RESUMO
Primary liver tumours in neonates with single-ventricle palliation are exceedingly rare. We present the first reported case of neonatal hepatoblastoma with severe Ebstein's anomaly following Starnes procedure. The patient's postoperative course highlights the challenges and complications in simultaneous management of these diagnoses. Transition from shunted single-ventricle physiology to bidirectional cavopulmonary connection improved end-organ function, permitting more aggressive hepatic malignancy treatment.
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Anomalia de Ebstein , Hepatoblastoma , Neoplasias Hepáticas , Coração Univentricular , Recém-Nascido , Humanos , Anomalia de Ebstein/diagnóstico , Anomalia de Ebstein/cirurgia , Anomalia de Ebstein/complicações , Hepatoblastoma/diagnóstico , Hepatoblastoma/cirurgia , Hepatoblastoma/complicações , Coração Univentricular/complicações , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/complicaçõesRESUMO
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare, genetically-inherited cardiomyopathy that may be fatal. We present the case of a 17 year old male who presented after a witnessed cardiac arrest with indeterminate echocardiogram and electrocardiogram (ECG) findings for a specific etiology. Genetic testing revealed a mutation in the PKP2 and DSC2 genes, consistent with ARVC. This report outlines the presentation of ARVC as an aborted sudden cardiac death episode in a previously asymptomatic teenager, investigations for ARVC and highlights the importance of adequate cardiopulmonary resuscitation in the overall prognosis. Implantable cardiac defibrillator (ICD) placement for secondary prevention is necessary.
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BACKGROUND: Aortic root translocation (Nikaidoh), Rastelli, and réparation à l'etage ventriculaire (REV) are repair options for transposition of the great arteries (TGA) with ventricular septal defects and left ventricular outflow tract obstruction (VSD-LVOTO) or double outlet right ventricle TGA type (DORV-TGA). METHODS: This retrospective study using The Society of Thoracic Surgeons Congenital Heart Surgery Database evaluates surgical procedure utilization and outcomes of patients undergoing repair of TGA-VSD-LVOTO and DORV-TGA with a Nikaidoh, Rastelli, or REV procedure. RESULTS: A total of 293 patients underwent repair at 82 centers (January 2010 to June 2019). Most patients underwent a Rastelli (n = 165, 56.3%) or a Nikaidoh (n = 119, 40.6%) operation; only 3.1% (n = 9) underwent a REV. High-volume centers performed the majority of the repairs. Fewer Nikaidoh than Rastelli patients had prior cardiac operations (n = 57 [48.7%] vs n = 102 [63.0%]; P = .004). Nikaidohs had longer median cardiopulmonary bypass time (227 [interquartile range (IQR), 167-299] minutes vs 175 [IQR, 133-225] minutes; P < .001) and median aortic cross-clamp times (131 [IQR, 91-175] minutes vs 105 [IQR, 82-141] minutes; P = .0015). Operative mortality was 3.1% (95% confidence interval [CI], 1.0%-7.0%; n = 5) for Rastelli, 4.4% (95% CI, 1.4%-9.9%; n = 5) for Nikaidoh, and 11.1% (95% CI, 0.3%-48.3%, n = 1) for REV. The rates of cardiac arrest, unplanned reoperation, mechanical circulatory support, prolonged ventilation, and permanent pacemaker placement were higher in the Nikaidoh population but with 95% CIs overlapping those of the other procedures. CONCLUSIONS: Rastelli and Nikaidoh procedures are the prevalent repair strategies for patients with DORV-TGA and TGA-VSD-LVOTO. Most are performed at high-volume institutions, and early outcomes are similar.
