In recent years, cannabis has been gaining increasing interest in both the medical research and clinical fields, with regard to its therapeutic effects in various disorders. One of the major fields of interest is its role as an anticonvulsant for refractory epilepsy, especially in the pediatric population. This paper presents and discusses the current accumulated knowledge regarding artisanal cannabis and Epidiolex®, a United States Food and Drug Administration (FDA)-approved pure cannabidiol (CBD), in epilepsy management in pediatrics, by reviewing the literature and raising debate regarding further research directions.
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.
Patients have an ongoing unmet need for effective therapies that reverse the cellular and functional damage associated with heart damage and disease. The discovery that ~1%–2% of adult cardiomyocytes turn over per year provided the impetus for treatments that stimulate endogenous repair mechanisms that augment this rate. Preclinical and clinical studies provide evidence that cell-based therapy meets these therapeutic criteria. Recent and ongoing studies are focused on determining which cell type(s) works best for specific patient population(s) and the mechanism(s) by which these cells promote repair. Here we review clinical and preclinical stem cell studies and anticipate future directions of regenerative medicine for heart disease.
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.
Objective: The growing availability of next-generation sequencing technologies has revolutionized medical genetics, facilitating discovery of causative genes in numerous Mendelian disorders. Nevertheless, there are still many undiagnosed cases. We report the experience of the Genetics Institute at Rambam Health Care Campus in rare disease diagnostics using whole-exome sequencing (WES).
Methods: Phenotypic characterization of patients was done in close collaboration with referring physi-cians. We utilized WES analysis for diagnosing families suspected for rare genetic disorders. Bioinformatic analysis was performed in-house using the Genoox analysis platform.
Results: Between the years 2014 and 2017, we studied 34 families. Neurological manifestations were the most common reason for referral (38%), and 55% of families were consanguineous. A definite diagnosis was reached in 21 cases (62%). Four cases (19%) were diagnosed with variants in novel genes. In addition, six families (18%) had strong candidate novel gene discoveries still under investigation. Therefore, the true diagnosis rate is probably even higher. Some of the diagnoses had a significant impact such as alerting the patient management and providing a tailored treatment.
Conclusions: An accurate molecular diagnosis can set the stage for improved patient care and provides an opportunity to study disease mechanisms, which may lead to development of tailored treatments. Data from our genetic research program demonstrate high diagnostic and novel disease-associated or causative gene discovery rates. This is likely related to the unique genetic architecture of the population in Northern Israel as well as to our strategy for case selection and the close collaboration between analysts, geneticists, and clinicians, all working in the same hospital.
To date, the only known effective treatment for celiac disease is a strict gluten-free diet for life. We reviewed the literature to evaluate the upper limit for gluten content in food, which would be safe for patients with celiac disease. Patients with celiac disease should limit their daily gluten intake to no more than 10–50 mg. Most health authorities define gluten-free products as containing less than 20 parts per million gluten.
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.
Mutations in FGF23, KL, and GALNT3 have been identified as the cause for the development of hyperphosphatemic familial tumoral calcinosis (HFTC). Patients with HFTC typically present in childhood or adolescence with periarticular soft tissue deposits that eventually progress to disrupt normal joint articulation. Mutations in the GALNT3 gene were shown to account for the hyperphosphatemic state in both HFTC and hyperostosis-hyperphosphatemia syndrome (HHS), the latter characterized by bone involvement. We present the case of a patient of a Druze ethnic origin with known HFTC that presented to our department with the first documented case of pathologic fracture occurring secondary to the disease. Our report introduces this new phenotypic presentation, suggests a potential role for prophylactic bone screening, and highlights the need for preconception genetic screening in selected populations.
Background: Eosinophils constitute 1%–5% of peripheral blood leukocytes, less in the presence of acute infections (referred to as eosinopenia). Studies indicate that eosinopenia can be used as a prognostic predictor for chronic obstructive pulmonary disease exacerbation, sepsis, or acute myocardial infarction disease. There are only a few studies about predicting mortality in emergency departments and intensive care units (ICUs). Prognostic studies about patients in ICUs are generally carried out using different scoring systems. We aimed to analyze if the eosinophil count can estimate the prognosis among non-traumatic patients who underwent cardiopulmonary resuscitation and were hospitalized in ICU thereafter.
Methods: The data were evaluated of 865 non-traumatic adult patients (>18 years of age) who were admitted with cardiopulmonary arrest or developed cardiopulmonary arrest during clinical follow-ups. Admission venous blood sample tests, complete blood count, and biochemical laboratory results were recorded. Arterial blood gas results were also evaluated. The mean results of the recorded laboratory results were compared between the surviving and non-surviving patients groups.
Results: There was a significant difference between the two groups in regard to platelet, eosinophil count, pH, PaO2, SaO2, and HCO3- (P<0.001 for all). In the multiple linear regression analysis, eosinophil counts were found to be an independent factor (odds ratio=0.03, 95% confidence interval 0.33–0.56, P<0.001) associated with the mortality after cardiopulmonary resuscitation.
Conclusion: Because admission eosinophil counts can be measured easily, they are inexpensive biomarkers that can be used for predicting the prognosis among the patients who have return of spontaneous circulation and are treated in ICUs.
Coronavirus disease 2019 (COVID-19) is a global respiratory disease with unique features that have placed all medical professionals in an alarming situation. Preeclampsia is a hypertensive disorder of pregnancy affecting 8%–10% of India’s pregnant population. Assuming that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells through the angiotensin-converting enzyme 2 (ACE2) receptor, the resulting symptoms are due to vasoconstriction, caused by disturbances in the renin–angiotensin system (RAS). Other features of preeclampsia include endothelial dysfunction due to placental ischemia, leading to imbalances in angiogenic and antiangiogenic factors which result in increased blood pressure, proteinuria, altered hepatic enzymes, renal failure, and thrombocytopenia, amongst others. The increased prevalence of preeclampsia that was seen among mothers with SARS-CoV-2 infection might be due to misdiagnosis, as COVID-19 and preeclampsia have coincidental medical features. The major similarities of SARS-CoV-2-infected and preeclamptic women are a rise in pro-inflammatory cytokines, and increased serum ferritin and thrombocytopenia. Therefore, differential diagnosis might be difficult in pregnant women with COVID-19 who present with hypertension and proteinuria, thrombocytopenia, or elevated liver enzymes. The most promising markers for earlier diagnosis of preeclampsia is soluble endoglin (sEng), pregnancy-associated plasma protein-A (PAPP-A), soluble fms-like tyrosine kinase 1 (sFlt-1), and placental growth factor (PlGF). Due to placental hypoxia, sFlt-1 will be overproduced, thus inhibiting PlGF, and this alteration will be observed in the circulation five weeks or more before the onset of symptoms. The sFlt-1/PlGF ratio may also be modified via infectious states, but unregulated levels of those mediators are related to placental insufficiency. Hence, pregnant women with COVID-19 may develop a preeclampsia-like syndrome that might be differentiated properly by angiogenic markers to avoid unnecessary interventions and induced preterm labor.
