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.

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.

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.

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.

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.

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.

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.

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.

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.

[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.

Possible branchiogenic carcinoma coinciding with metastatic papillary thyroid carcinoma.

We report the discovery of a cystic lesion of flat lining epithelium with areas of squamous carcinoma, associated with metastatic cervical nodes of a papillary thyroid cancer, and discuss the diagnostic possibilities.

Henoch-Schönlein purpura as a clinical presentation of small cell lung cancer.

Although exceptionally, Henoch-Schönlein purpura (HSP) may appear as a paraneoplastic syndrome. We report a patient presenting with HSP. A chest X-ray showed a pulmonary nodule, while biopsy of a transthoracic needle aspiration revealed small cell lung cancer. To the best of our knowledge, HSP as a clinical presentation of small cell lung cancer has not been previously reported.

The clinical spectrum of osteoarticular tuberculosis in non-human immunodeficiency virus patients in a defined area of northwestern Spain (1988-1997).

OBJECTIVE: To examine the frequency and clinical manifestations of osteoarticular tuberculosis in non-human immunodeficiency virus (HIV) patients during the past 10 years in a northwestern area of Spain. METHODS: The charts of all patients older than 14 years of age, not HIV-infected, and diagnosed as having osteoarticular tuberculosis at the Xeral-Calde Hospital from 1988 through 1997 were reviewed. All patients were residents of the region of Lugo. The diagnosis of osteoarticular tuberculosis was made on the basis of a positive culture for Mycobacterium tuberculosis from synovial fluid, joint tissue or paravertebral abscess or by histological findings of caseating granulomas in biopsied tissue. RESULTS: Thirty-two HIV-negative patients (20 men and 12 women) were diagnosed with osteoarticular tuberculosis. The average annual incidence rate of osteoarticular tuberculosis in the combined (male and female) non-HIV population > or = 15 years of age was 15.68/million (95% CI: 10.25; 21.11); males 20.02/million (95% CI: 11.25; 28.79); females 11.52/million (95% CI: 5.00; 18.03). The age at the time of diagnosis was 60.8 +/- 17.5 years. Peripheral monoarthritis was observed in 16 of the 32 cases. The knee was the most frequent site of peripheral tuberculous arthritis (31%), but involvement of the non-weight-bearing joints (50%) was also common. Spondylitis involving the lower thoracic and upper lumbar vertebrae (31%) and unilateral sacroiliitis (19%) were less commonly observed. In general, patients with osteoarticular tuberculosis had a long duration of symptoms of the disease prior to the diagnosis (median: 5.5 months). The tuberculin skin test was negative in 3 cases. Chest radiograph was abnormal in only 6 of 32 patients (19%). The ESR (mean +/- SD) at the time of diagnosis was 55.7 +/- 29.0 mm/hr. Computed tomography was very useful in detecting early involvement of the sacroiliac joints and in defining the extent of the abscesses and the severity of the involvement in patients with spondylitis. All patients received chemotherapy for tuberculosis. None of them suffered relapses of tuberculosis. CONCLUSION: Tuberculosis is a major source of osteoarticular complications in northwestern Spain. The prevailing low level of clinical suspicion may explain the long delay to the diagnosis in most patients. A greater awareness of the possibility of this severe complication, especially in the elderly people or in high-risk populations, would be advisable.

Relationship of the dose of intravenous gammaglobulin to the prevention of infections in adults with common variable immunodeficiency.

The objective was to assess clinical efficacy of 3 dosages of intravenous gammaglobulins to prevent infectious episodes in adult common variable immunodeficiency. We designed a randomized, double blind, dose-assessing study. The setting was at University Hospital, Out-patient Clinic. Our patients were twenty-one adult patients with common variable immunodeficiency. The measurements were comparative study of the number and severity of infections using 3 various dosages of intravenous gammaglobulins, each given monthly for M least 6 months. Results indicated four hundred and eighty-four infectious episodes occurred while giving 305 infusions of IVIG 200 mg/kg; 205 infectious episodes while giving 170 infusions of 400 mg/kg and 436 infectious episodes while giving 247 infusions of 600 mg/kg. The morbidity scores (infection/infusion) were 1.59, 1.21 and 1.77 respectively (p - N/S). There was no significant difference in the severity of infections on the above 3 dosages, and no difference in the duration of infection-free intervals. The conclusions resulted in no significant differences in morbidity in adult patients with common variable immunodeficiency treated in cross-over pattern with IVIG 200 mg/kg, 400 mg/kg and 600 mg/kg. Thus, high dosages of IVIG are not conferring better protection against infections in such patients.

