Suboptimal doses of low molecular weight heparin and acute venous thromboembolism. Data from the RIETE registry

The objective was to assess the use of suboptimal doses (60–149 UI kg⁻¹ day⁻¹) of low molecular weight heparin (LMWH) in the treatment of acute venous thromboembolism (VTE) in actual clinical practice and to evaluate the outcomes compared to standard doses (≥150 UI kg⁻¹ day⁻¹). Retrospective analysis of data from a multicenter registry of patients with VTE (RIETE; Registro Informatizado de Enfermedad TromboEmbólica). Patient characteristics, antithrombotic treatments, and 3-month outcomes were analyzed. We studied 12,302 patients with VTE; 10,524 patients were treated initially only with LMWH; 1,547 patients received suboptimal LMWH (mean = 122 UI kg⁻¹ day⁻¹), and 8,977 patients received full-dose LMWH (mean = 191 UI kg⁻¹ day⁻¹). The suboptimal group included significantly more patients with recent major bleeding, weight more than 100 kg, raised creatinine, or deep vein thrombosis. No significant differences in mortality rate (7.7 vs 7.8%), VTE recurrence (2.7 vs 2.3%), or fatal hemorrhage (0.6 vs 0.6%) occurred between the suboptimal and the standard group. Major bleeding episodes occurred more frequently in the patients with pulmonary embolism treated with suboptimal LMWH (4.5 vs 2.4%; p = 0.02). In the multivariate analysis, after adjusting for bleeding risk factors, major hemorrhage was not associated with the heparin dose. Suboptimal doses of LMWH are used in actual clinical practice in a reduced group of patients at an outcome rate not very different to that of standard doses. Bleeding episodes depend more on the patient’s characteristics than on the LMWH dose. Randomized trials should be performed to corroborate these results. A full list of the RIETE investigators is given in the Appendix.     

Teratoma of umbilical cord: a case report and literature review

Teratomas are tumors that arise from totipotent embryonic germ cells. The umbilical cord is an extremely rare site for this tumor, only 12 cases have been reported in the medical literature. Herein we describe an umbilical cord mass presenting necrosis with clinical and histopathological features that can be considered as another case of umbilical cord teratoma. We discuss the differential diagnosis and review the complete literature on this subject.     

Mutational screening of phospholamban gene in hypertrophic and idiopathic dilated cardiomyopathy and functional study of the PLN -42 C>G mutation

BACKGROUND: Phospholamban is an endogenous sarcoplasmic reticulum calcium ATPase inhibitor with a regulatory effect on cardiac contraction/relaxation coupling. Mutations in the phospholamban gene (PLN) have been associated with primary cardiomyopathies. AIMS: To screen for PLN mutations in our population of patients with primary cardiomyopathies and to perform functional analysis of the mutations identified. METHODS: We performed SSCP mutational screening and DNA sequencing of the PLN gene in 186 patients with either hypertrophic or dilated cardiomyopathy. To study promoter strength we constructed reporter plasmids containing the luciferase gene and performed transient transfection analysis in C6 and C2C12 cell lines. RESULTS: The PLN -42 C>G mutation was found in one patient with late onset familial apical hypertrophic cardiomyopathy. This mutation decreased phospholamban promoter activity by 43% and 47%, in C6 and C2C12 cell lines respectively. One son had mild apical hypertrophic cardiomyopathy and carried the mutation, another son with normal ECG and echocardiogram also had the mutation. CONCLUSION: The PLN -42 C>G mutation is associated with a benign form of apical hypertrophic cardiomyopathy in this family, though the presence of a healthy adult carrier suggests that other genetic and environmental factors could be involved. Otherwise, mutations in the PLN gene are not a frequent cause of cardiomyopathies in our population.     

