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1.
Am J Cardiol ; 215: 42-49, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38237796

RESUMEN

Invasive hemodynamic studies have shown improved left ventricular (LV) performances when cardiac resynchronization therapy/defibrillator is delivered through multipoint pacing (MPP). Nowadays, strategies have become available that allow studying the same hemodynamic parameters at a noninvasive level. The aim of the present study was to evaluate the clinical implication of using a patient-tailored approach for cardiac resynchronization therapy programming based on noninvasively assessed LV hemodynamics to identify the best biventricular pacing modality between standard single-site pacing (STD) and MPP for each patient. Therefore, 51 patients with heart failure (age 69 ± 9 years, 35 men, 27% ischemic etiology) implanted with cardiac resynchronization therapy/defibrillator underwent noninvasive LV function assessment through photoplethysmography before hospital discharge for addressing dP/dt and stroke volume in both pacing modalities (STD and MPP). The modality that performed better in terms of hemodynamic improvement was permanently programmed. Global longitudinal strain (GLS) was also assessed, and repeated at 3 months. Compared with intrinsic rhythm (928 ± 486 mm Hg/s), dP/dtmax showed a trend to increase in both biventricular pacing modes (1,000 ± 577 mm Hg/s in STD, 1,036 ± 530 mm Hg/s in MPP, p = NS). MPP was associated with a wider hemodynamic improvement than was STD and was the modality of choice in 34 of 51 patients (67%). GLS at predischarge did not differ between groups (-10.3 ± 3.8% vs -10.2 ± 3.5%), but significant improvement of ejection fraction at 1 month (34.4 ± 5.3%, p <0.001) and of GLS at 3 months (-12.9 ± 2.9%, p <0.005) was observed across the entire cohort. At 3 months, 77% of patients were classified as responders. Interestingly, long-term (3 years) follow-up unveiled a reduction in all-cause mortality in the MPP group compared with the STD group. In conclusion, cardiac resynchronization therapy programming guided by acute noninvasive hemodynamics favored MPP modality and caused short-term LV positive remodeling and improved long-term outcomes. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT04299360.


Asunto(s)
Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca , Masculino , Humanos , Persona de Mediana Edad , Anciano , Hemodinámica , Insuficiencia Cardíaca/terapia , Ventrículos Cardíacos , Alta del Paciente , Remodelación Ventricular
2.
Int J Cardiol ; 393: 131391, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37748521

RESUMEN

AIMS: Angiotensin receptor-neprilysin inhibitor (ARNi) and sodium-glucose co-transporter 2 inhibitor (SGLT2i) improve outcomes in heart failure with reduced ejection fraction (HFrEF) patients, however their effects in cardiac resynchronization therapy (CRT) recipients have been scarcely explored. This study investigated whether ARNi and SGLT2i 1) improve the rate of clinical and echocardiographic CRT response and 2) have different impact based on the ischemic or non-ischemic etiology. METHODS: HFrEF patients referred for CRT implant were grouped in no treatment (group 1), only ARNi (group 2) and both ARNi and SGLT2i (group 3). Clinical and echocardiographic response were evaluated at 12 months. RESULTS: A total of 178 patients were enrolled. At one-year follow-up, 74.4% patients in group 2 (p = 0.031) and 88.9% in group 3 (p = 0.014) were classified as clinical responders vs 54.5% in the no treatments group. In multivariable analysis, ARNi/SGLT2i use was an independent predictor of CRT response (OR 3.72; CI 95%, 1.40-10.98; p = 0.011), confirmed in both groups 2 and 3. At 12 months, the median Δ LVEF increase was 6% and 8.5% in groups 2 and 3 respectively, vs 4.5% in group 1 (p = 0.042 and p = 0.029) with significantly more echocardiographic responders in groups 2 and 3 (76% and 78% vs 50%, p = 0.003 and p = 0.036). Significantly more ischemic HFrEF patients than non-ischemic were considered clinical and echocardiographic responders in the treatment groups. CONCLUSIONS: ARNi alone or in combination with SGLT2i in CRT patients improves the clinical and echocardiographic response at 12 months. Ischemic patients seem to benefit more from these treatments.

