•The first WHO International standard (20/136) helped in the harmonization process.•The values expressed as BAU/mL confirmed a reduction in results’variability.•The harmonization data are very good ...within antigens and isotypes.•The individual immune monitoring should be performed using the same method.
SARS-CoV-2 antibody assays are relevant in managing the COVID-19 pandemic, providing valuable data on the immunization status of the population. However, current serology tests are highly variable, due to their different characteristics and to the lack of reference materials. The aim of the World Health Organization (WHO) first International Standard (IS) for anti-SARS-CoV-2 immunoglobulin is to harmonize humoral immune response assessment after natural infection or vaccination, and recommend reporting the results for binding activity in Binding Antibody Units (BAU).
This study analyzed six commercial quantitative anti-SARS-CoV-2 S-protein assays in a head-to-head comparison, using the manufacturers' conversion factors for the WHO IS to obtain BAU/mL values.
Our data showed good alignment up to 1000 BAU/mL, then began to disperse, exhibiting some discrepancies. Moreover, correlations among methods varied with Cohen’s Kappa ranging from 0.580 to 1.00, with the lowest agreement values for kits using different target antigens or different antibody isotypes, making it clear that the laboratory report should include this information. Values expressed as BAU/ml showed a reduced between-assays variability compared to AU/ml (median coefficients of variation 0.38 and 0.68, respectively; p < 0.001).
On the basis of these data at present anti-SARS CoV-2 serological assays’ results are not interchangeable, and, more importantly, individual immune monitoring should be performed with the same method.
During coronavirus disease 2019 (COVID‐19) pandemic, the early diagnosis of patients is a priority. Serological assays, in particular immunoglobulin (Ig)M and IgG anti‐severe acute respiratory ...syndrome coronavirus 2 (SARS‐CoV‐2), have today several applications but the interpretation of their results remains an open challenge. Given the emerging role of the IgA isotype in the COVID‐19 diagnostics, we aimed to identify the SARS‐CoV‐2 IgA antibodies in a COVID‐19 population seronegative for IgM. A total of 30 patients hospitalized in San Giovanni di Dio Hospital (Florence, Italy) for COVID‐19, seronegative for IgM antibodies, have been studied for anti‐SARS‐CoV‐2 antibodies. They all had a positive oro/nasopharyngeal swab reverse transcription‐polymerase chain reaction result. Assays used were a chemiluminescent assay measuring SARS‐CoV‐2 specific IgM and IgG (S + N) and an ELISA, measuring specific IgG (S1) and IgA antibodies against SARS‐CoV‐2. Among the 30 patients, eight were positive for IgA, seven were positive for IgG (N + S), and two for IgG (S1), at the first point (5‐7 days from the onset of symptoms). The IgA antibodies mean values at the second (9‐13 days) and third (21‐25 days) time points were even more than twice as high as IgG assays. The agreement between the two IgG assays was moderate (Cohen's K = 0.59; SE = 0.13). The inclusion of the IgA antibodies determination among serological tests of the COVID‐19 diagnostic is recommended. IgA antibodies may help to close the serological gap of the COVID‐19. Variations among anti‐SARS‐CoV‐2 IgG assays should be considered in the interpretation of results.
Highlights
The inclusion of SARS‐CoV‐2 IgA antibodies may increase the diagnostic sensitivity of the serological tests for COVID‐19
The early appearance and high concentrations of SARS‐CoV‐2 IgA antibodies make them good potential markers for identifying COVID‐19 patients.
Variations of anti‐SARS‐CoV‐2 IgG assays exist.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates pro-thrombotic changes. This, combined with its tropism for endothelium and lung structures, may explain its association with ...thrombotic events, reduction of pulmonary gas exchange, acute respiratory distress syndrome (ARDS) and a composite end-point (intensive care unit, invasive ventilation, death). This study aims to highlight the correlation between elevated D-dimer (an indirect thrombosis marker) and the increased rate of poor prognosis-associated conditions, and to introduce D-dimer-labelled anticoagulant administration as a potentially useful tool to prevent complications and positively influence coronavirus disease 2019 (COVID-19) course.
