Search for Dark Matter Axions with CAST-CAPP.

The CAST-CAPP axion haloscope, operating at CERN inside the CAST dipole magnet, has searched for axions in the 19.74 µeV to 22.47 µeV mass range. The detection concept follows the Sikivie haloscope principle, where Dark Matter axions convert into photons within a resonator immersed in a magnetic field. The CAST-CAPP resonator is an array of four individual rectangular cavities inserted in a strong dipole magnet, phase-matched to maximize the detection sensitivity. Here we report on the data acquired for 4124 h from 2019 to 2021. Each cavity is equipped with a fast frequency tuning mechanism of 10 MHz/ min between 4.774 GHz and 5.434 GHz. In the present work, we exclude axion-photon couplings for virialized galactic axions down to gaγγ = 8 × 10-14 GeV-1 at the 90% confidence level. The here implemented phase-matching technique also allows for future large-scale upgrades.

[Cognitive impairment as a predictor of functional decline after hospitalization: DECOFIRH Study]. / Deterioro cognitivo como factor independiente de riesgo hospitalario: estudio DECOFIRH.

AIM: Cognitive impairment is underdiagnosed in the elderly. We aimed to study the rate of positive responses to an informant-based questionnaires and functional disability after hospital discharge. PATIENTS AND METHODS: Observational prospective case series of patients aged 70-85 years-old admitted for hospitalization in an Internal Medicine ward. All medical records were reviewed and those patients with no previous diagnosis of dementia or related neurological conditions, no previous recent hospitalization or not having a caregiver were evaluated after signing an informed consent. A medical interview including the Alzheimer's Disease 8 (AD8), the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and Barthel Index was completed. Barthel Index was obtained three months after discharge. RESULTS: During a 3-month period a total of 809 admissions were screened and 79 (9.7%) fulfilled the study criteria. Patient's mean age was 80 years-old. Common comorbidities were arterial hypertension (83.5%), major surgery (54.4%) and heart disorders (50.6%). The most frequent cause of admission was infectious disease (37.9%). Test positivity for cognitive impairment was 30.3% for IQCODE and 34.1% for AD8. At admission 37.9% of the patients were functionally independent. At three months this percentage dropped to 24%. CONCLUSIONS: In this small sample size, almost a third of older patients, without major comorbidities or neurological disorders, admitted to a general hospital showed an informant-based suggestion of cognitive impairment previously undiagnosed. Functional impairment affects almost a quarter of these patients three months after admission.

TITLE: Deterioro cognitivo como factor independiente de riesgo hospitalario: estudio DECOFIRH.Objetivo. El deterioro cognitivo esta infradiagnosticado. El estudio DECOFIRH pretende detectar la tasa de deterioro cognitivo no conocido y su impacto en la situacion funcional de estos pacientes tras un ingreso hospitalario mediante cuestionarios realizados a un informador. Pacientes y metodos. Estudio observacional prospectivo realizado sobre una serie de casos, de pacientes comprendidos entre 70 y 85 años, que ingresan en el Servicio de Medicina Interna de un hospital terciario. Se excluyo a los pacientes con diagnostico de demencia o enfermedades neurologicas graves, asi como a los que habian sido hospitalizados recientemente. Los tests empleados en la deteccion de deterioro cognitivo fueron Alzheimer's Disease 8 (AD8) e Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Asimismo, se evaluo la situacion funcional mediante el indice de Barthel en el momento del ingreso y tres meses despues. Resultados. Durante los tres meses de seguimiento ingresaron 809 pacientes y cumplieron los criterios de inclusion 79 (9,7%) de ellos. Su edad media era de 80 años. Mediante el IQCODE se detecto una tasa de deterioro cognitivo del 30,3%, y con el AD8, del 34,1%. En el ingreso, el 37,9% de los pacientes era funcionalmente independiente. A los tres meses, este porcentaje cayo al 24%. Conclusiones. En nuestra muestra, casi un tercio de los ancianos sin comorbilidades sistemicas o neurologicas graves dio positivo para la deteccion de deterioro cognitivo segun nuestros tests basados en el informador, sin ser este conocido previamente. El deterioro funcional afecta casi a una cuarta parte de estos pacientes a los tres meses del ingreso.

