Re-evaluation of nailfold capillaroscopy in discriminating primary from secondary Raynaud's phenomenon and in predicting systemic sclerosis: a randomised observational prospective cohort study.

BACKGROUND: Primary Raynaud's phenomenon (pRP) is difficult to distinguish from secondary (sRP). Although nailfold capillaroscopy (NFC) may detect early alterations, no universal criteria yet discriminate between pRP from sRP. OBJECTIVES: To create and validate two NFC scores that could distinguish pRP from sRP and that could predict systemic sclerosis (SSc), respectively. METHODS: We performed NFC on two separate cohorts with isolated RP, and recorded number of capillaries per field, enlarged/giant capillaries, crossed/bizarre patterns, microhemorrhages, neoangiogenesis, rarefaction, edema, blood flow velocity, stasis. By multivariate regression analysis, we evaluated the adjusted prognostic role of these features in a derivation cohort of 656 patients. Results were used to construct algorithm-based prognostic scores (A and B). These scores were then tested on a confirmation cohort of 219 patients. RESULTS: Score A was unable to discriminate sRP from pRP (low negative predictive values with high positive predictive values for any cut-point); score B was unable to discriminate progression to SSc or a SSc-spectrum disorder (low positive predictive values with high negative predictive values for lower cut-points). CONCLUSION: NFC patterns, believed as specific, showed low discriminatory power and on their own are unable to reliably discriminate sRP from pRP or predict evolution to SSc.

Acute hospitalization in a cohort of patients with systemic sclerosis: a 10-year retrospective cohort study.

This study aimed at analysing the causes and predictors of acute hospitalization and mortality in a cohort of SSc. Retrospective analysis of all acute hospital admissions of SSc patients fulfilling the 2013 EULAR/ACR Classification Criteria, from a single-centre cohort of 95 patients, between 2010 and 2020. The total number of SSc patients registered in our hospital, in this period, was 123. Clinical data were collected from medical files of our institution and from the National Healthcare Registry platform. 53 patients needed acute hospitalization, in a total of 164 admissions. The most frequent causes for admission were: infectious diseases [27%; 70% due to pneumoniae, of which 74% had SSc-associated interstitial lung disease (ILD)], cardiac disease (16.5%), peripheral vascular disease [12.8%; all due to digital ulcers], pulmonary hypertension (PH) (9.8%) and ILD (9.1%). There was an increase in admissions due to cardiac disease over the 10 years of follow-up, and a decrease of ILD over the last 5 years. Fourteen patients died (in-hospital mortality of 9%) mainly due to pneumoniae (36%), heart failure (21%), neoplastic diseases (21%), PH (14%) and ILD (7%). From all the admissions due to infection 70.5% were under immunosuppression at the time of the hospitalization. The frequency of acute admissions superior to 1 was associated with infection (OR 2.29, 95%CI 1.11-4.71). There were several factors associated with both acute admissions and mortality, including: gender, race, digital ulcers, cardiac dysfunction, ILD and PH. Infection was the principal cause of acute hospitalization and mortality, mainly due to pneumoniae. Although a high percentage of those had ILD, it has been decreasing in the last years in our cohort, as a direct cause of hospital admission and mortality, possibly reflecting the advances in its management.

Sensorineural Hearing Loss and Systemic Autoimmune Disease: The Experience of a Systemic Immune-Mediated Diseases Unit.

Background Autoimmune inner ear disease (AIED) represents less than 1% of all cases of sensorineural hearing loss (SNHL) but its frequency may be underestimated due to lack of specific clinical and laboratory criteria. AIED can be associated with a systemic autoimmune disease (SAID) in 15%-30% of the cases. The objective of the present study was to characterize the clinical and prognostic factors of a cohort of patients with AIED. Materials and methods The authors conducted a retrospective descriptive analysis of a cohort of patients with AIED referred from the otorhinolaryngology department to a systemic immune-mediated diseases unit between March 2013 and November 2020. A consecutive sample of 39 patients with suspected AIED was referred. SNHL was defined as a fall of the hearing threshold of at least 30 decibels in three consecutive frequencies. Eight patients were excluded for not meeting the audiometric criteria or having confounding factors. The remaining 31 patients were included with a total of 50 affected ears. To classify the intensity of hearing loss, an arithmetic mean of pure tone was calculated. Normal hearing or mild hearing loss at the last pure tone audiometry of the follow-up were an indicator of good prognosis and were considered the outcome of interest. Results Thirty-two percent of the patients had an associated SAID. There were no differences regarding demographic and clinical characteristics when comparing patients with AIED alone and patients with AIED and a SAID, except for the positivity of antinuclear antibodies (ANA). ANA positivity was superior in patients with the association of AIED and a SAID when compared with patients with AIED alone (90% vs 50%; p=0.037). The SAID was diagnosed after the AIED in 70% of the patients, in which diagnosis of the SAID occurred a median of 4,2 (IQR 0.8-5.1) years after the diagnosis of the AIED. Normal audiometric evaluation or a mild hearing loss was achieved in 31% of the ears at the last audiometric evaluation. A normal audiometry or a mild hearing loss at the time of diagnosis was independently associated with a better outcome (31%, 14%, CI 1.71-273.69; p=0.018). Bilateral hearing loss was independently associated with a worse outcome (54%, 79%, CI 0.01-0.84; p=0.035). The use of systemic corticosteroids (p=0.941), transtympanic corticosteroids (p=0.700) and non-steroid immunomodulator drugs (p=0.986) did not affect prognosis. The presence of a SIAD did not affect the prognosis (p=0.986). Conclusions In this cohort, SAID was present in one-third of the patients with AIED. A good prognosis was achieved in one-third of the patients. A normal audiometry or mild disease at presentation was associated with a good outcome, whilst bilateral involvement was associated with a bad one. Association of a SAID did not seem to influence the hearing-related prognosis. Positivity of ANA antibodies may justify performing a complementary investigation to determine the presence of a SAID.

