Severe Isolated Thrombocytopenia After Clopidogrel and Pentoxifylline Therapy: a Case Report

INTRODUCTION: Clopidogrel is frequently associated with thrombotic thrombocytopenic purpura, however this drug is rarely related to severe isolated thrombocytopenia. Pentoxifylline has previously been associated with thrombocytopenia only once. To the best of our knowledge, this is the first report of severe isolated thrombocytopenia after therapy with both clopidogrel and pentoxyfilline. CASE PRESENTATION: We report the case of a 79-year-old Caucasian man who presented to our facility with intermittent claudication. He had obliterative arterial disease and started therapy with clopidogrel and pentoxifylline. His basal platelet count was 194 × 109 cells/L. At three days after the start of treatment, our patient had lower limb petechia and stopped taking clopidogrel and pentoxifylline. His platelet count lowered to 4 × 109 cells/L and our patient was admitted to hospital. Our patient had purpura with no other hemorrhages or splenomegaly. Results of a blood smear were normal, and a bone marrow study showed dysmegakaryopoiesis. Antiplatelet antibody test results were negative, as were all viral serology tests. Imaging study results were normal. Our patient was given immunoglobulin but there was no sustained platelet increase, so corticotherapy was started as the next treatment step. At five months after clopidogrel and pentoxifylline were discontinued, his platelet count continued increasing even after prednisolone was tapered. CONCLUSIONS: Severe isolated thrombocytopenia may appear as a side effect when using clopidogrel and pentoxifylline. These drugs are widely used by general physicians, internists, cardiologists and vascular surgeons. We hope this report will raise awareness of the need to monitor the platelet count in patients taking these drugs.

Mesenchymal Stem Cell Therapy in Heart Disease

Cardiovascular disease is among the main causes of mortality and morbidity worldwide. Despite significant advances in medical and interventional therapy, the prognosis of conditions such as ischemic heart disease is still dismal. There is thus a need to investigate new therapeutic tools, one of which is stem cell therapy. Hematopoietic stem cells are the most studied type, and the fact that their biology is relatively well understood has led to their being used in preclinical research and clinical trials. However, the results of some of these studies have been controversial, which has opened the way for studies on other cell types, such as mesenchymal stem cells. These cells have immunomodulatory properties which suggest that they have therapeutic potential in cardiology. In the present article, the authors review the state of the art regarding mesenchymal stem cells, from basic and translational research to their use in clinical trials on ischemic heart disease, heart failure and arrhythmias, and discuss possible future uses.

Inferior Vena Cava Filter Placement During Pregnancy: an Adjuvant Option When Medical Therapy Fails

The authors present a case of a 27-year-old multiparous woman, with multiple thrombophilia, whose pregnancy was complicated with deep venous thrombosis requiring placement of a vena cava filter. At 15th week of gestation, following an acute deep venous thrombosis of the right inferior limb, anticoagulant therapy with low-molecular-weight heparin (LMWH) was instituted without improvement in her clinical status. Subsequently, at 18 weeks of pregnancy, LMWH was switched to warfarin. At 30th week of gestation, the maintenance of high thrombotic risk was the premise for placement of an inferior vena cava filter for prophylaxis of pulmonary embolism during childbirth and postpartum. There were no complications and a vaginal delivery was accomplished at 37 weeks of gestation. Venal placement of inferior vena cava filters is an attractive option as prophylaxis for pulmonary embolism during pregnancy.

Zinc Therapy of Neurological Wilson's Disease in a Woman with Two Foetus with Agenesis of the Corpus Callosum

8A>C>86A G:EDGI: A patient diagnosed Wilson’s disease (WD) 22 years previously, successfully treated initially with zinc, developed neuropsychiatric disease after years of irregular therapy. Reassuming zinc therapy was successful. After a normal pregnancy, she had two therapeutic abortions for corpus callosum agenesis, and a missed abortion. We review the genetics, physiopathology, clinics and imagiologic response to zinc therapy, the problems of pregnancy in WD, advising to maintain therapy. A hypothetic cause for fetus brain anomaly would be hypocupremia due to zinc therapy, confronting with two other possibilities, one related to Wilson’s disease in itself, other due to a congenital syndrome of agenesis of the corpus callosum, impossible to diagnose by our available diagnostic methods.

