Objective
The primary objective of this study was to evaluate the safety of rituximab in antiphospholipid antibody (aPL)–positive patients with non‐criteria manifestations of antiphospholipid ...syndrome (APS). The secondary objectives were to evaluate the effect of rituximab on the aPL profile and to evaluate the efficacy of rituximab treatment for non‐criteria manifestations of APS.
Methods
In this 12‐month, phase II pilot study, adult aPL‐positive patients with thrombocytopenia, cardiac valve disease, skin ulcer, aPL nephropathy, and/or cognitive dysfunction received 2 doses of rituximab (1,000 mg) on days 1 and 15. Antiphospholipid antibody profiles and clinical outcome measures, which were categorized as complete response, partial response, no response, or recurrence, were analyzed at preset time points.
Results
Two of 19 patients experienced infusion reactions, resulting in early termination. Twelve serious adverse events and 49 nonserious adverse events were recorded. All patients who had positive results of lupus anticoagulant, anticardiolipin, and anti–β2‐glycoprotein I antibody tests at baseline had positive results at 24 weeks and 52 weeks. The numbers of patients with a complete response, a partial response, no response, and recurrence for the clinical outcome measures at 24 weeks were as follows: for thrombocytopenia, 1, 1, 2, and 0, respectively; for cardiac valve disease, 0, 0, 3, and not analyzed, respectively; for skin ulcer, 3, 1, 0, and 1, respectively; for aPL nephropathy, 0, 1, 0, and 0, respectively; and for cognitive dysfunction, 3, 1, 1, and not analyzed, respectively.
Conclusion
The results of this uncontrolled and nonrandomized pilot study suggest that the safety of rituximab in aPL‐positive patients is consistent with the safety profile of rituximab. Despite causing no substantial change in aPL profiles, rituximab may be effective in controlling some but not all non‐criteria manifestations of APS.
The American College of Rheumatology's case definitions for 19 neuropsychiatric syndromes in systemic lupus erythematosus (SLE) constitute a comprehensive classification of nervous system events in ...this disease. However, additional strategies are needed to determine whether a neuropsychiatric syndrome is attributable to SLE versus a competing comorbidity. Cognitive function is a clinical surrogate of overall brain health, with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of neuropsychiatric SLE (NPSLE), including abnormalities of the blood–brain barrier and autoantibody‐mediated production of proinflammatory cytokines. Advances in neuroimaging provide a platform to assess novel disease mechanisms in a noninvasive way. The convergence of more rigorous clinical characterization, validation of biomarkers, and brain neuroimaging provides opportunities to determine the efficacy of novel targeted therapies in the treatment of NPSLE.
The Randomized On versus Off Bypass trial reported conversion of 12.4% (n = 137) off-pump coronary artery bypass (OPCAB) patients and 3.6% (n = 40) on-pump cardiopulmonary bypass (CPB) patients. This ...paper explored outcomes after conversions.
Elective and urgent CABG patients (n = 2,203) at 18 sites were studied. Randomization within 54 participating surgeons occurred preoperatively, after which conversion occurred if clinically indicated. Conversion reasons and outcomes were captured prospectively with additional details retrospectively extracted from patient records by a core clinical group.
Conversion rates varied considerably across participating surgeons. Converted OPCAB patients had more right coronary disease and coronary targets less than 1.5 mm. Conversions were elective in 49.3% of cases, urgent in 27.2%, or emergent in 23.5%. Elective conversions were mainly for poor exposure-intramyocardial vessel (35.8%). Urgent and emergent conversions were usually for hemodynamic instability (89.2% and 75.0%, respectively). Compared with CPB and OPCAB patients, OPCAB-converted patients had more 30-day complications and deaths (composite outcome rate of 5.7% and 5.5% vs 17.5% respectively, p < 0.001). Thirty-day outcomes for OPCAB-converted patients trended worse for emergent versus elective conversions (31.3% vs 13.4%, respectively, p = 0.05). One-year composite outcome rate (death, nonfatal myocardial infarction or revascularization) in OPCAB-converted patients was worse than in CPB patients (13.5% vs 7.1%, p = 0.02), but similar to OPCAB-nonconverted (9.4%).
The OPCAB patients requiring conversion had worse 30-day and 1-year outcomes. The OPCAB patients with right coronary artery disease or small targets were more often converted. The 30-day composite outcome trended worst for emergent OPCAB conversions.
Observational studies have documented an off-pump over on-pump advantage for high-risk patients, including diabetic patients. Randomized trials have not confirmed this advantage. The VA Randomization ...On Versus Off Bypass (ROOBY) trial randomly assigned 2,203 coronary artery bypass graft surgery (CABG) patients at 18 sites to either on-pump (n=1,099) or off-pump (n=1,104) procedures. An a priori ROOBY aim was to evaluate treatment impact on diabetic patients.
