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.
Chronic pain is a common complaint among patients, and rheumatic diseases are a common cause for chronic pain. Current pharmacological interventions for chronic pain are not always useful or safe enough for long-term use. Cannabis and cannabinoids are currently being studied due to their potential as analgesics. In this review we will discuss current literature regarding cannabinoids and cannabis as treatment for rheumatic diseases. Fibromyalgia is a prevalent rheumatic disease that causes diffuse pain, fatigue, and sleep disturbances. Treatment of this syndrome is symptomatic, and it has been suggested that cannabis and cannabinoids could potentially alleviate some of the symptoms associated with fibromyalgia. In this review we cite some of the evidence that supports this claim. However, data on long-term efficacy and safety of cannabinoid and cannabis use are still lacking. Cannabinoids and cannabis are commonly investigated as analgesic agents, but in recent years more evidence has accumulated on their potential immune-modulatory effect, supported by results in animal models of certain rheumatic diseases. While results that demonstrate the same effect in humans are still lacking, cannabinoids and cannabis remain potential drugs to alleviate the pain associated with rheumatic diseases, as they were shown to be safe and to cause limited adverse effects.
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.
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.
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.
Aim: The aim of this study was to assess the density of the segmental branches of the middle cerebral artery (MCA) quantitatively as a predictor of acute ischemic stroke in patients without definitive infarct findings at cerebral parenchyma by non-contrast computed tomography (CT).
Clinical rationale for the study: The clinical rationale for the study is to evaluate if the measurement of Sylvian fissure dot sign (SDS) would help early management of patients with stroke at the emergency department.
Methods: Computed tomography scans of 101 patients admitted to the emergency department with stroke symptoms and/or signs were included in the study, retrospectively. In the patient group, the quantitative density of the segmental branches of the MCA in the Sylvian fissure was measured on the affected side and the contralateral side.
Results: Quantitative density of SDS was significantly higher on the ischemic side of the brain. Receiver operating characteristic (ROC) analysis showed a cut-off value of 38.5 Hounsfield units (HU) as a predictor for acute ischemic stroke, with a sensitivity and specificity of 79% and 92%, respectively.
Conclusion: Quantitative density of SDS on the affected side in patients without definitive cerebral infarct findings of parenchyma can be used in the emergency room as an objective predictor sign for the diagnosis of acute ischemic stroke. Considering this finding in the differential diagnosis of acute stroke patients in the emergency room has the potential to improve their clinical management, particularly for the patients without early parenchymal and vascular signs of stroke.
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.
Background: Overall accuracy measures of medical tests are often used with unclear interpretations.
Objectives: To develop methods of calculating the overall accuracy of medical tests in the patient population.
Methods: Algebraic equations based on Bayes’ theorem.
Results: A new approach is proposed for calculating overall accuracy in the patient population. Examples and applications using published data are presented.
Conclusions: The overall accuracy is the proportion of the correct test results. We introduce a clear distinction between the overall accuracy measures of medical tests that are aimed at the detection of a disease in a screening of populations for public health purposes in the general population and the overall accuracy measures of tests aimed at determining a diagnosis in individuals in a clinical setting. We show that the overall detection accuracy measure is obtained in a specific study that explores test accuracy among persons with known diagnoses and may be useful for public health screening tests. It is different from the overall diagnostic accuracy that could be calculated in the clinical setting for the evaluation of medical tests aimed at determining the individual patients’ diagnoses. We show that the overall detection accuracy is constant and is not affected by the prevalence of the disease. In contrast, the overall diagnostic accuracy changes and is dependent on the prevalence. Moreover, it ranges according to the ratio between the sensitivity and specificity. Thus, when the sensitivity is greater than the specificity, the overall diagnostic accuracy increases with increasing prevalence, and vice versa, that is, when the sensitivity is lower than the specificity, the overall diagnostic accuracy decreases with increasing prevalence so that another test might be more useful for diagnostic procedures. Our paper suggests a new and more appropriate methodology for estimating the overall diagnostic accuracy of any medical test. This may be important for helping clinicians avoid errors.
Objective: The objective of this study was to retrospectively review clinical data, management protocols, and clinical outcomes of patients with fibromatoses of head and neck region treated at our tertiary care center.
Methods: We retrospectively reviewed the medical records of 11 patients with confirmed histopathological diagnosis of fibromatosis registered in the Department of Head and Neck Surgery at Tata Memorial Centre, India, between 2009 and 2019. Various clinical and pathological features and treatment modalities were evaluated.
Results: Age at diagnosis ranged between 18 and 74 years, with a median age of 36 years. The female-to-male ratio was 5:6. Supraclavicular fossa (n=4) was the most common subsite of origin in the neck (n=8). The lateral (n=2) and posterior cervical regions (n=2) were other common neck subsites. Less commonly involved sites were the mandible (n=1), maxilla (n=1), and thyroid (n=1). A total of eight patients underwent surgery at other centers before being referred to us for further management. Out of a total 11 patients, nine patients had unresectable disease at presentation. Six of the patients with unresectable disease received a combination of weekly doses of vinblastine 6 mg/m2 and methotrexate 30 mg/m2 for a median duration of 6 months (range 6–18 months) followed by hormonal therapy with tamoxifen. Three patients received metronomic chemotherapy followed by hormonal therapy. One treatment-naive patient with fibromatosis of posterior cervical (suboccipital) region underwent R2 resection (excision of bulk of the tumor with preservation of critical structures) at our center along with adjuvant radiotherapy. One pregnant patient reported to us after undergoing surgery outside and defaulting radiotherapy. During median follow-up of 29 months (range 1–77 months), six patients had stable disease, and four patients had disease reduction. Disease progression was seen in one patient. The two-year progression-free survival (PFS) was 90% (95% CI 70%–100%).
Conclusion: Gross residual resection (R2) was the mainstay of surgical treatment in our series as obtaining clear surgical margins is seldom possible in these locally aggressive tumors. Radiotherapy, chemotherapy, and hormonal therapy are the other preferred and more conservative treatment modalities. The goal of surgery should be preserving function with minimal or no morbidity. As fibromatoses in the head and neck region are extremely rare, their treatment awaits the development of standard treatment protocols.
