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.
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. ...
Current leading figures in medical science usually focus on very specific topics and use cutting-edge technologies to broaden our knowledge in the field. The working environment of the 19th century was much different. Medical giants of that time such as Rudolph Virchow and Thomas Hodgkin had a wide-ranging scope of research and humanitarian interests and made enormous contributions to a variety of core areas of medicine and the well-being of mankind. The year 2016 marked the 150th anniversary of the death of Dr. Thomas Hodgkin. Even a brief review of his life and work proves the current relevance of the outstanding deeds of this exceptional physician, medical educator, and defender of human rights for the poor and underprivileged; his vision was far ahead of his time.
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.
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.
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.
Obstetric anal sphincter injuries (OASIs) following vaginal deliveries are the main reason for subsequent development of anal incontinence in women. The diagnosis of such tears is crucial for treating and preventing such a grave sequela. The reported rate of OASIs in Israel was between 0.1% and 0.6%, out of all vaginal births, which is 10-fold lower than that reported in Europe and the United States. Structured hands-on training in repair of OASIs in seven medical centers in Israel significantly increased the detection rate of third-degree perineal tears. The implementation of such programs is crucial for increasing awareness and detection rates of OASIs following vaginal deliveries.
Portraits of pregnant women are rare in Catholic Renaissance art. In seventeenth-century Holland, the Catholic rule of Spain had been thrown off and a Protestant Calvinistic republic emerged, freeing Dutch artists to choose an unorthodox subject matter for their paintings. The Golden Age of Holland was characterized by extreme wealth, originating from overseas trade, which fostered a marked interest in philosophy, science, medicine, as well as art. Despite this, portraiture of pregnancy remained uncommon. An exception to this rule was Jan Vermeer of Delft, who lived during the zenith of this era. Jan Vermeer painted fewer than 40 pictures, fathered 15 children, and died bankrupt and little appreciated at the age of 43. Vermeer confined himself almost entirely to images of women in various domestic situations, including three figures of pregnant women. In this framework, pregnancy could be viewed as an icon for fidelity and conformism to social expectations. In this paper we investigate the roots of this unusual icon in Vermeer’s oeuvre, and suggest that the use of pregnancy in his paintings could have been inspired by his Delft-resident contemporaries Antony van Leeuwenhoek and Reinier de Graaf, fathers of well-known and opposing theories of reproduction. These eminent scientists and Vermeer’s pregnant wife, who frequently served as his model, might have made pregnancy less mysterious and more realistic to the painter.
Objective: Data on the prevalence of patent processus vaginalis (PPV) and hernia in patients with cryptorchidism are controversial. While some pediatric surgeons do not dissect the processus vaginalis (PV), most prefer to do so to prevent hernia formation and to achieve an effective orchiopexy outcome. This study was performed to evaluate the importance of dissection and high ligation of the PV during treatment of undescended testis (UT).
Methods: The clinical findings and surgical procedures of 55 patients with UT were retrospectively investigated.
Results: The mean patient age was 2.5 (range 1.0–12.0) years. Non-palpable testis (NPT) was located on the right and left side in 39 and 16 patients, respectively. Ultrasonography revealed no testis in 10 patients and an atrophic testis in 7 patients. Seven patients had a parent with an inguinal hernia, and the silk sign or a PPV was detected during inguinoscrotal examination in 22 patients. Undescended testis repair was performed by an inguinal approach in all patients. The inguinal canal was opened in all patients; 42 patients had a wider-than-normal internal ring (>2.5 cm), and the posterior wall of the inguinal canal was consequently weakened. Two-stage orchiopexy was performed in 2 patients, and 15 underwent the Prentiss maneuver. In the remaining patients, the dissection was easily done, and the orchiopexy was performed without any difficulty. Scrotal edema and wound infection occurred in five and two patients, respectively. One patient presented with an atrophic testis, and three had recurrent UT. Inguinal hernia was not observed in any of the patients during the study period, and all procedures were performed on an outpatient basis.
Conclusion: High ligation of the PV is an effective method for successful orchiopexy and prevention of inguinal hernia in patients with NPT and UT.
Background: Crimean–Congo hemorrhagic fever (CCHF) is a tick-borne viral disease with a high mortality rate. Although CCHF has been widely investigated over the past decade, a review of the literature indicated no data on the prognostic capacity of the mean platelet volume-to-platelet count ratio (MPVPCR) and the red cell distribution width-to-platelet count ratio (RDWPCR) for the systemic inflammatory response in patients with CCHF. This study aimed to evaluate the prognostic ability of MPVPCR and RDWPCR on mortality in patients with CCHF.
Methods: A total of 807 patients that were admitted to the Cumhuriyet University Hospital’s Emergency Department from January 2010 to December 2018 were involved. The RDWPCR and MPVPCR were separately calculated via absolute blood red cell and platelet counts at the time of admission. Before performing receiver-operating characteristic (ROC) curve analysis to define the optimum cut-off values of MPVPCR and RDWPCR stepwise logistic regression analysis was used to determine the predictive factors related to mortality in CCHF patients.
Results: Values of both MPVPCR and RDWPCR were significantly lower in survivors than in non-survivors (MPVPCR: 0.20±0.23 versus 0.55±0.55, P<0.001; RDWPCR: 0.27±0.32 versus 0.77±0.77, P<0.001, respectively). The MPVPCR (odds ratio [OR], 5.95; P=0.048) was an independent predictor for the prognosis of mortality in CCHF patients. The area under the curve in the ROC curve analysis for MPVPCR was 0.876 with a cut-off of 0.21 (sensitivity 87%, specificity 76%).
Conclusion: At the time of admission, MPVPCR might be a useful predictor of mortality in patients with CCHF.