End-of-life decisions are made daily in intensive care units worldwide. There are numerous factors affecting these decisions, including geographical location as well as religion and attitudes of caregivers, patients, and families. There is a spectrum of end-of-life care options from full continued care, withholding treatment, withdrawing treatment, and active life-ending procedures.
The fetal “programming of adult diseases” has been previously reviewed. The descriptions were comprehensive, dealing with the effects of nutritional deprivation on the development of adult metabolic and cardiovascular diseases. During the past decade, research into this “programming” also expanded to the development of osteoporosis. The present review deals with the imbalance of bone mineral metabolism, “programmed” by maternal/fetal/infantile nutritional deprivation, and is illustrated with a family history from the Budapest Ghetto.
The growing practice of endoscopic surgery has changed the therapeutic management of selected head and neck cancers. Although a negative surgical margin in resection of neoplasm is the most important surgical principle in oncologic surgery, controversies exist regarding assessment and interpretation of the status of margin resection. The aim of this review was to summarize the literature considering the assessment and feasibility of negative margins in transoral laser microsurgery (TLM) and transoral robotic surgery (TORS). Free margin status is being approached differently in vocal cord cancer (1–2 mm) compared with other sites in the upper aerodigestive tract (2–5 mm). Exposure, orientation of the pathological specimen, and co-operation with the pathologist are crucial principles needed to be followed in transoral surgery. Piecemeal resection to better expose deep tumor involvement and biopsies taken from surgical margins surrounding site of resection can improve margin assessment. High rates of negative surgical margins can be achieved with TLM and TORS. Adjuvant treatment decision should take into consideration also the surgeon’s judgment with regard to the completeness of tumor resection.
Transoral laser microsurgery (TLM) was pioneered in the early 1970s as an approach to treat laryngeal pathology with precision and minimal thermal damage to the vocal cords. Over the last four decades, TLM has become an integral part of the treatment paradigm for patients with laryngeal cancer. TLM is one of the primary treatment options for early-stage laryngeal tumors. However, in recent years, surgeons have begun to develop TLM into a more versatile approach which can be used to address advanced laryngeal tumors. Although functional outcomes following TLM for advanced laryngeal disease are scarce, survival outcomes appear to be comparable with those reported for organ preservation strategies employing external beam radiation therapy (EBRT) and chemotherapy. In addition, TLM plays an important role in the setting of recurrent laryngeal cancer following primary irradiation. TLM has been demonstrated to decrease the need for salvage total laryngectomy resulting in improved functionality while retaining comparable oncologic outcomes. The aims of this review are to elucidate the indications, techniques, and oncological outcomes of TLM for advanced laryngeal cancers.
Head and neck cancers are the most common cancers in developing countries, especially in Southeast Asia. Head and neck cancers are more common in males compared to females. This is mainly attributed to tobacco, areca nut, alcohol, etc. Oral cancers are most common amongst all head and neck squamous cell cancers (HNSCC). HNSCC in the developing world differ from those in the Western world in terms of age, site of disease, etiology, and molecular biology. Poverty, illiteracy, advanced stage at presentation, lack of access to health care, and poor treatment infrastructure pose a major challenge in management of these cancers. The annual GDP (gross domestic product) spent on health care is very low in developing countries compared to the developed countries. Cancer treatment leads to a significant financial burden on the cancer patients and their families. Several health programs have been implemented to curb this rising burden of disease. The main aims of these health programs are to increase awareness among people regarding tobacco and to improve access to health care facilities, early diagnosis, treatment, and palliative care.
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.
Pregnancy is a physiological hypercoagulable state, preparing the mother for the hemostatic challenge of delivery. However, this is associated with an increased risk of venous thrombosis and placenta-mediated complications, which present major challenges for mother and fetus. Although these conditions are heterogeneous in their pathophysiology, hereditary and acquired thrombophilia has been associated with recurrent pregnancy loss and gestational vascular complications, such as early-onset pre-eclampsia and placental abruption. Prevention of such placenta-mediated complications, which collectively complicate up to 15% of pregnancies, is a major issue for women’s health. Prospective interventional studies stratified by current knowledge of pathophysiological mechanisms related to placental and systemic hemostatic alterations will impact on the management of pregnancies at risk of these complications.
Venous thromboembolism (VTE), the third most frequent acute cardiovascular syndrome, may cause life-threatening complications and imposes a substantial socio-economic burden. During the past years, several landmark trials paved the way towards novel strategies in acute and long-term management of patients with acute pulmonary embolism (PE). Risk stratification is increasingly recognized as a central cornerstone for an adequate diagnostic and therapeutic management of the highly heterogeneous population of patients with acute PE. Recently published European Guidelines emphasize the importance of clinical prediction rules in combination with imaging procedures (assessment of right ventricular function) and laboratory biomarkers (indicative of myocardial stress or injury) for identification of normotensive PE patients at intermediate risk for an adverse short-term outcome. In this patient group, systemic full-dose thrombolysis was associated with a significantly increased risk of intracranial bleeding, a complication which discourages its clinical application unless hemodynamic decompensation occurs. A large-scale clinical trial program evaluating new oral anticoagulants in the initial and long-term treatment of venous thromboembolism showed at least comparable efficacy and presumably increased safety of these drugs compared to the current standard treatment. Research is continuing on catheter-directed, ultrasound-assisted, local, low-dose thrombolysis in the management of intermediate-risk PE.
Intelligent Design (ID) burst onto the scene in 1996, with the publication of Darwin’s Black Box by Mi-chael Behe. Since then, there has been a plethora of articles written about ID, both pro and con. How-ever, most of the articles critical of ID deal with peripheral issues, such as whether ID is just another form of creationism or whether ID qualifies as science or whether ID should be taught in public schools. It is our view that the central issue is whether the basic claim of ID is correct. Our goal is fourfold: (I) to show that most of the proposed refutations of ID are unconvincing and/or incorrect, (II) to describe the single fundamental error of ID, (III) to discuss the historic tradition surrounding the ID controversy, showing that ID is an example of a “god-of-the-gaps” argument, and (IV) to place the ID controversy in the larger context of proposed proofs for the existence of God, with the emphasis on Jewish tradition.
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.
