONCLUSION: The VALID-CRT risk-stratification algorithm reliably predicts outcome and CRT response after CRT in an unselected, real-world population.
Asunto(s)
Terapia de Resincronización Cardíaca/métodos , Insuficiencia Cardíaca/terapia , Sistema de Registros , Medición de Riesgo/métodos , Función Ventricular Izquierda/fisiología , Remodelación Ventricular/fisiología , Anciano , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de TiempoRESUMEN
BACKGROUND: Throughout the world, emergency departments (ED) are characterized by overcrowding and excessive waiting times. Furthermore, the related delays significantly increase patient mortality and make inefficient use of resources to the detriment of the satisfaction of employees and patients. In this work, lean thinking is applied to the ED of Cardarelli Hospital of Naples with the aim of increasing patient flow, improving the processes that contribute to facilitating the flow of patients through the various stages of medical treatment and eliminating all bottlenecks (queue) as well as all activities that generate waste. METHODS: This project was performed at National Hospital A.O.R.N. A. Cardarelli of Naples. The historical times of access to the ED were analysed from January 2015 to June 2015, for a total of 16,563 records. Subsequently, starting in November 2015, corrective actions were implemented according to the Lean Approach. Data collected after the introduced improvements were collected from April 2016 to June 2016 and compared to those collected during the starting period. RESULTS: The results acquired before application of the Lean Thinking strategy illustrated the as-is process with its drawbacks. An analysis of the non-added value activities was performed to identify the procedures that need to be improved. After implementation of the corrective actions, we observed a positive increase in the performance of the ED, quantified as percentages of hospitalized patients according to triage codes and waiting times. CONCLUSION: This work demonstrates the applicability of Lean Thinking to ED processes and its effectiveness in terms of increasing the efficiency of services and reducing waste (waiting times).
Asunto(s)
Eficiencia Organizacional , Servicio de Urgencia en Hospital/organización & administración , Administración Hospitalaria , Flujo de Trabajo , Humanos , Italia , Estudios de Casos Organizacionales , Mejoramiento de la Calidad , Factores de Tiempo , Triaje/organización & administraciónRESUMEN
BACKGROUND: The European Society of Cardiology (ESC) Guidelines published in 2016 modified indications for cardiac resynchronization therapy (CRT) in comparison with the 2013 ESC Guidelines. The aim of this analysis was to evaluate the impact of the stricter criteria suggested by the 2016 ESC Guidelines on patient outcome in a real-world population. METHODS: We collected data on 930 consecutive patients with complete outcome information who had undergone CRT implantation from 2011 to 2013 from the CRT-MORE registry. Patients were classified according to 2013 (Reference) and 2016 (Current) ESC Guidelines. The primary end-point of the study was death from any cause and heart failure hospitalization. RESULTS: According to the Reference Guidelines, 650 (69.9%) patients met Class I indications, 190 (20.4%) Class IIa, 39 (4.2%) Class IIb and 51 (5.5%) Class III. According to the Current Guidelines, 563 (60.5%) patients met Class I indications, 145 (15.6%) Class IIa, 108 (11.6%) Class IIb and 114 (12.3%) Class III. On comparing the Reference and Current Guidelines, the 538 patients who confirmed their Class I indication had a better outcome in terms of freedom from the combined end-point of heart failure (HF) hospitalization or death from any cause (hazard ratio (HR) of 0.64; 95% CI 0.42 to 0.99; pâ¯=â¯0.0436) when compared to the 112 patients who lost their class I indication (84 moved to class IIb and 28 moved to class III). CONCLUSIONS: The stricter criteria for Class I CRT indication suggested by the 2016 ESC Guidelines excluded about 20% of patients with a worse prognosis. CLINICAL TRIAL REGISTRATION: CRT MORE: Cardiac Resynchronization Therapy Modular Registry URL: http://clinicaltrials.gov/Identifier:NCT01573091.
