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.
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.
Cancer patients have a pro-thrombotic state attributed to the ability of cancer cells to activate the coagula¬tion system and interact with hemostatic cells, thus tilting the balance between pro- and anticoagulants. Mechanisms underlying the coagulation system activation involve tumor cells, endothelial cells, platelets, and white blood cells. Anti-cancer therapies, including anti-angiogenic drugs, significantly increase the risk of thrombosis during treatment. Along with the role of coagulation proteins in the hemostatic system, these proteins also serve as growth factors to the tumor. Heparanase is a pro-angiogenic and pro-metastatic protein. Our previous studies have demonstrated that it enhances tissue factor (TF) activity and is present at high levels in tumor cells and patients’ blood. Strategies to attenuate heparanase effects by heparin mimetics or peptides interrupting the TF–heparanase interaction are good candidates to attenuate tumor growth and thrombotic manifestations.
Objectives: Research and theory suggests that socioeconomic status may affect diabetes control. We investigated the effect of socioeconomic status and ethnicity on glycated hemoglobin (HbA1c) in Arab and Jewish children with type 1 diabetes mellitus in northern Israel.
Methods: Data were collected from medical records of 80 Arab and 119 Jewish children attending a pediatric diabetes clinic in a tertiary health care center. Multivariate regression analysis was used to assess factors independently affecting HbA1c level.
Results: Mean age was 12.9±4.7 years. Arab families had more children compared to Jewish families (3.7±1.5 versus 2.9±1.2, respectively, P=0.0007). Academic education was significantly less common in Arab families (25% versus 66.2%, respectively, P=0.0001). Income of Jewish parents was significantly higher compared to that of Arab parents (7,868±2,018 versus 5,129±906 NIS/month, respectively, P=0.0001). Mean age at diagnosis of diabetes was 9.6±4.6 years and disease duration was 3.4±2.3 years in both groups. Half of Arab and Jewish children were treated with multiple insulin injections and half with insulin pumps. Mean number of self-glucose testing/day was higher in Jewish children than in Arab children (4.7±2.5 versus 4.0±1.5, respectively, P=0.033). Mean HbA1c was above recommendations, 9.5% (12.6 mmol/L) in Arab children and 8.7% (11.3 mmol/L) in Jewish children (P=0.004). In multivariate analysis, disease duration (P=0.010) and ethnicity (P=0.034 for Arabs versus Jews) were independently associated with HbA1c.
Conclusions: Both Arab and Jewish children failed to meet HbA1c goals, but this effect was significantly greater for Arabs. Ethnicity remained a predictor of failure even following adjustment for potential confounders.
Objectives: To study the correlation between the putative cancer stem cell (CSC) markers aldehyde dehydrogenase 1 (ALDH1), cluster of differentiation 44 (CD44), sex-determining region Y-box 2 (SOX2), and octamer-binding protein 4 (OCT4) and human papilloma virus (HPV) infection using p16, the surrogate marker of HPV in oral epithelial dysplasia (OED) and normal mucosa.
Methods: Five sections each from 40 histopathologically diagnosed cases of different grades of OED and 10 cases of normal oral mucosa without dysplasia were immunohistochemically stained with p16, ALDH1, CD44, SOX2, and OCT4, respectively.
Results: Expression of ALDH1 and SOX2 was significantly increased in OED cases, whereas CD44 and OCT4 expression was increased in normal mucosa. P16-positive OED cases showed upregulation of ALDH1 and OCT4 expression as compared to p16-negative cases, while CD44 and SOX2 expression was downregulated in p16-positive OED cases; however, the results were not statistically significant.
Conclusion: The present study indicated a suggestive link between p16 and cancer stem cell marker expression in HPV-associated OED, and that p16 has a significant role in CSC progression in OED. This is the first study to evaluate the expression of putative CSC markers in HPV-associated OED. However, low study numbers are a potential limiting factor in this study.
Introduction: Catch-up growth (CUG) in small-for-gestational age (SGA) infants is essential for their overall development. Knowledge about the factors influencing CUG might be critical in their effective management. Hence this study was performed with the aim of identifying factors that may influence CUG in SGA infants.
Methods: Asymmetrical SGA infants born at term were included in the study as per defined criteria, and their demographic details were recorded. Anthropometric data, feeding practice details, and intercurrent illnesses data were collected on follow-up at 6 weeks, 6 months, and 12–15 months of age. Catch-up growth weight was defined as improvement of weight to the normal range of -2 to +2 weight-for-age Z score (WAZ). Analysis was carried out using SPSS Expand 17 software. Chi-square test was used to find association between variables. Logistic regression analysis was used to measure effect. A P value of less than 0.05 was taken as significant.
