Effectiveness of the Dexamethasone Intravitreal Implant for Treatment of Patients with Diabetic Macular Oedema

Diabetic macular oedema (DMO) is a leading cause of vision loss in the working-age population worldwide. Corticosteroid drugs have been demonstrated to inhibit the expression of both the vascular endothelial growth factor (VEGF) gene and other anti-inflammatory mediators, such as prostaglandins. Triamcinolone, fluocinolone and dexamethasone are the main steroids that have been studied for the treatment of macular oedema. Over the last few years, several studies have suggested an important role for dexamethasone in the management of DMO. The dexamethasone intravitreal implant (DEX implant) (Ozurdex®; Allergan, Inc., Irvine, CA) is a novel approach approved by the US Food and Drug Administration (FDA) and by the EU for the intravitreal treatment of macular oedema after branch or central retinal vein occlusion, and for the treatment of non-infectious uveitis affecting the posterior segment of the eye. We reviewed manuscripts that had investigated the pharmacokinetics, efficacy and safety of the DEX implant regarding DMO treatment.

Continuous Infusion of Piperacillin/Tazobactam in Septic Critically Ill Patients - a Multicenter Propensity Matched Analysis

The clinical efficacy of continuous infusion of piperacillin/tazobactam in critically ill patients with microbiologically documented infections is currently unknown. We conducted a retrospective multicenter cohort study in 7 Portuguese intensive care units (ICU). We included 569 critically ill adult patients with a documented infection and treated with piperacillin/tazobactam admitted to one of the participating ICU between 2006 and 2010. We successfully matched 173 pairs of patients according to whether they received continuous or conventional intermittent dosing of piperacillin/tazobactam, using a propensity score to adjust for confounding variables. The majority of patients received 16g/day of piperacillin plus 2g/day of tazobactam. The 28-day mortality rate was 28.3% in both groups (p = 1.0). The ICU and in-hospital mortality were also similar either in those receiving continuous infusion or intermittent dosing (23.7% vs. 20.2%, p = 0.512 and 41.6% vs. 40.5%, p = 0.913, respectively). In the subgroup of patients with a Simplified Acute Physiology Score (SAPS) II>42, the 28-day mortality rate was lower in the continuous infusion group (31.4% vs. 35.2%) although not reaching significance (p = 0.66). We concluded that the clinical efficacy of piperacillin/tazobactam in this heterogeneous group of critically ill patients infected with susceptible bacteria was independent of its mode of administration, either continuous infusion or intermittent dosing.

Bombas de Efluxo em Pseudomonas Aeruginosa. Importância Clínica na Terapêutica

As infecções severas causadas por Pseudomonas Aeruginosa têm assumido na última década um papel de destaque, dado tratar-se de um microrganismo de difícil erradicação e com elevada resistência intrínseca e adquirida. Em P. aeruginosa foram caracterizados sete sistemas de bombas de efluxo, os quais contribuem para o desenvolvimento de fenótipos de multiresistência às classes de antibióticos clinicamente mais relevantes. Dado que a terapêutica seleccionada pode actuar como indutora e originar eventos mutacionais que promovem a hiperexpressão das bombas de efluxo, o tratamento destas infecções constitui um grande desafio terapêutico e impõe um conhecimento actualizado desta temática. Esta revisão foi assim desenvolvida com o intuito de rever a contribuição da hiperexpressão dos sistemas de bombas de efluxo em P.aeruginosa, na multirresistência aos antibióticos. Pretendeu-se também avaliar a possibilidade da utilização destes sistemas como alvos terapêuticos de modo a restabelecer a susceptibilidade aos antibióticos disponíveis.

Tranexamic Acid for Major Spinal Surgery in Children. A Retrospective Study

Introduction: Paediatric patients who undergo posterior spinal fusion surgery to correct scoliosis often require multiple blood transfusions. Tranexamic acid is a synthetic antifibrinolytic drug that reduces transfusion requirements in scoliosis surgery (1),(2),(3). Methods: To evaluate the efficacy of prophylactic tranexamic acid (TA) (initial dose of 10mg/kg and infusion of 1mg.kg(-1).h(-1)) in reducing perioperative blood transfusion requirements, we reviewed patients files and compared the amount of blood lost and blood transfused in the perioperative period of 12 patients (54.5%) that received TA and 10 patients (45.5%) who did not received TA. T-Student test was applied. Results: The average difference of blood losses (2,67 +/- 6,06ml) and blood transfused (212,9 +/- 101,1ml) between the two groups was not statistically significant (p>0.05). No thrombotic complications were detected in either group. Discussion: Results of the current study showed that prophylactic low dose of TA did not have a significant effect in the management of intraoperative blood loss and transfusion requirements in children undergoing scoliosis surgery. It is important to emphasize that our study is retrospective and that the size of the sample is small. Further studies are needed to evaluate the efficacy and safety of TA on paediatric scoliosis surgery.

