Impact of left ventricular ejection fraction on outcomes after left main revascularization: g-LM Registry.

AIMS: The impact of left ventricular dysfunction on clinical outcomes following revascularization is not well established in patients with unprotected left main coronary artery disease (ULMCA). In this study, we evaluated the impact of left ventricular ejection fraction (LVEF) on clinical outcomes of patients with ULMCA requiring revascularization with percutaneous coronary intervention (PCI) compared with coronary artery bypass graft (CABG). METHODS: The details of the design, methods, end points, and relevant definitions are outlined in the Gulf Left Main Registry: a retrospective, observational study conducted between January 2015 and December 2019 across 14 centres in 3 Gulf countries. In this study, the data on patients with ULMCA who underwent revascularization through PCI or CABG were stratified by LVEF into three main subgroups; low (l-LVEF <40%), mid-range (m-LVEF 40-49%), and preserved (p-LVEF ≥50%). Primary outcomes were hospital major adverse cardiovascular and cerebrovascular events (MACCE) and mortality and follow-up MACCE and mortality. RESULTS: A total of 2137 patients were included; 1221 underwent PCI and 916 had CABG. During hospitalization, MACCE was significantly higher in patients with l-LVEF [(10.10%), P = 0.005] and m-LVEF [(10.80%), P = 0.009], whereas total mortality was higher in patients with m-LVEF [(7.40%), P = 0.009] and p-LVEF [(7.10%), P = 0.045] who underwent CABG. There was no mortality difference between groups in patients with l-LVEF. At a median follow-up of 15 months, there was no difference in MACCE and total mortality between patients who underwent CABG or PCI with p-LVEF and m-LVEF. CONCLUSION: CABG was associated with higher in-hospital events. Hospital mortality in patients with l-LVEF was comparable between CABG and PCI. At 15 months' follow-up, PCI could have an advantage in decreasing MACCE in patients with l-LVEF.

Outcomes of Myocardial Revascularization in Diabetic Patients With Left Main Coronary Artery Disease: A Multicenter Observational Study From Three Gulf Countries.

BACKGROUND: Real-world data for managing patients with diabetes and left main coronary artery (LMCA) disease are scarce. We compared percutaneous coronary intervention (PCI) outcomes versus coronary artery bypass grafting (CABG) in diabetes and LMCA disease patients. METHODS: We retrospectively studied patients with LMCA presented to 14 centers from 2015 to 2019. The study included 2138 patients with unprotected LMCA disease; 1468 (68.7 %) had diabetes. Patients were grouped into; diabetes with PCI (n = 804) or CABG (n = 664) and non-diabetes with PCI (n = 418) or CABG (n = 252). RESULTS: In diabetes, cardiac (34 (5.1 %) vs. 22 (2.7 %); P = 0.016), non-cardiac (13 (2 %) vs. 6 (0.7 %); P = 0.027) and total hospital mortality (47 (7.1 %) vs. 28 (3.5 %); P = 0.0019), myocardial infarction (45 (6.8 %) vs. 11 (1.4 %); P = 0.001), cerebrovascular events (25 (3.8 %) vs. 12 (1.5 %); P = 0.005) and minor bleeding (65 (9.8 %) vs. 50 (6.2 %); P = 0.006) were significantly higher in CABG patients compared to PCI; respectively. The median follow-up time was 20 (10-37) months. In diabetes, total mortality was higher in CABG (P = 0.001) while congestive heart failure was higher in PCI (P = 0.001). There were no differences in major adverse cerebrovascular events and target lesion revascularization between PCI and CABG. Predictors of mortality in diabetes were high anatomical SYNTAX, peripheral arterial disease, chronic kidney disease, and cardiogenic shock. CONCLUSIONS: In this multicenter retrospective study, we found no significant difference in clinical outcomes during the short-term follow-up between PCI with second-generation DES and CABG except for lower total mortality and a higher rate of congestive heart failure in PCI group of patients. Randomized trials to characterize patients who could benefit from each treatment option are needed.

Idiopathic pulmonary fibrosis in Saudi Arabia: Demographic, clinical, and survival data from two tertiary care hospitals.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is rare and can be challenging to diagnose. Limited data is available from the Middle Eastern region, especially Saudi Arabia. METHODS: This was a retrospective study that looked at all the patients diagnosed with IPF between 2007 and 2012 at two tertiary care hospitals in Saudi Arabia. We collected the demographical, clinical, laboratory and radiological data from the patients' medical records. Medications administered and 1 year survival was also assessed. RESULTS: Between 2007and 2012, 134 IPF patients were identified. Their baseline characteristics (Mean ± SD) included: age 64 ± 13 years, body mass index 29 ± 8 kg/m(2), FEV1 56 ± 15 percent of predicted, FVC 53 ± 13 percent of predicted, FEV1/FVC 0.81 ± 0.09, total lung capacity 75 ± 13 percent of predicted, diffusing capacity of the lung for carbon monoxide 57 ± 15 percent of predicted, on home oxygen at presentation 71 (53%), mean ejection fraction 0.50 ± 0.07, mean pulmonary artery systolic pressure (via echocardiogram) 40 + 22 mmHg, presentation mean SpO292 ± 7%, presentation 6-min walk distance 338 ± 64 m and lowest SpO2 during 6-min walk test 88 ± 5%. Patients were predominantly female (56%), and 42% of patients had diabetes and were active smokers. The IPF patients' frequency of hospital admission (n = 99) was 2.4 ± 1.7 per year and duration of hospital stay (n = 99) was 17.4 ± 23.8 days. Overall 1 year survival in all IPF patients was good, 93% (124) patients remained alive after 1 year. CONCLUSIONS: In Saudi Arabia, IPF patients tended to be slightly older and the disease progression was somewhat slower than reported IPF cohorts in other populations. They had frequent hospital admissions and a long hospital length of stay. The influence of genetics and co-morbid diseases on the incidence and outcome of IPF should be explored further.

