Urological malignancies are a major source of morbidity and mortality in men over 40. Screening for those malignancies has a potential benefit of reducing both. However, even after more than two decades of screening for prostate cancer, the implications of most resulting information are still a matter of debate. Controversy extends over several aspects of prostate cancer screening programs, including age of onset, defining populations at risk, most appropriate intervals, as well as the optimal methods to be used for screening. The medical community is still divided regarding the effectiveness of prostate cancer-related death prevention and its benefits-to-harms ratio, reflecting an inconsistency regarding screening recommendations. Similarly, benefits of screening for urothelial and kidney tumors are yet lacking high- level evidence, although recent evidence supports screening of populations at risk. Clearly, the current era of evolving molecular and genetic biomarkers harbors the potential to change screening practice. In this paper, we review current guidelines as well as giving an update on new developments which might influence screening strategies in common urological malignancies.
Today medical imaging is an essential component of the entire health-care continuum, from wellness and screening, to early diagnosis, treatment selection, and follow-up. Patient triage in both acute care and chronic disease, imaging-guided interventions, and optimization of treatment planning are now integrated into routine clinical practice in all subspecialties. This paper provides a brief review of major milestones in medical imaging from its inception to date, with a few considerations regarding future directions in this important field.
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.
Chemotherapy-associated myocardial toxicity is increasingly recognized with the expanding armamentari¬um of novel chemotherapeutic agents. The onset of cardiotoxicity during cancer therapy represents a major concern and often involves clinical uncertainties and complex therapeutic decisions, reflecting a compro¬mise between potential benefits and harm. Furthermore, the improved cancer survival has led to cardio¬vascular complications becoming clinically relevant, potentially contributing to premature morbidity and mortality among cancer survivors. Specific higher-risk populations of cancer patients can benefit from pre¬vention and screening measures during the course of cancer therapies. The pathobiology of chemotherapy-induced myocardial dysfunction is complex, and the individual patient risk for heart failure entails a multifactorial interaction between the selected chemotherapeutic regimen, traditional cardiovascular risk factors, and individual susceptibility. Treatment with several specific chemotherapeutic agents, including anthracyclines, proteasome inhibitors, epidermal growth factor receptor inhibitors, vascular endothelial growth factor inhibitors, and immune checkpoint inhibitors imparts increased risk for cardiotoxicity that results from specific therapy-related mechanisms. We review the pathophysiology, risk factors, and imaging considerations as well as patient surveillance, prevention, and treatment approaches to mitigate cardiotox¬icity prior, during, and after chemotherapy. The complexity of decision-making in these patients requires viable discussion and partnership between cardiologists and oncologists aiming together to eradicate cancer while preventing cardiotoxic sequelae.
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.
We are proud to introduce you to the Fifteenth Annual Rambam Research Day, now established as a key annual event at Rambam Health Care Campus, Haifa, Israel, reflecting the diverse research activities on our campus.
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.
Anti-citrullinated protein antibodies (ACPAs) are highly specific serologic markers for rheumatoid arthritis (RA) and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD) enzymes present in polymorphonuclear cells (PMNs). Calcium ions (Ca2+) are required for PAD activation, but the intracellular Ca2+ concentration in normal cells is much lower than the optimal Ca2+ concentration needed for PAD activation. For this reason, it has been proposed that PAD activation, and thus citrullination, occurs only during PMN cell death when PAD enzymes leak out of the cells into the extracellular matrix, or extracellular Ca2+ enters the cells, with the high Ca2+ concentration activating PAD. Recently, using artificial in vitro systems to corroborate their hypothesis, Romero et al. demonstrated that “hypercitrullination,” citrullination of multiple intracellular proteins, occurs within synovial fluid (SF) cells of RA patients, and that only modes of death leading to membranolysis such as perforin-granzyme pathway or complement membrane attack complex activation cause hypercitrullination. In order for Romero’s hypothesis to hold, it is reasonable to surmise that PMN-directed lysis should occur in the rheumatoid joint or the circulation of RA patients. Research conducted thus far has shown that immunoglobulin G (IgG) targeting PMNs are present in RA SF and mediate PMN activation. However, the role of anti-PMN IgG in mediating complement activation and subsequent PMN lysis and hypercitrullination has not been fully evaluated.
Born in Portugal and the son of Marranos (Christianized Jews from Spain), Eliahu de Luna Montalto lived during a particularly harsh period for the Jewish people. Throughout Europe, the situation for Jews was unfavorable; laws had been passed forbidding them to live in England for the past 300 years, and for the past 200 years in France. Additionally, in France, while Jews were permitted to study at some universities, the practice of medicine was forbidden to them. It is within this context that Eliahu de Luna Montalto, who had returned to his original faith (Judaism), was recruited to the French court. This paper pays tribute to Montalto’s life and medical practice—so exemplary that the Queen of France would ask Montalto to serve at the court and receive Papal permission for Montalto openly to observe his faith as a Jew, this despite the objections of the King of France.
Autoinflammatory diseases (AID) are characterized by seemingly unprovoked self-limited attacks of fever and systemic inflammation potentially leading to amyloidosis. Familial Mediterranean fever (FMF) is the most common AID and therefore the most studied. Besides FMF, the other main hereditary AID are tumor necrosis factor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD), and cryopyrin-associated periodic fever syndrome (CAPS). These hereditary diseases result from a mutant gene that is involved in the regulation of inflammation, resulting in a characteristic clinical phenotype. The differential diagnosis of AID can be challenging due to a wide overlap in clinical manifestations. Moreover, a considerable proportion of patients present with autoinflammatory symptoms but without a pathogenetic variant on genetic analysis. Furthermore, non-hereditary AID, such as the periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA) syndrome, which is the most common AID in children worldwide, must be excluded in certain circumstances. Herein we shall review the main AID and describe a practical approach to diagnosis in a patient with a clinical suspicion of AID.
