Targeted therapies use an understanding of the pathophysiology of a disease in an individual patient. Although targeted therapy for systemic sclerosis (SSc, scleroderma) has not yet reached the level of patient-specific treatments, recent developments in the understanding of the global pathophysiology of the disease have led to new treatments based on the cells and pathways that have been shown to be involved in the disease pathogenesis. The presence of a B cell signature in skin biopsies has led to the trial of rituximab, an anti-CD20 antibody, in SSc. The well-known properties of transforming growth factor (TGF)-β in promoting collagen synthesis and secretion has led to a small trial of fresolimumab, a human IgG4 monoclonal antibody capable of neutralizing TGF-β. Evidence supporting important roles for interleukin-6 in the pathogenesis of SSc have led to a large trial of tocilizumab in SSc. Soluble guanylate cyclase (sGC) is an enzyme that catalyzes the production of cyclic guanosine monophosphate (cGMP) upon binding of nitric oxide (NO) to the sGC molecule. Processes such as cell growth and proliferation are regulated by cGMP. Evidence that sGC may play a role in SSc has led to a trial of riociguat, a molecule that sensitizes sGC to endogenous NO. Tyrosine kinases (TKs) are involved in a wide variety of physiologic and pathological processes including vascular remodeling and fibrogenesis such as occurs in SSc. This has led to a trial of nintedanib, a next-generation tyrosine-kinase (TK) inhibitor which targets multiple TKs, in SSc.
The use of cocaine continues to grow worldwide. One of the possible side-effects of cocaine is vasculitis. Two distinct vasculitic syndromes have been described due to cocaine. One is cocaine-induced midline destruc¬tive lesion, secondary to a direct vasoconstrictor effect of cocaine, inducing ischemic necrosis of the septal cartilage and perforation of the nasal septum, mimicking findings of granulomatosis with polyangiitis in the upper airways. The other is ANCA-associated vasculitis, attributed to the levamisole component that contaminates about 70% of the cocaine. This type of vasculitis may be myeloperoxidase (MPO) and proteinase 3 (PR3) positive, and its main manifestations are typical cutaneous findings, arthralgia, oto¬laryngologic involvement, and agranulocytosis. A high degree of suspicion and awareness is needed in order properly to diagnose and treat these patients.
The advent of sophisticated diagnostics has enabled the discovery of previously unknown arthropod-borne viruses like Chikungunya. This infection has become increasingly prevalent in the last 10 years across the Indian Ocean and has been brought to media attention by a recent outbreak in the Caribbean. The outbreak has been aided by a drastic rise in air travel, allowing infected individuals to transport the virus to pre¬viously unaffected regions. In addition, a recently documented viral mutation has allowed its transmission by the Aedes albopictus mosquito, therefore facilitating outbreaks in Southern Europe and the USA. The duration and extent of the arthritis seen peri- and post infection has become a topic of academic interest. Although published data are largely observational, there has been a definite increase in original research focusing on this. Symptoms can persist for years, particularly in older patients with pre-existing medical conditions. The etiology is still not fully understood, but viral persistence and immune activation within synovial fluid have been shown in mouse models. There have been no prospective clinical trials of treatment in humans; however, animal trials are in process. The mainstay of treatment remains anti-inflammatories and steroids where necessary. The clinical presentation seems to mimic common rheumatological conditions like rheumatoid arthritis; therefore recent recommendations suggest the use disease-modifying agents as a common practice for the specific syndrome. This review uses recent published data and draws on our own clinical experience to provide an overview of joint complications of Chikungunya infection.
Systemic sclerosis (SSc) is a multisystem disease characterized by functional and structural abnormalities of small blood vessels, fibrosis of the skin and internal organs, immune system activation, and autoimmunity. The gastrointestinal tract is involved in nearly all patients and is a source of significant morbidity and even mortality. The aim of this review is to summarize the pathogenesis and to provide a clinical approach to these patients.
