Total Aortic Arch Replacement With E-Vita OPEN PLUS Hybrid Prosthesis - Initial Experience From A Single Surgical Center.

We report a rare case of an advanced stage thymoma with right superior pulmonary lobe, superior vena cava, innominate vein and pericardium invasion in a patient with Good's syndrome. In a multidisciplinary discussion, surgical resection was deemed the best initial approach, since invaded structures could be safely managed. The tumor was fully resected and included partial resection of the superior pulmonary lobe, superior vena cava and innominate vein. The encircled right phrenic nerve was dissected from the tumor and preserved. The superior vena cava and innominate vein were reconstructed using autologous pericardium patch. Immunoglobulin replacement and radiotherapy were initiated afterwards. No signs of relapse at 6 months follow-up. In such advanced cases, aggressive surgical intervention should be considered as first line of treatment, as long as full resection can be anticipated, since complete resection is the leading factor for long-term prognosis.

[A retrospective study on the quality of life of patients with primary focal hyperhidrosis that underwent a video-assisted thoracoscopic sympathectomy]. / Avaliação do Impacto na Qualidade de Vida de Pacientes Diagnosticados com Hiperdrose Primária Submetidos a Simpaticectomia Torácica por Vídeo-Toracoscopia.

Backgroud: Primary focal hyperhidrosis affects between 1 to 4% of the general population, with a higher prevalence in teenagers and young adults. The condition is characterized by excessive sweating in 1 or more body part, most often the palms, face, armpits and soles. This condition causes a significant negative impact on patient's quality of life. The pathophysiology of focal hyperhidrosis is believed to be due to excessive sympathetic stimulation, and videothoracoscopic sympathectomy is a recognized form of treatment. The aim of this study is to evaluate the post-operative quality of life of patients who underwent thoracoscopic sympathectomy. MATERIALS AND METHODS: This is a retrospective study of fifty-four patients with primary focal hyperhidrosis submitted to bilateral thoracoscopic thoracic sympathectomy at the Center of Cardiothoracic Surgery of Casa de Saúde da Boavista, between January 2011 and December 2014. The Quality of Life questionnaire and the Hyperhidrosis Severity Scale questionnaire were used to evaluate the quality of life in the pre-operative period and 3 months after surgery. Further to this, data was collected regarding medium-term follow-up by telephone. All patients underwent general anesthesia and had bilateral video-assisted thoracoscopic resection of the sympathetic chain. RESULTS: The majority of patients are females 59.3% (32). The mean age is 30.8 ± 7.70 (between 16 and 49 years). Prior to surgery, 85% of the patients had severe hyperhidrosis. 79.6% of respondents stated that general discomfort was promoted by the condition, with the Funcional-Social domain being the most affected aspect of their life (61.1%). The rates of peri-operative complications and major post-operative complications were null, and minor complications were 5.5%. After 3 months, improvement in patient's quality of life and satisfaction level were of 100% and 96.3% respectively, however compensatory hyperhidrosis was observed in 53.7% of patients. 57.3% of the patients reported significant improvements in the Funcional-Social domain. Medium-term follow-up (mean=6 years) allowed for the evaluation of 31 patients (57.4% of the population), of whom 77.4% maintained compensatory hyperhidrosis. 93.5% reported to be highly satisfied with the surgical results and claimed to have improved their quality of life by 93.5%. 94% and 94.4% respectively of the patients evaluated in the medium term follow-up and after 3 months and in the medium term follow-up, recommend the surgery. CONCLUSION: Sympathectomy by video-assisted thoracoscopic surgery (VATS) is an effective and viable therapeutic option for primary focal hyperhidrosis patients. Despite compensatory hyperhidrosis being observed at time, this procedure produces very satisfactory results particularly in regard to the patient's post-operative quality of life.

