Le indicazioni al trattamento con immunoglobuline endovena nelle malattie reumatiche. [Indications for intra-venous immunoglobulin treatment in rheumatic diseases]

Con l’immissione in commercio delle Immunoglobuline per uso endovenoso (IVIG), che risale ormai al 1981, è stato possibile ampliarne enormemente le utilizzazioni terapeutiche, dimostrando l’efficacia di tale trattamento in condizioni cliniche le più diverse. In particolare, sulla base della progressiva acquisizione di conoscenze circa la capacità delle IVIG ad alte dosi di interferire a vari livelli col sistema immunitario, ne è stato proposto l’impiego in moltissime patologie su base autoimmunitaria o comunque dipendenti da meccanismi di tipo flogistico-immunitario. Ci limiteremo in questa sede a riportare le indicazioni al trattamento con IVIG, di quelle situazioni cliniche, di stretta competenza reumatologica, per le quali l’evidenza di efficacia sia sufficientemente solida, sia cioè basata su sperimentazioni cliniche allargate e adeguatamente controllate. Prima di procedere alla disamina degli aspetti terapeutici è tuttavia opportuno ricordare brevemente i meccanismi invocati per spiegare la potente attività immunomodulante di cui sono dotate le IVIG. I meglio conosciuti e documentati sono i seguenti

Surveillance of Influenza and Other Airborne Transmission Viruses during the 2021/2022 Season in Hospitalized Subjects in Tuscany, Italy

Winter in the northern hemisphere is characterized by the circulation of influenza viruses, which cause seasonal epidemics, generally from October to April. Each influenza season has its own pattern, which differs from one year to the next in terms of the first influenza case notification, the period of highest incidence, and the predominant influenza virus subtypes. After the total absence of influenza viruses in the 2020/2021 season, cases of influenza were again recorded in the 2021/2022 season, although they remained below the seasonal average. Moreover, the co-circulation of the influenza virus and the SARS-CoV-2 pandemic virus was also reported. In the context of the DRIVE study, oropharyngeal swabs were collected from 129 Tuscan adults hospitalized for severe acute respiratory infection (SARI) and analyzed by means of real-time polymerase chain reaction (RT-PCR) for SARS-CoV-2 and 21 different airborne pathogens, including influenza viruses. In total, 55 subjects tested positive for COVID-19, 9 tested positive for influenza, and 3 tested positive for both SARS-CoV-2 and the A/H3N2 influenza virus. The co-circulation of different viruses in the population requires strengthened surveillance that is no longer restricted to the winter months. Indeed, constant, year-long monitoring of the trends of these viruses is needed, especially in at-risk groups and elderly people

Autoimmune Calcium Channelopathies and Cardiac Electrical Abnormalities

Patients with autoimmune diseases are at increased risk for developing cardiovascular diseases, and abnormal electrocardiographic findings are common. Voltage-gated calcium channels play a major role in the cardiovascular system and regulate cardiac excitability and contractility. Particularly, by virtue of their localization and expression in the heart, calcium channels modulate pace making at the sinus node, conduction at the atrioventricular node and cardiac repolarization in the working myocardium. Consequently, emerging evidence suggests that calcium channels are targets to autoantibodies in autoimmune diseases. Autoimmune-associated cardiac calcium channelopathies have been recognized in both sinus node dysfunction atrioventricular block in patients positive for anti-Ro/La antibodies, and ventricular arrhythmias in patients with dilated cardiomyopathy. In this review, we discuss mechanisms of autoimmune-associated calcium channelopathies and their relationship with the development of cardiac electrical abnormalities

Marked QTc Prolongation and Torsades de pointes in Patients with Chronic Inflammatory Arthritis

Mounting evidence indicates that in chronic inflammatory arthritis (CIA), QTc prolongation is frequent and correlates with systemic inflammatory activation. Notably, basic studies demonstrated that inflammatory cytokines induce profound changes in potassium and calcium channels resulting in a prolonging effect on cardiomyocyte action potential duration, thus on the QT interval on the electrocardiogram. Moreover, it has been demonstrated that in rheumatoid arthritis (RA) patients, the risk of sudden cardiac death is significantly increased when compared to non-RA subjects. Conversely, to date no data are available about torsades de pointes (TdP) prevalence in CIA, and the few cases reported considered CIA only an incidental concomitant disease, not contributing factor to TdP development. We report three patients with active CIA developing marked QTc prolongation, in two cases complicated with TdP degenerating to cardiac arrest. In these patients, a blood sample was obtained within 24 h from TdP/marked QTc prolongation occurrence, and levels of IL-6, TNFα, and IL-1 were evaluated. In all three cases, IL-6 was markedly elevated, ~10 to 100 times more than reference values. Moreover, one patient also showed high circulating levels of TNFα and IL-1. In conclusion, active CIA may represent a currently overlooked QT-prolonging risk factor, potentially contributing in the presence of other "classical" risk factors to TdP occurrence. In particular, a relevant role may be played by elevated circulating IL-6 levels via direct electrophysiological effects on the heart. This fact should be carefully kept in mind, particularly when recognizable risk factors are already present and/or the addition of QT-prolonging drugs is required

Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register

Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria

Clinical features and outcomes of elderly hospitalised patients with chronic obstructive pulmonary disease, heart failure or both

Background and objective: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) mutually increase the risk of being present in the same patient, especially if older. Whether or not this coexistence may be associated with a worse prognosis is debated. Therefore, employing data derived from the REPOSI register, we evaluated the clinical features and outcomes in a population of elderly patients admitted to internal medicine wards and having COPD, HF or COPD + HF. Methods: We measured socio-demographic and anthropometric characteristics, severity and prevalence of comorbidities, clinical and laboratory features during hospitalization, mood disorders, functional independence, drug prescriptions and discharge destination. The primary study outcome was the risk of death. Results: We considered 2,343 elderly hospitalized patients (median age 81 years), of whom 1,154 (49%) had COPD, 813 (35%) HF, and 376 (16%) COPD + HF. Patients with COPD + HF had different characteristics than those with COPD or HF, such as a higher prevalence of previous hospitalizations, comorbidities (especially chronic kidney disease), higher respiratory rate at admission and number of prescribed drugs. Patients with COPD + HF (hazard ratio HR 1.74, 95% confidence intervals CI 1.16-2.61) and patients with dementia (HR 1.75, 95% CI 1.06-2.90) had a higher risk of death at one year. The Kaplan-Meier curves showed a higher mortality risk in the group of patients with COPD + HF for all causes (p = 0.010), respiratory causes (p = 0.006), cardiovascular causes (p = 0.046) and respiratory plus cardiovascular causes (p = 0.009). Conclusion: In this real-life cohort of hospitalized elderly patients, the coexistence of COPD and HF significantly worsened prognosis at one year. This finding may help to better define the care needs of this population

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes

Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription