Purpose. This is a population study of patients who were treated for vulvar cancer in a tertiary center in northern Israel, aimed to report clinical findings, treatment, and outcome.
Methods. A retrospective chart review of all medical records of consecutive patients who were treated for vulvar cancer in the years 1993–2012 was conducted. Data extracted from the medical records included demographics, histology, size of lesion, stage of disease at diagnosis, type of treatment, radiation dose, follow-up, recurrence, and survival.
Results. The study included 44 patients with a median age of 69.8 years (range, 42–93 years). Thirty-five (79.5%) of the patients were of Jewish descent, five were Arabic, and four were of other descent. The most common histology type was squamous cell carcinoma in 35 (79.5%) patients. Most patients were staged FIGO II–III at time of diagnosis. Surgery was the most common primary treatment modality (54.2%). Twenty-three (52.2%) patients had recurrent disease. Older age and more advanced stage at diagnosis were associated with increased mortality.
Conclusion. Vulvar cancer is common among elderly women with co-morbidities who present in advanced disease stage; all these factors are significant for survival.
The Registro Informatizado de Enfermedad TromboEmbólica (RIETE Registry) is an ongoing, international, prospective registry of consecutive patients with acute venous thromboembolism (VTE) designed to gather and analyze data on treatment patterns and outcomes in patients with acute VTE. It started in Spain in 2001, and 6 years later the database was translated into English with the aim to expand the Registry to other countries. In contrast to randomized controlled trials, there is no imposed experimental intervention: the management is determined solely by physicians. Thus, it provides data on patients with VTE in a real-world situation with an unselected patient population. Data from RIETE are hypothesis-generating and provide feedback from real-world clinical situations. So far, we learned about the natural history of VTE in patients with relative or absolute contraindications to anticoagulant therapy. We also learned interesting aspects on the natural history of VTE, and we built a number of prognostic scores to identify VTE patients at low, moderate, or high risk for adverse outcome.
Heparanase, a β-D-endoglucuronidase abundant in platelets that was discovered 30 years ago, is an enzyme that cleaves heparan sulfate side chains on the cell surface and in the extracellular matrix. It was later recognized as being a pro-inflammatory and pro-metastatic protein. We had earlier demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. We had shown that heparanase up-regulated the expression of the blood coagulation initiator tissue factor (TF) and interacted with the tissue factor pathway inhibitor (TFPI) on the cell surface membrane of endothelial and tumor cells, leading to dissociation of TFPI and resulting in increased cell surface coagulation activity. Moreover, we have demonstrated that heparanase directly enhanced TF activity which led to increased factor Xa production and subsequent activation of the coagulation system. Recently, heparanase inhibitory peptides derived of TFPI-2 were demonstrated by us to inhibit heparanase procoagulant activity and attenuate sepsis in mouse models.
Complex disorders are common in the human population and are caused by interplay between genetic and environmental factors. Therefore the quest for the genetic basis of such disorders has much similar-ity to deciphering the genetic basis of macro-evolutionary processes, such as speciation. Here I discuss conceptual connections between the principles underlying and processes occurring in disease and evo-lution. Special focus is given to the tremendous mitochondrial genetic variability in the population and within individuals and the impact of both types of variability on evolutionary processes and diseases.
Parkinson’s disease (PD) and Alzheimer’s disease (AD) are severe neurodegenerative disorders, with no drugs that are currently approved to prevent the neuronal cell loss characteristic in brains of pa-tients suffering from PD and AD, and all drug treatments are symptomatic and monomodal in their action. Due to the complex pathophysiology, including a cascade of neurotoxic molecular events that result in neuronal death and predisposition to depression and eventual dementia, and etiology of these disorders, an innovative approach towards neuroprotection or neurorestoration (neurorescue) is the development and use of multifunctional pharmaceuticals which can act at different brain regions and neurons. Such drugs target an array of pathological pathways, each of which is believed to contribute to the cascades that ultimately lead to neuronal cell death. In this short review, we discuss examples of novel multifunctional ligands that may have potential as neuroprotective-neurorestorative therapeutics in PD and AD, some of which are under development. The compounds discussed originate from synthetic chemistry as well as from natural sources.
