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1.
J Artif Organs ; 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38780672

RESUMEN

The shortage of organs for heart transplantation has created a need to explore the use of extended-criteria organs. We report the preliminary use of normothermic TransMedics Organ Care System-an ex vivo approach to preserve extended-criteria brain-dead donor hearts. This System maintains a normal temperature, provides continuous perfusion and oxygenation, reduces ischemic time, and enables additional viability assessment options. In a retrospective single-centre study conducted from April 2020 to March 2023, four extended criteria brain-dead donor hearts were perfused and monitored using the Organ Care System. Suitability for transplantation was assessed based on stable or decreasing lactate levels, along with appropriate perfusion parameters. The Organ Care for use of the Organ Care System were coronary artery disease, left ventricular hypertrophy, high-dose inotrope use in the donor, a downtime exceeding 20 min, and a left ventricular ejection fraction of 40-50%. Three out of the four donor hearts were transplanted, while one was discarded due to rising lactate concentration. The three recipients had a higher surgical risk profile for heart transplant. All showed normal cardiac function and no primary graft dysfunction postoperatively. At 2-3 years post-transplant, all recipients have a ventricular function of > 60%, with only one showing evidence of mild rejection. The Organ Care System enables the successful transplantation of marginal donor organs in high-risk recipients, showcasing the feasibility of recruiting donors with extended criteria. This technique is safe and promising, expanding the donor pool and addressing the organ shortage in heart transplantation in Hong Kong.

2.
Thromb J ; 19(1): 28, 2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33926467

RESUMEN

BACKGROUND: For patients taking warfarin and undergoing pacemaker or implantable cardioverter-defibrillator surgery, clinical evidence and guidelines support continuation of warfarin therapy, as opposed to interruption of warfarin therapy with heparin bridging. Interruption of warfarin without post-operative bridging therapy may be a feasible alternative but data is sparse. METHODS: This is a single-arm observational study including adults who had interruption of warfarin therapy without post-operative bridging therapy for cardiac implantable electronic device (CIED) surgery performed between 2010 and 2019 in a tertiary referral hospital. The primary outcome was a composite of all-cause mortality, arterial or venous thromboembolic events. The secondary outcomes were clinically significant device-pocket hematoma and other procedural complications. RESULTS: Of the 411 patients analysed including 257 patients (62.5%) who had mechanical heart valves, the primary outcome developed in 5 (1.2%) patients within 30 days after surgery, including death in 3 (0.7%) patients, transient ischemic attack in 1 (0.2%) patient and non-CNS embolism in 1 (0.2%) patient. Clinically significant hematomas occurred in 24 (5.8%) patients, including 15 (3.7%) requiring additional interruption of anti-coagulation and 6 (1.5%) requiring clot evacuation. Other procedural complications and bleeding events were rare (< 1%). CONCLUSIONS: Warfarin interruption without post-operative bridging therapy for CIED surgery was associated with low thromboembolic risks and acceptable bleeding risk. Randomized controlled trials are required to formulate an optimal approach to anti-coagulation management.

