Neurologic and Psychiatric Manifestations of Bradykinin-Mediated Angioedema: Old and New Challenges

Neurologic manifestations have been occasionally described in patients with bradykinin-mediated angioedema. The existing literature is currently limited to case series and case reports mainly described in the hereditary forms (HAE) concerning central nervous system (CNS) involvement. On the contrary, very little is known about peripheral and autonomic nervous system manifestations. CNS involvement in HAE may present with symptoms including severe headaches, visual disturbance, seizures, and various focal and generalized deficits. In addition, a stroke-like clinical picture may present in HAE patients. In turn, some drugs used in patients with cardiovascular and neurologic disorders, such as recombinant tissue plasminogen activator (r-tPA) and angiotensin-converting enzyme inhibitors (ACEI), may produce medication-induced angioedema, resulting in a diagnostic challenge. Finally, most patients with HAE have higher levels of psychological distress, anxiety, and depression. With this review, we aimed to provide an organized and detailed analysis of the existing literature on neurologic and psychiatric manifestations of HAE to shed light on these potentially invalidating symptoms and lay the foundation for further personalized diagnostic pathways for patients affected by this protean disease

Changes of Oxytocin and Serotonin Values in Dialysis Patients after Animal Assisted Activities (AAAs) with a Dog-A Preliminary Study

Simple Summary This study aimed to improve the moment of dialysis because the emotional management of a person during treatment can help to reduce stress, anxiety and depression. This process positively affects the acceptance and progress of treatment and improves the self-management of the disease, a very important achievement in chronic kidney disease. Serotonin and oxytocin are important neuromodulators of different human behaviours, such as affectivity and socialization, and are involved in the control of stress, anxiety and social cooperation. The relationship between humans and domestic animals provides psychophysical well-being and can facilitate interpersonal bonds by favouring mechanisms involved in social relations. Dogs due to their ethological characteristics, allow the establishment of an active relationship through play, communication and interaction. Animal-assisted activities (AAAs) are structured interventions aimed at improving the psychophysical conditions of people in stressful conditions. Our study was aimed at determining the circulating levels of serotonin and oxytocin in patients who participated in an AAAs program with a dog during dialysis treatment. Our study aimed to measure the levels of serotonin and oxytocin in patients affected by end-stage renal disease (ESRD), undergoing dialysis and participating in a program of animal-assisted activities (AAAs) with a dog. Ten patients with comparable levels of ESRD were enrolled. A blood sample was taken before the start of the study in order to establish basal levels. Eleven meetings were held once a week for 3 months during the last hour of dialysis, and blood samples were collected before and after AAAs. Two more meetings, one month apart from each other, were held two months later without the dog but with the same veterinarian zootherapist. Blood was drawn at the beginning and at the end of each meeting. The samples were then processed for the measurement of serotonin and oxytocin, and data obtained were analysed using analysis of variance with mixed effect models. The results show an increasing level of both serotonin and oxytocin between subsequent meetings with the dog and an increasing trend of inter-intervention levels. Overall, the results suggest that AAAs lead to modifications of serotonin and oxytocin levels, which are also accompanied by behavioural changes of patients

Immunogenicity and Safety of Anti-SARS-CoV-2 mRNA Vaccines in a Cohort of Patients with Hereditary Angioedema

Many factors may trigger hereditary angioedema (HAE) attacks. This study aims to gain insights into the benefits and potential risks of COVID-19 vaccination in HAE patients, focusing particularly on the possibility of triggering attacks. We enrolled 31 patients with HAE undergoing two doses of the SARS-CoV-2 mRNA Comirnaty-BioNTech/Pfizer vaccine. To evaluate the possible influence of the vaccine on disease control and attack frequency, we administered the angioedema control test (AECT) 4-week version before (T0), 21 days after the first dose (T1), and between 21 and 28 days after the second dose (T2). Despite 5 patients (16.1%) experiencing attacks within 72 h of the first dose administration, no significant variation in attack frequency was observed before and after vaccination [F(2,60) = 0.123; p = 0.799]. In addition, patients reported higher AECT scores at T1 and T2 compared to T0 [F(2,44) = 6.541; p < 0.05; post hoc p < 0.05)], indicating that the disease was rather more controlled after vaccinations than in the previous period. All patients showed a positive serological response to the vaccine without significant differences from healthy controls (U = 162; p = 0.062). These observations suggest that the vaccine administration is safe and effective in HAE patients

Predictive Response to Immunotherapy Score: A Useful Tool for Identifying Eligible Patients for Allergen Immunotherapy