Antibodies against HDL Components in Ischaemic Stroke and Coronary Artery Disease.

Quantitative and qualitative defects of high-density lipoprotein (HDL) are important in atherogenesis. In this study, we investigated whether antibodies against HDL components had additional value to conventional cardiovascular risk factors for the diagnosis of ischaemic stroke (IS) and coronary artery disease (CAD). Cross-sectional study was conducted on 53 patients with IS, 51 with CAD and 55 healthy controls, and in vitro studies to validate findings of the clinical study. We determined serum immunoglobulin G (IgG) antibodies against HDL (aHDL), apolipoproteins (aApoA-I, aApoA-II and aApoC-I) and paraoxonase-1 (aPON1) as well as PON1 activity (PON1a), total antioxidant capacity and biomarkers of endothelial activation (serum nitric oxide metabolites, 3-nitrotyrosine, VCAM-1 and ICAM-1); in vitro assays tested the capacity of IgG aHDL purified from high titer patients to inhibit PON1a and to reverse protective effect of HDL on endothelial cells. IgG aHDL, aApoA-I and aPON1 were higher in IS and CAD than controls (p < 0.001), predicted negatively PON1a and positively VCAM-1 and ICAM-1. By adding IgG aHDL and aApoA-I to a traditional cardiovascular risk factors model for IS and by adding IgG aHDL in a similar model for CAD, we obtained better discrimination of IS and CAD from healthy controls. IgG aHDL purified from IS and CAD inhibited PON1a by 38% (p < 0.01) and abrogated the protective effect of HDL on VCAM-1 expression by 126% compared with non-specific human IgG (p < 0.001). IgG against HDL components interfere with the antioxidant and anti-inflammatory properties of HDL and may represent novel biomarkers for vascular disease that need to be investigated in prospective studies.

Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.

AIMS: Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1 (men) or ≤50 mg dl-1 (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. RESULTS: The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1 , 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 µg ml-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.

Stress-related mucosal disease: incidence of bleeding and the role of omeprazole in its prophylaxis.

BACKGROUND: Upper gastrointestinal bleeding is the severe complication of stress-related mucosal disease in hospitalized patients. In intensive care units (ICU), risk factors are well defined and only mechanical ventilation and coagulopathy proved to be relevant for significant bleeding. On the contrary, in non-ICU settings there is no consensus about this issue. Nevertheless, omeprazole is still widely used in prophylaxis of bleeding. The objective of our study was to evaluate the relevance of stress-related mucosal disease bleeding in patients admitted to an internal medicine ward, and the role of omeprazole in its prophylaxis. METHODS: We conducted a retrospective study in which we analysed consecutive patients who were admitted to our ward over a year. We recorded demographic characteristics of the patients, potential risk factors for stress-related mucosal disease (clinical data, laboratory, and medication), administration of prophylactic omeprazole, and total cost of this prophylaxis. Patients with active gastrointestinal bleeding on the admission were excluded. We recorded every upper gastrointestinal bleeding event with clinical relevance. RESULTS: Five hundred and thirty-five patients, mean age 70 years, mean length of stay 9.6+/-7.7 days; 140 (26.2%) patients were treated with 40 mg of omeprazole intravenously, 193 (36.1%) with 20mg of omeprazole orally, and 202 (37.8%) patients had no prophylaxis. There was only one episode (0.2%) of clinically relevant bleeding. CONCLUSION: In patients admitted to an internal medicine ward, incidence of upper gastrointestinal bleeding as a complication of stress-related mucosal disease is low. We found that there is no advantage in prophylaxis with omeprazole.

Humoral mechanisms of atherogenesis.

The concept that atherosclerosis is an autoimmune disease is no longer controversial. Attention has been paid to cellular immune response, but current research is now focused on the humoral component of this complex disease. Heat shock proteins, oxidized low-density lipoproteins, beta2-glycoprotein 1, cardiolipins, and, more recently, high-density lipoproteins have been considered to be autoantigens that play a part in atherogenesis. The characterization and understanding of the mechanisms associated with the presence of these antigens and their respective autoantibodies might contribute to elucidating the atherosclerotic process. In the near future, immune modulation might constitute a very effective therapy of atherosclerosis.