Effect of technique on outcomes following bioresorbable vascular scaffold implantation: analysis from the ABSORB trials

BACKGROUND: Procedural technique may affect clinical outcomes after bioresorbable vascular scaffold (BVS) implantation. Prior studies suggesting such a relationship have not adjusted for baseline patient and lesion characteristics that may have influenced operator choice of technique and outcomes. OBJECTIVES: This study sought to determine whether target lesion failure (TLF) (cardiac death, target-vessel myocardial infarction, or ischemia-driven target lesion revascularization) and scaffold thrombosis (ScT) rates within 3 years of BVS implantation are affected by operator technique (vessel size selection and pre- and post-dilation parameters). METHODS: TLF and ScT rates were determined in 2,973 patients with 3,149 BVS-treated coronary artery lesions from 5 prospective studies (ABSORB II, ABSORB China, ABSORB Japan, ABSORB III, and ABSORB Extend). Outcomes through 3 years (and between 0 to 1 and 1 to 3 years) were assessed according to pre-specified definitions of optimal technique (pre-dilation, vessel sizing, and post-dilation). Multivariable analysis was used to adjust for differences in up to 18 patient and lesion characteristics...

Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein.

OBJECTIVES: This study assessed coronary artery endothelial function in patients with hypercholesterolemia before and after lipid lowering, using quantitative angiography to examine the acetylcholine (Ach) response along the entire analyzable vessel. BACKGROUND: Lipid lowering reverses endothelial dysfunction, but whether improvement occurs only in some segments and not others has not been established. Statistical correlation of improvement with specific lipid moieties remains undefined. METHODS: Quantitative angiography was performed after Ach (10(-6), 10(-5), 10(-4) M) in 29 patients with coronary atherosclerosis before and 18 +/- 5.2 months after lipid-lowering treatment (statins, bile sequestrant resins). Standard lipid moieties and markers of oxidized low density lipoprotein (LDL) (immunoglobulin G and M autoantibody titers to malondialdehyde-LDL, E06 epitope) were measured serially. RESULTS: Pre-treatment of the vessel diameters at control and with 10(-6)M, 10(-5) M and 10(-4) M Ach were 2.108 +/- 0.085, 2.086 +/- 0.087, 2.069 +/- 0.084 and 1.963 +/- 0.097 mm (M +/- SE), respectively, and increased at follow-up to 2.139 +/- 0.094, 2.119 +/- 0.086, 2.127 +/- 0.084 and 2.080 +/- 0.085 mm (p < 0.0001). Improvement in the most constricted and modest declination in the more dilated segments were observed. Change in the E06 and Apolipoprotein A-1 titers correlated with improved vasomotion (p = 0.027 and 0.005, respectively). The pre- and post-treatment levels of the E06 epitope, as well as the post-treatment IgM autoantibody titer to MDA-low density lipoprotein, also correlated (p < 0.028, < 0.001 and p < 0.004, respectively). CONCLUSIONS: Drug treatment reverses endothelial dysfunction, but the effect is heterogeneous. Most coronary segments show enhancement, while others show declination of dilation, underscoring the importance of assessing the entire analyzable artery. Improvement in vasomotion correlates most significantly with markers of plasma-oxidized low-density lipoprotein.

Does hysteroscopy improve upon the sensitivity of dilatation and curettage in the diagnosis of endometrial hyperplasia or carcinoma?

OBJECTIVE: The objective of this study was to determine whether hysteroscopy improved upon the diagnostic sensitivity of dilatation and curettage (D+C) in the detection of endometrial hyperplasia and carcinoma. METHODS: A retrospective chart review was conducted of all patients undergoing hysteroscopy/D+C for abnormal uterine bleeding between 1991 and 1995. Hysteroscopic impressions and D+C diagnoses were compared. RESULTS: Three hundred seventy-three patients were included in the study. Of the 61 patients with D+C demonstrating hyperplasia, the hysteroscopic impression was hyperplasia in 32 (52%). Of the 10 patients with D+C demonstrating carcinoma, the hysteroscopic impression was hyperplasia in 8 (80%) and carcinoma in 2 (20%). Two additional cases of carcinoma were diagnosed within 6 months of hysteroscopy/D+C, and both had been missed on both hysteroscopy and D+C. Of 204 patients with a normal hysteroscopic impression, 23 (11%) had hyperplasia on D+C. CONCLUSIONS: Hysteroscopy did not improve upon the sensitivity of D+C in the detection of endometrial hyperplasia or carcinoma.

Regulation of myocardial contractility: Insights from transgenic mice.

