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.
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.
On May 19, 2020, data confirmed that coronavirus 2019 disease (COVID-19) had spread worldwide, with more than 4.7 million infected people and more than 316,000 deaths. In this article, we carry out a comparison of the methods to calculate and forecast the growth of the pandemic using two statistical models: the autoregressive integrated moving average (ARIMA) and the Gompertz function growth model. The countries that have been chosen to verify the usefulness of these models are Austria, Switzerland, and Israel, which have a similar number of habitants. The investigation to check the accuracy of the models was carried out using data on confirmed, non-asymptomatic cases and confirmed deaths from the period February 21–May 19, 2020. We use the root mean squared error (RMSE), the mean absolute percentage error (MAPE), and the regression coefficient index R2 to check the accuracy of the models. The experimental results provide promising adjustment errors for both models (R2>0.99), with the ARIMA model being the best for infec¬tions and the Gompertz best for mortality. It has also been verified that countries are affected differently, which may be due to external factors that are difficult to measure quantitatively. These models provide a fast and effective system to check the growth of pandemics that can be useful for health systems and politi¬cians so that appropriate measures are taken and countries’ health care systems do not collapse.
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.
Quantification of the T cell receptor excision circles (TRECs) has recently emerged as a useful non-invasive clinical and research tool to investigate thymic activity. It allows the identification of T cell production by the thymus. Quantification of TREC copies has recently been implemented as the preferred test to screen neonates with severe combined immunodeficiency (SCID) or significant lymphopenia. Neonatal genetic screening for SCID is highly important in countries with high rates of consanguinous marriages, such as Israel, and can be used for early diagnosis, enabling prompt therapeutic intervention that will save lives and improve the outcome of these patients. TREC measurement is also applicable in clinical settings where T cell immunity is involved, including any T cell immunodeficiencies, HIV infection, the aging process, autoimmune diseases, and immune reconstitution after bone marrow transplantation.
TAKE-HOME MESSAGES
• Severe combined immunodeficiency, a life-threatening condition, can be detected by neonatal screening.
• The earlier the detection and the quicker the implementation of appropriate treatment, the greater the likelihood for improved outcome, even cure, for the affected children.
• TRECs and KRECs quantification are useful screening tests for severe T and B cell immunodeficiency and can be used also to evaluate every medical condition involving T and B cell immunity.
The term “neuropathic pain” (NP) refers to chronic pain caused by illnesses or injuries that damage peripheral or central pain-sensing neural pathways to cause them to fire inappropriately and signal pain without cause. Neuropathic pain is common, complicating diabetes, shingles, HIV, and cancer. Medications are often ineffective or cause various adverse effects, so better approaches are needed. Half a century ago, electrical stimulation of specific brain regions (neuromodulation) was demonstrated to relieve refractory NP without distant effects, but the need for surgical electrode implantation limited use of deep brain stimulation. Next, electrodes applied to the dura outside the brain’s surface to stimulate the motor cortex were shown to relieve NP less invasively. Now, electromagnetic induction permits cortical neurons to be stimulated entirely non-invasively using transcranial magnetic stimulation (TMS). Repeated sessions of many TMS pulses (rTMS) can trigger neuronal plasticity to produce long-lasting therapeutic benefit. Repeated TMS already has US and European regulatory approval for treating refractory depression, and multiple small studies report efficacy for neuropathic pain. Recent improvements include “frameless stereotactic” neuronavigation systems, in which patients’ head MRIs allow TMS to be applied to precise underlying cortical targets, minimizing variability between sessions and patients, which may enhance efficacy. Transcranial magnetic stimulation appears poised for the larger trials necessary for regulatory approval of a NP indication. Since few clinicians are familiar with TMS, we review its theoretical basis and historical development, summarize the neuropathic pain trial results, and identify issues to resolve before large-scale clinical trials.
This review describes some of the recent developments in imaging aspects of pain in the periphery. It is now possible to image nerves in the cornea non-invasively, to image receptor level expression and inflammatory processes in injured tissue, to image nerves and alterations in nerve properties, to image astrocyte and glial roles in neuroinflammatory processes, and to image pain conduction functionally in the trigeminal ganglion. These advances will ultimately allow us to describe the pain pathway, from injury site to behavioral consequence, in a quantitative manner. Such a development could lead to diagnostics determining the source of pain (peripheral or central), objective monitoring of treatment progression, and, hopefully, objective biomarkers of pain.
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.
The growing practice of endoscopic surgery has changed the therapeutic management of selected head and neck cancers. Although a negative surgical margin in resection of neoplasm is the most important surgical principle in oncologic surgery, controversies exist regarding assessment and interpretation of the status of margin resection. The aim of this review was to summarize the literature considering the assessment and feasibility of negative margins in transoral laser microsurgery (TLM) and transoral robotic surgery (TORS). Free margin status is being approached differently in vocal cord cancer (1–2 mm) compared with other sites in the upper aerodigestive tract (2–5 mm). Exposure, orientation of the pathological specimen, and co-operation with the pathologist are crucial principles needed to be followed in transoral surgery. Piecemeal resection to better expose deep tumor involvement and biopsies taken from surgical margins surrounding site of resection can improve margin assessment. High rates of negative surgical margins can be achieved with TLM and TORS. Adjuvant treatment decision should take into consideration also the surgeon’s judgment with regard to the completeness of tumor resection.
