Seroprevalence of neuronal antibodies in diseases mimicking autoimmune encephalitis.

Detection of neuronal antibodies for autoimmune encephalitis and paraneoplastic neurological syndromes relies on commercially available cell-based assays and lineblots. However, lineblots may reveal the presence of neuronal antibodies in patients with various non-autoimmune etiologies. Herein we describe patients with non-autoimmune etiologies (cohort B) and detectable neuronal antibodies and compare them to definite cases of autoimmune encephalitis (cohort A) for differences in clinical data. All patients positive for at least one neuronal antibody were retrospectively evaluated for autoimmune encephalitis and/or paraneoplastic neurological syndrome between 2016 and 2022. 39 cases in cohort B and 23 in cohort A were identified. In cohort B, most common diagnoses were neurodegenerative disorders in 9/39 (23.1%), brain tumors in 6/39 (15.4%) while most common detected antibodies were anti-titin (N10), anti-recoverin (N11), anti-Yo (N8) and all were detected in serum only. Differential aspects between cohort A and B were CSF pleocytosis (14/23 (60.8%) vs 11/35 (31.4%), p = 0.042, respectively), MRI features suggestive of encephalitis (6/23 (26.1%) vs 0 (0%), p = 0.002, respectively) and epilepsy restricted to temporal lobes (14/23 (60.9%) vs 2/30 (6.7%), p = 0.0003, respectively). A large proportion of lineblot results were non-specific when only serum was tested and were frequently found in non-autoimmune neurological conditions.

Association between PYTPN22 rs2476601, VEGF rs833070, TNFAIP3 rs6920220 Polymorphisms and Risk for Rheumatoid Arthritis in Early Undifferentiated Arthritis Patients: A Pilot Study.

Background and Objectives: About 40% of early undifferentiated arthritis (UA) progresses to rheumatoid (RA) or other chronic arthritis. Novel diagnostic tools predicting the risk for this progression are needed to identify the patients who would benefit from early aggressive treatment. Evidence on the role of single-nucleotide polymorphisms (SNPs) in the development of RA has emerged. The aim of our study was to investigate the association between rs2476601, rs833070, and rs6920220 SNPs and UA progression to RA. Materials and Methods: Ninety-two UA patients were observed for 12 months. At study entry, demographic and clinical characteristics were recorded, musculoskeletal ultrasonography was performed, and blood samples were drawn to investigate levels of inflammatory markers, rheumatoid factor (RF), anti-citrullinated protein antibodies (anti-CCP)detect SNPs. After 12 months, UA outcomes were assessed, and patients were divided into two (RA and non-RA) groups. The association between the risk of progression to chronic inflammatory arthritis and analyzed SNPs was measured by computing odds ratios (OR). Results: After a 12-month follow-up, 27 (29.3%) patients developed RA, and 65 (70.7%) patients were assigned to the non-RA group. The arthritis of 21 patients (22.8%) from the non-RA group resolved completely, while the other 44 (47.2%) patients were diagnosed with another rheumatic inflammatory disease. The patients who developed RA had a significantly greater number of tender and swollen joints (p = 0.010 and p = 0.021 respectively) and were more frequently RF or anti-CCP (p < 0.001), and both RF and anti-CCP positive (p < 0.001) at the baseline as compared with the patients in the non-RA group. No significant association between rs2476601 (OR = 0.99, p = 0.98), rs833070 (OR = 1.0, p = 0.97), and rs6920220 (OR = 0.48, p = 0.13) polymorphisms and the risk of developing RA were found. Conclusions: No association between analyzed SNPs and a greater risk to progress from UA to RA was confirmed, although patients with rs6920220 AA + AG genotypes had fewer tender joints at the disease onset.

Soluble CD146 in the detection and grading of intravascular and tissue congestion in patients with acute dyspnoea: analysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort.

