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International audience; AimsDilated cardiomyopathy (DCM) is a complex disease where genetics interplay with extrinsic factors. This study aims to compare the phenotype, management, and outcome of familial DCM (FDCM) and non‐familial (sporadic) DCM (SDCM) across Europe.Methods and resultsPatients with DCM that were enrolled in the prospective ESC EORP Cardiomyopathy & Myocarditis Registry were included. Baseline characteristics, genetic testing, genetic yield, and outcome were analysed comparing FDCM and SDCM; 1260 adult patients were studied (238 FDCM, 707 SDCM, and 315 not disclosed). Patients with FDCM were younger (P < 0.01), had less severe disease phenotype at presentation (P < 0.02), more favourable baseline cardiovascular risk profiles (P ≤ 0.007), and less medication use (P ≤ 0.042). Outcome at 1 year was similar and predicted by NYHA class (HR 0.45; 95% CI [0.25–0.81]) and LVEF per % decrease (HR 1.05; 95% CI [1.02–1.08]. Throughout Europe, patients with FDCM received more genetic testing (47% vs. 8%, P < 0.01) and had higher genetic yield (55% vs. 22%, P < 0.01).ConclusionsWe observed that FDCM and SDCM have significant differences at baseline but similar short‐term prognosis. Whether modification of associated cardiovascular risk factors provide opportunities for treatment remains to be investigated. Our results also show a prevalent role of genetics in FDCM and a non‐marginal yield in SDCM although genetic testing is largely neglected in SDCM. Limited genetic testing and heterogeneity in panels provides a scaffold for improvement of guideline adherence.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), initially born as anti-diabetic drugs, have shown many beneficial effects on the cardiovascular system, in particular against heart failure (HF). HF is a complex and multifaceted disease that requires a comprehensive approach. It should not be considered as a simplistic cardiac disease, but a systemic disease that leads to multisystemic organ failure and death. Exploiting their pleiotropic effects, SGLT2i are a very valid tool for HF treatment. Beyond the indication to reduce HF hospitalization and death risk, in patients with diabetes mellitus at high cardiovascular risk or with established cardiovascular event, SGLT2i administration reported beneficial effects regarding the wide spectrum of HF manifestations and stages, independently by diabetes mellitus presence. Recent evidence focuses on HF rehospitalization, cardiac and all-cause death reduction, as well as symptoms and quality of life improvement, in patients with chronic HF or with a recent HF decompensation episode. Given the recent finding about the SGLT2i usefulness in HF patients, further studies are needed to define the best administration timing to maximize the SGLT2i-derived beneficial effects.

Introduction: Biologic disease-modifying antirheumatic drugs (bDMARDs) play a pivotal role in the treatment of psoriatic arthritis (PsA). Despite this, their discontinuation due to inefficacy or adverse events is often observed. The aims of this study are to describe retention rates and treatment trends of anti-TNFα, anti-IL17, and anti-IL12/23R agents in patients with PsA and to identify factors associated with bDMARDs discontinuation in a real-world clinical setting. Methods: A retrospective cohort study based on the analysis of the three Italian prescription cohorts of patients with PsA has been performed. Survival analysis was performed using Kaplan-Meier curves and Cox proportional-hazards model. Results: During the follow up, which lasted 25.5 (12–60) months, 68 patients discontinued a bDMARD: 13 for primary failure, 12 for secondary failure, 15 for adverse events, 5 for remission, 12 because of lost at follow-up, and 11 for other causes. Cox proportional-hazards demonstrated that a shorter disease duration (HR 0.994991, 95% CI 0.9910336–0.9989647, p = 0.014) and first-line bDMARD (HR 0.5090986, 95% CI 0.3073519–0.8432722, p = 0.009) have a protective role on bDMARD retention rate, while the multivariable analysis failed in demonstrating an independent protective role of male sex on drug retention rate (p = 0.083). No significant differences in retention rate have been found regarding biologic drugs, combination therapy or monotherapy, and class of bDMARD (anti-TNFα or anti-pIL12/23R and anti-IL-17). Conclusions: This study shows that a shorter disease duration and treatment with a first-line bDMARD are predictors of bDMARDs retention rate, further highlighting the importance of early diagnosis of PsA.Key Points• No significant difference in retention among patients treated with anti-IL17A, anti-IL12/23R, and anti-TNFα agents has been demonstrated.• A shorter disease duration and first-line bDMARD treatment are associated with persistence in biologic treatment.

Introduction Delirium and sarcopenia are common, although underdiagnosed, geriatric syndromes. Several pathological mechanisms can link delirium and low skeletal muscle mass, but few studies have investigated their association. We aimed to investigate (1) the association between delirium and low skeletal muscle mass and (2) the possible role of calf circumference mass in finding cases with delirium. Methods The analyses were conducted employing the cross-sectional “Delirium Day” initiative, on patient 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes and hospices in Italy in 2017. Delirium was diagnosed as a 4 + score at the 4-AT scale. Low skeletal muscle mass was operationally defined as calf circumference ≤ 34 cm in males and ≤ 33 cm in females. Logistic regression models were used to investigate the association between low skeletal muscle mass and delirium. The discriminative ability of calf circumference was evaluated using non-parametric ROC analyses. Results A sample of 1675 patients was analyzed. In total, 73.6% of participants had low skeletal muscle mass and 24.1% exhibited delirium. Low skeletal muscle mass and delirium showed an independent association (OR: 1.50; 95% CI 1.09–2.08). In the subsample of patients without a diagnosis of dementia, the inclusion of calf circumference in a model based on age and sex significantly improved its discriminative accuracy [area under the curve (AUC) 0.69 vs 0.57, p Discussion and conclusion Low muscle mass is independently associated with delirium. In patients without a previous diagnosis of dementia, calf circumference may help to better identify those who develop delirium.

A positive nuclear scintigraphy with hydroxy bisphosphonate bone tracer (99mTc‐HPD) is believed to have high sensitivity (>99%) and specificity (91%) for the diagnosis of transthyretin amyloid cardiomyopathy. We report the case of an 85‐year‐old man with increased thickness of ventricular walls and a positive bone scintigraphy, who was unexpectedly found to have sarcomeric hypertrophic cardiomyopathy at left ventricular endomyocardial biopsy. Congo Red staining, immunohistochemistry, and transmission electronmicroscopy on six left ventricular samples scored negative for amyloidosis but were suggestive for sarcomeric hypertrophic cardiomyopathy. Genetic study did not show TTR and most commonly involved sarcomeric genes mutations. In hypertrophic cardiomyopathy focal cell necrosis related to demand/supply oxygen mismatch, small vessels disease or inflammation could be responsible of a false‐positive bone scintigraphy signal for transthyretin amyloidosis. Because of this, especially in view of a possible specific treatment, endomyocardial biopsy is highly recommended for the correct diagnosis of cardiomyopathies with hypertrophic phenotype.

We report a case of myopericarditis associated to SARS-CoV-2 infection with necrotizing coronary vasculitis of intramural vessels, giving rise to biventricular apical microaneurysms and to electrical instability. Negativity of myocardial polymerase chain reaction for the most common cardiotropic viruses and for SARS-CoV-2 suggested an immune-mediated myocardial and pericardial inflammatory disease. High dose (1 mg/Kg daily) prednisone and anti-viral (Remdesivir, IDA Business, Carrigtohill, County Cork, T45 DP77, Ireland) therapy led to resolution of cardiac inflammation and ventricular arrhythmias. Morpho-molecular characterization of endomyocardial tissue may improve the outcome in subjects with SARS-CoV-2-associated myopericarditis and coronary vasculitis.

We report a novel cardiomyopathy associated to Usher syndrome and related to combined mutation of MYO7A and Calreticulin genes. A 37‐year‐old man with deafness and vision impairment because of retinitis pigmentosa since childhood and a MYO7A gene mutation suggesting Usher syndrome, developed a dilated cardiomyopathy with ventricular tachyarrhythmias and recurrent syncope. At magnetic resonance cardiomyopathy was characterized by left ventricular dilatation with hypo‐contractility and mitral prolapse with valve regurgitation. At left ventricular endomyocardial biopsy, it was documented cardiomyocyte disconnection because of cytoskeletal disorganization of cell‐to‐cell contacts, including intercalated discs, and mitochondrial damage and dysfunction with significant reduction of adenosine triphosphate production in patient cultured fibroblasts. At an extensive analysis by next‐generation‐sequencing of 4183 genes potentially related to the cardiomyopathy a pathogenic mutation of calreticulin was found. The cardiomyopathy appeared to be functionally and electrically stabilized by a combination therapy including carvedilol and amiodarone at a follow‐up of 18 months.

