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Immune checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4, anti-programmed cell death 1, and anti-programmed cell death ligand 1 (PD-L1) antibodies, are currently widely used in oncology clinical practice, achieving considerable success in improving disease outcomes. New checkpoint targets are being discovered and investigated through basic science research and clinical trials. ICI remove negative regulatory immune signals on T cells, leading to immune activation and induction of antitumor immunity. Patients who receive ICI, however, are at risk for developing immune-related adverse events (irAEs), which are attributed to increased T cell activity against antigens in both tumors and in healthy tissues, to increased inflammatory cytokine levels, to increased levels of preexisting autoantibodies, and to enhanced complement-mediated inflammation. Arthritis is one of the most common irAEs. ICI-induced rheumatic irAEs are categorized by levels of severity which guide the choice of treatment options. Management of ICI-induced rheumatic irAEs includes the use of glucocorticoids, disease-modifying antirheumatic drugs (mainly methotrexate), and biological agents (e.g., tumor necrosis factor, interleukin-6 receptor, and CD20 inhibitors). This review aims to summarize the current ICI subtypes, their role in rheumatic irAEs development, and therapies current used in clinical practice to manage irAEs. In addition, we propose to use an ex vivo personalized diagnostic assay for the selection of the most effective ICI with antirheumatic drugs combinations that will inhibit the advancement of ICI-induced adverse events.

There is a constant pressure in industry to move away from platinum group metals (PGM) and achieve more environmentally friendly and sustainable production processes in the future. Recently developed Mn-based catalysts offer an interesting opportunity to complement established catalysts based on Ru. In this article, recent achievements in the field are highlighted and recent achievements in the collaboration of Solvias AG with the group of Prof. M. Clarke towards the implementation of these catalysts on industrial scale are outlined.

BackgroundAntibodies against N-methyl-D-aspartate receptors are the most commonly identified cause of autoimmune encephalitis. While predominantly associated with malignancies, cases of anti-N-methyl-D-aspartate receptor autoimmune encephalitis have been reported after infections with the herpes-simplex virus or, more recently, in patients with severe COVID-19 disease.Case presentationA previously healthy 17-year-old male adolescent acutely developed psychosis with auditory and visual hallucinations, fluctuating mental status, and an isolated seizure 5 weeks after a mildly symptomatic COVID-19 infection. The symptoms continued to worsen, accompanied by catatonia, and additional neurological symptoms developed during the initial antipsychotic treatment. A diagnostic workup revealed antibodies against N-methyl-D-aspartate receptors in the cerebrospinal fluid without other major abnormalities. After establishing the diagnosis, initiation of immunomodulatory therapy stopped the symptom progression and led to full recovery within 2 months.ConclusionThe case is remarkable in that anti-N-methyl-D-aspartate receptor autoimmune encephalitis developed shortly after a COVID-19 infection in an adolescent, despite the individual experiencing only mild COVID symptoms. The diagnosis should be considered in cases of acute-onset psychotic symptoms during or after COVID-19 infection, particularly in individuals without a prior psychiatric history, who present with atypical psychiatric or neurological features.

Contexto: Estudos anteriores indicam alta prevalência de estresse em pais de crianças com Transtorno de Espectro do Autismo (TEA) e impacto moderador da rede de apoio social. No entanto, poucos investigaram a relação entre essas variáveis e as crenças e práticas parentais no cuidado e estimulação de crianças com TEA. Objetivo: Avaliar associações entre estresse, rede social de apoio e crenças maternas/práticas em mães de crianças com TEA. Métodos: Este estudo transversal correlacional avaliou 52 mães (Midade = 37,50 anos) de crianças com TEA atendidas em quatro unidades de saúde pública do Estado de São Paulo. Foram aplicados um Questionário Sociodemográfico, o Inventário Lipp de Sintomas de Estresse, a Escala de Crenças Parentais e Práticas de Cuidado e a Escala de Rede Social de Apoio. Resultados: Observou-se alta prevalência (86,5%) de estresse clínico das participantes. A percepção de apoio social foi baixa, e mães com percepção de maior apoio social indicaram menores níveis de estresse. Embora as práticas de cuidado fossem em geral adequadas, mães com mais estresse realizavam menos atividades de estimulação com seus filhos. Conclusões: Os resultados reforçam a importância da avaliação e manejo do estresse, da rede social de apoio e da saúde mental das mães de crianças com TEA, para facilitar a adoção de práticas de estimulação que possam otimizar o desenvolvimento de crianças com alterações de neurodesenvolvimento.

