RESUMO
AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. METHODS: Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. RESULTS: The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. CONCLUSION: The present GL is directed to all physicians addressing people with obesity-working in hospitals, territorial services or private practice-and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.
Assuntos
Obesidade , Sobrepeso , Humanos , Obesidade/terapia , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/terapia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Adulto , Itália/epidemiologia , Comorbidade , Terapia Comportamental/métodos , Terapia Comportamental/normas , Guias de Prática Clínica como Assunto/normas , Gerenciamento Clínico , Cirurgia Bariátrica/métodosRESUMO
This guideline (GL) is aimed at providing a clinical practice reference for the management of adult patients with overweight or obesity associated with metabolic complications who are resistant to lifestyle modification. Surgeons, endocrinologists, gastroenterologists, psychologists, pharmacologists, a general practitioner, a nutritionist, a nurse and a patients' representative acted as multi-disciplinary panel. This GL has been developed following the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A systematic review and network meta-analysis was performed by a methodologic group. For each question, the panel identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for clinical practice recommendations. Consensus on the direction (for or against) and strength (strong or conditional) of recommendations was reached through a majority vote. The present GL provides recommendations about the role of both pharmacological and surgical treatment for the clinical management of the adult patient population with BMI > 27 kg/m2 and < 40 kg/m2 associated with weight-related metabolic comorbidities, resistant to lifestyle changes. The panel: suggests the timely implementation of therapeutic interventions in addition to diet and physical activity; recommends the use of semaglutide 2.4 mg/week and suggests liraglutide 3 mg/day in patients with obesity or overweight also affected by diabetes or pre-diabetes; recommends semaglutide 2.4 mg/week in patients with obesity or overweight also affected by non-alcoholic fatty liver disease; recommends semaglutide 2.4 mg/week as first-line drug in patients with obesity or overweight that require a larger weight loss to reduce comorbidities; suggests the use of orlistat in patients with obesity or overweight also affected by hypertriglyceridemia that assume high-calorie and high-fat diet; suggests the use of naltrexone/bupropion combination in patients with obesity or overweight, with emotional eating; recommends surgical intervention (sleeve gastrectomy, Roux-en-Y gastric bypass, or metabolic gastric bypass/gastric bypass with single anastomosis/gastric mini bypass in patients with BMI ≥ 35 kg/m2 who are suitable for metabolic surgery; and suggests gastric banding as a possible, though less effective, surgical alternative. The present GL is directed to all physicians addressing people with obesityworking in hospitals, territorial services or private practiceand to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.
Assuntos
Humanos , Adulto , Sobrepeso/complicações , Cirurgia Bariátrica , Obesidade/complicações , Fármacos Antiobesidade/uso terapêutico , Obesidade/tratamento farmacológicoRESUMO
Extracellular matrix (ECM) scaffolds isolated from valvulated conduits can be useful in developing durable bioprostheses by tissue engineering provided that anatomical shape, architecture, and mechanical properties are preserved. As evidenced by SEM, intact scaffolds were derived from porcine aortic valves by the combined use of Triton X-100 and cholate (TRI-COL) or N-cetylpyridinium (CPC) and subsequent nucleic acid removal by nuclease. Both treatments were effective in removing most cells and all the cytomembranes, with preservation of (1) endothelium basal membranes, (2) ECM texture, including the D-periodical interaction of small proteoglycans with normally D-banded collagen fibrils, and (3) mechanical properties of the treated valves. Ultrastructural features agreed with DNA, hexosamine, and uronic acid biochemical estimations. Calcification potential, assessed by a 6-week rat subdermal model, was significantly reduced by TRI-COL/nuclease treatment. This was not true for CPC only, despite better proteoglycan preservation, suggesting that nucleic acids also are involved in calcification onset. Human fibroblasts, used to repopulate TRI-COL samples, formed mono- or multilayers on surfaces, and groups of cells also were scattered within the valve leaflet framework. A biocompatible scaffolds of this kind holds promise for production of durable valve bioprostheses that will be able to undergo probable turnover and/or remodeling by repopulating recipient cells.
