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: 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.
Food security and nutrition were major drivers of cultural evolution by enabling sociotypic development and communal living after the Neolithic agricultural revolution some 12,000 years ago. The sociotype unites concepts from the sciences and the humanities; in concert with the genotype it determines an individual’s phenotype (observable traits and behavior), and together they advance societal culture. As such, the sociotype relates to an individual’s dynamic interactions with the surrounding social environment through¬out life and comprises three domains: the Individual, Relationships, and Context. Nutrition affects each domain, respectively, by ensuring the following dimensions of food security: utilization (metabolic fuel and health); accessibility (physical and economic); and availability (the right to nutritious food for all citi¬zens). The sociotype is influenced by multiple factors, including diet–gene interactions, allostasis, micro¬biota, oxytocin, and culturally through mate selection, family bonds, social communication, political ideol¬ogies, and values. Food security, sociotypes, and culture form a complex adaptive system to enable coping with the circumstances of life in health and disease, to achieve sustainable development, and to eradicate hunger. The current geopolitical unrest highlights the absolutely critical role of this system for global security, yet many challenges remain in implementing this paradigm for society. Therefore, sustainable food security must be considered a fundamental human right and responsibility for safeguarding the survival and progress of the sociotypes of humankind (Homo cultures) worldwide.
Background: External apical root resorption (EARR), an unwanted sequela of orthodontic treatment, is difficult to diagnose radiographically. Hence, the current scoping review was planned to generate critical evidence related to biomarkers in oral fluids, i.e. gingival crevicular fluid (GCF), saliva, and blood, of patients showing root resorption, compared to no-resorption or physiologic resorption.
Methods: A literature search was conducted in major databases along with a manual search of relevant articles in the library, and further search from references of the related articles in March 2021. The initial search was subjected to strict inclusion and exclusion criteria according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.
Results: Following PRISMA guidelines, 20 studies were included in the final review. The studies included human clinical trials and cross-sectional and prospective studies with/without control groups with no date/ language restriction. Various biomarkers identified in EARR included dentinal proteins, enzymes, cytokines, and salivary proteins. Severe resorption had higher dentin sialoprotein (DSP) and resorption protein concentrations as well as lower granulocyte-macrophage colony-stimulating factor (GM-CSF) as compared with mild resorption. Increased DSP and dentin phosphophoryn (DPP) expression was found in physiologic resorption. Compared to controls, resorbed teeth showed a higher receptor activator of nuclear factor kappa B ligand/ osteoprotegerin (RANKL/OPG) ratio. In contrast, levels of anti-resorptive mediators (IL-1RA, IL-4) was significantly decreased. Differences in force levels (150 g and 100 g) showed no difference in resorption, but a significant rise in biomarkers (aspartate transaminase [AST] and alkaline phosphatase [ALP]) for 150 g force. Moderate to severe resorption in young patients showed a rise in specific salivary proteins, requiring further validation. Limitations of the studies were heterogeneity in study design, biomarker collection, sample selection, and confounding inflammatory conditions.
Conclusions: Various biomarkers in biofluids indicate active resorption, while resorption severity was associated with DSP and GM-CSF in GCF, and a few salivary proteins. However, a robust study design in the future is mandated.
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.
Introduction: The second wave of coronavirus disease 2019 (COVID-19) led to the resurgence of opportunistic infections due to the injudicious use of steroids. Sinonasal mucormycosis was declared an epidemic in India during the pandemic. Mucormycosis was managed effectively by surgical debridement along with systemic amphotericin B. Currently, a resurgence of mucormycosis following initial treatment, in the form of fungal osteomyelitis of the frontal bone, is being seen in India.
Methods: This prospective study included 10 patients with fungal osteomyelitis of the frontal bone due to mucormycosis. All patients underwent surgical debridement of the sequestrum and involucrum, with systemic antifungal pharmacotherapy.
Results: The average duration of time until mucormycosis recurrence was 22 days following initial treatment (range 10–33 days). Patients presented with extracranial bossing following outer frontal cortex erosion (n=3), bicortical erosion (n=3), bifrontal involvement (n=2), dural involvement (n=3), and involvement of the brain parenchyma and prefrontal cortex (n=2). All cases underwent debridement of the entire sequestrous bone and involucrum until normal bone could be identified. The mean admission duration was 4 weeks (range 3–6 weeks). All treated patients are currently alive and without disease, confirmed by contrast-enhanced computed tomography.
Conclusion: Based on our experience, the successful treatment of fungal osteomyelitis due to mucormycosis requires a four-pronged approach: early detection, multidisciplinary management of comorbidities, surgical debridement of necrotic bone, and adequate systemic antifungal therapy.
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.
The aftermath of the Second World War and the Holocaust triggered mass migration of Jewish refugees to British Mandatory Palestine and, after 1948, the nascent State of Israel. Responding to this crisis, Jews in the Diaspora increased their commitment to facilitate immigration to Israel, particularly by supporting medical services to the Yishuv (pre-state Jewish Settlement). This paper explores the critical role played by Hadassah and other organizations in establishing direct medical services for Jewish immigrants during two key periods of Israel’s history: the end of British Mandatory Palestine (1944–1948) and the early years of the State of Israel (1948–1953). While the Immigrant Medical Services organization faced numerous challenges, this organization was essential in addressing the pressing healthcare needs of a burgeoning population amid morbidity and mortality concerns. An emphasis is placed on the challenges faced by these organizations and the commitment and resourcefulness of all involved, which ultimately shaped the foundation of Israel’s healthcare infrastructure.
Coronavirus disease-19 (COVID-19) is a pandemic infectious disease caused by a novel coronavirus. Infection can result in a wide range of clinical outcomes, from an asymptomatic condition to severe bilateral pneumonia and life-threatening conditions. Diagnosis is based on the combination of a history of exposure, clinical presentation, and real-time polymerase chain reaction (RT-PCR) assays. In endemic areas, imaging tests including computed tomography (CT), chest X-ray (CXR), and ultrasound (US) have been included in the diagnostic workup. Multiple and peripheral areas of parenchymal injury is the hallmark of COVID-19 lung infection, seen as ground-glass opacification and consolidation on CT, as hazy opacities on CXR, and as multiple B-lines and subpleural consolidations on US. Of these modalities, CT has the best sensitivity and specificity, while CXR has moderate sensitivity and unknown specificity. Both CT and CXR involve ionizing radiation, increase the risk of cross-infection, and require a long sterilization time. Ultrasound is the only modality used by clinicians. Early reports have shown promising results, comparable to CT. With high availability, the lowest risk of cross-infection, and a rapid sterilization process, US may potentially become the primary imaging tool for COVID-19 pulmonary injury. Lung US training programs are needed to provide clinicians with the ability to better implement this technique.
