Narcolepsy Treatment: Present and Future

Narcolepsy is a chronic, disabling sleep disorder with a significant diagnostic delay. Nowadays, treatment is focused on managing symptoms that impacts patient’s life, such as at workplace, social events or even at school, but not aimed cure the disease. However, we have pharmacological treatments that effectively help control the main symptoms (excessive daytime sleepiness, cataplexy, fragmentation of nocturnal sleep, sleep paralysis and hypnagogic and hypnopompic hallucinations). On the other hand, pharmacological treatment must be individualised as there are great variations in severity, order of appearance symptoms and development of the disease. We intend to expose the different symptomatic treatments recommended by clinical guidelines and the clinical management from a practical point of view. Future treatments include therapies based on the replacement of hypocretin or the administration of agonist receptors. Other techniques such as hypothalamic stem cell transplantation, gene replacement therapy or immunotherapy are also being investigated.

Relapse to cotinine seeking in rats: Differential effects of sex

Relapse is a defining feature of smoking and a significant challenge in cessation management. Elucidation of novel mechanisms underlying relapse may inform future treatments. Cotinine, the major metabolite of nicotine, has been shown to support intravenous self-administration in rats, suggesting it as one potential mechanism contributing to nicotine reinforcement. However, it remains unknown whether cotinine would induce relapse-like behaviors. The current study investigated relapse to cotinine seeking in two relapse models, the reinstatement of drug seeking and incubation of drug craving models. In the reinstatement model, rats were trained to self-administer cotinine, extinguished cotinine-associated responses, and underwent cue-, drug-, or stress-induced reinstatement. Conditioned cues associated with cotinine self-administration, cotinine (1-2 mg/kg), or the pharmacological stressor yohimbine (1.25-2.5 mg/kg) reinstated cotinine seeking. Female rats displayed more pronounced cue-induced, but not drug- or stress-induced reinstatement than male rats. In addition, an overall analysis revealed that female rats exhibited greater cotinine self-administration, but less extinction than male rats. In the incubation model, rats were trained to self-administer cotinine, and underwent forced withdrawal in home cages. Rats were tested for cue-induced cotinine seeking on both withdrawal day 1 and withdrawal day 18. Rats exhibited greater cotinine-seeking on withdrawal day 18 compared to withdrawal day 1, with no difference between male and female rats. These findings indicate that cotinine induces sex-dependent relapse to cotinine seeking in rats, suggesting that cotinine may be a novel mechanism contributing to relapse. These rat models are valuable preclinical tools for interrogation of neurobiological underpinnings of relapse to cotinine seeking.

Skin Barrier Dysregulation in Psoriasis

The skin barrier is broadly composed of two elements—a physical barrier mostly localised in the epidermis, and an immune barrier localised in both the dermis and epidermis. These two systems interact cooperatively to maintain skin homeostasis and overall human health. However, if dysregulated, several skin diseases may arise. Psoriasis is one of the most prevalent skin diseases associated with disrupted barrier function. It is characterised by the formation of psoriatic lesions, the aberrant differentiation and proliferation of keratinocytes, and excessive inflammation. In this review, we summarize recent discoveries in disease pathogenesis, including the contribution of keratinocytes, immune cells, genetic and environmental factors, and how they advance current and future treatments.

A biomarker and endophenotype for anorexia nervosa?

Objective: Recent research has suggested that a type of atypical eye movement, called square wave jerks, together with anxiety, may distinguish individuals with anorexia nervosa from those without anorexia nervosa and may represent a biomarker and endophenotype for the illness. The aim of this study was to identify the presence of this proposed marker in individuals currently with anorexia nervosa relative to healthy controls, and to identify the state independence and heritability of this putative marker by exploring whether it also exists in individuals who are weight-restored from anorexia nervosa and first-degree relatives (i.e. sisters of people with anorexia nervosa). Methods: Data from 80 female participants (20/group: current anorexia nervosa, weight-restored from anorexia nervosa, sisters of people with anorexia nervosa and healthy controls) were analysed. Square wave jerk rate was acquired during a fixation task, and anxiety was measured with the State Trait Anxiety Inventory. Results: Current anorexia nervosa, weight-restored from anorexia nervosa and sisters of people with anorexia nervosa groups made significantly more square wave jerks than healthy controls, but did not differ from one another. Square wave jerk rate and anxiety were found to discriminate groups with exceptionally high accuracy (current anorexia nervosa vs healthy control = 92.5%; weight-restored from anorexia nervosa vs healthy control = 77.5%; sisters of people with anorexia nervosa vs healthy control = 77.5%; p < .001). Conclusion: The combination of square wave jerk rate and anxiety was found to be a promising two-element marker for anorexia nervosa, and has the potential to be used as a biomarker or endophenotype to identify people at risk of anorexia nervosa and inform future treatments.