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Dupla Via de Saída do Ventrículo Direito , Cardiopatias Congênitas , Comunicação Interventricular , Cirurgiões , Transposição dos Grandes Vasos , Obstrução do Fluxo Ventricular Externo , Cardiopatias Congênitas/cirurgia , Comunicação Interventricular/cirurgia , Humanos , Lactente , Estudos Retrospectivos , Transposição dos Grandes Vasos/cirurgia , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/cirurgiaRESUMO
BACKGROUND: Donors with drowning or asphyxiation (DA) as a mechanism of death (MOD) are considered high risk in pediatric lung transplantation. We sought to evaluate whether recipients of DA donors had negatively impacted outcomes. METHODS: Pediatric recipients recorded in the United Network for Organ Sharing registry between 2000 and 2019 were included. Primary stratification was donor MOD. Propensity matching with a 1:1 ratio was performed to balance the DA and non-DA MOD donor cohorts. Cox multivariable regression was used to determine the risk-adjusted impact of donor MOD. A subanalysis of the effect of lung allocation score was also evaluated. RESULTS: A total of 1016 patients underwent bilateral lung transplantation during the study period, including 888 (85.6%) from non-DA donors and 128 (14.4%) from DA donors. Survival at 90 days, 1 year, and 2 years were similar in the matched and unmatched cohorts regardless of the donor MOD. Moreover, separate risk-adjusted analysis of drowning and asphyxiated donors was similar to other MOD donors at 30 days, 1 year, and 5 years. Similar survival findings persisted regardless of pretransplant lung allocation score. Although the rates of posttransplant stroke (1.0% versus 3.1%, P = 0.04) and the length of hospital stay (19 versus 22 d, P = 0.004) were elevated in the unmatched DA MOD recipients, these differences were mitigated after propensity matching. CONCLUSIONS: This study evaluated the impact of DA MOD donors in pediatric lung transplant recipients and found similar rates of complications and survival in a propensity-matched cohort. These data collectively support the consideration of DA MOD donors for use in pediatric lung transplantation.
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Asfixia , Afogamento , Transplante de Pulmão , Sistema de Registros , Doadores de Tecidos , Obtenção de Tecidos e Órgãos/métodos , Transplantados , Fatores Etários , Criança , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Extracorporeal life support (ECLS) is an essential component of a modern congenital cardiac surgery program. The circuit components and bedside management team may, however, vary among institutions. Here, we evaluate our initial experience with a modified ventricular assist device-based ECLS circuit primarily managed by the bedside nurse. We hypothesize that our outcomes are comparable to Extracorporeal Life Support Organization (ELSO) registry data. All patients who received ECLS from January 1, 2016 to December 31, 2019 at a single institution were included. Primary outcomes were survival to ECLS decannulation and discharge or transfer. Secondary outcomes included complications from ECLS. Data were compared to available ELSO registry data. Thirty-seven patients underwent 44 ECLS runs during the study period. Forty percent of patients had single ventricle physiology. Nearly 46% of patients received ECLS as part of extracorporeal cardiopulmonary resuscitation (eCPR). Survival to ECLS decannulation (68.2%) and survival to discharge or transfer (61.4%) did not differ from overall ELSO outcomes (69.7%, P = .870 and 50.7%, P = .136), as well as survival to discharge or transfer in a comparable cohort of ELSO centers (53.1%, P = .081). Patients with complications had a lower rate of survival to discharge or transfer but this did not reach statistical significance (47.7% vs. 75.0%, P = .455). Neurologic (50.0%), hemorrhagic (45.5%), and renal complications (31.8%) were most common in this cohort. A modified ventricular assist device-based ECLS circuit with primary management by the bedside nurse can provide comparable support in a neonatal and pediatric cardiac surgery population. Cost analyses and further delineation of the complication profile are necessary for a complete characterization of this system.
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Oxigenação por Membrana Extracorpórea/instrumentação , Cardiopatias Congênitas/cirurgia , Coração Auxiliar/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Criança , Pré-Escolar , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/estatística & dados numéricos , Feminino , Cardiopatias Congênitas/mortalidade , Coração Auxiliar/efeitos adversos , Humanos , Lactente , Recém-Nascido , Masculino , Alta do Paciente/estatística & dados numéricos , Transferência de Pacientes/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Despite significant improvement in outcomes with truncus arteriosus (TA) repair, right ventricular outflow tract (RVOT) reconstruction with a right ventricular to pulmonary artery (RV-to-PA) conduit remains a source of long-term reintervention and reoperation. This study evaluated our experience with reintervention in homograft and polytetrafluoroethylene (PTFE) RV-to-PA conduits in neonates. METHODS: Primary TA repairs from 2004 to 2016 at a single institution were included. Stratification was based on RVOT reconstruction with PTFE or homograft conduit. Primary outcome was operative conduit replacement. Secondary outcomes included the rates and types of catheter-based conduit interventions. RESULTS: Twenty-eight patients underwent primary TA repair and 89.3% (n = 25) of them had RVOT reconstruction with a homograft (28.0%, n = 7) or PTFE (72.0%, n = 18) conduit. Rates of reoperation for conduit replacement and catheter-based interventions were similar between those with PTFE and homograft conduits (85.7% vs 72.2%, P = .49 and 57.1% vs 83.3%, P = .11, respectively). Additionally, the median time to conduit replacement and catheter-based conduit interventions were comparable. In multivariable analysis, conduit size, but not conduit type, was a predictor of conduit revision (hazard ratio: 1.66, 95% confidence interval: 1.11-2.49, P = .02). At five-year and ten-year follow-up, patients with PTFE conduits had better survival than those with homograft conduits (100.0% vs 71.4%, P = .02); however, no mortalities were associated with conduit reoperations or catheter-based reinterventions. CONCLUSIONS: Polytetrafluoroethylene and homograft RVOT reconstruction in neonatal TA repair demonstrate similar durability as defined by reoperation and reintervention rates. The validation of the durability of PTFE conduits in neonatal TA repair requires confirmatory studies in larger cohorts.