Effects of a Shortage of Imiglucerase on Three Patients with Type I Gaucher Disease

Background: Children with Gaucher disease type I (GD1) are usually treated with enzyme replacement therapy (ERT) at a dose of 30-60U/Kg/2W. Recently, due to an acute shortage supply of imiglucerase, a reduced dose or a reduced infusion frequency was recommended. Objective: To evaluate the effects of a reduced infusion frequency of imiglucerase over 15 months of follow-up. Patients and Methods: Three patients (1M:2F) were treated with ERT since a median age of 7 years (range 5-12). Only one had bone crisis and Erlenmeyer deformations. Median duration of treatment before dose reduction was 3 years (range 1-8). ERT resulted in total regression of symptoms, normalization of hematological parameters and progressive improvement of chitotriosidase in all patients. In August 2009 infusion schedule was changed from a media 45U/Kg every two weeks to every four weeks. Results: All patients remained asymptomatic and with no major change on hematological parameters except for the patient with bone crisis who presented subnormal platelet count. All patients showed an upward trend in chitotriosidase values. Comments: Although a longer follow-up is needed, is probable that even children completely stabilized can probably not be kept on lower doses even though the reduction of frequency of the infusions represent a lower social burden.

Anestesia para a Distrofia Muscular Oculo-Faríngea: a Propósito de um Caso Clínico

A importância deste caso clínico particular prende-se com o facto da distrofia muscular oculo-faríngea ser uma forma rara de distrofia muscular com importantes implicações anestésicas. Doente de 64 anos com manifestações de distrofia muscular oculo-faríngea desde 1994, proposto para parotidectomia esquerda sob anestesia geral. Na avaliação pré-operatória evidência de ptose bilateral e envolvimento dos músculos esqueléticos proximais das extremidades ao exame neurológico. Foi programado para o primeiro tempo da sala operatória e foram tomadas todas as precauções inerentes ao alto risco para hipertermia maligna. Foi realizada uma indução de sequência rápida com propofol por TCI (target controlled infusion), perfusão contínua de remifentanil e uma dose de 0,9 mg/kg de rocurónio por via endovenosa com intubação endotraqueal sem intercorrências. Manutenção anestésica com anestesia endovenosa total. A propósito deste doente fomos rever as implicações e cuidados anestésicos a ter neste tipo de distrofia muscular pouco referida na literatura anestésica com apenas um artigo de há 15 anos descrevendo a sua abordagem anestésica.

Transplantation in Highly Sensitised Patients Treated with Intravenous Immunoglobulin and Rituximab

Renal transplant in highly sensitised patients is associated with increased morbidity. The aim of this retrospective study was to evaluate the clinical evolution of 30 highly sensitised deceased donor kidney transplants and the influence of different timing of B cell directed treatment and its importance in the outcome of these patients. All recipients had negative complement dependent lymphocytotoxicity cytotoxic T cell crossmatch and no identified anti human leucocyte antigen class I donor specific antibodies. T cell flow crossmatch was performed within 24h of transplantation with serum obtained pretransplant (historic, recent or baseline). Posttransplant flow crossmatch were performed prospectively starting on the 3rd posttransplantation day. The immunosuppressive regime included thymoglobulin, tacrolimus, mycofenolate mofetil and steroids. Positive flow crossmatch occurred in 20/29 patients by the 3rd posttransplantation day, and in 17/27 patients after the 3rd posttransplantation day. All patients were started on intravenous immunoglobulin before transplantation: in nine patients (group A) at 400mg/kg/day for five days; in the remaining 21 patients (group B), as a continued infusion of 2g/kg during 48h. In group A, Rituximab was added only in the presence of antibody mediated rejection; in group B, introduced on the 3rd posttransplantation day whenever a positive flow crossmatch (with serum obtained pre or posttransplant) was reported. Antibody mediated rejection was observed in 44.4% of patients in group A, and 19% of those in group B. Mean follow-up was 12.2±5.5 months. Overall allograft survival was 76.6%, 81% in group B, and 66.6% in group A. At last follow up, mean serum creatinine was 1.3±0.6 mg/dl. Renal transplantation with pretransplant positive flow crossmatch is highly associated with antibody mediated rejection, despite introduction of intravenous immunoglobulin pretransplantation. However high dose intravenous immunoglobulin for 48h plus Rituximab by the 3rd posttransplantation day reduce the incidence of antibody mediated rejection by more than 50% and allowed for allograft survival of 81% at one year, with an excellent renal function.

Monitorização à Distância no Seguimento de Portadores de Dispositivos Cardíacos Implantados

O aumento significativo registado nas implantações de dispositivos cardíacos, sobretudo como consequência dos benefícios demonstrados com a utilização de cardioversoresdesfibrilhadores e sistemas de ressincronização cardíaca na redução da mortalidade, trouxe para a prática clínica hospitalar o problema da gestão de recursos para responder ao crescimento exponencial do número de doentes em consultas regulares de seguimento especializado. A era das tecnologias da comunicação permitiu desenvolver sistemas de monitorização à distância, que são hoje uma realidade em franca expansão na Europa e nos Estados Unidos, com diversas vantagens e níveis de eficácia e segurança bem documentados. A sua utilização tem permitido obter um elevado grau de satisfação para o doente e médico, reduzindo o número de visitas hospitalares e os custos inerentes ao seguimento desta população. Os resultados dos diferentes estudos têm mostrado elevada capacidade na deteção mais precoce de problemas clínicos, arrítmicos ou de descompensação da insuficiência cardíaca, e de anomalias no funcionamento do dispositivo implantado. Apesar da experiência favorável com o recurso a esta metodologia de follow-up, são necessários estudos para avaliar o seu impacto clínico a longo prazo, em comparação com as consultas convencionais, bem como a introdução e adaptação da legislação referente a este tipo de evolução tecnológica aplicada à saúde. No presente artigo, revimos os aspetos técnicos e a evidência recente da relevância clínica da monitorização à distância em portadores de dispositivos cardíacos implantados.

