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1.
Br J Surg ; 107(8): 1042-1052, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31997313

RESUMO

BACKGROUND: Early cancer recurrence after oesophagectomy is a common problem, with an incidence of 20-30 per cent despite the widespread use of neoadjuvant treatment. Quantification of this risk is difficult and existing models perform poorly. This study aimed to develop a predictive model for early recurrence after surgery for oesophageal adenocarcinoma using a large multinational cohort and machine learning approaches. METHODS: Consecutive patients who underwent oesophagectomy for adenocarcinoma and had neoadjuvant treatment in one Dutch and six UK oesophagogastric units were analysed. Using clinical characteristics and postoperative histopathology, models were generated using elastic net regression (ELR) and the machine learning methods random forest (RF) and extreme gradient boosting (XGB). Finally, a combined (ensemble) model of these was generated. The relative importance of factors to outcome was calculated as a percentage contribution to the model. RESULTS: A total of 812 patients were included. The recurrence rate at less than 1 year was 29·1 per cent. All of the models demonstrated good discrimination. Internally validated areas under the receiver operating characteristic (ROC) curve (AUCs) were similar, with the ensemble model performing best (AUC 0·791 for ELR, 0·801 for RF, 0·804 for XGB, 0·805 for ensemble). Performance was similar when internal-external validation was used (validation across sites, AUC 0·804 for ensemble). In the final model, the most important variables were number of positive lymph nodes (25·7 per cent) and lymphovascular invasion (16·9 per cent). CONCLUSION: The model derived using machine learning approaches and an international data set provided excellent performance in quantifying the risk of early recurrence after surgery, and will be useful in prognostication for clinicians and patients.


ANTECEDENTES: la recidiva precoz del cáncer tras esofaguectomía es un problema frecuente con una incidencia del 20-30% a pesar del uso generalizado del tratamiento neoadyuvante. La cuantificación de este riesgo es difícil y los modelos actuales funcionan mal. Este estudio se propuso desarrollar un modelo predictivo para la recidiva precoz después de la cirugía para el adenocarcinoma de esófago utilizando una gran cohorte multinacional y enfoques con aprendizaje automático. MÉTODOS: Se analizaron pacientes consecutivos sometidos a esofaguectomía por adenocarcinoma y que recibieron tratamiento neoadyuvante en 6 unidades de cirugía esofagogástrica del Reino Unido y 1 de los Países Bajos. Con la utilización de características clínicas y la histopatología postoperatoria se generaron modelos mediante regresión de red elástica (elastic net regression, ELR) y métodos de aprendizaje automático Random Forest (RF) y XG boost (XGB). Finalmente, se generó un modelo combinado (Ensemble) de dichos métodos. La importancia relativa de los factores respecto al resultado se calculó como porcentaje de contribución al modelo. RESULTADOS: En total se incluyeron 812 pacientes. La tasa de recidiva a menos de 1 año fue del 29,1%. Todos los modelos demostraron una buena discriminación. Las áreas bajo la curva ROC (AUC) validadas internamente fueron similares, con el modelo Ensemble funcionando mejor (ELR = 0,791, RF = 0,801, XGB = 0,804, Ensemble = 0,805). El rendimiento fue similar cuando se utilizaba validación interna-externa (validación entre centros, Ensemble AUC = 0,804). En el modelo final, las variables más importantes fueron el número de ganglios linfáticos positivos (25,7%) y la invasión linfovascular (16,9%). CONCLUSIÓN: El modelo derivado con la utilización de aproximaciones con aprendizaje automático y un conjunto de datos internacional proporcionó un rendimiento excelente para cuantificar el riesgo de recidiva precoz tras la cirugía y será útil para clínicos y pacientes a la hora de establecer un pronóstico.