3.
ACS Photonics ; 10(5): 1566-1574, 2023 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-37215314

RESUMEN

The electron injection efficiency and the steady state absorptance at different photon energies for a composite system made of Au NPs embedded in a cerium oxide matrix are reported. Cerium oxide can be coupled with plasmonic nanoparticles (NPs) to improve its catalytic properties by visible-light absorption. The present work is a study of the ultrafast dynamics of excited states induced by ultraviolet and visible-light excitation in Au NPs combined with cerium oxide, aimed at understanding the excitation pathways. The data, obtained by femtosecond transient absorption spectroscopy, show that the excitation of localized surface plasmon resonances (LSPRs) in the Au NPs leads to an ultrafast injection of electrons into the empty 4f states of the surrounding cerium oxide. Within the first few picoseconds, the injected electrons couple with the lattice distortion forming a polaronic excited state, with similar properties to that formed after direct band gap excitation of the oxide. At sub-picosecond delay times, we observed relevant differences in the energetics and the time dynamics as compared to the case of band gap excitation of the oxide. Using different pump energies across the LSPR-related absorption band, the efficiency of the electron injection from the NPs into the oxide was found to be rather high, with a maximum above 30%. The injection efficiency has a different trend in energy as compared to the LSPR-related static optical absorptance, showing a significant decrease in low energies. This behavior is explained considering different deexcitation pathways with variable weight across the LSPR band. The results are important for the design of materials with high overall solar catalytic efficiency.

4.
J Arrhythm ; 38(3): 439-445, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35785398

RESUMEN

Background: The effects of lockdown on non-COVID patients are varied and unexpected. The aim is to evaluate the burden of cardiac arrhythmias during a lockdown period because of COVID-19 pandemics in a population implanted with cardiac defibrillators and followed by remote monitoring. Methods: In this retrospective, multicentre cohort study, we included 574 remotely monitored implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy-defibrillator (CRT-D) recipients implanted before January 1, 2019, at seven hospitals in the Campania region, comparing the burden of arrhythmias occurred during the lockdown period because of COVID-19 epidemics (from March 9 to May 1, 2020) with the arrhythmias burden of the corresponding period in 2019 (reference period). Data collection was performed through remote monitoring. Results: During the lockdown period, we observed ventricular tachyarrhythmias (ventricular tachycardia or fibrillation) in 25 (4.8%) patients while in seasonal reference period we documented ventricular tachyarrhythmias in 12 (2.3%) patients; the comparison between the periods is statistically significant (P < .04). Atrial arrhythmias were detected in 38 (8.2%) subjects during the lockdown period and in 24 (5.2%) during the reference period (P < .004). Conclusion: In seven hospitals in the Campania region, during the pandemic lockdown period, we observed a higher burden of arrhythmic events in ICD/CRT-D patients through device remote monitoring.

5.
J Arrhythm ; 38(2): 213-220, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35387134

RESUMEN

Aim: Remote monitoring (RM) of implantable cardiac devices has enabled continuous surveillance of atrial high rate episodes (AHREs) with well-recognized clinical benefits. We aimed to add evidence on the role of the RM as compared to conventional follow-up by investigating the interval from AHRE onset to physician's evaluation and reaction time in actionable episodes. Methods and Results: A total of 97 dual-chamber pacemaker recipients were followed with RM (RM-ON group; N = 64) or conventional in-office visits (RM-OFF group; N = 33) for 18 months. In-office visits were scheduled at 1, 6, 12, and 18 months in the RM-OFF group and at 1 and 18 months in the RM-ON group. The overall AHRE rate was 1.98 per patient-year (95% confidence interval [CI], 1.76-2.20) with no difference between the two groups (RM-ON vs. RM-OFF weighted-HR, 0.88; CI, 0.36-2.13; p = .78). In the RM-ON group, 100% AHREs evaluated within 11 days from onset, and within 202 days in the RM-OFF group, with a median evaluation delay 79 days shorter in the RM-ON group versus the RM-OFF group (p < .0001). Therapy adjustment in actionable AHREs occurred 77 days earlier in the RM-ON group versus the control group (p < .001). In the RM-ON group, there were 50% less in-office visits as compared to the RM-OFF group (p < .001). Conclusions: In our pacemaker population with no history of atrial fibrillation, RM allowed significant reduction of AHRE evaluation delay and prompted treatment of actionable episodes as compared to biannual in-office visit schedule.