Rapid spread of Clostridium difficile NAP1/027/ST1 in Chile confirms the emergence of the epidemic strain in Latin America.

Clostridium difficile infection has gained importance in recent years as a result of the rapid spread of epidemic strains, including hypervirulent strains. This study reports the molecular epidemiology of C. difficile obtained from hospitalized patients in Chile. Seven hundred and nineteen isolates of toxigenic C. difficile from 45 hospitals across the country were characterized through toxin profile, pulsed-field gel electrophoresis (PFGE), and sequencing of the tcdC gene. In addition, polymerase chain reaction (PCR) ribotyping and multilocus sequence typing (MLST) were performed on a subset of selected strains. PFGE typing of 719 isolates of C. difficile produced 60 PFGE patterns (subtypes). Subtype 1 was predominant (79% of isolates) and related to the hypervirulent strain (NAP1). Subtype 1 showed 73% relatedness with nine other subtypes, which had a similar tcdC deletion. Subtype 1 corresponded to ribotype 027 and ST1. This report shows the wide dissemination of the hypervirulent strain NAP1/027/ST1 in Chile.

Vascular- and pregnancy-related outcomes in patients with systemic lupus erythematosus with positive antiphospholipid profile and thrombocytopenia.

This study aimed to investigate whether patients with lupus and a positive antiphospholipid profile with thrombocytopenia are at a higher risk for obstetric complications or thrombotic events than patients without thrombocytopenia. We conducted a case-control study matched 3:1 by sex, age of systemic lupus erythematosus diagnosis, age at study start, disease duration and length of follow-up time. Time to first event following study start was compared using Kaplan-Meier curves and log-rank tests and it was not statistically significant. In this study setting and population, thrombocytopenia was not associated with a higher risk for obstetrical complications or thrombotic events.

The correlation between carotid artery atherosclerosis and clinical ischemic heart disease in lupus patients.

AIM: The extent of subclinical atherosclerosis can be assessed by ultrasound measurement of carotid intima-media thickness (cIMT) and total plaque area (TPA). We aimed to investigate the correlation between measures of atherosclerosis as documented on imaging studies of the carotid vasculature and clinical coronary artery disease (CAD) in systemic lupus erythematosus (SLE). METHODS: The study patients were recruited from the University of Toronto prospective cohort of SLE patients. Patients who had a history of CAD were compared to those without CAD. TPA and cIMT were measured using high-resolution optimized ultrasound systems. Logistic regression models were used to investigate the strength of association between ultrasound measures of atherosclerosis and CAD. The strength of association as expressed by odds ratio (OR) was compared between TPA and cIMT. RESULTS: A total of 103 SLE patients were analyzed (27 patients with a history of CAD). Carotid IMT correlated only moderately with TPA (r = 0.43, p < 0.001). Both measures were significantly associated with the presence of CAD. However, TPA showed a stronger association than cIMT (OR 9.55 vs. 2.02, respectively). TPA was also more strongly associated with dyslipidemia and hypertension compared to cIMT. CONCLUSIONS: In SLE patients, cIMT correlates only moderately with TPA, suggesting that they measure different phenotypes of atherosclerosis. Carotid TPA correlated better than cIMT with cardiovascular risk factors and CAD, suggesting that it may serve as a better tool for the investigation of atherosclerosis in SLE.

Changes in quality of life in the first 5 years of disease in a multicenter cohort of patients with systemic lupus erythematosus.

OBJECTIVE: The Medical Outcomes Study Short Form 36 (SF-36) is recommended to assess quality of life (QOL) in systemic lupus erythematosus (SLE). The aim of the current study was to assess QOL over time in the first 5 years of a multicenter inception cohort of patients with SLE. METHODS: An inception SLE cohort was assembled according to a standardized protocol between 2000 and 2012. In addition to clinical and laboratory assessments, patients completed the SF-36 at yearly intervals. Only patients who had ≥5 completed QOL questionnaires were included in these analyses. Generalized estimating equation models were run separately for each of the 8 subscales and for the physical and mental component summary scores, adjusting for repeated measures by patients. RESULTS: A total of 495 patients were included. The mean ± SD disease duration at the first visit was 5.3 ± 4.1 months. The mean ± SD age at enrollment was 35.8 ± 13.2 years. All 8 subscales and the 2 summary scores showed improvement in the first 2 years from enrollment. Between years 2 and 5, none of the subscales or summary scores showed any change. Minimum clinically important improvement was achieved by 35-56% of the patients and was influenced by demographic and disease factors. CONCLUSION: Unlike late-stage lupus, where QOL is stable over time, in patients with early disease, all subscales improve in early followup up to 2 years. Therefore, the SF-36 may be a sensitive outcome measure in early disease in patients with SLE.