Assuntos
Adenocarcinoma/cirurgia , Regras de Decisão Clínica , Neoplasias Esofágicas/cirurgia , Esofagectomia , Aprendizado de Máquina , Recidiva Local de Neoplasia/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Medição de Risco
2.
Ann Surg Oncol ; 24(2): 569-577, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27573522

RESUMO

OBJECTIVE: The purpose of this study was to investigate whether a long proximal oesophageal resection margin (PRM) is associated with improved survival after oesophagectomy for cancer and to identify the optimal margin to aim for in this patient group. METHODS: A prospectively maintained database identified 174 patients who underwent Ivor-Lewis oesophagectomy for cancer. Demographic, clinical, and pathological data were collected. X-tile software was used to identify the optimal resection point. Two models were analysed: single point resection with comparison of two groups (short and long), and two resection points with three groups (short, medium, and long) to provide a range. RESULTS: The median PRM was 4.0 cm (interquartile range: 2.5-6.0 cm). After adjustment for significant confounders, multivariable Cox PH analysis demonstrated that the optimal resection margin was 1.7 cm, and in the three-group analysis the optimum PRM was between 1.7 and 3 cm. In the two-group analysis, the long margin had no effect on DFS (p = 0.37), but carried a significantly improved overall survival (hazard ratio [HR] = 0.46, 95 % confidence interval [CI] 0.25-0.87, p = 0.02). In the three-group analysis, the medium and long groups had improved OS compared with the short group (on average 54 %, HR ≥ 0.45, p ≤ 0.04). The 5-year disease-free and overall survival rates were highest in the medium PRM group (48 and 57 % respectively). CONCLUSIONS: Optimal survival following oesophagectomy for cancer is achieved with a PRM > 1.7 cm, but a PRM > 3 cm does not yield a further survival advantage. Thus, the optimal PRM is likely to be between 1.7 and 3 cm.


Assuntos
Adenocarcinoma/cirurgia , Carcinoma de Células Pequenas/cirurgia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia , Margens de Excisão , Adenocarcinoma/patologia , Idoso , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
3.
Transpl Infect Dis ; 16(2): 213-24, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24589027

RESUMO

BACKGROUND: Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. METHODS: Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. RESULTS: A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. CONCLUSIONS: This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.


Assuntos
Blastomicose/epidemiologia , Coccidioidomicose/epidemiologia , Doenças Endêmicas , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Histoplasmose/epidemiologia , Transplante de Órgãos/efeitos adversos , Adolescente , Adulto , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Blastomicose/tratamento farmacológico , Criança , Coccidioidomicose/tratamento farmacológico , Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Comorbidade , Feminino , Histoplasmose/tratamento farmacológico , Humanos , Incidência , Itraconazol/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Fatores de Tempo , Estados Unidos/epidemiologia , Adulto Jovem
4.
Transpl Infect Dis ; 14(2): 213-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22093368

RESUMO

Post-transplantation histoplasmosis may be acquired via inhalation, may result from endogenous reactivation, or may be derived from the allograft. The Histoplasma and Aspergillus enzyme-linked immunoassays are increasingly being relied upon for rapid diagnosis of fungal infections, especially in immunocompromised patients. We describe 4 cases of solid organ transplant recipients who had histoplasmosis and a falsely positive Aspergillus galactomannan (GM) obtained from the serum or bronchoalveolar lavage (BAL) fluid. We also report our experience, testing for Histoplasma antigen (Ag) in specimens positive for Aspergillus GM. From January 2007 through December 2010, of 2432 unique patients who had positive Aspergillus GM tests, 514 (21%) were tested for Histoplasma Ag, and 27 were found to be positive. Most specimens that tested positive for both Aspergillus and Histoplasma were obtained by BAL. False-positive tests for Aspergillus GM can occur in immunosuppressed patients who have histoplasmosis, and may obscure the correct diagnosis.


Assuntos
Aspergillus/isolamento & purificação , Reações Falso-Positivas , Histoplasmose/diagnóstico , Mananas/isolamento & purificação , Transplante de Órgãos/efeitos adversos , Adulto , Antígenos de Fungos/isolamento & purificação , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Galactose/análogos & derivados , Histoplasma/imunologia , Histoplasma/isolamento & purificação , Humanos , Pessoa de Meia-Idade
5.
Transpl Infect Dis ; 14(3): 229-36, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22624726

