Free light chain UV quantification compared with immunochemical measurement: How dimers and monomers may influence the results

Serum κ and λ free light chain (FLC) levels are important for the management of plasma cell disorders. Immunochemical measurements on automated platforms with different reagents occasionally return different results that make them not interchangeable. The reasons for this behaviour are not clear and it is not known which result is the most accurate. The aim of the study is to quantify naturally occurring FLCs with a reference method (UV absorbance) in a sample devoid of other sources of UV absorbance. This was possible on a particular urine sample containing only lambda FLC proteins, dialyzed to clear it from low molecular weight UV absorbing compounds. The sample was submitted to Fast Protein Liquid Chromatography separation with a size-exclusion column in order to separate the FLC monomers and dimers. FLCs were also measured with the Freelite and N Latex FLC methods and the results were compared. The results demonstrated that the amount of FLC calculated on the basis of UV absorbance was overestimated by both immunochemical methods, and that the amount measured by the two reagents was affected by the different proportions of dimers or monomers. The present findings may be useful for the comprehension of the immunochemical measurement of FLC

A systematic review and meta-analysis on oncological radiotherapy in patients with a cardiac implantable electronic device: Prevalence and predictors of device malfunction in 3121 patients

Background: The number of patients with cardiac implantable electronic devices (CIEDs) undergoing radiotherapy (RT) for cancer treatment is growing. At present, prevalence and predictors of RT-induced CIEDs malfunctions are not defined. Methods: Systematic review and meta-analysis conducted following the PRISMA recommendations. PubMed, Scopus and Google Scholar were searched from inception to 31/01/2022 for studies reporting RT-induced malfunctions in CIEDs patients. Aim was to assess the prevalence of RT-induced CIEDs malfunctions and identify potential predictors. Results: Thirty-two out of 3962 records matched the inclusion criteria and were included in the meta-analysis. A total of 135 CIEDs malfunctions were detected among 3121 patients (6.6%, 95% confidence interval [CI]: 5.1%–8.4%). The pooled prevalence increased moving from pacemaker (PM) to implantable cardioverter defibrillator (ICD), and cardiac resynchronization therapy and defibrillator (CRT-D) groups (4.1%, 95% CI: 2.9–5.8; 8.2% 95% CI: 5.9–11.3; and 19.8%, 95% CI: 11.4–32.2 respectively). A higher risk ratio (RR) of malfunctions was found when neutron-producing energies were used as compared to non-neutron-producing energies (RR 9.98, 95% CI: 5.09–19.60) and in patients with ICD/CRT-D as compared to patients with PM/CRT-P (RR 2.07, 95% CI: 1.40–3.06). On the contrary, no association was found between maximal radiation dose at CIED >2 Gy and CIEDs malfunctions (RR 0.93; 95% CI: 0.31–2.76). Conclusions: Radiotherapy related CIEDs malfunction had a prevalence ranging from 4% to 20%. The use of neutron-producing energies and more complex devices (ICD/CRT-D) were associated with higher risk of device malfunction, while the radiation dose at CIED did not significantly impact on the risk unless higher doses (>10 Gy) were used

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

BACKGROUND: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The 'Atrial fibrillation Better Care' (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. METHODS: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. RESULTS: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58-0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52-0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58-0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56-0.98) and composite outcome (aHR: 0.76, 95%CI 0.60-0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. CONCLUSIONS: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

Yield of diagnosis and risk of stroke with screening strategies for atrial fibrillation: a comprehensive review of current evidence

Atrial fibrillation (AF) is the most prevalent arrhythmia worldwide. The presence of AF is associated with increased risk of systemic thromboembolism, but with the uptake of oral anticoagulant (OAC) and implementation of a holistic and integrated care management, this risk is substantially reduced. The diagnosis of AF requires a 30-s-long electrocardiographic (ECG) trace, irrespective of the presence of symptoms, which may represent the main indication for an ECG tracing. However, almost half patients are asymptomatic at the time of incidental AF diagnosis, with similar risk of stroke of those with clinical AF. This has led to a crucial role of screening for AF, to increase the diagnosis of population at risk of clinical events. The aim of this review is to give a comprehensive overview about the epidemiology of asymptomatic AF, the different screening technologies, the yield of diagnosis in asymptomatic population, and the benefit derived from screening in terms of reduction of clinical adverse events, such as stroke, cardiovascular, and all-cause death. We aim to underline the importance of implementing AF screening programmes and reporting about the debate between scientific societies’ clinical guidelines recommendations and the concerns expressed by the regulatory authorities, which still do not recommend population-wide screening. This review summarizes data on the ongoing trials specifically designed to investigate the benefit of screening in terms of risk of adverse events which will further elucidate the importance of screening in reducing risk of outcomes and influence and inform clinical practice in the next future

Factors Associated with Progression of Atrial Fibrillation and Impact on All-Cause Mortality in a Cohort of European Patients