Assuntos
Valva Aórtica/metabolismo , Bioprótese , Calcificação Fisiológica/fisiologia , Matriz Extracelular/metabolismo , Próteses Valvulares Cardíacas , Animais , Valva Aórtica/ultraestrutura , Técnicas de Cultura , Fibroblastos/metabolismo , Fibroblastos/ultraestrutura , Humanos , Masculino , Teste de Materiais , Ácidos Nucleicos/metabolismo , Ratos , Ratos Sprague-Dawley , Estresse Mecânico , Suínos , Engenharia Tecidual , Transplante de TecidosAssuntos
Neoplasias Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Ecocardiografia , Ecocardiografia Transesofagiana , Feminino , Seguimentos , Neoplasias Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/diagnóstico por imagem , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , PrevalênciaRESUMO
OBJECTIVES: Surgical repair of complete A-V canal defects (CAVCD) is a well established procedure which is currently performed in infancy. The aim of this study is to evaluate surgical results of correction in early infancy in comparison to older age. METHODS: From January 1985 to March 2001, 119 consecutive patients (age range 27 days to 83 months, mean 6.7 months) underwent repair of CAVCD in our Institution. Forms with unbalanced ventricles in association with Fallot's tetralogy or heterotaxia were excluded from this series. Fifty-eight patients (49%) underwent correction before 3 months of age (Group A), and 61 patients (51%) after 3 months (Group B). Surgical repair was accomplished with a double patch technique in 100 patients (84%). Associated surgical lesions were treated simultaneously in 48 patients (40%). RESULTS: There were 11 operative deaths (<30 days) (two in Group A (3.4%) and nine in Group B (15%)) (P = 0.05). The remaining patients were discharged home in good haemodynamic condition. Reoperation for postoperative left A-V incompetence occurred in five patients in Group A and in eight patients in Group B. There were eight late deaths (three in Group A and five in Group B), of which four were non-cardiac related. At a mean follow-up time of 80 months (range 2-184 months) 100 patients are asymptomatic and well, and free from oral medication. Echocardiographic examination showed absent or mild residual left A-V valve incompetence in 91 patients (49 in Group A and 42 in Group B) and moderate left A-V valve incompetence in nine patients (four in Group A and five in Group B). Kaplan-Meier survival estimates at 10 years were 90% for Group A and 75% for Group B. Kaplan-Meier freedom from reoperation at 10 years was 89% for Group A and 84% for Group B. CONCLUSIONS: Our data demonstrate that repair of CAVCD under 3 months of age is the ideal approach to this malformation with a lower mortality rate at operation compared to older patients. Logistic analysis showed that an operative age >3 months is, compared to an age < or =3 months, an incremental risk factor for hospital mortality with an odds ratio of 4.8 (95% confidence limit 1-23.5) (P = 0.05). In the long term, freedom from reoperation for left A-V valve incompetence is higher when compared to children repaired at an older age.
