Associations between diet composition, dietary pattern, and weight outcomes after bariatric surgery: a systematic review.

INTRODUCTION: Literature describing the impact of dietary intake on weight outcomes after bariatric surgery has not been synthesized. This study aimed to synthesize the evidence regarding any association between diet composition and weight outcomes post-bariatric surgery. METHODS: CINAHL, Cochrane, Embase, MEDLINE and Scopus were searched for adult studies up to June 2021 that assessed any association between dietary intakes (≥1-macronutrient, food group, or dietary pattern) and weight outcomes at 12-months or longer after bariatric surgery. Risk of bias and quality assessments were conducted using the Scottish Intercollegiate Guidelines Network checklists and the NHMRC's Level of Evidence and Grades for Recommendations. Study findings were presented according to the time of post-surgery dietary intake assessment (≤12months, between 12 and 24 months, ≥24months). RESULTS: 5923 articles were identified, 260 were retrieved for full text screening, and 36 were eligible for inclusion (9 interventional including five randomized-controlled trials, and 27 observational cohort studies; sample sizes: 20-1610; total sample: 5065; follow-up periods: 1 year-12 years; level of evidence: II to IV, risk of bias: low to high). Findings on the association between long-term weight outcomes and dietary composition up to 24-months were mixed. After 24-months, studies consistently suggested no significant associations between weight loss and macronutrient composition or core food group patterns, or between carbohydrate, protein or food group patterns and weight recurrence. A single cohort study reported a weak association between diet quality score and weight-recurrence after 24-months. CONCLUSION: There was no strong evidence to support significant associations between diet composition and weight outcomes post-bariatric surgery. The heterogeneity in study design and quality may reduce generalizability to external populations. Individualized dietary recommendations may be useful to support long-term post-surgery weight outcomes. More studies are needed to define and measure diet quality in this patient cohort. REGISTRATION: PROSPERO (CRD42021264120).

Delayed neutrophil apoptosis in granulomatosis with polyangiitis: dysregulation of neutrophil gene signature and circulating apoptosis-related proteins.

Objectives: Neutrophil apoptosis is mandatory for resolving inflammation and is regulated by expression of pro- and anti-apoptotic genes. We studied neutrophils isolated from patients with granulomatosis with polyangiitis (GPA) to investigate apoptosis alterations and to identify transcriptional and circulating factors affecting this process.Method: We enrolled 36 patients (18 in active stage, 18 in remission) and 18 healthy controls. Circulating levels of tumour necrosis factor-α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage migration inhibitory factor, plasminogen activator inhibitor-1, interferon-γ, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, platelet endothelial cell adhesion molecule-1, soluble Fas (sFas), sFas ligand, survivin, and pentraxin-3 (PTX3) were evaluated by enzyme-linked immunosorbent assay/Luminex; circulating apoptotic neutrophils by flow cytometry; and apoptosis-related gene transcripts by real-time polymerase chain reaction.Results: Patients had decreased fractions of circulating apoptotic neutrophils and delayed neutrophil apoptosis was present in vitro. Circulating levels of TNF-α, GM-CSF, sFas, and PTX3 were higher in GPA. Delayed neutrophil apoptosis was accompanied by decreased mRNA of pro-apoptotic genes and transcription factors (DIABLO, PMAIP1, BAX, CASP3, CASP7, RUNX3, E2F1, TP53) and increased anti-apoptotic CFLAR and BCL2A1 mRNA. TNF-α and sFas levels correlated with circulating apoptotic neutrophils and expression of apoptosis genes. Stimulation with TNF-α of neutrophils from controls significantly down-regulated E2F1 and CASP3 expression.Conclusions: Circulating neutrophils in GPA have anti-apoptotic phenotype involving both intrinsic and extrinsic pathways of apoptosis. This is accompanied by increased levels of circulating pro-survival factors (GM-CSF, TNF-α, sFas), independent of disease activity. Anti-apoptotic phenotype of neutrophils in GPA is reproduced by exposure to low concentrations of TNF-α.