Introdução: A Hiperidose Focal Primária afeta entre 1 a 4% da população, principalmente adolescentes e jovens- -adultos. É um distúrbio secundário a um excesso de estimulação simpática caracterizado por sudorese excessiva que pode envolver as mãos, a face, as axilas e os pés, representando um importante impacto negativo na qualidade de vida dos pacientes. A simpaticectomia vídeotoracoscópica é uma forma reconhecida de tratamento desta patologia. Este estudo tem como principal objetivo avaliar a qualidade de vida pós-cirúrgica dos pacientes submetidos a simpaticectomia por cirurgia toracoscópica videoassistida. Material e Métodos: Estudo retrospetivo de cinquenta e quatro pacientes com hiperidrose focal primária submetidos a simpaticectomia torácica por videotoracoscopia bilateral, na Clínica de Cirurgia Cardiotorácica da Casa de Saúde da Boavista, entre Janeiro de 2011 e Dezembro de 2014. Foram utilizados o questionário Quality of Life e a Hiperhidrosis Severity Scale na avaliação da qualidade de vida no pré-operatório e nos 3 meses após a cirurgia, bem como, a recolha de dados via telefónica num follow up a médio prazo. Todos os pacientes foram submetidos a anestesia geral e a técnica cirúrgica usada foi a secção da cadeia simpática bilateralmente por cirurgia vídeo-toracoscópica. Resultados: A maioria dos pacientes é do sexo feminino 59,2% (32). A idade média de idades é de 30,8 ± 7,70 (entre 16 e 49 anos). Antes da cirurgia, 85% dos pacientes apresentavam hiperidrose severa. O grau de desconforto geral promovido pela hiperidrose é de 79,6% sendo o domínio mais afetado o Funcional-Social (61,1%). Não houve complicações perioperatórias e pós-operatórias major. A taxa de complicações minor foi de 5,5%. Após 3 meses, obteve- -se um índice geral de 100% de melhoria na qualidade de vida dos pacientes e um grau de satisfação positivo de 96,3% apesar do aparecimento de hiperhidrose compensatória em 57,3% dos pacientes. O Domínio que apresentou melhorias significativas foi o Funcional-Social, em 55,5% dos pacientes. O follow up a médio prazo (média de 6 anos) permitiu avaliar 31 pacientes (57,4% da população) dos quais 77,4% mantém hiperhidrose compensatória. 93,5% Refere satisfação elevada com o resultado cirúrgico tendo melhorado a sua qualidade de vida em 93,5%. Dos pacientes avaliados no follow up a 3 meses e a médio prazo, 94,4% e 94,0% recomendam a cirurgia, respetivamente. Conclusão: A simpaticectomia por cirurgia toracoscópica videoassistida é uma opção terapêutica eficaz e viável da hiperidrose focal primária. Apesar da incidência de hiperidrose compensatória, é um procedimento bastante satisfatório no que respeita à qualidade de vida da grande maioria dos pacientes submetidos a este tipo de cirurgia.

Correction of adult-type VSD causing aortic valve endocarditis through aortotomy.

Ventricular septal defects are the most common congenital abnormality diagnosed in children but account for only 10 percent of congenital heart defects in adults. Although many defects close spontaneously before adulthood, many others persist, predisposing to endocarditis, and other complications. Herein, we report a case of a known, asymptomatic, perimembranous ventricular septal defects that has complicated at 53 years of age with the need for surgery due to native aortic valve endocarditis and concomitant severe aortic regurgitation. We opted to surgically repair the ventricular septal defects with a pericardial patch through the necessary aortotomy used for aortic valve replacement (Figure 1 and 2). The surgery was straightforward. Postoperative course was only marked by the need of a permanent pacemaker implantation due to a sick sinus syndrome, which was diagnosed before the surgery. Thus, we emphasize the role of surgery in repairing ventricular septal defects and the importance of choosing the appropriate approach, especially when concomitant heart lesions are present.