Sleep apnea-hypopnea syndrome and the heart

Cardiovascular and cerebrovascular diseases are the most common diseases in industrialized societies. The main objectives of this article were to summarize the physiological effects of sleep apnea on the circulatory system and to review how treatment of this condition influences cardiovascular disease. Acute sleep apnea has a number of hemodynamic consequences, such as pulmonary and systemic hypertension, increased ventricular afterload and reduced cardiac output, all of which result from sympathetic stimulation, arousal, alterations in intrathoracic pressure, hypoxia and hypercapnia. When chronic, sleep apnea-hypopnea syndrome is associated with systemic hypertension, ischemic heart disease, congestive heart failure, and Cheyne-Stokes respiration in patients with congestive heart failure. Nocturnal treatment with continuous positive airway pressure decreases both the number of central apneic episodes and blood pressure in patients with sleep apnea-hypopnea syndrome and arterial hypertension.     

Implication of ERBB2 as a Predictive Tool for Survival in Patients with Pancreatic Cancer in Histological Studies

Pancreatic cancer will be positioned by the year 2030 as the second cause of oncological death after lung cancer. The pathophysiology of the most common variety, which involves the adenocarcinoma of the pancreas, represents one of the main challenges for current oncology to explain its tumorigenesis and create a targeted treatment. The tumor microenvironment, metastatic capacity, and lack of early diagnosis lead patients to present advanced stages at the time of diagnosis. Despite numerous efforts, little progress has been made in clinical outcomes and with respect to the improved survival of these patients. For this reason, in recent years, numerous diagnostic tests, treatments, and possible approaches in the fields of radiotherapy, chemotherapy, immunotherapy, and surgery have been developed to find a combination of methods that improves life expectancy in patients diagnosed with this disease. On the other hand, the scientific community has made numerous advances in the molecular bases of pancreatic cancer since several oncogenetic pathways have been described and the markers expressed by the tumor have proven to be useful in the prognosis of pancreatic adenocarcinoma. These molecular alterations allow the study of possible therapeutic targets that improve the prognosis of these patients, but even numerous tumor cell-individual interactions must be explained to understand the underlying pathophysiology causing the high mortality. Therefore, the purpose of our study is to examine the expression of markers such as EGFR, Cyclin D1, andCDK4 in order to find a relationship with the possible long-term prognostic factors of patients affected by pancreatic ductal adenocarcinoma. Our results show that there is a prognostic role for ErbB2, EGFR, beta catenin, cyclin D1, and CDK4. Of these, we highlight the clinical importance of ErbB2 in the survival rates of patients who overexpress this component.     

Contribution of phospholipase A2 to the lethal potency of Bothrops alternatus (víbora de la cruz) venom

Purified phospholipase A2 from Bothrops alternatus venom is one single protein species with a molecular weight of 15,000 and isoelectric point 5.08. When injected i.p. or i.v. at a dose of 0.7 microgram/g body weight it is lethal to mice, eliciting a typical syndrome of dyspnea, tachycardia, arrhythmia and irreversible shock. Post mortem and histopathologic studies have demonstrated that the lungs (massive pulmonary hemorrhage), heart (foci of myocardial and endocardial necrosis with interfibrillar hemorrhage), liver (congestion, hepatocytic microvacuolization with zones of massive necrosis) and kidneys (foci of tubular and glomerular necrosis) were severely injured. Except for the less extensive hemorrhages and the significantly longer survival time, the observed lesions are similar to those observed after the injection of lethal doses of whole venom. The lethal potency of the purified enzyme (LD50 i.p. 0.14 microgram/g body weight) is 46-fold greater than that of the whole venom (LD50 i.p. 6.4 micrograms/g body weight). The contribution of phospholipase A2 to the overall lethal effect of B. alternatus venom is suggested by the decreased lethal potency of a venom sample in which a significant amount of phospholipase A2 has been removed and the full restoration of the lethal potency upon supplementation of the depleted sample with purified enzyme. It is concluded that phospholipase A2 is a major component responsible for lethality of the whole B. alternatus venom, while the contribution of other venom components appears to be significant mainly in reducing the time of survival.