Hematopoietic stem cell transplantation does not increase the risk of infection-related complications for pediatric patients with Hodgkin and non-Hodgkin lymphomas: A multicenter nationwide study.

BACKGROUND: Hodgkin (HL) and non-Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens; however, 15%-30% of lymphoma patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second-line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications (IC), remain unclear. OBJECTIVE: The aim of this population-based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD), and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL. PATIENTS AND METHODS: We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A), patients with rel/ref lymphoma treated with second-line chemotherapy (group B), and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center, and the data were analyzed centrally. RESULTS: Within 637 patients with primary lymphoma, at least one IC was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed, and in transplanted group, 28 (57.1%) out of 49 children were diagnosed with IC (P = .151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC were diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram-positives were predominant. The rate of multidrug-resistant bacteria was high, especially for Gram-negatives (41.1% in group A, 62.5% in group B, and 84.6% in group C). The infection-related mortality was comparable for each group. CONCLUSIONS: The incidence of IC was comparable during first- and second-line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy.

Facilitated expansion of Th17 cells in lupus nephritis patients.

The objective of this study was to investigate the mechanisms of T helper type 17 (Th17) expansion in lupus nephritis (LN) patients, and to determine whether or not it is associated with impaired function of regulatory T cells (Treg ). Major effector subsets of peripheral blood CD4+ T cells were assessed by flow cytometry in 33 LN patients with different activity of the disease and 19 healthy controls. The percentage of circulating Th17 cells was increased in LN (median = 1·2% of CD4+ compared to 0·6% in the control group, P < 0·01), while Treg cells remained unchanged (12·3 versus 12·1% in controls), resulting in a significantly lower Treg /Th17 ratio. Th17 expansion in the patient group was not related to LN activity, renal histology or blood and urine inflammatory biomarkers, but has been associated with a higher cumulative dose of cyclophosphamide. Treg cells in LN displayed mainly effector memory phenotype and expressed higher levels of transforming growth factor (TGF)-ß; however, their suppressant activity in lymphocyte proliferation assay was diminished compared to controls (~fourfold, P < 0·05). Co-culture of Treg and conventional CD4+ T cells resulted in marked suppression of the Th1 subset in both of the groups studied, but also in a potent expansion of Th17 cells, which in LN was twofold higher, as in controls (P < 0·05). In conclusion, our results demonstrate that Th17 expansion in LN is not increased during disease exacerbation, but is related to chronic immunosuppressive therapy. This immune signature is probably linked to the abnormal function of Treg cells, which were less suppressive in LN patients and even facilitated differentiation of Th17 cells.

Urinary cytokines and mRNA expression as biomarkers of disease activity in lupus nephritis.

Introduction Renal involvement is one of the most serious manifestations of systemic lupus erythematosus, but non-invasive assessment of inflammatory response in kidneys is challenging. In this study we aimed to validate markers of active lupus nephritis (LN) using urine immune profiling. Methods Urine and serum cytokines (17-plex array) and urine mRNA expression (∼40 immune and glomerular injury genes) were measured in LN patients with active disease ( n = 17) during remission ( n = 16) and in healthy subjects ( n = 18). Results Urine and serum levels of CCL2, CCL5 and CXCL10 were elevated in active LN as compared with disease remission (best discrimination for urine CXCL10 and CCL2) and correlated with LN activity. In the active disease, urinary cell transcriptome showed marked upregulation of proinflammatory cytokines (e.g. TNF, CCL2, CCL5, CXCL10), and type-1 immunity-related genes (e.g. CD3G, CD4, TBX21, IFNG). An active pattern of gene expression was also observed in four patients in remission, who had moderately increased urinary leucocyte count. Two patients from this group developed renal exacerbation during the following 3 months. Markers of type-17 immune axis (e.g. IL-17A) were not significantly increased in active LN. Conclusions Active LN patients were characterized by marked increase of proinflammatory mediators in the urine. Urine cytokines (CCL2 and CXCL10) and type-1 T-cell-related gene markers in the urine sediment had similar diagnostic performance in detection of active LN.

Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study.

Objective A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis. Methods In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards. Results In the initial study ( n = 247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed ( k = 0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0-29.3), p < 0.0001. Sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study ( n = 214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed ( k = 0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p < 0.0001. Sensitivity, specificity, LR + and LR- for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively. Conclusions IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS.

Altered preoperative coagulation and fibrinolysis are associated with myocardial injury after non-cardiac surgery.

BACKGROUND: Myocardial injury after non-cardiac surgery (MINS), a complication with unclear pathogenesis, occurs within the first 30 days after surgery and worsens prognosis. Hypercoagulability induced by surgery might contribute to plaque rupture, with subsequent thrombosis and myocardial injury. This study assessed haemostatic markers before surgery and evaluated their association with MINS. METHODS: This is a substudy of VISION, a prospective cohort study of perioperative cardiovascular events. Of 475 consecutive vascular surgery patients, 47 (9.9%) developed MINS, defined as postoperative high-sensitivity troponin ≥50 ng litre -1 , with ≥20% elevation from the preoperative concentration. The control group consisted of 84 non-MINS patients matched for patient characteristics and co-morbidities. The following preoperative markers of hypercoagulability and fibrinolysis were measured: antithrombin, factor VIII activity, von Willebrand factor concentration and activity, fibrinogen, D-dimer, plasmin-antiplasmin complex, and tissue plasminogen activator. Moreover, C-reactive protein and CD40L concentrations were measured to assess inflammatory activity. RESULTS: Patients with MINS compared with the non-MINS group had a significantly higher concentration of factor VIII (186 vs 155%, P =0.006), von Willebrand factor activity (223 vs 160%, P <0.001), von Willebrand factor concentration (317 vs 237%, P =0.02), concentrations of fibrinogen (5.6 vs 4.2 g litre -1 , P =0.03), D-dimer (1680.0 vs 1090.0 ng ml -1 , P =0.04), plasmin-antiplasmin complex (747 vs 512 ng ml -1 , P =0.002) and C-reactive protein (10 vs 4.5 mg litre -1 , P =0.02) but not antithrombin (95 vs 94%, P =0.89), tissue plasminogen activator (11 vs 9.7 ng ml -1 , P =0.06) and CD40L (8790 vs 8580 pg ml -1 , P =0.73). CONCLUSIONS: Preoperative elevation of blood markers of hypercoagulability in patients undergoing vascular surgery is associated with a higher risk of MINS. CLINICAL TRIAL REGISTRATION: NCT00512109.

Signs of impaired immunoregulation and enhanced effector T-cell responses in the primary antiphospholipid syndrome.

INTRODUCTION: We investigated whether primary antiphospholipid syndrome (PAPS) is characterized by a deficiency in immunoregulatory pathways, a phenomenon recently implicated in the pathogenesis of autoimmune diseases. METHODS: Serum levels of immunoregulatory (e.g., IL-10 and TGF-ß1) and proinflammatory (e.g., IL-17A) cytokines were measured in PAPS, systemic lupus erythematosus (SLE) with secondary APS (SAPS), or without APS, and in healthy controls (n = 40 in each group). In a subgroup of PAPS patients we also compared phenotype and function (flow cytometry) of regulatory T-cells (Treg) and cytokine production by effector T-cells. RESULTS: Our major finding was decreased levels of TGF-ß1 in PAPS and SAPS as compared to SLE without APS and controls. TGF-ß1 was the lowest in PAPS patients showing high levels of aPL IgG with significant negative correlation with the titer. SLE patients were characterized by lower serum levels of IL-2 and increased IL-17A, as compared to the other groups. The numbers of circulating Treg cells and their phenotype (e.g., FoxP3 isoforms) were not disturbed in PAPS. However, surface expression of latency associated peptide (binds TGF-ß) in activated FoxP3 + cells and in vitro production of TGF-ß1 were decreased in PAPS patients with high titers of aPL IgG. Moreover, frequencies of cytokine producing effector T-helper cells (including Th17) were significantly elevated in this group. CONCLUSIONS: PAPS patients with high titers of aPL IgG antibodies were characterized by decreased systemic levels of TGF-ß1 and its impaired production in vitro, suggesting impaired immunoregulation and enhanced adaptive autoimmune responses leading to the production of aPL antibodies.