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Implante de Prótese Vascular , Oclusão de Enxerto Vascular/cirurgia , Ventrículos do Coração/cirurgia , Politetrafluoretileno , Artéria Pulmonar/cirurgia , Persistência do Tronco Arterial/cirurgia , Enxerto Vascular , Aloenxertos , Prótese Vascular , Cateterismo Cardíaco , Feminino , Oclusão de Enxerto Vascular/epidemiologia , Sobrevivência de Enxerto , Humanos , Recém-Nascido , Masculino , Modelos de Riscos Proporcionais , Falha de Prótese , Procedimentos de Cirurgia Plástica , Reoperação , Estenose de Artéria Pulmonar/cirurgia , Transplante Homólogo , Resultado do TratamentoRESUMO
Intrathoracic left subclavian to common carotid artery translocation is advocated for patients undergoing vascular ring division in the setting of an enlarged Kommerell's diverticulum and aberrant left subclavian artery. This approach poses technical challenges in larger patients and patients with unfavorable body habitus. Supraclavicular left subclavian artery to common carotid translocation greatly simplifies this procedure in select patients.
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Aorta Torácica , Doenças da Aorta/diagnóstico , Anormalidades Cardiovasculares/diagnóstico , Divertículo/diagnóstico , Artéria Subclávia/anormalidades , Doenças da Aorta/complicações , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/cirurgia , Anormalidades Cardiovasculares/complicações , Anormalidades Cardiovasculares/diagnóstico por imagem , Anormalidades Cardiovasculares/cirurgia , Divertículo/complicações , Divertículo/diagnóstico por imagem , Divertículo/cirurgia , Dispneia/etiologia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/cirurgia , Humanos , Masculino , Artéria Subclávia/diagnóstico por imagem , Artéria Subclávia/cirurgia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVES: Turner syndrome (TS) and Marfan syndrome (MFS) are partially characterized by aortopathies with a risk of developing severe aortic dilation, stiffness and consequent dissection and aneurysm formation. The incidence of a bicuspid aortic valve (BAV) is also increased in TS. We investigated aortic stiffness in teenage TS and MFS patients and evaluated to what degree stiffness in TS patients is augmented by the presence of a BAV. METHODS: Fifty-seven patients with TS (n = 37) and MFS (n = 20), as well as 22 controls with similar age and size distribution underwent evaluation of thoracic aortic stiffness using phase-contrast magnetic resonance imaging. Calculated stiffness indices including pulse wave velocity (PWV), distensibility and relative area change (RAC) were collected to characterize the ascending aorta and descending aorta. PWV was also determined to evaluate global aortic arch stiffness. RESULTS: Patients with TS had reduced distensibility (0.43 vs 0.58%/mmHg, P < 0.05) and RAC (21 vs 29%, P < 0.01) in the ascending aorta when compared with normal controls. Similarly, patients with MFS had reduced ascending aortic distensibility (0.39 vs 0.58%/mmHg, P < 0.05) and RAC (22 vs 29%, P < 0.05). There were no differences in measured PWV in the ascending aorta. Patients with TS had significantly elevated PWV measured in the aortic arch when compared with controls (2.7 vs 1.9 m/s, P < 0.05). Patients with MFS had more prominent elevation in aortic arch PWV (4.2 vs 1.9 m/s, P < 0.01). The descending aortas had decreased distensibility (0.36 vs 0.55%/mmHg, P < 0.05) and RAC (18 vs 25%, P < 0.01) only in MFS patients. Additionally, 18 TS patients with a BAV were compared with 19 TS patients with a trileaflet aortic valve, without significant differences observed in any of the considered stiffness indices. CONCLUSIONS: TS and MFS teenage patients display evidence of increased aortic stiffness. In TS patients, this is focused in the ascending aorta and is independent of the presence of a BAV. MFS patients display a generalized reduction in compliance of the entire aorta.