As comunicações interventriculares são a lesão congénita mais comummente diagnosticada em idade pediátrica mas representam apenas 10% dos defeitos cardíacos congénitos em idade adulta. Apesar da maioria das comunicações interventriculares encerrarem espontaneamente antes da idade adulta, muitas persistem predispondo a endocardite e outras complicações. Apresentamos um caso de comunicação interventricular perimembranosa assintomática até à idade adulta, que complicou aos 53 anos com endocardite da válvula aórtica nativa associada a regurgitação aórtica severa, necessitando, por isso, de correção cirúrgica. Optamos pela correção cirúrgica implantando um retalho de pericárdio heterólogo através da aortotomia necessária para a substituição valvular aórtica (Figure 1 and 2). A cirurgia decorreu sem intercorrências. De referir apenas, no pós-operatório, a necessidade de implantação de um pacemaker permanente dado existência prévia de doença do nó sinusal. É de salientar a importância do papel da cirurgia na correção de comunicações interventriculares e a necessidade de escolher a abordagem cirúrgica mais apropriada, especialmente, quando existem lesões cardíacas concomitantes.

Improvement in left intraventricular pressure gradients after aortic valve replacement in aortic stenosis patients.

NEW FINDINGS: What is the central question of this study? Normal diastolic and systolic intraventricular pressure gradients are decreased when left ventricular filling and/or emptying are compromised. We hypothesized that in patients with severe aortic valve stenosis, a condition that interferes with ventricular filling and emptying, those gradients would be disturbed. What is the main finding and its importance? We showed the existence of intraventricular pressure gradients throughout the cardiac cycle in the human left ventricle. Moreover, we demonstrated, for the first time, that diastolic and systolic gradients, which are markers of normal ventricular filling and emptying, respectively, improved in patients with severe aortic valve stenosis immediately after valve replacement. The present study was conducted to characterize left intraventicular pressure gradients, which are markers of normal cardiac function, in patients with severe aortic stenosis, a condition that interferes with ventricular filling and emptying. In 10 patients (four male; mean age 71.3 ± 4.8 years old) undergoing aortic valve replacement, two high-fidelity pressure catheters were inserted inside the cavity of the left ventricle through an apical puncture and positioned in the apex and outflow tract below the aortic valve. Pressures were continuously acquired and gradients calculated as apical minus outflow tract pressure, before and immediately after aortic valve replacement. During early filling, we recorded a negative intraventricular gradient along the basal portion of the left ventricle in the apical direction (-0.82 ± 0.45 mmHg), which increased to -3.97 ± 0.42 mmHg after aortic valve replacement. In late filling, intraventricular flow was now directed towards the outflow tract, with a positive pressure gradient both before (+1.23 ± 0.37 mmHg) and after surgery (+2.12 ± 0.58 mmHg). During systole, before surgery we observed a positive pressure gradient between the apex and outflow tract during both rapid (+1.60 ± 0.21 mmHg) and slow ejection phases (+1.68 ± 0.12 mmHg), whereas after aortic valve replacement the positive gradient (+1.54 ± 0.15 mmHg) during rapid ejection was inverted (-3.92 ± 0.34 mmHg) during the slow ejection phase. We demonstrated that in patients with severe aortic stenosis both diastolic and systolic intraventricular pressure gradients are significantly attenuated but can be restored immediately after aortic valve replacement. The assessment and measurement of intraventricular pressure gradients and their modulation in pathophysiological conditions may provide novel insights into cardiac physiology.

[Leadership. A challenge for success!] / Liderança. Um desafio para o sucesso!

Leadership is now-a-days recognized as the essential and indispensable support for the success of an organization, whatever it may be. Motivate and manage a group with a certain objective, can be interpreted as the art of leading people and how to lead them to achieve successful results in a natural, driven and motivated way. Leadership efficiency depends on the leader and must be started by defining a goal, selecting a group of stakeholders, guiding them, recognizing each one´s way of doing things, evaluating individual skills and obtain a target of excellence. The elements that make up a group are not usually and always selected by who will manage them and this can transform the role of a leader in a constant and appealing experience. The challenge is to explore and analyse the various problems, to focus on the goal by jointly assessing it, to recognize individual capacities and skills and to plan, negotiate and apply everything that can contribute to the success.