RESUMO

Transmission of pathogens from donor to recipient is a potential complication of organ transplantation. Herein, we describe the clinical course and outcomes of 4 transplant recipients who received tissues from a donor with multi-organ infection with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Recipient 1 underwent simultaneous liver and kidney transplantation for alpha-1 antitrypsin deficiency and alcohol-related cirrhosis, and acute tubular necrosis, respectively. Soon after transplantation, he developed an infected hematoma and peritonitis due to KPC-producing K. pneumoniae despite receiving tigecycline prophylaxis. He was treated with a prolonged course of tigecycline, amikacin, and meropenem, in conjunction with surgical evacuation and percutaneous drainage of the infected fluid collections. Recipient 2 underwent living-donor liver transplantation for cholangiocarcinoma and primary sclerosing cholangitis using vein graft from the donor infected with KPC-producing K. pneumoniae. Culture of the preservation fluid containing the vein graft was positive for KPC-producing K. pneumoniae. The patient received preemptive amikacin and tigecycline, and he did not develop any infection (as evidenced by negative surveillance blood cultures). The isolates from the donor and Recipients 1 and 2 were indistinguishable by pulsed-field gel electrophoresis. Recipients 3 and 4 underwent kidney and heart transplantation, respectively; both patients received perioperative tigecycline prophylaxis and did not develop infections due to KPC-producing K. pneumoniae. All transplant recipients had good short-term outcomes. These cases highlight the importance of inter-institutional communication and collaboration to ensure the successful management of recipients of organs from donors infected with multidrug-resistant organisms.


Assuntos
Transplante de Coração , Hematoma/microbiologia , Transplante de Rim , Infecções por Klebsiella/transmissão , Klebsiella pneumoniae/isolamento & purificação , Transplante de Fígado , Peritonite/microbiologia , Idoso , Antibacterianos/uso terapêutico , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana Múltipla , Quimioterapia Combinada , Hematoma/tratamento farmacológico , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/enzimologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Soluções para Preservação de Órgãos , Peritonite/tratamento farmacológico , Doadores de Tecidos , Coleta de Tecidos e Órgãos , Adulto Jovem , beta-Lactamases/metabolismo
6.
Eur J Clin Microbiol Infect Dis ; 29(8): 961-7, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20505968

RESUMO

The aim of this study was to evaluate the efficacy and safety of rifampin for Staphylococcus aureus (SA) or coagulase negative staphylococci (CNS) prosthetic joint infection (PJI) treated with debridement and retention (D/R). We calculated the treatment failure cumulative incidence (TF) of a cohort of 101 patients with SA or CNS PJI treated with D/R and antimicrobial therapy. The effect of the use of a rifampin-based regimen was evaluated. Cox proportional hazards regression evaluated the association between treatment and time-to-TF controlling for the propensity to treat with rifampin and temporal confounders. Seven percent (1/14) of the prospective rifampin-treated patients, 32% (10/31) of the historical rifampin-treated patients and 38% (21/56) of the historical non-rifampin treated patients developed TF. After controlling for the propensity to treat with rifampin and American Society of Anesthesia scores, patients in the prospective cohort had a lower risk of TF compared to patients in the historical cohort not treated with rifampin (HR 0.11; 95%CI 0.01-0.84). None (0/14) of the patients in the prospective study developed hepatotoxicity. The outcome of staphylococcal PJI treated with D/R and rifampin-based regimens was better when compared with a historical cohort treated without rifampin.


Assuntos
Antibacterianos/administração & dosagem , Infecções Relacionadas à Prótese/tratamento farmacológico , Rifampina/administração & dosagem , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Estudos de Coortes , Desbridamento , Feminino , Humanos , Fígado/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/microbiologia , Infecções Relacionadas à Prótese/cirurgia , Rifampina/efeitos adversos , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/cirurgia , Staphylococcus/classificação , Resultado do Tratamento , Adulto Jovem
7.
Med Mycol ; 48(1): 85-9, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19212893

