The impact of antiphospholipid antibodies/antiphospholipid syndrome on systemic lupus erythematosus.

aPLs are a major determinant of the increased cardiovascular risk in patients with SLE. They adversely affect clinical manifestations, damage accrual and prognosis. Apart from the antibodies included in the 2006 revised classification criteria for APS, other non-classical aPLs might help in identifying SLE patients at increased risk of thrombotic events. The best studied are IgA anti-ß2-glycoprotein I, anti-domain I ß2-glycoprotein I and aPS-PT. Major organ involvement includes kidney and neuropsychiatric systems. aPL/APS severely impacts pregnancy outcomes. Due to increased thrombotic risk, these patients require aggressive cardiovascular risk factor control. Primary prophylaxis is based on low-dose aspirin in high-risk patients. Warfarin is the gold-standard drug for secondary prophylaxis.

Predictors of damage accrual and its impact on health-related quality of life of thrombotic antiphospholipid syndrome: Independent validation of the damage index for antiphospholipid syndrome (DIAPS).

OBJECTIVES: We aim to independently assess the validity of the damage index for antiphospholipid syndrome (DIAPS) in thrombotic antiphospholipid syndrome (APS) patients by exploring the prevalence and risk factors of organ damage and evaluating its impact on health-related quality of life (HR-QoL). METHODS: Cross-sectional study including all thrombotic APS patients (Sydney criteria) attending a Portuguese tertiary centre. Damage was assessed using the DIAPS, and HR-QoL using the 3- and 5-level EuroQol HR-QoL (EQ-D5-3L and 5L), and Visual Analogue Scale (VAS) applied via a phone questionnaire. Spearman's correlation between DIAPS and the HR-QoL scales was performed. Risk factors for damage accrual and HR-QoL impairment were explored using univariate and multivariate logistic regression. RESULTS: Among the 108 patients (female, 65.7%; white, 90.7%; primary APS, 75.9%; median disease duration, 6 years), damage (DIAPS≥1) developed in 48.2% of patients (mean ± SD DIAPS, 3.08 ± 1.83). DIAPS's neuropsychiatric domain was the most affected (24.2%), followed by the peripheral vascular domain (20.3%). No clinical, demographic nor laboratory parameters were significantly associated with damage. Regarding HR-QoL, pain/discomfort, anxiety/depression and usual activities domains were the most frequently impaired in both scales. DIAPS's domains correlated similarly with the EQ-5D-3L and 5L scales' individual domains. Female sex, medical disorders, secondary APS and type of presenting thrombosis (arterial) increased the risk of HR-QoL impairment. Total DIAPS was associated with higher odds of mobility, self-care and pain/discomfort impairment in both EQ-5D-3L and 5L scales but lost its independent risk in multivariable analysis. CONCLUSION: This external validation of DIAPS reinforces the ability of the score to correlate with HR-QoL while also highlighting risk factors for HR-QoL impairment other than damage accrual.

C-reactive protein-to-albumin ratio and six-month mortality in incident hemodialysis patients.

BACKGROUND: The first few months of hemodialysis (HD) are associated with a higher risk of mortality. Protein-energy malnutrition is a demonstrated major risk factor for mortality in this population. The C-Reactive Protein to Albumin ratio (CAR) has also been associated with increased mortality risk. The aim of this study was to determine the predictive value of CAR for six-month mortality in incident HD patients. METHODS: Retrospective analysis of incident HD patients between January 2014 and December 2019. CAR was calculated at the start of HD. We analyzed six-month mortality. A Cox regression was performed to predict six-month mortality and the discriminatory ability of CAR was determined using the receiver operating characteristic (ROC) curve. RESULTS: A total of 787 patients were analyzed (mean age 68.34 ± 15.5 years and 60.6% male). The 6-month mortality was 13.8% (n = 109). Patients who died were significantly older (p < 0.001), had more cardiovascular disease (p = 0.010), had central venous catheter at the start of HD (p < 0.001), lower parathyroid hormone (PTH) level (p = 0.014) and higher CAR (p = 0.015). The AUC for mortality prediction was 0.706 (95% CI (0.65-0.76), p < 0.001). The optimal CAR cutoff was ≥0.5, HR 5.36 (95% CI 3.21-8.96, p < 0.001). CONCLUSION: We demonstrated that higher CAR was significantly associated with a higher mortality risk in the first six months of HD, highlighting the prognostic importance of malnutrition and inflammation in patients starting chronic HD.

One-Year Mortality after Hemodialysis Initiation: The Prognostic Role of the CHA2DS2-VASc Score.

