Abstract: In the past 5 years the management of metastatic renal cell carcinoma has been revolutionized by the advent of anti-angiogenic treatments, particularly the multi-targeted kinase inhibitors. This revolution has put standard and experimental immunotherapy in the shade. However, it is likely that a subset of patients with advanced kidney cancer is still best served by immunotherapy. This article summarizes promising novel immunotherapeutic techniques to identify those patients who will benefit and to optimize outcomes for patients using novel immunotherapeutic approaches. ... Read more

Abstract: Chronic lymphocytic leukemia (CLL) is a malignancy mainly affecting elderly people and is still considered an incurable disease. Despite recent advances in CLL treatment, relapse rates are high and often accompanied by the development of resistance towards conventional chemotherapy. Thus, new agents are needed for the treatment of these patients. In recent years, our understanding of the biological mechanisms driving CLL pathogenesis has considerably improved, and novel treatment strategies are arising. This review summarizes recent insights in CLL biology and describes several new agents and treatment strategies that are currently explored in pre-clinical studies and early-phase clinical trials. ... Read more

Abstract: The evolution of the immune system has provided a multilevel system that interconnects the innate and adaptive immune systems to serve at least three central purposes: the defense from microbial pathogens, the capacity for discrimination of self- from non-self necessary for the prevention of autoimmune disease, and essential effector roles in wound repair and tissue remodeling. In recent studies, we have elucidated an unsuspected role for a class of naturally occurring autoreactive antibodies from the most primitive tier of B lymphocytes, which regulates fundamental functions of the innate immune system. Our findings also throw light onto long unresolved mysteries regarding the origins of the earliest waves of B lymphocyte development. ... Read more

Abstract: Migraine is a chronic disease with episodic attacks and a variable prognosis. In a subgroup, migraine evolves into a more protracted condition (migraine transformation or progression). Transformation of migraine may be subdivided into three partially overlapping forms. Clinical transformation describes the evolution from episodic into chronic migraine. Physiological transformation refers to alterations in nociceptive thresholds and in pain pathways that precede or accompany clinical transformation. Anatomical transformation refers to the emergence of definitive brain lesions (e.g., stroke and deep white matter lesions) in some migraineurs. Herein we conceptualize migraine as a progressive disease and discuss risk factors for transformation. ... Read more

Abstract: A recent Japanese Gynecologic Oncology Group phase III clinical trial in patients with ovarian cancer receiving the conventional paclitaxel-carboplatin combination once every 3 weeks or "dose-dense" paclitaxel once a week with carboplatin once every 3 weeks has reported a large progression free survival advantage for the dose-dense therapy. Recent advances in the molecular understanding of ovarian cancer point to molecular differences between paclitaxel and carboplatin sensitivity which link to the status of BRCA genes -- so called familial and sporadic "BRCAness." It may be that the change in the way we use paclitaxel allows us to more effectively target the heterogeneity of such intrinsic sensitivity/resistance to these agents in the adjuvant therapy of ovarian cancer, leading to significant improvement in the management of the disease. ... Read more

Abstract: Even when a breast cancer patient has only minimal lymph node involvement, additional therapy is needed. If women are not treated with adjuvant systemic therapy like chemotherapy and/or hormonal therapy, disease-free survival is reduced by 10% at 5-year follow-up. These are the main results from the MIRROR study, a Dutch cohort study in which all hospitals from The Netherlands have participated. The results were recently published in the New England Journal of Medicine (de Boer, 2009). The study was supported by a grant from the Netherlands Organization for Health Research and Development (945-06-509). ... Read more

Abstract: Tinnitus is the perception of sound with the absence of acoustic stimulus. It affects approximately 10% of the population. This is a symptom with a broad differential diagnosis. In some cases, tinnitus impacts significantly on patients' activities of daily living. Understanding how to differentiate between subjective and objective tinnitus is essential to the evaluation and management of these patients. The various causes of each type of tinnitus will be discussed. This review presents a general approach to tinnitus in order to facilitate timely diagnosis and management of this complex symptom. ... Read more

Abstract: Rasmussen encephalitis (RE) is characterized by chronic inflammation of one cerebral hemisphere which causes intractable epileptic seizures and progressive neurological deficits. Since antiepileptic pharmacotherapy is often ineffective the traditional therapy for Rasmussen encephalitis is hemispherectomy in one of its modern variants which renders the patient seizure free but leads to a severe deficit. To escape this dilemma, immunomodulatory therapeutic approaches such as rituximab, a monoclonal anti-CD20 antibody, offer an alternative and bear promising therapeutic potentials in Rasmussen encephalitis. ... Read more

Abstract: Gene therapy for inherited retinal degeneration has made major advances toward the ultimate goal of reversing blindness in human patients. With significant advances in recombinant viral vector design, safety and efficacy profiles have greatly improved. Although these recent advances have been applied to many different retinal diseases, one retinal degenerative disease, Leber congenital amaurosis, appears to have the greatest potential for reversing blindness. In pre-clinical animal studies, gene therapy for Leber congenital amaurosis has demonstrated visual recovery. Recently, in landmark clinical trials, preliminary results have indicated safety and efficacy for the use of gene therapy in Leber congenital amaurosis, thus laying the foundation for continued use of gene therapy in other forms of inherited blinding disease. ... Read more

Abstract: Lower urinary tract symptoms (LUTS), the overactive bladder syndrome (OAB), and detrusor overactivity (DO) are all conditions that can have major effects on quality of life and social functioning. Antimuscarinic drugs are first-line treatment -- they often have good initial response rates, but adverse effects and decreasing efficacy cause long-term compliance problems, and alternatives are needed. The recognition of the functional contribution of the urothelium, the spontaneous myocyte activity during bladder filling, and the diversity of nerve transmitters involved has sparked interest in both peripheral and central modulation of LUTS/OAB/DO pathophysiology. There may be several new possibilities to treat LUTS/OAB/DO. For example, β₃-adrenoceptor (AR) agonists (mirabegron), phosphodiesterase type 5 inhibitors (sildenafil, tadalafil, vardenafil), combinations (α₁-AR antagonist + antimuscarinic), and drugs with a central mode of action (tramadol, gabapentin) all have positive proof of concept documented in randomized, controlled trials. Which of these therapeutic principles will be developed to become clinically useful treatments remain to be established. ... Read more