Good morning. It is a great pleasure to share my thoughts with you here in Israel. The last day I was here was June 25, 2016, which was the day of the results of the Brexit referendum. My wife and I escaped feeling so depressed, but at least, we thought, we are leaving this behind; but when we came to Israel the only thing people wanted to talk about was the Brexit referendum!
Here I am today, on October 31, 2019, the day that we were meant to be leaving the European Union, so there is something with my connection with Israel and Brexit that I don’t understand! Let me start by saying that we have the privilege of being participants in a biomedical and health science revolution. I don’t think that is overstating it. We are living in an extraordinary, exciting time. Let me remind you of some of these fields that are moving so fast.
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.
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.
To the Editor,
We read with great interest the original research published by Anatoli Stav et al.1 in which they com-pared supraclavicular (SCL), infraclavicular (ICL), and axillary (AX) approaches to the brachial plexus with ultrasonography for upper limb surgeries.1 They concluded that all approaches can be used to provide adequate anesthesia for upper limb sur-geries below the shoulder. Nevertheless, they also experienced some sparing and failed blocks: 3 patients from the SCL group, 3 from the ICL group, and 4 from the AX group had a positive pin-prick test; 2 patients from the AX group received sedation supplementation; and 1 patient in the AX group experienced ulnar sparing which required a general anesthetic. ...
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.
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.
To the Editor, the article of Krutikov and Manson1 was interesting. However, no comment was made on the impact and related clinical epidemiology of the chikungunya virus (CHIKV) infection during the 2014–2015 epidemics in Latin America, the most recent area affected by CHIKV. Certainly, persistent musculoskeletal manifestations of the disease have been shown to affect a highly variable proportion of infected patients (even >87%). Following the epidemics in La Réunion Island and India,2 and now in Latin America, this disease is having a significant impact. ...
To the Editor, Dr Nair’s letter to the editor regarding the failed nerve blocks mentioned in our paper, “Comparison of the supraclavicular, infraclavicular and axillary approaches for ultrasound-guided brachial plexus block for surgical anesthesia”,1 raised several points that I believe are worth looking at in more detail. We are grateful for Dr Nair’s comments which have contributed to the furthering of scholarly discourse.
In general, Dr Nair’s letter relates to the blocks that our research classified as failed. He then discusses various approaches and suggests the reason for the failures of the axillary approach blocks.
Roderigo Lopez, former Physician-in-Chief to Queen Elizabeth I of England, was a controversial figure in his time and continues to be the subject of controversy. Much has been written about his religious practice, politics, and guilt, or lack thereof, with regard to charges of treason to the Crown. However, the fact remains that Lopez was the only physician to the Crown to be sentenced to death. All evidence points to an anti-Semitic mindset that played in the background. Yet Lopez so endeared himself to the Queen that although he was indeed sentenced to death, almost all of his property was restored to his family. This brief paper pays tribute to the Jewish physician, Roderigo Lopez, whose story was indeed a triumph over prejudice, despite his fate.
To evaluate the decrease in luteinizing hormone (LH) levels following gonadotropin-releasing hormone (GnRH) antagonist administration in in vitro fertilization (IVF) cycles, data were retrospectively collected from 305 consecutive IVF or intracytoplasmic sperm injection (ICSI) cycles of patients who underwent ovarian stimulation with gonadotropins and were treated with GnRH antagonist for the prevention of premature luteinization. We compared the percent change in LH concentration from stimulation start to that observed before ovulation triggering in patients with or without anovulation. Anovulatory patients were younger, with higher body mass index (BMI), and demonstrated higher ovarian reserve parameters as compared to ovulatory patients. The decline in LH concentration was almost two-fold greater in anovulatory versus ovulatory patients. Numbers of oocytes, fertilizations, cleavage stage embryos, and transferred embryos were similar; however, implantation rates were higher in anovulatory versus ovulatory patients. Older patients (age ≥39) showed a smaller decline in LH levels as compared to younger ones (age <39) and exhibited poor IVF outcomes. There is a wide range of pituitary responses to GnRH antagonists. Anovulatory patients are more susceptible to GnRH antagonists and therefore demonstrate over-suppression of the pituitary. Older patients demonstrate a reduced pituitary response to GnRH antagonists than younger ones. Cycle scheduling with estradiol pretreatment did not influence LH decline, nor IVF treatment outcomes.