SLEDAI-2K Responder Index 50 captures 50% improvement in disease activity over 10 years.

OBJECTIVES: To determine the frequency and the time to complete recovery identified by Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and the time to partial recovery identified by the SLEDAI-2K Responder Index 50 (SRI-50) in three laboratory systems over 10 years. METHODS: This is a retrospective analysis of the data available from the Toronto Lupus Clinic over the last 10 years. Patients with SLEDAI-2K renal, immunological and hematologic active descriptors were identified. The percentage of descriptors with partial and complete recovery was studied at one year and over the study period. Descriptive analysis and the Kaplan-Meier estimator were applied to study the time to partial and complete recovery. RESULTS: Of the 795 patients, 94% had an active system at some point during the study period. Partial recovery was shown in 66% of patients by SRI-50 for at least one descriptor over the study period. None of these partial findings identified would have been captured using SLEDAI-2K alone. The time to partial recovery identified by SRI-50 was shorter than the time to complete recovery identified by SLEDAI-2K. CONCLUSION: The SRI-50 is a valid responder index derived form SLEDAI-2K and is very helpful in identifying clinically important improvement in active laboratory descriptors in an efficient time.

Evolution of disease burden over five years in a multicenter inception systemic lupus erythematosus cohort.

OBJECTIVE: We describe disease activity, damage, and the accrual of key autoantibodies in an inception systemic lupus erythematosus (SLE) cohort. METHODS: The Systemic Lupus International Collaborating Clinics (SLICC) International Research Network, comprising 27 centers from 11 countries, has followed an inception cohort of SLE patients yearly according to a standardized protocol. Of these patients, 298 were followed for a minimum of 5 years and constitute the study population. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K) and damage was assessed using the SLICC/American College of Rheumatology Damage Index (SDI). Antinuclear antibody (ANA), anti-DNA, and anticardiolipin antibody (aCL) levels and lupus anticoagulant were assessed yearly. Descriptive statistics were generated and repeated-measures general linear models were used to evaluate SLEDAI-2K and SDI over time between whites and nonwhites. RESULTS: Of the 298 patients, 87% were women, 55% were white, 12% were African American, 14% were Asian, 16% were Hispanic, and 2% were categorized as "other." At enrollment, the mean age was 35.3 years, the mean SLEDAI-2K score was 5.9, and the mean disease duration was 5.5 months. Mean SLEDAI-2K scores decreased in the first year and then remained low. SLEDAI-2K scores were significantly lower at each year in whites compared to nonwhites. Mean SDI scores increased progressively over 5 years; there was no significant difference between whites and nonwhites. As expected, ANA positivity was high and anti-DNA positivity was relatively low at enrollment, and both increased over 5 years. Although lupus anticoagulant increased slightly over 5 years, aCL positivity did not. CONCLUSION: Disease activity in newly diagnosed patients decreases over their first 5 years, while damage increases. Antibody positivity ran variable courses over this period.

SLEDAI-2K 10 days versus SLEDAI-2K 30 days in a longitudinal evaluation.

The objective of the study was to evaluate SLEDAI-2K 30 days over time and to compare with the original SLEDAI-2K 10 days. Forty-one patients seen at The University of Toronto Lupus Clinic were followed at monthly intervals for 12 months. The SLEDAI-2K score was completed twice, once for a 10-day window and again for a 30-day window using the same definitions for the descriptors. Four hundred and nineteen patient-visits in 41 patients were recorded for both SLEDAI-2K for a 10-day and a 30-day window. One hundred and fifty-one patient-visits had a SLEDAI-2K activity score of 0 and 268 patient-visits had varying levels of disease activity in the range 1-15. In all but one patient-visit there was an agreement between the SLEDAI-2K 10 days and 30 days. SLEDAI-2K 30 days scores were concordant with SLEDAI-2K 10 days scores, both in patients in remission and in patients with a spectrum of disease activity levels followed monthly over 1 year. SLEDAI-2K 30 days was validated against SLEDAI-2K 10 days in a longitudinal evaluation over 1 year. We recommend the use of SLEDAI-2K 30 days in clinical studies and clinical trials.