BACKGROUND: CKD is a significant cause of morbidity, cardiovascular and all-cause mortality. CHA2DS2-VASc is a score used in patients with atrial fibrillation to predict thromboembolic risk; it also appears to be useful to predict mortality risk. The aim of the study was to evaluate CHA2DS2-VASc scores as a tool for predicting one-year mortality after hemodialysis is started and for identifying factors associated with higher mortality. METHODS: Retrospective analysis of patients who started hemodialysis between January 2014 and December 2019 in Centro Hospitalar Universitário Lisboa Norte. We evaluated mortality within one year of hemodialysis initiation. The CHA2DS2-VASc score was calculated at the start of hemodialysis. RESULTS: Of 856 patients analyzed, their mean age was 68.3 ± 15.5 years and the majority were male (61.1%) and Caucasian (84.5%). Mortality within one-year after starting hemodialysis was 17.8% (n = 152). The CHA2DS2-VASc score was significantly higher (4.4 ± 1.7 vs. 3.5 ± 1.8, p < 0.001) in patients who died and satisfactorily predicted the one-year risk of mortality (AUC 0.646, 95% CI 0.6-0.7, p < 0.001), with a sensitivity of 71.7%, a specificity of 49.1%, a positive predictive value of 23.9% and a negative predictive value of 89.2%. In the multivariate analysis, CHA2DS2-VASc ≥3.5 (adjusted HR 2.24 95% CI (1.48-3.37), p < 0.001) and central venous catheter at dialysis initiation (adjusted HR 3.06 95% CI (1.93-4.85)) were significant predictors of one-year mortality. CONCLUSION: A CHA2DS2-VASc score ≥3.5 and central venous catheter at hemodialysis initiation were predictors of one-year mortality, allowing for risk stratification in hemodialysis patients.

Immunosuppression Therapy in Acquired Hemophilia A: Pursuing an Optimal Regimen.

Acquired hemophilia A (AHA) is a rare bleeding disorder occurring mostly in elderly persons, caused by inhibition of factor VIII (FVIII). It is generally detected prior to surgery by an isolated prolonged activated partial thromboplastin time (aPTT) not correcting on mixing studies, with subsequent identification of reduced FVIII levels and presence of FVIII inhibitor. It is treated with hemostatics and immunosuppressants, which may increase the risk for life-threatening opportunistic infections. A 79-year-old woman with idiopathic acquired FVIII inhibition and severe bleeding presented with anemia, isolated and prolonged aPTT, low FVIII activity (<1%), and elevated FVIII inhibitor titer (471 Bethesda units per milliliter [BU/mL]). Initially, she was treated with recombinant activated factor VII and steroids. However, several hematomas appeared, one of which caused airway compression that required orotracheal intubation. Cyclophosphamide, rituximab (RTX), and activated prothrombin complex concentrate were initiated, resulting in clinical and laboratory resolution after five weeks. Cyclophosphamide and RTX were maintained for six and four weeks more, respectively. After 12 weeks of oral immunosuppression, the patient was readmitted due to antibiotic-resistant Pseudomonas aeruginosa sepsis, which resulted in death. Infection secondary to immunosuppression is the leading cause of death of patients with AHA. In AHA, combination therapy was shown to be more effective than monotherapy, but it was also identified to increase the risk of infection. Age, FVIII activity <1%, and FVIII inhibitor titers >20 BU are predictors of adverse events and poor prognosis in AHA patients. Additional studies are needed to clarify the ideal drug regimens and the need for prophylactic antibiotics in this population.

The Effect of Chronic and Inhospital Exposure to Renin-Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients.

BACKGROUND: Controversies exist about the effect of renin-angiotensin system inhibitors (RASi) on coronavirus disease 2019 (COVID-19) outcome. The inhospital use of RASi and its effect on inflammatory sate are still poorly studied during the COVID-19 pandemic. OBJECTIVES: We aimed to compare the impact of previous and inhospital RASi exposure on the outcome and inflammatory response of COVID-19 patients. METHODS: Single-centre, ambispective analysis of hospitalized adult COVID-19 patients at Hospital de Santa Maria, Lisbon, between March and August 2020 was performed. We excluded asymptomatic patients and those admitted due to another disease. The primary outcome was inhospital all-cause mortality. Illness severity was assessed based on the development of acute respiratory distress syndrome/acute lung injury (ARDS/ALI), intensive care unit (ICU) admission, and need for invasive mechanical ventilation (IMV). We used C-reactive protein (CRP), ferritin, and interleukin 6 (IL-6) as surrogate markers of the inflammatory response. RESULTS: From a total of 432 patients, 279 were selected, among whom 133 (47.7%) were receiving a RASi. Chronic treatment with RASi was not associated with the risk of death (OR 1.24, 95% CI 0.66-2.31, p=0.500), ARDS/ALI development (OR 1.12, 95% CI 0.67-1.86, p=0.676), ICU admission (OR 1.11, 95% CI 0.67-1.84, p = 0.686), and IMV need (OR 1.03, 95% CI 0.58-1.84, p=0.917) in a univariable and multivariable analysis. Inhospital RASi withdrawing was associated with the risk of death (OR 4.38, 95% CI 1.11-17.21, p=0.035) and ARDS/ALI development (OR 4.33, 95% CI 1.49-12.6, p=0.007), the latter remaining significant after adjustment. Previous exposure to RASi was associated with lower CRP levels at admission (p=0.018). IL-6 levels were significantly higher in those patients whose RASi were stopped (p=0.024). CONCLUSION: Previous and inhospital exposure to RASi was not associated with mortality nor severity of COVID-19. This study supports current guidance on RASi management during the COVID-19 pandemic.

