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.
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.
Metallic drug-eluting stents have led to significant improvements in clinical outcomes but are inherently limited by their caging of the vessel wall. Fully bioresorbable scaffolds (BRS) have emerged in an effort to overcome these limitations, allowing a “leave nothing behind” approach. Although theoretically appealing, the initial experience with BRS technology was limited by increased rates of scaffold thrombosis compared with contemporary stents. This review gives a broad outline of the current BRS technologies and outlines the refinements in BRS design, procedural approach, lesion selection, and post-procedural care that resulted from early BRS trials.
Objectives: To assess the impact of different types of anemia and of concomitant non-cardiovascular chronic illnesses on outcomes of patients with ST-segment elevation myocardial infarction (STEMI) and baseline anemia admitted to the Intensive Cardiac Care Unit.
Methods: Based on the mean corpuscular volume, anemia was stratified into: microcytic (<80 fL), normocytic (≥80, <96 fL), and macrocytic (≥96 fL). Data on concomitant chronic non-cardiovascular illnesses including malignancies were carefully collected. Endpoints included in-hospital bleeding as well as all-cause mortality at long-term follow-up.
Results: Of 1,390 patients with STEMI, 294 patients had baseline anemia (21.2%), in whom normocytic, microcytic, and macrocytic anemia was present in 77.2%, 17.0%, and 5.8% patients, respectively. In-hospital bleeding occurred in 25 (8.5%) of the study population without significant differences between the three groups. At a mean follow-up of 5.5±3.5 years, 104 patients (35.4%) had died. Mortality was the highest in patients with macrocytic anemia, followed by patients with normocytic anemia and microcytic anemia (58.8%, 37.0%, and 20.0%, respectively; P=0.009). Chronic non-cardiovascular condition was identified as an independent predictor of both in-hospital bleeding (odds ratio=2.57, P=0.01) and long-term mortality (hazard ratio [HR] 1.54, P=0.019). Performance of coronary angiography within index hospitalization was associated with lower long-term mortality (HR 0.38, P=0.001). Mean corpuscular volume did not predict either in-hospital bleeding or mortality.
Conclusions: Chronic non-cardiovascular illnesses are highly prevalent among patients with STEMI and baseline anemia, and are strongly associated with higher in-hospital bleeding and long-term mortality. Type of anemia is not related to prognosis post-STEMI.
The surgical management of cerebral and skull base lesions has evolved greatly in the last few decades. Still, a complete resection of lesions abutting critical neurovascular structures carries significant morbidity. Stereotactic radiosurgery (SRS) has emerged as an increasingly accepted treatment option. Minimally invasive, SRS results in excellent tumor control and low complication rates in patients with moderate-size tumors. The management of large cerebral and skull base tumors remains a formidable challenge. In such large tumors, radical surgical extirpation offers a significantly higher risk of neurological deficit, and SRS alone cannot be used because of the elevated incidence of radiation-induced complications known to be associated with large-volume tumors. With increasing treatment volumes, SRS-associated tumor control rates decrease and complication rates increase. Planned subtotal resection (STR) with adjuvant SRS (adaptive hybrid surgery [AHS]) has gained increasing interest in recent years as a multimodal approach. In AHS, a planned STR (aimed at decreasing surgical morbidity) followed by SRS to a preplanned residual tumor aids in harnessing advantages offered by both approaches. Although intuitive and reasonable, this paradigm shift from maximal resection at all cost has not been adopted widely. Combining open micro¬surgery with SRS requires a good understanding of both surgical and SRS modalities and their respective safety–efficacy features. We present a review and discussion on AHS as a modern, multidisciplinary treatment approach. Available data and views are discussed for vestibular schwannoma (VS) as a sample tumor. Other indications for AHS are mentioned in brief.
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.
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.
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.
