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  • Coronary Stenosis Physiology and Novel Technologies

    An accurate functional assessment of coronary artery stenosis is pivotal in the management and clinical outcomes of patients. The hemodynamic relevance of coronary artery stenoses can be assessed using coro-nary flow surrogates, namely fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). This review provides an overview of these indexes, their clinical relevance, as well as a review of the literature supporting their use. It also reviews novel image-based FFR (e.g. FFRangio), the evidence showing the accuracy of this technique when compared to conventional wire-based techniques, as well as the clinical implications of non-invasive coronary artery stenosis functional assessments.
  • The Ethics of Error in Medicine

    The practice of medicine forces medical practitioners to make difficult and challenging choices on a daily basis. On the one hand we are obligated to cure with every resource available, while on the other hand we put the patient at risk because our treatments are flawed. To understand the ethics of error in medicine, its moral value, and the effects, error must first be defined. However, definition of error remains elusive, and its incidence has been extraordinarily difficult to quantify. Yet, a health care system that acknowledges error as a consequence of normative ethical practice must create systems to minimize error. Error reduction, in turn, should attempt to decrease patient harm and improve the entire health care system. We discuss a number of ethical and moral considerations that arise from practicing medicine despite anticipated error.
  • Precision Medicine in Relapsed and Refractory Childhood Cancers: Single-center Experience, Literature Review, and Meta-analysis

    Objective: To date, the understanding of pediatric tumor genomics and how these genetic aberrations correlate with clinical outcome is lacking. Here, we report our experience with the next-generation sequencing (NGS) test program and discuss implications for the inclusion of molecular profiling into clinical pediatric oncology trials. We also aimed to explore studies on NGS in pediatric cancers and to quantify the variability of finding actionable mutations and the clinical implications. Methods: We present a retrospective case series of all patients whose tumor tissue underwent NGS tests during treatment in our department. We also reviewed the literature and carried out a meta-analysis to explore studies on NGS in pediatric cancers. Results: In 35/37 (94%) patients, we found at least one genomic alteration (GA); mean number of GAs per patient was 2 (range, 0–67), while 164 GAs were detected. Only 3 (8%) patients received precision medicine due to their GAs for a mean of 9 months (range, 5–14 months). Four studies were included in the meta-analysis. The pooled positive actionable mutation rate was 52% (95% CI 39%–66%), and the pooled rate of children who received precision medicine was 10% (95% CI 3%–20%). Conclusions: In children and young adults with high-risk, recurrent, or refractory malignancies, tumor profiling results have clinical implications, despite barriers to the use of matched precision therapy.
  • Extracorporeal Membrane Oxygenation (ECMO)—A Lifesaving Technology. Review and Single-center Experience

    Objective: Extracorporeal membrane oxygenation is used to bypass the cardiopulmonary system in a severe heart or/and lung failure, mainly in intractable conditions where all other therapy options fail or are unfeasible. Extracorporeal membrane oxygenation (ECMO) is a well-established therapeutic option in such circumstances for neonatal, pediatric, and adult patients. Managing a patient with ECMO requires dedicated and specific management. The importance and necessity of this essential technology in life-threatening cardio-respiratory rescue prompted Rambam Health Care Campus to implement it and make it available as a service to the population in northern Israel. This article includes a brief review of extracorporeal life support and a report of our single-center experience since the establishment of the service. Methods: The ECMO unit was established in 2014 under the responsibility of the Cardiac Surgery Department. The ECMO service was initiated by a well-planned program with consideration of all aspects including economics, education and training, the specialist team and equipment needed, strategies for medication, and ethical challenges. Results: Between February 2014 and May 2018, 65 patients were treated with ECMO; 43 patients received veno-arterial ECMO for cardiac support (66%), while 22 received veno-venous ECMO for respiratory support (34%). The in-hospital mortality was 56%. Conclusions: Extracorporeal membrane oxygenation is an effective therapy that is constantly growing in use and provides a therapy that can replace previous options. To establish such a service requires a planned program and concerted effort. Our single-center experience presented a good learning curve and showed the feasibility as well as the efficacy of the ECMO procedure in life-threatening conditions.
  • Deep Epicardial Laceration after Cardiopulmonary Resuscitation: A Case Report

    Effective chest compressions have been proven to be a key element in a successful cardiopulmonary resuscitation (CPR). However, unintended injuries have been described in the medical literature for decades, including major intrathoracic injuries. We present a case of an 80-year-old man after a successful CPR who was later diagnosed with deep epicardial laceration as a result of effective chest compressions.
  • Inappropriate Journal Authorship, Disputes, Plagiarism, and Mistrust in the Institution: Different Beasts ... Same Problem

