Biologics and Targeted Synthetic Drugs Can Induce Immune-Mediated Glomerular Disorders in Patients with Rheumatic Diseases: An Updated Systematic Literature Review

Objective: Our objective was to update the understanding of the development of paradoxical immune-mediated glomerular disorders (IGDs) in patients with rheumatic diseases treated with biologics and targeted synthetic drugs (ts-drugs). Methods: A systematic literature review was performed by searching PubMed for articles published between 1 January 2014 and 1 January 2020 reporting on the development of IGD in adult patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis or systemic lupus erythematosus (SLE) who were receiving biologics or ts-drugs. IGDs were classified on the basis of clinical, laboratory and histopathological data as (1) glomerulonephritis associated with systemic vasculitis (GNSV), (2) isolated autoimmune renal disorder (IARD) or (3) glomerulonephritis in SLE and in lupus-like syndrome (GNLS). The World Health Organization-Uppsala Monitoring Centre (WHO-UMC) system for standardized case causality assessment was applied to evaluate the causal relationship between IGD and specific drugs. The classification was based on a six-category scale, where the “certain” and “probable” categories were deemed clinically relevant relationships. Results: The literature search retrieved 875 articles. Of these, 16 articles reported IGD data, for a total of 25 cases. According to the WHO-UMC assessment, the strength of the causal relationship between IGDs and investigated drugs was higher for anti-tumor necrosis factor-α agents (a clinically relevant relationship was found in four of six cases), abatacept (one of two cases), tocilizumab (two cases), ustekinumab (one case) and tofacitinib (one case) than for rituximab (nine cases), belimumab (three cases) or secukinumab (one case), which showed a weak causal relationship with these paradoxical events. No cases associated with apremilast or baricitinib were found. The retrieved cases were classified as 11 GNLS, seven IARD and seven GNSV. Conclusions: Biologics and ts-drugs can cause IGDs. These events are rare, and the causative effect of a specific drug is hard to establish. When a patient is suspected of having an IGD, the drug should be discontinued, and treatment for the new-onset renal disorder should be promptly started

Gene expression profiling of monozygotic twins affected by psoriatic arthritis

Introduction: Psoriatic Arthritis (PsA) is a multifactorial disease, where the relative burden of genetic, epigenetic and environmental factors in clinical course and damage accrual is not yet definitively clarified. In clinical practice, there is a real need for useful candidate biomarkers in PsA diagnosis and disease progression, by exploring its underlying transcrip-tomic and epigenomic mechanisms. This work aims to profile the transcriptome in mono-zygotic (MZ) twins with psoriatic arthritis (PsA) highly concordant for clinical presentation, but discordant for the radiographic outcomes’ severity. Methods: We describe i) the clinical case of two MZ twins; ii) their comparative gene expression profiling (HTA 2.0 Affymetrix) and iii) signal pathways and pathophysiological processes in which differentially expressed genes are involved (in silico analysis by the IPA software, QIAGEN). Results: One hundred sixty-three transcripts and 36 coding genes (28 up and 8 down) were differentially expressed between twins, and in the brother with the most erosive form, the transcriptomic profiling highlights the overexpression of genes known to be involved in immunomodulatory processes and on a broad spectrum of PsA manifestations. Discussion: Twins’ clinical cases are still a gold mine in medical research: twin brothers are ideal experimental models in estimating the relative importance of genetic versus nongenetic components as determinants of complex phenotypes, non-Mendelian and multifactorial diseases as PsA

Patient Involvement in Shared Decision-Making: Do Patients Rate Physicians and Nurses Differently?

Background. Shared decision-making implies that patients and healthcare professionals make decisions together about clinical exams, available treatments, choice of options, and the benefit or downside of every choice. Patients involved in the shared decision-making process are more compliant with treatments and have a reduced risk of complications related to the pathology. In Italy, patient involvement in caring processes is still barely investigated. Aim. To investigate patients’ perceptions about shared decision-making with physicians and nurses, respectively, and to examine the relationship between shared decision-making and patient satisfaction and perceived quality of care/treatment. Methods. The study was performed between March and June 2019 in two wards of one Italian hospital. A questionnaire was administered to inpatients at the time of admission and again at discharge, including demographic information and measurement scales regarding patient involvement in shared decision-making, patient satisfaction, and perceived quality of treatment/care. Results. A total of 151 out of 301 patients completed questionnaires at both admission and discharge. Patients’ scores for shared decision-making (information, patient needs, treatment planning) were significantly different for physicians and nurses. At both admission and discharge, patients rated shared decision-making significantly higher for physicians compared to nurses, while there were no differences in their satisfaction ratings. Patient ratings of physicians did not change from admission (information: mean (M) = 3.50, standard deviation (SD) = 0.81; patient need: M = 3.05, SD = 1.05; treatment planning: M = 2.75, SD = 1.23) to discharge (information: M = 3.50, SD = 0.79; patient need: M = 3.17, SD = 1.02; treatment planning: M = 2.66, SD = 1.23) (p = 0.924, p = 0.098, p = 0.293, respectively), but patients’ ratings of nurses’ behavior increased significantly from admission (information: M = 2.44, SD = 1.23; patient need: M = 2.27, SD = 1.17; treatment planning: M = 2.12, SD = 1.19) to discharge (information: M = 2.62, SD = 1.22; patient need: M = 2.53, SD = 1.24; treatment planning: M = 2.35, SD = 1.21) (p = 0.019, p = 0.001, p = 0.003, respectively). Attention to patients’ needs was the key determinant of both satisfaction with nurses (OR = 3.65, 95% CI = 1.31–10.14, p = 0.013) and perceived quality of care (OR = 3.97, 95% CI = 1.49–10.55, p = 0.006). Providing appropriate information about disease progress and treatments was a key determinant of both satisfaction with physicians (OR = 19.75, 95% CI = 7.29–53.55, p < 0.001) and perceived quality of treatment (OR = 8.03, 95% CI = 3.25–19.81, p < 0.001). Discussion. Nurses should be sensitized to involving patients in the decision-making process, especially upon hospital admission. Specific training about effective communication techniques can be implemented to manage relationships with patients in different caring situations. Practical implications and future directions are discussed

