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.
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.
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.
Objective of the work: Pancreatic cancer (PC) is a deadly disease that is most commonly diagnosed at an incurable stage. Early diagnosis is the most important factor for improving prognosis. Evidence is beginning to accumulate that screening and surveillance may lead to the early detection of precursor lesions and/or pancreatic cancer in asymptomatic individuals. Proper screening methods and identification of such precursor lesions may enable effective pre-emptive interventions to prevent further fatalities. The primary objective of this project was to examine the feasibility of identifying precursor or early cancerous lesions in high-risk individuals by endoscopic ultrasound (EUS) screening to prevent the deaths from pancreatic cancer.
Research aim: Pancreatic cancer screening guidelines, based on consensus opinions, have been applied in various tertiary centers around the world; however, evidence for effectiveness is lacking. At Rambam Health Care Campus, we have established a cohort of high-risk individuals, and we report our local 10-year experience results of screening for pancreatic cancer.
Methods: Between 2008 and 2018, a cohort of 123 asymptomatic high-risk individuals came for annual/biannual EUS screening for pancreatic cancer. Retrospective and prospectively collected data were obtained, analyzed, and compared on the basis of several variables. These variables include age at beginning of screening, gender, smoking, obesity, diabetes, and presence of tumor markers, as well as the patients’ personal and family history of cancers. Findings on each EUS are described.
Results: Three patients out of 123 underwent potentially life-saving surgery as a result of this screening program. All of these three had only one first-degree relative (FDR) with pancreatic cancer at the time of their first screenings, but two eventually had a second FDR with PC. Findings from 296 EUS exams regarding smoking, obesity, and other risk factors are presented. Minor, possibly trivial, EUS findings are found to be common. Detection of precursor pancreatic lesions is feasible with EUS screenings.
Conclusions: Adherence was an important limiting factor in screening. Better stratification of patients according to specific risk factors, including thorough genetics and family history, may direct when and how to initiate screening. International collaborations, such as the International Cancer of Pancreas Screening (CAPS) Consortium, of which Rambam is a collaborating partner, are needed to collate evidence for impact of screening to prevent pancreatic cancer morbidity and mortality, and are essential to achieve proof of concept. Different countries with varying health-care systems and budgets can find variance of appropriateness of screening procedures.
Objective: Diabetes mellitus (DM), characterized by chronic hyperglycemia, is attributed to relative insulin deficiency or resistance, or both. Studies have shown that yoga can modulate parameters of insulin resis¬tance. The present study explored the possible beneficial effects of integrated yoga therapy with reference to glycemic control and insulin resistance (IR) in individuals with diabetes maintained on standard oral medical care with yoga therapy, compared to those on standard oral medical care alone.
Methods: In this study, the subjects on yoga intervention comprised 35 type 2 diabetics, and an equal number of volunteers constituted the control group. Subjects ranged in age from 30 to 70 years, with hemoglobin A1c (HbA1c) test more than 7%, and were maintained on diabetic diet and oral hypoglycemic agents. Blood samples were drawn prior to and after 120 days of integrated yoga therapy intervention. Fasting blood glucose (FBG), post-prandial blood glucose (PPBG), HbA1c, insulin, and lipid profile were assessed in both the intervention and control groups.
Results: The intervention group revealed significant improvements in body mass index (BMI) (0.7 kg/m2 median decrease; P=0.001), FBG (20 mg/dL median decrease; P<0.001), PPBG (33 mg/dL median decrease; P<0.001), HbA1c (0.4% median decrease; P<0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (1.2 median decrease; P<0.001), cholesterol (13 mg/dL median decrease, P=0.006), triacylglycerol (22 mg/dL median decrease; P=0.027), low-density lipo¬protein (6 mg/dL median decrease; P=0.004), and very-low-density lipoprotein levels (4 mg/dL median decrease; P=0.032). Increases in high-density lipoprotein after 120 days were not significant (6 mg/dL median increase; P=0.15). However, when compared to changes observed in patients in the control group, all these improvements proved to be significant.
Conclusion: Administration of integrated yoga therapy to individuals with diabetes leads to a significant improvement in glycemic control, insulin resistance, and key biochemical parameters.
Objective: Congenital nasopharyngeal masses (CNMs) are rare. Presenting symptoms vary, and the differential diagnoses cover a wide spectrum of possibilities. As it is uncommon, most examples discussed in literature are described as case reports or series. Guidelines on CNM patient management do not exist. In this study, we present two (2) cases of neonates with CNMs that were encountered at our tertiary center. Additionally, to best elaborate a comprehensive, case-based approach to CNM management, we offer an up-to-date, diagnosis-to-treatment review of current literature.
Methods: Case series and systematic literature review.
Results: Twenty-eight (28) studies are included since January 2000 to October 2021, with a total of 41 cases. Most common diagnosis was teratoma (78%). Female-to-male ratio was 2.5:1. Twenty percent of cases presented prenatally with polyhydramnios or elevated alpha-fetoprotein. Postnatally, the presenting symptoms most frequently encountered were respiratory distress (78%), oral mass (52%), and feeding difficulties (29%). Seventy-five percent of affected newborns showed symptoms within the first 24 hours of life. Forty percent of cases had comorbidities, especially in the head and neck region.
Conclusions: Congenital nasopharyngeal masses can be detected antenatally, or symptomatically immediately after birth. Airway protection is a cornerstone in the management. Selecting the right imaging
modality and convening a multidisciplinary team meeting are important toward the planning of next steps/therapeutic approach. Typically, a transnasal or transoral surgical approach will be deemed sufficient to address the problem, with a good overall prognosis.
