Escalating SARS-CoV-2 specific humoral immune response in rheumatoid arthritis patients and healthy controls.

Background: Immunocompromised patients are at particular risk of Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection and previous findings suggest that the infection or vaccination induced immune response decreases over time. Our main goal was to investigate the SARS-CoV-2-specific immune response in rheumatoid arthritis patients and healthy controls over prolonged time. Methods: The SARS-CoV-2-specific humoral immune response was measured by Elecsys Anti-SARS-CoV-2 Spike (S) immunoassay, and antibodies against SARS-CoV-2 nucleocapsid protein (NCP) were also evaluated by Euroimmun enzyme-linked immunosorbent assay (ELISA) test. The SARS-CoV-2-specific T-cell response was detected by an IFN- γ release assay. Results: We prospectively enrolled 84 patients diagnosed with rheumatoid arthritis (RA) and 43 healthy controls in our longitudinal study. Our findings demonstrate that RA patients had significantly lower anti-S antibody response and reduced SARS-CoV-2-specific T-cell response compared to healthy controls (p<0.01 for healthy controls, p<0.001 for RA patients). Furthermore, our results present evidence of a notable increase in the SARS-CoV-2-specific humoral immune response during the follow-up period in both study groups (p<0.05 for healthy volunteers, p<0.0001 for RA patients, rank-sum test). Participants who were vaccinated against Coronavirus disease-19 (COVID-19) during the interim period had 2.72 (CI 95%: 1.25-5.95, p<0.05) times higher anti-S levels compared to those who were not vaccinated during this period. Additionally, individuals with a confirmed SARS-CoV-2 infection exhibited 2.1 times higher (CI 95%: 1.31-3.37, p<0.01) anti-S levels compared to those who were not infected during the interim period. It is worth noting that patients treated with targeted therapy had 52% (CI 95%: 0.25-0.94, p<0.05) lower anti-S levels compared to matched patients who did not receive targeted therapy. Concerning the SARS-CoV-2-specific T-cell response, our findings revealed that its level had not changed substantially in the study groups. Conclusion: Our present data revealed that the level of SARS-CoV-2-specific humoral immune response is actually higher, and the SARS-CoV-2-specific T-cell response remained at the same level over time in both study groups. This heightened humoral response, the nearly permanent SARS-CoV-2-specific T-cell response and the coexistence of different SARS-CoV-2 variants within the population, might be contributing to the decline in severe COVID-19 cases.

To treat or not to treat rheumatoid arthritis with glucocorticoids? A reheated debate.

The therapeutic landscape of rheumatoid arthritis (RA) has rapidly evolved in the last few decades. At the same time, recommendations for the management of the disease suggest to minimize glucocorticoids (GCs) use in RA patients. Major concerns are the risk of long-term adverse events and the difficulties in discontinuing GCs once initiated. However, real-world data show that up to 50% of RA patients continue to take GCs during the disease course. Adverse events of GCs usually occur after a long-term use, which can limit the generalizability of randomized controlled trials (RCTs) proving no or minimal harm. Observational studies show conflicting results regarding the safety of GSs and are subjected to a high risk of bias, including indication bias. Thus, whether or not GCs should be used in the management of RA is still a matter of debate. The main reasons to support GCs use are the ability to rapidly suppress joint inflammation while waiting for the full effect of conventional synthetic disease-modifying antirheumatic drugs (csDMARD) and the acknowledged efficacy on radiographic progression in early RA. The main reasons to avoid GCs use in RA are that their potential risks may outweigh their benefits and there is no agreement on the minimal daily dosage of GC which can be considered safe.

[Investigation of visuospatial memory in obsessive-compulsive disorder using the Rey-Osterrieth Complex Figure Test].

Based on previous results the cognitive profile of patients with obsessive-compulsive disorder (OCD) is determined by the impairment of executive and visual-spatial memory functions. The Rey-Osterrieth Complex Figure (ROCF) is a widely used tool for examining visual-spatial memory disorders. Several scoring systems can be used to evaluate the ROCF and the most widespread is the original Osterrieth evaluation system. The Boston Qualitative Scoring System (BQSS) is a new, much more detailed scoring system than the Osterrieth, which allows both quantitative and a more detailed qualitative analysis of ROCF. In our study, we analyzed the copying and immediate recall performance of 24 OCD and 24 age- and education-matched healthy control subjects using the Osterrieth and BQSS scoring systems. Our research had two main goals, (1) to examine the diff erences in visualspatial memory performance shown by the OCD group compared to the control group, and (2) to compare the Osterrieth and BQSS scoring systems in one clinical sample. Based on both the Osterrieth and BQSS scoring systems, our results show that the OCD group performed significantly worse in the recall phase, but not in the copy phase. According to our results both scoring systems can be effectively used to examine the functioning of visual-spatial memory in OCD patients. While the Osterrieth evaluation system is faster and more widespread, the BQSS scoring system examines detailed qualitative aspects in addition to quantitative indicators.

