The use of forward genetics to analyze mammalian biology has been dramatically accelerated by methods that make it possible instantly to determine which mutation causes a phenotype. Now it is possible to discover gene function as rapidly as mutations can be created and screened: approximately 1,000 coding changes per week are interrogated in our laboratory. Moreover, it is possible to know approximately how much damage has been done to the genome over time. We estimate that we have damaged or destroyed about one-quarter of all protein encoding genes and tested the effects of variant alleles within these genes three times or more in a set of phenotypic assays that interest us. Only about two years were required to reach this level of saturation.
Objective: The optimal treatment of deep vein thrombosis (DVT) is anticoagulation therapy. Inferior vena cava filter (IVC) placement is another option for the prevention of pulmonary embolism (PE) in patients with deep vein thrombosis. This is used mostly in patients with a contraindication to anticoagulant therapy. The purpose of the present study was to compare the two options.
Methods: A retrospective cohort study of two groups of patients with DVT: patients who received an IVC filter and did not receive anticoagulation due to contraindications; and patients with DVT and similar burden of comorbidity treated with anticoagulation without IVC insertion. To adjust for a potential misbalance in baseline characteristics between the two groups, we performed matching for age, gender, and Charlson’s index, which is used to compute the burden of comorbid conditions. The primary outcome was an occurrence of a PE.
Results: We studied 1,742 patients hospitalized with the diagnosis of DVT in our hospital;93 patients from this population received IVC filters. Charlson’s score index was significantly higher in the IVC filter group compared with the anticoagulation group. After matching of the groups of patients according to Charlson’s score index there were no significant differences in primary outcomes.
Conclusion: Inferior vena cava filter without anticoagulation may be an alternative option for prevention of PE in patients with contraindications to anticoagulant therapy.
Cannabis is the most widely used recreational drug worldwide and is used by some patients with inflam-matory bowel disease (IBD) to ameliorate their disease. Whereas epidemiological studies indicate that as many as 15% of IBD patients use cannabis, studies inspecting cannabis use in IBD are few and small. We have conducted several studies looking at the use of cannabis in IBD. In Crohn’s disease, we demonstrated that cannabis reduces the Crohn’s disease activity index (CDAI) by >100 points (on a scale from 0-450).Two small studies in ulcerative colitis showed a marginal benefit. However, no improvement was observed in inflammatory markers or in endoscopic score in either disease. Many questions regarding cannabis use in IBD remain unanswered. For example, cannabis is a complex plant containing many ingredients, and the synergism or antagonism between them likely plays a role in the relative efficacy of various cannabis strains. The optimal doses and mode of consumption are not determined, and the most common form of consump¬tion, i.e. smoking, is unacceptable for delivering medical treatment. Cannabis is a psychotropic drug, and the consequences of long-term use are unknown. Despite all these limitations, public opinion regards cannabis as a harmless drug with substantial medical efficacy. In Israel, the number of licenses issued for the medical use of cannabis is rising rapidly, as are the acknowledged indications for such use, but good-quality evidence for the effectiveness of cannabis is still lacking. Further studies investigating the medical use of cannabis are urgently needed.
Over the past decade the phenomenon of cannabis as a legitimate form of treatment for pain has overwhelmed the medical community, especially in the field of pain. From a status of a schedule 1 substance having no currently accepted medical use and being considered to have high potential for abuse, its use has mushroomed to over 50,000 legal medical users per year in Israel alone. There appear to be many reasons behind this phenomenon—medical, sociological, and economical. Thus, what is cannabis? An abusive substance or a medication? Should it be incorporated into current biomedical practice, and how should it be administered? Finally, what is the evidence for the beneficial and detrimental effects of cannabis? This article reviews and discusses the current literature regarding the beneficial and the detrimental effects of medical cannabis in the treatment of pain. We further discuss the problems and challenges facing the medical community in this domain and offer a practical approach to deal with these challenges.
Objective: The aim of this cross-sectional questionnaire-based study was to identify associations between the doses of cannabinoids and terpenes administered, and symptoms of attention deficit hyperactivity disorder (ADHD).