Assuntos
Defeitos dos Septos Cardíacos/cirurgia , Fatores Etários , Criança , Pré-Escolar , Feminino , Seguimentos , Defeitos dos Septos Cardíacos/mortalidade , Humanos , Lactente , Modelos Logísticos , Masculino , Reoperação , Risco , Resultado do TratamentoRESUMO
OBJECTIVE: One and one half ventricle repair is a surgical option for congenital cardiac anomalies characterised by right ventricle (RV) hypoplasia and/or dysplasia. METHODS: From March 1994 to March 2001, eight patients (mean age 9.1 years, range 7 months to 35 years) with hypoplastic and/or dysplastic RV underwent correction of their intracardiac anomaly in association with a BCPS (one and one half ventricle repair). Preoperative diagnoses included: Ebstein's anomaly of tricuspid valve (TV) in two, inlet ventricular septal defect (VSD) in association with straddling/overriding TV in two patients, pulmonary atresia-intact ventricular septum in one, tertralogy of Fallot in association with complete atrioventricular canal defect in one, truncus arteriosus in one and heterotaxy syndrome with VSD and anomalous systemic venous return in one. Four patients underwent previous surgery which included: main pulmonary artery (MPA) banding in two patients, pulmonary valvotomy, central shunt and right ventricular outflow tract reconstruction in one, pulmonary artery separation from truncus arteriosus and modified Blalock-Taussig shunt in one, and MPA closure in one. Two patients underwent a bidirectional cavo-pulmonary shunt before the one and a one half ventricle repair. Associated cardiac lesions were treated simultaneously. RESULTS: There were no hospital deaths. All the patients were discharged home in good clinical conditions. There were no late deaths or reoperations. At mean follow-up of 29.8 months (range 8 months to 7.3 years) all the patients are alive and in good general conditions. MPA percutaneous balloon dilation was performed in two patients at 33 and 4 months, respectively, both after MPA reconstruction (which was previously ligated) and dilation of the left pulmonary artery branch in one patient, repeated twice at 10 and 14 months from repair, for a hypoplastic left pulmonary artery after truncus arteriosus repair. CONCLUSIONS: Surgical treatment of congenital cardiac anomalies in the presence of a hypoplastic and or a dysplastic RV by means of one and one half ventricle repair has the advantage of reducing the surgical risk for biventricular repair, and compared to the Fontan circulation, it maintains a low right atrium pressure, a pulsatile pulmonary blood flow and improves the systemic oxygen saturation. Short and medium-term results are promising. Longer follow-up is needed, to prove the efficacy of such a repair, in the long term.
Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cardiopatias Congênitas/cirurgia , Ventrículos do Coração/anormalidades , Ventrículos do Coração/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Seguimentos , Derivação Cardíaca Direita , Humanos , Lactente , Masculino , Complicações Pós-OperatóriasRESUMO
OBJECTIVE: One and one half ventricle repair is a surgical option for congenital cardiac anomalies characterised by right ventricle (RV) hypoplasia and/or dysplasia. METHODS: From March 1994 to March 2001, eight patients (mean age 9.1 years, range 7 months to 35 years) with hypoplastic and/or dysplastic RV underwent correction of their intracardiac anomaly in association with a BCPS (one and one half ventricle repair). Preoperative diagnoses included: Ebstein's anomaly of tricuspid valve (TV) in two, inlet ventricular septal defect (VSD) in association with straddling/overriding TV in two patients, pulmonary atresia-intact ventricular septum in one, tertralogy of Fallot in association with complete atrioventricular canal defect in one, truncus arteriosus in one and heterotaxy syndrome with VSD and anomalous systemic venous return in one. Four patients underwent previous surgery which included: main pulmonary artery (MPA) banding in two patients, pulmonary valvotomy, central shunt and right ventricular outflow tract reconstruction in one, pulmonary artery separation from truncus arteriosus and modified Blalock-Taussig shunt in one, and MPA closure in one. Two patients underwent a bidirectional cavo-pulmonary shunt before the one and a one half ventricle repair. Associated cardiac lesions were treated simultaneously. RESULTS: There were no hospital deaths. All the patients were discharged home in good clinical conditions. There were no late deaths or reoperations. At mean follow-up of 29.8 months (range 8 months to 7.3 years) all the patients are alive and in good general conditions. MPA percutaneous balloon dilation was performed in two patients at 33 and 4 months, respectively, both after MPA reconstruction (which was previously ligated) and dilation of the left pulmonary artery branch in one patient, repeated twice at 10 and 14 months from repair, for a hypoplastic left pulmonary artery after truncus arteriosus repair. CONCLUSIONS: Surgical treatment of congenital cardiac anomalies in the presence of a hypoplastic and or a dysplastic RV by means of one and one half ventricle repair has the advantage of reducing the surgical risk for biventricular repair, and compared to the Fontan circulation, it maintains a low right atrium pressure, a pulsatile pulmonary blood flow and improves the systemic oxygen saturation. Short and medium-term results are promising. Longer follow-up is needed, to prove the efficacy of such a repair, in the long term.