Addition of epidermal growth factor receptor inhibitors to standard chemotherapy increases survival of advanced head and neck squamous cell carcinoma patients: A systematic review and meta-analysis.

Head and neck squamous cell carcinoma (HNSCC) is among the common tumors associated with high mortality. The aim of our meta-analysis was to determine how additional anti-epidermal growth factor receptor (EGFR) therapy to standard chemotherapy affects the progression-free (PFS) and overall survival (OS) of the patients, besides the most common side effects. We used CENTRAL, MEDLINE, and Embase databases until October 26, 2020, and included 13 eligible randomized controlled trials in our systematic research. The pooled hazard ratios (HR) for the main outcomes from the original data were estimated and for the other dichotomous outcomes, odds ratios (ORs) with their 95% confidence intervals (CI) were calculated. Addition of EGFR inhibitors to conventional chemotherapy significantly decreased the death and disease progression (for PFS HR: 0.68, 95% CI: 0.55-0.81, I2  = 65.5%, p = 0.005) and mortality (for OS HR: 0.83, 95% CI: 0.72-0.94, I2  = 42.3%, p = 0.076). In the EGFR inhibitor group, we revealed an increased chance of the over Grade 3 skin rashes (OR: 4.86; 95% CI: 1.52-15.49, I2  = 2.3%, p = 0.407), and all Grade skin rashes (OR: 18.32, 95% CI: 8.07-41.60, I2  = 56.6%, p = 0.032). Despite their unwanted dermatological side effects, the addition of EGFR inhibitors is recommended to be included in advanced HNSCC therapy.

Janus Kinase Inhibitors Improve Disease Activity and Patient-Reported Outcomes in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of 24,135 Patients.

Pain, fatigue, and physical activity are major determinants of life quality in rheumatoid arthritis (RA). Janus kinase (JAK) inhibitors have emerged as effective medications in RA and have been reported to exert direct analgesic effect in addition to reducing joint inflammation. This analysis aims to give an extensive summary of JAK inhibitors especially focusing on pain and patient reported outcomes (PRO). MEDLINE, CENTRAL, Embase, Scopus, and Web of Science databases were searched on the 26 October 2020, and 50 randomized controlled trials including 24,135 adult patients with active RA met the inclusion criteria. JAK inhibitors yielded significantly better results in all 36 outcomes compared to placebo. JAK monotherapy proved to be more effective than methotrexate in 9 out of 11 efficacy outcomes. In comparison to biological disease-modifying antirheumatic drugs, JAK inhibitors show statistical superiority in 13 of the 19 efficacy outcomes. Analgesic effect determined using the visual analogue scale and American College of Rheumatology (ACR) 20/50/70 response rates was significantly greater in the JAK group in all comparisons, and no significant difference regarding safety could be explored. This meta-analysis gives a comprehensive overview of JAK inhibitors and provides evidence for their superiority in improving PROs and disease activity indices in RA.

Differences in the serum metabolome and lipidome identify potential biomarkers for seronegative rheumatoid arthritis versus psoriatic arthritis.

OBJECTIVES: The differential diagnosis of seronegative rheumatoid arthritis (negRA) and psoriasis arthritis (PsA) is often difficult due to the similarity of symptoms and the unavailability of reliable clinical markers. Since chronic inflammation induces major changes in the serum metabolome and lipidome, we tested whether differences in serum metabolites and lipids could aid in improving the differential diagnosis of these diseases. METHODS: Sera from negRA and PsA patients with established diagnosis were collected to build a biomarker-discovery cohort and a blinded validation cohort. Samples were analysed by proton nuclear magnetic resonance. Metabolite concentrations were calculated from the spectra and used to select the variables to build a multivariate diagnostic model. RESULTS: Univariate analysis demonstrated differences in serological concentrations of amino acids: alanine, threonine, leucine, phenylalanine and valine; organic compounds: acetate, creatine, lactate and choline; and lipid ratios L3/L1, L5/L1 and L6/L1, but yielded area under the curve (AUC) values lower than 70%, indicating poor specificity and sensitivity. A multivariate diagnostic model that included age, gender, the concentrations of alanine, succinate and creatine phosphate and the lipid ratios L2/L1, L5/L1 and L6/L1 improved the sensitivity and specificity of the diagnosis with an AUC of 84.5%. Using this biomarker model, 71% of patients from a blinded validation cohort were correctly classified. CONCLUSIONS: PsA and negRA have distinct serum metabolomic and lipidomic signatures that can be used as biomarkers to discriminate between them. After validation in larger multiethnic cohorts this diagnostic model may become a valuable tool for a definite diagnosis of negRA or PsA patients.

