Anti-citrullinated protein autoantibodies (ACPAs) are the major autoantibodies in rheumatoid arthritis (RA). Anti-citrullinated protein autoantibodies are directed against different citrullinated antigens, including filaggrin, fibrinogen, vimentin, and collagen. Presence of ACPA is associated with joint damage and extra-articular manifestations, suggesting that ACPAs are most likely pathogenic autoantibodies in RA. In vitro, ACPAs induce macrophage tumor necrosis factor alpha (TNF-α) production, osteoclastogenesis, and complement activation. These autoantibodies also induce the formation of neutrophil extracellular traps (NETs). Additionally, ACPAs induce pathogenic cytokines expression and oxidative stress in immune cells derived from RA patients. The aim of this review is to show the pathogenic roles of these autoantibodies in RA.
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.
Inflammation induced by toxins, micro-organisms, or autoimmunity may result in pathogenic fibrosis, leading to long-term tissue dysfunction, morbidity, and mortality. Immune cells play a role in both induction and resolution of fibrosis. γδ T cells are an important group of unconventional T cells characterized by their expression of non-major histocompatibility complex restricted clonotypic T cell receptors for non-peptide antigens. Accumulating evidence suggests that subsets of γδ T cells in experimentally induced fibrosis following bleomycin treatment, or infection with Bacillus subtilis, play pro-inflammatory roles that instigate fibrosis, whereas the same cells may also play a role in resolving fibrosis. These processes appear to be linked at least in part to the cytokines produced by the cells at various stages, with interleukin (IL)-17 playing a central role in the inflammatory phase driving fibrosis, but later secretion of IL-22, interferon γ, and CXCL10 preventing pathologic fibrosis. Moreover, γδ T cells appear to be involved, in an antigen-driven manner, in the prototypic human fibrotic disease, systemic sclerosis (SSc). In this paper we review in brief the scientific publications that have implicated γδ T cells in fibrotic diseases and their pro- and anti-fibrotic effects.
Epidemiological studies have shown that patients with psoriatic arthritis (PsA) are often affected by numerous comorbidities that carry significant morbidity and mortality. Reported comorbidities include diabetes mellitus, obesity, metabolic syndrome, cardiovascular diseases, osteoporosis, inflammatory bowel disease, autoimmune eye disease, non-alcoholic fatty liver disease, depression, and fibromyalgia. All health care providers for patients with PsA should recognize and monitor those comorbidities, as well as understand their effect on patient management to ensure an optimal clinical outcome.
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.
We are proud to introduce you to the Thirteenth Rambam Research Day, now established as a key annual event at Rambam Health Care Campus (Rambam), reflecting the diverse research activities on our campus...
Introduction: The primary non-pharmacological management recommended for patients with osteoporosis (OP) is exercise, but whether it should be high-force, resistive, or other means can be obscure.
Objective: To describe the role of exercises in osteoporotic fracture prevention, identify effects and potential risks of high-force exercises, detect the optimal exercises to combat OP, and explore the challenges that might arise from interventions.
Methods: A search on MEDLINE and Cochrane databases was conducted on the role of exercises in preventing osteoporotic fractures from 1989 onwards, leading to 40 results, including op-ed pieces, qualitative studies, randomized clinical trials (RCTs) (n=5), and RCT follow-up studies (n=1). Articles deemed relevant to the objectives were analyzed and summarized. Data on effects of vitamin D and calcium supplementation were later gathered from different sources as well.
Results: High-intensity, resistive strength training provided the maximum benefit in increasing bone mineral density (BMD) levels, muscle mass, and reduction in fractures, while posture and balance exercises only improved mobility. High-force exercises did not increase fractures and were associated with increases in BMD. Interventions including exercises, vitamin D, and calcium intake had limited effect when used as single interventions, while vitamin D and calcium may potentially cause increases of cardiovascular events.
Conclusion: A long-term regular exercise program designed to improve postural stability, mobility, and mechanical efficiency, alongside an increased vitamin D and dietary calcium intake, is most effective in preventing OP and reducing osteoporotic fractures.
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.
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.
Functional sexual pain disorders in women are a particular challenge to the gynecologist, inasmuch as phobic avoidance and guarding on the part of the patient lead to difficulties in the gynecological examination and diagnosis. In some such cases examination may even be impossible. Vaginismus is the commonly diagnosed etiology of such cases. This article offers an overview of vaginismus and approaches to its treatment but also examines a subset of penetration-avoidant patients who do not appear to have a pain component. We have reviewed this separate category conceptually and clinically, and propose that this case subset be separated from the diagnosis of vaginismus and designated as vaginal penetration phobia (VPP). We further propose that this category be diagnosed as one of several possible presentations of phobic disorder, under the rubric of mental health disorder, and thus be separated from gynecology. The nosological implications are raised.
