Left-Atrial Appendage Thrombosis in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation

BackgroundData about the impact of left-atrial appendage thrombosis (LAAT) on early safety and mortality in patients undergoing transfemoral transcatheter aortic valve implantation (TF-TAVI) are scarce. We aimed to investigate the prevalence and predictors of LAAT and the outcome associated with this condition in patients treated by TF-TAVI.MethodsRetrospective data analysis was derived from a prospective single-centre registry comparing patients with and without LAAT regarding early safety at 30 days, according to Valve Academic Research Consortium-2 (VARC-2) and 2-year mortality.ResultsLAAT was found in 7.6% of the whole cohort (n = 2527) and in 16.6% in those patients with known pre-existing atrial fibrillation (AF cohort, n = 1099). Compared with controls, patients with LAAT were sicker, indicated by a higher Society of Thoracic Surgeons (STS) score and burden of comorbidities. Neither VARC-2–defined early safety at 30 days nor the rate of stroke was different between LAAT and controls in both the whole (early safety: 29.2% vs 24.2%, P = 0.123; stroke: 5.9% vs 4.7%, P = 0.495) and AF cohort (early safety: 29.1% vs 22.9%, P = 0.072; stroke: 5.6% vs 3.3%, P = 0.142). Evaluating the whole cohort in a univariate analysis, the 2-year mortality was significantly higher in LAAT compared with controls (hazard ratio, 1.41; 95% confidence interval, 1.07-1.86; P = 0.014). However, multivariate analysis of the whole cohort and the AF cohort revealed no association between LAAT and 2-year mortality.ConclusionsLAAT was frequent in patients undergoing TF-TAVI— in particular, in patients with histories of AF—but it was not associated with an increase in periprocedural complications and did not predict 2-year mortality.     

Abdominal infections in patients with acute leukaemia: a prospective study applying ultrasonography and microbiology

A prospective study of 62 chemotherapy-induced neutropenic episodes in patients with acute leukaemia was conducted to determine the incidence and causes of abdominal infections, and to assess the diagnostic value of the combined use of ultrasonography (US) and microbiology. Each patient underwent US of liver, gallbladder and complete bowel before chemotherapy, on days 2-4 after the end of chemotherapy and in cases of fever, diarrhoea or abdominal pain. US was combined with a standardized clinical examination and a broad spectrum of microbiological investigations. From January to August 2001, 243 US examinations were performed. The overall incidence of abdominal infectious diseases was 17.7% (11 out of 62, 95% confidence interval (CI): 9-29%). Four patients (6.5%) developed neutropenic enterocolitis; two of them died, two survived. Bowel wall thickening (BWT) > 4 mm in these four patients ranged from 5.8 to 23.6 mm and was detected only in one patient with mucositis. In three other patients (4.8%) Clostridium difficile, and in one patient (1.6%) Campylobacter jejuni, caused enterocolitis without BWT. Cholecystitis was diagnosed in three patients (4.8%) and hepatic candidiasis was strongly suspected in one patient. Abdominal infections caused by gastroenteritis viruses, cytomegalovirus (CMV) or Cryptosporidium were not observed. We conclude that in neutropenic patients with acute leukaemia receiving chemotherapy: (i) BWT is not a feature of chemotherapy-induced mucositis and should therefore be considered as sign of infectious enterocolitis; (ii) viruses, classic bacterial enteric pathogens (Salmonella, Shigella, Yersinia, Campylobacter, Aeromonas, Vibrio subsp., enterohaemorrhagic Escherichia coli) and Cryptosporidium have a very low incidence; and (iii) abdominal infections may be underestimated when US is not used in every patient with abdominal pain.     

Subclinical coronary atherosclerosis is more pronounced in men and women with lower socio-economic status: associations in a population-based study. Coronary atherosclerosis and social status.

BACKGROUND: Social inequalities of manifest coronary heart diseases are well documented in modern societies. Less evidence is available on subclinical atherosclerotic disease despite the opportunity to investigate processes underlying this association. Therefore, we examined the relationship between coronary artery calcification as a sign of subclinical coronary atherosclerosis, socio-economic status and established cardiovascular risk factors in a healthy population. DESIGN: Cross-sectional. METHODS: In a population-based sample of 4487 men and women coronary artery calcification was assessed by electron beam computed tomography quantified by the Agatston score. Socio-economic status was assessed by two indicators, education and income. First, we investigated associations between the social measures and calcification. Second, we assessed the influence of cardiovascular risk factors on this association. RESULTS: After adjustment for age, men with 10 and less years of formal education had a 70% increase in calcification score compared with men with high education. The respective increase for women was 80%. For income the association was weaker (among men 20% higher for the lowest compared with the highest quartile; and among women 50% higher, respectively). Consecutive adjustment for cardiovascular risk factors significantly attenuated the observed association of socio-economic status with calcification. CONCLUSIONS: Social inequalities in coronary heart diseases seem to influence signs of subclinical coronary atherosclerosis as measured by coronary artery calcification. Importantly, cumulation of major cardiovascular risk factors in lower socio-economic groups accounted for a substantial part of this association.     