Background: Hyperinsulinemia and insulin resistance occurs in obese patients with primary hypertension independent of diabetes and obesity. This study was aimed at assessing serum fasting insulin levels, the homeostatic model assessment for insulin resistance (HOMA-IR), and serum lipid levels in non-obese patients with primary hypertension when compared to normotensive subjects.
Methods: This observational study comprised 100 patients over 18 years of age, divided into two groups. The hypertensive group comprised non-obese patients with primary hypertension (n=50); the normotensive group comprised normotensive age- and sex-matched individuals (n=50). Patients with diabetes, impaired fasting glucose, obesity, and other causative factors of insulin resistance were excluded from the study. Serum fasting insulin levels and fasting lipid profiles were measured, and insulin resistance was calculated using HOMA-IR. These data were compared between the two groups. Pearson’s correlation coefficient was used to assess the extent of a linear relationship between HOMA-IR and to evaluate the association between HOMA-IR and systolic and diastolic blood pressures.
Results: Mean serum fasting insulin levels (mIU/L), mean HOMA-IR values, and fasting triglyceride levels (mg/dL) were significantly higher in the hypertensive versus normotensive patients (10.32 versus 6.46, P<0.001; 1.35 versus 0.84, P<0.001; 113.70 versus 97.04, P=0.005, respectively). The HOMA-IR levels were associated with systolic blood pressure (r value 0.764, P=0.0005).
Conclusion: We observed significantly higher fasting insulin levels, serum triglyceride levels, and HOMA-IR reflecting hyperinsulinemia and possibly an insulin-resistant state among primary hypertension patients with no other causally linked factors for insulin resistance. We observed a significant correlation between systolic blood pressure and HOMA-IR.
Background and Objective: Medical cannabis is becoming an acceptable treatment modality in medicine, especially for pain relief. Concurrently, cannabis use is becoming more prevalent worldwide, a public demand-driven trend despite the lack of established scientific basis. This observational open-label study sought to investigate the effectiveness of cannabis therapy for alleviating low back pain symptoms.
Methods: Two types of cannabis treatment modalities were sequentially administered to chronic low back pain patients. After an initial 1-month washout period (WO1), the first modality was cannabidiol (CBD)-rich sublingual extract treatment administered for 10 months. Following another washout period, the second modality, Δ⁹-tetrahydrocannabinol (THC)-rich smoked inflorescence (whole dried cannabis flowers) was administered for 12 months.
Results: Enrolled in the study were 24 patients whose advanced imaging studies (i.e. computerized tomography or magnetic resonance imaging of the lumbar spine) revealed disc herniation or spinal stenosis. Three patients dropped out of extract therapy treatment but resumed study participation to receive THC-rich smoking therapy. After a minimum of 2 years, cannabis therapy had reduced lower back pain symptoms, as assessed by Oswestry Disability Index, the SF-12 patient-reported outcome questionnaire, and the visual analogue scale. Pain reduction was not significant during the extract treatment part of the study; however, pain reduction was significant during the inhaled therapy part of the study.
Conclusions: Our findings indicate that inhaled THC-rich therapy is more effective than CBD-rich sublingual extract therapy for treating low back pain and that cannabis therapy is safe and effective for chronic low back pain.
Rheumatoid diseases, including rheumatoid arthritis, osteoarthritis, and fibromyalgia, are characterized by progressive inflammation in the musculoskeletal system, predominantly affecting the joints and leading to cartilage and bone damage. The resulting pain and ongoing degradation of the musculoskeletal system contribute to reduced physical activity, ultimately impacting quality of life and imposing a substantial socioeconomic burden. Unfortunately, current therapeutics have limited efficacy in slowing disease progression and managing pain. Thus, the development of novel and alternative therapies is imperative. Cannabinoids possess beneficial properties as potential treatments for rheumatoid diseases due to their anti-inflammatory and analgesic properties. Preclinical studies have demonstrated promising results in halting disease progression and relieving pain. However, there is a scarcity of patient clinical studies, and the available data show mixed results. Consequently, there are currently no established clinical recommendations regarding the utilization of cannabis for treating rheumatoid diseases. In this review, we aim to explore the concept of cannabis use for rheumatoid diseases, including potential adverse effects. We will provide an overview of the data obtained from preclinical and clinical trials and from retrospective studies on the efficacy and safety of cannabis in the treatment of rheumatoid diseases.
Alternating hemiplegia of childhood (AHC) is a complex neurodevelopmental disorder characterized by paroxysmal and transient events of unilateral or bilateral paresis, usually occurring before 18 months of age. Mutations in the ATP1A3 gene, mainly p.Asp801Asn, p.Glu815Lys, and p.Gly947Arg at the protein level, are found in around 80% of the individuals with AHC. Interestingly, these mutations reflect the degree of severity of the neurological symptoms (p.Glu815Lys > p.Asp801Asn > p.Gly947Arg). Some channels involved in this disorder are N-type voltage-gated calcium channels, ATP-sensitive potassium channels, and the sodium/calcium exchanger. In this context, the management of AHC should be divided into the treatment of attacks, prophylactic treatment, and management of comorbidities commonly found in this group of individuals, including epilepsy, attention-deficit/hyperactivity disorder, aggressive behavior, cognitive impairment, movement disorders, and migraine. The importance of an integrated approach with a multidisciplinary team, such as neuropsychologists and dietitians, is worth mentioning, as well as the follow-up with a neurologist. In the present study, we propose new diagnostic criteria for AHC, dividing it into clinical, laboratory, supporting, and atypical features. Also, we review the location of the mutations in the ATP1A3 protein of individuals with AHC, rapid-onset dystonia-parkinsonism (RDP) variants, and early infantile epileptic encephalopathy (variants with hemiplegic attack). We also include a section about the animal models for ATP1A3 disorders.