OBJECTIVES: To evaluate the potential of soluble cluster of differentiation 146 (sCD146) in the detection and grading of congestion in patients with acute dyspnoea. DESIGN: Subanalysis of the prospective observational Lithuanian Echocardiography Study of Dyspnoea in Acute Settings (LEDA) cohort. SETTING: Two Lithuanian university centres. PARTICIPANTS: Adult patients with acute dyspnoea admitted to the emergency department. METHODS: Congestion was assessed using clinical and sonographic parameters. All patients underwent sCD146 and N-terminal pro-B-type natriuretic peptide (NT-proBNP) testing. RESULTS: The median value of sCD146 concentration in the study cohort (n=437) was 405 (IQR 315-509) ng/mL. sCD146 was higher in patients with peripheral oedema than in those without (median (IQR) 472 (373-535) vs 400 (304-501) ng/mL, p=0.009) and with pulmonary rales than in those without (439 (335-528) vs 394 (296-484) ng/mL, p=0.001). We found a parallel increase of estimated right atrial pressure (eRAP) and sCD146 concentration: sCD146 was 337 (300-425), 404 (290-489) and 477 (363-572) ng/mL in patients with normal, moderately elevated and high eRAP, respectively (p=0.001). In patients with low NT-proBNP, high sCD146 distinguished a subgroup with a higher prevalence of oedema as compared with patients with low levels of both biomarkers (76.0% vs 41.0%, p=0.010). Moreover, high sCD146 indicated a higher prevalence of elevated eRAP, irrespective of NT-proBNP concentration (p<0.05). CONCLUSION: sCD146 concentration reflects the degree of intravascular and tissue congestion assessed by clinical and echocardiographic indices, with this association maintained in patients with low NT-proBNP. Our data support the notion that NT-proBNP might represent heart stretch while sCD146 rather represents peripheral venous congestion.

Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase Levels.

BACKGROUND In this paper we report on the link between increased tryptase levels and prevalence of allergen-specific immunoglobulin E (IgE) in patients with anaphylaxis. The main aim of the study was to assess the corelation between elevated tryptase levels and allergen-specific immunoglobulin E (IgE) in anaphylactic reactions, mastocytosis, and other types of allergic reactions. MATERIAL AND METHODS We enrolled 60 adult patients, aged 18-68 years (mean age 45±8 years). The subjects were divided into 3 groups (20 patients in each group) according to the serum tryptase changes: group 1 consisted of patients with anaphylaxis (serum tryptase level ≥11.4 µg/l), group 2 consisted of patients with mastocytosis (serum tryptase level ≥20.0 µg/l), and group 3 consisted of patients with other allergic reactions with no anaphylaxis as an atopic control group (serum tryptase level <11.4 µg/l). The test material was venous blood serum samples. The allergen-specific IgE assay was carried out by immunoblot. Tryptase concentration was determined by immunoenzymatic assay. RESULTS Allergen-specific IgE was found in 73% of all subjects: 75% in the anaphylactic group, 55% in the mastocytosis group, and 90% in the atopic control group. Polysensitization was common and was significantly different among groups. In the atopic group, there were more patients allergic to 4-7 allergens (P<0.05). CONCLUSIONS We did not find a strong correlation between allergen-specific IgE levels and elevated tryptase levels.

VEGF Profile in Early Undifferentiated Arthritis Cohort.

Background and Objectives: Early undifferentiated arthritis (UA) is a group of inflammatory joint diseases that are not classified under any specific rheumatic or connective tissue disorder and might evolve into chronic inflammatory arthritis or may be a self-limiting condition. Early recognition and treatment are crucial for the future course of the disease. Vascular endothelial growth factor (VEGF) is an angiogenic regulator that induces the growth of new capillary blood vessels, which are important in joint invasion and destruction during the progression of chronic inflammatory arthritis. The aim of this study was to assess VEGF levels associated with sociodemographic, clinical, laboratory, and ultrasound findings in the early UA patient cohort as well as to evaluate VEGF as a potential prognostic marker for arthritis outcomes. Materials and Methods: Seventy-six patients with inflammatory arthritis in at least one joint, with a duration of arthritis <12 months at the study entry that did not meet any rheumatic disease classification criteria, were enrolled after informed consent was obtained. Patient's sociodemographic, laboratory data, and clinical disease characteristics were recorded, VEGF levels were measured, and ultrasound (US) of tender and swollen joints was performed. Results: VEGF levels had positive correlation with conventional rheumatic disease activity and diagnostic markers: erythrocyte sedimentation rate (ESR), C−reactive protein (CRP), and rheumatoid factor (RF) (p < 0.05). RF-positive patients had higher VEGF values (p = 0.024). A statistically higher number of patients whose VEGF levels were below the median value presented with active infection (p = 0.046). In patients with a higher number of swollen joints, and a higher score of synovitis and power doppler (PD) seen on US, VEGF levels were statistically significantly higher. Patients who after 12-month follow-up developed rheumatoid arthritis (RA) had statistically higher VEGF levels at baseline compared with those who developed spondyloarthropathies (p = 0.028). Conclusions: This study demonstrated that VEGF levels significantly represented inflammatory processes that were present in the joints (number of swollen joints, synovitis, and PD changes) of the early UA cohort.