Results: Out of 324 SGA infants born at term, 119 completed 12–15-month follow-up, of which 69.7% had achieved CUG weight. Exclusive breastfeeding >4 months, continued breastfeeding until 12–15 months, and absence of diarrheal episodes were positively associated with CUG. Pregnancy-induced hypertension, gestational diabetes, and maternal overweight/obesity were negatively associated with CUG. Maternal education status, conception age, gravida status, mode of delivery, vitamin D and iron supplementation, and intercurrent respiratory infections were not associated with CUG. On multivariate analysis, continued breastfeeding and absence of diarrheal episodes were independent factors associated with CUG.
Conclusion: Breastfeeding practice, especially continued breastfeeding, and the absence of diarrheal illness are the key determinants for achieving CUG weight in term SGA infants, particularly in settings where resources are limited.
Objective: This study examined the reliability of the various parameters obtained in diagnostic ureteroscopy for upper-tract urothelial carcinoma (UTUC) in predicting the degree of differentiation in the final pathological report after radical nephroureterectomy (RNU).
Methods: We conducted a retrospective review of patients undergoing RNU at a single tertiary hospital between 2000 and 2020. Only patients who underwent preoperative diagnostic ureteroscopy (URS) were included. The results of urine selective cytology, endoscopic appearance of the tumor, and biopsy taken during ureteroscopy were compared to the final pathological report.
Results: In total, 111 patients underwent RNU. A preliminary URS was performed in 54. According to endoscopic appearance, 40% of the “solid”-looking tumors were high grade (HG), while 52% of those with a papillary appearance were low grade (LG). Positive cytology predicted HG tumors in 86% of cases. However, 42% of patients with negative cytology had HG disease. The biopsies acquired during URS showed that HG disease findings matched the final pathology in 75% of cases. However, 25% of patients noted as being HG, based on URS biopsies, were noted to have LG disease based on nephroureterectomy biopsies. Full analyses revealed that 40% of the cases diagnosed as LG based on the URS biopsies actually had HG disease.
Conclusions: Direct tumor observation of papillary lesions, negative cytology, and biopsies indicating LG disease are of low predictive value for classifying the actual degree of tumor differentiation. No single test can accurately rule out HG disease. In light of the rising use of neo-adjuvant chemotherapy in UTUC, a reliable predictive model should be developed that accurately discriminates between HG and LG disease.
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.
Today, in the 21st century, most people are aware of the term genocide. However, few people are aware that this term only entered the English language in the 1940s, as a result of the dedicated work of a brilliant and successful man who deprived himself of a private family life so that he could be free to fight for his ideas. Although Raphael Lemkin was instrumental in the recognition of genocide by the United Nations, he died too early and was buried with no honor. This paper reviews the life and work of Raphael Lemkin, and his triumph in seeing genocide recognized as a crime.
Background: Patellar instability comprises a group of pathologies that allow the patella to move out of its trajectory within the trochlear groove during walking. Symptomatic patients who need surgery commonly undergo soft tissue procedures such as medial patellofemoral ligament repair to strengthen the ligaments that hold the patella in place. However, soft-tissue repairs may be insufficient in patients suffering from patellar maltracking, which is characterized by an unbalanced gliding of the patella within its route. In these patients, a different approach is advised. We aim to provide the mid-term clinical outcomes of the Fulkerson distal realignment operation in selected patients with non-traumatic patellar maltracking.
Methods: The clinical outcomes of the Fulkerson distal realignment operation performed in 22 knees of 21 patients were evaluated by a self-administered subjective International Knee Documentation Committee (IKDC) score and the Tegner–Lysholm knee scoring scale.
Results: Before surgery, the median IKDC score was 52, and the median Tegner–Lysholm score was 56. Following surgery (mean follow-up 48 months, range 24–156), the median IKDC and the Tegner–Lysholm scores were 67 and 88, respectively. The improvement was statistically significant (P=0.001 and P=0.002 for IKDC and Tegner–Lysholm scores, respectively). Associated procedures included patella microfracture due to grade III–IV cartilage lesion (International Cartilage Repair Society grading system) in four patients, retinacular releases in three patients, medial capsular augmentations in two patients, and medial patellofemoral ligament reconstruction in two patients. One patient with Ehlers–Danlos disease required excessive medialization of the tibial tuberosity. Surgery-related complications occurred in three patients.
Discussion: Surgical correction of patellar maltracking with Fulkerson distal realignment combined with associated procedures in individual patients was associated with an increase in subjective and functional clinical scores at medium-term follow-up. Particular attention should address pathologies associated with patellar maltracking and managed accordingly.
Level of evidence: 4c (case series).