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Aorta/fisiopatologia , Síndrome de Marfan/fisiopatologia , Síndrome de Turner/fisiopatologia , Rigidez Vascular/fisiologia , Adolescente , Aorta/diagnóstico por imagem , Aorta/patologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/patologia , Aorta Torácica/fisiopatologia , Valva Aórtica/anormalidades , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/fisiopatologia , Doença da Válvula Aórtica Bicúspide , Estudos de Casos e Controles , Criança , Feminino , Doenças das Valvas Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/fisiopatologia , Hemodinâmica/fisiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Síndrome de Marfan/diagnóstico por imagem , Síndrome de Marfan/patologia , Síndrome de Turner/diagnóstico por imagem , Síndrome de Turner/patologia , Adulto JovemRESUMO
We present the case of a type AB thymoma in a 69-year-old man with previous coronary artery bypass grafting (CABG) in whom angiography revealed a left internal mammary artery graft supplying blood flow to a thymic neoplasm, which simultaneously occluded the graft. This required a redo sternotomy, lysis of pericardial adhesions, complete thymectomy, and redo one vessel off-pump CABG. This case seeks to sensitize physicians to the possibility of coronary adverse events in patients with a previous CABG in the setting of management of mediastinal neoplasms, and it presents the novel findings on cardiac imaging associated with this case.
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Anastomose de Artéria Torácica Interna-Coronária/efeitos adversos , Neoplasias do Mediastino/irrigação sanguínea , Neovascularização Patológica/etiologia , Timoma/irrigação sanguínea , Idoso , Humanos , MasculinoRESUMO
OBJECTIVES: Sarcomas involving the mediastinum are rare and aggressive tumours with a poor prognosis. We reviewed our experience to evaluate outcomes and survival for patients who undergo surgical resection. METHODS: A retrospective review of 35 patients who underwent resection of sarcomas that involved the mediastinum at a single institution over a 15-year period was conducted. RESULTS: Fifteen patients (43%) had sarcomas originating from the great vessels, 15 (43%) the heart and 5 (15%) the chest wall. The most common subtype was leiomyosarcoma (n = 10, 29%). Twenty patients (57%) underwent resection of primary tumours, 11 (31%) of metastases and 4 (11%) of recurrences. Sixteen patients (46%) had Stage IV disease. An R0 resection was achieved in 17 patients (49%). Fourteen (40%) had an R1 resection and 4 (11%) an R2. Thirty cases (85%) were performed on cardiopulmonary bypass (CPB). Twenty-three patients (65%) required resection of adjacent structures. Eight cases (23%) were performed on an urgent basis. Morbidity and mortality were 37 and 6%, respectively. Overall median survival was 33 months (range 7-171 months). Median overall survival for Stage IV disease was 5 months compared with 27 months for all others (P = 0.26). Two-, 5- and 10-year survivals for the cohort were 50, 35 and 25%, respectively. Incomplete resection was associated with poor long-term survival. Median survival was 101 months for R0, 21 months for R1 and 9 months for R2 resection. CONCLUSIONS: CPB and concomitant resection of intrathoracic structures may be required for local tumour control in sarcomas that involve the mediastinum, and should not be considered contraindications to resection as they may offer the best opportunity for prolonged survival in selected cases.
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Neoplasias do Mediastino/cirurgia , Sarcoma/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Neoplasias do Mediastino/epidemiologia , Neoplasias do Mediastino/patologia , Mediastino/cirurgia , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoma/epidemiologia , Sarcoma/patologia , Adulto JovemRESUMO
Most cases of intussusception in adults are secondary to a pathologic condition that serves as a lead point. Intussusception has been reported in the bariatric literature, typically due to intussusception of the jejunojejunostomy. However, other causes of intussusception should be considered, including a Meckel's diverticulum (MD). Simple diverticulectomy or segmental resection is the preferred treatment since the malignancy rate is low. We present an interesting case of a patient with past surgical history of open Roux-en-Y gastric bypass who presented with intussusception. Intraoperatively, an MD was encountered and treated with diverticulectomy. 4 months later, she re-presented with recurrent intussusception and was subsequently taken back to the operating room for revision of her jejunojejunostomy. The postoperative course was uncomplicated.