Introduction Spondyloarthrits (SpA) share clinical, genetic and immunological features with Inflammatory Bowel Diseases (IBD), and enteropathic SpA (eSpA) represent the clinical evidence of the association between gut and joint diseases. This cross-sectional study aimed to report data of eSpA patients collected from the first Italian database. Patients and methods A specific web-based interface has been created to insert and collect the main clinical, serologic and imaging data from patients with eSpA, as well as disease activity, comorbidities and treatment, in a real-life scenario. Results Data were collected in 14 Italian centers (7 rheumatology and 7 gastroenterology units). A total of 347 eSpA patients were enrolled in the study. Type 1 peripheral eSpA was the most frequent form. Crohn’ Disease (CD) was the most represented IBD. CD activity was similar among eSpA, whereas UC activity was slightly higher in the axial and mixed form than in the peripheral eSpA. The disease was active in less than half of axial eSpA patients and in only 18% of patients with peripheral eSpA. Furthermore, most of the patients had an inactive IBD. Nineteen percent of the total eSpA patients were free of therapy at the time of the enrollment and 61% of the patients were receiving biotechnological agents. Conclusions The multidisciplinary management of eSpA patients, favored by this ad hoc created web-based platform, allowed to obtain data from the largest eSpA cohort. The information coming of this database might advance knowledge of eSpA and improve their standard of care.

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis that may be present in near 30% of patients affected by psoriasis (PsO), clinically characterized by inflammation of periarticular (e.g., enthesis) and articular structures. Recently, an autoimmune footprint of PsA pathogenesis has been demonstrated with the presence of autoantigens and related autoantibodies in PsA patients' sera. In this context, histological features of PsA synovitis supports the relevance of an autoimmune pathogenesis of the disease. Since there is no currently validated test for PsA, the analysis of PsA synovial tissue revealed pathognomonic characteristics of PsA that may support the clinician in the clinical practice. PsA synovitis is characterized by a sublining infiltrate with T and B cells, vascular proliferation and a relative thin lining layer of proliferating intimal synoviocytes. PsA synovial histopathology shows that ectopic lymphoid-neogenesis with an increase of IL-23 expression. These new pathogenetics features and the systemic nature of the disease raised the concept of a Systemic Psoriatic Disease (SysPsD), characterized by multiple extra-cutaneous and -articular manifestations, highlightening the great heterogeneity of this condition. SyPsD represents a heterogeneous chronic inflammatory condition with a wide spectrum of phenotypical manifestations. The purpose of this review is to describe the new pathogenetic mechanisms and the different clinical pictures of SysPsD, with the ultimate goal of improving the knowledge of this heterogeneous chronic inflammatory condition.

We previously showed that 1 month of transcutaneous electrical nerve stimulation (TENS) reduces movement-evoked pain and fatigue in women with fibromyalgia (FM). Using data from this study (Fibromyalgia Activity Study with TENS [FAST]), we performed a responder analysis to identify predictors of clinical improvement in pain and fatigue with TENS, validated these models using receiver operator characteristic, and determined number needed to treat and number needed to harm. Participants were randomly assigned to active-TENS (2-125 Hz; highest-tolerable intensity), placebo-TENS, or no-TENS for 1 month. At the end of the randomized phase, placebo-TENS and no-TENS groups received active-TENS for 1 month. The predictor model was developed using data from the randomized phase for the active-TENS group (n = 103) and validated using data from placebo-TENS and no-TENS groups after active-TENS for 1 month (n = 155). Participant characteristics, initial response to TENS for pain and fatigue, sleep, psychological factors, and function were screened for association with changes in pain or fatigue using a logistic regression model. Predictors of clinical improvement in pain were initial response to pain and widespread pain index (area under the curve was 0.80; 95% confidence interval: 0.73-0.87). Predictors of clinical improvement in fatigue were marital status, sleep impairment, and initial response to TENS (area under the curve was 0.67; 95% confidence interval: 0.58-0.75). Number needed to treat for pain and fatigue ranged between 3.3 and 5.3. Number needed to harm ranged from 20 to 100 for minor TENS-related adverse events. The response to an initial 30-minute TENS treatment predicts who responds to longer-term TENS use in women with FM, making this a clinically useful procedure. Number needed to treat and number needed to harm suggest that TENS is effective and safe for managing pain and fatigue in FM.

Objective Individuals with chronic pain conditions often report movement as exacerbating pain. An increasing number of researchers and clinicians have recognized the importance of measuring and distinguishing between movement-evoked pain (MEP) and pain at rest as an outcome. This scoping review maps the literature and describes MEP measurement techniques. Materials and methods The scoping review utilized 6 databases to identify original studies that targeted pain or movement-related outcomes. Our search returned 7322 articles that were screened by title and abstract by 2 reviewers. The inclusion criteria focused on the measurement of MEP before, during, and after movement tasks in adults with chronic pain. Studies of children below 18 years of age or with nonhuman animals, case studies, qualitative studies, book chapters, cancer-related pain, non-English language, and abstracts with no full publish text were excluded from the study. Results Results from 38 studies revealed great variation in the measurement of MEP, while almost all of the studies did not provide an explicit conceptual or operational definition for MEP. In addition, studies collectively illuminated differences in MEP compared with rest pain, movement provocation methods, and pain intensity as the primary outcome. Discussion These results have clinically significant and research implications. To advance the study of MEP, we offer that consistent terminology, standardized measurement (appropriate for pain type/population), and clear methodological processes be provided in research publications. On the basis of the findings, we have put forth a preliminary definition of MEP that may benefit from the continued scholarly dialog.

INTRODUCTION: Remote monitoring (RM) has significantly transformed the standard of care for patients with cardiac electronic implantable devices It provides easy access to valuable information, such as arrhythmic events, acute decompensation manifestations and device-related issues, without the need of in-person visits METHODS: Starting March 1st, 332 patients were introduced to a RM program during the Italian lockdown in order to limit the risk of in-hospital exposure to Severe Acute Respiratory Syndrome-Coronavirus-2 Patients were categorized into two groups based on the modality of RM delivery [home (n=229) vs office (n= 103) delivered] The study aimed at assessing the efficacy of the new follow-up protocol, assessed as mean RM Activation Time (AT) and need for technical support Additionally, patients' acceptance and anxiety status were quantified via the Home Monitoring Acceptance and Satisfaction Questionnaire and the Generalized Anxiety Disorder 7-item scale RESULTS: AT time was

In the 2 decades since The Joint Commission on Accreditation of Healthcare Organizations designated pain as the fifth vital sign, practitioners have become increasingly aware of the numerous challenges associated with the assessment and management of pain in older adults. Comprehensive pain assessment relies not only on the availability of assessment tools, but also on a clinician's knowledge, training, prior experience, and keen awareness of their own implicit bias and how it may influence their assessment and decisions. The purpose of this project was to develop, implement, and evaluate outcomes of a two-part online learning module on home healthcare clinicians' knowledge of pain. A quasi-experimental, one-group pretest posttest design was used. Of the 94 clinicians who volunteered, 54 participants completed all modules and surveys. Mean posttest scores (58.7%) were significantly higher than pretest scores (50.7%; n = 54, T = 3.08, p-value = 0.003). The strongest gains in learning occurred for those with lower pretest scores. The mean difference between posttest and pretest scores did not vary among job titles. There was no significant difference in posttest scores among job titles. A higher mean pretest score was associated with greater years of clinical experience, but did not significantly affect mean posttest scores. These findings suggest elearning is an effective educational approach to improve home healthcare clinicians' pain knowledge, particularly those who lack a sufficient knowledge base at the outset.

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy typically associated with psoriasis (PsO). The pathogenesis is strictly related to the association among the presence of genetic risk alleles and innate and acquired immune response with dramatic consequences on bone remodeling. Clinically, PsA patients may present heterogenicity of articular and periarticular manifestations that may be associated with the presence of comorbidities making treatment decision challenging in patients management. The identification of patient-targeted therapies is still a critical issue. Actually, several biological and synthetic drugs are promising in terms of efficacy and safety profile. National and international treatment recommendations support clinicians in the decision of the best treatment, although they may have limits basically related to updates and different outcomes included in the clinical studies evaluated. The aim of this narrative review is therefore to give guidance for clinicians for PsA patients treatment. For this purpose, we evaluated evidence on biological therapies efficacy used for PsA treatment. Specifically, we reviewed data on biological therapies, Janus kinases (JAK) inhibitors, and drugs with a new mechanism of action that are part of the treatment pipeline. The concept of "switching" and "swapping" is also described, as well as data concerning special populations such as pregnant women and elderly patients.

