Angiographic success and procedural complications in patients undergoing retrograde percutaneous coronary chronic total occlusion interventions: A weighted meta-analysis of 3482 patients from 26 studies

Background

The efficacy and safety profile of retrograde chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We sought to perform a weighted meta-analysis of the success and complication rates of retrograde CTO PCI.

Methods

We conducted a meta-analysis of 26 studies published between 2006 and April 2013 reporting in-hospital outcomes of retrograde CTO PCI. Data on procedural success, frequency of death, emergent coronary artery bypass graft surgery (CABG), stroke, myocardial infarction (MI), perforation, tamponade, stent thrombosis, major vascular or bleeding events, contrast nephropathy, and radiation skin injury were collected.

Results

A total of 26 studies with 3482 patients and 3493 target CTO lesions were included. Primary retrograde CTO PCI was attempted in 52.4%. Pooled estimates of outcomes were as follows: procedural success 83.3% [95% confidence interval (CI): 79.0% to 87.7%]; death 0.7% (95% CI: 0.5% to 1.2%); urgent CABG 0.7% (95% CI: 0.4% to 1.2%); tamponade 1.4% (95% CI: 1.0% to 2.2%); collateral perforation 6.9% (95% CI: 4.6% to 10.4%); coronary perforation 4.3% (95% CI: 1.2% to 15.4%); donor vessel dissection 2% (95% CI: 0.9% to 4.5%); stroke 0.5% (95% CI: 0.2% to 1.0%); MI 3.1% (95% CI: 0.2% to 5.0%); Q wave MI 0.6% (95% CI: 0.4% to 1.1%); vascular access complications 2% (95% CI: 0.9% to 4.5%); contrast nephropathy 1.8% (95% CI: 0.8% to 3.7%); and wire fracture and equipment entrapment 1.2% (95% CI: 0.6% to 2.5%).

Conclusions

Retrograde CTO PCI is associated with high procedural success rate and acceptable risk for procedural complications.     

Coagulopathy in COVID‐19

The COVID‐19 pandemic has become an urgent issue in every country. Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)‐like massive intravascular clot formation is frequently seen in this cohort. Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19. The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent. Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation. In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19. The mechanisms of the coagulopathy are not fully elucidated, however. It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved. Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.     

Computer analysis of the surface EMG during isometric exercise

A computer program is described which can provide either on-line or off-line analysis of the surface electromyogram (EMG) in man during submaximal isometric contractions. The intention of the program was to quantify the tension developed by, and the degree of fatigue induced in muscle during this form of exertion from the surface EMG. Six male and female volunteers served as subjects to test the program by exerting brief isometric contractions of their handgrip muscles at tensions ranging from 3 to 100% of their maximum strength and fatiguing isometric contractions at tensions ranging between 20 and 95% of their maximum strength. The results of these experiments showed that the program was able to estimate the tension developed by muscle within an average of 2.4% of the subject's maximum strength and estimate the duration of fatigue contractions within an average of 3.5% of the actual recorded endurance. The applications of this form of analysis to work physiology are discussed.     

Macrophage PPAR gamma is required for normal skeletal muscle and hepatic insulin sensitivity and full antidiabetic effects of thiazolidinediones

PPAR gamma is required for fat cell development and is the molecular target of antidiabetic thiazolidinediones (TZDs), which exert insulin-sensitizing effects in adipose tissue, skeletal muscle, and liver. Unexpectedly, we found that inactivation of PPAR gamma in macrophages results in the development of significant glucose intolerance plus skeletal muscle and hepatic insulin resistance in lean mice fed a normal diet. This phenotype was associated with increased expression of inflammatory markers and impaired insulin signaling in adipose tissue, muscle, and liver. PPAR gamma-deficient macrophages secreted elevated levels of factors that impair insulin responsiveness in muscle cells in a manner that was enhanced by exposure to FFAs. Consistent with this, the relative degree of insulin resistance became more severe in mice lacking macrophage PPAR gamma following high-fat feeding, and these mice were only partially responsive to TZD treatment. These findings reveal an essential role of PPAR gamma in macrophages for the maintenance of whole-body insulin action and in mediating the antidiabetic actions of TZDs.     