6.
ESC Heart Fail ; 8(6): 5204-5212, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34514741

RESUMEN

AIMS: There are conflicting data on the benefit of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with permanent atrial fibrillation (AF). We aimed to compare patient outcomes according to the presence or absence of permanent AF at device implantation. METHODS AND RESULTS: We retrospectively analysed remote monitoring data from 1141 CRT defibrillators. Propensity score with inverse-probability weighting method was used to balance AF and sinus rhythm (SR) groups. Analysis endpoints included total mortality, appropriate defibrillation shocks, and CRT percentage. There were 229 patients (20.1%) in the AF group and 912 patients (79.9%) in the SR group. Compared with SR patients, AF patients were older (median age, 77 vs. 72 years, P < 0.001), more frequently male (82.5% vs. 75.5%, P = 0.02), and had higher heart rate (75.7 vs. 71.0 b.p.m., P < 0.001). Of the 229 AF patients, 162 (70.7%) received suboptimal CRT (<98%) and 67 (29.3%) had adequate CRT (≥98%). During a median follow-up of 24 months, total mortality did not differ between AF and SR groups (propensity-score-weighted hazard ratio, HR 1.32 [95% confidence interval, 0.82-2.15], P = 0.25). The risk of appropriate shocks was significantly higher in the AF group with <98% CRT than in the SR group (weighted-HR, 1.99 [1.21-3.26], P = 0.006) and was similar in the AF group with ≥98% CRT versus the SR group (1.29 [0.66-2.53], P = 0.45). During follow-up, sinus rhythm was recovered in 23 patients in the AF group (10%) after a median time of 106 (42-256) days. The rate of sinus rhythm recovery in the AF group was 4.5 (95% CI, 2.8-6.7) per 100 patient-years; the rate of permanent AF occurrence in the SR group was 2.5 (95% CI, 1.9-3.3) per 100 patient-years. CONCLUSIONS: Although mortality was similar across patient groups, patients with permanent AF and suboptimal CRT had twofold higher risk of appropriate shocks than SR patients or AF patients with CRT ≥ 98%.


Asunto(s)
Fibrilación Atrial , Terapia de Resincronización Cardíaca , Anciano , Fibrilación Atrial/epidemiología , Fibrilación Atrial/terapia , Terapia de Resincronización Cardíaca/métodos , Desfibriladores , Humanos , Masculino , Estudios Retrospectivos , Resultado del Tratamiento
7.
J Clin Med ; 10(7)2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33916276

RESUMEN

BACKGROUND: More and more heart failure (HF) patients aged ≥ 75 years undergo cardiac resynchronization therapy (CRT) device implantation, however the data regarding the outcomes and their predictors are scant. We investigated the mid- to long-term outcomes and their predictors in CRT patients aged ≥ 75 years. METHODS: Patients in the Cardiac Resynchronization Therapy Modular (CRT MORE) Registry were divided into three age-groups: <65 (group A), 65-74 (group B) and ≥75 years (group C). Mortality, hospitalization, and composite event rate were evaluated at 1 year and during long-term follow-up. RESULTS: Patients (n = 934) were distributed as follows: group A 242; group B 347; group C 345. On 12-month follow-up examination, 63% of patients ≥ 75 years displayed a positive clinical response. Mortality was significantly higher in patients ≥ 75 years than in the other two groups, although the rate of hospitalizations for HF worsening was similar to that of patients aged 65-74 (7 vs. 9.5%, respectively; p = 0.15). Independent predictors of death and of negative clinical response were age >80 years, chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD). Over long-term follow-up (1020 days (IQR 680-1362)) mortality was higher in patients ≥ 75 years than in the other two groups. Hospitalization and composite event rates were similar in patients ≥ 75 years and those aged 65-74 (9 vs. 11.8%; p = 0.26, and 26.7 vs. 20.5%; p = 0.06). CONCLUSION: Positive clinical response and hospitalization rates do not differ between CRT recipients ≥ 75 years and those aged 65-74. However, age > 80 years, COPD and CKD are predictors of worse outcomes.