Erythropoietin mediates terminal granulocytic differentiation of committed myeloid cells with ectopic erythropoietin receptor expression.

OBJECTIVES: The precise role of hematopoietic cytokine/cytokine receptor interactions in lineage-restricted hematopoietic differentiation giving rise to mature blood cells of diverse function is incompletely defined. To study lineage-specific effects of cytokines during terminal hematopoietic differentiation, we examined the ability of erythropoietin (Epo) to mediate terminal granulocytic differentiation and induction of myeloid gene expression in committed myeloid cells, engineered to ectopically express Epo receptor (EpoR). METHODS: A cell culture model for granulocyte-macrophage colony stimulating factor (GM-CSF)-mediated granulocytic differentiation was used. EpoR was introduced by retrovirus-mediated gene transfer into multipotential, hematopoietic murine cell line EML, from which GM-CSF-responsive, promyelocytic EPRO cells were generated. In EPRO cells ectopically expressing EpoR, we examined the ability of Epo to mediate granulocytic differentiation and determined whether Epo-mediated neutrophil differentiation is associated with a pattern of myeloid gene expression comparable to that induced by GM-CSF. RESULTS: Studies of EpoR function in myeloid EPRO cells revealed that Epo/EpoR interaction can mediate terminal granulocytic differentiation of committed myeloid cells. In EPRO cells expressing EpoR, Epo-mediated neutrophil differentiation was associated with surface CD11b/CD18 (Mac-1) expression and induction of mRNA expression of specific myeloid genes including lactoferrin, gelatinase and C/EBPepsilon, in a manner similar to GM-CSF-mediated differentiation. CONCLUSIONS: These results indicate that Epo can deliver differentiative signals along a non-erythroid lineage, providing evidence for interchangeable cytokine receptor signals that mediate terminal differentiation of committed myeloid cells.

Xenotransplantation of immunodeficient mice with mobilized human blood CD34+ cells provides an in vivo model for human megakaryocytopoiesis and platelet production.

The study of megakaryocytopoiesis has been based largely on in vitro assays. We characterize an in vivo model of megakaryocyte and platelet development in which human peripheral blood stem cells (PBSCs) differentiate along megakaryocytic as well as myeloid/lymphoid lineages in sublethally irradiated nonobese diabetic/severe combined immunodeficient (NOD-SCID) mice. Human hematopoiesis preferentially occurs in the bone marrow of the murine recipients, and engraftment is independent of exogenous cytokines. Human colony-forming units-megakaryocyte (CFU-MK) develop predominantly in the bone marrow, and their presence correlates with the overall degree of human cell engraftment. Using a sensitive and specific flow cytometric assay, human platelets are detected in the peripheral blood from weeks 1 to 8 after transplantation. The number of circulating human platelets peaks at week 3 with a mean of 20 x 10(9)/L. These human platelets are functional as assessed by CD62P expression in response to thrombin stimulation in vitro. Exogenous cytokines have a detrimental effect on CFU-MK production after 2 weeks, and animals treated with these cytokines have no circulating platelets 8 weeks after transplantation. Although cytokine stimulation of human PBSCs ex vivo led to a significant increase in CFU-MK, CD34+/41+, and CD41+ cells, these ex vivo expanded cells provided only delayed and transient platelet production in vivo, and no CFU-MK developed in vivo after transplantation. In conclusion, xenogeneic transplantation of human PBSCs into NOD/SCID mice provides an excellent in vivo model to study human megakaryocytopoiesis and platelet production.

Purification and properties of a Ca(2+)-independent barbed-end actin filament capping protein, CapZ, from human polymorphonuclear leukocytes.

In human polymorphonuclear leukocytes (PMN), changes in the actin architecture are critical for the shape changes required for chemotaxis and phagocytosis. Barbed-end capping proteins are likely to regulate actin assembly in PMN. The previously identified barbed-end blocking proteins in PMN, gelsolin and CapG, require Ca(2+) to initiate capping of actin filaments. Because chemoattractants can stimulate PMN actin assembly by a calcium-independent signal transduction pathway, we sought to purify a calcium-independent barbed-end capping activity from PMN cytoplasmic extracts. A Ca(2+) -insensitive actin polymerization inhibitory activity was partially purified from human PMN [Southwick & Stossel (1981) J. Biol. Chem 256, 3030]. Using five column chromatography steps, we purified the protein to homogeneity as assessed by silver staining. Purification was associated with an increase in specific activity of greater than 40 X. Western blot analysis identified the protein as the nonmuscle isoform of the heterodimeric capping protein capZ. Human PMN capZ has an apparent disassociation constant of 3 nM for capping in the presence or absence of micromolar Ca(2+), as assessed by both pyrenylactin elongation and depolymerization assays. Similar to the activity reported for the actin polymerization inhibitor, activity of PMN capZ was inhibited by increasing the KC1 concentration from 0.1 M to 0.6 M. The capping function was also inhibited by phosphatidylinositol 4,5-bisphosphate (PIP(2)) micelles, with half-maximal inhibition occurring at 5.5 micrograms mL(-1). PMN capZ did not nucleate actin assembly, sequester actin monomers, or sever actin filaments. Quantitative Western blot analysis revealed that capZ levels corresponded to 0.7-1.0% of the total human PMN cytoplasmic protein. Given its abundance and high affinity for barbed filament ends, capZ is likely to play an important role in the calcium-independent regulation of actin filament assembly associated with PMN chemotaxis.