Therapy for inflammatory bowel diseases (IBD) has developed during recent years. Despite the availability of new therapeutic modalities, overall therapy success remains modest, and complete remission is usually achieved and maintained in approximately 30% of patients only. This observation can be explained by a number of reasons. First, the involvement of multiple genetic loci combined with differential environmental exposures suggests that IBD represent a continuum of disorders rather than distinct homogeneous disease entities. This diversity is translated into different disease course patterns, wherein some patients experience quiescent disease whereas others suffer from a relentless disease course. Hence, basic disease pathogenesis sets the stage for differential treatment responses. To date, IBD therapy is based on immunosuppression which does not take basic disease variability into account. Treatments are prescribed based on statistical considerations related to the response of the average patient in clinical trials rather than on personal considerations. Treatment outcomes can potentially be improved if physiologic considerations are inte¬grated into the drug selection process. In one approach, drugs can be targeted at known patient dysfunc¬tional processes such as in the case of patients carrying autophagy-related genetic polymorphisms being treated with rapamycin, a drug that inhibits mTOR inhibitor and enhances autophagy. Another alternative would be to use a systems approach to perform unsupervised, high-throughput screening in order to derive predictive treatment biomarkers and mechanistic insights associated with response to specific drug therapy. Additional predictive markers for drug safety are needed as well. Caveats and directions for needed future studies are outlined.
Background: The use of electric bicycles (E-bikes) has dramatically increased over the last decade. E-bikes offer an inexpensive, alternative form of transport, but also pose a new public health challenge in terms of safety and injury prevention.
Objective: The aim of this study was to describe the epidemiology and severity of E-bike related injuries among children treated in the emergency department (ED) and to compare these to manual bicycle related injuries.
Methods: A retrospective observational study of all pediatric patients presenting to the ED between December 2014 and November 2015 with an injury related to E-bike or manual bicycle use. Data including demographics, diagnosis, injury severity score (ISS), and outcome were compared.
Results: A total of 196 cyclist injuries presented to the ED; 85 related to E-bike use and 111 to manual bicycle riders. The mean age of E-bikers was 13.7 years (7.5–16 years) and of manual bicycle riders was 9.9 years (3–16 years). Injuries to the head and the extremities were common in both groups. E-bikers had significantly more intra-abdominal organ injury (P=0.047). Injury severity scores were low overall, but injuries of higher severity (ISS>9) only occurred among the E-bikers.
Conclusions: Pediatric E-bike injuries tend to be more severe than those sustained during manual bicycle riding. Further research into bicycle and other road and pavement users could lead to enhanced regulation regarding E-bike usage.
United States (US) and European Union (EU) laws attempt to counterbalance the presumed discrimination of children in drug treatment and drug development. The US Food and Drug Administration (FDA)-rewarded pediatric studies with antidepressants triggered in 2004 an FDA black-box warning of suicidality in young patients. Fewer antidepressants were prescribed, and the number of completed suicides of young persons increased. The dilemma between this warning and the need to adequately treat young depressed patients remains unsolved. We analyzed the history of drug development, the evolving view of diseases in young patients, US/EU pediatric laws, and pediatric studies triggered by FDA/European Medicines Agency (EMA) in depression and other diseases on the background of developmental pharmacology; financial, institutional, and other interests; and the literature. The FDA/EMA define children administratively, not physio¬logically, as <17 (FDA)/<18 years old (EMA). But young persons mature physiologically well before their 17th/18th birthday. Depression occurs in young persons, has special characteristics, but is not fundamentally different from adult depression. Young persons are not another species. Regulatory requirements for “pediatric” studies focus on “pediatric” labels. Many “pediatric” studies, including those in depression, lacked and lack medical sense and harm patients by placebo treatment although effective drugs exist. The FDA has partially abandoned separate “pediatric” efficacy studies, but not in psychiatry. Clinicians, parents, institutional review boards, and ethics committees should become aware of questionable “pediatric” studies, should re-evaluate ongoing ones, consider to suspend them, and to reject new ones. The concept of separate “pediatric” drug approval needs to be abandoned.
Objectives: To analyze, perioperatively and in follow-up, transilluminated powered phlebectomy (TIPP), a surgical technique for the treatment of varicose veins.
Method: Retrospective study in one medical institution of patients undergoing TIPP between July 2015 and December 2017. Data analyzed included demographic data, surgery, and results. Postoperatively, pain was evaluated by a 10-point visual analogue scale. The Venous Clinical Severity Score (VCSS) was assessed 5–8 weeks following surgery.
Results: Sixty-six patients with extensive varicosities who underwent TIPP were included. Postoperative pain scores were higher in patients undergoing bilateral compared to unilateral TIPP (visual analogue score 7 versus 5; P=0.031). Following surgery, the VCSS improved in 81.8% (54/66) of the patients. However, 39.7% (25/63; data missing in 3 patients) reported that they would not be willing to undergo a similar procedure in the future. Pain was the most common reason for dissatisfaction.