RESUMO

The primary objective of the study was to investigate the risk factors for Histoplasma capsulatum fungemia. We conducted a retrospective case-control study among patients with histoplasmosis seen at Mayo Clinic in Rochester from 1 January 1991 through 31 December 2005. Blood cultures were prepared from specimens obtained from 111 patients with a diagnosis of histoplasmosis of which 55 had demonstrated H. capsulatum fungemia whereas the cultures of the remaining 56 patients were negative. The mean age of the patients was 56 years, of which 70% men and 95% were white. In univariate analysis, immunocompromised status (OR 2.9, P=0.008), peripheral leukocyte count (WBC)<3000 cells/mm(3) (OR 7.3, P<0.001), albumin<3.5 g/ dl (OR 3.1, P=0.018), and Charlson score of>4 (OR 2.9, P=0.022) were associated with H. capsulatum fungemia, but age>55 years was not (OR 1.4, P=0.38). In multivariable analysis, immunocompromised status (OR 2.4, P=0.043) and WBC<3000 cells/mm(3) (OR 6.5, P=0.001) remained significant factors associated with H. capsulatum fungemia. Immunocompromised status and WBC<3000 cells/ mm(3) are independent risk factors for the development of H. capsulatum fungemia.


Assuntos
Fungemia/epidemiologia , Histoplasma/isolamento & purificação , Histoplasmose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Fungemia/microbiologia , Histoplasmose/microbiologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Minnesota , Estudos Retrospectivos , Fatores de Risco
8.
Transpl Infect Dis ; 10(6): 413-8, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18564981

RESUMO

Whipple's disease is a very rare chronic multisystemic bacterial disease characterized by diarrhea, malabsorption, fever, and polyarthritis. Ocular manifestations occur very rarely. Previous reports have suggested that the use of immunosuppressive drugs appears to accelerate or exacerbate the clinical course of Whipple's disease; however, the illness has yet to be reported in the setting of transplantation. Herein, we describe what we believe is the first reported case of Whipple's disease after transplantation. The patient is a 51-year-old woman who developed progressive visual floaters and blurring of vision 30 years after living-related kidney transplantation for an autosomal-dominant polycystic kidney disease. Her allograft was functioning well on maintenance immunosuppressive therapy with azathioprine and prednisone when she developed visual abnormalities. Transient weight loss, gastrointestinal symptoms, and migratory polyarthralgia predated the onset of ocular disease by several years. The diagnosis of Whipple's bilateral vitreitis and chorioretinitis was confirmed by polymerase chain reaction analysis demonstrating Tropheryma whipplei nucleic acid in vitreous fluid and peripheral blood sample as well as by demonstration of the bacilli by cytopathology. Intraocular vancomycin, intravenous ceftriaxone, and prolonged course of oral trimethoprim-sulfamethoxazole therapy led to clinical improvement and recovery of visual acuity.


Assuntos
Coriorretinite/etiologia , Infecções Oculares Bacterianas/etiologia , Transplante de Rim/efeitos adversos , Rim Policístico Autossômico Recessivo/cirurgia , Complicações Pós-Operatórias/etiologia , Tropheryma/isolamento & purificação , Corpo Vítreo/microbiologia , Doença de Whipple/etiologia , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Coriorretinite/microbiologia , Coriorretinite/patologia , DNA Bacteriano/análise , Quimioterapia Combinada , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/tratamento farmacológico , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/tratamento farmacológico , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Tropheryma/genética , Corpo Vítreo/patologia , Doença de Whipple/diagnóstico , Doença de Whipple/tratamento farmacológico
9.
Drugs Today (Barc) ; 52(1): 7-16, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26937491

RESUMO

Isavuconazole is a new azole antifungal drug with a broad antifungal spectrum that includes yeasts, molds and dimorphic fungi. Its prodrug, isavuconazonium sulfate, is currently approved in the United States and Europe for the treatment of the two of the most common and most challenging invasive fungal infections in clinical practice, invasive aspergillosis and invasive mucormycosis. It is available in both oral and intravenous formulations for once-a-day dosing and has favorable safety profile and drug interaction potential in comparison to voriconazole. Its role in the treatment of other fungal infections, besides aspergillosis and mucormycosis, remains to be determined. Similarly, its efficacy in prophylaxis against invasive fungal infections or its utility in patients with prior azole exposure is yet to be elucidated in clinical studies.