OBJECTIVES: Peripherally directed treatments (targeted exercise, surgery) can reduce, but not fully eliminate, pain for up to 40% of patients with Achilles tendinopathy. The objectives of the present study were (1) to identify indicators of altered central processing in participants with Achilles tendinopathy compared to controls, and (2) to determine which indicators of altered central processing would persist after a local anesthetic injection in patients with Achilles tendinopathy. DESIGN: Mechanistic clinical trial. METHODS: Forty-six adults (23 with chronic Achilles tendinopathy, 23 matched controls) repeated (1) a movement-evoked pain rating, (2) motor performance assessment, (3) pain psychology questionnaires, and (4) quantitative sensory testing. Participants with Achilles tendinopathy received a local anesthetic injection before repeat testing and controls did not. Mixed-effects analyses of variance examined the effects of group, time, and group by time. RESULTS: The Achilles tendinopathy group had movement-evoked pain, motor dysfunction, and higher pain psychological factors (pain catastrophizing, kinesiophobia) compared to controls (P.05). In those with Achilles tendinopathy, local anesthetic injection eliminated pain and normalized the observed deficits in heel-raise performance and pain catastrophizing (group-by-time effect, P.05). CONCLUSION: People with Achilles tendinopathy had elevated pain psychological factors and motor dysfunction but no signs of nociplastic pain with quantitative sensory testing. Removal of nociceptive input normalized movement-evoked pain and some indicators of altered central processing (motor dysfunction, pain catastrophizing), but not kinesiophobia.

Objectives Delirium is commonly seen in older adults with multimorbidity, during a hospitalization, resulting from the interplay between predisposing factors such as advanced age, frailty, and dementia, and a series of precipitating factors. The association between delirium and specific multimorbidity is largely unexplored so far although of potential key relevance for targeted interventions. The aim of the study was to check for a potential association of multimorbidity with delirium in a large cohort of older patients hospitalized for an acute medical or surgical condition. Design This is a cross-sectional study nested in the 2017 Delirium Day project. Setting and Participants The study includes 1829 hospitalized patients (age: 81.8, SD: 5.5). Of them, 419 (22.9%) had delirium. Methods Sociodemographic and medical history were collected. The 4AT was used to assess the presence of delirium. The Charlson Comorbidity index was used to assess multimorbidity. Results The results identified neurosensorial multimorbidity as the most prevalent, including patients with dementia, cerebrovascular diseases, and sensory impairments. In light of the highest co-occurrence of 3 neurosensorial chronic conditions, we could hypothesize that a baseline altered brain functional and neural connectivity might determine the vulnerability signature for incipient overall system disruption in presence of acute insults. Conclusions and Implications Eventually, our findings moved a step forward in supporting the key importance of routine screening for sensory impairments and cognitive status of older patients for the highest risk of in-hospital delirium. In fact, preventive interventions could be particularly relevant and effective in preventing delirium in such vulnerable populations and might help refining this early diagnosis.

BACKGROUND: Tendinopathy is a common cause of elbow pain in the active population. Ultrasound Guided Tenotomy (USGT) is a minimally invasive treatment option for cases recalcitrant to conservative management. Several case studies have shown promising preliminary results of USGT for common extensor tendinopathy and common flexor tendinopathy, but none have included USGT for triceps tendinopathy. This larger retrospective study evaluates the effectiveness and safety of USGT for all elbow tendinopathy sites at short and long-term follow-up. METHODS: Retrospective chart review identified 131 patients [144 procedures] (mean age ± SD, 48.1 ± 9.8 years; mean body mass index ± SD, 32.2 ± 7.7 kg/m(2); 59% male) with elbow tendinopathy (104 common extensor tendinopathy; 19 common flexor tendinopathy; 8 triceps tendinopathy) treated with USGT over a 6-year period by a single physician. Pain and quality of life measures were collected at baseline. Pain, quality of life, satisfaction with outcome, and complications were collected at short-term (2, 6, 12 week) and long-term (median 2.7 years IQR= 2.0 to 4.0 years) follow-up. RESULTS: Overall, USGT for elbow tendinopathy decreased pain from moderate/severe at baseline to mild/occasional at short-term and long-term follow-up (p< 0.01). Quality of life assessments showed significant improvement in physical function at short and long-term follow-up (p< 0.01). The majority (70%) of patients were satisfied with the procedure. There was a 0% complication rate. CONCLUSION: Benefits of USGT include pain relief, improved physical function, and high patient satisfaction. USGT is a safe minimally invasive treatment for refractory elbow tendinopathy.

Objective: Sensory deficits are important risk factors for delirium but have been investigated in single-center studies and single clinical settings. This multicenter study aims to evaluate the association between hearing and visual impairment or bi-sensory impairment (visual and hearing impairment) and delirium. Design: Cross-sectional study nested in the 2017 "Delirium Day" project. Setting and participants: Patients 65 years and older admitted to acute hospital medical wards, emergency departments, rehabilitation wards, nursing homes, and hospices in Italy. Methods: Delirium was assessed with the 4AT (a short tool for delirium assessment) and sensory deficits with a clinical evaluation. We assessed the association between delirium, hearing and visual impairment in multivariable logistic regression models, adjusting for: Model 1, we included predisposing factors for delirium (ie, dementia, weight loss and autonomy in the activities of daily living); Model 2, we added to Model 1 variables, which could be considered precipitating factors for delirium (ie, psychoactive drugs and urinary catheters). Results: A total of 3038 patients were included; delirium prevalence was 25%. Patients with delirium had a higher prevalence of hearing impairment (30.5% vs 18%; P < .001), visual impairment (24.2% vs 15.7%; P < .01) and bi-sensory impairment (16.2% vs 7.5%) compared with those without delirium. In the multivariable logistic regression analysis, the presence of bi-sensory impairment was associated with delirium in Model 1 [odds ratio (OR) 1.5, confidence interval (CI) 1.2-2.1; P = .00] and in Model 2 (OR 1.4; CI 1.1-1.9; P = .02), whereas the presence of visual and hearing impairment alone was not associated with delirium either in Model 1 (OR 0.8; CI 0.6-1.2, P = .36; OR 1.1; CI 0.8-1.4; P = .42) or in Model 2 (OR 0.8, CI 0.6-1.2, P = .27; OR 1.1, CI 0.8-1.4, P = .63). Conclusions and implications: Our findings support the importance of routine screening and specific interventions by a multidisciplinary team to implement optimal management of sensory impairments and hence prevention and the management of the patients with delirium.

Background New messenger RNA (mRNA) and adenovirus-based vaccines (AdV) against Coronavirus disease 2019 (COVID-19) have entered large scale clinical trials. Since healthcare professionals (HCPs) and armed forces personnel (AFP) represent a high-risk category, they act as a suitable target population to investigate vaccine-related side effects, including headache, which has emerged as a common complaint. Methods We investigated the side-effects of COVID-19 vaccines among HCPs and AFP through a 38 closed-question international survey. The electronic link was distributed via e-mail or via Whatsapp to more than 500 contacts. Responses to the survey questions were analyzed with bivariate tests. Results A total of 375 complete surveys have been analyzed. More than 88% received an mRNA vaccine and 11% received AdV first dose. A second dose of mRNA vaccine was administered in 76% of individuals. No severe adverse effects were reported, whereas moderate reactions and those lasting more than 1 day were more common with AdV (P=0.002 and P=0.024 respectively). Headache was commonly reported regardless of the vaccine type, but less frequently, with shorter duration and lower severity that usually experienced by participants, without significant difference irrespective of vaccine type. Conclusions Both mRNA and AdV COVID-19 vaccines were safe and well tolerated in a real-life subset of HCPs and AFP subjects.

Background: Abnormal aldosterone signaling is a recognized source of cardiovascular damage. Its influence on cardiomyocyte structure, function, and hormonal receptors when associated with heart failure is still unreported. Methods: Twenty-six consecutive patients with heart failure (LVEF &lt, 40%) and normal coronaries and valves underwent left ventricular endomyocardial biopsy (EMB) for evaluation of myocardial substrate. Biopsy samples were processed for histology, electron microscopy, immunohistochemistry, and Western blot analysis of myocardial aldosterone receptor and aquaporin-1 correlated with plasma aldosterone (AD) and renin activity (PRA). Eight patients with virus-negative inflammatory cardiomyopathy (ICM) had a control EMB after 6 months of immunosuppressive therapy and recovery of cardiac function with re-evaluation of cardiomyocyte structure and receptor expression. Results: EMB in addition to the diagnosis of myocarditis (15 cases), dilated cardiomyopathy CM (6), alcohol CM (2), and diabetic CM (3) showed vacuolar degeneration and cloudy swelling of cardiomyocytes corresponding at electron microscopy to ions and water accumulation into cytosol, membrane-bound vesicles, nucleus, and other organelles, and was associated with an increased AD, PRA, and myocardial expression of aldosterone receptor (2.6 fold) and aquaporin 1 (2.7 fold). In the 8 patients recovered from ICM, cardiomyocyte diameter reduced with disappearance of intracellular vacuoles and normalization of cytosol, nucleus, and cell organelles’ electron-density, along with down-regulation of aldosterone receptor and aquaporin-1. Conclusion: Human heart failure is associated with overexpression of myocardial aldosterone receptor and aquaporin-1. These molecular changes are paralleled by intracellular water overloading and cardiomyocyte swelling and dysfunction. Cardiac recovery is accompanied by down-regulation of hormonal receptors and normalization of cell structure and composition.