Macrophages from lupus-prone MRL mice are characterized by abnormalities in Rho activity, cytoskeletal organization, and adhesiveness to extracellular matrix proteins

Macrophages (mphi) from prediseased mice of the major murine models of lupus have an identical defect in cytokine expression that is triggered by serum and/or apoptotic cells. It is striking that cytokine expression in the absence of serum and apoptotic cells is equivalent to that of nonautoimmune mice. Here, we show that mphi from prediseased lupus-prone MRL/MpJ (MRL/+) or MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) mice also have reversible abnormalities in morphology, cytoskeletal organization, and adhesive properties. In the presence of serum, MRL mphi adhered in increased numbers to a variety of extracellular matrix proteins compared with mphi from two nonautoimmune strains. However, in the absence of serum, adhesion by MRL mphi was similar to that of nonautoimmune mphi. Increased adhesion by MRL mphi was also observed in the presence of apoptotic, but not necrotic, cells. The morphology and actin-staining pattern of adherent MRL mphi were consistent with reduced activity of Rho, a cytoskeletal regulator. Indeed, MRL mphi cultured in the presence of serum had markedly decreased levels of active Rho compared with nonautoimmune mphi. It is remarkable that when cultured in the absence of serum, MRL mphi displayed normal Rho activity and cytoskeletal morphology. Addition of a Rho inhibitor to normal mphi reproduced the morphologic and cytoskeletal abnormalities observed in MRL mphi. Taken together, our findings support the hypothesis that mphi from MRL and other systemic lupus erythematosus-prone mice have an apoptotic, cell-dependent, autoimmune phenotype that affects a broad range of mphi functions, including cytokine gene expression and Rho-dependent cytoskeletal regulation.     

Proposed criteria for mixed-dust pneumoconiosis: definition, descriptions, and guidelines for pathologic diagnosis and clinical correlation

We defined mixed-dust pneumoconiosis (MDP) pathologically as a pneumoconiosis showing dust macules or mixed-dust fibrotic nodules (MDF), with or without silicotic nodules (SN), in an individual with a history of exposure to mixed dust. We defined the latter arbitrarily as a mixture of crystalline silica and nonfibrous silicates. According to our definition of MDP, therefore, MDF should outnumber SN in the lung to make a pathologic diagnosis of MDP. In the absence of confirmation of exposure, mineralogic analyses can be used to support the pathologic diagnosis. The clinical diagnosis of MDP requires the exclusion of other well-defined pneumoconioses, including asbestosis, coal workers’ pneumoconiosis, silicosis, hematite miners’ pneumoconiosis, welders’ pneumoconiosis, berylliosis, hard metal disease, silicate pneumoconiosis, diatomaceous earth pneumoconiosis, carborundum pneumoconiosis, and corundum pneumoconiosis. Typical occupations associated with the diagnosis of MDP include metal miners, quarry workers, foundry workers, pottery and ceramics workers, and stonemasons. Irregular opacities are the major radiographic findings in MDP (ILO 1980), in contrast to silicosis, in which small rounded opacities predominate. Clinical symptoms of MDP are nonspecific. MDP must be distinguished from a variety of nonoccupational interstitial pulmonary disorders.     

Rho activation regulates CXCL12 chemokine stimulated actin rearrangement and restitution in model intestinal epithelia

Chemokines are critical regulatory factors that direct migration, proliferation and maturation of receptor expressing target cells within gut mucosa. The aim of the present study was to define the cellular mechanisms whereby engagement of the essential chemokine CXCL12 to CXCR4 regulates restitutive epithelial cell migration. Non-transformed IEC-6 cells or polarized T84 epithelial monolayers were wounded and F-actin accumulation assessed using fluorescence microscopy and flow cytometry. Immunoblot analysis, pull-down assays, fluorescence microscopy and wound healing assays defined activation of Rho, Rho-kinase (ROCK), and myosin light chain (MLC) and the role for those Rho effectors in CXCL12-regulated epithelial restitution. CXCL12 increased RhoGTP and F-actin localization to the leading edge of wounded IEC-6 and T84 monolayers. CXCL12 congruently stimulated an increase in active MLC that was inhibited by blockade of ROCK and myosin light chain kinase and regulated epithelial migration. Our data in model intestinal epithelia suggest CXCR4 and CXCL12 may function as an autocrine and paracrine mucosal signaling network regulating the competency of the epithelial barrier to withstand injury and mediate repair following damage.