An online database search (PubMed, Google Scholar, Scopus, Web of Science and Cochrane) was performed between 13 March and 10 April 2020. The most relevant keywords were "D-dimer", "SARS-CoV-2", "COVID-19", "thrombosis" and "ARDS". Selection was independently conducted by three reviewers. References and previews of accepted articles were evaluated. Data inclusion/extraction inaccuracy was limited by the work of three reviewers. Selection bias reduction was addressed by thoughtfully designing the search protocol. Quality assessment was performed with the Newcastle-Ottawa Scale. The systematic review protocol was not registered because we anticipated the very limited available evidence on the topic and due to the urgency of the study.
16 studies were evaluated. Good-quality criteria were reached in 13 out of 16 studies. D-dimer was increased and significantly higher in COVID-19 patients compared with healthy controls, in COVID-19 patients with severe disease or a composite end-point compared with non-severe disease, in ARDS compared with non-ARDS patients and in deceased ARDS patients compared with ARDS patients who survived (all p<0.001). COVID-19 patients treated with anticoagulants demonstrated lower mortality compared with those not treated (p=0.017).
Correlations exist between COVID-19 infection, severe elevation of D-dimer levels, and increase in the rate of complications and composite end-point. The appropriateness of early and continuous D-dimer monitoring and labelled anticoagulation as management tools for COVID-19 disease deserves accurate investigation, to prevent complications and reduce interventions.
The "cognitive reserve" (CR) theory posits that higher premorbid cognitive activities can mitigate the effects of brain damage. This study aimed to investigate the association between CR and ...long-term functional autonomy in patients surviving a severe traumatic brain injury (sTBI).
Data were collected from the database of inpatients with severe acquired brain injury in a rehabilitation unit admitted from August 2012 to May 2020.
Patients that had incurred an sTBI, aged 18+ years, completing the phone Glasgow Outcome Scale-Expanded at follow-up (pGOS-E) in absence of previous brain trauma or neurological disease, or cognitive disorders were included. Patients with severe brain injury from non-traumatic etiologies were not included in the study.
In this longitudinal study, all patients underwent a multidimensional assessment including the cognitive reserve index questionnaire (CRIq), the coma recovery scale-revised, the level of cognitive functioning, the Disability Rating Scale (DRS), and the Galveston Orientation and Amnesia Test at admission. At discharge, functional scales were administered again together with the Glasgow Outcome Scale. The pGOS-E was assessed at follow-up.
pGOS-E.
A total of 106 patients/caregivers underwent the pGOS-E after 5.8 3.6 years from the event. Among them, 46 (43.4%) died after discharge, and 60 patients men: 48 (80%); median age: 54 years; median time post-onset: 37 days; median education level: 10 years; median CRIq total score: 91 were included in the analysis exploring the association between pGOS-E and demographic data, cognitive reserve surrogates, and clinical variables at admission and discharge from the rehabilitation unit. A younger age (
= -0.035,
= 0.004) and a lower DRS category at discharge (
= -0.392,
= 0.029) were significantly related to a higher long-term functional autonomy in the multivariate analysis.
Long-term functional autonomy was not influenced by CR as assessed through the educational level and the CRIq.
Intensive treadmill training (TT) has been documented to improve gait parameters and functional independence in Parkinson's Disease (PD), but the optimal intervention protocol and the criteria for ...tailoring the intervention to patients' performances are lacking. TT may be integrated with augmented virtual reality (AVR), however, evidence of the effectiveness of this combined treatment is still limited. Moreover, prognostic biomarkers of rehabilitation, potentially useful to customize the treatment, are currently missing. The primary aim of this study is to compare the effects on gait performances of TT + AVR versus TT alone in II-III stage PD patients with gait disturbance. Secondary aims are to assess the effects on balance, gait parameters and other motor and non-motor symptoms, and patient's satisfaction and adherence to the treatment. As an exploratory aim, the study attempts to identify biomarkers of neuroplasticity detecting changes in Neurofilament Light Chain concentration T0-T1 and to identify prognostic biomarkers associated to blood-derived Extracellular Vesicles.
