SPANISH NATIONAL REGISTRY OF BELIMUMAB IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

BackgroundBelimumab (BLM) is a monoclonal antibody that inhibits B-lymphocyte stimulating factor (BlyS) approved as a specific treatment for systemic lupus erythematosus (SLE) in 2011. We present the experience with BLM in a Spanish cohort with more than 460 patients.ObjectivesTo describe demographic characteristics, efficacy and safety of BLM in patients with SLE in Spanish population since its approval.MethodsDescriptive, retrospective, multicenter study in patients diagnosed with SLE according to EULAR/ACR 2019, SLICC and/or ACR 1997 diagnostic criteria. Data regarding SLE patients treated with BLM were collected from medical records (2011-2022). Demographic features, efficacy, laboratory variables, SLEDAI, renal involvement, steroid dose, administration routes and safety were assessed. To see whether a trend in BLM prescription had changed or not over time, two periods of time were analyzed: 2011-2016 (period1) and 2017-2022 (period2).ResultsBaseline characteristics of patients are summarized in Table 1.A total of 462 patients (36 hospitals) were included, 50.9% were on intravenous (IV), 34% on subcutaneous (SC) and 15.1% switched from IV to SC route. The median number of pre-BLM csDMARD use was 2.0 (2.0-3.0), being hydroxychloroquine (HCQ) the most frequently used (94.5%). Fifty-two patients were treated with IV cyclophosphamide with a median of 6 bolus received. At the time of BLM start, 443 patients were on prednisone with a median dose of 6.2 mg (5.0-10.0). Significant decreases in prednisone dose, SLEDAI and anti-DNA antibodies were observed from baseline until the last visit, whereas complement C3 and C4 values raised (Figure 1). A total of 118 patients (27.4%) had renal involvement with a median proteinuria of 1.0 g/day (0.5-2.4). Renal biopsy was done in 102 out of 118 patients, being class IV (33%), class III (21%) and class V (16%) the most frequently reported. After BLM, 73.3% of these patients improved (median proteinuria of 0.2 g/day (0.1-0.7).In period1, 100 patients started BLM compared to 362 in period2. The median time from SLE diagnosis to BLM begin was 7.1 (4.0-13.7) and 6.2 (2.1 -14.4) years in period1 and period2, respectively (p=0.454). We found a trend to use more csDMARD before BLM treatment in period1: 2.5 (2-3) vs. 2 (2-3) (p=0.088).A total of 143 (30.5%) patients discontinued treatment mostly due to inefficacy (55.9%) and infections (11.9%). In fact, 116 patients developed infections, mostly mild;2 patients died, 16 had COVID-19 and 4 patients developed tumors requiring discontinuation of the drug.ConclusionIn our cohort of SLE patients in a real-world setting, BLM has been effective, safe and seems to be a good choice to treat renal involvement.References[1]Navarra SV, Guzmán RM, Gallacher AE, et al. Lancet. 2011;377(9767):721-31.[2]Stohl W, Hiepe;rt al. Arthritis Rheum. 2012;64(7):2328-37.[3]Furie R, Rovin BH, Houssiau F, et al. N Engl J Med. 2020;383(12):1117-1128.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Molecular point-of-care tests: efficiency of RT-LAMP in the rapid diagnosis of COVID-19 to assess hospital access.

Background: Safe hospital access needs rapid testing for SARS-CoV-2 to enable rationale use of limited resources. The current standard method for Coronavirus detection is the RT-qPCR. This study aimed to determine the diagnostic performance of the new rapid RT-LAMP test, compared to RT-qPCR, and his efficiency for rapid hospital access through the Emergency Department (E.D.). Method(s): 1576 UTM nasopharyngeal swabs, collected in E.D., have been tested for SARS-CoV-2 infection, using a kit RTLAMP. The same samples were also analyzed with a traditional RT-qPCR assay and the results have been compared in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Result(s): The assay has demonstrated a sensitivity of 73.3% (95%CI: 62.4/82.0) and specificity of 87.1% (95%CI: 85.3/88.7), PPV 22.1%, NPV 98.5%. Conclusion(s): ICGENE RNA RT-LAMP kit (ICGENEHEALTH;Enbiotech, Angri, Salerno, Italy) efficiently exclude the presence of infection and reliably detects infectious patients (with Ct<30). RNA RT-LAMP could replace rRTPCR where there is the need to rapidly identify potentially contagious individuals, but its low PPV suggests that positive results should be confirmed by a reference method.Copyright © 2022 EDIZIONI MINERVA MEDICA.

Comparative Benefits and Risks Associated with Currently Authorized COVID-19 Vaccines.