Current and Future Treatments in Primary Ciliary Dyskinesia

Primary ciliary dyskinesia (PCD) is a rare genetic ciliopathy in which mucociliary clearance is disturbed by the abnormal motion of cilia or there is a severe reduction in the generation of multiple motile cilia. Lung damage ensues due to recurrent airway infections, sometimes even resulting in respiratory failure. So far, no causative treatment is available and treatment efforts are primarily aimed at improving mucociliary clearance and early treatment of bacterial airway infections. Treatment guidelines are largely based on cystic fibrosis (CF) guidelines, as few studies have been performed on PCD. In this review, we give a detailed overview of the clinical studies performed investigating PCD to date, including three trials and several case reports. In addition, we explore precision medicine approaches in PCD, including gene therapy, mRNA transcript and read-through therapy.

Treatments for HBV: A Glimpse into the Future

The hepatitis B virus is responsible for most of the chronic liver disease and liver cancer worldwide. As actual therapeutic strategies have had little success in eradicating the virus from hepatocytes, and as lifelong treatment is often required, new drugs targeting the various phases of the hepatitis B virus (HBV) lifecycle are currently under investigation. In this review, we provide an overview of potential future treatments for HBV.

Highlights from ASCO-GI 2021 from EORTC Gastrointestinal tract cancer group

Last year the field of immunotherapy was finally introduced to GI oncology, with several changes in clinical practice such as advanced hepatocellular carcinoma or metastatic colorectal MSI-H. At the virtual ASCO-GI symposium 2021, several large trial results have been reported, some leading to a change of practice. Furthermore, during ASCO-GI 2021, results from early phase trials have been presented, some with potential important implications for future treatments. We provide here an overview of these important results and their integration into routine clinical practice.

Reaction-Diffusion on a Spatial Mathematical Model of Cancer Immunotherapy with Effector Cells and IL-2 Compounds’ Interactions

Immunotherapy is one of the future treatments applicable in most cases of cancer including malignant cancer. Malignant cancer usually prevents some genes, e.g., p53 and pRb, from controlling the activation of the cell division and the cell apoptosis. In this paper, we consider the interactions among the cancer cell population, the effector cell population that is a part of the immune system, and cytokines that can be used to stimulate the effector cells called the IL-2 compounds. These interactions depend on both time and spatial position of the cells in the tissue. Mathematically, the spatial movement of the cells is represented by the diffusion terms. We provide an analytical study for the constant equilibria of the reaction-diffusion system describing the above interactions, which show the initial behaviour of the tissue, and we conduct numerical simulation that shows the dynamics along the tissue that represent the immunotherapy effects. In this case, we also consider the steady-state conditions of the system that show the long-time behaviour of these interactions.

MO200COVID-19 PANDEMIC INCREASED ADVANCE CARE PLANNING DEMAND

Background and Aims Advance care planning (ACP) enables competent patients to define goals and preferences for future treatments and care, to discuss these goals and preferences with relatives, and if appropriate to record these preferences. After many years of political and social debates, in December 2017 the first advance directive and care planning legislation was approved in Italy. Nevertheless, citizens’ awareness of these issues is scarce as well as the integration of the advance care planning process into clinical routine. The latest data reported to the Italian Parliament by the Ministry of Health indicated that advance directives have been completed by 62030 people, approximately 1.1% of Italian adult population. However, during the last months, the COVID-19 pandemic solicited taking steps towards promoting an advance care planning culture. Indeed, the need of proposing ACP to patients have been recently stressed both by medical associations and national and local institutional documents. Method Since November 2020, our nephrology unit adopted a protocol approved by Ethical committee by Physician Order of Florence, aimed to conduct ACP interventions with dialysis patients. Firstly, all patients were informed about the possibility to taking part in one or more advance care planning conversations with their nephrologist. Secondly, a semi-structured guide to the conversation was created in order to support physicians in conducting the ACP intervention. Finally, patients along with nephrologist and their relatives, could documented their preferences for future treatments and care. Results From November to March only one patient asked to receive an ACP intervention. However, since COVID-19 spread in Italy last March, the number of patients who demanded ACP raised up. In the period from April to July, 15 out of 110 hemodialysis patients treated in our center asked for an ACP intervention and filled-in an advance directive. Specifically, no patients required an immediate discontinuation of dialysis, nevertheless 80% of them stated that would not like to continue with dialysis in case he/she was no longer able to self-determine (e.g. permanent loss of capacity to communicate with others). All patients except one have appointed a personal representative (usually their partner). In the eventuality of cardiac arrest, 60% of patients asked for cardiopulmonary resuscitation. Finally, all patients expressed the wish to spend the last days of life at home. Conclusion The COVID-19 pandemic raised up the number of dialysis patients who required to taking part in a advance care planning intervention. In this sense, the pandemic can be an opportunity for consolidate advance care planning in Italy as well as in other countries, where these interventions are not well known by people and not yet regularly offered in the clinical routine. Using a semi-structured interview for the ACP interview can help the nephrologist to discuss future care and end-of-life topics with their patients.