3.
J Natl Compr Canc Netw ; 12(1): 50-7, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24453292

RESUMEN

An association between diabetes mellitus and pancreatic ductal adenocarcinoma (PDA) has long been recognized. This article assesses the effect of the baseline hemoglobin-A1c (HbA1c) value on the clinical outcomes of patients with PDA. HbA1c values were prospectively collected on 656 consecutive patients presenting to a pancreas multidisciplinary cancer clinic from 2009 to 2012. Patients were diagnosed with benign pancreatic disease (BPD) or biopsy-confirmed resectable (R), borderline/locally advanced (BL), or metastatic (M) PDA. Excluded were those with prior treatment for PDA or a history of chronic diabetes mellitus (>1-year or unknown duration), resulting in a final cohort of 284 patients. Of 284 patients, 44 had benign disease, 62 had R-PDA, 115 had BL-PDA, and 63 had M-PDA. Patients with malignant disease (R-, BL-, and M-PDA) collectively had a higher average HbA1c value than patients with BPD (6.1% vs 5.6%; P<.001). Among patients with PDA (n=240), HbA1c values of 6.5% or greater were significantly associated with inferior overall survival (OS) compared with patients with HbA1c values less than 6.5% (hazard ratio [HR], 1.74; OS, 10.2 vs 13.0 months; P=.007), along with other known prognostic factors, such as age of 65 years or older, ECOG performance status of 1 or greater, carbohydrate antigen 19-9 level greater than 90, tumor size larger than 3 cm, and disease stage. HbA1c values of 6.5% or greater remained in the final predictive model using backward elimination (HR, 1.46; P=.097), indicating that HbA1c values of 6.5% or greater influence OS of patients with PDA even when accounting for other known prognostic factors. HbA1c level at presentation is significantly higher in patients with PDA than patients with BPD and seems to affect survival.


Asunto(s)
Adenocarcinoma/sangre , Adenocarcinoma/patología , Hemoglobina Glucada/metabolismo , Neoplasias Pancreáticas/sangre , Adenocarcinoma/terapia , Anciano , Complicaciones de la Diabetes/sangre , Diabetes Mellitus/sangre , Diabetes Mellitus/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Pronóstico , Análisis de Supervivencia
4.
J Interv Cardiol ; 26(6): 556-60, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24118226

RESUMEN

OBJECTIVES: The aim of this study was to examine the angiographic result and its outcome predictors using the combination of paclitaxel-eluting balloon (PEB) and Genous stent. BACKGROUND: This approach to treat coronary stenoses is a logical strategy to strike a balance between minimizing restenosis and stent thrombosis. METHODS: From November 2010 to June 2012, 40 symptomatic patients with 44 de novo coronary lesions of diameter stenosis ≥ 50% were treated with the combination of PEB and Genous stents. Angiographic and clinical follow-up were intended at 6 and 9 months, respectively. RESULTS: The mean age of patients was 61 ± 11 years, with male predominance (83%). Diabetes mellitus and end-stage renal failure on peritoneal dialysis were found in 15 (38%) and 10 (25%) patients, respectively. Patients received dual antiplatelet therapy for 5.1 ± 1.5 months post procedure. The size and length of PEB used was larger than the stents (3.13 ± 0.46 mm and 28 ± 9 mm vs. 2.98 ± 0.36 mm and 23 ± 7 mm). Restudy angiography was performed on 41 (95%) lesions in 37 (93%) patients at 5.9 ± 1.7 months. Angiographic restenosis was seen in 5 (12%) lesions, and significantly associated with diabetes mellitus and dialysis dependency; the late lumen loss was 0.38 ± 0.37 mm. At 9-month follow-up, no stent thrombosis was observed. CONCLUSIONS: The use of PEB combined with Genous stent is associated with a reasonably low restenosis and late lumen loss, whereas diabetes mellitus and renal failure with dialysis are poor predictors of angiographic restenosis.


Asunto(s)
Angioplastia Coronaria con Balón/métodos , Aleaciones de Cromo , Estenosis Coronaria/terapia , Paclitaxel/administración & dosificación , Stents , Angiografía Coronaria , Reestenosis Coronaria/prevención & control , Femenino , Predicción , Humanos , Masculino , Persona de Mediana Edad , Stents/efectos adversos
5.
Ann Surg Oncol ; 19(6): 1980-7, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22290566