Biologically Active Adrenomedullin (bio-ADM) is of Potential Value in Identifying Congestion and Selecting Patients for Neurohormonal Blockade in Acute Dyspnea.

PURPOSE: This study was designed to evaluate the role of biologically active adrenomedullin (bio-ADM) in congestion assessment and risk stratification in acute dyspnea. METHODS: This is a sub-analysis of the Lithuanian Echocardiography Study of Dyspnea in Acute Settings. Congestion was assessed by means of clinical (peripheral edema, rales) and sonographic (estimated right atrial pressure) parameters. Ninety-day mortality was chosen for outcome analysis. RESULTS: There were 1188 patients included. Bio-ADM concentration was higher in patients with peripheral edema at admission (48.2 [28.2-92.6] vs 35.4 [20.9-59.2] ng/L, P < .001). There was a stepwise increase in bio-ADM concentration with increasing prevalence of rales: 29.8 [18.8-51.1], 38.5 [27.5-67.1], and 51.1 [33.1-103.2] ng/L in patients with no rales, rales covering less than one-half, and greater than or equal to one-half of the pulmonary area, respectively (P < 0.001). Bio-ADM concentration demonstrated gradual elevation in patients with normal, moderately, and severely increased estimated right atrial pressure: 25.1 [17.6-42.4] ng/L, 36.1 [23.1-50.2], and 47.1 [30.7-86.7] ng/L, respectively (P < .05). Patients with bio-ADM concentration >35.5 ng/L were at more than twofold increased risk of dying (P < .001). Survival in those with high bio-ADM was significantly modified by neurohormonal blockade at admission (P < .05), especially if NT-proBNP levels were lower than the median (P = .002 for interaction). CONCLUSION: Bio-ADM reflects the presence and the degree of pulmonary, peripheral, and intravascular volume overload and is strongly related to 90-day mortality in acute dyspnea. Patients with high bio-ADM levels demonstrated survival benefit from neurohormonal blockade.

Readmission following both cardiac and non-cardiac acute dyspnoea is associated with a striking risk of death.

AIMS: Readmission and mortality are the most common and often combined endpoints in acute heart failure (AHF) trials, but an association between these two outcomes is poorly investigated. The aim of this study was to determine whether unplanned readmission is associated with a greater subsequent risk of death in patients with acute dyspnoea due to cardiac and non-cardiac causes. METHODS AND RESULTS: Derivation cohort (1371 patients from the LEDA study) and validation cohort (1986 patients from the BASEL V study) included acute dyspnoea patients admitted to the emergency department. Cox regression analysis was used to determine the association of 6 month readmission and the risk of 1 year all-cause mortality in AHF and non-AHF patients and those readmitted due to cardiovascular and non-cardiovascular causes. In the derivation cohort, 666 (49%) of patients were readmitted at 6 months and 282 (21%) died within 1 year. Six month readmission was associated with an increased 1 year mortality risk in both the derivation cohort [adjusted hazard ratio (aHR) 3.0 (95% confidence interval, CI 2.2-4.0), P < 0.001] and the validation cohort (aHR 1.8, 95% CI 1.4-2.2, P < 0.001). The significant association was similarly observed in AHF (aHR 3.2, 95% CI 2.1-4.9, P < 0.001) and other causes of acute dyspnoea (aHR 2.9, 95% CI 1.9-4.5, P < 0.001), and it did not depend on the aetiology [aHR 2.2, 95% CI 1.6-3.1 for cardiovascular readmissions; aHR 4.1, 95% CI 2.9-5.7 for non-cardiovascular readmissions (P < 0.001 for both)] or timing of readmission. CONCLUSION​S: Our study demonstrated a long-lasting detrimental association between readmission and death in AHF and non-AHF patients with acute dyspnoea. These patients should be considered 'vulnerable patients' that require personalized follow-up for an extended period.