For the purpose of reducing maternal and neonatal morbidity, elective single transfer (eSET) in in vitro fertilization (IVF) was first proposed in 1999. The purpose of this review is to summarize recent oral debate between a proponent and an opponent of expanded eSET utilization in an attempt to determine whether a blanket eSET policy, as is increasingly considered, is defensible. While eSET is preferable when possible, and agreed upon by provider and patient, selective double embryo transfer (DET) must be seriously entertained if deemed more appropriate or is desired by the patient. Patient autonomy, let alone prolonged infertility and advancing age, demand nothing less. Importantly, IVF-generated twins represent only 15.7% of the national twin birth rate in the United States. Non-IVF fertility treatments have been identified as the main cause of all multiple births for quite some time. However, educational and regulatory efforts over the last decade, paradoxically, have exclusively only been directed at the practice of IVF, although IVF patient populations are rapidly aging. It is difficult to understand why non-IVF fertility treatments, usually applied to younger women, have so far escaped attention. This debate on eSET utilization in association with IVF may contribute to a redirection of priorities.
Final oocyte maturation is a crucial step in in vitro fertilization, traditionally achieved with a single bolus of human chorionic gonadotropin (hCG) given 36 hours before oocyte retrieval. This bolus exposes the patient to the risks of ovarian hyperstimulation syndrome (OHSS), particularly in the face of ovarian hyper-response to gonadotropins. Although multiple measures were developed to prevent OHSS, gonadotropin-releasing hormone (GnRH) agonist triggering is now globally recognized as the best approach to achieve this goal. The first report on the use of GnRH agonist as ovulation trigger in the context of OHSS prevention came from the Rambam Health Care Campus, Haifa, Israel and appeared in 1988. This review details the events that culminated in worldwide acceptance of this measure and describes its benefit in the field of assisted reproductive technology.
Dr Gerald Loewi was Senior Research Scientist and Consultant Pathologist at the Medical Research Council (MRC) Rheumatism Research Unit at Taplow, England and subsequently the MRC Clinical Research Centre, Harrow, England. An immunologist with a background in pathology, he made major contributions to our understanding of the immunopathology of rheumatoid arthritis and other rheumatic disorders. With his colleagues, he developed a more sophisticated concept of what were initially thought to be primary autoimmune or degenerative diseases but are now recognized as much more complex disease processes. He was one of the first to initiate close collaboration between clinicians and scientists in rheumatology research and practice.
Pelvic organ prolapse affects approximately 8% of women, and the demand for pelvic organ prolapse surgery is expected to increase by nearly 50% over the next 40 years. The surgical techniques used to correct pelvic organ prolapse have evolved over the last 10 years, with multiple well-designed studies addressing the risks, outcomes, reoperation rates, and optimal surgical approaches. Here we review the most recent evidence on the route of access, concomitant procedures, and synthetic materials for augmenting the repair. Ultimately, this review highlights that there is no optimal method for correcting pelvic organ prolapse and that the risks, benefits, and approaches should be discussed in a patient-centered, goal-oriented approach to decision-making.
A growing body of evidence implicates that maternal inflammation during pregnancy is associated with increased risk of neurodevelopmental disorders in the offspring. The pathophysiological mechanisms by which maternal inflammation evokes fetal brain injury and contribute to long-term adverse neurological outcomes are not completely understood. In this review, we summarize our 10 years’ research experience on maternal inflammation and the implications upon the fetal/offspring brain. We review our findings regarding the underlying mechanisms that connects maternal inflammation and fetal brain injuries (e.g. cytokines, oxidative stress), we discuss our imaging, pathological and behavioral test results which support brain damage following maternal inflammation and finally we describe some of the therapeutic strategies which might prevent the damage.
The changing science of the urinary microbiota and microbiome has both clinical and research implications. This review manuscript provides an overview of the state of this science, as well as a discussion of the potential for prevention, diagnosis, and treatment of human disease. The history of techniques used for clinical detection of infection are placed into context along with the modern methods of bacterial detection and identification.
