We are proud to introduce you to the Fifteenth Annual Rambam Research Day, now established as a key annual event at Rambam Health Care Campus, Haifa, Israel, reflecting the diverse research activities on our campus.
Background: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in India. The aggressiveness of OSCC is analyzed not only based on the dysplastic features and tumor infiltration pattern, but also by means of the stromal changes that pave the way for an invasion into the connective tissue. The role of elastic fibers in the progression of OSCC is still unknown because of sparse literature and the masking effect of overlying inflammatory cells and the lower number of elastic fibers in the lamina propria. The present study provides further insight into the qualitative assessment of elastic fibers in various grades of dysplasia and OSCC.
Objectives: To analyze the morphological changes exhibited by the elastic fibers in epithelial dysplasia and OSCC.
Materials and methods: Two sections were cut from each of 60 samples of varying grades of OSCC and 60 samples of varying grades of epithelial dysplasia followed by staining with hematoxylin and eosin and Verhoeff–Van Gieson stain.
Results: Statistically significant results were obtained for qualitative analysis of elastic fibers. A change in density and orientation to overlying epithelium and tumor islands was seen on progressing from well-differentiated to poorly differentiated OSCC and in progressing grades of dysplasia.
Conclusion: The uniqueness of this study lies in the exploration of elastic fibers in dysplasia and well-differentiated OSCC, a less explored field. The study of the connective tissue stromal changes can be used as an adjunct to histological grading.
Background: United States (US) and European Union (EU) legislation attempts to counterbalance the presumed discrimination in pediatric drug treatment and development.
Methods: We analyzed the history of drug development, US/EU pediatric laws, and pediatric studies required by US/EU regulatory authorities and reviewed relevant literature.
Results: The US and EU definitions of a child are defined administratively (rather than physiologically) as being aged <17 years and <18 years, respectively. However, children mature physiologically well before their seventeenth or eighteenth birthdays. The semantic blur for these differing definitions may indicate certain conflicts of interest.
Conclusions: Pediatric healthcare today is better than ever. Regulatory-related requirements for “pediatric” studies focus on labeling. Most of these studies lack medical usefulness and may even harm pediatric patients through administration of placebo and/or substandard treatment, despite the resultant publications, networking, patent extensions, and strengthened regulatory standing. Clinicians, parents, and ethics committees should be aware of these issues. New rules are needed to determine new pharmaceutical dose estimates in prepubescent patients, and when/how to clinically confirm them. Internet-based structures to divulge this information should be established between drug developers, clinicians, and regulatory authorities. A prerequisite for the rational use of pharmaceuticals in children would be to correct the flawed concept that children are discriminated against in drug treatment and development, and to abandon separate pediatric drug approval processes.
Objective: To review current medical literature on the risks and potential benefits of e-cigarette use and its permissibility under Jewish law.
Methods: A survey of current medical literature about the risks and potential benefits of e-cigarette use, and a review of existing rabbinic literature regarding both combustible and e-cigarette products.
Results: E-cigarettes contain fewer harmful materials than do combustible cigarettes. However, they are not risk-free. Their skyrocketing use among youth is of concern, as e-cigarettes lead to nicotine addiction and are a gateway to combustible cigarettes. Preliminary data indicate that e-cigarettes increase the risk of myocardial infarction, chronic obstructive pulmonary disease (COPD), and emphysema and are no more effective as aids to smoking cessation than US Food and Drug Administration (FDA)-approved interventions with acceptable safety profiles. Few halakhic decisors have opined on the permissibility of e-cigarettes, but extrapolating from halakhic discussions regarding combustible cigarettes strongly suggests that they would prohibit e-cigarettes based on government warnings and preliminary data demonstrating increased risk of cardiovascular and respiratory diseases, at the least because of possible danger (safek sakana). Among youth and pregnant women, for whom e-cigarettes are particularly dangerous and for whom the government has administered explicit warnings, a Jewish legal prohibition should be absolute. There is a unique obligation to prevent youth from obtaining these products. Jewish law might also prohibit deriving benefit from the sale or advertisement of these products.