Relationship between cardiac symptoms, myocardial perfusion defects and coronary angiography findings in systemic lupus erythematosus.

Coronary angiography is generally regarded as the 'gold standard' test for diagnosing coronary artery disease (CAD). We sought to determine the relationship between cardiac symptoms and findings of coronary angiography and myocardial perfusion scintigraphy (MPS) in patients with systemic lupus erythematosus (SLE). Medical records of all SLE patients who underwent coronary angiography while attending our clinic over 24 years were reviewed, noting the indication for the test and its findings. Among patients who had MPS within 6 months prior to coronary angiography, a contingency table was used to rate the agreement between the two tests. Among the 35 patients who underwent coronary angiography, 31 had the test to investigate cardiac symptoms. Among the symptomatic patients, 17 (55%) had an abnormal angiogram with one or more plaques, while 14 (45%) had normal angiograms. All four asymptomatic patients had normal angiograms. Compared to those with normal angiograms, patients with abnormal angiograms had a higher mean number of cardiovascular risk factors per patient (1.6 ± 1.4 vs. 0.6 ± 1.0, p = 0.02). Twenty-four patients had both angiography and MPS. Overall, the agreement between angiography and MPS was poor (κ = 0, p = 0.0008), with 14 (58.3%) patients having perfusion defects and normal angiograms. A proportion of SLE patients with cardiac symptoms do not have plaques on coronary angiography. Overall there is poor agreement between the findings of coronary angiography and MPS in SLE, suggesting mechanisms of ischemia other than plaques.

Burden of autoantibodies and association with disease activity and damage in systemic lupus erythematosus.

OBJECTIVES: To determine whether immunological burden of autoantibodies as reflected by the number of cumulative antibodies present at inception and after 3 and 5 years is associated with or predicts subsequent disease activity and damage in lupus. METHODS: Patients with SLE followed from inception at a single centre between 1992 and 2007 were included. Twelve autoantibodies were assayed in each patient at years 1, 3 and 5 of disease. The relationship between the burden of autoantibodies and outcomes, SDI (Systemic Lupus International Collaborative Clinics Damage Index), AMS (Adjusted Mean SLEDAI-2K) and AMS excluding anti-ds DNA (AMS-DNA) was evaluated as an association and as prediction. We determined the association between autoantibody burden and outcomes at years 1, 3 and 5 and the prediction using autoantibody burden at year 1 and year 3 to predict outcomes at years 3 and 5 respectively. RESULTS: Between 1992 and 2007, 235 inception patients were identified. Of these, 223, 163 and 129 patients had 10 or more autoantibodies tested at years 1, 3 and year 5 following diagnosis respectively. There was no association between the burden at years 1, 3 and 5 and outcome measures at years 1, 3 and 5 respectively. Furthermore, burden of autoantibodies at years 1 and 3 did not predict the outcome measures at years 3 and 5 respectively. CONCLUSIONS: Immunological burden in SLE at years 1, 3 or 5 as reflected by the number of autoantibodies found, was not associated with or predictive of subsequent disease activity or damage over time.

Atherosclerotic vascular events in a multinational inception cohort of systemic lupus erythematosus.