BackgroundAchilles tendinopathy (AT) rehabilitation traditionally includes progressive tendon loading exercises. Recent evidence suggests a biopsychosocial approach that incorporates patient education on psychosocial factors and mechanisms of pain can reduce pain and disability in individuals with chronic pain. This is yet to be examined in individuals with AT.ObjectiveThis study aims to compare the effects on movement-evoked pain and self-reported function of pain education as part of a biopsychosocial approach with pathoanatomical education for people with AT when combined with a progressive tendon loading exercise program.MethodsA single-site, randomized, double-blind, placebo-controlled clinical trial will be conducted in a university-based hospital in a laboratory setting and/or by telehealth. A total of 66 participants with chronic (>3 months) midportion or insertional AT will be randomized for the Tendinopathy Education of the Achilles (TEAch) study. All participants will complete progressive Achilles tendon loading exercises over 12 weeks and will be encouraged to continue with self-selected exercises as tolerated. All participants will complete 6-7 one-to-one sessions with a physical therapist to progress exercises in a standardized manner over 8 weeks. During the last 4 weeks of the intervention, participants will be encouraged to maintain their home exercise program. Participants will be randomized to 1 of 2 types of education (pain education or pathoanatomic), in addition to exercise. Pain education will focus on the biological and psychological mechanisms of pain within a biopsychosocial framing of AT. Pathoanatomic education will focus on biological processes within a more traditional biomedical framework of AT. Evaluation sessions will be completed at baseline and 8-week follow-up, and self-reported outcome measures will be completed at the 12-week follow-up. Both groups will complete progressive Achilles loading exercises in 4 phases throughout the 12 weeks and will be encouraged to continue with self-selected exercises as tolerated. Primary outcomes are movement-evoked pain during heel raises and self-reported function (patient-reported outcome measure information system—Physical Function). Secondary outcomes assess central nervous system nociceptive processing, psychological factors, motor function, and feasibility.ResultsInstitutional review board approval was obtained on April 15, 2019, and study funding began in July 2019. As of March 2020, we randomized 23 out of 66 participants. In September 2020, we screened 267 individuals, consented 68 participants, and randomized 51 participants. We anticipate completing the primary data analysis by March 2022.ConclusionsThe TEAch study will evaluate the utility of pain education for those with AT and the effects of improved patient knowledge on pain, physical function, and clinical outcomes.International Registered Report Identifier (IRRID)DERR1-10.2196/19111

Background: Ocular involvement in Psoriatic Arthritis (PsA) patients is mainly associated with uveitis but there remains a paucity of data on dry eye and retinal abnormalities. We aimed to analyze dry eye and subclinical retinal abnormalities in a cohort of PsA patients sine-psoriasis (PsO). Methods: PsA patients sine-PsO were enrolled. Best-corrected-visual-acuity, ocular-surface-disease-index (OSDI), Schirmer test, tear film breakup-time, standard-automated-perimetry (SAP, mean deviation&mdash, MD, pattern standard deviation&mdash, PSD), fundus-perimetry (FP), and spectral-domain-optical-coherence-tomography (SD-OCT) were performed. Results: A total of 80 eyes from 40 PsA patients with moderate-severe disease activity, and 70 eyes from 35 healthy control (HC) were evaluated. Higher dry eye prevalence occurred in PsA than HC (p &lt, 0.0001). ESR was positively related with OSDI (p &lt, 0.001) and negatively related with Schirmer (p = 0.007). In PsA, SAP registered higher MD (p &lt, 0.0001) and higher PSD (p = 0.005) in comparison with HC. PSD resulted positively correlated with ESR (p = 0.04) and CRP (p = 0.01), while MD showed a negative correlation with CRP (p = 0.01). Both FP mean differential sensitivity and mean defect were lower in PsA then HC (p &lt, 0.0001). In PsA, FP differential sensitivity was directly related with cumulative steroids (p = 0.02). Conclusions: In PsA patients sine-PsO, dry eye and subclinical abnormalities in visual functions occurred being potentially related to systemic inflammation.

Background Oral migalastat has recently been approved for the treatment of Anderson-Fabry disease (FD) in patients aged ≥16 years with amenable mutations on the basis of two phase III trials, FACETS and ATTRACT. However, with the introduction of migalastat into clinical practice, it is important to correctly identify the patients who may gain the most benefits from this therapy. Due to the relatively recent availability of migalastat, its role in clinical practice still has to be included in guidelines or recommendations. On these bases, a multidisciplinary group of Italian Experts in the treatment of FD has run the GALA project, with the aim to collect the opinions of expert physicians and to propose some starting points for an experience-based use of migalastat. Results Overall, although studies and data from longer-term follow-up with migalastat are still emerging, available evidence is consistent in showing that this molecule does represent a suitable therapy for the treatment of FD, in patients aged ≥16 years and with amenable mutations. The use of migalastat as an oral option appears to be overall safe, and experience thus far indicates potential for improving quality of life, controlling GI symptoms, stabilizing renal function and reducing cardiac hypertrophy. Conclusion Migalastat can be considered either as a first-line therapy – given its efficacy, extensive tissue penetration, convenient oral regimen, and the current limited therapeutic options available – or in patients on enzyme-replacement therapy (ERT) who experience side effects, with poor compliance to chronic i.v. therapy, or with clinical evidence of progression of the disease.

Objective To evaluate prevalence and clinical features of immune-related adverse events (irAEs) to immune checkpoint inhibitors (ICIs) in accordance with the gender of treated cancer patients. Methods A systematic review of the medical literature was conducted by searching all available clinical data up to December 2019 in several databases using a combination of MESH terms related to immune checkpoint inhibitors, autoimmunity, and gender. Analyzed data were related to all FDA approved ICIs and respective indications in cancer. Results According to data from the literature, male display a slightly lower frequencies of ICIs-related endocrinopathies compared with females, specifically thyroid dysfunction. On the contrary, ICIs-hypophysitis has been reported at higher rates among males compared with females. ICI-induced Sicca/Sjogren’s syndrome showed a more frequent occurrence in men than the idiopathic primary form. No differences in gender distribution seem to arise in hematologic and gastrointestinal-irAEs. Interestingly, the gender distribution of neurologic and vascular ICIs-irAEs appears male-dominant. Conclusions The present systematic review highlights for the first time that the distribution of patients experiencing irAEs associated with ICIs changes among the genders according to the specific drug used, the frequency of the cancer and of the autoimmune conditions in the general population.

Background: Few studies have evaluated the effectiveness of adalimumab in the real-life setting in psoriatic arthritis (PsA).Objective: To evaluate the 2-year retention rate of adalimumab in PsA patients. Potential baseline parameters influencing persistence on treatment were also evaluated.Methods: PsA patients from 16 Italian Rheumatology Units treated with adalimumab as first- or second-line biological therapy were retrospectively evaluated. Adalimumab retention rate was evaluated at 12 and 24 months. Logistic regression was used to evaluate the association between predictor variables and adalimumab retention rate.Results: From 424 patients (53.5% male, aged 48.3 ± 12.8 years) who started treatment with adalimumab, 367 (86.6%) maintained treatment for 12 months and 313 (73.8%) for 2 years. At 24-months, Disease Activity in PsA (DAPSA) remission (defined as ≤4) and Low Disease Activity (LDA) (≤14) were achieved in 22.8% and 44.4% of patients, respectively. Adalimumab treatment significantly decreased the number of tender (7.0 ± 5.7 at baseline vs. 2.3 ± 3.5 at 24 months, p < 0.001) and swollen joints (2.7 ± 2.8 at baseline vs. 0.4 ± 0.9 at 24 months, p < 0.001), DAPSA (25.5 ± 10.9 at baseline vs. 11.0 ± 8.4 at 24 months, p < 0.001), PASI (5.3 ± 5.7 at baseline vs. 2.7 ± 2.8 at 24 months, p < 0.001) and CRP (3.8 ± 6.3 at baseline vs. 1.2 ± 1.7 at 24 months, p < 0.001). Among a range of laboratory and clinical variables, only female gender was associated with improved adalimumab persistence at 24 months (OR: 1.98, 95% CI: 1.2–3.2, p = 0.005).Conclusions: Independent of a range of predictor variables, adalimumab was shown to be effective, while maintaining a high retention rate after 2 years in PsA patients.