Asunto(s)
Terapia de Resincronización Cardíaca/normas , Cardiología/normas , Cardiopatías/diagnóstico , Cardiopatías/terapia , Guías de Práctica Clínica como Asunto/normas , Sociedades Médicas/normas , Anciano , Terapia de Resincronización Cardíaca/métodos , Cardiología/métodos , Estudios de Cohortes , Europa (Continente)/epidemiología , Femenino , Estudios de Seguimiento , Cardiopatías/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios ProspectivosRESUMEN
RATIONALE: Nowadays, the monitoring and prevention of healthcare-associated infections (HAIs) is a priority for the healthcare sector. AIMS AND OBJECTIVES: In this article, we report on the application of the Lean Six Sigma (LSS) methodology to reduce the number of patients affected by sentinel bacterial infections who are at risk of HAI. METHODS: The LSS methodology was applied in the general surgery department by using a multidisciplinary team of both physicians and academics. Data on more than 20 000 patients who underwent a wide range of surgical procedures between January 2011 and December 2014 were collected to conduct the study using the departmental information system. The most prevalent sentinel bacteria were determined among the infected patients. The preintervention (January 2011 to December 2012) and postintervention (January 2013 to December 2014) phases were compared to analyze the effects of the methodology implemented. The methodology allowed the identification of variables that influenced the risk of HAIs and the implementation of corrective actions to improve the care process, thereby reducing the percentage of infected patients. RESULTS: The improved process resulted in a 20% reduction in the average number of hospitalization days between preintervention and control phases, and a decrease in the mean (SD) number of days of hospitalization amounted to 36 (15.68), with a data distribution around 3 σ. The LSS is a helpful strategy that ensures a significant decrease in the number of HAIs in patients undergoing surgical interventions. The implementation of this intervention in the general surgery departments resulted in a significant reduction in both the number of hospitalization days and the number of patients affected by HAIs. CONCLUSIONS: This approach, together with other tools for reducing the risk of infection (surveillance, epidemiological guidelines, and training of healthcare personnel), could be applied to redesign and improve a wide range of healthcare processes.
Asunto(s)
Infecciones Bacterianas/prevención & control , Infección Hospitalaria/prevención & control , Procedimientos Quirúrgicos Operativos/métodos , Gestión de la Calidad Total/organización & administración , Adhesión a Directriz , Humanos , Capacitación en Servicio/organización & administración , Tiempo de Internación , Guías de Práctica Clínica como Asunto , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Vigilancia de GuardiaRESUMEN
BACKGROUND: Because 20% to 40% of patients undergoing cardiac resynchronization therapy (CRT) do not respond to it, identification of potential factors predicting response is a relevant research topic. HYPOTHESIS: There is a possible association between right ventricular function and response to CRT. METHODS: We analyzed 227 patients from the Cardiac Resynchronization Therapy Modular Registry (CRT-MORE) who received CRT according to current guidelines from March to December 2013. Response to therapy was defined as a decrease of ≥15% in left ventricular end-systolic volume (LVESV) at 6 months. RESULTS: The tricuspid annular plane systolic excursion (TAPSE) value that best predicted improvement in LVESV (sensitivity 68%, specificity 54%) was 17 mm. Stratifying patients according to TAPSE, LVESV decreased ≥15% in 78% of patients with TAPSE >17 mm (vs 59% in patients with TAPSE ≤17 mm; P = 0.006). At multivariate analysis, TAPSE >17 mm was independently associated with LVESV improvement (odds ratio: 1.97, 95% confidence interval: 1.03-3.80, P < 0.05), together with ischemic etiology (odds ratio: 0.39, 95% confidence interval: 0.20-0.75, P < 0.01). These results were confirmed for New York Heart Association class III to IV patients (79% echocardiographic response rate in patients with TAPSE >17 mm vs 55% in patients with TAPSE <17 mm; P = 0.012). CONCLUSIONS: Baseline signs of right ventricular dysfunction suggest possible remodeling after CRT. A TAPSE value of 17 mm was identified as a good cutoff for predicting a better response to CRT in patients with both mildly symptomatic and severe heart failure.