This article provides a systematic assessment of the efficacy, risks, and methodological quality of evidence from five major publicly available vaccine trials. Results from Pfizer-BioNTech mRNA, Moderna-US NIH mRN-1273, AstraZeneca-Oxford ChAdOx1 nCov-19, Gamaleya GamCovidVac (Sputnik V), and Ad26.COV2.S Johnson & Johnson vaccines were included. Extracted benefits and risks data from each trial were summarized using the GRADE approach denoting the overall certainty of evidence along with relative and absolute effects. Relative risk reduction across all five vaccine trials ranged from 45% to 96%. Absolute risk reduction in symptomatic COVID-19 ranged from 6 to 17 per 1000 across trials. None of the vaccines were associated with a significant increase in serious adverse events compared to placebo. The overall certainty of evidence varied from low to moderate. All five vaccines are effective and safe, but suggest room for improvement in the conduct of large-scale vaccine trials. Certainty of evidence was downrated due to risk of bias, which can be mitigated by improving transparency and thoroughness in conduct and reporting of outcomes.

Evaluation of Loop-mediated isothermal amplification (LAMP) method as an effective molecular point-of-care technique for the rapid diagnosis of SARS-CoV-2 infection

Background: The novel Coronavirus disease-2019 (Covid-19) pandemic emergency is a concrete example of the existing gap between availability of advanced diagnostics and need for cost-effective methodology. The current standard method for Coronavirus detection is the reverse transcription-PCR (RT-PCR), but the recent validation of a new rapid SARS-CoV-2 RT-LAMP assay offers an alternative diagnostic pathway. Unlike PCR tests, LAMP (loop-mediated isothermal amplification) do not require sequential changes of temperature and so can turnaround test results more rapidly. We explored the diagnostic effectiveness of LAMP compared with RTqPCR traditional assay.Methods: A sample of 1652 UTM NP swabs (collected from suspected or non suspected patient of ED) were tested for SARS Cov2 infection, using IC GENE SARS-CoV-2 POC (Enbiotech) that detect two specific viral targets: S gene and N gene. After a rapid termal RNA extraction protocol, a Real Time amplifier and fluorescence reader allowed us to achieve the result (simultaneously, and up to 12 samples per run) in a time between 30 and 60 minutes. The same samples were further analyzed with a RT-qPCR traditional assay (Cephied Xpert Xpress® SARS cov-2 and Altona RealStar® SARS-cov-2 RT-PCR).Results: The technical performance of assay demonstrated a sensitivity of 72.2 % (95%CI: 61.4/80.8) and specificity of 86.8 % (95%CI: 85.0/88.4), VPP 21.5%, VPN 98.4%, in comparison to current standard of care RT-qPCR testing after RNA extraction, across all samples tested (CT <45 by RTqPCR), increasing to a sensitivity of 96.6 % for those samples with a higher viral load (CT <25 by RTqPCR). Our results shows that main limitation of LAMP is the high number of false positive samples (80% of all positive test). Conclusions: in our experience the ICGene RNA RT-LAMP kit only reliably detects very strong positives patients (Ct<25), however, statistically, these are the most infectious cases and so the most urgent to find quickly, particularly in vulnerable settings. Whereby RNA RT-LAMP could replace rRT-PCR where there is need to rapidly identify highly contagious individuals within emergency departments, ensuring results still get laboratory confirmation with highly sensitive nucleic acid amplification testing (NAAT).

Efficiency of rapid POC antigen in frontline screening for SARS-CoV-2 infection at emergency department admissionc

Background: In the emergency department (ED) setting, rapid testing for SARS-CoV-2 enables early but rationale use of limited isolation resources. The use of Antigen Point Of Care tests (POC Antigen) might be an essential tool especially for the Turn Arround Time of response, but it is necessary to clarify whether POC Antigen can be used safely specially for 'rule-out' (valid negative testing). Methods: Since September 2020, we have implemented POC antigen evaluation in nasopharyngeal (dNP) dry swab (SD Biosensor Standard F COVID-19 Ag FIA) in the first level evaluation path of the patient at ED admission. In each suspected or not suspected COVID-19 patient two sequential dNP swabs were obtained for RTPCR viral tests and for POC Antigen. All the results were retrospectively assessed for the performance, in comparison to the RT-PCR (Cepheid Xpert Xpress SARSCoV-2 and Altona RealStar® SARS-CoV-2 RT-PCR), in terms of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: We included n = 3645 patients from the ED. The sensitivity of the POC Antigen was 73.0 (95%CI: 66.6/78.5)% and the specificity was 97.2 (95%CI: 96.6/97.7)% with a SARSCoV-2 prevalence of 5.8%;the PPV was 61.8 (95%CI: 55.7/67.7)% and NPV 98.3 (95%CI: 97.8/98.7)%. Thus, n = 57 patients showed false negative POC Antigen results and n = 85 false positive POC Antigen. All positive POC Antigen were quickly confirmed. All the false negative POC Antigen results were tested with high productivity tool. The performance of the POC Antigen was compared with a cut-off threshold cycle (Ct) value of RT-PCR. In patients with Ct values η32, the sensitivity was 79.8 (95%CI: 73.6/84.8)% and the (NPV) 98.8 (95%CI: 98.4/99.2)%. In patients with Ct values η28, the sensitivity was 88.5 (95%CI: 82.9/92.4)% and the (NPV) 99.4 (95%CI: 99.1/99.6)%. In patients with Ct values η25, the sensitivity was 98.1 (95%CI: 94.5/99.3)% and the (NPV) 99.9 (95%CI: 99.7/100)%. Conclusions: We conclude that the use of POC Antigen allowed a rapid classification and an early identification of COVID-19 Infection. In asymptomatic patients, the use of the antigen ensured a low risk of transmission of the infection, being rarely associated to low CT values, index of high viral load.