BackgroundOxygen consumption is an important index to evaluate in cardiac patients, particularly those with heart failure, and is measured in the setting of advanced cardiopulmonary exercise testing. However, technological advances now allow for the estimation of this parameter in many consumer and medical-grade wearable devices, making it available for the medical provider at the initial evaluation of patients. We report a case of an apparently healthy male aged 40 years who presented for evaluation due to an Apple Watch (Apple Inc) notification of low cardiac fitness. This alert triggered a thorough workup, revealing a diagnosis of familial nonischemic cardiomyopathy with severely reduced left ventricular systolic function. While the use of wearable devices for the measurement of oxygen consumption and related parameters is promising, further studies are needed for validation. ObjectiveThe aim of this report is to investigate the potential utility of wearable devices as a screening and risk stratification tool for cardiac fitness for the general population and those with increased cardiovascular risk, particularly through the measurement of peak oxygen consumption (VO2). We discuss the possible advantages of measuring oxygen consumption using wearables and propose its integration into routine patient evaluation and follow-up processes. With the current evidence and limitations, we encourage researchers and clinicians to explore bringing wearable devices into clinical practice. MethodsThe case was identified at Sheba Medical Center, and the patient’s cardiac fitness was monitored through an Apple Watch Series 6. The patient underwent a comprehensive cardiac workup following his presentation. Subsequently, we searched the literature for articles relating to the clinical utility of peak VO2 monitoring and available wearable devices. ResultsThe Apple Watch data provided by the patient demonstrated reduced peak VO2, a surrogate index for cardiac fitness, which improved after treatment initiation. A cardiological workup confirmed familial nonischemic cardiomyopathy with severely reduced left ventricular systolic function. A review of the literature revealed the potential clinical benefit of peak VO2 monitoring in both cardiac and noncardiac scenarios. Additionally, several devices on the market were identified that could allow for accurate oxygen consumption measurement; however, future studies and approval by the Food and Drug Administration (FDA) are still necessary. ConclusionsThis case report highlights the potential utility of peak VO2 measurements by wearable devices for early identification and screening of cardiac fitness for the general population and those at increased risk of cardiovascular disease. The integration of wearable devices into routine patient evaluation may allow for earlier presentation in the diagnostic workflow. Cardiac fitness can be serially measured using the wearable device, allowing for close monitoring of functional capacity parameters. Devices need to be used with caution, and further studies are warranted.

Abstract The COVID–19 pandemic has caused considerable interest worldwide in antiviral surfaces, and there has been a dramatic increase in the research and development of innovative material systems to reduce virus transmission in the past few years. The International Organization for Standardization (ISO) norms 18,184 and 21,702 are two standard methods to characterize the antiviral properties of porous and non-porous surfaces. However, during the last years of the pandemic, a need for faster and inexpensive characterization of antiviral material was identified. Therefore, a complementary method based on an Inactivated Virus System (InViS) was developed to facilitate the early-stage development of antiviral technologies and quality surveillance of the production of antiviral materials safely and efficiently. The InViS is loaded with a self-quenched fluorescent dye that produces a measurable increase in fluorescence when the viral envelope disintegrates. In the present work, the sensitivity of InViS to viral disintegration by known antiviral agents is demonstrated and its potential to characterize novel materials and surfaces is explored. Finally, the InViS is used to determine the fate of viral particles within facemasks layers, rendering it an interesting tool to support the development of antiviral surface systems for technical and medical applications.

Treatment with biological agents has become standard of care in treatment of immune-mediated diseases (IMD), including rheumatoid arthritis and psoriatic arthritis. Yet, a significant proportion of patients experience loss of response to biologics, need treatment escalation, or develop side effects. During the past decade, new biologic agents with different targeted molecular pathways have been approved for treatment of IMD, introducing the possibility of concomitant dual biologic therapy. The role of dual biologic therapy targeting different inflammatory pathways has become an area of great interest in the field of IMD, addressing the unmet clinical need of patients with refractory diseases and treatment of comorbidities, such as osteoporosis, asthma, atopic dermatitis, and urticaria. Despite the increasing use of biologics as a dual therapy across different indications, there is a paucity of data concerning the safety of the simultaneous use of more than one biological agents. The purpose of this review is to summarize the current literature on the use of dual biologics in patients with rheumatoid arthritis and psoriatic arthritis, addressing the potential adverse effects associated with combination therapy, and highlighting future directions in the use of this novel therapeutic modality.

Abstract Background Despite elevated prevalence rates of prenatal (antenatal) anxiety across studies (13–21%), and prenatal people’s use of the Internet to search for pregnancy-related information and support, research investigating prenatal people’s experiences with online mental health communication, such as blogs, is lacking. This study examined blog entries focused on anxiety in pregnancy to better understand prenatal people’s Internet discourse concerning their experiences with anxiety. Methods A Google search using the keywords “anxiety,” “pregnant,” and “blog” resulted in N = 18 blogs that met inclusion criteria (public blog written in English describing a personal experience with prenatal anxiety in 250 words or more). Blog content was analyzed using a thematic analytic approach based on grounded theory principles. Results Three main themes capturing prenatal people’s experiences with anxiety as written in public blog content were developed from qualitative analyses: 1) etiology (subthemes: before pregnancy, during the current pregnancy, related to a previous pregnancy), 2) triggers (subthemes: uncertainty, perceived lack of control, and guilt and shame for not having a normal pregnancy), and 3) symptoms (subthemes: intertwined emotional, cognitive and physical symptoms, in addition to behavioural symptoms). Conclusions Our findings demonstrate a need for perinatal professionals to address anxiety symptoms and triggers in pregnancy. One way to address this may be by providing credible information regarding prenatal mental and physical health to pregnant people through online mediums, such as blogs. Bloggers often discussed experiencing a combination of emotional, cognitive, physical, and behavioural symptoms, which suggests that medical and mental health professionals should work collaboratively to provide care for prenatal people experiencing anxiety. Furthermore, Cognitive Behavioural Therapy (CBT) addresses these types of symptoms, which suggests that interventions developed or adapted to meet this populations’ needs could employ this therapeutic approach. Future research should explore the reasons why prenatal people experiencing anxiety engage with blogs, the characteristics of bloggers and readers, the impact of the blogging experience on both the blogger and their audience, and the information quality of blog content.

Abstract The study assessed chronic myocardial, coronary and systemic effects of intracoronary supersaturated oxygen (SSO2) therapy. Left anterior descending coronary arteries of 40 swine were stented and randomized to 90-min selective intracoronary infusion of SSO2 (pO2 760–1000 mmHg) or normoxemic saline. In 20 out of 40 animals, SSO2 delivery followed a 60-min balloon occlusion to induce myocardial infarction (MI). In both normal and MI models, intracoronary treatment with hyperoxemic SSO2 therapy showed no evidence of coronary thrombosis. There were no biologically relevant differences between treatments at either time point in regard to coronary intervention site healing and neointimal growth. No signs of any myocardial or systemic toxicity were observed after 7 or 30 days. A trend was observed toward reduced incidence of microscopic MI scars and reduced infarct size in histopathology, as well as toward better recovery of echocardiographically evaluated global and regional contractility at 30 days. No treatment related infarcts or thromboemboli were observed in the downstream organs.

Abstract Background During the perinatal period (including pregnancy and up to 12 months after childbirth), expectant and new mothers are at an elevated risk of developing depression. Inadequate knowledge about perinatal depression and treatment options may contribute to the low help-seeking rates exhibited by perinatal people. The Internet can be an accessible source of information about perinatal depression; however, the quality of this information remains to be evaluated. The purpose of this study was to assess the quality of perinatal depression information websites. Methods After review, 37 websites were included in our sample. To assess overall website quality, we rated websites based on their reading level (Simple Measure of Gobbledegook; SMOG), information quality (DISCERN), usability (Patient Education Materials Assessment Tool; PEMAT), and visual design (Visual Aesthetics of Website Inventory; VisAWI). Results Websites often exceeded the National Institute of Health's recommended reading level of grades 6–8, with scores ranging from 6.8 to 13.5. Website information quality ratings ranged from 1.8 to 4.3 out of 5, with websites often containing insufficient information about treatment choices. Website usability ratings were negatively impacted by the lack of information summaries, visual aids, and tangible tools. Visual design ratings ranged from 3.2 to 6.6 out of 7, with a need for more creative design elements to enhance user engagement. Conclusions This study outlines the characteristics of high-quality perinatal depression information websites. Our findings illustrate that perinatal depression websites are not meeting the needs of users in terms of reading level, information quality, usability, and visual design. Our results may be helpful in guiding healthcare providers to reliable, evidence-based online resources for their perinatal patients.