Detection of aquaporin-4 antibodies for patients with CNS inflammatory demyelinating diseases other than typical MS in Lithuania.

OBJECTIVES: Neuromyelitis optica (NMO) is frequently associated with aquaporin-4 autoantibodies (AQP4-Ab); however, studies of NMO in Lithuania are lacking. Therefore, the main objective of our study is to assess positivity for AQP4-Ab in patients presenting with inflammatory demyelinating central nervous system (CNS) diseases other than typical multiple sclerosis (MS) in Lithuania. MATERIALS AND METHODS: Data were collected from the two largest University hospitals in Lithuania. During the study period, there were 121 newly diagnosed typical MS cases, which were included in the MS registry database. After excluding these typical MS cases, we analyzed the remaining 29 cases of other CNS inflammatory demyelinating diseases, including atypical MS (n = 14), acute transverse myelitis, TM (n = 8), acute disseminated encephalomyelitis, ADEM (n = 3), clinically isolated syndrome, CIS (n = 2), atypical optic neuritis, ON (n = 1), and NMO (n = 1). We assessed positivity for AQP4-Ab for the 29 patients and evaluated clinical, laboratory, and instrumental differences between AQP4-Ab seropositive and AQP4-Ab seronegative patient groups. RESULTS: AQP4-Ab test was positive for three (10.3%) patients in our study, with initial diagnoses of atypical MS (n = 2) and ADEM (n = 1). One study patient was AQP4-Ab negative despite being previously clinically diagnosed with NMO. There were no significant clinical, laboratory, or instrumental differences between the groups of AQP4-Ab positive (3 [10.3%]) and negative (26 [89.7%]) patients. CONCLUSIONS: AQP4-Ab test was positive for one-tenth of patients with CNS inflammatory demyelinating diseases other than typical MS in our study. AQP4-Ab testing is highly recommended for patients presenting with not only TM and ON but also an atypical course of MS and ADEM.

Glutathione and glutathione S-transferase levels in patients with liver metastases of colorectal cancer and other hepatic disorders.

BACKGROUND/AIMS: Glutathione and glutathione S-transferases (GST) are involved in cell defence against reactive oxygen species, which induces oxidative stress and are associated with different chronic diseases. The aim of the present study was to determine the differences in reduced glutathione (GSH) and GST levels in patients with different liver diseases. MATERIALS AND METHODS: Overall, 114 patients were enrolled in this study: 58 patients with colorectal cancer (18 without and 40 with liver metastases), 27 with liver steatosis, 29 with alcoholic cirrhosis and a group of 40 healthy volunteers. The levels of GSH and GST in blood serum were evaluated by enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's guidelines. RESULTS: Significant differences in GSH and GST levels were observed in most of the groups compared to the healthy volunteers (GSH: 52.72 µg/mL, GST: 0.53 ng/mL): with hepatic steatosis (GSH: 17.04 µg/mL, p < 0.001; GST: 5.89 ng/mL, p < 0.001), alcoholic cirrhosis (GSH: 62.04 µg/mL, p < 0.003; GST: 0.94 ng/mL, p < 0.001) and liver metastases (GSH: 37.84 µg/mL, p < 0.001, GST: 1.25 ng/mL, p=0.747). CONCLUSION: The different GSH and GST levels in patients with colorectal cancer liver metastases, liver steatosis and alcoholic cirrhosis indicate the differences in antioxidative system damage and its compensatory possibilities and could serve as potential biomarkers for its correction.

Therapeutic Plasma Exchange in Multiple Sclerosis Patients with Abolished Interferon-beta Bioavailability.