RESUMEN

PURPOSE: The optimal dosage and frequency of platinum-based chemoradiotherapy (CRT) regimen for treating advanced head and neck squamous cell carcinoma remains unresolved. This study aims to compare the toxicity and efficacy of weekly versus more dose-intensive cisplatin-based CRTs. METHODS: We reviewed 155 stage III/IV head and neck squamous cell carcinoma patients with no evidence of distant metastasis treated with one of two CRT regimens from 2000 to 2010 at Greater Baltimore Medical Center. Twice-daily radiation was provided as a split course over a 45-day period. Regimen A consisted of concomitant cisplatin (30 mg/m2/1 h) weekly for 6 cycles; regimen B consisted of concomitant cisplatin (12 mg/m2/1 h) and 5-fluorouracil (600 mg/m2/20 h) on days 1 through 5 and days 29 through 33. Main outcome measures included acute toxicities (myelosuppression, neurotoxicity, nephrotoxicity, gastrointestinal dysfunction), unplanned hospitalizations, and disease control at 12 months. RESULTS: Patients on regimen A were much less likely to experience ototoxicity due to their treatment (0% vs. 9.8%, P = 0.04). They were more likely to experience thrombocytopenia acutely (46% vs. 26%, P = 0.02), but the toxicity was not limiting (grade 1­2). No significant differences exist in the incidence of other toxicities or unplanned hospitalizations. At 1 year, 97% of patients on A vs. 86% of patients on regimen B were free of disease (P = 0.11). CONCLUSIONS: With concurrent radiotherapy, low-dose, single-agent, weekly cisplatin is less likely than higher-dose daily cisplatin plus 5-fluorouracil provided at the beginning and end of treatment to be associated with ototoxicity. The preliminary data suggest at least equivalent efficacy, but longer follow-up is required.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma de Células Escamosas/terapia , Quimioradioterapia/efectos adversos , Neoplasias de Cabeza y Cuello/terapia , Traumatismos por Radiación/etiología , Enfermedad Aguda , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Cisplatino/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Neoplasias de Cabeza y Cuello/mortalidad , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia
6.
Interact Cardiovasc Thorac Surg ; 34(6): 1180-1182, 2022 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-34962277

RESUMEN

Patients suffering from end-stage heart failure also suffer from multiple cardiovascular comorbidities such as abdominal aortic aneurysm (AAA). Mechanical support with left ventricular assist device with open repair of AAA repair has rarely been reported in literature. The authors describe a 60-year-old male with end-stage heart failure and a symptomatic AAA with sequential left ventricular assist device insertion and open AAA repair with aortic cross-clamping.


Asunto(s)
Aneurisma de la Aorta Abdominal , Insuficiencia Cardíaca , Corazón Auxiliar , Procedimientos Quirúrgicos Torácicos , Aneurisma de la Aorta Abdominal/complicaciones , Aneurisma de la Aorta Abdominal/diagnóstico por imagen , Aneurisma de la Aorta Abdominal/cirugía , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/cirugía , Humanos , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares
8.
BMJ Open ; 10(9): e038194, 2020 09 25.
Artículo en Inglés | MEDLINE | ID: mdl-32978200

RESUMEN

INTRODUCTION: Current international guidelines recommend non-vitamin K oral anticoagulants (NOACs) for stroke prevention among patients with non-valvular atrial fibrillation (AF) at significant ischaemic stroke risk given the superior safety and comparable efficacy of NOACs over warfarin. Nonetheless, the safety and effectiveness of NOACs have not been evaluated in patients with AF with underlying moderate or severe mitral stenosis (MS), hence the recommended stroke prevention strategy remains warfarin therapy. METHOD AND ANALYSIS: MS remains disproportionately prevalent in Asian countries compared with the developed countries. This prospective, randomised, open-label trial with blinded endpoint adjudication aims to evaluate the safety and efficacy of dabigatran for stroke prevention in AF patients with moderate or severe MS. Patients with AF aged ≥18 years with moderate or severe MS not planned for valvular intervention in the coming 12 months will be randomised in a 1:1 ratio to receive dabigatran 110 mg or 150 mg two times per day or warfarin with international normalised ratio 2-3 in an open-label design. Patients with estimated creatinine clearance <30 mL/min, or with a concomitant indication for antiplatelet therapy will be excluded. The primary outcome is a composite of stroke and systemic embolism. Secondary outcomes are ischaemic stroke, systemic embolism, haemorrhagic stroke, intracranial haemorrhage, major bleeding and death. The estimated required sample size is approximately 686 participants. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Review Board of the University of Hong Kong and Hong Kong West Cluster, Hospital Authority, Hong Kong for Fung Yiu King Hospital, Grantham Hospital, Queen Mary Hospital and Tung Wah Hospital in Hong Kong. Results will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04045093); pre-results.