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OBJECTIVE: To determine comfort and knowledge among obstetrician/gynecologists and general surgeons regarding recommendations for cancer screening for women with Lynch syndrome. METHODS: A questionnaire on Lynch syndrome was administered to all obstetrician/gynecologists and general surgeons at a hospital in New York, USA. RESULTS: Fifty obstetrician/gynecologists and 62 general surgeons completed the survey (67% response rate). Physicians were more comfortable counseling on colon cancer than endometrial cancer screening (51% vs 28%; P<0.001). Obstetrician/gynecologists were more comfortable than general surgeons counseling patients on endometrial cancer screening (36% vs 21%; P=0.090) but less comfortable counseling patients on colon cancer screening (36% vs 63%; P=0.008). There was no significant difference between the specialties in the number of knowledge-based questions answered correctly. Furthermore, there was no correlation between a physician's perceived knowledge and number of correct answers. CONCLUSION: Most physicians did not report being comfortable counseling about recommendations for endometrial cancer screening. While obstetrician/gynecologists reported greater comfort than general surgeons, we found no significant difference in disease knowledge between the groups. Because appropriate cancer screening can improve the outcomes of patients with Lynch syndrome, physicians must be knowledgeable and comfortable with screening recommendations for both endometrial and colon cancer, regardless of clinical specialty.
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Competência Clínica , Neoplasias Colorretais Hereditárias sem Polipose , Detecção Precoce de Câncer , Neoplasias do Endométrio/diagnóstico , Ginecologia , Obstetrícia , Cirurgiões , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Colorretais Hereditárias sem Polipose/genética , Aconselhamento , Feminino , HumanosRESUMO
The GATA4 transcription factor is implicated in promoting cardiogenesis in combination with other factors, including TBX5, MEF2C and BAF60C. However, when expressed in embryonic stem cells (ESCs), GATA4 was shown to promote endoderm, not cardiac mesoderm. The capacity of related GATA factors to promote cardiogenesis is untested. We found that expression of the highly related gene, Gata5, very efficiently promotes cardiomyocyte fate from murine ESCs. Gata5 directs development of beating sheets of cells that express cardiac troponin T and show a full range of action potential morphologies that are responsive to pharmacological stimulation. We discovered that by removing serum from the culture conditions, GATA4 and GATA6 are each also able to efficiently promote cardiogenesis in ESC derivatives, with some distinctions. Thus, GATA factors can function in ESC derivatives upstream of other cardiac transcription factors to direct the efficient generation of cardiomyocytes.
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Diferenciação Celular/fisiologia , Células-Tronco Embrionárias/fisiologia , Fatores de Transcrição GATA/metabolismo , Coração/embriologia , Morfogênese/fisiologia , Miócitos Cardíacos/citologia , Animais , Células-Tronco Embrionárias/metabolismo , Citometria de Fluxo , Imuno-Histoquímica , Camundongos , Miócitos Cardíacos/metabolismo , Técnicas de Patch-Clamp , Reação em Cadeia da Polimerase em Tempo Real , Troponina T/metabolismoRESUMO
Proper dosing of specific antibiotics in morbidly obese patients has been studied inadequately. However, these data are beneficial as this patient population is at an increased risk to develop postoperative infections. Cefepime is an antibiotic used for the treatment of both gram-positive and especially gram-negative infections; administration of the appropriate dose in the morbidly obese population is crucial. We therefore examined the pharmacokinetics of cefepime in patients with body mass index >40 kg/m(2). Ten morbidly obese patients, with a mean [±SD] estimated glomerular filtration rate of 108.4 ± 34.6 mL/min, undergoing elective weight loss surgical procedures were administered cefepime in addition to standard prophylactic cefazolin and studied. Serial serum cefepime concentrations were analyzed after dosing using a validated high performance liquid chromatography method. Pharmacokinetics and duration above the minimum inhibitory concentration (MIC) were determined using a protein binding value of 15% and a MIC threshold of 8 µg/mL. Mean free cefepime concentrations for t = 30, 120, and 360 min were 69.6, 31.6, and 9.2 µg/mL, respectively. The dosing interval was calculated to maintain the free concentration above the MIC (fT > MIC) for 60% of the interval. This was determined to be 10.12 h, including time for infusion. There was no toxicity. Based on this analysis, an increased dose of 2 g every 8 h is necessary to maintain an adequate fT > MIC throughout the dosing interval. Further studies are necessary to determine the efficacy of this regimen in the settings of active infections and critical illness.