Assuntos
Antifúngicos/uso terapêutico , Nitrilas/uso terapêutico , Piridinas/uso terapêutico , Triazóis/uso terapêutico , Ensaios Clínicos como Assunto , Interações Medicamentosas , Humanos , Micoses/tratamento farmacológico , Nitrilas/efeitos adversos , Nitrilas/metabolismo , Nitrilas/farmacologia , Piridinas/efeitos adversos , Piridinas/metabolismo , Piridinas/farmacologia , Triazóis/efeitos adversos , Triazóis/metabolismo , Triazóis/farmacologia
10.
Bone Marrow Transplant ; 51(1): 2-12, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26191950

RESUMO

Increased use of novel agents and autologous stem cell transplantation has led to a significant improvement in PFS and overall survival in patients with multiple myeloma. Despite improved treatment strategies, most patients eventually relapse due to persistent low levels of disease in the bone marrow. Increasingly sensitive methods to measure or detect such disease have been evaluated, including multi-parametric flow cytometry, PCR, next-generation sequencing and imaging modalities. The following literature review examines current methods for detecting and monitoring minimal or measurable residual disease (MRD) in the post-transplant setting. Improved methods for detecting MRD will refine the current definitions of remission and could guide treatment approaches.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Mieloma Múltiplo , Reação em Cadeia da Polimerase Multiplex , Transplante de Células-Tronco , Animais , Autoenxertos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Mieloma Múltiplo/terapia , Reação em Cadeia da Polimerase Multiplex/métodos , Neoplasia Residual
11.
Arch Intern Med ; 146(12): 2341-3, 1986 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-3535720

RESUMO

To determine the clinical impact of enhanced detection of Staphylococcus aureus by a lysis-centrifugation (LC) blood culture system, consecutive cases of S aureus bacteremia during a seven-month period were reviewed. Of 77 clinically significant cases, the LC system detected 70 cases (91%) while a conventional broth system detected 67 cases (87%). Of 60 cases detected by both systems, the LC system was positive earlier than the broth system by one or more days in 34 cases (57%) and later in none. It also detected more (12 vs four of 13) patients with persistent bacteremia who were receiving antimicrobial treatment. Forty-three patients (56%) did not receive appropriate antimicrobial therapy until cultures were reported positive. Enhanced detection of S aureus bacteremia is a clinically important advantage of the LC blood culture technique.


Assuntos
Técnicas Bacteriológicas , Sepse/microbiologia , Staphylococcus aureus/isolamento & purificação , Centrifugação , Humanos , Estudos Retrospectivos , Sepse/tratamento farmacológico , Fatores de Tempo
12.
Transplantation ; 64(1): 66-73, 1997 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-9233703

RESUMO

BACKGROUND: The optimal prophylactic regimen to prevent cytomegalovirus (CMV) infection and disease in orthotopic liver-transplant patients remains to be established. We tested whether a combination of intravenous ganciclovir (GCV) followed by high dosages of oral acyclovir (ACV) for 4 months provided a higher degree of protection from CMV than oral ACV alone. METHODS: One hundred sixty-seven liver-transplant recipients were randomized to receive 120 days of antiviral treatment starting at the time of transplantation consisting of either ACV 800 mg orally four times daily (n=84) or 14 days of GCV 5 mg/kg intravenously every 12 hr followed by oral ACV 800 mg four times daily (n=83). Prospective laboratory and clinical surveillance was performed to determine primary endpoints (onset of CMV infection and CMV disease) and secondary endpoints (rates of fungal and bacterial infection, allograft rejection, and survival after transplantation). One-year event rates are presented as cumulative percentages. RESULTS: During the first year after transplantation, CMV infection developed in 57% of patients treated with ACV and in 37% of patients treated with GCV + ACV (P=0.001). CMV disease developed in 23% of patients treated with ACV and in 11% of patients treated with GCV + ACV (P=0.03). In seronegative recipients of allografts from CMV-seropositive donors (D+/R-), CMV disease developed in 58% of patients treated with ACV and in 25% of patients treated with GCV + ACV (P=0.04). In the D+/R- group, 54% of patients treated with ACV and 17% of patients treated with GCV + ACV developed infection with Candida albicans (P=0.05). CONCLUSIONS: Prophylaxis of CMV infection in liver-transplant patients with 14 days of intravenous GCV followed by high-dosage oral ACV is more effective than high-dosage oral ACV alone at reducing CMV infection and disease, even for patients in the D+/R- CMV serological group.