Localized cold urticaria after vaccination in a child: A case and literature review

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COVID-19 Vaccine Hesitancy among Italian Healthcare Workers: Latent Profiles and Their Relationships to Predictors and Outcome

Vaccine hesitancy and conspiracy beliefs among healthcare workers (HCWs) represent operational priorities that require urgent attention. Identifying and classifying specific subpopulation of hesitancy is crucial to customize educational and intervention strategies to enhance the acceptance and uptake rate of vaccination. Thus, the main purpose of our study was to empirically identify latent profiles of vaccine hesitancy among Italian HCWs adopting a person-centered approach and investigating their relationships with antecedents and intention to get a fourth dose of COVID-19 vaccine. We conducted latent profile analyses (LPA) to identify different configurations of vaccine hesitancy based on five antecedents of vaccination: confidence, complacency, constraints, calculation, and collective responsibility among a sample of Italian HCWs (n = 573). LPA revealed four distinct profiles: believer (61.5%), middler (24.7%), hesitant (9.00%), and rejecter (4.7%). Having conspiracy beliefs was associated with a greater likelihood of membership in all but believer. Finally, the likelihood of intention to get a fourth dose of COVID-19 vaccine was lowest in the rejector and hesitant profiles. Theoretical contributions and implications for practice are discussed

Current smoking predicts inadequate response to methotrexate monotherapy in rheumatoid arthritis patients naïve to DMARDs: Results from a retrospective cohort study

Identifying predictors of inadequate response to methotrexate (MTX) in rheumatoid arthritis (RA) is key to move from a "trial and error" to a "personalized medicine" treatment approach where patients less likely to adequately respond to MTX monotherapy could start combination therapy at an earlier stage. This study aimed to identify potential predictors of inadequate response to MTX in RA patients naïve to disease modifying anti-rheumatic drugs.Data from a real-life cohort of newly diagnosed RA patients starting MTX (baseline, T0) as first-line therapy were analyzed. Outcomes, assessed after 6 months (T1), were defined as failure to achieve a disease activity score 28 (DAS28) low disease activity (LDA) or a good/moderate response to MTX, according to the European League Against Rheumatism (EULAR) response criteria. Logistic regression was used to assess the associations between baseline variables and the study outcomes.Overall, 294 patients (60.5% females, median age 54.5 years) with a median disease duration of 7.9 months were recruited. At T1, 47.3% of subjects failed to achieve LDA, and 29.3% did not have any EULAR-response. In multivariate analysis, significant associations were observed between no LDA and current smoking (adjusted odds ratio [adjOR] 1.79, P = .037), female gender (adjOR 1.68, P = .048), and higher DAS28 (adjOR 1.31, P = .013); and between no EULAR-response and current smoking (adjOR: 2.04, P = .019), age (adjOR: 0.72 per 10-years increases, P = .001), and higher erythrocyte sedimentation rate (adjOR: 0.49; P = .020). By contrast, there were no associations between past smoker status and study outcomes.In summary, in our real-life cohort of disease modifying anti-rheumatic drug naïve RA patients, current smoking habit independently predicts inadequate response to MTX. This, together with other independent predictors of response to treatment identified in our study, might assist with personalized monitoring in RA patients. Further studies are required to investigate whether smoking quitting strategies enhance the therapeutic response to MTX

The universality class of absorbing phase transitions with a conserved field

We investigate the critical behavior of systems exhibiting a continuous absorbing phase transition in the presence of a conserved field coupled to the order parameter. The results obtained point out the existence of a new universality class of nonequilibrium phase transitions that characterizes a vast set of systems including conserved threshold transfer processes and stochastic sandpile models.Comment: RevTeX, 4 pages, 3 EPS figure