Comorbid association of obstructive sleep apnea (OSA) and thrombotic primary antiphospholipid syndrome (tPAPS): A more severe phenotype?

OBJECTIVE: We aimed to evaluate the frequency of obstructive sleep apnea (OSA) in patients with thrombotic primary antiphospholipid syndrome (tPAPS), to investigate the performance of screening tools for OSA in this scenario and to compare clinical/laboratorial differences in tPAPS patients with and without OSA. METHODS: We consecutively enrolled patients with tPAPS to undergo sleep studies using a portable monitor. OSA was defined as apnea-hypopnea index ≥15 events/h. Frequency of OSA in tPAPS was evaluated and compared with age-, gender-, and BMI-matched controls (1:3 ratio) from the Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil). Next, we tested the performance of three different screening tools for assessing OSA in patients with tPAPS. Finally, patients with tPAPS were stratified according to OSA status comparing their clinical and laboratory characteristics (including damage burden measured by Damage Index for Antiphospholipid Syndrome [DIAPS] and biomarkers associated with thrombosis) using standard statistical procedures. RESULTS: Fifty-two patients were included for analysis (females: 82.7%; mean age: 48 ± 14 years; body-mass index: 31.1 ± 6.5 Kg/m2; 25% with moderate-severe OSA). When compared to matched controls from ELSA-Brasil (n = 115), there was no significant differences in the frequencies of OSA (tPAPS: 12/42 [28.6%] vs. controls: 35/115 [30.4%], p = 0.821). Among screening tools, NoSAS had the highest area under ROC curve (AUC 0.806, CI 95% 0.672-0.939, p = 0.001), followed by STOP-Bang (AUC 0.772, CI 95% 0.607-0.938, p = 0.004). Patients with comorbid tPAPS and OSA presented higher levels of von Willebrand factor (vWF) (median 38.9 vs. 32.6, p = 0.038) and DIAPS (median 5 vs. 2, p = 0.020), when compared to those without OSA. OSA remained statistically associated with higher DIAPS, even after controlling for age, disease duration and BMI. CONCLUSION: OSA is common in patients with tPAPS, with rates comparable to a non-referred population. Both NoSAS and STOP-Bang scores seems to be useful for screening OSA in these patients. Patients with tPAPS+OSA had higher damage burden and higher levels of vWF, which might suggest a more severe phenotype of tPAPS in this scenario.

Cognitive dysfunction and serum levels of brain-derived neurotrophic factor (BDNF) in primary anti-phospholipid syndrome (PAPS).

OBJECTIVES: Cognitive dysfunction (CD) is a poorly understood non-stroke central neurological manifestation in anti-phospholipid syndrome (APS). Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays an important role in neural plasticity and could potentially be a biomarker of CD in primary APS (PAPS). The aim of the study is to assess CD in PAPS patients and to evaluate its association with clinical data, anti-phospholipid antibodies and serum BDNF levels. METHODS: This cross-sectional study compared 44 PAPS patients and 20 healthy controls matched for age, gender and education. PAPS patients and controls underwent a standardized cognitive examination. The demographic, clinical and laboratory characteristics of patients were recorded. Serum BDNF was measured by Enzyme Linked Immunosorbent. RESULTS: Fourteen (31.8%) of the 44 patients with PAPS had CD compared with only one (5%) healthy control (P =0.019). PAPS patients presented lower serum BDNF levels when compared with controls (P =0.007). Lower levels of BDNF were associated with CD in PAPS patients (P =0.032). In the univariate analysis, a positive association was found between CD and livedo reticularis, deep vein thrombosis, stroke, seizure, smoking as well as a negative association with Mini Mental State Examination and serum BDNF. According to multivariate analysis, the only independent predictor of CD in PAPS was stroke (OR 137.06; 95% CI: 4.73, 3974.32; P =0.004). CONCLUSIONS: CD is commonly reported in PAPS patients; however, its assessment lacks in standards and objective screening tests. The association between CD and low serum BDNF suggests that this neurotrophin can be a promising biomarker for PAPS cognitive impairment.

Global antiphospholipid syndrome score and anti-ß2-glycoprotein I domain I for thrombotic risk stratification in antiphospholipid syndrome: A four-year prospective study.

OBJECTIVE: This study aimed to assess prospectively the role of anti-ß2-glycoprotein I domain I antibody (aß2GPI-DI) and the Global Antiphospholipid Syndrome Score (GAPSS) in identifying antiphospholipid syndrome (APS) patients at higher risk of a new event. METHODS: Thrombotic APS patients were followed from May 2013 to July 2017. At baseline, we measured lupus anticoagulant, IgG/IgM anticardiolipin, anti-ß2-glycoprotein I, antiphosphatidylserine-prothrombin (aPS/PT) and IgG aß2GPI-DI, and calculated GAPSS for each patient. RESULTS: A total of 44 patients (age 43 ± 10 years, 89% female, 73% primary APS) were followed for 39 months (range 9-46 months). Four new thromboses occurred, two of them after vitamin K antagonist interruption. Recurrent patients presented higher GAPSS (median 20) and were triple and aß2GPI-DI positive; non-recurrent patients had lower GAPSS (median 10.5, range 0-20) and lower ratio of triple (33%) and aß2GPI-DI positivities (38%). aß2GPI-DI was associated with higher GAPSS (median 19 vs. 7, p < 0.001; Pearson correlation 0.82, p < 0.001) and had a greater proportion of triple (83% vs. 4%, p < 0.001) and aPS/PT positivity (94% vs. 50%, p = 0.002). CONCLUSION: Our data show a significant correlation between a validated risk score such as GAPSS and the novel antiphospholipid antibody aß2GPI-DI. Future studies are needed. However, one could speculate a role of aß2GPI-DI as a risk-stratifying tool for thrombotic events in APS.