Long-Term Evaluation of Recurrence after Photodynamic Therapy with Topical Methyl Aminolevulinate for Non-Melanoma Skin Cancer: a Hospital-Based Study

Introduction & Objectives: Several factors may influence the decision to pursue nonsurgical modalities for the treatment of non-melanoma skin cancer. Topical photodynamic therapy (PDT) is a non-invasive alternative treatment reported to have a high efficacy when using standardized protocols in Bowen’s disease (BD), superficial basal cell carcinoma (BCC) and in thin nodular BCC. However, long-term recurrence studies are lacking. The aim of this study was to evaluate the long-term efficacy of PDT with topical methylaminolevulinate (MAL) for the treatment of BD and BCC in a dermato-oncology department. Materials & Methods: All patients with the diagnosis of BD or BCC, treated with MAL-PDT from the years 2004 to 2008, were enrolled. Treatment protocol included two MAL-PDT sessions one week apart repeated at three months when incomplete response, using a red light dose of 37-40 J/cm2 and an exposure time of 8’20’’. Clinical records were retrospectively reviewed, and data regarding age, sex, tumour location, size, treatment outcomes and recurrence were registered. Descriptive analysis was performed using chi square tests, followed by survival analysis with the Kaplan-Meier and Cox regression models. Results: Sixty-eight patients (median age 71.0 years, P25;P75=30;92) with a total of 78 tumours (31 BD, 45 superficial BCC, 2 nodular BCC) and a median tumour size of 5 cm2 were treated. Overall, the median follow-up period was 43.5 months (P25;P75=0;100), and a total recurrence rate of 33.8% was observed (24.4 % for BCC vs. 45.2% for BD). Estimated recurrence rates for BCC and BD were 5.0% vs. 7.4% at 6 months, 23.4% vs. 27.9% at 12 months, and 30.0% vs. 72.4% at 60 months. Both age and diagnosis were independent prognostic factors for recurrence, with significantly higher estimated recurrence rates in patients with BD (p=0.0036) or younger than 58 years old (p=0.039). The risk of recurrence (hazard ratio) was 2.4 times higher in patients with BD compared to superficial BCC (95% CI:1.1-5.3; p=0.033), and 2.8 times higher in patients younger than 58 years old (95% CI:1.2-6.5; p=0.02). Conclusions: In the studied population, estimated recurrence rates are higher than those expected from available literature, possibly due to a longer follow-up period. To the authors’ knowledge there is only one other study with a similar follow-up period, regarding BCC solely. BD, as an in situ squamous cell carcinoma, has a higher tendency to recur than superficial BCC. Despite greater cosmesis, PDT might no be the best treatment option for young patients considering their higher risk of recurrence.

Vulvar Lichen Sclerosus: Efficacy of Photodynamic Therapy Under Conscious Sedation with Inhaled 50% Nitrous Oxide and Oxygen Mixture

Anogenital lichen sclerosus is a chronic, inflammatory, mucocutaneous disorder of significant morbidity. Common symptoms include pruritus, pain, dysuria, and dyspareunia, frequently of difficult control. Photodynamic therapy (PDT) may be an effective therapeutic option in selected cases refractory to first--‐line treatment options. However, procedure--‐related pain is a limiting factor in patient adherence to treatment. Conscious sedation and analgesia with a ready--‐to--‐use gas mixture of nitrous oxide and oxygen is useful in short--‐term procedures. It provides a rapid, effective, and short--‐lived effect, without the need for anesthesiology support. A 75--‐year--‐old woman presented with a highly symptomatic, histologically confirmed vulvar lichen sclerosus, with at least 15 years of evolution. Pain, pruritus, and dysuria were intense and disabling. Treatment with ultrapotent topical corticosteroids proved to be ineffective despite patient compliance. She was then referred for PDT. A total of 3 sessions were performed, held at a mean interval of 9 weeks, and under the analgesic and sedative effect of nitrous oxide/oxygen gas. Response to treatment was evaluated through a daily, self--‐reported pain rating scale. Dysuria remitted completely after the first PDT session. An 80% reduction in pruritus and pain was observed after the third session, and has been sustained for the past six months without further need for topical corticotherapy. Treatment sessions were well tolerated and pain-- free, with no side effects to report. PDT appears to be effective in the symptomatic treatment of vulvar lichen sclerosus. To the authors’ knowledge this is the first case reporting the use of inhaled nitrous oxide/oxygen gas mixture during PDT performed in the genital area. Its analgesic and sedative effects may increase patients’ adherence to this painful procedure. Furthermore, given its safety, it can be easily managed in outpatient clinics by trained dermatologists.

Renal Replacement Therapy in Critically Ill Patients - What Modality Should We Choose?

A lesão renal aguda é uma complicação comum nas unidades de cuidados intensivos. A mortalidade do doente crítico que requer diálise é extremamente elevada, apesar dos avanços significativos dos cuidados prestados a estes doentes. Há várias décadas que se discute o tipo de modalidade dialítica a oferecer a estes doentes (continua ou intermitente) e os principais fatores que pesam na decisão clínica são os meios e a experiência do centro, bem como a condição clínica do doente. Vários estudos tentaram estabelecer a melhor abordagem ao doente crítico com lesão renal aguda e necessidade dialítica, em termos de sobrevida do doente e recuperação renal. Nesta revisão tentarei resumir as evidências disponíveis sobre este tema.