Background: Paroxysmal atrial fibrillation (AF) may often progress towards more sustained forms of the arrhythmia, but further research is needed on the factors associated with this clinical course. Methods: We analyzed patients enrolled in a prospective cohort study of AF patients. Patients with paroxysmal AF at baseline or first-detected AF (with successful cardioversion) were included. According to rhythm status at 1 year, patients were stratified into: (i) No AF progression and (ii) AF progression. All-cause death was the primary outcome. Results: A total of 2688 patients were included (median age 67 years, interquartile range 60–75, females 44.7%). At 1-year of follow-up, 2094 (77.9%) patients showed no AF progression, while 594 (22.1%) developed persistent or permanent AF. On multivariable logistic regression analysis, no physical activity (odds ratio [OR] 1.35, 95% CI 1.02–1.78), valvular heart disease (OR 1.63, 95% CI 1.23–2.15), left atrial diameter (OR 1.03, 95% CI 1.01–1.05), or left ventricular ejection fraction (OR 0.98, 95% CI 0.97–1.00) were independently associated with AF progression at 1 year. After the assessment at 1 year, the patients were followed for an extended follow-up of 371 days, and those with AF progression were independently associated with a higher risk for all-cause death (adjusted hazard ratio 1.77, 95% CI 1.09–2.89) compared to no-AF-progression patients. Conclusions: In a contemporary cohort of AF patients, a substantial proportion of patients presenting with paroxysmal or first-detected AF showed progression of the AF pattern within 1 year, and clinical factors related to cardiac remodeling were associated with progression. AF progression was associated with an increased risk of all-cause mortality

The SIMI Gender ‘5 Ws’ Rule for the integration of sex and gender-related variables in clinical studies towards internal medicine equitable research

Biological sex and sociocultural gender matter when it comes to health and diseases. They have been both proposed as the undeniable gateways towards a personalized approach in care delivery. The Gender Working Group of the Italian Society of Internal Medicine (SIMI) was funded in 2019 with the aim of promoting good practice in the integration of sex and gender domains in clinical studies. Starting from a narrative literature review and based on regular meetings which led to a shared virtual discussion during the national SIMI congress in 2021, the members of the WG provided a core operational framework to be applied by internal medicine (IM) specialists to understand and implement their daily activity as researchers and clinicians. The SIMI Gender '5 Ws' Rule for clinical studies has been conceptualized as follows: Who (Clinical Internal Medicine Scientists and Practitioners), What (Gender-related Variables-Gender Core Dataset), Where (Clinical Studies/Translational Research), When (Every Time It Makes Sense) and Why (Explanatory Power of Gender and Opportunities). In particular, the gender core dataset was identified by the following domains (variables to collect accordingly): relations (marital status, social support, discrimination); roles (occupation, caregiver status, household responsibility, primary earner, household dimension); institutionalized gender (education level, personal income, living in rural vs urban areas); and gender identity (validated questionnaires on personality traits). The SIMI Gender '5 Ws' Rule is a simple and easy conceptual framework that will guide IM for the design and analysis of clinical studies

Immunotherapy with an HIV-DNA Vaccine in Children and Adults

Therapeutic HIV immunization is intended to induce new HIV-specific cellular immune responses and to reduce viral load, possibly permitting extended periods without antiretroviral drugs. A multigene, multi-subtype A, B, C HIV-DNA vaccine (HIVIS) has been used in clinical trials in both children and adults with the aim of improving and broadening the infected individuals’ immune responses. Despite the different country locations, different regimens and the necessary variations in assays performed, this is, to our knowledge, the first attempt to compare children’s and adults’ responses to a particular HIV vaccine. Ten vertically HIV-infected children aged 4–16 years were immunized during antiretroviral therapy (ART). Another ten children were blindly recruited as controls. Both groups continued their antiretroviral treatment during and after vaccinations. Twelve chronically HIV-infected adults were vaccinated, followed by repeated structured therapy interruptions (STI) of their antiretroviral treatment. The adult group included four controls, receiving placebo vaccinations. The HIV-DNA vaccine was generally well tolerated, and no serious adverse events were registered in any group. In the HIV-infected children, an increased specific immune response to Gag and RT proteins was detected by antigen-specific lymphoproliferation. Moreover, the frequency of HIV-specific CD8+ T-cell lymphocytes releasing perforin was significantly higher in the vaccinees than the controls. In the HIV-infected adults, increased CD8+ T-cell responses to Gag, RT and viral protease peptides were detected. No augmentation of HIV-specific lymphoproliferative responses were detected in adults after vaccination. In conclusion, the HIV-DNA vaccine can elicit new HIV-specific cellular immune responses, particularly to Gag antigens, in both HIV-infected children and adults. Vaccinated children mounted transient new HIV-specific immune responses, including both CD4+ T-cell lymphoproliferation and late CD8+ T-cell responses. In the adult cohort, primarily CD8+ T-cell responses related to MHC class I alleles were noted. However, no clinical benefits with respect to viral load reduction were ascribable to the vaccinations alone. No severe adverse effects related to the vaccine were found in either cohort, and no virological failures or drug resistances were detected

Notulae to the Italian alien vascular flora: 2

In this contribution, new data concerning the Italian distribution of alien vascular flora are presented. It includes new records, exclusions and confirmations for Italy or for Italian administrative regions for taxa in the genera Ageratum, Aster, Buddleja, Cedrus, Centranthus, Cephalotaxus, Clerodendrum, Cotoneaster, Cyperus, Honorius, Lantana, Ligustrum, Morus, Muscari, Oenothera, Opuntia, Platycladus, Plumbago, Pseudotsuga, Sedum, Sporobolus, Stachys, Ulmus and Yucca. A nomen novum, Stachys talbotii, is proposed as a replacement name for Sideritis purpurea