A specific predictive tool of allergen immunotherapy (AIT) outcome has not been identified yet. This study aims to evaluate the efficacy of a disease score referred to as Predictive Response to Immunotherapy Score (PRIS) to predict the response to AIT and identify eligible patients. A total of 110 patients diagnosed with allergic rhinitis with or without concomitant asthma were enrolled in this study. Before beginning sublingual immunotherapy (SLIT), patients were evaluated by analyzing clinical and laboratory parameters. A specific rating was assigned to each parameter to be combined in a total score named PRIS. At baseline (T0) and follow-up [after 12 (T12) and 24 months (T24) of SLIT], a Visual Analogue Scale (VAS) was used to calculate a mean symptom score (MSS). Finally, the percentage variation between the MSS at T0 and at T12 [ΔMSS-12(%)] and T24 [ΔMSS-24 (%)] was measured. We observed a significant improvement of symptoms at T12 and T24 compared to T0 in all groups undergoing SLIT. PRIS was effective in predicting ΔMSS-24 (%) in patients treated with single-allergen SLIT. In addition, PRIS was effective in predicting ΔMSS-24 (%) in both patients with only rhinitis and with concomitant asthma. PRIS assessment can represent a useful tool to individuate potential responders before SLIT prescription

The N-Formyl Peptide Receptors and Rheumatoid Arthritis: A Dangerous Liaison or Confusing Relationship?

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by a progressive symmetric inflammation of the joints resulting in bone erosion and cartilage destruction with a progressive loss of function and joint deformity. An increased number of findings support the role of innate immunity in RA: many innate immune mechanisms are responsible for producing several cytokines and chemokines involved in RA pathogenesis, such as Tumor Necrosis Factor (TNF)-α, interleukin (IL)-6, and IL-1. Pattern recognition receptors (PRRs) play a crucial role in modulating the activity of the innate arm of the immune response. We focused our attention over the years on the expression and functions of a specific class of PRR, namely formyl peptide receptors (FPRs), which exert a key function in both sustaining and resolving the inflammatory response, depending on the context and/or the agonist. We performed a broad review of the data available in the literature on the role of FPRs and their ligands in RA. Furthermore, we queried a publicly available database collecting data from 90 RA patients with different clinic features to evaluate the possible association between FPRs and clinic-pathologic parameters of RA patients

Coronary artery calcium score: we know where we are but not where we may be

Cardiac computed tomography angiography (CCTA) has emerged as a cost-effective and time-saving technique for excluding coronary artery disease. One valuable tool obtained by CCTA is the coronary artery calcium (CAC) score. The use of CAC scoring has shown promise in risk assessment and stratification of cardiovascular disease. CAC scores can be complemented by plaque analysis to assess vulnerable plaque characteristics and further refine risk assessment. This paper aims to provide a comprehensive understanding of the value of the CAC as a prognostic tool and its implications for patient risk assessment, treatment strategies and outcomes. CAC scoring has demonstrated superior ability in stratifying patients, especially asymptomatic individuals, compared to traditional risk factors and scoring systems. The main evidence suggests that individuals with a CAC score of 0 had a good long-term prognosis, while elevated CAC score is associated with increased cardiovascular risk. Finally, the clinical power of CAC scoring and the develop of new models for risk stratification could be enhanced by machine learning algorithms

Risk of Getting COVID-19 in People With Multiple Sclerosis

Background and Objectives Several studies have assessed risk factors associated with the severity of COVID-19 outcomes in people with multiple sclerosis (PwMS). The potential role of disease-modifying therapies (DMTs) and demographic and clinical factors on the risk of acquiring SARS-CoV-2 infection has not been evaluated so far. The objective of this study was to assess risk factors of contracting SARS-CoV-2 infection in PwMS by using data collected in the Italian MS Register (IMSR). Methods Acase-control (1:2) studywas set up. Cases included PwMSwith a confirmed diagnosis ofCOVID-19, and controls included PwMS without a confirmed diagnosis of COVID-19. Both groups were propensity score–matched by the date of COVID-19 diagnosis, the date of last visit, and the region of residence. No healthy controls were included in this study. COVID-19 risk was estimated by multivariable logistic regression models including demographic and clinical covariates. The impact of DMTs was assessed in 3 independent logistic regression models including one of the following covariates: last administeredDMT, previousDMTsequences, or the place where the last treatment was administered. Results A total of 779 PwMS with confirmed COVID-19 (cases) were matched to 1,558 PwMS without COVID-19 (controls). In all 3 models, comorbidities, female sex, and a younger age were significantly associated (p &lt; 0.02)with a higher risk of contractingCOVID-19. Patients receiving natalizumab as last DMT(OR[95%CI]: 2.38 [1.66–3.42], p &lt; 0.0001) and those who underwent an escalation treatment strategy (1.57 [1.16–2.13], p = 0.003) were at significantly higher COVID-19 risk. Moreover, PwMS receiving their last DMT requiring hospital access (1.65 [1.34–2.04], p &lt; 0.0001) showed a significant higher risk than those taking self-administered DMTs at home. Discussion This case-control study embedded in the IMSR showed that PwMS at higher COVID-19 risk are younger, more frequently female individuals, and with comorbidities. Long-lasting escalation approach and last therapies that expose patients to the hospital environment seem to significantly increase the risk of SARS-CoV2 infection in PwMS. Classification of Evidence This study provides Class III evidence that among patients with MS, younger age, being female individuals, having more comorbidities, receiving natalizumab, undergoing an escalating treatment strategy, or receiving treatment at a hospital were associated with being infected with COVID-19. Among patients with MS who were infected with COVID-19, a severe course was associated with increasing age and having a progressive form of MS, whereas not being on treatment or receiving an interferon beta agent was protective