Asunto(s)
Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca/terapia , Disfunción Ventricular Izquierda/terapia , Disfunción Ventricular Derecha/fisiopatología , Función Ventricular Derecha , Anciano , Anciano de 80 o más Años , Terapia de Resincronización Cardíaca/efectos adversos , Distribución de Chi-Cuadrado , Ecocardiografía , Femenino , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/fisiopatología , Humanos , Italia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Sistema de Registros , Factores de Riesgo , Índice de Severidad de la Enfermedad , Volumen Sistólico , Factores de Tiempo , Resultado del Tratamiento , Válvula Tricúspide/fisiopatología , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Derecha/diagnóstico por imagen , Función Ventricular Izquierda , Remodelación VentricularRESUMEN
The aim of the study was to report the clinical results in patients with high-risk prostate cancer treated with pelvic intensity-modulated radiation therapy (IMRT) and simultaneous integrated boost (SIB) to the prostate area. A total of 110 patients entered our study, 37 patients presented with localized prostate cancer and radiological evidence of node metastases or ≥15% estimated risk of lymph node (LN) involvement, while 73 patients underwent postoperative adjuvant or salvage irradiation for biochemical or residual/recurrent disease, LN metastases, or high risk of harboring nodal metastases. All patients received androgen deprivation therapy (ADT) for 2 years. The median follow-up was 56.5 months. For the whole patient group, the 3- and 5-year freedom from biochemical failure were 82.6% and 74.6%, respectively, with a better outcome in patients treated with radical approach. The 3- and 5-year freedom from local failure were 94.4% and 90.2%, respectively, while the 3- and 5-year distant metastasis-free survival were 87.8% and 81.7%, respectively. For all study patients, the rate of freedom from G2 acute rectal, intestinal, and urinary toxicities was 60%, 77%, and 61%, respectively. There was no G3 acute toxicity, ≥G2 late intestinal toxicity, or G3 late urinary or rectal toxicity. The 3- and 5-year ≥G2 freedom from late rectal toxicity rate were 98% and 95%, respectively, while the 3- and 5-year ≥G2 freedom from late urinary toxicity rate were 95% and 88%, respectively. The study concludes that pelvic IMRT and SIB to the prostatic area in association with 2-year ADT was a well-tolerated technique, providing high disease control in patients with prostate cancer requiring LN treatment.
Asunto(s)
Neoplasias de la Próstata/patología , Neoplasias de la Próstata/radioterapia , Radioterapia de Intensidad Modulada , Anciano , Anciano de 80 o más Años , Fraccionamiento de la Dosis de Radiación , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/mortalidad , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: A high prevalence of atrial fibrillation/atrial flutter (AF/AFl) has been reported in small series of Brugada patients, with discordant data. OBJECTIVE: The purpose of this study was to analyze, in a large population of Brugada patients, the prevalence of AF/AFl, its correlation with prognosis, and the efficacy of hydroquinidine (HQ) treatment. METHODS: Among 560 patients with Brugada type 1 ECG (BrECG), 48 (9%) had AF/AFl. Three groups were considered: 23 patients with BrECG pattern recognized before AF/AFl (group 1); 25 patients first diagnosed with AF/AFl in whom Class IC antiarrhythmic drugs administered for cardioversion/prophylaxis unmasked BrECG (group 2); and 512 patients without AF/AFl (group 3). Recurrence of AF/AFl and occurrence of ventricular arrhythmias were evaluated at follow-up. RESULTS: Mean age was 47 ± 15 years, 59 ± 11 years, and 44 ± 14 years in groups 1, 2, and 3, respectively. Seven subjects (32%) in group 1 had syncope/aborted sudden death, 1 (4%) in group 2, and 122 (24%) in group 3. Ventricular arrhythmia occurred in three patients in group 1, none in group 2, and 10 in group 3 at median follow-up of 51, 68, and 41 months, respectively. Nine patients in group 1 and nine in group 2 received HQ for AF/AFl prophylaxis; on therapy, none had AF/AFl recurrence. CONCLUSION: Prevalence of AF/AFl in Brugada patients is higher than in the general population of the same age. Patients in group 1 are younger than those in group 2 and have a worse prognosis compared to both groups 2 and 3. HQ therapy has proved useful and safe in patients with AF/AFl and BrECG.