8.
J Clin Med ; 10(9)2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33922775

RESUMEN

AIMS: The occurrence of ventricular arrhythmias (VAs) in ischemic heart disease (IHD) patients is related to the presence and extent of fibrotic/scar tissue. As coronary atherosclerosis is the underlying cause of myocardial ischemia and fibrosis, in IHD patients implanted with an implantable cardioverter defibrillator (ICD) we investigated the relation between the VA burden and the complexity of coronary atherosclerotic lesions. METHODS AND RESULTS: In IHD patients who underwent coronary angiography and ICD implant, the Syntax scores I and II (SSI-II), as index of the severity of the coronary atherosclerotic disease, and the occurrence of VA were assessed. Overall 144 patients were included (123 males). Of these 22 patients (15%) experienced at least one episode of VA (cycle length 298 ± 19 msec) that required ICD intervention. The number of episodes per patient and per year was 4 ± 6 and 2.8 ± 4, respectively. Patients that experienced a VA compared to those free from arrhythmic events did not have distinct baseline clinical characteristics except for a higher SS I and SS II (21 (IQR 13-38) vs. 16 (IQR 10-23); p = 0.037; and 50 (IQR 39-62) vs. 42 (IQR 34-50); p = 0.012). In the binary logistic regression analyses the SS I and II were the only independent predictors of VA occurrence. A higher SS II was also associated with an earlier time to first event (p = 0.005). CONCLUSION: Higher SS I-II scores reflect a more severe coronary atherosclerosis and are associated with a greater VA burden. Further studies are needed to better clarify the ability of SSI-II to stratify the risk of IHD patients to develop life-threatening VA.

9.
J Clin Med ; 9(7)2020 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-32646007

RESUMEN

BACKGROUND: Insulin resistance (IR) in patients with type 2 diabetes mellitus (T2DM) represents a predictor of coronary artery disease (CAD). However, how IR is able to impact the severity of coronary atherosclerosis in non-diabetic patients is unknown. OBJECTIVES: We investigated the relation between the IR and the extent and severity of coronary atherosclerosis in non-diabetic patients referred to coronary angiography (CA) Methods: Consecutive patients undergoing to CA for acute coronary syndromes or stable angina were analyzed. The IR was assessed by mean of the homeostasis model assessment of insulin resistance (HOMA-IR) whereas the SYNTAX score (SS) was used as index of the severity of coronary atherosclerosis Results: Overall, 126 patients were included, with a median SS of 12 (IQR 5.25-20.5). Patients were divided in four groups according to the distribution in quartiles of SS (SS1-2-3-4). A significant correlation between HOMA-IR and SS was observed, especially in women. A progressive increase of HOMA-IR was observed in parallel with the increasing severity (from SS1 to SS4) and extension (1-2-3-vessel disease) of coronary atherosclerosis. Multivariable analysis showed that the HOMA-IR was the strongest independent predictor of severe (SS4) and extensive (three-vessel disease) coronary atherosclerosis. CONCLUSION: Insulin resistance goes hand in hand with the extension and severity of coronary atherosclerosis in non-diabetic patients. The HOMA index is an independent predictor of three-vessel disease at CA. The HOMA index could be useful for risk stratification of CAD even in absence of T2DM.