Asunto(s)
Fibrilación Atrial , Isquemia Encefálica , Estenosis de la Válvula Mitral , Accidente Cerebrovascular , Administración Oral , Adolescente , Adulto , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico , Dabigatrán/efectos adversos , Hong Kong , Humanos , Estenosis de la Válvula Mitral/complicaciones , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento
9.
J Clin Endocrinol Metab ; 94(1): 109-14, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18940876

RESUMEN

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) is a clinical condition that is notoriously difficult to manage; the relative risk of adverse cardiovascular events in these patients compared with euthyroid patients is largely unknown. OBJECTIVE: We compared the clinical characteristics and major adverse cardiovascular events (MACE) in AIT and euthyroid patients. METHOD: Patients at a tertiary referral center who had been prescribed amiodarone for at least 3 months were retrospectively analyzed. Baseline clinical characteristics, laboratory parameters, and outcome events were evaluated. MACE was defined as cardiovascular mortality, myocardial infarction, stroke and heart failure, or ventricular arrhythmias that required hospitalization. RESULTS: A total of 354 patients (61.8 +/- 14.1 yr; 64.7% male) with a mean follow-up of 48.6 +/- 26.7 months were studied. AIT, euthyroid status, and amiodarone-induced hypothyroidism were identified in 57 (16.1%), 224 (63.3%), and 73 (20.6%) patients, respectively. No differences in baseline clinical characteristics were observed between AIT and euthyroid patients. Nonetheless AIT patients demonstrated a higher MACE rate (31.6 vs. 10.7%, P < 0.01), mostly driven by a higher rate of ventricular arrhythmias that required admission (7.0 vs. 1.3%, P = 0.03). Cox-regression multivariate analysis revealed that AIT (hazard ratio 2.68; confidence interval 1.53-4.68; P < 0.01) and left ventricular ejection fraction less than 45% (hazard ratio 2.52; confidence interval 1.43-4.42; P < 0.01) were independent predictors of MACE. CONCLUSION: In patients prescribed long-term amiodarone therapy, occurrence of AIT is associated with a 2.7-fold increased risk of MACE. Regular and close biochemical surveillance is thus advisable to identify and treat this high-risk group of patients.


Asunto(s)
Amiodarona/efectos adversos , Antiarrítmicos/efectos adversos , Enfermedades Cardiovasculares/mortalidad , Tirotoxicosis/inducido químicamente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Función Ventricular Izquierda/efectos de los fármacos
10.
Hong Kong Med J ; 15(5): 378-80, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19801696

RESUMEN

We report a patient with isolated left ventricular non-compaction diagnosed by echocardiography and cardiac magnetic resonance imaging. She developed refractory congestive heart failure and subsequently underwent successful heart transplantation. This type of cardiomyopathy is thought to be caused by the arrest of normal embryogenesis of the endocardium and myocardium. The spectrum of clinical, radiological, and pathological abnormalities is discussed.


Asunto(s)
Cardiomiopatía Hipertrófica/terapia , Trasplante de Corazón , Disfunción Ventricular Izquierda/terapia , Adulto , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico , Ecocardiografía/métodos , Femenino , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Humanos , Imagen por Resonancia Magnética/métodos , Disfunción Ventricular Izquierda/complicaciones , Disfunción Ventricular Izquierda/diagnóstico
11.
J Thorac Dis ; 10(Suppl 16): S1899-S1904, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30026977

RESUMEN

Clinical lung transplant was first performed in Hong Kong in 1995. In the early years, the volume of activity was very low. There has been a clear trend of increasing volume in the past few years. The recipient pathology is very different from the International Society for Heart and Lung Transplantation (ISHLT) database, with complete absence of cystic fibrosis and alpha-1-antitrypsin deficiency, and a predominance of diseases of the pulmonary circulation. Lymphangioleiomyomatosis (LAM) has a much higher representation on the waiting list than the ISHLT. The survival of patients who received a lung transplant in Hong Kong compares favorably with international data.