Asunto(s)
Antiarrítmicos/uso terapéutico , Fibrilación Atrial/complicaciones , Aleteo Atrial/complicaciones , Síndrome de Brugada/complicaciones , Síndrome de Brugada/fisiopatología , Electrocardiografía , Quinidina/análogos & derivados , Adulto , Arritmias Cardíacas/complicaciones , Arritmias Cardíacas/tratamiento farmacológico , Fibrilación Atrial/prevención & control , Aleteo Atrial/prevención & control , Síndrome de Brugada/tratamiento farmacológico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Quinidina/uso terapéuticoRESUMEN
BACKGROUND: Feasibility of whole breast hypofractionated radiotherapy schedules in breast conserving therapy is recognized however concerns remain about the role of the boost dose on the overall treatment's potential toxicity. In this study we report on the possibility to quantitatively evaluate radiation induced toxicity in patients treated with an abbreviated course with major concern in the irradiated boost region. METHODS: Eighty-nine patients who underwent conservative surgery for early-stage breast cancer followed by adjuvant accelerated hypofractionated whole breast radiotherapy were included in this study to assess skin and subcutaneous tissue late toxicity by means of ultrasonographic quantitative examination. For each patient the skin thickness was measured at four positions: on the irradiated breast, in the boost region and in the corresponding positions in the contra-lateral not treated breast. All patients were scanned by the same radiologist to reduce potential inter-operator variability, the operator was blind to the scoring of the patient CTCv3 late toxicity as well as patient treatment characteristics. Ultrasound assessment and clinical evaluation were compared. RESULTS: The median time between the end of adjuvant radiotherapy and ultrasound examination was 20.5 months. The measured mean skin thickness in the irradiated breast was 2.13 ± 0.72 mm while in the mirror region of the contra-lateral healthy breast was 1.61 ± 0.29 mm. The measured mean skin thickness in the irradiated boost region was 2.25 ± 0.79 mm versus 1.63 ± 0.33 mm in the corresponding region of contra-lateral healthy breast. The mean increment in skin thickness respect to the counterpart in the healthy breast was 0.52 ± 0.67 mm and 0.62 ± 0.74 mm for the breast and the boost region respectively. A significant direct correlation was found between the increment in skin thickness in the irradiated breast and in the boost region with fibrosis (G ≥ 1). CONCLUSIONS: In this study results from a breast cancer hypofractionated schedule in terms of late skin toxicity are reported. In particular our study confirms that late cutaneous reactions can be reliably assed by ultrasonographic examination, also discriminating between regions irradiated at different doses, and that this instrumental evaluation is in agreement with clinical stated toxicity.
Asunto(s)
Neoplasias de la Mama/radioterapia , Traumatismos por Radiación/diagnóstico por imagen , Traumatismos por Radiación/etiología , Piel/diagnóstico por imagen , Piel/efectos de la radiación , Adulto , Anciano , Neoplasias de la Mama/cirugía , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Persona de Mediana Edad , Radioterapia Adyuvante/efectos adversos , Enfermedades de la Piel/diagnóstico por imagen , Enfermedades de la Piel/etiología , UltrasonografíaRESUMEN
BACKGROUND: To investigate the potential dosimetric and clinical benefits of Deep Inspiration Breath-Hold (DIBH) technique during radiotherapy of breast cancer compared with Free Breathing (FB). METHODS: Eight left-sided breast cancer patients underwent a supervised breath hold during treatment. For each patient, two CT scans were acquired with and without breath hold, and virtual simulation was performed for conventional tangential fields, utilizing 6 or 15 MV photon fields. The resulting dose-volume histograms were calculated, and the volumes of heart/lung irradiated to given doses were assessed. The left anterior descending coronary artery (LAD) mean and maximum doses were calculated, together with tumour control probability (TCP) and normal tissue complication probabilities (NTCP) for lung and heart. RESULTS: For all patients a reduction of at least 16% in lung mean dose and at least 20% in irradiated pulmonary volumes was observed when DIBH was applied. Heart and LAD maximum doses were decreased by more than 78% with DIBH. The NTCP values for pneumonitis and long term cardiac mortality were also reduced by about 11% with DIBH. The NTCP values for pericarditis were zero for both DIBH and FB. CONCLUSION: Delivering radiation in DIBH conditions the dose to the surrounding normal structures could be reduced, in particular heart, LAD and lung, due to increased distance between target and heart, and to reduced lung density.