Methods: Participants were adult patients licensed for medical cannabis (MC) treatment who also reported a diagnosis of ADHD by a physician. Data on demographics, ADHD, sleep, and anxiety were collected using self-report questionnaires. Data collected on MC treatment included administration route, cultivator, cultivar name, and monthly dose. Comparison statistics were used to evaluate differences in reported parameters between low (20–30 g, n=18) and high (40–70 g, n=35) MC monthly dose and low adult ADHD self-report scale (ASRS, 0–5) score (i.e. ≤3.17 score, n=30) or high ASRS score (i.e. ≥3.18 score, n=29) subgroups.
Results: From the 59 patients that answered the questionnaire, MC chemovar could be calculated for 27 (45%) of them. The high MC monthly dose group consumed higher levels of most phyto-cannabinoids and terpenes, but that was not the case for all of the cannabis components. The high dose consumers and the ones with lower ASRS score reported a higher occurrence of stopping all ADHD medications. Moreover, there was an association between lower ASRS score subgroup and lower anxiety scores. In addition, we found an association between lower ASRS score and consumption of high doses of cannabinol (CBN), but not with ∆-9-tetrahydrocannabinol (THC).
Conclusion: These findings reveal that the higher-dose consumption of MC components (phyto-cannabinoids and terpenes) is associated with ADHD medication reduction. In addition, high dosage of CBN was associated with a lower ASRS score. However, more studies are needed in order to fully understand if cannabis and its constituents can be used for management of ADHD.
Mechanical thrombectomy (MT) has revolutionized the treatment of large-vessel occlusion stroke and markedly improved patient outcomes. Unfortunately, there remains a large proportion of patients that do not benefit from this technology. This review takes a look at recent and upcoming technologies that may help to increase the number of MT-treated patients, thereby improving their outcomes. To that end, an overview of digital health solutions, innovative pharmacological treatment, and futuristic robotic endovascular interventions is provided.
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.
Objective: Inhalational drugs used in treating asthma have several side effects including those on oral tissues. We therefore designed a study to analyze the effects of inhalational drugs on the buccal mucosal cells of the oral cavity.
Methods: Smears were obtained from clinically normal buccal mucosa of 20 randomly selected asthmatic patients who had been under inhalational therapy for at least 6 months. The Papanicolaou-stained smears were then analyzed for average nuclear area, average cytoplasmic area, and average nuclear area:cyto¬plasmic area ratio for each patient, and the values were compared with those of 10 healthy controls.
Results: A statistically significant decrease in cytoplasmic area (P<0.001) was found in asthmatic patients compared to controls. A significant increase in mean nuclear area:cytoplasmic area ratio (P<0.001) was noted in asthmatic patients when compared to controls.
Conclusion: Prolonged use of inhalational drugs in patients diagnosed with asthma is associated with changes in oral epithelial cells. There is a need to assess whether these are the direct adverse effects of such drugs and whether they have any long-term impact on oral tissues.
Iatrogenesis is more common in neonatal intensive care units (NICUs) because the infants are vulnerable and exposed to prolonged intensive care. Sixty percent of extremely low-birth-weight infants are exposed to iatrogenesis. The risk factors for iatrogenesis in NICUs include prematurity, mechanical or non-invasive ventilation, central lines, and prolonged length of stay. This led to the notion that “less is more.” In the delivery room delayed cord clamping is recommended for term and preterm infants, and suction for the airways in newborns with meconium-stained fluid is not performed anymore. As a symbol for a less aggressive attitude we use the term neonatal stabilization rather than resuscitation. Lower levels of oxygen saturations are accepted as normal during the first 10 minutes of life, and if respiratory assistance is needed, we no longer use 100% oxygen but 0.21–0.3 FiO2, depending on gestational age and the level of oxygen saturation. We try to avoid endotracheal ventilation by using non-invasive respiratory support and administering continuous positive airway pressure early on, starting in the delivery room. If surfactant is needed, non-invasive methods of surfactant administration are utilized. Use of central lines is shortened, and early feeding of human milk is the routine. Permissive hypercapnia is allowed, and continuous non-invasive monitoring not only of the O2 but also of CO2 is warranted. “Kangaroo care” and Newborn Individualized Developmental Care and Assessment Program (NIDCAP) together with a calm atmosphere with parental involvement are encouraged. Whether “less is more,” or not enough, is to be seen in future studies.
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.