OBJECTIVE: To describe vascular events during an 8-year followup in a multicenter systemic lupus erythematosus (SLE) inception cohort and their attribution to atherosclerosis. METHODS: Clinical data, including comorbidities, were recorded yearly. Vascular events were recorded and attributed to atherosclerosis or not. All of the events met standard clinical criteria. Factors associated with atherosclerotic vascular events were analyzed using descriptive statistics, t-tests, and chi-square tests. Stepwise multivariate logistic regression was used to assess the association of factors with vascular events attributed to atherosclerosis. RESULTS: Since 2000, 1,249 patients have been entered into the cohort. There have been 97 vascular events in 72 patients, including: myocardial infarction (n = 13), angina (n = 15), congestive heart failure (n = 24), peripheral vascular disease (n = 8), transient ischemic attack (n = 13), stroke (n = 23), and pacemaker insertion (n = 1). Fifty of the events were attributed to active lupus, 31 events in 22 patients were attributed to atherosclerosis, and 16 events were attributed to other causes. The mean +/- SD time from diagnosis to the first atherosclerotic event was 2.0 +/- 1.5 years. Compared with patients followed for 2 years without atherosclerotic events (n = 615), at enrollment, patients with atherosclerotic vascular events were more frequently white, men, older at diagnosis of SLE, obese, smokers, hypertensive, and had a family history of coronary artery disease. On multivariate analysis, only male sex and older age at diagnosis were associated factors. CONCLUSION: In an inception cohort with SLE followed for up to 8 years, there were 97 vascular events, but only 31 were attributable to atherosclerosis. Patients with atherosclerotic events were more likely to be men and to be older at diagnosis of SLE.

Vitamin D insufficiency in a large female SLE cohort.

The objective of this study was to determine the vitamin D status and its relationship with disease and therapy features and with bone mineral density in women with systemic lupus erythematosus. Non-pregnant systemic lupus erythematosus women with dual-energy X-ray absorptiometry and vitamin D measurements performed between May 1 2005 and August 31 2006 were studied. In each patient, the lowest T-score of the first dual-energy X-ray absorptiometry scan during the study period was used. In postmenopausal women, a T-score > or = 1.0 standard deviation was considered normal, between -1.0 and -2.5 standard deviations osteopenia and < or = 2.5 standard deviations osteoporosis; in premenopausal women a T-score > or = 2.5 standard deviations was normal and < or = 2.5 standard deviations defined as reduced bone density. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were determined at the time of dual-energy X-ray absorptiometry. A 25-hydroxyvitamin D level of <80 nmol/L was defined as sub-optimal and a level <40 nmol/L as deficient. Demographic and clinical variables were investigated for association with vitamin D levels by univariate and multivariate analyses. One-hundred and twenty-four systemic lupus erythematosus women had dual-energy X-ray absorptiometry scans and vitamin D assays performed during the study period. Sub-optimal 25-hydroxyvitamin D levels were found in 82 (66.7%) and deficient 25-hydroxyvitamin D levels in 22 (17.9%) patients. The disease-related features examined at the time of vitamin D assays or bone mineral density showed no correlation with vitamin D levels by univariate analyses. Neither 25-hydroxyvitamin D nor 1,25-dihydroxyvitamin D was associated with bone mineral density status among these patients. A multivariate logistic regression model identified season, cumulative glucocorticoid exposure, and serum creatinine as being associated with 25-hydroxyvitamin D levels, whereas ethnicity, glucocorticoid exposure, and serum creatinine were associated with 1,25-dihydroxyvitamin D levels. In conclusion, sub-optimal vitamin D status is common in women with systemic lupus erythematosus and is related to season, cumulative glucocorticoid dose, and serum creatinine.

Variability and correlates of high sensitivity C-reactive protein in systemic lupus erythematosus.

In the general population, high-sensitivity C-reactive protein (hsCRP), a marker of inflammation, is relatively stable over time and independently predicts cardiovascular events. Systemic lupus erythematosus (SLE), a chronic inflammatory disease, is strongly associated with coronary artery disease (CAD). The objective of this study was to determine the variability and correlates of hsCRP in patients with SLE. Two cohorts from the University of Toronto Lupus Clinic, one with newly diagnosed and the other with prevalent SLE for 4 or more years, were selected. HsCRP was measured on serially collected samples, and hsCRP levels were ranked according to quartiles of cardiovascular risk. Correlates of hsCRP were determined using multivariate regression modelling with analysis of repeated measures. Among 58 patients in the inception cohort, over time, 36 (62%) moved from one hsCRP risk quartile to another. Among 414 patients in the prevalent cohort, 294 (71.0%) moved from one risk quartile to another. In both cohorts, within-patient variance comprised the majority of total variance in hsCRP levels. In multivariate regression analysis, hsCRP increased with age (P = 0.002), postmenopausal status (P = 0.03), smoking (P = 0.007) and presence of infection (P = 0.0001) and decreased with use of immunosuppressives (P = 0.02). There is marked variability of hsCRP level over time in SLE, regardless of disease duration. This variability is due to age and SLE treatment, menopausal status, smoking and the occurrence of infection. The variability of hsCRP in SLE casts doubt over its usefulness as an independent predictor of CAD risk in this disease and potentially in other chronic inflammatory diseases.