Objectives: (1) Validate thresholds for minimal, low, moderate, and high fear of movement on the 11-item Tampa Scale of Kinesiophobia (TSK-11), and (2) Establish a patient-driven minimal clinically important difference (MCID) for Achilles tendinopathy (AT) symptoms of pain with heel raises and tendon stiffness.Methods: Four hundred and forty-two adults with chronic AT responded to an online survey, including psychosocial questionnaires and symptom-related questions (severity and willingness to complete heel raises and hops). Kinesiophobia subgroups (Minimal ≤ 22, Low 23–28, Moderate 29–35, High ≥ 36 scores on the TSK-11), pain MCID subgroups (10-, 20-, 30-, >30-points on a 0- to 100-point scale), and stiffness MCID subgroups (5, 10, 20, >20 min) were described as median [interquartile range] and compared using non-parametric statistics.Results: Subgroups with higher kinesiophobia reported were less likely to complete three heel raises (Minimal = 93%, Low = 74%, Moderate = 58%, High = 24%). Higher kinesiophobia was associated with higher expected pain (Minimal = 20.0 [9.3–40.0], Low = 43.0 [20.0–60.0], Moderate = 50.0 [24.0–64.0], High = 60.5 [41.3–71.0]) yet not with movement-evoked pain (Minimal = 25.0 [5.0–43.0], Low = 31.0 [18.0–59.0], Moderate = 35.0 [20.0–60.0], High = 43.0 [24.0–65.3]). The most common pain MCID was 10 points (39% of respondents). Half of respondents considered a 5-min (35% of sample) or 10-min (16%) decrease in morning stiffness as clinically meaningful.Conclusions: Convergent validity of TSK-11 thresholds was supported by association with pain catastrophizing, severity of expected pain with movement, and willingness to complete tendon loading exercises. Most participants indicated that reducing their pain severity to the mild range would be clinically meaningful.

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical syndrome responsible for high mortality and morbidity rates. It has an ever growing social and economic impact and a deeper knowledge of molecular and pathophysiological basis is essential for the ideal management of HFpEF patients. The association between HFpEF and traditional cardiovascular risk factors is known. However, myocardial alterations, as well as pathophysiological mechanisms involved are not completely defined. Under the definition of HFpEF there is a wide spectrum of different myocardial structural alterations. Myocardial hypertrophy and fibrosis, coronary microvascular dysfunction, oxidative stress and inflammation are only some of the main pathological detectable processes. Furthermore, there is a lack of effective pharmacological targets to improve HFpEF patients’ outcomes and risk factors control is the primary and unique approach to treat those patients. Myocardial tissue characterization, through invasive and non-invasive techniques, such as endomyocardial biopsy and cardiac magnetic resonance respectively, may represent the starting point to understand the genetic, molecular and pathophysiological mechanisms underlying this complex syndrome. The correlation between histopathological findings and imaging aspects may be the future challenge for the earlier and large-scale HFpEF diagnosis, in order to plan a specific and effective treatment able to modify the disease’s natural course.

Background: Nonrestorative sleep is commonly reported by individuals with fibromyalgia, but there is limited information on the reliability and responsiveness of self-reported sleep measures in this population.Objectives: (1) Examine the reliability and validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) sleep measures in women with fibromyalgia, and (2) Determine the responsiveness of the PROMIS sleep measures to a daily transcutaneous electrical nerve stimulation (TENS) intervention in women with fibromyalgia over 4 weeks compared with other measures of restorative sleep.Methods: In a double-blinded, dual-site clinical trial, 301 women with fibromyalgia were randomly assigned to utilize either Active-TENS, Placebo-TENS, or No-TENS at home. Measures were collected at baseline and after 4 weeks of treatment. To assess self-reported sleep, the participants completed three PROMIS short forms: Sleep Disturbance, Sleep-Related Impairment, Fatigue, and the Pittsburgh Sleep Quality Index (PSQI). To assess device-measured sleep, actigraphy was used to quantify total sleep time, wake after sleep onset, and sleep efficiency. Linear mixed models were used to examine the effects of treatment, time, and treatment*time interactions.Results: The PROMIS short forms had moderate test–retest reliability (ICC 0.62 to 0.71) and high internal consistency (Cronbach's alpha 0.89 to 0.92). The PROMIS sleep measures [mean change over 4 weeks, 95% confidence interval (CI)], Sleep Disturbance: −1.9 (−3.6 to −0.3), Sleep-Related Impairment: −3 (−4.6 to −1.4), and Fatigue: −2.4 (−3.9 to −0.9) were responsive to improvement in restorative sleep and specific to the Active-TENS group but not in the Placebo-TENS [Sleep Disturbance: −1.3 (−3 to 0.3), Sleep-Related Impairment: −1.2 (−2.8 to 0.4), Fatigue: −1.1 (−2.7 to 0.9)] or No-TENS [Sleep Disturbance: −0.1 (−1.6 to 1.5), Sleep-Related Impairment: −0.2 (−1.7 to 1.4), Fatigue: –.3 (−1.8 to 1.2)] groups. The PSQI was responsive but not specific with improvement detected in both the Active-TENS: −0.9 (−1.7 to −0.1) and Placebo-TENS: −0.9 (−1.7 to 0) groups but not in the No-TENS group: −0.3 (−1.1 to 0.5). Actigraphy was not sensitive to any changes in restorative sleep with Active-TENS [Sleep Efficiency: −1 (−2.8 to 0.9), Total Sleep Time: 3.3 (−19.8 to 26.4)].Conclusion: The PROMIS sleep measures are reliable, valid, and responsive to improvement in restorative sleep in women with fibromyalgia.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT01888640.

Systemic Lupus Erythematosus (SLE) is a connective tissue disease that involves multiple organs. Ocular structures and visual pathways can be affected in SLE because of disease-related eye involvement or drug toxicity. All the part of the eye may be interested with an external, anterior involvement, responsible of the dry eye disease, or posterior (retina) and neuro-ophtalmic manifestations. Retinopathy in SLE is suggestive of high disease activity being a marker of poor visual outcome and prognosis for survival. The early diagnosis is thus the key to a better management and successful treatment. Antimalarial drugs are the cornerstone of SLE treatment and recently the American Academy of Ophthalmology updated the recommendations for hydroxychloroquine retinal toxicity screening which includes the standard automated visual fields and the spectral domain optical coherent tomography. More recently new imaging techniques have been investigated to assess retinal function and reveal subclinical eye involvement. In this review we focalize on the evidence of eye manifestations in SLE, the eye drug toxicity related to antimalarial agents and steroids, and the methods employed for the eye screening. Moreover, the future perspectives on new techniques, such as the optical coherence tomography angiography, are dissected giving new insights on evaluation of microvasculature of the retina and choroid in SLE.

Background: The inflammatory involvement of the enthesis in the course of psoriasis is accompanied by structural abnormalities detectable by ultrasound. The most common of these abnormalities is the thickening of the tendon at the insertion site. Aims: The aim of the present study was to compare the thickness of entheses of patients with psoriatic arthritis, only skin psoriasis, and healthy controls. Methods: A cross-sectional study was conducted in a cohort of patients affected with either only skin psoriasis or psoriatic arthritis as well as in a control group. Eight entheses sites were scanned by ultrasound bilaterally. The following entheseal characteristics were collected and recorded in a predefined database: entheseal thickness, bone erosions, enthesis calcifications (enthesophytes), presence of blood flow, and presence of bursitis. All the detected entheseal changes were scored, and the data was statistically analyzed. Results: The major differences in enthesis thickness between only skin psoriasis and psoriatic arthritis patients were found at the following sites: (i) olecranon tuberosity, (ii) superior pole of the patella, and (iii) medial epicondyle of femur. The thickness of the medial collateral ligament at the site of the femoral origin was increased in psoriatic arthritis, but not in both only skin psoriasis and healthy controls. The score obtained by adding the thickness of all the 8 examined entheses for each patient showed significant differences among the three groups (psoriatic arthritis: 81.3; only skin psoriasis 74.4; Controls: 67.6; P < 0.0001). Interestingly, we found that in psoriatic arthritis patients, the highest enthesis thickening was seen in entheses affected by bone erosions. Limitations: The small sample of patients studied is a limiting factor in this study. Conclusions: Our data demonstrated that the ultrasound measurement of the enthesis thickness enables a distinction between patients with psoriatic arthritis from those with only skin psoriasis. It is a useful method to improve diagnostic accuracy, especially in patients without clear clinical signs of enthesitis.