Asunto(s)
Neoplasias de la Mama/radioterapia , Radiometría/métodos , Mecánica Respiratoria/fisiología , Técnicas de Imagen Sincronizada Respiratorias/métodos , Adulto , Anciano , Neoplasias de la Mama/diagnóstico por imagen , Contencion de la Respiración , Femenino , Corazón/diagnóstico por imagen , Humanos , Pulmón/diagnóstico por imagen , Persona de Mediana Edad , Radiografía , Radioterapia Adyuvante , Radioterapia Conformacional/métodos , Radioterapia Guiada por ImagenRESUMEN
While it is well accepted that the left prefrontal cortex plays a critical role in planning and problem-solving tasks, very little is known about the role of the right prefrontal cortex. We addressed this issue by testing five neurological patients with focal lesions to right prefrontal cortex on a real-world travel planning task, and compared their performance with the performance of five neurological patients with focal lesions to left prefrontal cortex, five neurological patients with posterior lesions, and five normal controls. Only patients with lesions to right prefrontal cortex generated substandard solutions compared to normal controls. Examination of the underlying cognitive processes and strategies revealed that patients with lesions to right prefrontal cortex approached the task at an excessively precise, concrete level compared to normal controls, and very early locked themselves into substandard solutions relative to the comparison group. In contrast, the behavior of normal controls was characterized by a judicious interplay of concrete and abstract levels/modes of representations. We suggest that damage to the right prefrontal system impairs the encoding and processing of more abstract and vague representations that facilitate lateral transformations, resulting in premature commitment to precise concrete patterns, and hasty albeit substandard conclusions (because the space of possibilities has not been properly explored).
Asunto(s)
Objetivos , Corteza Prefrontal/lesiones , Solución de Problemas/fisiología , Adulto , Afecto/fisiología , Anciano , Atención , Cognición/fisiología , Interpretación Estadística de Datos , Escolaridad , Función Ejecutiva/fisiología , Femenino , Lateralidad Funcional/fisiología , Humanos , Pruebas de Inteligencia , Aneurisma Intracraneal/patología , Aneurisma Intracraneal/psicología , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Corteza Prefrontal/patología , Accidente Cerebrovascular/patología , Accidente Cerebrovascular/psicología , Adulto JovenRESUMEN
Chromatin immunoprecipitation in M14 melanoma cells showed that the protein ERp57 (endoplasmic reticulum protein 57) binds to DNA in the proximity of STAT3 in a subset of STAT3-regulated genes. In the same cells, IL-6 induced a significant increase of the expression of one of these genes, i.e. CRP. Upon depletion of ERp57 by RNA interference, the phosphorylation of STAT3 on tyrosine 705 was decreased, and the IL-6-induced activation of CRP expression was completely suppressed. In vitro experiments showed that ERp57 is also required for the binding of STAT3 to its consensus sequence on DNA. Thus ERp57, previously shown to associate with STAT3 in the cytosol and in the nuclear STAT3-containing enhanceosome, is a necessary cofactor for the regulation of at least a subset of STAT3-dependent genes, probably intervening both at the site of STAT3 phosphorylation and at the nuclear level.