Kinetic, thermodynamic and physical-chemical study of the removal of copper from cachaça using coconut fibers.

The use of coconut fiber as a copper adsorbent in cachaça was optimised, and changes in the chemical quality of the beverage were observed by analytical techniques. The influence of the adsorbent mass and copper concentration parameters was investigated using the Central Composite Design, and the optimum condition was obtained through the use of Response Surface Methodology. The equilibrium of the adsorption reaction was obtained within 120 min. The kinetic data were better adjusted for the Elovich model (Elovich and Zhabrova 1939) and the isotherm data for the Sips model (Sips 1948). The maximum adsorption capacity was 1.38 mg g-1. Slight changes in the physicochemical quality of the beverage were observed, including a decrease in volatile acidity and alcohol content. Copper levels in cachaça decreased from 8.57 mg L-1 to 4.97 mg L-1 after adsorption. Therefore, the use of biomass as a metal ion adsorbent in beverages can be successfully employed.

Enhanced type I interferon gene signature in primary antiphospholipid syndrome: Association with earlier disease onset and preeclampsia.

OBJECTIVE: Recently, two studies demonstrated that a relevant percentage of primary antiphospholipid syndrome (PAPS) patients had an upregulation of interferon (IFN) genes. However, 20%-28% of these patients had anti-dsDNA, a highly specific systemic lupus erythematosus (SLE) autoantibody. This study aimed to determine the prevalence of the type I IFN signature in the peripheral blood mononuclear cells of PAPS patients without specific SLE autoantibodies and search for its clinical associations. METHODS: Fifty-three PAPS patients (Sydney's criteria) were consecutively selected and age-matched with 50 healthy controls. A third group of nonimmune-mediated thrombophilia patients was also included. The expression of 41 IFN-induced genes was analyzed using real time quantitative PCR. A principal component analysis determined which genes composed the IFN signature, and the z-score was calculated. An ROC curve defined the signature cut-off. RESULTS: Six genes remained in the IFN signature DNAJA1, IFIT5, IFI27, MX1, IFI6, and TYK2. The ROC cutoff was 3.9-fold (AUC = 0.706, S = 0.49, E = 0.86, PPV = 0.79, NPV = 0.61). The type I IFN signature was present in 49% of the patients with PAPS compared with 14.0% of the healthy controls and 17% of the nonimmune-mediated thrombophilia patients (p < .0001). The IFN signature was associated with a younger age at the first antiphospholipid syndrome event (p = .023) and with preeclampsia (p = .032). CONCLUSION: Our results indicate that PAPS patients without lupus-specific antibodies have an enhanced type I IFN gene signature that is not observed in nonimmune-mediated thrombophilia. Also, this overexpression of type I IFN-regulated genes associated with an earlier onset of antiphospholipid syndrome event and preeclampsia.

The adjusted global antiphospholipid syndrome score (aGAPSS) and the risk of recurrent thrombosis: Results from the APS ACTION cohort.

OBJECTIVES: To assess whether patients with antiphospholipid syndrome (APS) and history of recurrent thrombosis have higher levels of adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) when compared to patients without recurrent thrombosis. METHODS: In this cross-sectional study of antiphospholipid antibody (aPL)-positive patients, we identified APS patients with a history of documented thrombosis from the AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository ("Registry"). Data on aPL-related medical history and cardiovascular risk factors were retrospectively collected. The aGAPSS was calculated at Registry entry by adding the points corresponding to the risk factors: three for hyperlipidemia, one for arterial hypertension, five for positive anticardiolipin antibodies, four for positive anti-ß2 glycoprotein-I antibodies and four for positive lupus anticoagulant test. RESULTS: The analysis included 379 APS patients who presented with arterial and/or venous thrombosis. Overall, significantly higher aGAPSS were seen in patients with recurrent thrombosis (arterial or venous) compared to those without recurrence (7.8 ±â€¯3.3 vs. 6 ±â€¯3.9, p<0.05). When analyzed based on the site of the recurrence, patients with recurrent arterial, but not venous, thrombosis had higher aGAPSS (8.1 ± SD 2.9 vs. 6 ±â€¯3.9; p<0.05). CONCLUSIONS: Based on analysis of our international large-scale Registry of aPL-positive patients, the aGAPSS might help risk stratifying patients based on the likelihood of developing recurrent thrombosis in APS.