Aim To investigate the contribution of unaffected cardiomyocytes in Fabry disease cardiomyopathy. Findings Left ventricular (LV) endomyocardial biopsies from twenty-four females (mean age 53 ± 11 ys) with Fabry disease cardiomyopathy were studied. Diagnosis of FD was based on the presence of pathogenic GLA mutation, Patients were divided in four groups according with LV maximal wall thickness (MWT): group 1 MWT ≤ 10.5 mm, group 2 MWT 10.5–15 mm, group 3 MWT 16–20 mm, group 4 MWT > 20 mm. At histology mosaic of affected and unaffected cardiomyocytes was documented. Unaffected myocytes’ size ranged from normal to severe hypertrophy. Hypertrophy of unaffected cardiomyocytes correlated with severity of MWT (p

Importance Evidence emerged concerning how inflammatory arthritis and mood disorders can often occur in the same patient and show a similar clinical pattern. An overview of the rheumatological and psychiatric aspects of these diseases can certainly be useful for the improvement of patients' clinical and therapeutic management. Objective The aim of this narrative review was to summarize existing literature about common pathogenetic and clinical aspects as a means of improving management and therapeutic approach in patients affected by rheumatoid arthritis, psoriatic arthritis and spondyloarthritis. Outcomes such as disease activity indexes and patient reported outcomes (PROs) were considered. Findings Common pathogenetic pathways emerged between inflammatory arthritis and mood disorders. Pro-inflammatory mechanisms, such as TNFα, IL-6, IL-17 and oxidative stress factors as well as neurotransmitter alterations at the level of CNS and blood–brain barrier (BBB) cells are involved. The activation of these common pathogenetic pathways is, also, affected by the same triggers, such as smoking, stress, lifestyle, and evidence has emerged concerning the possibility of the clinical efficacy of using the same therapeutic approaches. Conclusions The main causes of the variability in clinical studies outcomes are the rheumatological diseases considered, the prevalence of depression in the general population and in patients with rheumatological diseases and the type of depressive symptom examined. Patients affected by inflammatory arthritis can present symptoms and signs in common with mood disorders, leading to possible clinical overlap. There are still few studies analyzing this concept: they are extremely heterogeneous, both in the characteristics of the population taken into consideration and in the methods used for the definition of depressive disorder, but the suggestions of the data obtained so far are promising and deserve to be pursued.

Background Rivaroxaban is a direct inhibitor of activated Factor X (FXa), an anti-inflammatory protein exerting a protective effect on the cardiac valve and vascular endothelium. We compare the effect of Warfarin and Rivaroxaban on inflammation biomarkers and their contribution to heart valve calcification progression and renal preservation in a population of atrial fibrillation (AF) patients with chronic kidney disease (CKD) stage 3b – 4. Methods This was an observational, multicenter, prospective study enrolling 347 consecutive CKD stage 3b – 4 patients newly diagnosed with AF: 247 were treated with Rivaroxaban and 100 with Warfarin. Every 12 months, we measured creatinine levels and cardiac valve calcification via standard trans-thoracic echocardiogram, while plasma levels of inflammatory mediators were quantified by ELISA at baseline and after 24 months. Results Over a follow-up of 24 months, long-term treatment with Rivaroxaban was associated with a significative reduction of cytokines. Patients treated with Rivaroxaban experienced a more frequent stabilization/regression of valve calcifications comparing with patients treated with Warfarin. Rivaroxaban use was related with an improvement in kidney function in 87.4% of patients, while in those treated with Warfarin was reported a worsening of renal clearance in 98% of cases. Patients taking Rivaroxaban experienced lower adverse events (3.2% vs 49%, p-value Conclusions Our findings suggest that Rivaroxaban compared to Warfarin is associated with lower levels of serum markers of inflammation. The inhibition of FXa may exert an anti-inflammatory effect contributing to reduce the risk of cardiac valve calcification progression and worsening of renal function.

Background Direct oral anticoagulants (DOACs) are recommended as first-line anticoagulants in patients with atrial fibrillation (AF). However, in patients with cancer and AF the efficacy and safety of DOACs are not well established. Objective We performed a meta-analysis comparing available data regarding the efficacy and safety of DOACs vs vitamin K antagonists (VKAs) in cancer patients with non-valvular AF. Methods An online search of Pubmed and EMBASE libraries (from inception to May, 1 2020) was performed, in addition to manual screening. Nine studies were considered eligible for the meta-analysis involving 46,424 DOACs users and 182,797 VKA users. Results The use of DOACs was associated with reduced risks of systemic embolism or any stroke (RR 0.65; 95% CI 0.52–0.81; p 0.001), ischemic stroke (RR 0.84; 95% CI 0.74–0.95; p 0.007) and hemorrhagic stroke (RR 0.61; 95% CI 0.52–0.71; p 0.00001) as compared to VKA group. DOAC use was associated with significantly reduced risks of major bleeding (RR 0.68; 95% CI 0.50–0.92; p 0.01) and intracranial or gastrointestinal bleeding (RR 0.64; 95% CI 0.47–0.88; p 0.006). Compared to VKA, DOACs provided a non-statistically significant risk reduction of the outcomes major bleeding or non-major clinically relevant bleeding (RR 0.94; 95% CI 0.78–1.13; p 0.50) and any bleeding (RR 0.91; 95% CI 0.78–1.06; p 0.24). Conclusions In comparison to VKA, DOACs were associated with a significant reduction of the rates of thromboembolic events and major bleeding complications in patients with AF and cancer. Further studies are needed to confirm our results.

ObjectivesTo evaluate in a multicentric Italian cohort of patients with psoriatic arthritis (PsA) on secukinumab followed for 24 months: (1) the long-term effectiveness and safety of secukinumab, (2) the drug retention rate and minimal disease activity (MDA), (3) differences in the outcomes according to the biological treatment line: biologic-naïve patients (group A) versus multifailure (group B) patients.MethodsConsecutive patients with PsA receiving secukinumab were evaluated prospectively. Disease characteristics, previous/ongoing treatments, comorbidities and follow-up duration were collected. Disease activity/functional/clinimetric scores and biochemical values were recorded at baseline (T0), 6(T6), 12(T12) and 24(T24) months. Effectiveness was evaluated overtime with descriptive statistics; multivariate Cox and logistic regression models were used to evaluate predictors of drug-discontinuation and MDA at T6. Infections and adverse events were recorded.Results608 patients (41.28% men; mean (SD) age 52.78 (11.33)) were enrolled; secukinumab was prescribed as first-line biological treatment in 227 (37.34%) patients, as second (or more)-line biological treatment in 381 (62.66%). Effectiveness of secukinumab was shown with an improvement in several outcomes, such as Ankylosing Spondylitis Disease Activity Score (T0=3.26 (0.88) vs T24=1.60 (0.69) ;p=0.02) and Disease Activity Index for Psoriatic Arthritis (T0=25.29 (11.14) vs T24=7.69 (4.51); pgroup A showed lower Psoriasis Area Severity Index (p=0.04), erythrocyte sedimentation rate and C reactive protein (p=0.03 ;p=0.05) and joint count (p=0.03) compared with group B. At T24, MDA was achieved in 75.71% of group A and 70.37% of group B. Treatment was discontinued in 123 (20.23%) patients, mainly due to primary/secondary loss of effectiveness, and in 22 due to adverse events. Retention rate at T24 was 71% in the whole population, with some difference depending on secukinumab dosage (p=0.004) and gender (p=0.05).ConclusionsIn a real-life clinical setting, secukimumab proved safe and effective in all PsA domains, with notable drug retention rate.

Objective.Spondyloarthritis (SpA) is among the most frequent extraintestinal manifestations of inflammatory bowel diseases (IBD). In this study, we aimed to validate the DETection of Arthritis in Inflammatory boweL diseases (DETAIL) questionnaire in a multicenter cohort of patients with IBD enrolled at 11 gastroenterology units.Methods.From October 2018 to March 2019, consecutive adult patients with IBD, either Crohn disease or ulcerative colitis, independently filled out the DETAIL questionnaire in the outpatient waiting room. Within 2 weeks a blinded rheumatologist assessed all the patients, irrespective of the DETAIL results, and classified them to be affected or not by SpA. The performance of the questions was evaluated through Bayesian analysis.Results.Overall, 418 patients with IBD filled out the DETAIL questionnaire. Upon rheumatological evaluation, 102 (24.4%) patients received a diagnosis of SpA. Of the 6 questions, the best performances were found in question 6 [positive likelihood ratio (LR)+ 3.77], reporting inflammatory back pain at night, and in question 3 (LR+ 3.31), exploring Achilles enthesitis. The presence of back pain lasting > 3 months (LR+ 2.91), back pain with inflammatory features (LR+ 2.55), and a history of dactylitis (LR+ 2.55), also showed a fairly good performance, whereas a history of peripheral synovitis was slightly worse (LR+ 2.16). The combination of at least 3 questions answered affirmatively yielded a posttest probability of SpA of 80% or more. The presence of alternative diagnoses, such as osteoarthritis or fibromyalgia, represented a minor confounder.Conclusion.The DETAIL questionnaire is a useful tool for the early detection of SpA in IBD.