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Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Cefalosporinas/administração & dosagem , Cefalosporinas/farmacocinética , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecção da Ferida Cirúrgica/tratamento farmacológico , Cefepima , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Feminino , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana , Resultado do TratamentoRESUMO
BACKGROUND: Gram-negative bacterial resistance to antibiotics is of increasing concern. Carbapenem resistance among strains of Klebsiella pneumoniae is a relatively new phenomenon. Resistance attributable to production of carbapenemases is notoriously difficult to combat. METHODS: Case report and review of the pertinent English-language literature. RESULTS: A patient, hospitalized for aortic dissection complicated by intra-abdominal catastrophe and acute kidney injury, developed bacteremia exhibiting meropenem non-susceptibility secondary to expression of bla(KPC-2). High-dose, continuous-infusion meropenem achieved serum drug concentrations above the minimum inhibitory concentration and eradicated the infection. CONCLUSION: This is the first report of a meropenem-non-susceptible carbapenamase-positive Klebsiella pneumoniae blood stream infection treated successfully with high-dose, continuous-infusion meropenem. Application of this regimen in certain patients, such as those with mild-to-moderate renal insufficiency, may be a reasonable option for multi-drug-resistant nosocomial infections.
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Antibacterianos/administração & dosagem , Bacteriemia/tratamento farmacológico , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/enzimologia , Tienamicinas/administração & dosagem , beta-Lactamases/metabolismo , Antibacterianos/farmacocinética , Bacteriemia/microbiologia , Humanos , Infusões Intravenosas/métodos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificação , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Soro/química , Tienamicinas/farmacocinética , Resultado do Tratamento , Resistência beta-LactâmicaRESUMO
BACKGROUND: The impact of large vessel extension (LVE) as a prognostic factor for adrenocortical carcinoma (ACC) is not fully understood. This study aimed to assess outcome of ACC in the presence and absence of LVE. METHODS: A retrospective review of 57 patients undergoing curative intent resection for ACC over 10 years is presented comparing those with and without LVE. LVE was defined as vascular wall invasion or intraluminal extension of the neoplasm into the inferior vena cava or renal vein. Preoperative diagnostics, operative details, pathology, overall survival (OS), and recurrence-free survival (RFS) were analyzed. RESULTS: Multivariable regression analysis showed a significant association for decreased survival with Stage III and IV disease and LVE. Patients with LVE had more functional neoplasms, greater preoperative serum hormone levels, and more positive margins than those without LVE. Median OS was 6 years and RFS 3 years. Kaplan-Meier analysis demonstrated a significant decrease in OS and RFS with LVE. Median OS with and without LVE was 18 vs 111 months and median RFS was 11 vs 64 months. Three-year OS with and without LVE were 29% vs 93% and 3 year RFS was 15% vs 67%. CONCLUSION: In addition to systemic and lymph node metastases, LVE is associated with poorer OS and RFS.
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Neoplasias do Córtex Suprarrenal/cirurgia , Veias Renais/patologia , Veia Cava Inferior/patologia , Adolescente , Neoplasias do Córtex Suprarrenal/mortalidade , Neoplasias do Córtex Suprarrenal/patologia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de TempoRESUMO
Investigation of the mechanistic bases and physiological importance of cAMP regulation of HCN channels has exploited an arginine to glutamate mutation in the nucleotide-binding fold, an approach critically dependent on the mutation selectively lowering the channel's nucleotide affinity. In apparent conflict with this, in intact Xenopus oocytes, HCN and HCN-RE channels exhibit qualitatively and quantitatively distinct responses to the tyrosine kinase inhibitor, genistein -- the estrogenic isoflavonoid strongly depolarizes the activation mid-point of HCN1-R538E, but not HCN1 channels (+9.8 mV + or - 0.9 versus +2.2 mV + or - 0.6) and hyperpolarizes gating of HCN2 (-4.8 mV + or - 1.0) but depolarizes gating of HCN2-R591E (+13.2 mV + or - 2.1). However, excised patch recording, X-ray crystallography and modeling reveal that this is not due to either a fundamental effect of the mutation on channel gating per se or of genistein acting as a mutation-sensitive partial agonist at the cAMP site. Rather, we find that genistein equivalently moves both HCN and HCN-RE channels closer to the open state (rendering the channels inherently easier to open but at a cost of decreasing the coupling energy of cAMP) and that the anomaly reflects a balance of these energetic effects with the isoform-specific inhibition of activation by the nucleotide gating ring and relief of this by endogenous cAMP. These findings have specific implications with regard to findings based on HCN-RE channels and kinase antagonists and general implications with respect to interpretation of drug effects in mutant channel backgrounds.