Anti-Tumor Necrosis Factor Alpha-Induced Drug Eruptions: One Patient, More Than a Pattern

Background: Tumor necrosis factor alpha (TNFα) antagonists are effective in treating several immune-inflammatory diseases, including psoriasis and inflammatory bowel disease. The paradoxical and unpredictable induction of psoriasis and psoriasiform skin lesions is a recognized adverse event, although of unclear aetiology. However, histological analysis of these eruptions remains insufficient, yet suggesting that some might constitute a new pattern of adverse drug reaction, rather than true psoriasis. Case report: The authors report the case of a 43-year-old woman with severe recalcitrant Crohn disease who started treatment with infliximab. There was also a personal history of mild plaque psoriasis without clinical expression for the past eight years. She developed a heterogeneous cutaneous eruption of psoriasiform morphology with pustules and crusts after the third infliximab infusion. The histopathological diagnosis was of a Sweet-like dermatosis. The patient was successfully treated with cyclosporine in association with both topical corticosteroid and vitamin D3 analogue. Three weeks after switching to adalimumab a new psoriasiform eruption was observed, histologically compatible with a psoriasiform drug eruption. Despite this, and considering the beneficial effect on the inflammatory bowel disease, it was decided to maintain treatment with adalimumab and to treat through with topicals, with progressive control of skin disease. Discussion: Not much is known about the pathogenesis of psoriasiform eruptions induced by biological therapies, but genetic predisposition and Koebner phenomenon may contribute to it. Histopathology can add new facets to the comprehension of psoriasiform reactions. In fact, histopathologic patterns of such skin lesions appear to be varied, in a clear asymmetry with clinical findings. Conclusion: The sequential identification in the same patient of two clinical and histopathologic patterns of drug reaction to TNFα antagonists is rare. Additionally, to the authors’ knowledge, there is only one other description in literature of a TNFα antagonist-induced Sweet-like dermatosis, emphasizing the singularity of this case report.

National Registry on Cardiac Electrophysiology (2012)

Based on a survey sent to Portuguese centers that perform diagnostic and interventional electrophysiology and/or implantable cardioverter-defibrillator (ICD) implantations, the authors analyze the number and type of procedures performed during 2012 and compare these data with previous years. In 2012, a total of 2561 diagnostic electrophysiologic studies were performed, which were followed by ablation in 2017 cases, representing a steady situation compared with the previous year. There was a 12% increase in the number of ablation procedures for atrial fibrillation, making it for the first time the most frequent indication for ablation, overtaking atrioventricular nodal reentrant tachycardia. The total number of first ICD implantations was 1048 (around 100 per million population), of which 375 were cardiac resynchronization devices (BiV ICDs). This represents a slight decrease (3.3%) in the total number of new implants, with an increase of 10% in the number of BiV ICDs compared to the previous year. However, there was a considerable increase in the number of ICD generator replacements, resulting in an overall increase of 3.5% in implantations performed in 2012. Some comments are made regarding developments in this activity and its current status, and on some factors that may influence the dynamics of this area of interventional cardiology.

Short QT Syndrome Presenting As Syncope: How Short Is Too Short?

We report the case of a 52-year-old man who presented to our emergency department (ED) after three episodes of syncope in the seven hours before admission. During his stay in the ED he had recurrent ventricular tachycardia (VT) requiring external electrical cardioversion. A 12-lead electrocardiogram (ECG) showed a short QT (SQT) interval (270 ms, QTc 327 ms), with frequent R-on-T extrasystoles triggering sustained polymorphic VT. After exclusion of other precipitating causes, the patient was diagnosed as having SQT syndrome (SQTS) according to the Gollob criteria. To our knowledge, this is the first known documentation of an SQT-caused arrhythmic episode on a 12-lead ECG, as well as the first reported case of SQTS in Portugal. The patient received an implantable cardioverter-defibrillator and was discharged. At a follow-up assessment 14 months later he was symptom-free, interrogation of the device showed no arrhythmic events, and the ECG showed a QT interval of 320 ms (QTc 347 ms).

Intracoronary Delivery of Human Mesenchymal/Stromal Stem Cells: Insights from Coronary Microcirculation Invasive Assessment in a Swine Model

BACKGROUND: Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status. OBJECTIVES: To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance. METHODS: Healthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups. RESULTS: CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted. CONCLUSION: Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.