IHD is determined by an inadequate coronary blood supply to the myocardium, and endothelial dysfunction may represent one of the main pathophysiological mechanisms involved. Genetic predisposition to endothelial dysfunction has been associated with IHD and its clinical manifestation. However, studies are often confounding and inconclusive for several reasons, such as interethnic differences. Validation of results in larger cohorts and new populations is needed. The aim of this study is to evaluate the associations between the allelic variants of the eNOS rs1799983 single-nucleotide polymorphism, IHD susceptibility and its clinical presentation. Methods: A total of 362 consecutive patients with suspected myocardial ischemia were enrolled. Patients were divided into three groups: G1, coronary artery disease (CAD), G2, coronary microvascular dysfunction (CMD), and G3, a control group with anatomically and functionally normal coronary arteries. Analysis of three allelic variants, GT, GG and TT, of rs1799983 for the NOS3 gene, encoding for eNOS, was performed. Results: rs1799983_GT was significantly more expressed by the ischemic groups (G1 and G2) compared to G3. The TT variant was significantly more expressed by the G1 group, compared to the G2 group. Among ischemic patients, GT was significantly more expressed in patients with acute coronary syndrome (ACS) presentation, compared to other clinical presentations. In the multivariate analysis, the allelic variant GT was found to potentially represent an independent predictor of IHD and ACS presentation. Conclusion: The presence of the SNP rs1799983_GT, encoding for eNOS, is an independent risk factor for IHD and, remarkably, for ACS presentation, independently of cardiovascular risk factors. These results may be useful for the prediction of IHD development, particularly with an acute clinical manifestation. They may allow the early identification of patients at high risk of developing IHD with an ACS, promoting a genetic-based prevention strategy against IHD.

Background although frailty and delirium are among the most frequent and burdensome geriatric syndromes, little is known about their association and impact on short-term mortality. Objective to examine, in hospitalized older persons, whether frailty is associated with delirium, and whether these two conditions, alone or in combination, affect these patients’ 30-day survival. Design observational study nested in the Delirium Day project, with 30-day follow-up. Setting acute medical wards (n = 118) and rehabilitation wards (n = 46) in Italy. Subjects a total of 2,065 individuals aged 65+ years hospitalized in acute medical (1,484 patients, 71.9%) or rehabilitation (581 patients, 28.1%) wards. Methods a 25-item Frailty Index (FI) was created. Delirium was assessed using the 4AT test. Vital status was ascertained at 30 days. Results overall, 469 (22.7%) patients experienced delirium on the index day and 82 (4.0%) died during follow-up. After adjustment for potential confounders, each FI score increase of 0.1 significantly increased the odds of delirium (odds ratio, OR: 1.66 [95% CI: 1.45–1.90]), with no difference between the acute (OR: 1.65 [95% CI: 1.41–1.93]) and rehabilitation ward patients (OR: 1.71 [95% CI: 1.27–2.30]). The risk of dying during follow-up also increased significantly for every FI increase of 0.1 in the overall population (OR: 1.65 [95% CI: 1.33–2.05]) and in the acute medical ward patients (OR: 1.61 [95% CI: 1.28–2.04]), but not in the rehabilitation patients. Delirium was not significantly associated with 30-day mortality in either hospital setting. Conclusions in hospitalized older patients, frailty is associated with delirium and with an increased risk of short-term mortality.

Background Cardiovascular disease (CVD) can occur in COVID-19 and has impact on clinical course. Data on CVD prevalence in hospitalized COVID-19 patients and sequelae in survivors is limited. Aim of this prospective study carried out on consecutive unselected COVID-19 population, was to assess: 1) CVD occurrence among hospitalized COVID-19 patients, 2) persistence or new onset of CVD at one-month and one-year follow-up. Methods Over 30 days n = 152 COVID-19 patients underwent cardiovascular evaluation. Standard electrocardiogram (ECG), Troponin and echocardiography were integrated by further tests when indicated. Medical history, arterial blood gas, blood tests, chest computed tomography and treatment were recorded. CVD was defined as the occurrence of a new condition during the hospitalization for COVID-19. Survivors attended a one-month follow-up visit and a one-year telephone follow-up. Results Forty-two patients (28%) experienced a wide spectrum of CVD with acute myocarditis being the most frequent. Death occurred in 32 patients (21%) and more frequently in patients who developed CVD (p = 0.032). After adjustment for confounders, CVD was independently associated with death occurrence. At one-month follow-up visit, 7 patients (9%) presented persistent or delayed CVD. At one-year telephone follow-up, 57 patients (48%) reported persistent symptoms. Conclusion Cardiovascular evaluation in COVID-19 patients is crucial since the occurrence of CVD in hospitalized COVID-19 patients is common (28%), requires specific treatment and increases the risk of in-hospital mortality. Persistence or delayed presentation of CVD at 1-month (9%) and persistent symptoms at 1-year follow-up (48%) suggest the need for monitoring COVID-19 survivors.

Despite important advances in diagnosis and treatment, heart failure (HF) remains a syndrome with substantial morbidity and dismal prognosis. Although implementation and optimization of existing technologies and drugs may lead to better management of HF, new or alternative strategies are desirable. In this regard, basic science is expected to give fundamental inputs, by expanding the knowledge of the pathways underlying HF development and progression, identifying approaches that may improve HF detection and prognostic stratification, and finding novel treatments. Here, we discuss recent basic science insights that encompass major areas of translational research in HF and have high potential clinical impact.

Psoriatic arthritis (PsA) is an inflammatory arthropathy, associated with skin and/or nail psoriasis. Real world data on efficacy and safety of TNF-α blockers in the elderly with PsA are lacking. The aim of this study was to evaluate the effectiveness, through the achievement of minimal disease activity (MDA), drug discontinuation rate, and safety in elderly patients with PsA on TNF-α blockers. A multicenter, observational study was carried out in four Italian centers. The assessment of disease activity and safety were performed at the start of anti-TNF-α (T0), at 6 months (T6) and at 12 months (T12). A total of 145 PsA patients were included in the study. At baseline 68 (46.9%) patients were on etanercept, 60 (41.3%) on adalimumab, 11 (7.6%) on golimumab, and 6 (4.1%) on infliximab. All the variables concerning PsA activity showed a statistically significant improvement when comparing T6 and T12 with T0. After 6 and 12 months of therapy, respectively, 31 (22.6%) and 71 (51.8%) patients achieved MDA (p

Psoriatic arthritis (PsA) can start in subjects aged over 60 years, defined as late-onset PsA. In late-onset PsA, the weight of family history and genetic background appears less significant when compared with younger onset PsA, whereas obesity and smoking have been suggested as potential risk factors. In patients with late-onset PsA, erosive polyarticular or oligoarticular patterns are more frequent than other phenotypes. Laboratory findings usually show an increase in levels of acute phase reactants, including erythrocyte sedimentation rate and C-reactive protein. The drugs used for the management of young PsA subjects represent the same therapeutic armamentarium used in patients with late-onset disease. However, in elderly subjects, these anti-inflammatory, immunomodulatory and immunosuppressive therapies, including newer biologic therapies, represent an important challenge due to age aspects, increased frequency of comorbidities and associated polypharmacotherapy. There is a need for more evidence around treatment strategy for these patients in order to identify the best balance between the benefits and risks of pharmacological agents. This is important for establishing how treatment should ideally be tailored to the characteristics of any single patient and to the presence of complex age- and disease-related aspects. The objective of this review is to focus on pathogenetic, clinical and therapeutic aspects of late-onset PsA and the management of elderly PsA patients.

Diet is a modifiable factor implicated in chronic systemic inflammation, and the mediterranean dietary pattern is considered to be a healthy model in terms of morbidity and mortality. The main aim of this study was to evaluate the adherence to the mediterranean diet in patients with Psoriatic Arthritis (PsA) and its impact on disease activity. A cross-sectional observational study was conducted in a cohort of 211 consecutive PsA patients. We evaluated PsA activity by disease activity index for PSoriatic Arthritis (DAPSA) and composite psoriatic disease activity index (CPDAI). The NCEP-ACT III criteria were used to identify subjects with MetS, and in each subject, we evaluated body mass index (BMI). A validated 14-item questionnaire for the assessment of adherence to the mediterranean diet (PREDIMED) was recorded for all the enrolled subjects. Patients showed a median age of 55 (48-62) and disease duration was 76 (36-120) months. 27.01% of patients were classified as having MetS. The median of the mediterranean diet score (MDS) was 7 (6-9). A moderate adherence to mediterranean diet was found in 66.35% of the entire cohort; 15.64% and 18.01% of the patients showed low- and high adherence to the dietary pattern, respectively. We found a negative association between DAPSA and adherence to mediterranean diet (B = - 3.291; 95% CI - 5.884 to - 0.698). DAPSA was positively associated with BMI (B = 0.332; 95% CI 0.047-0.618) and HAQ ( B = 2.176; 95% CI 0.984-3.368). Results from our study evidenced that in PsA patients, higher levels of disease activity as measured by DAPSA correlated with low adherence to mediterranean diet, suggesting potential benefit of antinflammatory properties of this dietary pattern.