BACKGROUND: Neutralizing antibodies (NAb) to interferon-beta (IFN-ß) are associated with reduced bioactivity and efficacy of IFN-ß in multiple sclerosis (MS). The myxovirus resistance protein A (MxA) gene expression is one of the most appropriate markers of biological activity of exogenous IFN-ß. We hypothesized that therapeutic plasma exchange (TPE) can restore the ability of IFN-ß to induce the MxA mRNA expression and that maintenance plasmapheresis can sustain the bioavailability of IFN-ß. MATERIAL AND METHODS: Eligible patients underwent 4 primary separate plasma exchange sessions. After the induction TPE sessions, they were transferred to maintenance plasmapheresis. Bioactivity of IFN-ß was expressed as in vivo MxA mRNA induction in whole blood using RT-qPCR. RESULTS: Six patients with low IFN-ß bioavailability detected by the MxA mRNA response were included. Four patients became biological responders after induction plasmapheresis. In 2 patients an increase of MxA mRNA expression was found, but the values persisted below the cut-off and the patients remained as "poor biological responders". The effect of maintenance plasmapheresis was transient: MxA mRNA expression values reverted to the baseline levels after 1-2 months. CONCLUSIONS: Therapeutic plasma exchange is able to restore the bioavailability of IFN-ß in the majority of studied patients, but the effect of TPE on the IFN-ß bioavailability was transient.

Pre-operative high sensitive C-reactive protein predicts cardiovascular events after coronary artery bypass grafting surgery: a prospective observational study.

C-reactive protein is a powerful independent predictor of cardiovascular events in patients with coronary artery disease. The relation between C-reactive protein (CRP) concentration and in-hospital outcome, after coronary artery bypass grafting (CABG), has not yet been established. The study aims to evaluate the predictive value of pre-operative CRP for in-hospital cardiovascular events after CABG surgery. High-sensitivity CRP (hs-CRP) levels were measured pre-operatively on the day of surgery in 66 patients scheduled for elective on pump CABG surgery. Post-operative cardiovascular events such as death from cardiovascular causes, ischemic stroke, myocardial damage, myocardial infarction and low output heart failure were recorded. During the first 30 days after surgery, 54 patients were free from observed events and 14 developed the following cardiovascular events: 10 (15%) had myocardial damage, four (6%) had low output heart failure and two (3%) suffered stroke. No patients died during the follow-up period. Serum concentration of hs-CRP > or = 3.3 mg/l (cut-off point obtained by ROC analysis) was related to higher risk of post-operative cardiovascular events (36% vs 6%, P = 0.01), myocardial damage (24% vs 6%, P = 0.04) and low output heart failure (12% vs 0%, P = 0.04). Multivariate logistic regression analysis showed that hs-CRP > or = 3.3 mg/l ( P = 0.002, O.R.: 19.3 (95% confidence interval (CI) 2.9-128.0)), intra-operative transfusion of red blood cells ( P = 0.04, O.R.: 9.9 (95% C.I. 1.1-85.5)) and absence of diuretics in daily antihypertensive treatment ( P = 0.02, O.R.: 15.1 (95% C.I. 1.4-160.6) were independent predictors of combined cardiovascular event. Patients having hs-CRP value greater or equal to 3.3 mg/l pre-operatively have an increased risk of post-operative cardiovascular events after on pump coronary artery bypass grafting surgery.

Markers of endothelial dysfunction after cardiac surgery: soluble forms of vascular-1 and intercellular-1 adhesion molecules.

Endothelium forms an inner layer of vascular wall. It plays an important role in inflammatory process, regulation of vascular tone, and synthesis of thromboregulatory substances. Leukocyte and endothelium interactions during inflammation are regulated by different families of adhesion molecules. Increased levels of soluble forms of adhesion molecules have been detected in the circulating blood in conditions such as autoimmune diseases, transplant rejection, ischemia-reperfusion injury in addition to neutrophil- and endothelial membrane-bound forms reflecting the level of endothelial dysfunction. It is known that endothelial dysfunction is a risk factor for ischemic events such as stroke, myocardial infarction, unstable angina pectoris, ventricle fibrillation, necessity of revascularisation procedures, and death from cardiovascular reasons. Clinical studies showed that cardiac surgery has an impact on vascular endothelial function as well. The amount of endothelium-derived soluble forms of vascular-1 and intercellular-1 adhesion molecules increases after cardiopulmonary bypass suggesting endothelial dysfunction. However, further investigations are needed to be done to support the evidence that endothelial dysfunction proceeding heart surgery is one of the reasons of tissue ischemia-reperfusion injury.