Hormone replacement therapy in women with systemic lupus erythematosus and risk of cardiovascular disease.

We sought to determine the impact of hormone replacement therapy (HRT) on the occurrence of coronary artery disease (CAD) in women with systemic lupus erythematosus (SLE). Women in the University of Toronto lupus database who had taken HRT with no history of CAD were compared with all post-menopausal female patients with no history of HRT or CAD. Chi-squared and t-tests were used to compare the risk factors of CAD and Kaplan-Meier curve, log rank test and proportional hazard model with time-dependent covariates were used to compare the time from entry into the clinic to occurrence of CAD. A total of 114 HRT-user patients with no history of CAD were compared with 227 post-menopausal non-HRT user SLE controls. The groups were similar with respect to lupus anticoagulant, antiphospholipid antibody, cumulative steroid dose and classic cardiac risk factors. A similar percentage of patients developed CAD in the control (13.7%) and HRT (11.4%) groups. There was no difference in the time to development of CAD. In the multivariate analysis, HRT was not a risk factor for CAD. Only age (P = 0.0001, HR = 1.11, 95% CI = 1.05, 1.17) and SLEDAI-2K (P = 0.0001, HR = 1.10, 95% CI = 1.05, 1.16) were significantly associated with the risk of CAD. In this small group of patients with SLE, HRT alone did not appear to predispose to CAD.

Economic benefits for the family of inactivated subunit virosomal influenza vaccination of healthy children aged 3-14 years during the annual health examination in private paediatric offices.

Taking the results of a prospective cohort study by our group that evaluated the effectiveness of the inactivated subunit virosomal influenza vaccine (Inflexal V), Crucell-Berna) in the prevention of influenza-related diseases and the reduction of its negative economic consequences, the economic costs and benefits for the family of vaccinating a theoretical cohort of 1000 healthy children aged 3-14 years with no risk factors with one dose of vaccine during the yearly health examination were quantiified. The economic analysis was carried out from the family perspective and the time horizon of the study was established at 6 months. In the base case, the net present value was 21,551.62 euros (21.5 euros per vaccinated child), and the benefit-cost ratio was 2.15, meaning that 1.15 euros is saved per euro invested.

Association of killer cell immunoglobulin-like receptor genotypes with vascular arterial events and anticardiolipin antibodies in patients with lupus.

To determine whether killer cell immunologlobulin-like receptor (KIR) genotypes are associated with vasculitis, vascular arterial events or anticardiolipin (aCL) antibodies in patients with lupus. A total of 304 patients followed prospectively at the University of Toronto Lupus Clinic were assessed for the occurrence of vasculitis and vascular arterial events. Molecular HLA-C and KIR (presence or absence of KIR2DL1, 2DL2, 2DL3, 2DS1 and 2DS2) genotyping were performed. Chi-square and logistic regression were used to analyse association between KIR genes and vascular arterial events and aCL antibodies. In patients with vascular arterial events, there was a significant increase in KIR2DS2 (60% vs 45%, P = 0.02) and in KIR2DL2 (62% vs 47%, P = 0.01) compared with patients without events. There was no increase in activating KIR genotypes in patients with vasculitis. In patients with aCL antibodies, significant increases were seen in KIR2DS2 (54% vs 41%, P = 0.03) and KIR2DL2 (58% vs 41%, P = 0.003), but KIR2DL3 was decreased (87% vs 95%, P = 0.03). Logistic regression confirmed independent association of KIR2DS2 with vascular arterial events. We found an increase in KIR2DS2 in lupus patients with vascular arterial events, but not in patients with vasculitis.