The neurovascular unit is a key player in brain development, homeostasis, and pathology. Mental stress affects coagulation, while severe mental illnesses, such as recurrent depression and schizophrenia, are associated with an increased thrombotic risk and cardiovascular morbidity. Evidence indicates that the hemostatic system is involved to some extent in the pathogenesis, morbidity, and prognosis of a wide variety of psychiatric disorders. The current review focuses on emerging data linking coagulation and some psychiatric disorders.
This paper is provided for the convenience of our readers and represents a full edited transcription of the Rambam Grand Rounds Lecture by Dr. Richard Horton, Editor-in-Chief of The Lancet. The lecture was given on October 2, 2014. The Editorial Board wishes to express its gratitude to Dr. Horton for giving permission to present his Rambam Grand Rounds lecture in Rambam Maimonides Medical Journal, in both the original video format and in this printed form.
On May 28, 2014, colleagues from the Mayo Clinic visited Rambam Health Care Campus to gather and exchange ideas and knowledge. American and Israeli caregivers and scientists shared with each other the daily challenges of their practice in many and varied settings. This issue is dedicated to the presentations given and the collaborative efforts we are building as a result of that visit. We hope this issue will serve as an example of the fruitfulness of international collaboration to enhance and propagate medical knowledge worldwide.
An anniversary is not only a point of memory—it provides the opportunity for self-examination and paves the way to the future. Every anniversary marks a starting-point that was preceded by a vision. The beginning of any vision is a personal dream—someone wants to improve or repair the world as far as he is able. The vision motivates action; in its aftermath comes the reality. This is the 21st issue of Rambam Maimonides Medical Journal. This issue is particularly important as it marks the completion of five years of creative work pursuing our vision for a high-caliber scientific medical journal. Our vision has become reality.
Whilst painting the vault of the Sistine Chapel, Michelangelo Buonarroti left an autographical sketch that revealed a prominence at the front of his hyper-extended neck. This image was recently diagnosed as goiter. The poet Michelangelo in a sonnet dated 1509 described himself as being afflicted by goiter similarly to the cats in the northern Italian Lombardy, a region with endemic goiter. Several narratives extended this sonnet into a pathological theory. The analyses of Michelangelo’s works, however, his portraits and self-portraits, of poems and major biographies, have not indicated the likelihood of goiter. This investigation makes an attempt to assess the diagnosis on clinical as well as iconographical grounds.
As I shared in my January 2015 editorial, the furor surrounding publication in The Lancet of the open letter by P. Manduca et al. carried potential for bad and for good. Here at Rambam Health Care Campus, we have chosen and will continue to look for the good.
The Lumenis® High-power Holmium Laser (120H) has a unique modulated pulse mode, Moses™ technology. Moses technology modulates the laser pulse to separate the water (vapor bubble), then deliver the remaining energy through the bubble. Proprietary laser fibers were designed for the Moses technology. Our aim was to compare stone lithotripsy with and without the Moses technology.
Methods. We designed a questionnaire for the urologist to fill immediately after each ureteroscopy in which the Lumenis 120H was used. We compared procedures with (n=23) and without (n=11) the use of Moses technology. Surgeons ranked the Moses technology in 23 procedures, in comparison to regular lithotripsy (worse, equivalent, better, much better). Laser working time and energy use were collected from the Lumenis 120H log.
During 4 months, five urologists used the Lumenis 120H in 34 ureteroscopy procedures (19 kidney stones, 15 ureteral stones; 22 procedures with a flexible ureteroscope, and 12 with a semi-rigid ureteroscope). Three urologists ranked Moses technology as much better or better in 17 procedures. In 2 cases, it was ranked equivalent, and in 4 cases ranking was not done. Overall, laser lithotripsy with Moses technology utilized laser energy in less time to achieve a satisfying stone fragmentation rate of 95.8 mm3/min versus 58.1 mm3/min, P=0.19. However, this did not reach statistical significance.
Conclusion. The new Moses laser technology demonstrated good stone fragmentation capabilities when used in everyday clinical practice.
Despite daunting circumstances, history is full of stories of men and women incarcerated by the Nazis, who risked their lives to save others. In some cases, the moral dilemma faced by these people presented an unquestionable challenge—particularly for those in the medical profession who had taken an oath to save life. This paper presents the dramatic stories of Dr. Gisella Perl and Dr. Erno Vadasz. Although their choices were markedly different, their goals were the same—to save as many lives as possible.
Objective. To compare the reported accuracy and sensitivity of the various modalities used to diagnose autism spectrum disorders (ASD) in efforts to help focus further biomarker research on the most promising methods for early diagnosis.
Methods. The Medline scientific literature database was searched to identify publications assessing potential clinical ASD biomarkers. Reports were categorized by the modality used to assess the putative markers, including protein, genetic, metabolic, or objective imaging methods. The reported sensitivity, specificity, area under the curve, and overall agreement were summarized and analyzed to determine weighted averages for each diagnostic modality. Heterogeneity was measured using the I2 test.
Results. Of the 71 papers included in this analysis, each belonging to one of five modalities, protein-based followed by metabolite-based markers provided the highest diagnostic accuracy, each with a pooled overall agreement of 83.3% and respective weighted area under the curve (AUC) of 89.5% and 88.3%. Sensitivity provided by protein markers was highest (85.5%), while metabolic (85.9%) and protein markers (84.7%) had the highest specificity. Other modalities showed degrees of sensitivity, specificity, and overall agree¬ments in the range of 73%–80%.
Conclusions. Each modality provided for diagnostic accuracy and specificity similar or slightly higher than those reported for the gold-standard Autism Diagnostic Observation Schedule (ADOS) instrument. Further studies are required to identify the most predictive markers within each modality and to evaluate biological pathways or clustering with possible etiological relevance. Analyses will also be necessary to determine the potential of these novel biomarkers in diagnosing pediatric patients, thereby enabling early intervention.
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.