Asunto(s)
Melanoma/patología , Proteína Disulfuro Isomerasas/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Transcripción Genética , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , ADN/metabolismo , Humanos , Proteína Disulfuro Isomerasas/química , Proteína Disulfuro Isomerasas/deficiencia , Proteína Disulfuro Isomerasas/genética , Interferencia de ARNRESUMEN
The protein ERp57/GRP58 is a member of the protein disulfide isomerase family and is also a glucose-regulated protein, which, together with the other GRPs, is induced by a variety of cellular stress conditions. ERp57/GRP58 is mainly located in the endoplasmic reticulum (ER), but has also been found in the cytoplasm and in the nucleus, where it can bind DNA. In order to identify a possible correlation between the stress-response and the nuclear location of ERp57/GRP58, its binding sites on DNA in HeLa cells have been searched by chromatin immunoprecipitation and cloning of the immunoprecipitated DNA fragments. Following sequencing of the cloned fragments, 10 DNA sequences have been securely identified as in vivo targets of ERp57/GRP58. Nine of them are present in the non-coding regions of identified genes, and seven of these in introns. The features of some of these DNA sequences, that is, DNase hypersensitivity, proximity of MAR regions, and homology to the non-coding regions of orthologue genes of mouse or rat, are compatible with a gene expression regulatory function. Considering the nature of the genes concerned, two of which code for DNA repair proteins, we would suggest that at least part of the mechanism of action of ERp57/GRP58 takes place through the regulation of these, and possibly other still unidentified, stress-response genes.
Asunto(s)
Núcleo Celular/metabolismo , Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica/fisiología , Proteína Disulfuro Isomerasas/metabolismo , Estrés Fisiológico/metabolismo , Animales , Secuencia de Bases/genética , Sitios de Unión/genética , Núcleo Celular/genética , ADN/análisis , ADN/genética , ADN/metabolismo , Reparación del ADN/genética , Proteínas de Unión al ADN/genética , Células HeLa , Humanos , Intrones/genética , Ratones , Unión Proteica , Proteína Disulfuro Isomerasas/química , Proteína Disulfuro Isomerasas/genética , Ratas , Homología de Secuencia de Ácido Nucleico , Especificidad de la Especie , Estrés Fisiológico/genéticaRESUMEN
STAT3 has been found constitutively activated in M14 melanoma cell line, as previously found in other melanoma cells. Using EMSA, DNA affinity experiments, and chromatin immunoprecipitation, STAT3 was found in M14 to bind the alpha2-macroglobulin gene enhancer in association with the protein disulfide isomerase isoform ERp57. The two proteins have also been found to be associated when bound to the SIE sequence in HepG2 cells stimulated by IL-6. In both cases an anti-ERp57 antibody hinders the binding of STAT3 to its consensus sequence on DNA, indicating that ERp57 is a necessary component of the DNA-bound STAT3 complex. Considering the functional association of the two proteins, the overexpression of ERp57 observed in a variety of transformed cells might be relevant to the oncogenic properties of STAT3.
Asunto(s)
Carcinoma Hepatocelular/metabolismo , Núcleo Celular/metabolismo , ADN de Neoplasias/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Choque Térmico/metabolismo , Isomerasas/metabolismo , Melanoma/metabolismo , Transactivadores/metabolismo , Sitios de Unión , Línea Celular Tumoral , Núcleo Celular/química , ADN de Neoplasias/química , Proteínas de Unión al ADN/química , Proteínas de Choque Térmico/química , Humanos , Isomerasas/química , Unión Proteica , Proteína Disulfuro Isomerasas , Factor de Transcripción STAT3 , Transactivadores/químicaRESUMEN
HP1 is a conserved chromosomal protein, first discovered in Drosophila, which is predominantly associated with the heterochromatin of many organisms. Recently, it has been shown that HP1 is required for telomere capping, telomere elongation, and transcriptional repression of telomeric sequences. Several studies have suggested a model for heterochromatin formation and epigenetic gene silencing in different species that is based on interactions among histone methyltransferases (HMTases), histone H3 methylated at lysine 9 (H3-MeK9), and the HP1 chromodomain. This model has been extended to HP1 telomeric localization by data showing that H3-MeK9 is present at all of the telomeres. Here, we tested this model, and we found that the capping function of HP1 is due to its direct binding to telomeric DNA, while the silencing of telomeric sequences and telomere elongation is due to its interaction with H3-MeK9.