Conclusions: Extrapolating from rabbinic literature regarding combustible cigarettes, the preliminary data establishing the dangers of e-cigarettes and the government warnings against usage would render these products prohibited under Jewish law, especially for youth and pregnant women.
Objective: The World Health Organization’s (WHO) guidelines for cancer pain management were intentionally made simple in order to be widely implemented by all physicians treating cancer patients. Referrals to pain specialists are advised if pain does not improve within a short time. The present study examined whether or not a reasonable use of the WHO guideline was made by non-pain specialists prior to referral of patients with cancer-related pain to a pain clinic.
Methods: Cancer patients referred to a pain specialist completed several questionnaires including demographics, medical history, and cancer-related pain; the short-form McGill Pain Questionnaire (SF-MPQ); and the Short Form Health Survey SF-12. Data from referral letters and medical records were obtained. Treatments recommended by pain specialists were recorded and categorized as “unjustified” if they were within the WHO ladder framework, or “justified” if they included additional treatments.
Results: Seventy-three patients (44 women, 29 men) aged 55 years (range, 25–85) participated in the study. Their pain lasted for a mean of 6 (1–192) months. Mean pain intensity scores on a 0–10 numerical rating scale were 7 (2–10) at rest and 8 (3–10) upon movement. Most patients complied with their referring physician’s recommendations and consumed opioids. Adverse events were frequent. No significant correlation was found between the WHO analgesic medication step used and mean pain levels reported. There were 63 patient referrals (85%) categorized as “unjustified,” whereas only 11 patients (15%) required “justified” interventions.
Conclusions: These findings imply that analgesic treatment within the WHO framework was not reasonably utilized by non-pain specialists before referring patients to pain clinics.
Background: The use of electric bicycles (E-bikes) has dramatically increased over the last decade. E-bikes offer an inexpensive, alternative form of transport, but also pose a new public health challenge in terms of safety and injury prevention.
Objective: The aim of this study was to describe the epidemiology and severity of E-bike related injuries among children treated in the emergency department (ED) and to compare these to manual bicycle related injuries.
Methods: A retrospective observational study of all pediatric patients presenting to the ED between December 2014 and November 2015 with an injury related to E-bike or manual bicycle use. Data including demographics, diagnosis, injury severity score (ISS), and outcome were compared.
Results: A total of 196 cyclist injuries presented to the ED; 85 related to E-bike use and 111 to manual bicycle riders. The mean age of E-bikers was 13.7 years (7.5–16 years) and of manual bicycle riders was 9.9 years (3–16 years). Injuries to the head and the extremities were common in both groups. E-bikers had significantly more intra-abdominal organ injury (P=0.047). Injury severity scores were low overall, but injuries of higher severity (ISS>9) only occurred among the E-bikers.
Conclusions: Pediatric E-bike injuries tend to be more severe than those sustained during manual bicycle riding. Further research into bicycle and other road and pavement users could lead to enhanced regulation regarding E-bike usage.
To the Editor,
I am writing in response to Dr Sharon Galper Grossman’s recent fascinating article, “Vape Gods and Judaism—E-cigarettes and Jewish Law.”1 The author extrapolates from rabbinic literature regard-ing combustible cigarettes and suggests that the preliminary data establishing the dangers of e-cigarettes, and the government warnings against usage, would render these products prohibited under Jewish law, especially for youth and pregnant women.
Objective. To compare the reported accuracy and sensitivity of the various modalities used to diagnose autism spectrum disorders (ASD) in efforts to help focus further biomarker research on the most promising methods for early diagnosis.
Methods. The Medline scientific literature database was searched to identify publications assessing potential clinical ASD biomarkers. Reports were categorized by the modality used to assess the putative markers, including protein, genetic, metabolic, or objective imaging methods. The reported sensitivity, specificity, area under the curve, and overall agreement were summarized and analyzed to determine weighted averages for each diagnostic modality. Heterogeneity was measured using the I2 test.