    We would like to thank Professor Marshall Lichtman for his letter, his interesting proposal, and using this venue to promote discussion of the topic. Professor Lichtman proposed a numerical calculation for authorship based on the authors’ perceptions of their relative contribution to a scientific publication, an idea also suggested by Jozsef Kovacs. The only limitation imposed by this system is that the total of all authors’ fractional contributions to any one publication equals no more than one. Lichtman’s interesting proposal serves as a disincentive to offer gift authorship to colleagues whose contributions were minimal, if they contributed at all.
  • Familial Occurrence of Isolated Late-onset Nasolacrimal Duct Obstruction in Two Unrelated Families

    Late-onset nasolacrimal duct obstruction (NLDO) as a result of inflammatory processes causing dacryostenosis is a common entity affecting mostly women. While a few mechanisms have been suggested as contributors to the expression of NLDO, the trigger for the inflammation remains mostly unknown. Familial predilection for this condition has not been previously reported. We present two families with multiple individuals affected with congenital or late-onset NLDO, describe the signs and symptoms of the affected individuals, and explore their medical history for any contributing factors. Family A, spanning four generations, included 7 female patients affected by late-onset NLDO. Family B, spanning two generations, included 8 individuals affected by either congenital or late-onset NLDO. This case series suggests a familial predisposition to NLDO, apparently with an autosomal dominant inheritance pattern. Further studies are needed to elucidate the molecular basis of this genetic predisposition.
  • The Centrality of Trust in Academic Publishing Lies with the Corresponding Author

    To the Editor: I have followed, with great interest, the passionate debate held between Lichtman, and Ashkenazi and Olsha in Rambam Maimonides Medical Journal. Lichtman put forward a curious and enlightening proposal to offer a fractional value to each author, depending on the value of their relative contribution, with the total amounting to 1, as a way to reduce authorship abuses, such as gift or guest authorship, which are two very prevalent forms of authorship abuses in academic publishing today.
  • Interpreting PPV and NPV of Diagnostic Tests with Uncertain Prevalence

    Objective: Medical decision-making is often uncertain. The positive predictive value (PPV) and negative predictive value (NPV) are conditional probabilities characterizing diagnostic tests and assessing diagnostic interventions in clinical medicine and epidemiology. The PPV is the probability that a patient has a specified disease, given a positive test result for that disease. The NPV is the probability that a patient does not have the disease, given a negative test result for that disease. Both values depend on disease incidence or prevalence, which may be highly uncertain for unfamiliar diseases, epidemics, etc. Probability distributions for this uncertainty are usually unavailable. We develop a non-probabilistic method for interpreting PPV and NPV with uncertain prevalence. Methods: Uncertainty in PPV and NPV is managed with the non-probabilistic concept of robustness in info-gap theory. Robustness of PPV or NPV estimates is the greatest uncertainty (in prevalence) at which the estimate’s error is acceptable. Results: Four properties are demonstrated. Zeroing: best estimates of PPV or NPV have no robustness to uncertain prevalence; best estimates are unreliable for interpreting diagnostic tests. Trade-off: robustness increases as error increases; this trade-off identifies robustly reliable error in PPV or NPV. Preference reversal: sometimes sub-optimal PPV or NPV estimates are more robust to uncertain incidence or prevalence than optimal estimates, motivating reversal of preference from the putative optimum to the sub-optimal estimate. Trade-off between specificity and robustness to uncertainty: the robustness increases as test-specificity decreases. These four properties underlie the interpretation of PPV and NPV. Conclusions: The PPV and NPV assess diagnostic tests, but are sensitive to lack of knowledge that generates non-probabilistic uncertain prevalence and must be supplemented with robustness analysis. When uncertainties abound, as with unfamiliar diseases, assessing robustness is critical to avoiding erroneous decisions.
  • Management of Failed Surgery for Anterior Glenohumeral Instability: Synopsis of Clinical Evidence

    Failed surgical treatment of anterior shoulder instability should be treated according to clinical principles similar to primary stabilization by addressing risk factors related to the damaged static glenohumeral stabilizers (labrum, capsule and its components, and bony damage to the humeral head and scapular glenoid). In relatively rare conditions when failed primary surgery involves patients with functionally low demands, conservative treatment by strengthening dynamic muscular stabilizers might be considered; otherwise, surgical revision should be strongly considered aimed at improving quality of life. Although the overall failure rate following primary and revision surgery is expected to be below 4%, it is clear that revision surgery is technically demanding. Therefore, the initial recognition and correction of the exact pathology causing glenohumeral instability is crucial to avoid failure of primary surgery and to facilitate the success of the revision procedure, if necessary.