Assuntos
Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/uso terapêutico , Transplante de Fígado , Aciclovir/administração & dosagem , Adulto , Infecções por Citomegalovirus/epidemiologia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/prevenção & controle , Taxa de Sobrevida
13.
Mayo Clin Proc ; 74(10): 1030-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10918871

RESUMO

The quinolones are broad-spectrum antibacterial agents that have a novel mechanism of action. As synthetic compounds, these agents have been developed extensively to optimize antimicrobial activity, pharmacokinetic properties, and drug safety. Although earlier quinolones were effective only in the genitourinary and gastrointestinal tracts and only had activity against aerobic gram-negative bacteria, newer quinolones have wider potential applications and a broader spectrum of activity. Some of the newer quinolones will have a role in the treatment of community-acquired pneumonia and intra-abdominal infections. Ciprofloxacin remains the most potent quinolone against Pseudomonas aeruginosa. Among the quinolones, important differences exist in renal and hepatic elimination and dose-adjustment regimens. Although there are many Food and Drug Administration-approved indications for some of the newer quinolones, the quinolones are the drug of choice for only a few infections. Quinolone-resistant bacteria are being increasingly identified and emerge under selective pressure created by extensive use.


Assuntos
Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacocinética , Infecções Bacterianas/tratamento farmacológico , Interações Medicamentosas , Fluoroquinolonas , Humanos
14.
Mayo Clin Proc ; 66(9): 914-8, 1991 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1921501

RESUMO

Although several studies have shown that sarcoidosis and tuberculosis are the most common causes of granulomatous hepatitis (GH), these studies were biased because results of unselected liver biopsies and autopsy reports were included. We reviewed the medical records of patients diagnosed with GH at the Mayo Clinic between September 1976 and October 1985 for the current study. Our study group consisted of 45 women and 43 men (mean age, 54.2 years). Overall, 65 patients (74%) were symptomatic; the rest had only liver enzyme abnormalities. The mean duration of symptoms was 19.1 months. Assessment of these patients and a comprehensive workup for infectious agents or other causes revealed idiopathic GH confined to the liver in 50%, sarcoidosis with confirmed extrahepatic disease in 22%, drug-related GH in 6%, tuberculosis in 3%, and other causes in 19%. Our study found a much higher frequency of idiopathic GH than previously published reports, and it represents the largest number of cases of idiopathic liver granulomas reported in a single series.


Assuntos
Granuloma/etiologia , Hepatite/etiologia , Biópsia , Feminino , Granuloma/diagnóstico , Granuloma/patologia , Hepatite/diagnóstico , Hepatite/patologia , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Minnesota , Estudos Retrospectivos , Sarcoidose/complicações , Tuberculose/complicações
15.
Mayo Clin Proc ; 62(11): 1007-12, 1987 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3312850

RESUMO

The fluoroquinolones are a new class of antimicrobial agents structurally related to nalidixic acid. They have a broad spectrum of activity against pathogens, including Pseudomonas aeruginosa, other multiresistant gram-negative bacteria, and methicillin-resistant Staphylococcus aureus but not anaerobes. They are well absorbed after oral administration, and some achieve serum and tissue levels well exceeding the minimal inhibitory concentrations for susceptible bacteria. Adverse reactions are rare, and when they occur they are usually mild. Use of quinolones should be avoided in children because of possible damage to developing cartilage. These agents should prove useful in the treatment of urinary tract infections caused by bacteria resistant to other oral agents, bacterial gastroenteritis, and gonococcal infections. The use of quinolones may potentially reduce the cost of treatment of certain systemic infections caused by multiantimicrobial resistant organisms because outpatient oral therapy is possible.