Assuntos
Cardiopatias Congênitas/cirurgia , Adolescente , Adulto , Procedimentos Cirúrgicos Cardíacos/métodos , Criança , Pré-Escolar , Feminino , Derivação Cardíaca Direita , Ventrículos do Coração/anormalidades , Ventrículos do Coração/cirurgia , Humanos , Lactente , Masculino , Complicações Pós-OperatóriasRESUMO
BACKGROUND AND AIMS: The longevity of the mechanical heart valve prosthesis is an advantage when compared with its biological counterpart, although the former carries a risk of thrombosis depending on valve design, materials and host-related interface; therefore, a patient with a mechanical valve prosthesis, particularly in mitral position, is at risk for systemic thromboembolism even when properly anticoagulated. PATIENTS AND METHODS: We report a case of a 60-year-old woman who underwent a mitral valve replacement with a St. Jude Medical (SJM) standard bileaflet mechanical heart valve. RESULTS: On the twelfth post-operative day a primary thrombosis with blockage of the anterior valve leaflet occurred. CONCLUSIONS: Aware of the risk of recurrent thromboembolism in this special clinical framework and possible cerebral bleeding in case of thrombolysis, we replaced the prosthesis with a new biologic porcine valve, the SJM Biocor.
Assuntos
Implante de Prótese de Valva Cardíaca/efeitos adversos , Estenose da Valva Mitral/cirurgia , Seleção de Pacientes , Reoperação , Terapia Trombolítica , Trombose/etiologia , Trombose/terapia , Doença Aguda , Bioprótese , Ecocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Estenose da Valva Mitral/etiologia , Recidiva , Cardiopatia Reumática/complicações , Fatores de Risco , Trombose/diagnósticoAssuntos
Transplante de Coração/tendências , Transplante de Células , Rejeição de Enxerto/prevenção & controle , Humanos , Terapia de Imunossupressão/métodos , Infecções Oportunistas/prevenção & controle , Seleção de Pacientes , Complicações Pós-Operatórias/prevenção & controle , Doadores de Tecidos , Obtenção de Tecidos e ÓrgãosAssuntos
Transplante de Coração/estatística & dados numéricos , Imunossupressores/uso terapêutico , Neoplasias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Azatioprina/uso terapêutico , Biópsia , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Feminino , Seguimentos , Transplante de Coração/mortalidade , Humanos , Masculino , Miocárdio/patologia , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Fatores de TempoRESUMO
OBJECTIVE: Hemodynamic and clinical performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus aortic valves (St Jude Medical, Inc, St Paul, Minn) were compared with those of 21-mm and 23-mm St Jude Medical standard cuff aortic valves in the first such multicenter, prospective, randomized study. Hemodynamic Plus valves are mechanical, bileaflet prostheses suitable for the small aortic anulus. METHODS: Patients with 21-mm and 23-mm anulus diameters were randomized to receive either a Hemodynamic Plus or a standard cuff valve. Postoperatively and at 6 months after the operation, patients underwent 2-dimensional Doppler echocardiography. Ejection fraction, cardiac output, peak gradient, mean gradient, effective orifice area, effective area index, and performance index were calculated. Postoperative and 6-month echocardiographic measurements and their variations across observation times were analyzed statistically. RESULTS: Of the 140 patients enrolled, 5 died at operation and 1 died of aortic dissection during the follow-up period. Eight patients were lost to follow-up. A total of 125 patients completed the study. In 1 patient a sewing cuff escaped intraoperatively. At 6 months the 21-mm and 23-mm Hemodynamic Plus valves showed significantly lower peak gradients and mean gradients than those of the 21-mm and 23-mm standard cuff valves. The 21-mm Hemodynamic Plus valves had gradients similar to those of the 23-mm Hemodynamic Plus valves. The effective orifice area did not differ significantly between the Hemodynamic Plus and standard cuff valves at either measurement. No valve mismatch was found in the 4 groups of patients. A more enhanced decrease of peak gradients and mean gradients and a more enhanced increase of effective orifice areas, effective area indices, and performance indices were found across observation times for patients with Hemodynamic Plus valves compared with those with standard cuff valves. CONCLUSIONS: Clinical hemodynamic performances of 21-mm and 23-mm St Jude Medical Hemodynamic Plus valves correspond closely with those of standard cuff valves, and gradients are substantially better than those of standard cuff valves of the same diameter. Therefore, use of this valve may minimize the need for aortic anulus enlargement. Early follow-up results with the Hemodynamic Plus valves were excellent, although more time is required to confirm this outcome.