A liderança é hoje reconhecida como o suporte essencial e imprescindível para o sucesso de uma organização, seja ela qual for. Liderar pode ser interpretado como a arte de conduzir pessoas e o modo de as levar a alcançar resultados com êxito de uma forma natural, dirigida e motivada. A eficiência da liderança depende do líder e deve ser iniciada com a definição de um objetivo, passar pela seleção de um grupo de intervenientes, pela sua orientação, pelo reconhecimento do modo de fazer de cada um, pela avaliação das competências individuais e orientar de forma a somar resultados de excelência. Os elementos que constituem o grupo a liderar não são habitualmente selecionados por quem os vai dirigir e isso pode transformar o papel de líder num desafio constante e aliciante. O desafio passa por saber explorar e analisar os diversos problemas, focalizar o objetivo avaliando em conjunto o que é pretendido, saber reconhecer as capacidades e competências individuais e planear, negociar e implementar as diversas competências individuais que possam contribuir para o sucesso.

Rapid Pacing for Thoracic Endovascular Aortic Repair: a Case Report.

INTRODUCTION: Endovascular aortic interventions are suitable alternatives to open surgery, being less invasive and having lower mortality and complications. Accurate positioning of the stent graft is a critical point because of systolic thrush. Techniques used to prevent it include pharmacological (antihypertensive drugs, nitroglycerin, adenosine) and mechanical methods (temporary caval occlusion by balloon). Rapid Right Ventricular Pacing (RRVP) is an emerging alternative with good patient tolerance and low level of complications. METHODS: A 79 years-old male, American Society of Anaesthesiology (ASA) status 3 (hypertension, chronic obstructive pulmonary disease and hyperuricemia), with an aortic arch aneurysm previously submitted to an ascendant aortic debranching, was proposed for Thoracic Endovascular Aortic Repair (TEVAR). ASA standard, invasive blood pressure, depth of anaesthesia and cerebral oximetry monitoring were used. RESULTS: Patient was sedo-analgesiated with Midazolam 2mg and Fentanyl 100mcg. A flow directed Pacing catheter was passed through an 8.5FR introducer inserted in right internal jugular vein. RRVP was tested to a cardiac frequency of 180 without patient complaint. Two vascular Valiant Thoracic endoprosthesis were placed through a femoral access. At the time of testing position and prothesis deployment, RRVP was started and systolic blood pressure dropped to 50mmHg. After stopping the RRVP in both placements, normal rhythm and blood pressure were observed. No relevant changes in cerebral monitoring were found. Final angiography showed no endoleak of prosthesis. The patient was admitted at Post- -Anaesthetic Care Unit and discharged after 24hours. CONCLUSION: RRVP results in accelerated heart rate, with consequent decrease of intra-aortic blood flow, allowing more precise graft deployment without displacement, which is associated with lower incidence of endoleak. The faster onset of RRVP and rapid return to normal values can shorten the duration of the procedure. The procedure is done with minimal sedation, important in individuals with poor clinical status. This also allows to continually monitor the patient's neurologic status, possibly detecting any prosthetic displacement or acute event. Most complications are puncture- related. Rhythm-associated complications can occur in patients with heart diseases. In this case, no cardiac events were found. RRVP has been used in TEVAR with reliable results and is a good option for difficult cases. It's associated with a lower incidence of complications and less secondary effects than traditional measures, allowing to maintain patients with mild sedation, shortening hospital's length of stay. RRVP seems to be advantageous over traditional methods of controlling blood pressure in patients submitted to TEVAR.

Analgesia Management for Mitral Valve Repair Via Minithoracotomy - A Case Report.