Assuntos
Antibacterianos , Oxazinas , Quinolinas , Adolescente , Adulto , Infecções Bacterianas/tratamento farmacológico , Ciprofloxacina/efeitos adversos , Ciprofloxacina/farmacologia , Resistência Microbiana a Medicamentos , Enoxacino , Feminino , Humanos , Ácido Nalidíxico/efeitos adversos , Naftiridinas/efeitos adversos , Naftiridinas/farmacologia , Norfloxacino/efeitos adversos , Norfloxacino/farmacologia , Ofloxacino , Oxazinas/efeitos adversos , Oxazinas/farmacologia
16.
Mayo Clin Proc ; 66(12): 1249-59, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1749294

RESUMO

The fluoroquinolone class of antibiotics promises to become as diverse and as important as beta-lactam agents. The fluoroquinolones inhibit bacterial DNA gyrase and are bactericidal. All fluoroquinolones have potent activity against most gram-negative bacteria; ciprofloxacin is the most active against Pseudomonas aeruginosa. Activity against gram-positive organisms is variable; methicillin-resistant Staphylococcus aureus has acquired resistance to the fluoroquinolones at an alarming rate. Currently available quinolones do not have, but new quinolone agents likely will have, substantial activity against anaerobic bacteria. Some quinolones are also active against Mycobacterium, Chlamydia, and Mycoplasma organisms. All fluoroquinolones have excellent absorption after oral administration; however, this process can be impaired by the presence of aluminum- or magnesium-containing antacids and by zinc, iron, or calcium supplements. Ciprofloxacin is also available for intravenous use. Although most fluoroquinolones do not achieve adequate cerebrospinal fluid levels, penetration into other tissues is excellent. Dosage adjustments for renal and hepatic dysfunction vary among the quinolones. Although side effects are rare, concomitant use of caffeine or theophylline with some quinolones may cause toxicity to the central nervous system. Because they may affect the development of cartilage, all fluoroquinolones are contraindicated in children, adolescents, and pregnant or breast-feeding women.


Assuntos
Anti-Infecciosos , 4-Quinolonas , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Anti-Infecciosos/uso terapêutico , Protocolos Clínicos/normas , Interações Medicamentosas , Resistência Microbiana a Medicamentos , Humanos , Testes de Sensibilidade Microbiana
17.
Mayo Clin Proc ; 67(7): 676-84, 1992 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-1434904

RESUMO

Infection remains a major cause of morbidity and mortality after cardiac transplantation. Most infections occur during the first few months after transplantation. Although late infection does occur, the risk of infection during maintenance immunosuppression is low in the absence of recurrent rejection that necessitates augmentation of suppression of the immune response. Before cardiac transplantation, the risk factors for infectious disease in potential candidates should be assessed. A detailed history of past infections should be elicited, and patients should be screened for the presence of active indolent infection. In addition, potential donors must be thoroughly assessed for organ-transmittable infection. Many common infections that may occur after cardiac transplantation can be prevented with the use of appropriate prophylactic regimens directed toward cytomegalovirus, Toxoplasma gondii, Pneumocystis carinii, and herpes simplex virus. Periodic surveillance serologic tests and cultures after cardiac transplantation facilitate early diagnosis and prompt institution of appropriate therapy.


Assuntos
Transplante de Coração , Controle de Infecções , Complicações Pós-Operatórias/prevenção & controle , Transplante de Coração/efeitos adversos , Humanos , Infecções/etiologia , Doadores de Tecidos
18.
Mayo Clin Proc ; 73(2): 153-6, 1998 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9472999

RESUMO

A 24-year-old woman with recurrent Hodgkin's lymphoma, stage IIB nodular sclerosing type, underwent an autologous bone marrow transplantation. Forty-five days after transplantation, an upper respiratory tract infection developed that progressed to respiratory distress necessitating mechanical ventilation. An open-lung biopsy demonstrated diffuse alveolar damage. After an extensive search for the cause of the respiratory compromise, we detected respiratory syncytial virus in a bronchoalveolar lavage specimen. The patient was immediately treated with aerosolized ribavirin and intravenous immunoglobulin; her symptoms resolved, and she was extubated 4 days after initiation of therapy.


