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.
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.
TO THE EDITOR
We read with interest the report by Yeshayahu about four minors who were diagnosed late with non-COVID-19 diseases during the COVID-19 pandemic (Rambam Maimonides Med J 2021;12:e0017. doi: 10.5041/RMMJ.10431 ). We would like to emphasize that, firstly, such delays are not limited to minors, and secondly, that also in minors should we distinguish the administrative and the physiological meanings of the term “child” and hence distinguish administratively defined “chil¬dren” who bodily are already mature from those young patients who bodily are indeed still children.
Objective: Israeli hospitals were confronted with a major national outbreak of carbapenemase-producing Enterobacterales (CPE) starting in 2006, caused predominantly by monoclonal Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae. Our hospital, Rambam Health Care Campus (RHCC), was one of the medical centers affected by this outbreak. We aimed to investigate the changing epidemiology of CPE at RHCC since 2006.
Methods: This was a retrospective observational cohort study performed in Northern Israel (Haifa) at RHCC, which is a primary tertiary acute care academic hospital. The study included all patients who had acquired CPE at RHCC between January 2005 and December 2020.
Results: The proportion of patients infected with K. pneumoniae dropped from 100% of all CPE in the first years to 28% (37/134) in 2020. In 2014, the carbapenemase in 94% of all CPE patients (89/95) was KPC. This decreased to 56% in 2020, while New Delhi metallo-β-lactamase (NDM) and OXA-48 carbapenemases increased from 4% and 2% to 29% (39/134) and 12.7% (17/134) of CPE, respectively.
Conclusions: The CPE epidemic evolved from KPC-producing K. pneumoniae to involve different Enterobacterales and carbapenemases. Our results are a microcosm of the current global epidemiology attesting to globalization in bacteriology. The results have implications for infection control and antibiotic treatment of CPE infections.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a rare systemic small-vessel disease, with heterogeneous clinical manifestations. While arthralgia and myalgia are common in the disease course, frank myositis is exceedingly rare. Immune-mediated necrotizing myopathy (IMNM) is a subtype of idiopathic inflammatory myopathies (IIMs), characterized by severe myositis. We report herein a case of prominent diffuse myositis with shared features of AAV and IMNM.
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were elaborated to allow authors of such papers to identify quality articles for inclusion in their scholarly work. However, we have identified several issues that point to an over-reliance on the PRISMA guidelines. Firstly, we question the rigor of implementation by authors and the rigor of verification by peer reviewers and editors, and whether they have screened papers to ensure adherence to the PRISMA guidelines. Secondly, we have identified cases where the PRISMA criteria led to as much as 99.97% of the published literature being ignored, suggesting that valid publications meeting these criteria might be at risk of being ignored. Thirdly, we have noted that exclusion is not only a quantitative problem—it is also a qualitative one, since the screening procedure groups all non-conforming literature into one basket. Fourthly, we have noted that seven copies of the PRISMA guidelines exist. This being the case, which one should be cited? To replace over-reliance on PRISMA screening, we encourage authors, peer reviewers, and editors to publish systematic reviews and meta-analyses that respect the dual criteria of scientific plausibility and diversity of included papers.
At the time of writing, in July 2020, the COVID-19 pandemic has already inflicted dramatic international restrictions, including airports closing and limiting international travel. It has been suggested that re-opening of airports should involve and even rely on testing travelers for COVID-19. This paper discusses the methodology of estimating the detection and diagnostic accuracy of COVID-19 tests. It explains the clear distinction between the technical characteristics of the tests, the detection measures, and the diagnostic measures that have clinical and public health implications. It demonstrates the importance of the prevalence of COVID-19 in terms of determining the ability of a test to yield a diagnosis. We explain the methodology of evaluating diagnostic tests, using the predictive summary index (PSI), and the minimum number of tests that need to be performed in order to correctly diagnose one person, which is estimated by 1/PSI. In a population with low prevalence, even a high-sensitivity test may lead to a high percentage of false positive diagnoses, resulting in the need for multiple high-cost tests to achieve a correct diagnosis. Thus, basing a policy for opening airports on diagnostic testing, even with the best test for COVID-19, has some limits.
The COVID-19 pandemic is different from previous pandemic diseases in many ways. One of them relates to the literature. There is an exponential increase in the number of articles since April 2020. Also, and equally drastic, is how readily available they are to the general reader. It will be interesting to analyze (in the future) if advances in information age have played any significant role in the battle against our current pandemic.
Dr. Thorakkal Shamim has written a very interesting letter and comment. It is important to hear details about vaccine hesitancy in different countries or regions. I’m especially watchful of our American style of antivaccine activism gaining a foothold abroad. Hence, we need more information about this in the searchable biomedical literature.
When patients undergoing ventral or incisional hernia repair are reoperated for recurrence with an incidence rate of 16.0% following open repair and 18.8% following minimally invasive repair, it is time for re-evaluation of the real benefit of laparoscopy in ventral hernia repair.