Circulating mitochondrial DNA in serum of patients with granulomatosis with polyangiitis.

Neutrophil is a key cell in pathophysiology of granulomatosis with polyangiitis. Recently, neutrophil extracellular traps were described in this disease. Mitochondrial DNA is also released during traps formation. We measured circulating cell-free mitochondrial and genomic DNA in serum of patients with granulomatosis with polyangiitis. Subjects with the disease (14 active and 11 in remission stage) and 10 healthy controls were enrolled. Quantitative real-time polymerase chain reaction (PCR) was used to measure 79 base pairs (bp) and 230 bp mtDNA fragments. Alu repeats were quantified to evaluate abundance of nuclear DNA in serum at the presence of plasmid control. Both fragments of mtDNA (79 bp and 230 bp) and genomic DNA were elevated significantly in granulomatosis with polyangiitis compared to controls. Only the shorter 79 bp mtDNA correlated with active stage of granulomatosis with polyangiitis and clinical symptoms. A mechanism of extracellular release of mitochondrial DNA accompanies the active stage of the disease. Circulating mtDNA is extremely high in untreated patients. This suggests that biomarker properties of mtDNA are useful for monitoring of treatment.

Summary of the 9th meeting of the European Forum on Antiphospholipid Antibodies.

The 9th meeting of the European Forum on Antiphospholipid Antibodies (Euro aPL Forum) was held in Krakow, Poland, on 16-18 May 2013. This was an excellent occasion for the exchange of information on current research in the area of antiphospholipid syndrome (APS), as well as a starting point for many new research projects. About 120 physicians and researchers from various medical specialities representing 15 European countries, USA, Argentina and Israel attended the event. This report summarizes the major studies and new research projects presented during the Forum.

Disseminated nocardiosis mimicking exacerbation of pulmonary sarcoidosis.

Nocardiosis is a rare, mixed suppurative and granulomatous, bacterial infection that can affect various organs, but most commonly lungs. Clinical manifestation is usually uncharacteristic; can mimic fungal, parasitic and mycobacterial infections or malignancy. Presentation can be also similar to that of the other granulomatous diseases, among them sarcoidosis. We present an unusual case of disseminated nocardiosis in a patient diagnosed before with sarcoidosis and treated with glucocorticoids. Clinical symptoms initially mimicked exacerbation of pulmonary sarcoidosis. The course of disease was severe.

Dermoscopy of external ear melanoma (EEM).

External ear melanoma (EEM) belongs to extremely rare melanoma locations. So far, only single cases of EEM have been described in terms of dermoscopic presentations. This case study report presents dermoscopic patterns of EEM in six patients. The retrospective case study was based on medical documentation (epidemiological, anamnestic, clinical, videodermoscopic, and histopathologic) of consecutive patients who were diagnosed with melanoma located on the external ear between January 2013 and May 2021 in three diagnostic dermatologic centers. In four of six cases, the melanoma was placed on the helix. The histopathological diagnoses included 1/6 lentigo maligna and 5/6 invasive melanomas. The dermoscopic pattern of facial melanoma (FM) was present in 3/6 cases, 1/6 exhibited the typical superficial spreading pattern (one with nodular invasion), 1/6 the multicomponent asymmetric pattern, and 1/6 the hypomelanotic type. Five melanomas presented numerous (3-6) dermoscopic structures characteristic for each dermoscopic subtype. In conclusion, dermoscopy has proved effective for detection of both difficult and easy-to-diagnose EEM, but also in differentiating their dermoscopic subtypes.

12-hydroxy-eicosatetraenoic acid (12-HETE): a biomarker of Churg-Strauss syndrome.

BACKGROUND: Churg-Strauss syndrome (CSS) shares similarities with asthma and hypereosinophilic syndrome (HES). Eicosanoids--important inflammatory and signaling molecules--are present in exhaled breath condensate (EBC) and broncho-alveolar lavage fluid (BALF). OBJECTIVES: To assess eicosanoid profile both in EBC and BALF of CSS subjects searching for a pattern characteristic of this syndrome. METHODS: EBCs from 23 CSS patients, 30 asthmatics, 12 HES patients and 54 healthy controls (HC) were assessed quantitatively for 19 eicosanoids by a high-performance liquid chromatography - tandem mass spectrometry (HPLC-MS/MS). In addition, in 21 of 23 CSS subjects and in nine asthmatics, eicosanoids were determined in BALF. RESULTS: EBC from CSS patients showed markedly elevated levels of 12-HETE as compared with other studied groups. BALF was characterized by a significant elevation of 12-HETE and its metabolite 12-tetranor HETE in CSS as compared with asthma. Clinical activity of CSS correlated with 12-HETE and its metabolites levels in BALF, but not in EBC. CONCLUSION AND CLINICAL RELEVANCE: CSS is clearly distinguished from bronchial asthma, and HES by a marked increase in 12-HETE concentration in both EBC and BALF. This points to a possible new pathogenic mechanism in CSS and may help in future in establishing the diagnosis of CSS.

Avidity of anti-ß2-glycoprotein I antibodies in patients with antiphospholipid syndrome.

Antibodies against ß(2)-glycoprotein I (anti-ß(2)GPI) are one of the hallmarks of the antiphospholipid syndrome (APS). However, they are heterogenic regarding their epitope specificity, pathogenic mechanisms and their avidity. In the current study we present some outstanding issues about avidity of anti-ß(2)GPI antibodies. Our results confirmed that high avidity anti-ß(2)GPI are associated with thrombosis and APS, while in low avidity anti-ß(2)GPI group non-APS (predominantly systemic lupus erythematosus) patients prevailed.

Registry of inherited bleeding disorders in Poland--current status and potential role of the HemoRec database.

We present data collected in HemoRec, an Internet-based platform implemented in 2006 in 15 haemophilia treatment centres in Poland and compare them with the national registry of inherited bleeding disorders established since 1991 at the Institute of Haematology and Blood Transfusion in Warsaw. We also analyse the current status of haemophilia treatment in Poland as well as future perspectives. Data on 1102 patients registered in HemoRec were analysed and compared with 4294 patients in the national registry (status as at 17.08.2009). The number of patients with severe haemophilia, mild/moderate haemophilia and von Willebrand in HemoRec is 530, 328 and 54 (respectively), compared with 1199, 1167 and 1128 in the national registry. The mean age of all haemophilic patients registered in HemoRec is 26.2 years, compared with 37.3 years in the general Polish male population in 2008. The number of haemophilic patients with inhibitor registered in HemoRec is 102 compared with 155 in the national registry (resulting in a prevalence of 14.9% of all severe haemophilia A and 1.6% of all severe haemophilia B patients). HemoRec includes data on a representative group of Polish haemophilic patients, mostly with haemophilia and haemophilia with inhibitor. von Willebrand's disease is largely under-registered in Poland. The survival of Polish haemophilic patients is shorter than that in the general population. The number of inhibitor patients in Poland is relatively large and should be decreased by wider availability of immunotolerance induction in 2010.

Association of heart structure and function abnormalities with laboratory findings in patients with systemic lupus erythematosus.