INTRODUCTION: Minimally invasive cardiac surgery (MICS), via minithoracotomy, is thought to be a fast track to extubation and recovery after surgery. Chronic pain, due to intercostal nerve injury, develops in up to 50% of postthoracotomy patients.A number of regional anaesthesia and analgesia techniques may be employed, and the anaesthesiologists play a key role in facilitating optimal outcomes after surgery. METHODS: We report a case of postoperative pain management with a local anesthetic infiltration for MICS. RESULTS: A 63-year-old woman, 80kg, American Society Anaesthesiology (ASA) physical status 3 [arterial hypertension, atrial fibrillation (AF), rheumatic mitral stenosis and class II NYHA heart failure] was presented for an elective minimally invasive mitral valve repair through a minithoracotomy and cryoablation of AF. No relevant facts were found on pre-operative evaluation. Calculated EuroScore II was 1.55%. After premedication with intravenous (IV) midazolam 1.5mg, radial arterial and jugular central venous catether were placed. General anaesthesia was induced with IV remifentanil 1mcg/kg/h, propofol 50mg, rocuronium 1mg/ kg. A transesophageal echocardiography probe was inserted atraumatically, which revealed thickened mitral valve leaflets. ASA standard, invasive blood pressure, central venous pressure, depth of anaesthesia and cerebral oximetry monitoring were used. Urine output and arterial blood gas were measured periodically. A right lateral minithoracotomy was performed. After cardiopulmonary bypass (CPB) by femoral cannulation, cryoablation was performed followed by placement of the mechanical prosthesis. Total bypass time was 186min including 139min aortic cross-clamping time. At the ending of CPB, there was no need for inotropic support. Analgesia with paracetamol 1g, tramadol 100mg and morphine 10mg was performed after protamine reversion. Immediately before closure of skin, catheter was placed nearly to intercostal space (figures 1, 2) and ropivacaine 0,75% 75mg was administered. Anaesthesia and surgery were uneventful. Patient was shifted to intensive care unit (ICU), being extubated 3 hours after surgery. There was no need for additional bolus of ropivacaine during 2 days of ICU stay. She was discharged home on the 4th postoperative day, without complications. In a telephone interview 3 weeks after surgery, the patient referred no pain and good satisfaction with analgesia management. CONCLUSION: Thoracotomy incisions are associated with severe pain, leading to a decrease in pulmonary function, an increase in metabolic and hormonal activity and increased cardiac morbidity. Regional analgesia techniques have an opioid-sparing effect, reducing stress response and pain chronification. The local infiltration through catheter with local anaesthetics allows excellent analgesia for 8-12 hours, providing a route of additional analgesia according to pain control.

Mid-term outcomes of mitral valve repair in a low-volume hospital.

INTRODUCTION: Mitral valve repair is feasible for all patients with mitral regurgitation and its advantages are well documented; however, there is general agreement that it is technically demanding and that success rates are related to volume/ experience centers. The aim of this study was to evaluate the clinical and echocardiographic mid-term outcomes of patients who underwent a mitral repair in a low-volume hospital. METHODS AND RESULTS: Between 2009 and 2014, 55 patients (23 female) with mitral regurgitation underwent mitral repair. The mean age was 60.7±11.4 years (range, 21-81 yr). The most prevalent cardiovascular risk factors were: hypertension 61.8%, dyslipidemia 47.3% and diabetes 21.8%. Nine patients (16.4%) were in class III-IV of NYHA and ten (18.2%) had atrial fibrillation. Repair procedures included mitral ring annuloplasty (n=55), quadrangular resection (n=20), chordal replacement (n=13) and commissuroplasty (n=5). Postoperative complications included atrial fibrillation 16.4%, check bleeding 3.6%, wound infection 1.8% and renal failure 1.8%. The hospital mortality rate was 1.8%. Follow-up echocardiography (median 19±5 months) revealed trivial or no mitral regurgitation in 38.2%, mild (1+) in 34.5% and severe (3+) only in 3 patients. CONCLUSION: In the current era, patients undergoing successful mitral valve repair have low mortality and morbidity even in low-volume hospitals.