Single-center, randomized controlled single-blind trial comparing TT + AVR vs. TT in II-III stage PD patients with gait disturbances. Assessment will be performed at baseline (T0), end of training (T1), 3 (T2) and 6 months (T3, phone interview) from T1. The primary outcome is difference in gait performance assessed with the Tinetti Performance-Oriented Mobility Assessment gait scale at T1. Secondary outcomes are differences in gait performance at T2, in balance and spatial-temporal gait parameters at T1 and T2, patients' satisfaction and adherence. Changes in falls, functional mobility, functional autonomy, cognition, mood, and quality of life will be also assessed at different timepoints. The G*Power software was used to estimate a sample size of 20 subjects per group (power 0.95,
< 0.05), raised to 24 per group to compensate for potential drop-outs. Both interventions will be customized and progressive, based on the participant's performance, according to a predefined protocol.
This study will provide data on the possible superiority of AVR-associated TT over conventional TT in improving gait and other motor and non-motor symptoms in persons with PD and gait disturbances. Results of the exploratory analysis could add information in the field of biomarker research in PD rehabilitation.
Preliminary evidence in the literature suggests a high prevalence of malnutrition (undernutrition) in patients with severe acquired brain injuries (sABI), with an expected negative impact on clinical ...outcomes and pressure ulcers (PUs) in particular. In a retrospective cohort study on patients discharged from intensive care units (ICU) and admitted to an intensive rehabilitation unit (IRU), the risk of malnutrition was systematically assessed, in addition to standard clinical procedures (including PUs evaluation), using two different tools: the Malnutrition Universal Screening Tool (MUST) and the Controlling Nutritional Status (CONUT) tool. Eighty-eight patients were included in the analysis. A high proportion (79.5%) of patients with sABI suffered from PUs, being older and more frequently men, with a longer ICU stay between the event and admission to IRU, and a greater MUST score. At discharge, when compared to patients whose PUs had healed, those with persisting PUs were more often men and had the worst cognitive performance at admission. As for nutritional risk, the baseline CONUT score was identified as an independent negative predictor of PUs at discharge by the logistic regression model. In conclusion, the assessment of nutritional risk using simple standard tools may be useful in the clinical evaluation of sABI patients with PUs.
Purpose
Visual unilateral spatial neglect (VUSN) is a neuropsychological condition commonly experienced after stroke whereby patients are unable to attend to stimuli on the controlesional side of ...their space. VUSN can occur in the personal, peripersonal, and/or extrapersonal portion of patient’s space. Traditional paper-and-pencil neuropsychological tests are widely used to evaluate VUSN, but they assess peripersonal VUSN. Instead, personal and extrapersonal neglect are less easily evaluated. The aim of this study was to present normative values for the Visual Scanning Test (VST), a new neuropsychological tool to quantitatively assess the extrapersonal VUSN.
Methods
Eighty-six healthy subjects took part in the study (61 female), with a mean age of 52.8 years (SD = 17.0) and a mean of 14.0 years of education (SD = 5.2). The VST involved a visual search for a target between similar visual distractors, projected in the far space. The test was administered twice to each participant, with an interval of 2 weeks. From the recorded data, it was possible to obtain indexes related to the reaction times and to the accuracy of the performance on the VST.
Results
Multiple linear regression analysis revealed that age and education significantly influenced VST-derived indexes. From the regression analysis, a correction grid for raw scores was built. Adjusted scores were then ranked, and by means of a non-parametric procedure, tolerance limits (both outer and inner one-sided) were defined.
Conclusions
The present study provided normative data for the VST in an Italian population useful for both clinical and research purposes.