Integrating functional MRI information into conventional 3D radiotherapy planning of CNS tumors. Is it worth it?

The purpose of our study was to examine the potential benefits of integrating functional MRI (fMRI) information into the 3D-based planning process for central nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2009, ten patients with astrocytoma (both low and high-grade histological type) were enrolled in this study. Before the planning process, conventional CT planning, postoperative MR, and individual functional MRI examinations were conducted. For the functional MRI examination four types of conventional stimuli were applied: acoustic, visual, somatosensory, and numeric. To examine the potential benefits of using fMRI-based information, three different types of theoretical planning were applied and compared: 3D conformal plan without fMRI information, 3D conformal plan with fMRI information, and IMRT plan with fMRI information. DVH analysis and the NTCP model were used for plan comparison. When comparing planning methods, distance-related subgroups were generated and studied. By using the additional fMRI information, a significantly higher sparing effect can be achieved on these ORs (both with conventional 3D-based planning and IMRT). In cases when the OR-PTV distance is less than 1 cm, IMRT seems to be a significantly better choice than conventional 3D-based techniques. IMRT also has an additional sparing effect on the optic tract and brainstem, especially for locations close to the midline. Our results demonstrated that using fMRI information in conventional 3D-based treatment planning has the potential benefit of significant dose reduction for the critical organs, with no compromise in PTV coverage even when using conventional 3D planning. fMRI can be widely used in low-grade cases (long life expectancy, lower acute and late toxicity) and also in cases with high-grade astrocytomas or distant metastases (higher dose to PTV with better sparing of risk organs). In cases when the OR-PTV distance is less than 1 cm, IMRT should be the choice of treatment for a higher sparing effect on functional active areas. Longer imaging and clinical follow up are needed to confirm the real sparing effect on these functional areas.

Integrating functional MRI information into radiotherapy planning of CNS tumors-early experiences.

The purpose of our study was to examine the integration of functional MRI (fMRI) information into 3D based planning process of the central nervous system (CNS) malignancies. Between 01.01.2008 and 01.12.2008 four patients with astrocytoma were enrolled to this study. Before the planning process conventional planning CT, postoperative MR and individual functional MRI examinations were delivered. For the functional MRI examination the following four types of stimulus were applied: acoustic, visual, somatosensory and numeral. Three different theoretical planning situations were applied and compared: 3D conformal plan without fMRI information, 3D conformal plan with fMRI information and IMRT plan with fMRI information. For plan comparison DVH analysis, and NTCP model were used. fMRI based OR definition resulted in 4 additional OR's in the contouring process. As these cases demonstrate, an average of 50% dose reduction was achieved in OR, OR2 and OR3 with IMRT and fMRI based 3D planning, especially in case of midline localization and big tumor extent. IMRT provides additional sparing effect in the optic tract and brainstem, especially for localizations close to the midline. Our results demonstrated that using fMRI information in conventional 3D based treatment planning potentially benefits significant dose reduction in critical organs, with no compromise in PTV coverage. fMRI can be widely used even in low grade cases (long life expectancies, lower acute and late toxicity in radiotherapy) and in cases with high grade astrocytomas or metastases (higher dose to PTV with better risk organ sparing in radiotherapy).

Atrophy and decreased activation of fronto-parietal attention areas contribute to higher visual dysfunction in posterior cortical atrophy.

Voxel-based morphometry and functional magnetic resonance imaging demonstrated severe atrophy and decreased activation of visual attention areas and occipital lobes in a patient with early posterior cortical atrophy compared with healthy controls and patients with early Alzheimer's disease. Our complex approach indicates that structures responsible for attention can be damaged early in posterior cortical atrophy and may contribute to the characteristic decline in higher visual functions.