Botanical-drug interactions: a scientific perspective.

There is a continued predisposition of concurrent use of drugs and botanical products. A general lack of knowledge of the interaction potential together with an under-reporting of botanical use poses a challenge for the health care providers and a safety concern for patients. Botanical-drug interactions increase the patient risk, especially with regard to drugs with a narrow therapeutic index (e.g., warfarin, cyclosporine, and digoxin). Examples of case reports and clinical studies evaluating botanical-drug interactions of commonly used botanicals in the US are presented. The potential pharmacokinetic and pharmacodynamic bases of such interactions are discussed, as well as the challenges associated with the interpretation of the available data and prediction of botanical-drug interactions. Recent FDA experiences with botanical products and interactions including labeling implications as a risk management strategy are highlighted.

[Cardiac papillary fibroelastoma of the mitral valve. Case report]. / Fibroelastoma papilar cardíaco da válvula mitral. Caso clínico.

Cardiac papillary fibroelastomas (CPF) are rare primary cardiac tumors with predilection for heart valves, being increasingly incidentally discovered due to the widespread use of echocardiography. Most of them are asymptomatic, but they are a potential source of systemic emboli, stroke, myocardial infarction and sudden death. This report describes the case of a 70-year-old female with previous transient ischaemic attacks and an echocardiographic finding of a mass in the mitral valve. Surgery was performed with complete resection of the tumor and preservation of the mitral valve. Pathological evaluation confirmed the diagnosis of cardiac papillary fibroelastoma.

Plasmonic Metal Nanoparticles Hybridized with 2D Nanomaterials for SERS Detection: A Review.

In SERS analysis, the specificity of molecular fingerprints is combined with potential single-molecule sensitivity so that is an attractive tool to detect molecules in trace amounts. Although several substrates have been widely used from early on, there are still some problems such as the difficulties to bind some molecules to the substrate. With the development of nanotechnology, an increasing interest has been focused on plasmonic metal nanoparticles hybridized with (2D) nanomaterials due to their unique properties. More frequently, the excellent properties of the hybrids compounds have been used to improve the drawbacks of the SERS platforms in order to create a system with outstanding properties. In this review, the physics and working principles of SERS will be provided along with the properties of differently shaped metal nanoparticles. After that, an overview on how the hybrid compounds can be engineered to obtain the SERS platform with unique properties will be given.

[Mitral valve replacement in patiens with previous right pneumonectomy]. / Subtituição da válvula mitral em doentes com pneumectomia direita prévia.

Adequate exposure of the mitral valve is essential to the safe and effective performance of valve replacement. After a right pneumonectomy, shift of the mediastinum and reduction in respiratory function makes cardiac surgery challenging not only for the surgeon but also for the anaesthetist. We report our experience on performing mitral valve replacement in two patients with previous right pneumonectomy to highlight certain important features while managing these patients.

[Coronary surgery in high risk patients]. / Cirurgia coronária em doentes de alto risco.

Increasing longevity, better standard of care and new developments in different fields of knowledge as in cardiac medical therapy or interventional cardiology has lead to an increasing number of patients with complex coronary disease and severe comorbidity requiring cardiac surgery. Performing coronary bypass grafting surgery in very sick patients has become a daily challenge for anaesthesiologists and cardiac surgeons. Many of these patients are in risk for a catastrophic peri-operative course, with extensive use of medical resources, and deceiving results. Decision on when to operate a patient, choice of the appropriate operation and perioperative management are of critical importance. Risk calculation is a key stone in the decision process, it allows identify high risk patients, predict their outcome, choose the best therapy based on available evidence and of resources.

