Ischemic Burden Reduction and Long-Term Clinical Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention

ObjectivesThe authors sought to evaluate the impact of ischemic burden reduction after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) on long-term prognosis and cardiac symptom relief.BackgroundThe clinical benefit of CTO PCI is questioned.MethodsIn a high-volume CTO PCI center, 212 patients prospectively underwent quantitative [¹⁵O]H₂O positron emission tomography perfusion imaging before and three months after successful CTO PCI between 2013-2019. Perfusion defects (PD) (in segments) and hyperemic myocardial blood flow (hMBF) (in ml · min^?1 · g^?1) allocated to CTO areas were related to prognostic outcomes using unadjusted (Kaplan-Meier curves, log-rank test) and risk-adjusted (multivariable Cox regression) analyses. The prognostic endpoint was a composite of all-cause death and nonfatal myocardial infarction.ResultsAfter a median [interquartile range] of 2.8 years [1.8 to 4.3 years], event-free survival was superior in patients with ≥3 versus <3 segment PD reduction (p < 0.01; risk-adjusted p = 0.04; hazard ratio [HR]: 0.34 [95% confidence interval (CI): 0.13 to 0.93]) and with hMBF increase above (Δ≥1.11 ml · min^?1 · g^?1) versus below the population median (p < 0.01; risk-adjusted p < 0.01; HR: 0.16 [95% CI: 0.05 to 0.54]) after CTO PCI. Furthermore, event-free survival was superior in patients without versus any residual PD (p < 0.01; risk-adjusted p = 0.02; HR: 0.22 [95% CI: 0.06 to 0.76]) or with a residual hMBF level >2.3 versus ≤2.3 ml · min^?1 · g^?1 (p < 0.01; risk-adjusted p = 0.03; HR: 0.25 [95% CI: 0.07 to 0.91]) at follow-up positron emission tomography. Patients with residual hMBF >2.3 ml · min^?1 · g^?1 were more frequently free of angina and dyspnea on exertion at long-term follow-up (p = 0.04).ConclusionsPatients with extensive ischemic burden reduction and no residual ischemia after CTO PCI had lower rates of all-cause death and nonfatal myocardial infarction. Long-term cardiac symptom relief was associated with normalization of hMBF levels after CTO PCI.     

Validation of the short-form WOMAC function scale for the evaluation of osteoarthritis of the knee

This study validates the short-form WOMAC function scale for assessment of conservative treatment of osteoarthritis of the knee. Data were collected before treatment and six and nine months later, from 100 patients with osteoarthritis of the knee to determine the validity, internal consistency, test-retest reliability, floor and ceiling effects, and responsiveness of the short-form WOMAC function scale. The scale showed high correlation with the traditional WOMAC and other measures. The internal consistency was good (Cronbach alpha: 0.88 to 0.95) and an excellent test-retest reliability was found (Lin's concordance correlation coefficient (rho(c)): 0.85 to 0.94). The responsiveness was adequate and comparable to that of the traditional WOMAC (standardised response mean 0.56 to 0.44 and effect size 0.64 to 0.57) and appeared not to be significantly affected by floor or ceiling effects (0% and 7%, respectively). The short-form WOMAC function scale is a valid, reliable and responsive alternative to the traditional WOMAC in the evaluation of patients with osteoarthritis of the knee managed conservatively. It is simple to use in daily practice and is therefore less of a burden for patients in clinical trials.     

PM–Scl‐75 is the main autoantigen in patients with the polymyositis/scleroderma overlap syndrome

Objective

To compare the autoantigenicity of the recently described N‐terminally elongated PM–Scl‐75 protein with that of PM–Scl‐100 and the originally defined PM–Scl‐75 polypeptide, and to determine its value for analyzing sera from patients with the polymyositis (PM)/scleroderma overlap syndrome.

Methods

Serum samples obtained from patients with the PM/scleroderma overlap syndrome and from patients with several other diseases were analyzed for the presence of autoantibodies reactive with recombinant PM–Scl‐100 and PM–Scl‐75 (both the original and the longer form) proteins, in an enzyme‐linked immunosorbent assay (ELISA).

Results

Autoantibodies recognizing the longer PM–Scl‐75 protein isoform were detected in 28% of the patients with PM/scleroderma. This percentage is slightly higher than that for PM–Scl‐100 (25%) and is significantly higher than that for the previously defined PM–Scl‐75 protein (11%). In addition, we identified a significant number of patients who had anti–PM–Scl‐75 but not anti–PM–Scl‐100 antibodies. This finding contrasts with what has been previously reported for the shorter version of the PM–Scl‐75 protein.

Conclusion

Our data indicate that use of the long PM–Scl‐75 isoform in addition to PM–Scl‐100 in ELISAs significantly increases the number of patients in whom anti–PM‐Scl autoantibodies can be detected.

     

Placental NAD(P)H oxidase mediated superoxide generation in early pregnancy

Early placental development is characterised by rapid cell differentiation and migration, matrix remodelling and angiogenesis. The enzyme NAD(P)H oxidase is a major source of superoxide anions implicated in signalling pathways regulating these processes in other systems. It is also thought to be involved in oxygen sensing and regulation of the expression of antioxidant genes. We therefore investigated NAD(P)H oxidase activity in placental tissues in early pregnancy and at term, and correlated this with antioxidant capacity. We collected placental tissues from women undergoing termination of pregnancy (n=19; gestational age 11(+6)+/-1(+0) weeks), and those with elective caesarean section at term after uncomplicated pregnancy (n=15; gestational age 38(+6)+/-0(+4) weeks). Tissues were assayed for superoxide production, using lucigenin chemiluminescence, and three independent markers of antioxidant capacity. In human placentas from normal deliveries at term substantial basal NAD(P)H activity was present. Activity was almost threefold higher in early pregnancy (P<0.0001). This was paralleled by higher total antioxidant capacity (P<0.0001), tissue glutathione concentrations (P<0.01) and gluthathione S-transferase enzyme activity (P<0.05) when compared to corresponding term placental values. NAD(P)H oxidase mediated superoxide generation could be an important modulator of the antioxidant defence response in early pregnancy.     

Diagnosing coronary artery disease with hybrid PET/CT: It takes two to tango

The noninvasive diagnosis of coronary artery disease (CAD) is a challenging task. Although a large armamentarium of imaging modalities is available to evaluate the functional consequences of the extent and severity of CAD, cardiac perfusion positron emission tomography (PET) is considered the gold standard for this purpose. Alternatively, noninvasive anatomical imaging of coronary atherosclerosis with coronary computed tomography angiography (CCTA) has recently been successfully implemented in clinical practice. Although each of these diagnostic approaches has its own merits and caveats, functional and morphological imaging techniques provide fundamentally different insights into the disease process and should be considered to be complementary rather than overlapping. Hybrid imaging with PET/CT offers the possibility to evaluate both aspects nearly simultaneously, and studies have demonstrated that such a comprehensive assessment results in superior diagnostic accuracy, better prognostication, and helps in guiding clinical patient management. The aim of this review is to discuss the value of stand-alone CCTA and PET in CAD, and to summarize the available data on the surplus value of hybrid PET/CT including its strengths and limitations.