12.
ERJ Open Res ; 4(1)2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29531959

RESUMEN

Current guideline-recommended screening for pulmonary hypertension in patients with systemic sclerosis has not been evaluated in systemic lupus erythematosus (SLE), which is disproportionately prevalent in Asians. This multicentre, cross-sectional screening study aims to study the prevalence of pulmonary hypertension among SLE patients using these guidelines, and identify independent predictors and develop a prediction model for pulmonary hypertension in SLE patients. SLE patients from participating centres will undergo an echocardiography- and biomarker-based pulmonary hypertension screening procedure as in the DETECT study. Standard right heart catheterisation will be provided to patients with intermediate or high echocardiographic probability of pulmonary hypertension. Those with low echocardiographic probability will rescreen within 1 year. The primary measure will be the diagnosis and types of pulmonary hypertension and prevalence of pulmonary hypertension in SLE patients. The secondary measures will be the predictors and prediction models for pulmonary hypertension in SLE patients. The estimated sample size is approximately 895 participants. The results of the SOPHIE study will be an important contribution to the literature of SLE-related pulmonary hypertension and may be immediately translatable to real clinical practice. Ultimately, this study will provide the necessary evidence for establishing universal guidelines for screening of pulmonary hypertension in SLE patients.

13.
Am J Cardiol ; 97(3): 409-11, 2006 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-16442406

RESUMEN

Patients on warfarin for mechanical heart valves are at increased risk for thromboembolic events and intracranial hemmorhage. In current guidelines, a low dose of vitamin K is the recommended treatment for moderate over-anticoagulation based on studies in which only minority patients participating had mechanical heart valves. We performed a randomized controlled trial to compare the efficacy and safety profile of low-dose intravenous vitamin K and fresh frozen plasma (FFP) for patients with mechanical heart valves and mild to moderate over-anticoagulation (international normalized ratio [INR] 4 to 7). In a 24-month period, we randomized 102 patients to (1) vitamin K or (2) FFP. The baseline INR at presentation between the vitamin K group and the FFP group was 4.61 +/- 0.007 vs 4.78 +/- 0.07 (p = 0.11). Six hours after treatment, patients in the FFP group had a significantly lower mean INR compared with the vitamin K group (2.75 +/- 0.06 vs 3.44 +/- 0.10, p = 0.01). No patient in both groups had over-correction (INR < 2). One week later, there was no significant difference in mean INR between both groups (2.7 +/- 0.11 vs 2.56 +/- 0.12, p = 0.41). Fifty-eight percent of patients in the FFP group and 51% in the vitamin K group had an INR within the target range. There were no adverse reactions or outcomes in both groups. In conclusion, intravenous low-dose vitamin K is a safe alternative to FFP infusion for warfarin overdose in patients with mechanical heart valves.


Asunto(s)
Anticoagulantes/efectos adversos , Trastornos de la Coagulación Sanguínea/inducido químicamente , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Coagulantes/administración & dosificación , Prótesis Valvulares Cardíacas , Plasma , Vitamina K/administración & dosificación , Warfarina/efectos adversos , Transfusión de Componentes Sanguíneos , Femenino , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Infusiones Intravenosas , Relación Normalizada Internacional , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
15.
Am J Cardiol ; 117(4): 640-646, 2016 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-26718231