Actively treated diabetic patients (n=835, receiving oral hypoglycemic or insulin medications) received off-pump CABG (n=402) or on-pump CABG (n=433). The primary ROOBY trial endpoints were a short-term composite (30-day operative death or major complications) and a 1-year composite (death, nonfatal acute myocardial infarction, or repeat revascularization). Secondary ROOBY endpoints included 1-year all-cause death, 1-year graft patency, 1-year changes from baseline in neurocognitive status and health-related quality of life, and costs.
Diabetic patients' risk factors at baseline were balanced across treatments. For diabetic patients, the primary short-term composite outcome rate showed a worse trend for off-pump (8.0%) than on-pump (3.9%, p=0.013), with no difference in the 1-year primary composite outcome or 1-year death rate. One-year patency was 83.1% off-pump versus 88.4% on-pump (p=0.004). No differences were found in neurocognitive, health-related quality of life, discharge cost, and 1-year cumulative cost.
Concordant with the ROOBY trial's overall findings, off-pump CABG yielded no advantage over on-pump CABG for actively treated diabetic patients. The 1-year graft patency was lower and the short-term composite trended higher for off-pump CABG, with no other significant outcome or cost differences.
Information on the benefits of pulmonary rehabilitation (PR) in patients with idiopathic pulmonary fibrosis (IPF) is growing, but PR's effects on certain important outcomes is lacking.
We conducted a ...pilot study of PR in IPF and analyzed changes in functional capacity, fatigue, anxiety, depression, sleep, and health status from baseline to after completion of a standard, 6-week PR program.
Six-min walk distance improved a mean ± standard error 202 ± 135 feet (P = .01) from baseline. Fatigue Severity Scale score also improved significantly, declining an average 1.5 ± 0.5 points from baseline. There were trends toward improvement in anxiety, depression, and health status.
PR improves functional capacity and fatigue in patients with IPF. (Clinical Trials.gov registration NCT00692796.)
The Randomized On versus Off Bypass trial found no difference for a global cognitive outcome measure for patients receiving on-pump versus off-pump coronary artery bypass graft surgery (CABG). In ...this report, we present the baseline patient characteristics that were predictive of post-CABG cognitive decline as well as compare cognitive outcomes between treatment arms.
A neuropsychological battery was administered preoperatively and at 1 year after undergoing CABG. Stepwise regression was used to identify demographic or clinical risk factors associated with cognitive decline. Neuropsychological data were converted to demographically corrected T scores to provide impairment levels.
Overall 1,156 patients (581 on-pump, 575 off-pump) completed match-paired neuropsychological assessments at baseline and 1-year follow-up. Baseline cognitive score, age, education level, and ethnicity predicted cognitive decline after CABG. Only 20% of either group had mild impairment at baseline on three of the test scores, and less than 10% had severe impairment on individual tests at either time. Few subjects in either group transitioned to clinically impaired levels at follow-up on individual tests.
At baseline, lower cognitive function, older age, lower education, and ethnicity other than white were predictive of cognitive decline after CABG. Patients in both groups demonstrated low frequencies of cognitive impairment on individual tests at baseline and follow- up, and few patients in either group were classified as impaired at 1-year follow-up on individual tests. In general, the Randomized On versus Off Bypass study documented that neither on-pump nor off-pump CABG adversely impacts long-term brain function.
Background Heavy smokers perform worse on neuropsychological assessment than age-matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest ...amount of variance in cognition. The current objective was to determine whether carotid artery stiffness is associated with cognition in former smokers beyond the effects of amount of smoking and pulmonary function. Methods and Results Eighty-four former smokers including individuals across a spectrum of airflow limitation severity were included: 30 without chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease GOLD 0 with normal spirometry and lung computed tomography), 31 with mild-moderate chronic obstructive pulmonary disease (GOLD 1-2), and 23 with severe-very severe chronic obstructive pulmonary disease (GOLD 3-4). Participants completed questionnaires, spirometry, carotid ultrasonography, and neuropsychological testing. Multiple linear regression was used to determine whether carotid artery stiffness is associated with neuropsychological performance in 4 cognitive domains after adjusting for age, sex, pack-years of smoking, estimated premorbid intellectual functioning, and airflow limitation. Higher carotid artery β-stiffness index was associated with reduced executive functioning-processing speed in the fully adjusted model (β=-0.49, SE=0.14;
=0.001). Lower premorbid intellectual function, male sex, and presence of airflow limitation (GOLD 1 or 2 and GOLD 3 or 4) were also associated with worse executive functioning-processing speed. β-Stiffness index was not significantly associated with performance in other cognitive domains. Conclusions Carotid artery stiffness is associated with worse performance on executive functioning-processing speed in former smokers beyond the effects of aging, amount of past smoking, severity of airflow limitation, and hypoxemia. Future research should examine whether carotid stiffness can be used to identify former smokers at risk for subsequent cognitive impairment.