10.
ESC Heart Fail ; 6(6): 1266-1273, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31833232

RESUMEN

AIMS: Data regarding contrast-induced nephropathy (CIN) after cardiac resynchronization therapy (CRT) implant are limited. We aimed to investigate the incidence and determinants of CIN and its impact on CRT response and outcomes. METHODS AND RESULTS: Patients who underwent CRT implant were retrospectively analysed, and CIN was defined as an increase of serum creatinine ≥0.3 mg/dL or ≥1.5 times the baseline value. Response to CRT was defined as a reduction of left ventricle end-systolic volume (LVESV) of 15% or the increase of five percentage points in ejection fraction (EF) as assessed by echocardiography at 6 months. Follow-up visits were scheduled at 3, 6, and 12 months. Contrast-induced nephropathy occurred in 13/107 patients (12%). Among baseline clinical, echocardiographic, and laboratory characteristics, only a high baseline serum creatinine was associated with the occurrence of CIN. Symptoms, EF, and LVESV at 6 months improved in both CIN and non-CIN patients, and the rate of responders to CRT was similar. Among responders, at 6 months, those with CIN had significantly lower EF (28.5% vs. 35.7% P = 0.003). At a median follow-up of 112 weeks, 43% of patients experienced a clinical event with similar incidence in CIN and non-CIN patients, and likewise survival was similar. Non-responders to CRT had worse survival while among responders those with CIN had worse survival than non-CIN patients (71% vs. 90%, P = 0.0035). CONCLUSIONS: The incidence of CIN is rather high. Although CIN does not influence response to CRT overall, however among responders impairs the recovery of EF and survival.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Terapia de Resincronización Cardíaca/efectos adversos , Medios de Contraste/efectos adversos , Insuficiencia Cardíaca/terapia , Anciano , Anciano de 80 o más Años , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Volumen Sistólico/fisiología
11.
Sci Rep ; 9(1): 7888, 2019 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-31133712

RESUMEN

Arterial hypertension is a leading risk factor for developing atrial fibrillation. CHA2DS2-VASc score can help to decide if patients with atrial fibrillation need anticoagulation. Whether CHA2DS2-VASc may predicts incident atrial fibrillation and how it interacts with left atrial dilatation is unknown. We tested this hypothesis in a large registry of treated hypertensive patients. From 12154 hypertensive patients we excluded those with prevalent atrial fibrillation (n 51), without follow-up (n 3496), or carotid ultrasound (n 1891), and low ejection fraction (i.e. <50%, n 119). A CHA2DS2-VASc score ≥3 was compared with CHA2DS2-VASc score ≤2. Incident symptomatic or occasionally detected atrial fibrillation was the end-point of the present analysis. At baseline, 956 (15%) patients exhibited high CHA2DS2-VASc; they were older, most likely to be women, obese and diabetic, with lower glomerular filtration rate, and higher prevalence of left ventricular hypertrophy, left-atrial dilatation and carotid plaque (all p < 0.005). Prevalent Stroke/TIA was found only in the subgroup with high CHA2DS2-VASc. During follow-up (median = 54 months) atrial fibrillation was identified in 121 patients, 2.57-fold more often in patients with high CHA2DS2-VASc (95% Cl 1.71-4.86 p < 0.0001). In multivariable Cox analysis, CHA2DS2-VASc increased incidence of atrial fibrillation by 3-fold, independently of significant effect of left-atrial dilatation (both p < 0.0001) and other markers of organ damage. Incident AF is more than doubled in hypertensive patients with CHA2DS2-VASc ≥3. Coexisting CHA2DS2-VASc score >3 and LA dilatation identify high risk subjects potentially needing more aggressive management to prevent AF and associated cerebrovascular ischemic events.


Asunto(s)
Fibrilación Atrial/epidemiología , Atrios Cardíacos/fisiopatología , Hipertensión/complicaciones , Índice de Severidad de la Enfermedad , Adulto , Factores de Edad , Anciano , Fibrilación Atrial/etiología , Fibrilación Atrial/fisiopatología , Diabetes Mellitus/epidemiología , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/epidemiología , Humanos , Hipertensión/diagnóstico , Hipertensión/fisiopatología , Incidencia , Italia/epidemiología , Masculino , Persona de Mediana Edad , Sistema de Registros/estadística & datos numéricos , Medición de Riesgo/métodos , Factores de Riesgo , Factores Sexuales , Accidente Cerebrovascular/epidemiología
12.
J Atr Fibrillation ; 11(2): 2075, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30505383