Does Parkinson's Disease Increase the Risk of Atrial Fibrillation? Insights From Electrocardiogram and Risk Scores From a Case-Control Study.

Background: Previous studies suggested that Parkinson's Disease (PD) patients could have an increased risk of atrial fibrillation. However, data supporting this association is not robust. We aimed to compare the potential risk of atrial fibrillation associated with PD in an age and gender matched case-control study, comparing the p-wave indexes from electrocardiograms and clinical risk scores among groups. Methods: A cross-sectional case-control study was performed. All subjects included in the analysis were clinically evaluated and subjected to a 12-lead electrocardiogram. Two blinded independent raters measured the p-wave duration. Subjects were classified as having normal P-wave duration (<120 ms), partial IAB (P-wave duration ≥ 120 ms, positive in inferior leads), and advanced IAB (p-wave duration ≥ 120 ms with biphasic morphology in inferior leads). Atrial fibrillation risk scores (CHARGE-AF, HATCH, and HAVOC) were calculated. Results: From 194 potential participants, three were excluded from the control group due to a previous diagnosis of atrial fibrillation. Comparing the PD patients (n = 97) with controls (n = 95), there were no statistically significant differences regarding the mean p-wave duration (121 ms vs. 122 ms, p = 0.64) and proportion of advanced interatrial block (OR = 1.4, 95%CI = 0.37-5.80, p = 0.58). All patients had a low or medium risk of developing atrial fibrillation based on the clinical scores. There were no differences between the PD patients and controls regarding the mean values of CHARGE-AF, HATCH, and HAVOC. Conclusions: Our results do not support the hypothesis that PD patients have an increased risk of atrial fibrillation based on the p-wave predictors and atrial fibrillation clinical scores.

Low-Dose Colchicine in Coronary Artery Disease　- Systematic Review and Meta-Analysis.

Background: Recent studies have revealed the benefits of using colchicine, a drug with anti-inflammatory properties, in coronary artery disease (CAD). This study systematically reviewed the benefits and risks of low-dose colchicine in patients with CAD. Methods and Results: We searched for randomized controlled trials (RCTs) in MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science databases (March 2020). Efficacy and safety outcomes were evaluated. Estimates are expressed as risk ratios (RRs) and 95% confidence intervals (95% CIs). Heterogeneity was assessed with I2 test. Confidence in the pooled evidence was appraised using the GRADE framework. Colchicine reduced the rate of major adverse cardiovascular events (RR 0.65; 95% CI 0.49-0.86; 6 RCTs; I2=50%; 11,718 patients; GRADE, moderate confidence), acute coronary syndrome (RR 0.64; 95% CI 0.46-0.90; I2=47%; 7 RCTs; 11,955 patients; GRADE, very low confidence), stroke (RR 0.49; 95% CI 0.30-0.78; I2=0%; 6 RCTs; 11,896 patients; GRADE, moderate confidence), and cardiovascular interventions (RR 0.61; 95% CI 0.42-0.89; I2=40%; 4 RCTs; 11,284 patients; GRADE, high confidence). Colchicine did not increase the risk of adverse events, except for gastrointestinal events (RR 1.54; 95% CI 1.11-2.13; I2=72%; 9 RCTs; 12,374 patients; GRADE, very low confidence). Conclusions: Low-dose colchicine in patients with CAD is associated with beneficial effects on prognosis, although an increased risk of gastrointestinal events was confirmed.

Erythematous Papular Rash: A Dermatological Feature of COVID-19.

COVID-19 is the clinical expression of the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection. Most patients have mild symptoms, but a significant proportion have severe or critical disease, which can include cardiac injury, sepsis, acute kidney failure and respiratory failure. It is also worth highlighting the increasing number of reported COVID-19 cases with dermatological disease/manifestations. The cutaneous clinical spectrum is wide and includes maculopapular, urticarial, varicelliform and petechial rashes, pseudo perniosis, livedo reticularis, and pityriasis rosea-like, violaceous and pustular lesions. Until the physiological mechanism is fully understood, it is important to describe these manifestations, which could help identify a typical pattern. This report describes a cutaneous manifestation in a COVID-19 patient. LEARNING POINTS: SARS-CoV-2 presents with multiple symptoms with the dermatological manifestations currently under-recognized.Clinicians should be aware of patients presenting only with cutaneous symptoms, which in some cases are the initial clinical feature of COVID-19.