Myocardial contraction occurs when calcium (Ca(2+)) is released from the sarcoplasmic reticulum, binding troponin C and allowing actin and myosin to cross link. Ca(2+) release and uptake is closely regulated by G protein-coupled ß-adrenergic receptors through the action of the second messenger cAMP. An increase in cAMP level leads to phosphorylation of key regulatory proteins affecting intracellular Ca(2+) homeostasis. The ß-adrenergic receptors themselves are regulated by a set of specific kinases, termed the G-protein-coupled receptor kinases (GRKs). The study of this complex system in vivo has recently been advanced by the development of transgenic and gene-targeted (knockout) mouse models. Combining transgenic technology with sophisticated physiological measurements of cardiac hemodynamics is an extremely powerful approach to the study of myocardial contractility and its regulation. This review focuses on several recent transgenic mouse models that have increased our understanding of the regulation of cardiac contractility.

Doxycycline prophylaxis for shigellosis.

The efficacy of oral doxycycline, 100 mg/d for 14 days, in reducing the incidence of shigellosis in newcomers to an area hyperendemic for the disease was examined in a double-blind, placebo-controlled trial. Of 107 entrants, 100 completed the study; 50 received the drug and 50 received a placebo. Diarrheal disease and associated symptoms were monitored for 8 weeks. Starting on the 3rd day of the trial, an outbreak was observed, and Shigella flexneri type 2a was isolated from 6 subjects. Eight of the subjects in the treatment group had diarrhea (16%) compared with 37 in the placebo group (74%), providing a 79% protection rate. There was no significant difference in the occurrence of accompanying symptoms between the subjects suffering from diarrhea in both groups, but the duration of disease was shorter in the treatment group. Serologic study of the outbreak showed no significant difference in antibody response to S flexneri between the treatment (14 of 43) and placebo (18 of 39) groups. Doxycycline prophylaxis apparently is effective and probably does not prevent subclinical infection.

Autoimmune diseases other than lupus share common anti-DNA idiotypes.

We examined the sera of 170 patients with various autoimmune diseases other than systemic lupus erythematosus (SLE) for the presence of an anti-DNA antibody idiotype termed 16/6 and known to occur with high frequency in sera of patients with SLE. The idiotype was found in 6/15 sera from patients with polymyositis (49%), 3/18 with multiple sclerosis (17%), 3/18 with primary Sjögren's syndrome (18%), 9/40 with autoimmune thyroid diseases (23%), 2/35 with myasthenia gravis (6%), and 3/42 patients with rheumatoid arthritis (7%). The idiotype was not detected among 12 patients with scleroderma or 77 normal controls. The presence of the 16/6 idiotype was associated with the presence of another anti-DNA idiotype termed 134-Id. Serum samples were also tested for activity against DNA, various synthetic polynucleotides, and cardiolipin. The serum activity against these antigens was found to be polyspecific, though overlap in reaction against the various polynucleotides was not absolute. The 16/6 idiotype is thought to be coded by a germline gene. The presence of this idiotype in various autoimmune diseases points to a pathophysiologic link between the diseases.

Detection of anti-histone activity in sera of patients with monoclonal gammopathies.

Sera from 249 patients with monoclonal gammopathies (85 multiple myeloma, 92 benign monoclonal gammopathies, 53 cryoglobulinemia, 19 Waldenström's macroglobulinemia) were examined for the presence of anti-histone activity. Thirty-four sera were found positive. In 12 of these cases the serum monoclonal immunoglobulins were purified and in all, the anti-histone activity appeared to reside in the monoclonal component. None of the patients had symptomatology of lupus despite high titers of anti-histone activity. This study demonstrates an anti-histone activity of monoclonal components of patients with monoclonal gammopathies.

The detection of a common idiotype of anti-DNA antibodies in the sera of patients with monoclonal gammopathies.

The sera of 265 patients with monoclonal gammopathies were examined for the presence of a dominant idiotype of the anti-DNA antibody [16/6 idiotype (Id)] and for anti-DNA activity. An enzyme-linked immunosorbent assay (ELISA) with a rabbit anti-16/6 antibody revealed 23 (8.7%) sera that contained increased concentrations of the idiotype. Seven of the patients had benign monoclonal gammopathy, three multiple myeloma, three Waldenström macroglobulinemia, five essential mixed cryoglobulinemia, and five monoclonal cryoglobulinemia. In 5 of the 23 sera, antinuclear activity was also noted. In 11 of the 16/6 Id-positive sera the anti-nucleic acid antibody reactions were found to be polyspecific, reacting with polydeoxythymidilic acid and polyinosinic acid, in addition to single-stranded DNA and double-stranded DNA. Similar results were achieved with the purified serum monoclonal components. The specificity of the idiotype analysis was demonstrated with an unrelated dominant idiotype of anti-HBsAg antibody. In none of the patients, except one (with essential mixed cryoglobulinemia), was lupus symptomatology noted.