Acute Myocardial Infarction with Non-Obstructive Coronary Arteries - Stratifying the Risk of a "new" Clinical Entity using an "Old" Tool

Abstract Background Some of the patients admitted for acute myocardial infarction have non-obstructive coronary artery disease (MINOCA). Their prognosis is not always benign, making it necessary the development of tools for risk stratification of these patients. Objectives To describe the characteristics of a sample of patients admitted for suspected MINOCA and to evaluate the prognostic value of GRACE score in this population. Methods This was a retrospective, observational, single-center, cohort study involving 56 consecutive patients with MINOCA. During one-year follow-up, patients were assessed for mortality and major adverse cardiovascular events (MACE) - a composite of all-cause mortality and hospitalization due to acute myocardial infarction, heart failure, ischemic stroke, and acute limb ischemia. Statistical analysis was performed using a non-parametric approach, with the Mann-Whitney U test for quantitative variables and ROC curves for assessing the discriminatory power of the Grace score in predicting cardiovascular events. The level of significance was set at 5%. Results Of the 56 MINOCA patients included in the study (median age 67 years), 55.4% were female. During the one-year follow-up, mortality rate was 5.5% and 9.1% of patients had MACE. A higher GRACE score was associated with mortality (p = 0.019; AUC 0.907; 95%CI 0.812-1.000; cut off 138) and MACE (p =0.034; AUC 0.790; 95%CI 0.632-0.948; cutoff 114). Conclusion The definition of MINOCA includes various diagnoses and prognoses, and the GRACE score is useful for risk stratification of patients with this condition.

Hepatobiliary transporters in drug-induced cholestasis: a perspective on the current identifying tools.

INTRODUCTION: Impaired bile formation leads to the accumulation of cytotoxic bile salts in hepatocytes and, consequently, cholestasis and severe liver disease. Knowledge of the role of hepatobiliary transporters, especially the bile salt export pump (BSEP), in the pathogenesis of cholestasis is continuously increasing. AREAS COVERED: This review provides an introduction into the role of these transport proteins in bile formation. It addresses the clinical relevance and pathophysiologic consequences of altered functions of these transporters by genetic mutations and drugs. In particular, the current practical aspects of identification and mitigation of drug candidates with liver liabilities employed during drug development, with an emphasis on preclinical screening for BSEP interaction, are discussed. EXPERT OPINION: Within the potential pathogenetic mechanisms of acquired cholestasis, the inhibition of BSEP by drugs is well established. Interference of a new compound with BSEP transport activity should raise a warning sign to conduct follow-up experiments and to monitor liver function during clinical development. A combination of in vitro screening for transport interaction, in silico predicting models, and consideration of physicochemical and metabolic properties should lead to a more efficient screening of potential liver liability.

Towards quantitation of the effects of renal impairment and probenecid inhibition on kidney uptake and efflux transporters, using physiologically based pharmacokinetic modelling and simulations.

BACKGROUND AND OBJECTIVES: The kidney is a major drug-eliminating organ. Renal impairment or concomitant use of transporter inhibitors may decrease active secretion and increase exposure to a drug that is a substrate of kidney secretory transporters. However, prediction of the effects of patient factors on kidney transporters remains challenging because of the multiplicity of transporters and the lack of understanding of their abundance and specificity. The objective of this study was to use physiologically based pharmacokinetic (PBPK) modelling to evaluate the effects of patient factors on kidney transporters. METHODS: Models for three renally cleared drugs (oseltamivir carboxylate, cidofovir and cefuroxime) were developed using a general PBPK platform, with the contributions of net basolateral uptake transport (T up,b) and apical efflux transport (T eff,a) being specifically defined. RESULTS AND CONCLUSION: We demonstrated the practical use of PBPK models to: (1) define transporter-mediated renal secretion, using plasma and urine data; (2) inform a change in the system-dependent parameter (≥10-fold reduction in the functional 'proximal tubule cells per gram kidney') in severe renal impairment that is responsible for the decreased secretory transport activities of test drugs; (3) derive an in vivo, plasma unbound inhibition constant of T up,b by probenecid (≤1 µM), based on observed drug interaction data; and (4) suggest a plausible mechanism of probenecid preferentially inhibiting T up,b in order to alleviate cidofovir-induced nephrotoxicity.