Trial registration
ClinicalTrials.gov
ID: NCT03931798
Despite progress in surgery and care, hip fracture (HF) remains a catastrophic event, burdened with high risk of mortality and disability. This study aims at identifying predictors of recovering ...ambulation after intensive inpatient rehabilitation within the Tuscany Region HF rehabilitation pathway.
All HF patients referred from acute care to the two Massa-Carrara Rehabilitation facilities January 2015-June 2017 were enrolled. Comorbidity Total Score (CIRS) defined high- or low-care setting referral. Recovery of ambulation, with or without aid, (assessed by SAHFE) was the primary outcome. Personal data, comorbidity, cognitive (MMSe) and pre-fracture function (mRANKIN) were recorded on admission. Outcomes included hospital readmission, length of stay (LOS) and home discharge. Urinary catheter, bedsores, disability (modified Barthel Index-mBI), communication disability (CDS), trunk control (TCT), pain (NRS), and ambulation were recorded (admission-discharge).
Of 352 patients enrolled (age 83.9 ± 7.1; 80% women), 1 died and 6 were readmitted to acute-care hospital; 97% patients referred to high-care, and 64% referred to low-care, presented moderate-high comorbidity on admission. Median LOS was 22 days; 95% patients were discharged back home; daily functional gain (mBIscore/LOS) was 1.3 ± 0.7. Patients who recovered ambulation on discharge were 84%. Older age, higher comorbidity, bladder catheter, impaired trunk control, worse cognitive and functional status on admission, and pre-fracture disability were associated to poor outcome, but only higher comorbidity and impaired communication on admission predicted failure to recover ambulation on discharge.
In HF patients entitled to intensive inpatient rehabilitation, moderate-high comorbidity and impaired communication are frequent findings and predict rehabilitation failure.
Objective
to identify the predictors of mortality in a cohort of nonagenarians inside the “Mugello study” after 10 years follow-up.
Methods
Information on sociodemographic data, cognitive and ...functional status, lifestyle, medical history, and drug use was collected from 433 non-selected participants aged 90-99 years, living in the Mugello area (Italy). Participants were followed over 10 years and their dates of death were retrieved from the municipal registers. Cox regression analysis was used to determine significant potential prognostic factors.
Results
The mortality rate was 96.5%. Cox proportional hazards analysis showed that a lower cognitive status was significantly associated with higher mortality as well as a poorer functional status, a higher comorbidity, and a higher number of drugs consumption.
Discussion
Impaired cognitive function, loss of functional independence, higher comorbidity, and higher drugs intake were the stronger predictors of mortality.
Life expectancy has increased over the last century and a growing number of people is reaching age 90 years and over. However, data on nonagenarians' health trends are scarce due to difficulties in ...investigating this specific population. This study aims to identify risk factors for one-year mortality in nonagenarians using data collected within the "Mugello Study".
Complete information on sociodemographic data, cognitive and functional status, lifestyle, medical history, and drug use was collected from 433 nonagenarians, as well as information about survival after 1 year from the interview.
The sample included 314 women (72.5%) and 119 men (27.5%) with a median age of 92 years (range 90-99 years). The mortality rate was 20.3% (88 deaths). After adjustment for age and sex, a significantly higher risk of dying within 12 months was observed in individuals with more severe cognitive impairment (HR = 5.011, p < 0.001), more severe disability in basic activities of daily living (HR = 4.193, p < 0.001), sedentary lifestyle (HR = 3.367, p < 0.001), higher number of drugs assumed (HR = 1.118, p = 0.031), and kidney dysfunction (HR = 2.609, p = 0.004). When all the variables were included in the analysis, only older age (HR = 1.079, p = 0.048), lower cognitive function (HR = 2.859, p = 0.015), sedentary lifestyle (HR = 2.030, p = 0.026), and kidney dysfunction (HR = 2.322, p = 0.018) remained significantly associated with reduced survival.
Data from the Mugello study support the hypothesis that survival at 12 months in nonagenarians is not a stochastic process and that older age, reduced cognitive function, sedentary lifestyle, and the presence of kidney dysfunction are associated with mortality.
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