RESUMEN

The aim of the study was to evaluate the relation between tricuspid regurgitation (TR) severity and liver stiffness (LS) in patients with TR. A total of 131 patients with various degrees of TR secondary to left-sided heart valve disease were enrolled. Severity of TR was quantitatively assessed by proximal isovelocity surface area-derived effective regurgitant orifice (ERO). Patients were divided into 2 groups: 48 with mild-moderate TR (ERO <0.4 cm(2)) and 83 with severe TR (ERO ≥0.4 cm(2)). Transient elastography was used to measure the level of LS, an established marker of liver fibrosis, with the threshold of significant LS set at ≥12.5 kPa. Patients with severe TR had a higher LS and prevalence of significant LS than those with mild-moderate TR. Furthermore, LS and significant LS independently correlated with TR-ERO, right atrial pressure and inferior vena cava (IVC) diameter. The presence of a large TR-ERO (≥0.4 cm(2)) and IVC diameter (>2.15 cm(2)) provided a high specificity of 78% for significant LS. In conclusion, the present study demonstrates that TR-ERO, right atrial pressure, and IVC diameter are important parameters associated with LS in patients with TR.


Asunto(s)
Diagnóstico por Imagen de Elasticidad/métodos , Hígado/diagnóstico por imagen , Insuficiencia de la Válvula Tricúspide/diagnóstico por imagen , Válvula Tricúspide/diagnóstico por imagen , Disfunción Ventricular Izquierda/diagnóstico por imagen , Anciano , Ecocardiografía Doppler en Color , Ecocardiografía Tridimensional , Elasticidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Insuficiencia de la Válvula Tricúspide/complicaciones , Disfunción Ventricular Izquierda/complicaciones
16.
Biochem Biophys Rep ; 5: 335-345, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28955840

RESUMEN

Patients with Danon disease may suffer from severe cardiomyopathy, skeletal muscle dysfunction as well as varying degrees of mental retardation, in which the primary deficiency of lysosomal membrane-associated protein-2 (LAMP2) is considerably associated. Owing to the scarcity of human neurons, the pathological role of LAMP2 deficiency in neural injury of humans remains largely elusive. However, the application of induced pluripotent stem cells (iPSCs) may shed light on overcoming such scarcity. In this study, we obtained iPSCs derived from a patient carrying a mutated LAMP2 gene that is associated with Danon disease. By differentiating such LAMP2-deficient iPSCs into cerebral cortical neurons and with the aid of various biochemical assays, we demonstrated that the LAMP2-deficient neurons are more susceptible to mild oxidative stress-induced injury. The data from MTT assay and apoptotic analysis demonstrated that there was no notable difference in cellular viability between the normal and LAMP2-deficient neurons under non-stressed condition. When exposed to mild oxidative stress (10 µM H2O2), the LAMP2-deficient neurons exhibited a significant increase in apoptosis. Surprisingly, we did not observe any aberrant accumulation of autophagic materials in the LAMP2-deficient neurons under such stress condition. Our results from cellular fractionation and inhibitor blockade experiments further revealed that oxidative stress-induced apoptosis in the LAMP2-deficient cortical neurons was caused by increased abundance of cytosolic cathepsin L. These results suggest the involvement of lysosomal membrane permeabilization in the LAMP2 deficiency associated neural injury.

17.
Contemp Clin Trials ; 50: 143-9, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27520932

RESUMEN

OBJECTIVE: Yttrium-90 (Y-90) radioembolization is an emerging treatment option for unresectable neuroendocrine liver metastases (NELM). However, the data regarding this treatment are currently limited. This study evaluates the efficacy and tolerability of Y-90 radioembolization and identifies prognostic factors for radiographic response and survival. METHODS AND MATERIALS: Thirty-eight patients underwent Y-90 radioembolization for NELM at our institution between April 2004 and February 2012. Patients were assessed radiographically (RECIST criteria, enhancement), serologically, and clinically at 1month, and then at every 3months after treatment for tumor response, toxicity, and survival outcomes. RESULTS: Median length of follow-up was 17.0months (IQR, 9.0-37.0). Median survival was 29.2months. Three patients (9%) had a radiographic complete response to treatment, 6 (17%) had a partial response, 21 (60%) had stable disease, and 5 (14%) developed progressive disease. Two factors were significantly associated with a good radiographic response (complete/partial response): islet cell histological subtype (p=0.043) and hepatic tumor burden ≥33% (p=0.031). Multivariate analysis revealed that patients requiring multiple Y-90 treatments (HR 2.9, p=0.035) and patients who had previously failed systemic therapy with octreotide/chemotherapy (HR 4.4, p=0.012) had worse survival. Grade 3 serologic toxicity was observed in 2 patients (5%; hyperbilirubinemia, elevated alkaline phosphatase) after treatment. Grade 3 non-serologic toxicities included abdominal pain (11%), fatigue (11%), nausea/vomiting (5%), ascites (5%), dyspnea (3%), diarrhea (3%), and peripheral edema (3%). No grade 4 or 5 toxicity was reported. CONCLUSIONS: Y-90 radioembolization is a promising treatment option for inoperable NELM and is associated with low rates of grade≥3 toxicity.