KEY WORDS: Rasagiline multimodal drugs, antiapoptotic, neuroprotection, neurorestoration, Parkinson’s disease, Alzheimer’s disease
Catheter ablation is a first-line treatment for many cardiac arrhythmias and is generally performed under X-ray fluoroscopy guidance. However, current techniques for ablating complex arrhythmias such as atrial fibrillation and ventricular tachycardia are associated with sub-optimal success rates and prolonged radiation exposure. Pre-procedure 3-D magnetic resonance imaging (MRI) has improved understanding of the anatomic basis of complex arrhythmias and is being used for planning and guidance of ablation procedures. A particular strength of MRI compared to other imaging modalities is the ability to visualize ablation lesions. Post-procedure MRI is now being applied to assess ablation lesion location and permanence with the goal of identifying factors leading to procedure success and failure. In the future, intra-procedure real-time MRI, together with the ability to image complex 3-D arrhythmogenic anatomy and target additional ablation to regions of incomplete lesion formation, may allow for more successful treatment of even complex arrhythmias without exposure to ionizing radiation. Development of clinical grade MRI-compatible electrophysiology devices is required to transition intra-procedure MRI from preclinical studies to more routine use in patients.
The contributions of Jewish American surgeons in the nineteenth and early twentieth century at a time in which prejudice against ethnic and religious minorities was commonplace in the United States are detailed. The contributions of Jewish American surgeons and the positions they attained subsequent to a change in attitude toward religious minorities in the United States are presented as a comparison.
This paper describes the rapid evolution of modern liver surgery, starting in the middle of the twentieth century. Claude Couinaud studied and described the segmental anatomy of the liver, Thomas Starzl performed the first liver transplantations, and Henri Bismuth introduced the concept of anatomical resections. Hepatic surgery has developed significantly since those early days. To date, innovative techniques are applied, using cutting-edge technologies: Intraoperative ultrasound, techniques of vascular exclusion of the liver, new devices for performing homeostasis and dissection, laparoscopy for resections, and new drugs that allow the resection of previously unresectable tumors. The next stage in liver surgery will probably be the implementation of a multidisciplinary holistic approach to the liver-diseased patient that will ensure the best and most efficient treatments in the future.
After direct impact of the trauma, crush syndrome is the second most frequent cause of death after mass disasters. However, since crush syndrome is quite rare in daily practice, mistakes are frequent in the treatment of these cases. This paper summarizes the etiopathogenesis of traumatic rhabdomyolysis and of crush syndrome-based acute kidney injury. The clinical and laboratory features, prophylaxis, and treatment of crush cases are summarized as well. The importance of early and energetic fluid resuscitation is underlined for prophylaxis of acute kidney injury. Since there is chaos, and an overwhelming number of victims, logistic drawbacks create a specific problem in the treatment of crush victims after mass disasters. Potential solutions for logistic hurdles and disaster preparedness scenarios have also been provided in this review article.
Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis, and angiogenesis. Recently we have demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. Heparanase was shown to up-regulate tissue factor (TF) expression and interact with tissue factor pathway inhibitor (TFPI) on the cell surface, leading to dissociation of TFPI from the cell membrane of endothelial and tumor cells, resulting in increased cell surface coagulation activity. More recently, we have shown that heparanase directly enhances TF activity, resulting in increased factor Xa production and activation of the coagulation system. Data indicate increased levels and possible involvement of heparanase in vascular complications in pregnancy. Taking into account the prometastatic and proangiogenic functions of heparanase, overexpression in human malignancies, and abundance in platelets and placenta, its involvement in the coagulation machinery is an intriguing novel arena for further research.