The American College of Rheumatology's case definitions for 19 neuropsychiatric syndromes in systemic lupus erythematosus (SLE) constitute a comprehensive classification of nervous system events in ...this disease. However, additional strategies are needed to determine whether a neuropsychiatric syndrome is attributable to SLE versus a competing comorbidity. Cognitive function is a clinical surrogate of overall brain health, with applications in both diagnosis and determination of clinical outcomes. Ischemic and inflammatory mechanisms are both key components of the immunopathogenesis of neuropsychiatric SLE (NPSLE), including abnormalities of the blood-brain barrier and autoantibody-mediated production of proinflammatory cytokines. Advances in neuroimaging provide a platform to assess novel disease mechanisms in a noninvasive way. The convergence of more rigorous clinical characterization, validation of biomarkers, and brain neuroimaging provides opportunities to determine the efficacy of novel targeted therapies in the treatment of NPSLE.
Coronary-artery bypass grafting (CABG) surgery may be performed either with cardiopulmonary bypass (on pump) or without cardiopulmonary bypass (off pump). We report the 5-year clinical outcomes in ...patients who had been included in the Veterans Affairs trial of on-pump versus off-pump CABG.
From February 2002 through June 2007, we randomly assigned 2203 patients at 18 medical centers to undergo either on-pump or off-pump CABG, with 1-year assessments completed by May 2008. The two primary 5-year outcomes were death from any cause and a composite outcome of major adverse cardiovascular events, defined as death from any cause, repeat revascularization (CABG or percutaneous coronary intervention), or nonfatal myocardial infarction. Secondary 5-year outcomes included death from cardiac causes, repeat revascularization, and nonfatal myocardial infarction. Primary outcomes were assessed at a P value of 0.05 or less, and secondary outcomes at a P value of 0.01 or less.
The rate of death at 5 years was 15.2% in the off-pump group versus 11.9% in the on-pump group (relative risk, 1.28; 95% confidence interval CI, 1.03 to 1.58; P=0.02). The rate of major adverse cardiovascular events at 5 years was 31.0% in the off-pump group versus 27.1% in the on-pump group (relative risk, 1.14; 95% CI, 1.00 to 1.30; P=0.046). For the 5-year secondary outcomes, no significant differences were observed: for nonfatal myocardial infarction, the rate was 12.1% in the off-pump group and 9.6% in the on-pump group (P=0.05); for death from cardiac causes, the rate was 6.3% and 5.3%, respectively (P=0.29); for repeat revascularization, the rate was 13.1% and 11.9%, respectively (P=0.39); and for repeat CABG, the rate was 1.4% and 0.5%, respectively (P=0.02).
In this randomized trial, off-pump CABG led to lower rates of 5-year survival and event-free survival than on-pump CABG. (Funded by the Department of Veterans Affairs Office of Research and Development Cooperative Studies Program and others; ROOBY-FS ClinicalTrials.gov number, NCT01924442 .).
On-pump versus off-pump coronary-artery bypass surgery Shroyer, A Laurie; Grover, Frederick L; Hattler, Brack ...
New England journal of medicine/The New England journal of medicine,
11/2009, Volume:
361, Issue:
19
Journal Article
Peer reviewed
Open access
Coronary-artery bypass grafting (CABG) has traditionally been performed with the use of cardiopulmonary bypass (on-pump CABG). CABG without cardiopulmonary bypass (off-pump CABG) might reduce the ...number of complications related to the heart-lung machine.
We randomly assigned 2203 patients scheduled for urgent or elective CABG to either on-pump or off-pump procedures. The primary short-term end point was a composite of death or complications (reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure) before discharge or within 30 days after surgery. The primary long-term end point was a composite of death from any cause, a repeat revascularization procedure, or a nonfatal myocardial infarction within 1 year after surgery. Secondary end points included the completeness of revascularization, graft patency at 1 year, neuropsychological outcomes, and the use of major resources.
There was no significant difference between off-pump and on-pump CABG in the rate of the 30-day composite outcome (7.0% and 5.6%, respectively; P=0.19). The rate of the 1-year composite outcome was higher for off-pump than for on-pump CABG (9.9% vs. 7.4%, P=0.04). The proportion of patients with fewer grafts completed than originally planned was higher with off-pump CABG than with on-pump CABG (17.8% vs. 11.1%, P<0.001). Follow-up angiograms in 1371 patients who underwent 4093 grafts revealed that the overall rate of graft patency was lower in the off-pump group than in the on-pump group (82.6% vs. 87.8%, P<0.01). There were no treatment-based differences in neuropsychological outcomes or short-term use of major resources.
At 1 year of follow-up, patients in the off-pump group had worse composite outcomes and poorer graft patency than did patients in the on-pump group. No significant differences between the techniques were found in neuropsychological outcomes or use of major resources. (ClinicalTrials.gov number, NCT00032630.).
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