Asunto(s)
Embolización Terapéutica/métodos , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/terapia , Tumores Neuroendocrinos/patología , Radioisótopos de Itrio/uso terapéutico , Factores de Edad , Anciano , Anciano de 80 o más Años , Embolización Terapéutica/efectos adversos , Femenino , Humanos , Masculino , Microesferas , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Proteínas de Xenopus , Radioisótopos de Itrio/administración & dosificación , Radioisótopos de Itrio/efectos adversos , Proteína Gli3 con Dedos de Zinc
18.
Circulation ; 105(23): 2746-52, 2002 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-12057989

RESUMEN

BACKGROUND: Mechanoelectrical feedback caused by atrial dilatation plays an important role in atrial fibrillation (AF). To test the hypothesis that remodeling is reversible by reducing atrial stretch, we investigated electrophysiological changes after a reduction of left atrial (LA) pressure in patients undergoing percutaneous balloon mitral commissurotomy (PBMC). METHODS AND RESULTS: In 22 patients with chronic AF who were undergoing PBMC for mitral stenosis, internal cardioversion was successful in 19 patients (86%). Twelve patients with sinus rhythm acted as controls. Mean LA pressure was significantly reduced after PBMC (18.5+/-5.9 mm Hg versus 10.2+/-4.1 mm Hg; P<0.001). The effective refractory period (ERP), conduction delay (CD), and the index of heterogeneity (CoV) of the ERP and CD were compared. Changes in LA pressure were only significantly correlated with AF vulnerability (r=0.7; P=0.02) and CoV of CD (r=0.3; P=0.03). There were no significant changes in ERP and CD immediately after PBMC in the AF group. However, the overall CoV of ERP was reduced in the AF group after PBMC. There were homogenous, although not significant, increases in regional ERP in the control group immediately after PBMC. Atrial CD and CoV of CD were significantly reduced after PBMC in the control group; this was most prominent within the regions of the LA. CONCLUSIONS: AF vulnerability and CoV of CD correlated significantly with LA pressure. A homogenous increase in regional ERPs could be demonstrated in the control group after an immediate reduction of atrial stretch, whereas the recovery course of electrical remodeling was prolonged and heterogenous in the AF group. Regional conductions were irreversible in patients with preexisting AF.


Asunto(s)
Angioplastia Coronaria con Balón , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/cirugía , Estenosis de la Válvula Mitral/cirugía , Fibrilación Atrial/etiología , Fibrilación Atrial/patología , Función Atrial , Fenómenos Biomecánicos , Enfermedad Crónica , Dilatación Patológica , Electrocardiografía , Técnicas Electrofisiológicas Cardíacas , Retroalimentación , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Humanos , Cinética , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
19.
Circulation ; 105(4): 438-45, 2002 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-11815425