Heightened delay discounting has been linked to adverse smoking cessation outcomes, including among light cigarette users. Few studies have evaluated delay discounting's proposed mechanism, preference reversal (concurrent increases in valuation of/craving for desired objects), and none have done so in naturalistic settings. We examined how person‐level delay discounting moderated the within‐person association between cigarette valuation and craving among very light daily cigarette users who were financially incentivized to abstain. Forty participants completed a baseline delay‐discounting task and intermittent ratings of cigarette valuation and craving during the incentivized abstinence attempt. Subjects earned monetary rewards for abstinence on a descending schedule (e.g., $20 on Days 1 and 2 and $2.50 on Days 9 and 10). Consistent with preference reversals, there was a positive association between cigarette valuation and craving. This relation was moderated by delay discounting (stronger among those with low discounting rates) and by monetary reinforcement amount (stronger on days with low reinforcement). Additionally, subjects were more likely to report stronger cravings on days with high monetary reinforcement, with this effect moderated by delay discounting (stronger among those with low discounting rates). The results suggest that heightened delay discounting may not confer risk for preference reversal among very light daily cigarette users who are attempting abstinence. [ABSTRACT FROM AUTHOR]

Abstract Background Elevated blood pressure among adolescents has been shown to be associated with future adverse cardiovascular outcomes and early onset diabetes. Most data regarding systolic and diastolic blood pressure trends are based on surveys of selected populations within 10–20-year periods. The goal of this study was to characterize the secular trend of blood pressure given the rising prevalence of adolescent obesity. Methods This nationwide population-based study included 2,785,515 Israeli adolescents (41.6% females, mean age 17.4 years) who were medically evaluated and whose weight, height and blood pressure were measured, prior to mandatory military service between 1977 and 2020. The study period was divided into 5-year intervals. Linear regression models were used to describe the P for trend along the time intervals. Analysis of covariance was used to calculate means of blood pressure adjusted for body mass index. Results During the study period, the mean body mass index increased by 2.1 and 1.6 kg/m2 in males and females, respectively (P for trend

Julia Berman,1,2,* Victoria Furer,2,3,* Mark Berman,2,3 Ofer Isakov,1,2 Devy Zisman,4,5 Amir Haddad,4 Ori Elkayam2,3 1Department of Medicine ‘T’, Sourasky Medical Center, Tel Aviv, Israel; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; 3Department of Rheumatology, Sourasky Medical Center, Tel Aviv, Israel; 4Rheumatology Unit, Carmel Medical Center, Haifa, Israel; 5The Ruth and Bruce Rappaport Faculty of Medicine,Technion, Haifa, Israel*These authors contributed equally to this workCorrespondence: Julia Berman Email juliab@tlvmc.gov.ilObjective: To assess the clinical response to ixekizumab following secukinumab failure in patients with psoriatic arthritis.Methods: A retrospective multi-center observational study included psoriatic arthritis (PsA) patients with a history of treatment with secukinumab, further treated with ixekizumab. Primary endpoint was primary response to treatment (drug survival > 6 months); secondary endpoints were changes in disease activity indices from initiation of ixekizumab to 6 and 12 months later and overall drug survival.Results: Of 23 PsA patients, 86% (n = 20) received more than two TNF inhibitors (TNFi). Median secukinumab treatment time was 15 months (IQR 10– 21.5 months). Subsequently, 19 patients (83%) had a primary response to ixekizumab. Overall treatment duration during follow-up period for primary responders was 14 months (IQR 10– 20.5). Reasons for ixekizumab cessation were worsening psoriasis (27%), peripheral arthritis (27%), both (47%), worsening of axial disease (13%), and adverse events (6%). Articular disease indices including Disease Activity Index for Psoriatic Arthritis (DAPSA), tender joints count (TJC) and Simplified Disease Activity Index (SDAI) were significantly lower at 6 and 12 months (DAPSA 1.5– 2 levels reduction; p = 0.018 and 1– 1.5 levels reduction; p = 0.031, respectively; TJC − 2.16 [− 4.0, − 0.3]; p = 0.025 and − 1.69 [− 3.09, − 0.28]; p = 0.022, respectively; SDAI − 10.13 [− 16.4, − 3.8], p = 0.003 and − 12.2 [− 17.1, − 7.2], p = 0.0002, respectively). PASI75 at 6 and 12 months was achieved by 63% and 57%, respectively, and PASI100 at 6 and 12 months by 31% and 21%, respectively.Conclusion: Patients with resistant PsA, including inadequate response to secukinumab, demonstrated a good response to ixekizumab, albeit limited on time. Within class switch from secukinumab to ixekizumab may be a plausible therapeutic option in PsA patients following secukinumab failure.Keywords: secukinumab, ixekizumab, arthritis, psoriatic, duration of therapy, antibodies, monoclonal, humanized, psoriasis