Conclusions: Transilluminated powered phlebectomy was associated with considerable pain and discom¬fort in many patients included in this study. For this reason, it should be reserved for a select group of patients in whom other treatment options are limited; TIPP could be considered in the following cases: patients with a large number of varicosities, reoperations, after extensive thrombophlebitis, obesity, or following bariatric surgery.
Beyond the increase in medical knowledge and biotechnology during the last decades, doctors have adopted professional norms that would have been considered heretical only two generations ago. The changes transpired between the 1970s and 1990s, and generated controversies between those who upheld the traditional values of patient care, and those who welcomed the new professional norms. Professor Dr Johannes Juda Groen (1903–1990) predicted and promoted some of these changes. As early as the 1940s through the 1960s, he recognized the need to teach interviewing skills and advocated an orientation to patients, rather than to diseases; he supported decision-making based on evidence, rather than on personal experience and pathophysiologic rationale; and he demonstrated that psychosocial determinants predict, rather than only correlate with, disease. These views led to confrontations with the medical establishments in the Netherlands and in Israel. Still, many of his colleagues recognized the value of his contributions. The author, for one, admires Groen’s commitment in challenging the prevailing clinical wisdom after the end of World War 2, and his courage in opposing the views of his colleagues.
Background: There is a consensus among the halachic authorities that life-saving actions override Sabbath prohibitions. They are painstaking in securing that the sanctity of the Sabbath is maintained but that not a single life be lost.
Objective: This manuscript examines if and when a relative’s presence at the bedside of a seriously ill individual is potentially life-saving against the backdrop of the scientific literature. It specifically addresses the permissibility of traveling in a motorized vehicle, generally prohibited on the Sabbath, to be with one’s relative in hospital for the provision of emotional support.
Methods: Discourse of the halachic issues in the context of the scientific literature.
Results: Stress, mental or physical, has been determined as a potentially life-threatening condition in many disease entities. The literature attests to both the patient’s and the professionals’ perception of the curative potential of the presence of loved ones by advocating for the patient and relieving stress in the hospital experience. Emotional support from a loved one is perceived by some patients as vital to survival. There is halachic consensus that a patient’s perception of the emotional need for a relative’s presence is sufficient to permit overriding rabbinic prohibitions. Torah prohibitions, which may be overridden for medical needs, may be overridden for emotional support, providing a health professional or family member attests to the fulfilment of this specific need as diminishing the danger to the patient’s life. In certain cases, the latter contingency is unnecessary.
Conclusions: Emotional support has an impact on the patient’s health status; the degree to which its impact is strong enough to save life is still being studied. As more data from scientific studies emerge, they may be relevant to sharpening the halachic rulings with respect to the issue at hand.
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.
Sacroiliitis, inflammation of the sacroiliac joint (SIJ), is the hallmark of ankylosing spondylitis and spondyloarthritis (SpA) in general. The arsenal of recommended diagnostic modalities for imaging of the SIJ is scanty and, in practice, includes only conventional X-rays and magnetic resonance imaging (MRI). This review suggests that bone scintigraphy, particularly single-photon emission computed tomography (SPECT) with calculation of indices, or SPECT in combination with low-dose computed tomography (CT) can be a sensitive and specific tool for the diagnosis of sacroiliitis and can be used as part of the individualized approach to the diagnosis of axial SpA. In addition, [18F]fluoride positron emission tomography (PET)/CT imaging and immunoscintigraphy, using labeled monoclonal anti-cytokine anti-bodies, are promising methods of current scientific interest in this field.
Long-standing diabetes leads to structural and functional alterations in both the micro- and the macro-vasculature. Designing therapies to repair these abnormalities present unique and sophisticated challenges. Vascular endothelial cells are the primary cells damaged by hyperglycemia-induced adverse effects. Vascular stem cells that give rise to endothelial progenitor cells and mesenchymal progenitor cells represent an attractive target for cell therapy for diabetic patients. In this review, we shed light on challenges and recent advances surrounding stem cell therapies for diabetes vascular complications and discuss limitations for their clinical adoption.
A physician is a valued member of society on whom many individuals rely for both professional advice and support during times where they may feel to be at a disadvantage, whether it be physically or mentally. An issue on the rise today concerns the population of smokers in our society. Many are coming to share the opinion that physicians should not provide treatments for smokers. Some of the opinions are based on the claim that smokers are morally responsible for their medical conditions. But, providing care in a fair manner includes not treating differently those who suffer from addiction. Moreover, it is important to recognize that allocating medical resources based on moral responsibility will undermine the physician–patient relationship which is necessary for the practice of medicine. Many countries have codes and policies that physicians must legally follow in terms of providing treatments. With acceptance of the fact that the patient may be unable to execute the decisions made by the physician, it is the legal duty of the physician to provide care and not abandon the patient. An analysis of the many policies around the world brings forward certain changes that must be made in order to make sure that physicians fulfil their legal duty, which is to provide care. As such, this article looks into the existing ethical dilemma in treating smokers around the world, with a review of some policies that will guide our approach in this matter.