RESUMEN

BACKGROUND: Remote Monitoring (RM) has been introduced for several years and nowadays most pacemakers are equipped with such a technology. RM can provide early detection of high atrial rate episodes (AHREs) onset and enable prompt medical intervention. However, there are still little data on the clinical reactions triggered by the AHRE detected by RM of pacemaker recipients and on their possible benefit on patients' outcome. METHODS/DESIGN: The RAPID study is a multicenter, prospective, non-interventional study designed to compare the time from onset to first physician's evaluation of AHRE episode with arrhythmic burden ≥5% (72 minutes) for pacemaker recipients without atrial fibrillation history, between patients followed with RM or conventionally with annual in-hospital visits. A total of 98 patients with implanted dual-chamber pacemaker, assigned to RM-OFF or RM-ON according to ordinary clinical site practice, will be followed for a total of 18 months. After the implant, patients will perform their first in-hospital follow-up visit at 1 month and then, in the RM-OFF group, patients will perform an in-hospital FU every 6 months, while in the active group, patients will be continuously monitored via RM until study termination. All AHREs and consequent medical interventions will be collected over the entire study period. DISCUSSION: The ongoing RAPID study will provide additional information on the role of RM in the management of AHRE detected in pacemaker patients without documented atrial fibrillation history in ordinary clinical practice.

13.
Eur J Heart Fail ; 20(6): 1000-1010, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29314582

RESUMEN

AIMS: Circulating levels of microRNAs (miRNAs) are emergent promising biomarkers for cardiovascular disease. Altered expression of miRNAs has been related to heart failure (HF) and cardiac remodelling. We measured the concentration gradients across the coronary circulation to assess their usefulness to diagnose HF of different aetiologies. METHODS AND RESULTS: Circulating miRNAs were measured in plasma samples simultaneously obtained from the aorta and the coronary venous sinus in patients with non-ischaemic HF (NICM-HF, n = 23) ischaemic HF (ICM-HF, n = 41), and in control patients (n = 11). A differential modulation of circulating levels of miR-423, -34a, -21-3p, -126, -199 and -30a was found across the aetiology groups. Interestingly, a positive transcoronary gradient was found for miR-423 (P < 0.001) and miR-34a (P < 0.001) only in the ICM-HF group. On the contrary, a positive gradient was found for miR-21-3p (P < 0.001) and miR-30a (P = 0.030) only in the NICM-HF group. Finally, no significant variations were observed in the transcoronary gradient of miR-126 or miR-199. CONCLUSIONS: The present findings suggest that circulating levels of miRNAs are differentially expressed in patients with HF of different aetiologies. The presence of a transcoronary concentration gradient suggests a selective release of miRNAs by the failing heart into the coronary circulation. The presence of aetiology-specific transcoronary concentration gradients in HF patients might provide important information to better understand their role in HF, and suggests they could be useful biomarkers to distinguish HF of different aetiologies.


Asunto(s)
MicroARN Circulante/sangre , Circulación Coronaria/fisiología , Vasos Coronarios/diagnóstico por imagen , Insuficiencia Cardíaca/sangre , Anciano , Biomarcadores/sangre , Cateterismo Cardíaco , MicroARN Circulante/genética , Angiografía Coronaria , Vasos Coronarios/fisiopatología , Femenino , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
14.
Clin Cancer Res ; 8(6): 1808-15, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12060621