Assuntos
Valva Aórtica , Próteses Valvulares Cardíacas , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Feminino , Seguimentos , Hemodinâmica , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Desenho de Prótese , UltrassonografiaRESUMO
BACKGROUND: Structural and phenotypic changes of cardiomyocytes characterize atrial fibrillation. We investigated whether changes in the glucose-regulated protein GRP94, which is essential for cell viability, occur in the presence of chronic atrial fibrillation. METHODS AND RESULTS: Samples of fibrillating atrial myocardium obtained from both goat and human hearts were analyzed for GRP94 expression by an immunologic approach. In goats, atrial fibrillation was induced and maintained for 2, 4, 8, and 16 weeks. After 16 weeks of atrial fibrillation, cardioversion was applied and followed by 8 weeks of sinus rhythm. GRP94 levels doubled in goat atrial myocytes after 4 to 16 weeks of fibrillation with respect to normal atria and returned to control levels in atrial myocardium of cardioverted goats. Immunohistochemical analyses confirm that GRP94 increase occurred within cardiomyocytes. Significantly, increased levels of GRP94 were also observed in samples from human fibrillating atria. In the absence of signs of myocyte irreversible damage, the GRP94 increase in fibrillating atria is comparable to GRP94 levels observed in perinatal goat myocardium. However, calreticulin, another endoplasmic reticulum protein highly expressed in perinatal hearts, does not increase in fibrillating atria, whereas inducible HSP70, a cytoplasm stress protein that is expressed in perinatal goat hearts at levels comparable to those observed in the adult heart, shows a significant increase in chronic fibrillating atria. CONCLUSIONS: Our data demonstrate a large, reversible increase in GRP94 in fibrillating atrial myocytes, which may be related to the appearance of a protective phenotype.
Assuntos
Fibrilação Atrial/metabolismo , Regulação da Expressão Gênica , Proteínas de Choque Térmico HSP70/biossíntese , Proteínas de Membrana/biossíntese , Proteínas Musculares/biossíntese , Miocárdio/metabolismo , Adaptação Fisiológica , Adulto , Animais , Animais Recém-Nascidos , Fibrilação Atrial/genética , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Cálcio/metabolismo , Diferenciação Celular , Doença Crônica , Cardioversão Elétrica , Retículo Endoplasmático/metabolismo , Feminino , Cabras , Proteínas de Choque Térmico HSP70/genética , Coração/fisiopatologia , Humanos , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Mitocôndrias Cardíacas/metabolismo , Proteínas Musculares/genética , Fenótipo , Retículo Sarcoplasmático/metabolismoRESUMO
Myocardial involvement by metastatic lymphoma progressively leads to severe contractile impairment and fatal outcome. Correct diagnosis is often late due to misleading presentation signs. We report on a case of extensive cardiac involvement of a T-cell thymic lymphoma in a young woman, necessitating emergent extracorporeal membrane oxygenation (ECMO) circulatory support, with satisfactory hemodynamic recovery and subsequent ECMO weaning. Unfortunately, the following clinical course was rapidly fatal. This case seems to confirm that early aggressive instrumental diagnosis is crucial before severe myocardial impairment can prevent any therapeutic option. Extensive use of transesophageal echocardiographic examination and early endomyocardial biopsy are highly recommended.