Henoch-Schönlein purpura as clinical presentation of a myelodysplastic syndrome.

Small-vessel vasculitis may be a paraneoplastic syndrome. It may be associated with haematologic malignancies and less frequently with solid tumors. We describe a patient with myelodysplastic syndrome presenting as Henoch-Schönlein Purpura. To our knowledge this association has not previously reported.

Clinical characteristics and response to newer quinolones in Legionella pneumonia: a report of 28 cases.

Twenty-eight (11.6%) out of 241 Spanish patients enrolled in an international phase III clinical trial of mild to moderate community-acquired pneumonia (CAP) comparing gemifloxacin vs. trovafloxacin were diagnosed of Legionnaires' disease. A definite diagnosis was established by seroconversion in 13 patients of whom only 2 had a positive Legionella urinary antigen. The remaining 15 patients were possible Legionella infections based on a single elevated IgG titer (> or = 1:512). All patients had a radiologically confirmed diagnosis of pneumonia, 5 (19%) patients were older than 65, comorbidity was present in 9 (33%), and 10 (36%) had to be hospitalized. Fifteen patients were treated with oral gemifloxacin (320 mg/day) and 13 with oral trovafloxacin (200 mg/day). Overall, clinical success occurred in 25 (89.3%) patients after 7 days of treatment and only 1 patient needed a 14-day treatment. There were only one adverse event withdrawal and one clinical failure, and no patients died. In light of the favorable clinical outcome, the use of newer fluoroquinolones seems adequate for the treatment of suspected or proven Legionella pneumonia.

[Delayed reposition of gastrostomy tube using Savary's dilators]. / Reposición diferida de sonda de gastrostomía utilizando dilatadores de Savary.

The delay in substituting a gastrostomy tube after removal leads to the gastrocutaneous tract closure and to the impossibility of putting other nourishment tube without needing another complete endoscopic procedure. We have used the technique described by Tsang through the one which and using Savary's dilators, the stenosed gastrocutaneous tract after accidental removal of the tube, is dilated permitting to put in a simple way a new one. We accomplished the procedure in three patients that attended by removal of the probe and severe stenosis of the stoma. In all they and under endoscopic control we put a new tube in a way rapid and without complications.

Hospitalization due to adverse drug reactions and drug interactions before and after HAART.

OBJECTIVE: To characterize and compare the rates of adverse drug reactions (ADRs) and interactions on admission in two, one-year periods: pre-highly active antiretroviral therapy (HAART) (phase 1) and post-HAART (phase 2). DESIGN: Retrospective chart review. SETTING: University-affiliated tertiary care centre. POPULATION STUDIED: HIV-positive patients admitted to hospital. MAIN RESULTS: In phase 1, 436 of 517 admissions, and, in phase 2, 323 of 350 admissions were analyzed. Over 92% of patients were male, with a mean age of 38 years. Significant differences (P<0.05) in the mean length of stay (12.08 versus 10.02 days), the CD4 counts (99.25 versus 129.45) and the number of concurrent diseases (4.20 versus 3.63) were found between phase 1 and 2, respectively. The mean number of medications taken (5.52 versus 5.94) and the rates of hospitalization with ADRs (20.4% versus 21.4%) or interactions (2.5% versus 2.16%) were similar between the two phases. Antiretrovirals were more common in ADR admissions post-HAART (21.3% versus 36.2%), while antiparasitics, psychotherapeutics and antineoplastics were more common pre-HAART. Other classes of drugs involved in both phases were sulphonamides, narcotics, ganciclovir, foscarnet, antimycobacterials and antifungals. ADR causality was possible or probable in more than 80% of cases. Over 60% of ADRs were grades 3 to 4, and about 85% were either the main or contributing reason for admission. About 65% of patients had at least partial recovery at the time of discharge. In phases 1 and 2, 8.9% and 2.9% of admissions,respectively, with ADRs were fatal. CONCLUSIONS: Although hospitalizations with ADRs and interactions were similar in both phases, HAART therapy has had a significant impact on the incidence and nature of ADRs at St Michael's Hospital, Wellesley Central Site, Toronto, Ontario.