In the last decade, we have observed an increased public and scientific interest in the clinical applications of medical cannabis. Currently, the application of cannabinoids in cancer patients is mainly due to their analgesic and anti-emetic effects. The direct effects of phyto-cannabinoids on cancer cells are under intensive research, and the data remain somewhat inconsistent. Although anti-proliferative properties were observed in vitro, conclusive data from animal models and clinical trials are lacking. Since immunotherapy of malignant diseases and bone marrow transplantation are integral approaches in hemato-oncology, the immuno-modulatory characteristic of cannabinoids is a fundamental aspect for consideration. The effect of cannabinoids on the immune system is presently under investigation, and some evidence for its immuno-regulatory properties has been shown. In addition, the interaction of cannabinoids and classical cytotoxic agents is a subject for further investigation. Here we discuss the current knowledge of cannabinoid-based treatments in preclinical models and the limited data in oncological patients. Particularly, we address the possible contradiction between the direct anti-tumor and the immune-modulatory effects of cannabinoids. Better understanding of the mechanism of cannabinoids influence is essential to design therapies that will allow cannabinoids to be incorporated into the clinic.
To the Editor,
We read with great interest the retrospective article of Tekin and Engin that investigated the prognostic significance of the ratio of mean platelet volume (MPV) to platelet count ratio (MPVPCR) in patients with Crimean-Congo hemorrhagic fever (CCHF). The authors found that MPVPCR was significantly lower in survivors than in non-survivors, and there-fore they suggested that this ratio could be used as a mortality marker. We think there are other factors that might have affected the results of this study.
Heart valve diseases are common disorders with five million annual diagnoses being made in the United States alone. All heart valve disorders alter cardiac hemodynamic performance; therefore, treatments aim to restore normal flow. This paper reviews the state-of-the-art clinical and engineering advancements in heart valve treatments with a focus on hemodynamics. We review engineering studies and clinical literature on the experience with devices for aortic valve treatment, as well as the latest advancements in mitral valve treatments and the pulmonic and tricuspid valves on the right side of the heart. Upcoming innovations will potentially revolutionize treatment of heart valve disorders. These advancements, and more gradual enhancements in the procedural techniques and imaging modalities, could improve the quality of life of patients suffering from valvular disease who currently cannot be treated.
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.
Three-dimensional (3D) printing is based on additive technology in which layers of materials are gradually placed to create 3D objects. The world of 3D printing is a rapidly evolving field in the medical industry as well as in most sectors of our lives. In this report we present current technological possibilities for 3D print¬ing in the surgical field. There are different 3D printing modalities and much confusion among clinicians regarding the differences between them. Three-dimensional printing technologies can be classified based on the basic material used: solid, liquid, and powder. We describe the main printing methods from each modality and present their advantages while focusing on their applications in different fields of surgery, starting from 3D printing of models for preoperative planning up to patient-specific implants (PSI). We present the workflow of 3D printing for the different applications and our experience in 3D printing surgical guides as well as PSI. We include examples of 3D planning as well as clinical and radiological imaging of cases. Three-dimensional printing of models for preoperative planning enhances the 3D perception of the planned operation and allows for preadaptation of surgical instruments, thus shortening operation duration and improving precision. Three-dimensional printed PSI allow for accurate reconstruction of anatomic relations as well as efficiently restoring function. The application of PSI is expanding rapidly, and we will see many more innovative treatment modalities in the near future based on this technology.
Stents are widely use in endoscopic urological procedures. One of the most important indications is the treatment of urinary tract strictures. Allium™ Medical has introduced several types of stents for the treatment of different types of urinary tract strictures, based on anatomic location. All the stents are made of nitinol and coated with a co-polymer that reduces encrustations. These stents are self-expandable and have a large caliber and a high radial force. They have different shapes, designed especially for the treatment of each type of stricture. One of the most important features of Allium-manufactured stents is the ease of removal, due to their special unraveling feature. The company has introduced the Bulbar Urethral Stent (BUS) for treatment of bulbar urethral strictures; a rounded stent available in different lengths. Initial data on 64 patients with bulbar urethral stricture treated with the BUS showed a significant improvement in symptoms, with minimal complications and few adverse events. For treatment of prostate obstruction in patients unfit for surgery or unwilling to undergo a classical prostatic surgery, the Triangular Prostatic Stent (TPS) was introduced, which has a triangular shape that fits in the prostatic urethra. Its body has a high radial force attached to an anchor (which prevents migration) through a trans-sphincteric wire (which reduces incontinence rate). Initial data on 51 patients showed significant improvement in symptoms and in urinary peak flow rate, with a relatively small number of complications. The Round Posterior Stent (RPS) was designed for treatment of post radical prostatectomy bladder neck contracture. This short, round stent has an anchor, which is placed in the bladder neck. This stent being relatively new, the clinical data are still limited. Ureteral strictures can be treated with the Ureteral Stent (URS), which is round-shaped, available in different lengths, and has an anchor option (for very distal or very proximal strictures). We have previously published data on 107 URSs inserted in patients with ureteral stricture due to several etiologies, including patients who failed previous treatment. All patients were asymptomatic for a long period of follow-up after stent removal, with only one case of re-stenosis. In this paper, we review the urological “covered” stents produced by Allium Medical with the relevant clinical data available at the present time.
TO THE EDITOR
I read with interest the letter by Klaus Rose et al. regarding the article about delayed diagnosis of severe medical conditions during the coronavirus disease 2019 (COVID-19) pandemic.1 The author stressed the importance of recognizing that delayed presentation of patients, during the COVID-19 pandemic, was not limited to the pediatric population. I agree with this important point, and the article does not claim otherwise. The presented cases are pediatric, given that they took place in a pediatric department, but it is reasonable to assume that adults have faced the same challenges.
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.
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.
Background: Transthyretin (TTR), also known as prealbumin, has been suggested as an indicator of protein and nutritional status.
Objective: The aim of this study was to examine the maternal and umbilical cord (UC) TTR in relation to intrauterine growth, and the serum TTR of preterm infants in relation to nutritional status and growth.
Methods: After application of exclusion criteria, 49 preterm infants (mean gestational age and birth-weight 32.9±2.9 weeks and 1822±556 g) were included in the study. Transthyretin was sampled at birth and on days 14, 28 or at discharge with growth parameters and nutritional laboratories.
Results: Mean UC and maternal TTR were positively correlated (8.5±2.4 mg/dL and 20.4±7.0 mg/dL, r=0.31, P=0.07). Umbilical cord TTR was neither an index of maturity nor of intrauterine growth. Umbilical cord TTR was higher in females (9.4±2.6 versus 7.6±1.8 mg/dL, P=0.015). Maternal TTR was lower in twin pregnancies (16.8±4.9 versus 22.5±7.3 mg/dL, P=0.007). Although TTR levels gradually increased over time in correlation with post-menstrual and chronological ages (r=0.24, P=0.011 and r=0.40, P<0.001, respectively), there was no correlation to weight gain (r=0.10, P=0.41), nutritional status, protein intake, or laboratories. The only significant correlations were between TTR and glucose and triglycerides levels (r=0.51, P<0.001 for both).
Conclusions: Although TTR levels increased over time, we could not demonstrate significant correlations between TTR and indices of the nutritional status in preterm infants at birth or during the neonatal course.