Pregnancy requires a special management in women with inflammatory rheumatic diseases (RDs), with the aim of controlling maternal disease activity and avoiding fetal complications. Despite the heterogeneous course of RDs during pregnancy, their impact on pregnancy largely relates to the extent of active inflammation at the time of conception. Therefore, accurate evaluation of disease activity is crucial for the best management of pregnant patients. Nevertheless, there are limitations in using conventional measures of disease activity in pregnancy, as some items included in these instruments can be biased by symptoms or by physiological changes related to pregnancy and the pregnancy itself may influence laboratory parameters used to assess disease activity. This article aims to summarize the current literature about the available instruments to measure disease activity during pregnancy in RDs. Systemic lupus erythematosus is the only disease with instruments that have been modified to account for several adaptations which might interfere with the attribution of signs or symptoms to disease activity during pregnancy. No modified-pregnancy indices exist for women affected by other RDs, but standard indices have been applied to pregnant patients. The current body of knowledge shows that the physiologic changes that occur during pregnancy need to be either adapted from existing instruments or developed to improve the management of pregnant women with RDs. Standardized instruments to assess disease activity during pregnancy would be helpful not only for clinical practice but also for research purposes. info:eu-repo/semantics/publishedVersion

Background Manifestation of arrhythmias in otherwise normal heart suggests a possible compromise of conduction tissue. It, however, remains, usually, a supposition with limited therapeutical implications. Purpose Reporting histology of inflammation/infection of conduction tissue as a cause of arrhythmic phenotype of myocarditis. Material and methods Among 420 patients with a biopsy proven myocarditis diagnosed from 2009 to 2019, 42 presented with an arrhythmic phenotype and normal cardiac anatomy and function (LVEF >50%). Of the latter, 12 subjects (28.5%; M 9; F 3; mean age 44,75±14.9 years) had included in a left ventricular endomyocardial biopsy sections of conduction tissue (CT). CT was identified by recognition of morphological Aschoff and Monckeberg criteria and positive immunostaining for HCN4. CT inflammation was defined by ≥7 CD3+ T lymphocytes with focal necrosis of adjacent cells. Cause of CT inflammation was investigated by polymerase chain reaction (PCR) of 2 frozen endomyocardial samples, immunohistochemistry for the identified viral antigens and for Tall like receptor 4 (TLR4). Results Four pts presented with non-sustained ventricular tachycardia (nsVT), seven pts with sustained (S) VT, 1 died during hospitalization because of ventricular fibrillation (VF). Inflammatory involvement of CT was documented in all 12 pts. PCR was positive for Influenza A virus in 2 pts and HHV2 in 1 with positive CT immunostaining for related antigens. In the remaining 8 pts negative PCR for viral genomes and overexpression of TLR4 suggested an immune-mediated pathway of CT inflammation. Pts with Influenza A myocarditis and CT infection responded to tamiflu (1 cp bid for 5 days) with ECG normalization while the pt with HHV2 infection died. The 8 pts with virus-negative myocarditis and TLR4 overexpession were treated with steroids and azathioprine based on TIMIC protocol. Seven of them had no more repetitive ventricular ectopic beats at Holter of 2 weeks follow-up. Conclusions Arrhythmic phenotype of myocarditis is caused by elective inflammation/infection of CT. Molecular characterization of CT damage may bring to pharmacologic control of arrhythmias in up to 75% of cases. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Project ERA-CVD “Transnational Research Projects on Cardiovascular Diseases”

Background The TIMIC trial demonstrated the short term efficacy of immunosuppression (IMS) in virus-negative inflammatory cardiomyopathy. However long term outcome of patients responsive to this treatment is still unclear. Purpose To assess the long term outcome of patients enrolled in the TIMIC trial. Methods The 85 (51 M, 34 F, 42.7±14.7 years) patients with endomyocardial biopsy proven virus-negative chronic inflammatory cardiomyopathy, enrolled in the TIMIC trial and treated either with prednisone and azathioprine (prednisone 1mg kg–1 day–1 for 4 weeks followed by 0.33 mg kg–1 day–1 for 5 months and azathioprine 2 mg kg–1 day–1 for 6 months) or placebo for 6 months, were evaluated in a long-term follow-up of up to 18 years (mean 15.2±2.0 SD, range 12–18 ys). Patients treated with placebo at the end of the 6-month enrollment because of the lack of improvement received IMS for further 6 months. Results At 6 months' follow-up 89% patients showed a significant improvement of left ventricular ejection fraction compared to baseline (LVEF rising from 27.0±5.7 to 46.2±6.4, % p This improvement was maintained in the long term follow-up (LVEF 51.1±6.4%, p Conclusion Immunosuppressive therapy of virus negative inflammatory cardiomyopathy warrants in susceptible patients a long term recovery of heart function with very low incidence of recurrences, that respond to a new TIMIC protocol dose treatment. Long term efficacy of TIMIC-IMS therapy Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): AIFA

Ischemic heart disease still represents a large burden on individuals and health care resources worldwide. By conventions, it is equated with atherosclerotic plaque due to flow-limiting obstruction in large–medium sized coronary arteries. However, clinical, angiographic and autoptic findings suggest a multifaceted pathophysiology for ischemic heart disease and just some cases are caused by severe or complicated atherosclerotic plaques. Currently there is no well-defined assessment of ischemic heart disease pathophysiology that satisfies all the observations and sometimes the underlying mechanism to everyday ischemic heart disease ward cases is misleading. In order to better examine this complicated disease and to provide future perspectives, it is important to know and analyze the pathophysiological mechanisms that underline it, because ischemic heart disease is not always determined by atherosclerotic plaque complication. Therefore, in order to have a more complete comprehension of ischemic heart disease we propose an overview of the available pathophysiological paradigms, from plaque activation to microvascular dysfunction.

Background Enteropathic Spondyloarthritis (ESpA) belongs to the group of Spondyloarthritis (SpA) tipically associated with inflammatory bowel disease (IBD) as Crohn9s Disease (CD) and Ulcerative Colitis (UC). Joint pain is the most common (22–33%) and significant extra-intestinal manifestation in patients with IBD and its management requires reumatological and gastroenterological competence in collaboration. No data concerning the Health-related quality of life (HRQoL) have been evaluated in patients affected by ESpA. Objectives Prospective study was performed in a combined GastroIntestinal and RHEumatologic “GI-Rhe” clinic, in order to evaluate: 1) prevalence and characteristics of articular manifestations in a group of IBD patients; 2) quality of life, state of health and well-being in ESpA patients. Methods Patients affected by IBD who presented muscolo-skeletal pain between February 2013 and September 2016 (CD 264 and UC 142) were enrolled. New diagnosis, disease management, adverse events as well as laboratory evaluations were assessed every 3 months during the follow-up. Disease activity, function and quality of life in ESpA patients were assessed by ASDAS-CRP, HAQ-S and EuroQol questionnaire. Results A total of 427 patients were evaluated for joint involvement (Table 1). The prevalence of SpA in IBD patients was 49.6% (n=212: UC 71 (43.3%), CD 141 (53.4%)), suggesting that the majority of patients with IBD who complain arthralgia may have a concomitant SpA. Other rheumatologic diseases were detected in the study population in 215 patients defined as IBD non-SpA. There was a significantly higher prevalence of active intestinal disease in patients with SpA with respect to IBD-non SpA (CD: CDAI>150 in 18.4% vs 8.2% p=0.004; UC: Mayo score >3 in 15.5% vs 0%, p=0.0004). The evaluation of the EuroQoL demonstrated a mean value of 0.59 in IBD-SpA patients and of 0.55 in IBD non-SpA (Figure 1A). In IBD-SpA, the health related status was: decent 69.8%, good 17.9% and bad 9.4%. In IBD-non SpA, the health related status was: decent in 74.8%, good in 17.7% and bad in 7% of patients. In both groups, none of the patients had a neither exceptional nor great perception of QoL. No significant differences were observed between the two groups (Figure 1B-C). Conclusions The joint clinic facilitates diagnosis and management of SpA and IBD. Although IBD-SpA patients showed higher IBD disease activity than IBD-non SpA one, both groups of patients have a good health related QL. Disclosure of Interest None declared

We read with interest the letter entitled ‘Gender gap in rheumatology: speaker representation at annual conferences’ by Kanika Monga and Jean Liew published in the Annals of the Rheumatic Diseases .1 The authors highlight the issue of a gender gap among speakers and moderators at the academic conferences investigating female representation at the American College of Rheumatology (ACR) in 2017 and 2018. Overall, the proportion of female speakers and moderators was 42.8%–47% and the gap was higher in the clinician sessions presentations compared with basic science ones (45.8% vs 40.5%). The highest proportion of female representation was detected in Alliance for Human Research Protection sessions (65.3%), and the lowest in Meet the Professors and workshop sessions (34.4% and 28.7%). Indeed, the gender gap was narrower as compared with other conferences.2 Recently, European League Against Rheumatism (EULAR) established a task force on gender equity …