Conventional risk factors of coronary artery disease fail to explain the increased frequency of cardiovascular morbidity in patients with systemic lupus erythematosus (SLE). The study was conducted to determine possible association between the heart structure and function abnormalities with established prognostic value assessed by non-invasive imaging techniques and markers of autoimmune and inflammatory phenomena typical for SLE. Echocardiography and single photon emission computerized tomography (SPECT; Tc-99m-MIBI) at rest were performed in 60 SLE patients in a stable clinical condition of their disease. Laboratory evaluation included serum levels of C-reactive protein (CRP), complement C3c and C4 components and antiphospholipid antibodies (aPL). The latter included serum anticardiolipin (aCL) and anti-ß2-glycoprotein I (antiß2GPI) antibodies, both of IgG and IgM class, and lupus anticoagulant (LA) in plasma. Echocardiography revealed pathologic thickening of valvular leaflets and/or pericardium in more than 60% of patients. Right ventricular systolic pressure (RVSP) was elevated (>30 mmHg) in 16.7%. Myocardial perfusion defects were present in 36.7% of patients, despite normal ECG recordings and a lack of clinical symptoms of myocardial ischaemia. There was a significant association between thickening of valvular leaflets and/or pericardium and high CRP and low C3c and C4 concentrations. On the other hand, increased RVSP and the presence of myocardial perfusion defects were associated with the presence of anticardiolipin and antiß2GPI antibodies of the IgG class. Increased anticardiolipin IgG levels predicted perfusion defects in SPECT study with 100% sensitivity and 68% specificity, whereas elevated antiß2GPI IgG levels predicted RVSP elevation (>30 mmHg) with 100% sensitivity and 78% specificity. In stable SLE patients pericardial and valve abnormalities may be associated with markers of an ongoing inflammation. Also, pulmonary systolic pressure elevation and myocardial perfusion defects are combined with elevated levels of anticardiolipin and antiß2GPI antibodies of the IgG class. These results indicate that even clinically silent pulmonary hypertension and myocardial perfusion defects in SLE patients could be causally related to the presence of antiphospholipid antibodies.

The avidity of anti-beta2-glycoprotein I antibodies in patients with or without antiphospholipid syndrome: a collaborative study in the frame of the European forum on antiphospholipid antibodies.

OBJECTIVE: The objective of this study was to extend the findings of the preliminary study by measuring the avidity of IgG anti-ß2-glycoprotein I antibodies (anti-ß2-GPI) on a larger group of patients with primary or secondary antiphospholipid syndrome (APS) and anti-ß2-GPI positive patients without APS in the frame of the European Forum on antiphospholipid antibodies (aPL). METHODS: Serum from 137 patients with primary APS, APS associated with autoimmune diseases, and patients with autoimmune diseases other than APS from five EU rheumatology centres were tested for anti-ß2-GPI antibodies. The 109 patients who were sera positive for anti-ß2-GPI by the in-house anti-ß2-GPI enzyme-linked immunosorbent assay (ELISA) at the Immunology Laboratory, UMC Ljubljana were selected for further testing on avidity with chaotropic anti-ß2-GPI ELISA. RESULTS: High, low and heterogeneous avidity IgG anti-ß2-GPI was found in 32/109, 17/109 and 60/109 patients respectively. Significantly more patients with APS were in the high avidity than in the low avidity anti-ß2-GPI group, while the opposite was observed for non-APS (both p < 0.001). The most common clinical feature among patients with high avidity anti-ß2-GPI was thrombosis, mainly due to venous thrombosis (p < 0.01 and p < 0.001, versus low avidity anti-ß2-GPI group). CONCLUSION: Patients with or without APS had anti-ß2-GPI of high, low or heterogeneous avidity. High avidity anti-ß2-GPI was associated with thrombosis and APS, while in the low avidity anti-ß2-GPI group non-APS (predominantly SLE) patients prevailed. Determination of anti-ß2-GPI avidity should be considered in the analytical strategies for further differentiation of patients with anti-ß2-GPI antibodies.

Impaired cardiovascular autonomic nervous system function in patients with Churg-Strauss syndrome.