Assuntos
Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/secundário , Linfoma de Células T/diagnóstico , Choque Cardiogênico/etiologia , Neoplasias do Timo/diagnóstico , Adulto , Ecocardiografia Transesofagiana , Oxigenação por Membrana Extracorpórea/métodos , Evolução Fatal , Feminino , Neoplasias Cardíacas/terapia , Humanos , Linfoma de Células T/complicações , Linfoma de Células T/terapia , Índice de Gravidade de Doença , Neoplasias do Timo/terapiaAssuntos
Transplante de Coração , Paraproteinemias/epidemiologia , Fatores Etários , Análise de Variância , Ciclosporina/administração & dosagem , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Humanos , Imunossupressores/administração & dosagem , Incidência , Masculino , Pessoa de Meia-Idade , Paraproteinemias/imunologia , Estudos Retrospectivos , Fatores de Risco , Fatores de TempoAssuntos
Cardiomiopatias/cirurgia , Transplante de Coração , Miopatias Mitocondriais/complicações , Distrofias Musculares/complicações , Adulto , Cardiomiopatias/complicações , Cardiomiopatias/metabolismo , Desmina/metabolismo , Distrofina/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Miopatias Mitocondriais/metabolismo , Distrofias Musculares/metabolismoAssuntos
Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/epidemiologia , Rejeição de Enxerto/imunologia , Neoplasias Cutâneas/epidemiologia , Análise de Variância , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Hospedeiro Imunocomprometido , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: Management of cyclosporine (CsA)-associated hyperuricemia in heart transplantation (HT) is difficult. Because of the myelotoxicity of combined allopurinol and azathioprine, we tested sulfinpyrazone. METHODS: We studied 120 HT recipients (109 men; mean age at HT, 52+/-10 years). All had received allopurinol for at least 6 months, which was stopped for 1 month before initiation of sulfinpyrazone. Mean follow-up from HT to onset of sulfinpyrazone (200 mg/day) was 59+/-41 months. We stopped the drug after 6+/-2 months. We compared CsA level and daily dose, serum creatinine, blood urea, and uric acid at onset and before interruption of sulfinpyrazone and, as control, in the last 6 months of allopurinol. RESULTS: Mean uricemia decreased with allopurinol (0.58+/-0.12 vs. 0.41+/-0.07 mmol/liter, p = 0.0001) as well as with sulfinpyrazone (0.51+/-0.13 vs. 0.40+/-0.12 mmol/liter, p = 0.0001). Mean creatinine increased (171+/-42 and 164+/-35 micromol/liter, p = 0.01) with allopurinol, whereas it tended to decrease with sulfinpyrazone (160+/-35 and 154+/-48 micromol/liter, p = NS). Mean urea did not change with allopurinol (14+/-5 vs. 15+/-7 mmol/liter, p = NS), but fell with sulfinpyrazone (14.01+/-5 vs. 12.60 +/-5 mmol/liter, p = 0.0004). Mean CsA levels were constant with allopurinol (193+/-73 vs. 188+/-65 ng/ml, p = NS), although CsA dose was slightly reduced (2.7+/-0.8 vs. 2.6+/-0.8 mg/kg/day, p = 0.007). Conversely, CsA levels dropped with sulfinpyrazone (183+/-89 vs. 121 +/-63 ng/ml, p = 0.0001) despite an increase in CsA daily dose (2.6 +/-0.9 vs. 2.8+/-0.9 mg/kg/day, p = 0.0001). Two subjects were treated for acute rejection. We observed no other side effects. In HT recipients sulfinpyrazone, as an alternative to allopurinol, is effective in achieving metabolic control of hyperuricemia. However, this drug reduced CsA levels, thus the risk of rejection is present.