RESUMEN

BACKGROUND: Biventricular pacing has been proposed to improve symptoms and exercise capacity in patients with advanced heart failure and wide electrocardiographic wave complexes. This study investigated the effect of biventricular pacing on reverse remodeling and the underlying mechanisms. METHODS AND RESULTS: Twenty-five patients with NYHA class III to IV heart failure and electrocardiographic wave complex duration >140 ms receiving biventricular pacing therapy were assessed serially up to 3 months after pacing and when pacing was withheld for 4 weeks. Tissue Doppler echocardiography was performed using a 6-basal, 6-mid segmental model to assess the time to peak sustained systolic contraction (T(S)). There was significant improvement of ejection fraction, dP/dt, and myocardial performance index; decrease in mitral regurgitation, left ventricular (LV) end-diastolic (205+/-68 versus 168+/-67 mL, P<0.01) and end-systolic volume (162+/-54 versus 122+/-42 mL, P<0.01); and improved 6-minute hall-walk distance and quality of life score after pacing for 3 months. The mechanisms of benefits were as follows: (1) improved LV synchrony, as evident by homogeneous delay of T(S) to a timing close to the latest (usually the lateral) segment abolishing the intersegmental difference in T(S) and decreasing the standard deviation of T(S) within the left ventricle (37.7+/-10.9 versus 29.3+/-8.3 ms, P<0.05); (2) improved interventricular synchrony; and (3) shortened isovolumic contraction time (122+/-57 versus 82+/-36 ms, P<0.05) but increased diastolic filling time. These benefits are pacing dependent, because withholding the pacing resulted in varying speeds in the loss of cardiac improvements. CONCLUSIONS: Biventricular pacing reverses LV remodeling and improves cardiac function. Improvement of LV mechanical synchrony seems to be the predominant mechanism.


Asunto(s)
Estimulación Cardíaca Artificial/métodos , Ecocardiografía Doppler/métodos , Insuficiencia Cardíaca/diagnóstico por imagen , Insuficiencia Cardíaca/terapia , Ventrículos Cardíacos , Remodelación Ventricular , Anciano , Femenino , Insuficiencia Cardíaca/fisiopatología , Ventrículos Cardíacos/fisiopatología , Hemodinámica , Humanos , Cinética , Masculino , Modelos Cardiovasculares , Contracción Miocárdica , Periodicidad , Disfunción Ventricular/diagnóstico por imagen , Disfunción Ventricular/fisiopatología , Disfunción Ventricular/terapia , Disfunción Ventricular Izquierda/diagnóstico por imagen , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/terapia
20.
J Oncol Pract ; 11(2): e216-21, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25563703

RESUMEN

INTRODUCTION: The objectives of this study were to evaluate quality of life (QoL) in patients presenting to the Johns Hopkins Pancreas Multidisciplinary Clinic (PMDC), and to examine associations between disease status, performance status, and QoL in order to identify patient subgroups that are most at risk for reduced QoL. PATIENTS AND METHODS: Data from 77 patients were evaluated. At initial presentation, disease and performance status were assessed, as well as QoL, which was obtained with the European Organisation for Research and Treatment of Cancer QLQ-PAN26 questionnaire. Statistical analyses examined associations between QoL, disease status, and performance status. RESULTS: Digestive symptoms (P < .003) significantly differed by pancreatic disease status (resectable, resected, locally advanced, and metastatic). Patients with a worse performance status, defined as Eastern Cooperative Oncology Group ≥ 1, were more likely to report symptomatic pancreatic pain (P = .001), digestive symptoms (P = .017), cachexia (P = .004), and ascites (P < .001) compared with patients with a performance status of 0. The majority (92%) of patients reported a significant fear of future health problems, regardless of disease status or performance status. CONCLUSION: Although several measures of QoL have been observed in all patients, certain measures appear to correlate specifically with worse disease status. Therefore, routine assessment of QoL is suggested in order to guide treatment decisions. Further investigation on optimizing the use of QoL measures and patient-reported outcomes to better tailor management is warranted.


Asunto(s)
Neoplasias Pancreáticas/patología , Calidad de Vida , Índice de Severidad de la Enfermedad , Anciano , Instituciones Oncológicas , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/epidemiología , Autoinforme
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