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.
Background: Resection of oral cavity carcinoma often leads to complex defects causing functional and aesthetic morbidity. Providing optimum reconstruction with free flaps becomes challenging in a high-volume center setting with constrained resources. Hence, understanding the local flap technique for reconstructing oral cancer defects is prudent.
Materials and Methods: This study is a retrospective analysis of prospectively operated cases of oral cavity resections which were subsequently reconstructed using local flaps from 2019 to 2022. Patients who underwent reconstruction with either melolabial flap, islanded facial artery myomucosal (FAMM) flap, submental flap, supraclavicular artery island (SAI) flap, infrahyoid flap, or platysma myocutaneous flap (PMF) were included in this analysis. Eligible patients were followed up to evaluate functional outcomes like oral feeding and to analyze the Performance Status Scale for Head and Neck Cancer.
Results: The study included 104 patients. The tongue was the most common subsite, resulting in most hemiglossectomy defects, which were reconstructed using the melolabial flap procedure. Buccal mucosa defects in our series were reconstructed using the supraclavicular flap, whereas the submental flap procedure was the choice for lower lip-commissure defects. Complications such as partial and total flap loss, deep neck infection, and donor site complications like infection and gaping, oral cutaneous fistula, parotid fistula, and seroma were analyzed; the supraclavicular flap presented with a majority of complications.
Conclusion: Local flaps are an alternative to free flap reconstruction in select cases with optimum functional outcomes and minimal donor site morbidity. This article comprehensively reviews the surgical steps for various local flap procedures in oral cancer defects.
In December 2019, the first cases of a new contagious disease were diagnosed in the city of Wuhan, the capital of Hubei province in China. Within a short period of time the outbreak developed exponentially into a pandemic that infected millions of people, with a global death toll of more than 500,000 during its first 6 months. Eventually, the novel disease was named coronavirus disease 2019 (COVID-19), and the new virus was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Similar to all known pandemics throughout history, COVID-19 has been accompanied by a large degree of fear, anxiety, uncertainty, and economic disaster worldwide. Despite multiple publications and increasing knowledge regarding the biological secrets of SARS-CoV-2, as of the writing of this paper, there is neither an approved vaccine nor medication to prevent infection or cure for this highly infectious disease. Past pandemics were caused by a wide range of microbes, primarily viruses, but also bacteria. Characteristically, a significant proportion of them originated in different animal species (zoonoses). Since an understanding of the microbial cause of these diseases was unveiled relatively late in human history, past pandemics were often attributed to strange causes including punishment from God, demonic activity, or volatile unspecified substances. Although a high case fatality ratio was common to all pandemic diseases, some striking clinical character¬istics of each disease allowed contemporaneous people to clinically diagnose the infection despite null microbiological information. In comparison to past pandemics, SARS-CoV-2 has tricky and complex mech¬anisms that have facilitated its rapid and catastrophic spread worldwide.
Increasing evidence points towards mitochondria as crucial players in the initiation and progression of auto-immune and degenerative disorders, to which impaired cell metabolism is but a facet of the subjacent etiopathogenesis. This review aims to introduce the reader to essential concepts of mitochondrial abnormalities in idiopathic inflammatory myopathy (IIM), underscoring inclusion-body myositis and dermatomyositis. Far surpassing the initial simplistic view of being responsible for energy generation, mitochondria have gathered attention regarding their role in inflammatory processes, being able to fuel autoimmunity, as shown by the presence of anti-mitochondrial antibodies (AMAs) in up to 10% of IIM patients. As cellular respiration takes place, mitochondrial metabolites might help to shape the pro-inflammatory milieu in affected muscle, beyond generating reactive oxygen species, which are well-recognized inducers of damage-associated molecular patterns. A series of mitochondrial components might facilitate the sterile activation of pro-inflammatory cells and the production of several cytokines responsible for enhancing auto-immune responses. Marked variation in the mitochondrial genome has also been reported in IIM patients. As such, we summarize key historical and recent advances linking aberrations and instabilities of mitochondrial DNA to impaired muscle function. Besides discussing mitochondrial dysfunction as an essential part of IIM development, we also highlight possible associations between presence of AMAs and a particular phenotype of IIM, with its own characteristic clinical and radiological pattern. Finally, we present promising treatment approaches targeting mitochondria, while briefly discussing experimental models for gaining deeper insight into the disease process, and ultimately leading to novel drug development.
Major improvements in medical diagnostics and treatments in Dutch hospital care during the second half of the 19th century led to a shift from a nearly exclusive focus on indigent patients to an increasing proportion of hospital beds dedicated to paying middle-class patients. To accommodate this change, three private non-sectarian hospitals for middle-class patients were established in Amsterdam between 1857 and 1902. However, the two Jewish hospitals in the Dutch capital, the Dutch Jewish Ashkenazi hospital (NIZ), and the Portuguese Jewish hospital (PIZ), initially established exclusively for poor Jews, were much slower to respond to the trend of increasing hospital care for the middle class. This study examines how these hospitals addressed the needs of both poor and middle-class patients in the first decades of the 20th century as well as the success of the Centrale Israelitische Ziekenverpleging (CIZ, Central Jewish hospital) that was established solely for middle-class Jewish patients. The report also investigates how, after the devastation of the Amsterdam Jewish community during WW2, the CIZ managed to remain and today is the only ritually observant Jewish hospital unit in the Netherlands.