Assuntos
Transplante de Medula Óssea , Pneumonia/complicações , Pneumonia/virologia , Alvéolos Pulmonares/virologia , Infecções por Vírus Respiratório Sincicial/complicações , Adulto , Antivirais/uso terapêutico , Líquido da Lavagem Broncoalveolar/virologia , Feminino , Doença de Hodgkin/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Pneumonia/terapia , Infecções por Vírus Respiratório Sincicial/terapia , Ribavirina/uso terapêutico , Transplante Autólogo
19.
Chest ; 109(4): 1119-24, 1996 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8635345

RESUMO

OBJECTIVE: To describe a cluster of donor-transmitted cases of invasive aspergillosis. DESIGN: Case series of epidemiologically linked cases of invasive aspergillosis. SETTING: Two tertiary care centers with solid-organ transplant programs. PATIENTS: Two kidney recipients, one heart recipient, and the single donor. MEASUREMENTS: Routine clinical, microbiological, and pathologic investigation as dictated for patient care. Epidemiologic analysis to establish linkage among cases. RESULTS: Three allografts (two kidneys and a heart) from a single donor transmitted invasive aspergillosis to the recipients. Three weeks after transplantation, the two kidney recipients had fever and urine cultures positive for Aspergillus fumigatus. The infected kidneys had multiple Aspergillus abscesses and had to be removed to cure the patients. The heart recipient had a negative workup when a diagnosis of aspergillosis was made for the kidney recipients but presented three months later with aspergillus endocarditis with hematogenous spread to the eyes and to the skin. Treatment included eye surgery, aortic valve replacement, and antifungal therapy; control of infection ensued. The donor was intensely immunosuppressed (17 days post-liver transplantation with death from intracerebral bleeding) but had no clinical or autopsy evidence of aspergillosis. Donor tracheal secretions obtained at the time of organ harvest later grew A fumigatus. CONCLUSION: Expanded criteria for organ donation have to be balanced against infectious risk to organ recipients. A fumigatus can be transmitted from a subclinically infected donor to solid-organ transplant recipients.


Assuntos
Aspergilose/transmissão , Aspergillus fumigatus , Transplante de Coração/efeitos adversos , Transplante de Rim/efeitos adversos , Infecções Oportunistas/transmissão , Doadores de Tecidos , Abscesso/microbiologia , Adulto , Aspergillus fumigatus/isolamento & purificação , Dermatomicoses/patologia , Endocardite/microbiologia , Infecções Oculares Fúngicas/patologia , Feminino , Humanos , Nefropatias/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/microbiologia , Transplante Homólogo
20.
J Heart Lung Transplant ; 17(7): 732-6, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9703241

RESUMO

BACKGROUND: Kaposi's sarcoma is an endothelial tumor rarely diagnosed after heart transplantation. We report on a patient originally from Africa in whom Kaposi's sarcoma developed in association with Kaposi's sarcoma-associated herpesvirus. METHODS: A man from Ghana had constitutional symptoms associated with multiple pulmonary nodules that developed 3 months after heart transplantation. Kaposi's sarcoma was diagnosed by thorascopic biopsy. Treatment consisted of reducing immunosuppression therapy and adding famciclovir treatment. Symptoms resolved within 1 month after treatment, and no disease progression was observed for 5 months. The patient died suddenly 8 months after heart transplantation; autopsy revealed occlusion of the left anterior descending coronary artery and grade 3A rejection. Extensive Kaposi's sarcoma was observed in the lungs and gastrointestinal tract at autopsy. RESULTS: Pathologic analysis of the tumor demonstrated features consistent with Kaposi's sarcoma. Polymerase chain reaction and in situ hybridization demonstrated the presence of Kaposi's sarcoma-associated herpesvirus. CONCLUSION: Kaposi's sarcoma rarely is diagnosed after transplantation. Patients infected with Kaposi's sarcoma-associated herpesvirus may be at increased risk. Screening for Kaposi's sarcoma-associated herpesvirus may be indicated in patients at risk. The role of antiviral medications and immunization in the treatment and prevention of the disorder is unknown.


Assuntos
Transplante de Coração , Herpesvirus Humano 8/isolamento & purificação , Neoplasias Pulmonares/virologia , Complicações Pós-Operatórias/virologia , Sarcoma de Kaposi/virologia , 2-Aminopurina/análogos & derivados , 2-Aminopurina/uso terapêutico , Antivirais/uso terapêutico , Famciclovir , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco
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