Identification of Soft Tissue-Mimicking Materials and Application in the Characterization of Sensors for Lung Sounds

Early diagnosis of pulmonary implications is fundamental for the treatment of several diseases, such as idiopathic pulmonary fibrosis, rheumatoid arthritis, connective tissue diseases and interstitial pneumonia secondary to COVID-19 among the many. Recent studies prove that a wide class of pulmonary diseases can be early detected by auscultation and suitably developed algorithms for the analysis of lung sounds. Indeed, the technical characteristics of sensors have an impact on the quality of the acquired lung sounds. The availability of a fair and quantitative approach to sensors’comparison is a prerequisite for the development of new diagnostic tools. In this work the problem of a fair comparison between sensors for lung sounds is decoupled into two steps. The first part of this study is devoted to the identification of a synthetic material capable of mimicking the acoustic behavior of human soft tissues;this material is then adopted as a reference. In the second part, the standard skin is exploited to quantitatively compare several types of sensors in terms of noise floor and sensitivity. The proposed methodology leads to reproducible results and allows to consider sensors of different nature, e.g. laryngophone, electret microphone, digital MEMS microphone, mechanical phonendoscope and electronic phonendoscope. Finally, the experimental results are interpreted under the new perspective of equivalent sensitivity and some important guidelines for the design of new sensors are provided. These guidelines could represent the starting point for improving the devices for acquisition of lung sounds. IEEE

16S rRNA gene sequencing of rectal swab in patients affected by COVID-19

COronaVIrus Disease-2019 (COVID-19) is a pandemic respiratory infection caused by a new betacoronavirus, the Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2). Few data are reported on the gut microbiota in COVID-19 patients. 16S rRNA gene sequencing was performed to reveal an altered composition of the gut microbiota in patients with COVID-19 pneumonia admitted in intensive care unit (ICU) (i-COVID19), or in infectious disease wards (w-COVID19) as compared to controls (CTRL). i-COVID19 patients showed a decrease of Chao1 index as compared to CTRL and w-COVID19 patients indicating that patients in ICU displayed a lower microbial richness while no change was observed as for Shannon Index. At the phylum level, an increase of Proteobacteria was detected in w-COVID19 patients as compared to CTRL. A decrease of Fusobacteria and Spirochetes has been found, with the latter decreased in i-COVID19 patients as compared to CTRL. Significant changes in gut microbial communities in patients with COVID-19 pneumonia with different disease severity compared to CTRL have been identified. Our preliminary data may provide valuable information and promising biomarkers for the diagnosis of the disease and, when validated in larger cohort, it could facilitate the stratification of patients based on the microbial signature.

Real-world implementation and adaptation to local settings of first trimester preeclampsia screening in Italy: A systematic review

Background: Preeclampsia (PE) is a multisystem disease of pregnancy representing a major cause of maternal and perinatal morbidity and mortality. Early identification of pregnancies at risk of developing PE is crucial for implementing preventive strategies. The effectiveness of PE screening in the first trimester is widely recognized and endorsed by several guidelines, but unfortunately real-world implementation of this practice within local settings remains difficult. Methods: We performed a systematic review of the literature to understand the critical issues hampering the implementation of PE screening procedures in Italy. All studies on first trimester PE screening in the Italian population were eligible for inclusion. Key-concepts relevant for implementation of PE screening in Italy were extracted and analysed qualitatively. Results: Nine articles were selected and included. Lack of evidence concerning the topic of PE screening in Italy was shown. Major critical issues found encompassed healthcare personnel education, training of sonographers, economic coverage for biochemical markers and adjustment of algorithms based on population characteristics. Conclusions: Identification and adaptation of specific protocols to local settings and population characteristics is critical for successful implementation of early PE screening in Italy. This process has the potential to improve pregnancy outcomes and to save valuable health-care resources, particularly scarce in the COVID-19 era. There is an urgent need for research studies on specific local populations focussing on subtle details capable of maximizing PE screening uptake. This action will likely potentiate PE screening implementation reducing the burden and the cost of perinatal and maternal complications.

Transient plasma cell dyscrasia in COVID-19 patients linked to IL-6 triggering.

An unusual clonal gammopathy was reported in COVID-19 patient but whether this anomaly is related or not to the disease has not yet been clarified. To this aim, we selected a cohort of 35 COVID-19 patients swab positive and investigated serological levels of IL-6, immune response to major viral antigens and electrophoretic profile. Elevated levels of IL-6 were accompanied by a significative humoral response to viral Spike protein, revealing an altered electrophoretic profile in the gamma region. We can conclude that elevated levels of IL-6 triggers humoral response inducing a transient plasma cell dyscrasia in severe COVID-19 patients.