OBJECTIVES: Although peripheral nervous system involvement in patients with Churg-Strauss syndrome (CSS) has been described, little is known about its autonomic part. Autonomic nervous system (ANS) function can be assessed by studying heart rate variability (HRV) and a decrease in the spectrum of HRV correlates with ANS impairment. METHODS: Out of 24 CSS patients we chose 12 (four males, eight females, aged 40 ± 8.3 years) in disease remission and without cardiac involvement. Twelve age- and sex-matched healthy volunteers served as a control group. All underwent 24-h electrocardiogram (ECG) Holter recordings. HRV was calculated from 1-h segments, including: total power (TP), ultra-low frequency (ULF), very low frequency (VLF), low frequency (LF), and high frequency (HF) powers as well as normalized LF (LF%) and HF (HF%) powers and the LF to HF power ratio (LF/HF). RESULTS: The CSS patients showed decreased HRV parameters in the 1-h domains: TP (2038 vs. 3622 ms(2), p = 0.001), HF (561 vs. 1574 ms(2), p < 0.001), LF (672 vs. 1050 ms(2), p < 0.01), and VLF (544 vs. 738 ms(2), p = 0.016). However, LF% and LF/HF ratio were markedly higher in CSS patients than in controls (53.4% vs. 39%, p < 0.001 and 1.1 vs. 0.64, p < 0.001), whereas HF% was lower in CSS than in controls (46.6% vs. 61%, p < 0.001). These results were independent of duration of the disease, eosinophil count, corticosteroids, or peripheral nerve involvement in the past. CONCLUSIONS: The CSS patients show impaired HRV parameters, indicating parasympathetic ANS dysfunction in addition to peripheral nervous system involvement.

Central nervous system involvement as a major manifestation of rheumatoid arthritis.

A 58-year-old woman with an 8-year history of seropositive rheumatoid arthritis was admitted with right hemiparesis, history of seizures, fever, weight loss and headaches. Her blood tests revealed the presence of rheumatoid factor, elevated C-reactive protein and anti-cyclic citrullinated peptide antibodies (>200 RU/ml). Examination of cerebrospinal fluid demonstrated pleocytosis (118 cells/mm(3), predominantly lymphocytes) with elevated protein level (58 mg/dl); cultures were negative. Magnetic resonance imaging findings were suggestive for meningoencephalitis. Short course of high-dose corticosteroids and cyclophosphamide led to clinical improvement. Rheumatoid vasculitis was probably responsible for neurological symptoms.

Identification of high thrombotic risk triple-positive antiphospholipid syndrome patients is dependent on anti-cardiolipin and anti-ß2glycoprotein I antibody detection assays.

Essentials Triple-positivity is associated with a high risk for a first thrombotic event and recurrence. Identification of triple-positives is dependent on the solid phase assay used. In triple-positivity, IgM only adds value in thrombotic risk stratification together with IgG. Thrombotic risk in triple-positive patients with IgM only, depends on the platform. ABSTRACT: Background The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPL). Triple-positivity (i.e. positivity for lupus anticoagulant [LAC], anti-cardiolipin [aCL] and anti-ß2glycoprotein I [aß2GPI] antibodies) is associated with a high thrombotic risk. Objectives We investigated the variability in triple-positivity detection by measuring the same samples with four commercially available solid phase assays. In addition, the added clinical value of aPL in LAC-positive patients was investigated, as well as the association of IgM triple-positivity and thrombosis. Patients/Methods We included 851 patients from seven European medical centers. Anti-CL and aß2GPI IgG/IgM antibodies were determined by four platforms: BioPlex® 2200, ImmunoCap® EliA, ACL AcuStar® and QUANTA Lite ELISA® . Results Triple-positivity detection by solid phase assays varied, ranging from 89 up to 118 in thrombotic APS patients (n = 258), of which 86 were detected independent of the platform. Lupus anticoagulant positivity resulted in an odds ratio (OR) for thrombosis of 3.4; triple-positivity (irrespective of the isotype) increased the OR from 4.3 up to 5.2, dependent on the platform. Triple-positivity solely for the IgM isotype did not increase the OR for thrombosis compared with LAC positivity. The highest OR for thrombosis was reached for positivity for IgG and IgM aß2GPI and aCL (8.6 up to 28.9). Conclusions Triple-positivity proved to be highly associated with thrombosis, but identification is assay dependent. Within triple-positivity, IgM antibodies only have an added clinical value in patients positive for IgG antibodies.