Validation of in vivo myocardial strain measurement by magnetic resonance tagging with sonomicrometry

OBJECTIVES: This study was designed to validate strain measurements obtained using magnetic resonance tagging with spatial modulation of magnetization (SPAMM). We compared circumferential segment shortening measurements (%S) obtained using SPAMM to sonomicrometry %S in a canine model with (n = 28) and without (n = 3) coronary artery ligation. BACKGROUND: Magnetic resonance tagging enables noninvasive measurement of myocardial strain, but such strain measurements have not yet been validated in vivo. METHODS: Circumferential sonomicrometry crystal pairs were placed in apical myocardium at ischemic risk in ligation studies and in adjacent and remote myocardium. The %S was obtained from closely juxtaposed sonomicrometry and SPAMM sites. RESULTS: Paired data were available from 19 of 31 studies. Both methods distinguished remote from ischemic function effectively (p = 0.014 for SPAMM and p = 0.002 for sonomicrometry). SPAMM %S was similar to sonomicrometry %S in ischemic myocardium (2 +/- 3 vs. 0 +/- 3 p = 0.067) but was slightly higher than sonomicrometry %S in remote myocardium (11 +/- 10 vs. 7 +/- 5, p = 0.033). End-systolic (n = 30) and late systolic (n = 34) SPAMM %S correlated well with sonomicrometry %S (r = 0.84, p < 0.0001 and r = 0.88, p < 0.0001). CONCLUSIONS: Magnetic resonance tagging using SPAMM can quantitate myocardial strain in ischemic and remote myocardium. This study validates its application in scientific investigation and clinical assessment of patients with myocardial ischemia.     

Mediators of asthma: nitric oxide

Endogenous nitric oxide is an ubiquitous gaseous molecule that regulates many aspects of human airway biology including the modulation of airway and vascular smooth muscle tone. It is generated from the three different enzymes nitric oxide synthases (NOS) -1, -2 and -3 which are all expressed in pulmonary cells. NOS-1 is localised primarily to neuronal structures, where NO is a mediator of the inhibitory Non-Adrenergic Non-Cholinergic System and NOS-3 is present in endothelial cells. While these enzymes are constitutively expressed, NOS-2 is an inducible enzyme independent of calcium and highly induced in inflammatory diseases such as allergic asthma, where NO may act beneficial or deleterious depending on the site of and amount of generation. The use of NO-donor compounds or classical unselective NOS inhibitors did not lead to significant therapeutical effects in asthmatic patients. Insights on the precise role of NO in asthma can only be achieved by targeting NO generation selectively. More potent and selective NOS-2 inhibitors have to clarify a role of NOS-modification based therapy in clinical routine. NO can also be detected in the exhaled air. Increased levels of exhaled NO in asthmatic patients may be useful for a non-invasive determination of airway inflammation.     

Low Hemoglobin and Radiographic Damage Progression in Early Rheumatoid Arthritis: Secondary Analysis From a Phase III Trial

Objective

To study low blood hemoglobin concentrations as a predictor of radiographic damage progression in patients with rheumatoid arthritis (RA).

Methods

Post hoc analyses were performed in patients from the PREMIER trial with early RA undergoing 2 years of adalimumab (ADA), methotrexate (MTX), or ADA + MTX combination therapy. Low disease activity was defined as a score <3.2 on the 28‐joint Disease Activity Score using the C‐reactive protein level (DAS28‐CRP), and clinical response by the American College of Rheumatology criteria for 20% improvement at week 24. Baseline or mean hemoglobin concentrations over time, or anemia as defined using sex‐specific World Health Organization criteria, were analyzed in mixed‐effects models for longitudinal data in men and women as predictors of progressive joint damage, as measured by the modified total Sharp/van der Heijde score (ΔSHS). Data were adjusted for treatment and other patient characteristics, including the DAS28‐CRP.

Results

Baseline hemoglobin was inversely associated with ΔSHS in adjusted analyses (P < 0.05 for both sexes). Baseline anemia predicted greater ΔSHS in MTX‐treated patients over 104 weeks, and in ADA‐ and combination‐treated patients over 26 weeks. Lower hemoglobin concentrations over time, as well as time with anemia, were associated with greater damage progression (P < 0.001). The effect of low hemoglobin concentrations on joint damage progression remained significant, even in patients achieving low disease activity.

Conclusion

Low hemoglobin is a DAS28‐CRP‐independent predictor of radiographic joint damage progression in MTX‐treated patients with early RA. This effect decreases over time in ADA‐ and combination‐treated patients, and in clinical responders irrespective of treatment modality.