Pain medicine in Israel and in the world has reached a crisis. The lack of available pain medicine services is resulting in the unsatisfactory treatment for chronic pain sufferers. The main causes of this crisis are: 1) the high prevalence of chronic pain, reaching levels of 17% in the adult population;2) the lack of appropriate training of primary care physicians in the field of chronic pain management; and 3) the paucity of consultation services in the field of chronic pain.
In this journal article, we propose a possible model for the solution of the problem, based upon levels of treatment according to the severity of the disease and upon training of primary and secondary care physicians in the treatment of pain. According to the model, the vast majority of treatment and management will take place in the community after appropriate training of primary care physicians. More complex cases will be referred to secondary care community-based pain clinics manned by physicians with further in-depth training. Only the most complex of patients, or those needing specialized treatment such as invasive analgesic therapy, will be referred to tertiary pain centers manned by specialists in pain medicine.
Implementation of this model will necessitate training of primary care physicians and the establishment of secondary care facilities and can, in our opinion, pose a pragmatic solution for the hundreds of thousands of patients suffering from chronic pain.
Objectives: There are only sporadic reports on the clinical behavior and appropriate treatment of anaplastic seminoma. This retrospective study summarizes our experience with the anaplastic variant of classical (typical) seminoma.
Methods: Between 1986 and 2006, seven anaplastic seminoma patients were staged and treated at the Northern Israel Oncology Center. Staging procedures included meticulous physical and neurological examinations, complete blood count, full biochemistry profile, specific tumor markers, testicular ultrasound, and other radiological measures. All patients underwent inguinal orchiectomy and were staged properly. Six patients had stage I disease, and one patient had stage IIA disease. Patients were irradiated with doses ranging from 2,500 to 3,000 cGy, and the stage IIA patient received an additional 1,000 cGy boost to radiographically involved lymph nodes.
Results: After a mean follow-up of 11 years, six patients are alive with no evidence of disease. One patient died due to an unknown, non-oncological, cause, unrelated to his previous testicular tumor, while in complete remission.
Conclusions: Despite the low patient numbers and the retrospective nature of our study, it can be concluded that radiotherapy treatment for early-stage anaplastic seminoma patients might achieve the same excellent survival as for classical seminoma. However, the general consensus achieved through large-scale studies suggests that active surveillance should be offered to all stage I seminoma patients, regardless of the pathologic variant.
Squamous cell carcinoma of the larynx continues to be the commonest head and neck cancer in many Western countries. The larynx plays a key role for many essential functions, including breathing, voice production, airway protection, and swallowing. The goals of laryngeal cancer treatment are thus to provide best possible oncologic control, while optimizing functional outcomes.
In recent decades, the treatment paradigm for advanced laryngeal cancer has shifted from one of primary surgery (total laryngectomy) as gold standard, toward non-surgical organ-preserving treatment using radiotherapy or chemoradiotherapy. However, concerns have emerged regarding functional outcomes after chemoradiotherapy, as well as possible decreased overall survival in patients with laryngeal cancer.
The purpose of the present review is to review surgical and non-surgical options for treatment of advanced laryngeal cancer, as well as the evidence supporting each of these.
Oropharyngeal cancer represents a growing proportion of head and neck malignancies. This has been associated with the increase in infection of the oropharynx by oncogenic strains of human papillomavirus (HPV). Transoral robotic surgery (TORS) has opened the door for minimally invasive surgery for HPV-related and non-HPV-related oropharyngeal cancer. Compared to traditional open surgical approaches, TORS has been shown to improve functional outcomes in speech and swallowing, while maintaining good oncologic outcomes.
Parkinson’s disease (PD) and Alzheimer’s disease (AD) are severe neurodegenerative disorders, with no drugs that are currently approved to prevent the neuronal cell loss characteristic in brains of pa-tients suffering from PD and AD, and all drug treatments are symptomatic and monomodal in their action. Due to the complex pathophysiology, including a cascade of neurotoxic molecular events that result in neuronal death and predisposition to depression and eventual dementia, and etiology of these disorders, an innovative approach towards neuroprotection or neurorestoration (neurorescue) is the development and use of multifunctional pharmaceuticals which can act at different brain regions and neurons. Such drugs target an array of pathological pathways, each of which is believed to contribute to the cascades that ultimately lead to neuronal cell death. In this short review, we discuss examples of novel multifunctional ligands that may have potential as neuroprotective-neurorestorative therapeutics in PD and AD, some of which are under development. The compounds discussed originate from synthetic chemistry as well as from natural sources.
KEY WORDS: Rasagiline multimodal drugs, antiapoptotic, neuroprotection, neurorestoration, Parkinson’s disease, Alzheimer’s disease