Assuntos
Ciclosporina/antagonistas & inibidores , Transplante de Coração , Imunossupressores/antagonistas & inibidores , Sulfimpirazona/farmacologia , Uricosúricos/farmacologia , Alopurinol/efeitos adversos , Alopurinol/uso terapêutico , Creatinina/sangue , Ciclosporina/efeitos adversos , Ciclosporina/sangue , Interações Medicamentosas , Feminino , Seguimentos , Rejeição de Enxerto/terapia , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ureia/sangue , Ácido Úrico/sangueRESUMO
BACKGROUND: This study was aimed at investigating whether a circadian rhythm of peripheral resistance exists in patients with orthotopic cardiac transplantation (OCT) and whether it parallels that of blood pressure (BP). METHODS: BP and leg flow and resistance (plethysmography) were monitored for 24 hours in 13 denervated OCT recipients and 13 control patients with native heart, matched for casual blood pressure. RESULTS: On the basis of BP trend, control patients showed a BP reduction during sleep, whereas OCT recipients did not. Leg resistance was significantly lower and leg flow significantly higher during sleep than during waking in all patients, and the extent of the nocturnal decrease was similar in the two categories. CONCLUSIONS: The decrease in leg resistance in patients confined to bed for 24 hours is caused by peripheral mechanisms and does not depend on the autonomic control of the heart. The nocturnal decline in BP depends, on the contrary, on cardiac control and is lost in patients with denervated heart.
Assuntos
Monitorização Ambulatorial da Pressão Arterial , Pressão Sanguínea/fisiologia , Ritmo Circadiano/fisiologia , Transplante de Coração/fisiologia , Perna (Membro)/irrigação sanguínea , Adulto , Sistema Nervoso Autônomo/fisiologia , Velocidade do Fluxo Sanguíneo/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pletismografia , Prognóstico , Resistência Vascular/fisiologiaRESUMO
BACKGROUND: The frequency of skin tumors of all types and specifically of squamous cell carcinoma (SCC) is increased in heart transplantation (HT), but the predisposing risk factors are controversial. METHODS AND RESULTS: We studied 300 patients (age 49+/-15 years, 258 men, mean follow-up 4.6 years, follow-up range 1 month to 12 years) who were receiving standard double (cyclosporin plus azathioprine) or triple (cyclosporin plus azathioprine plus prednisone) therapy. The first-year rejection score was calculated for endomyocardial biopsy samples (International Society for Heart and Lung Transplantation grade 0=0, 1A=1, 1B=2, 2=3, 3A=4, 3B=5, and 4=6) and used as an indirect marker of the level of immunosuppression. Multivariate analysis (Cox regression) included age at HT, sex, skin type, first-year rejection score, presence of warts and solar keratosis, lifetime sunlight exposure, and first-year cumulative dose of steroids. The incidence of skin tumors of all types increased from 15% after 5 years to 35% after 10 years after HT according to life-table analysis. Age at HT of >50 years (P:=0.03, RR=5.3), skin type II (P:=0.05, RR=2.6), rejection score of 19 (P:=0.003, RR=5.7), solar keratosis (P:=0.001, RR=6.9), and lifetime sunlight exposure of >30 000 hours (P:=0.0003, RR=7.6) were risk factors for SCC. CONCLUSIONS: Older age at HT, light skin type, solar keratosis, greater sunlight exposure, and high rejection score in the first year were independently associated with an increased risk of SCC. The progressive increase in cancer frequency during follow-up and the association with high rejection scores suggest that both the length and level of immunosuppression may be relevant. Because cumulative immunosuppressive load is cumbersome to calculate, a high rejection score in the first year may provide a useful predictor for patients at risk.