Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Chronic Coronary Syndrome: A Double-Blind, Randomized, Sham-Controlled Trial.

The Clinical Efficacy of Permanent Internal Mammary Artery Occlusion in Chronic Coronary Syndrome (CLIMACCS) trial, a randomized, sham-controlled trial, tested the clinical efficacy of permanent internal mammary artery (IMA) device occlusion on symptoms in patients with chronic coronary syndrome (CCS), coronary artery occlusive blood supply, and myocardial ischemia. This was a prospective trial in 101 patients with CCS randomly allocated (1:1) to IMA device occlusion (verum group) or to IMA sham intervention (placebo group). The primary study end point was the change in treadmill exercise time (ET) (ΔET in seconds) at 6 weeks after trial intervention. Secondary study end points were the changes in collateral flow index (CFI) and angina pectoris during a simultaneous 1-minute proximal balloon occlusion of a coronary artery. CFI is the ratio between simultaneous mean coronary occlusive, divided by mean aortic pressure, both subtracted by central venous pressure. In the verum and placebo groups, the ET changed from 398 ± 176 seconds to 421 ± 198s in the verum group (p = 0.1745) and from 426 ± 162 seconds to 430 ± 166 seconds in the placebo group (p = 0.55); ΔET amounted to +23 ± 116s and +4 ± 120 seconds, respectively (p = 0.44). CFI change during follow-up equaled +0.022 ± 0.061 in the verum and -0.039 ± 0.072 in the placebo group (p <0.0001). Angina pectoris at follow-up during the coronary balloon occlusion for CFI measurement had decreased or disappeared in 20 of 48 patients in the verum group and in 9 of 47 patients in the placebo group (p = 0.0242). In conclusion, permanent IMA device occlusion tends to augment treadmill ET in response to increased coronary artery occlusive blood supply, which is reflected by mitigated symptoms and signs of myocardial ischemia.

Major low-energy trauma results in non-specific immunoglobulin generation without evidence for specific autoantibody production: A prospective cohort study.

Cellular debris resulting from large trauma might overwhelm the scavenger mechanisms and lead to autoimmune reactions. We analysed whether a major well-defined trauma in humans induces laboratory signs of transient autoimmunity in the months after the insult. We included 50 patients with pertrochanteric femur fracture undergoing intramedullary nail osteosynthesis in a prospective cohort study and followed them at 3-4 days, 6 weeks, 12 weeks and 12 months postoperatively. By standard techniques, we assessed levels of total immunoglobulins, anti-nuclear antibodies (ANA), anti-cardiolipin antibodies, anti-dsDNA antibodies and anti-C1q antibodies, as well as antibodies against cytomegalovirus (CMV) as a control. Blood leukocyte differential and lymphocyte subpopulations were determined at baseline and in the first two postoperative samples. The mean age of the patients reached 80.1 years, and 23 (46%) completed all visits. Serum concentrations of total IgG, IgM and IgA increased at all follow-up time points. The ANA fluorescence light intensity units increased at 12 weeks and 12 months postoperatively (p < 0.0001), but the proportion of ANA-positive patients did not change (35%). The values of anti-C1q mildly increased at all follow-up visits, but not the ratio to total IgG. Anti-dsDNA remained negative in all patients, and anti-cardiolipin IgG/IgM antibodies did not change. Anti-CMV IgG antibodies increased significantly at all follow-up visits, without change in the ratio to total IgG. Flow cytometry showed an increased proportion of B-cells 3-4 days postoperatively. In conclusion, major musculoskeletal trauma in elderly patients induces a generalized non-specific increase in immunoglobulin production without laboratory signs for enhanced systemic autoimmunity.

Algorithm for real-time analysis of intracoronary electrocardiogram.

Introduction: Since its first implementation in 1985, intracoronary (ic) electrocardiogram (ECG) has shown ample evidence for its diagnostic value given the higher sensitivity for myocardial ischemia detection in comparison to surface ECG. However, a lack of online systems to quantitatively analyze icECG in real-time prevents its routine use. The present study aimed to develop and validate an autonomous icECG analyzing algorithm. Materials and methods: This is a retrospective observational study in 100 patients with chronic coronary syndrome. From each patient, a non-ischemic as well as ischemic icECG at the end of a 1-min proximal coronary balloon occlusion was available. An ECG expert as well as the newly developed algorithm for autonomous icECG analysis measured the icECG ST-segment shift in mV for each icECG tracing. Results: Intraclass correlation coefficient (ICC) demonstrated low variability between the two methods (ICC = 0.968). Using the time point of icECG recording as allocation reference for absent or present myocardial ischemia, ROC-analysis for ischemia detection by the manually determined icECG ST-segment shift showed an area under the curve (AUC) of 0.968 ± 0.021 (p < 0.0001). AUC for the algorithm analysis was 0.967 ± 0.023 (p < 0.0001; p = 0.925 for the difference between the ROC curve AUCs). Time to complete analysis was below 1,000 ms for the autonomous icECG analysis and above 5 min for manual analysis. Conclusion: A newly developed autonomous icECG analysing algorithm detects myocardial ischemia with equal accuracy as manual ST-segment shift assessment. The algorithm provides the technical fundament for an analysing system to quantitatively obtain icECG in real-time.

Epitope-Specific Anti-C1q Autoantibodies in Systemic Lupus Erythematosus.

Objective: In patients with systemic lupus erythematosus (SLE) complement C1q is frequently targeted by autoantibodies (anti-C1q), that correlate best with active renal disease. Anti-C1q bind to largely unknown epitopes on the collagen-like region (CLR) of this highly functional molecule. Here we aimed at exploring the role of epitope-specific anti-C1q in SLE patients. Methods: First, 22 sera of SLE patients, healthy controls and anti-C1q positive patients without SLE were screened for anti-C1q epitopes by a PEPperMAP® microarray, expressing CLR of C1q derived peptides with one amino acid (AA) shift in different lengths and conformations. Afterwards, samples of 378 SLE patients and 100 healthy blood donors were analyzed for antibodies against the identified epitopes by peptide-based ELISA. Relationships between peptide-specific autoantibodies and SLE disease manifestations were explored by logistic regression models. Results: The epitope mapping showed increased IgG binding to three peptides of the C1q A- and three of the C1q B-chain. In subsequent peptide-based ELISAs, SLE sera showed significantly higher binding to two N-terminally located C1q A-chain peptides than controls (p < 0.0001), but not to the other peptides. While anti-C1q were associated with a broad spectrum of disease manifestations, some of the peptide-antibodies were associated with selected disease manifestations, and antibodies against the N-terminal C1q A-chain showed a stronger discrimination between SLE and controls than conventional anti-C1q. Conclusion: In this large explorative study anti-C1q correlate with SLE overall disease activity. In contrast, peptide-antibodies are associated with specific aspects of the disease suggesting epitope-specific effects of anti-C1q in patients with SLE.