Age and years in practice as factors associated with needlestick and sharps injuries among health care workers in a Portuguese hospital.

Health care workers are attributed to the group at highest risk of occupationally acquired bloodborne diseases as the result of contact with blood and body fluids. A cross sectional study was conducted between November 2009 and February 2010 in the North of Portugal, to identify potential risk factors for needlestick and sharps injuries. A questionnaire was provided to 363 health care professionals. Logistic regression was used to identify risk factors associated to needlestick and sharps injuries, calculating odds ratio (OR) and their 95% confidence interval (CI). Sixty-five percent of health care workers (64.5%, 234/363) reported needlestick and sharps injuries in the previous 5 years. Of the injured workers, 74.8% were nurses. Of the total injuries reported, the commonest were from syringe needle unit. The multivariate logistic regression model showed that the strongest risk factor was having more than 10 years or more of work in health services (OR 3.37, 95% CI 1.82, 6.24). Another significantly related factor was being over 39 years-old (OR 1.94, 95% CI 1.03, 3.63). In Portugal, there is a lack of epidemiological evidence related to needlestick and sharps injuries. Considering that patients infected with hepatitis B and C virus are commonly encountered in the hospital environment and that the prevalence of HIV infection in Portugal is one of the highest in Europe, these results should be considered in the design of biosafety strategies at the Hospital Center.

Evaluation of exposure change of nonrenally eliminated drugs in patients with chronic kidney disease using physiologically based pharmacokinetic modeling and simulation.

Chronic kidney disease, or renal impairment (RI) can increase plasma levels for drugs that are primarily renally cleared and for some drugs whose renal elimination is not a major pathway. We constructed physiologically based pharmacokinetic (PBPK) models for 3 nonrenally eliminated drugs (sildenafil, repaglinide, and telithromycin). These models integrate drug-dependent parameters derived from in vitro, in silico, and in vivo data, and system-dependent parameters that are independent of the test drugs. Plasma pharmacokinetic profiles of test drugs were simulated in subjects with severe RI and normal renal function, respectively. The simulated versus observed areas under the concentration versus time curve changes (AUCR, severe RI/normal) were comparable for sildenafil (2.2 vs 2.0) and telithromycin (1.6 vs 1.9). For repaglinide, the initial, simulated AUCR was lower than that observed (1.2 vs 3.0). The underestimation was corrected once the estimated changes in transporter activity were incorporated into the model. The simulated AUCR values were confirmed using a static, clearance concept model. The PBPK models were further used to evaluate the changes in pharmacokinetic profiles of sildenafil metabolite by RI and of telithromycin by RI and co-administration with ketoconazole. The simulations demonstrate the utility and challenges of the PBPK approach in evaluating the pharmacokinetics of nonrenally cleared drugs in subjects with RI.

[Escherichia coli's endocarditis in a prosthetic aortic valve - diagnostic and therapeutic particularities]. / Endocardite por escherichia coli em válvula aórtica protésica - particularidades do diagnóstico e tratamento.

Escherichia coli endocarditis is a rare condition, even though bacteriemia by such agent is common. The infection, normally from a urinary origin, may, in fact, progress without major hemodynamic disturbance and minimal symptoms, regardless its ability of destruction of heart's valvular apparatus. We present a case report of a 68-year-old man, with a history of aortic valvular mechanic prosthesis, dyslipidemia and hypertension, admitted at the emergency room with refractory fever and urinary tract symptoms. On the hypothesis of endocarditis, he was submitted to transesofagic echocardiography that suggested a prosthetic vegetation, without hemodynamic dysfunction. E. coli was cultured from the blood soon after, and antibiotics adapted according to sensibility testing. Nevertheless, the patient deteriorated, both clinically and echocardiographically, with development of periprosthesis abscess, detachment of the prosthesis and extension of the infection to other valves, with hemodynamic dysfunction. The infection was only restrained with a surgical approach, which reflects the importance of this therapeutic weapon in these situations, including the correct timing.