Results. Of the 71 papers included in this analysis, each belonging to one of five modalities, protein-based followed by metabolite-based markers provided the highest diagnostic accuracy, each with a pooled overall agreement of 83.3% and respective weighted area under the curve (AUC) of 89.5% and 88.3%. Sensitivity provided by protein markers was highest (85.5%), while metabolic (85.9%) and protein markers (84.7%) had the highest specificity. Other modalities showed degrees of sensitivity, specificity, and overall agree¬ments in the range of 73%–80%.
Conclusions. Each modality provided for diagnostic accuracy and specificity similar or slightly higher than those reported for the gold-standard Autism Diagnostic Observation Schedule (ADOS) instrument. Further studies are required to identify the most predictive markers within each modality and to evaluate biological pathways or clustering with possible etiological relevance. Analyses will also be necessary to determine the potential of these novel biomarkers in diagnosing pediatric patients, thereby enabling early intervention.
Background: The ratio between the fetal umbilical artery pulsatility index (UA-PI) and the middle cerebral artery pulsatility index (MCA-PI) is termed the cerebroplacental ratio (CPR). The CPR represents fetal blood flow redistribution at the early stages of placental insufficiency; moreover, it has predictive value for adverse intrapartum and neonatal outcomes. However, internationally accepted reference ranges for CPR are lacking.
Objective: This study sought to establish UA-PI, MCA-PI, and CPR reference ranges in low-risk, normal-growth singleton fetuses during the third trimester of pregnancy.
Methods: A retrospective cohort cross-sectional study was performed in the obstetrics ultrasound unit of a university hospital in Israel. We reviewed all fetal and maternal electronic records of pregnant women referred for ultrasound assessment during the third trimester between January 2014 and January 2019. We included only singleton pregnancies with normal anatomy scans and a normal third-trimester estimated fetal weight. The UA-PI, MCA-PI, and CPR reference ranges were reconstructed for each of the vessels for each gestational age between 29 and 41 weeks.
Results: A total of 560 pregnancies met the inclusion criteria. Satisfactory waveforms and measurements were obtained in all cases. At least 18 women enrolled at each gestational week. The MCA-PI and CPR val-ues showed a similar parabolic curve during the third trimester of pregnancy, with a peak value at 32 and 33 gestational weeks, respectively. The UA-PI showed a linear and gradual decrease over the gestational age.
Conclusions: In this study we established UA-PI, MCA-PI, and CPR reference ranges in low-risk, normal-growth singleton fetuses during the third trimester based on the Israeli population.
Background: There are very limited data on the prognostic capacity of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) for the systemic inflammatory response in pediatric trauma (PT) patients. The purpose of this study was to evaluate the prognostic ability of NLR and PLR on mortality in pediatric trauma patients.
Methods: This study looked at 358 PT patients who were admitted to the Cumhuriyet University Hos-pital’s Emergency Department between January 2010 and June 2018. The NLR and PLR were calculated by dividing the blood neutrophil count and blood platelet count, respectively, by the lymphocyte count, at the time of admission. After performing a stepwise logistic regression analysis to determine the predictive factors on the mortality risk of post-traumatic systemic inflammatory response syndrome (SIRS), receiver operating characteristic (ROC) curve analysis was used to define the optimum cut-off values of the NLR and the PLR parameters for survival.
Results: The NLR, and PLR values were significantly higher in survivors than in non-survivors (NLR, 6.2±5.7 versus 2.6±2.5, P<0.001; PLR, 145.3±85.0 versus 46.2±25.2, P<0.001 ). The NLR (odds ratio [OR], 3.21; P=0.048), PLR (OR, 0.90; P=0.032), blood glucose (OR, 1.02; P=0.024), and Injury Severity Score (ISS) (OR, 1.28; P=0.011) were independent predictors of the mortality risk in PT patients. The area under the curve in the ROC curve analysis was 0.764 with a cut-off of 2.77 (sensitivity 70%, specificity 77%) for the NLR; and 0.928 with a cut-off of 61.83 (sensitivity 90%, specificity 85%) for the PLR.
Conclusion: Acquiring the NLR and PLR at the time of admission could be a useful predictor for mortality in PT patients.