RESUMEN

PURPOSE: The quest for prognostic molecular markers in prostatic carcinoma is still in progress. Many proteins have already been screened by immunohistochemistry with the aim to find the most reliable indicator of progressive disease. In this study, we evaluated the expression of pRb2/p130, p107, p27(kip1), p53, mdm-2, and Ki-67 (MIB-1) by immunohistochemistry in 24 prostate carcinomas compared with the paired expression of normal prostates. EXPERIMENTAL DESIGN: Expression of the different proteins in normal and pathological specimens was evaluated by the Wilcoxon test. A matrix of correlation (Spearman coefficient) was used to evaluate the possible association in expression among the different proteins. Logistic regression analysis was used to test the multivariable prognostic value of the levels of protein expression for the probability of disease development. RESULTS: p53 and Ki-67 (MIB-1) showed a higher expression in cancer than in normal tissue (P = 0.006 and <0.001, respectively). pRb2/p130, p107, and p27(kip1) showed an overall lower expression in cancer, but the difference between cytoplasmic and nuclear expression was always higher for cancer (Ps, from <0.001 to 0.016). mdm-2 expression was lower in cancer, but the difference between cytoplasmic and nuclear expression was not significant (P = 0.571) when compared with that in normal tissue. A positive correlation between p27 and pRb2/p130 levels expressed, in normal and cancer counterparts in the same sample, as the difference between cytoplasmic and nuclear protein concentrations (P = 0.045) was found. Additionally, p107 expression showed an inverse correlation with Ki-67 (MIB-1) expression in the most aggressive tumors (P = 0.046). Logistic regression output showed that Ki-67 (MIB-1) and pRb2/p130 (expressed as differences between cytoplasmic and nuclear concentrations) were the variables associated with a higher risk of cancer. The highest value was reported for Ki-67 (MIB-1) (odds ratio, 2.11), followed by pRb2/p130 (odds ratio, 1.01). pRb2/p130 alone was associated with a sensitivity (rate of cases having a posterior probability of disease >/=0.5) of 61% with a false positive rate of 22%. Ki-67 (MIB-1) alone yielded a sensitivity of 69% and a false positive rate of 14%. The combined model (Ki-67 + pRb2/p130) yielded a sensitivity of 83% with a false positive rate of 17%. Interestingly, one specimen in which we also found a high-grade prostatic intraepithelial neoplasia showed the progressive loss of pRb2/p130 from normal prostatic cells to prostatic intraepithelial neoplasia cells, suggesting that in prostatic cancer, lack of expression of the tumor suppressor gene pRb2/p130 could be involved in the progression of the disease, from an early stage. CONCLUSIONS: This study showed that all of the proteins but mdm-2 were expressed at a different rate in normal and pathological prostate specimens. Multivariate analysis showed that pRb2/p130 and p107 may be involved in the pathogenesis and progression of prostate cancers, and that the expression of the retinoblastoma-related protein pRb2/p130 along with Ki-67 (MIB-1), expressed as differences between cytoplasmic and nuclear concentrations, could be considered new parameters to be evaluated in discriminating patients at a higher risk for prostate cancer.


Asunto(s)
Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias de la Próstata/metabolismo , Proteínas , Adenocarcinoma/patología , Adulto , Anciano , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Humanos , Técnicas para Inmunoenzimas , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Proteínas Nucleares/metabolismo , Fosfoproteínas/metabolismo , Pronóstico , Neoplasias de la Próstata/patología , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-mdm2 , Proteína p107 Similar a la del Retinoblastoma , Proteína p130 Similar a la del Retinoblastoma , Proteína p53 Supresora de Tumor/metabolismo , Proteínas Supresoras de Tumor/metabolismo
15.
Skull Base ; 12(3): 125-30, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-17167664

RESUMEN

The registration accuracy of skin- and bone-implanted fiducials using a frameless stereotactic system were analyzed prospectively.Twenty-eight patients underwent resection of intra-axial neoplasmas after both skin- and bone-implantable fiducial markers were placed. Both sets of fiducials were independently co-registered to a magnetic resonance imaging data set acquired preoperatively using the ISG Viewing Wandtrade mark. Root mean square errors were recorded as an objective measure of registration accuracy of the two types of fiducials.Root mean square errors of bone-implanted fiducials registration were lower than those of skin fiducials; however, this difference was not statistically significant (p = 0.206).The registration accuracy of skin- and bone-implanted fiducials appears to be similar. Still, bone-implanted fiducials may be advantageous compared to skin fiducials when re-registration of the patient-image space is desired intraoperatively such as during major drift in the patient's position or after surgical repositioning.

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