Assuntos
AMP Cíclico/fisiologia , Canais de Cátion Regulados por Nucleotídeos Cíclicos/efeitos dos fármacos , Canais de Cátion Regulados por Nucleotídeos Cíclicos/fisiologia , Genisteína/farmacologia , Ativação do Canal Iônico/fisiologia , Canais de Potássio/efeitos dos fármacos , Canais de Potássio/fisiologia , Animais , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Ativação do Canal Iônico/efeitos dos fármacos , Camundongos , Canais de Potássio/genética , Estrutura Terciária de ProteínaRESUMO
BACKGROUND: The clinical significance of papillary thyroid microcarcinoma (PTMC) tumors < or =1 cm is widely debated. The objective of this study was to compare conventional papillary thyroid carcinoma (PTC) (tumors >1 cm) to PTMC and assess for differences in tumor characteristics and patient outcome. METHODS: A retrospective chart review of patients with PTC or PTMC who were followed for a minimum of 3 years postoperatively and managed at a single academic institute was performed. RESULTS: Of 202 patients in the study, 66 (32.7%) had PTMC and 136 (67.3%) had conventional PTC. Patient and tumor characteristics including tumor multifocality, extrathyroidal extension, angiolymphatic invasion, and lymph node metastasis were similar between both groups. Twenty-one percent of the PTMC tumors were discovered incidentally. Patients with conventional PTC were significantly more likely to undergo treatment with radioactive iodine therapy compared to PTMC patients (86.4% vs. 66.7%, respectively, p < 0.003). Disease recurrence was observed in 40 patients and was not statistically different between the two groups; 11 (16.7%) in PTMC and 29 (21.3%) in conventional PTC, p = 0.57. Within the PTMC group, tumors of patients that recurred were significantly larger than those who remained disease free (8.1 mm vs. 6.4 mm, p < 0.05). None of the patients with incidental PTMC had disease recurrence. Angiolymphatic invasion was the only significant prognostic indicator of recurrence on multivariate analysis (p < 0.02). CONCLUSIONS: Nonincidental PTMC can have aggressive tumor features and disease recurrence similar to conventional PTC. These tumors should be managed like any other papillary thyroid malignancy.
Assuntos
Carcinoma Papilar/diagnóstico , Carcinoma/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Idoso , Carcinoma/classificação , Carcinoma/secundário , Carcinoma/terapia , Carcinoma Papilar/classificação , Carcinoma Papilar/secundário , Carcinoma Papilar/terapia , Diagnóstico Diferencial , Feminino , Humanos , Achados Incidentais , Radioisótopos do Iodo/uso terapêutico , Modelos Logísticos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia , Radioterapia Adjuvante , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Terminologia como Assunto , Neoplasias da Glândula Tireoide/classificação , Neoplasias da Glândula Tireoide/secundário , Neoplasias da Glândula Tireoide/terapia , Tireoidectomia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
We explored the structural basis of voltage sensing in the HCN1 hyperpolarization-activated cyclic nucleotide-gated cation channel by examining the relative orientation of the voltage sensor and pore domains. The opening of channels engineered to contain single cysteine residues at the extracellular ends of the voltage-sensing S4 (V246C) and pore-forming S5 (C303) domains is inhibited by formation of disulfide or cysteine:Cd(2+) bonds. As Cd(2+) coordination is promoted by depolarization, the S4-S5 interaction occurs preferentially in the closed state. The failure of oxidation to catalyze dimer formation, as assayed by Western blotting, indicates the V246C:C303 interaction occurs within a subunit. Intriguingly, a similar interaction has been observed in depolarization-activated Shaker voltage-dependent potassium (Kv) channels at depolarized potentials but such an intrasubunit interaction is inconsistent with the X-ray crystal structure of Kv1.2, wherein S4 approaches S5 of an adjacent subunit. These findings suggest channels of opposite voltage-sensing polarity adopt a conserved S4-S5 orientation in the depolarized state that is distinct from that trapped upon crystallization.