Conscious Sedation with Inhaled 50% Nitrous Oxide/Oxygen Premix in Photodynamic Therapy Sessions for Vulvar Lichen Sclerosus Treatment

Photodynamic therapy has been described as an effective therapeutic option in selected cases of anogenital lichen sclerosus that are refractory to first-line treatments. However, procedure-related pain is a limiting factor in patient adherence to treatment. The authors report the case of a 75-year-old woman with highly symptomatic vulvar lichen sclerosus, successfully treated with photodynamic therapy. An inhaled 50% nitrous oxide/oxygen premix was administered during sessions, producing a pain-relieving, anxiolytic, and sedative effect without loss of consciousness. This ready-to-use gas mixture may be a well-tolerated and accepted alternative to classical anesthetics in Photodynamic therapy, facilitating patients' adherence to illumination of pain-prone areas.

The Proarrhythmic Effect of Cardiac Resynchronization Therapy: an Issue that Should Be Borne in Mind

The demonstrated benefits of cardiac resynchronization therapy (CRT) in reducing mortality and hospitalizations for heart failure, improving NYHA functional class and inducing reverse remodeling have led to its increasing use in clinical practice. However, its potential contribution to complex ventricular arrhythmias is controversial.We present the case of a female patient with valvular heart failure and severe systolic dysfunction, in NYHA class III and under optimal medical therapy, without previous documented ventricular arrhythmias. After implantation of a CRT defibrillator, she suffered an arrhythmic storm with multiple episodes of monomorphic ventricular tachycardia (VT), requiring 12 shocks. Subsequently, a pattern of ventricular bigeminy was observed, as well as reproducible VT runs induced by biventricular pacing. Since no other vein of the coronary sinus system was accessible, it was decided to implant an epicardial lead to stimulate the left ventricle, positioned in the left ventricular mid-lateral wall. No arrhythmias were detected in the following six months. This case highlights the possible proarrhythmic effect of biventricular pacing with a left ventricular lead positioned in the coronary sinus venous system.

Health-Related Quality of Life Impact of a Triple Combination of Olmesartan Medoxomil, Amlodipine Besylate and Hydrochlorotiazide in Subjects with Hypertension

BACKGROUND: A post-hoc analysis was performed on the data from a 54 weeks phase III study (ClinicalTrials.gov identifier: NCT00923091) to measure changes in the health-related quality of life (HRQoL) of 2,690 patients aged ≥18 with moderate-to-severe hypertension who received one of six doses of olmesartan/amlodipine/hydrochlorothiazide (OLM/AML/HCTZ), using the MINICHAL and EQ-5D instruments. METHODS: Descriptive statistics were used to assess blood pressure and HRQoL scores over the study period. Analysis of covariance (ANCOVA) was used to identify those factors that could possibly have influenced HRQoL. Linear regression was used to assess the relationship between changes in blood pressure and HRQoL scores. RESULTS: Patients' baseline MINICHAL mood and somatic domains scores were 5.5 and 2.6. Over the study period HRQoL improved as both MINICHAL scores decreased by 31-33%. Patients' baseline EQ-5D index and VAS scores were 0.9 and 73.4 respectively, increasing by 6% and 12% over the study period. Patients' QALY gain over the 54 weeks study period was estimated to be 0.029 QALYs. The ANCOVA showed that changes in patients' HRQoL was likely to have been influenced by patients' achievement of blood pressure control, the amount of concomitant medication and patients' last used dosage strength of antihypertensive. Linear regression showed that blood pressure improvement may have been associated with improved HRQoL. CONCLUSIONS: This study showed that OLM/AML/HCTZ reduced blood pressure and significantly increased blood pressure control whilst improving patients' HRQoL. Achieving blood pressure control, amount of concomitant medication and dosage strength of antihypertensive impacted on patients' HRQoL.

Long-Term Recurrence of Nonmelanoma Skin Cancer after Topical Methylaminolevulinate Photodynamic Therapy in a Dermato-Oncology Department

BACKGROUND: Most available studies on the efficacy of topical photodynamic therapy focus on short-to medium-term results. Long-term data are scarce. OBJECTIVE: To evaluate the long-term efficacy of photodynamic therapy with topical methylaminolevulinate to treat Bowen's disease and basal cell carcinoma in the clinical practice setting of a dermato-oncology department. METHODS: The study included patients diagnosed with Bowen's disease or basal cell carcinoma, and who received photodynamic therapy from 2004 to 2008. Treatment protocol and clinical follow-up were standardized. The primary endpoint was clinically observed recurrence in a previous photodynamic therapy-treated area. Descriptive and survival analyses were performed. RESULTS: A total of 31 Bowen's disease lesions and 44 superficial basal cell carcinoma were treated, with a median follow-up of 43.5 months. Recurrence was observed in 14 Bowen's disease lesions (53.8%) and in 11 superficial basal cell carcinoma (33.3%). Significantly higher estimates for recurrence rates were found in patients with Bowen's disease (p=0.0036) or those aged under 58 years (p=0.039). The risk of recurrence was higher in patients with Bowen's disease than in those with superficial basal cell carcinoma and younger patients. CONCLUSIONS: Recurrence should be considered when choosing to treat non-melanoma skin cancer with photodynamic therapy. Younger age and Bowen's disease were independent predictors for long-term recurrence, suggesting the need to establish an extended period of follow-up for this subset of patients.