One‐Year Follow‐Up of Nonrandomized Comparison between Coronary Artery Bypass Grafting Surgery and Drug‐Eluting Stent for the Treatment of Unprotected Left Main Coronary Artery Disease in Elderly Patients (Aged ≥75 Years)

Purpose: The present observational study compares in‐hospital and 12‐month clinical outcomes in elderly patients with unprotected left main coronary artery disease treated either with coronary artery bypass grafting or drug‐eluting stent. Methods: From January 2004 to December 2007, 211 patients (pts) with unprotected left main coronary artery (ULMCA) stenosis, aged 75 or older, underwent coronary revascularization either with coronary artery bypass graft (CABG) (106 pts) or drug‐eluting stent (DES) (105 pts). The decision to treat with CABG or percutaneous coronary intervention (PCI) was dependent on the patient's and the physician's choice. The occurrence of major adverse cardiac or cerebrovascular events (MACCE: death, nonfatal myocardial infarction, or stroke) and revascularizations was recorded after 1 year of follow‐up. A multivariate logistic regression analysis was performed using a propensity score method to take potential baseline differences between groups into account. Results: In‐hospital MACCE rates were 5.7% and 3.8% in the CABG and PCI groups, respectively (P = 0.748). After 1 year of follow‐up, these rates were, respectively, 13.9% and 14.9% (P = 0.841), and rates for target vessel revascularization at 12 months were 1.0% and 13.9% (P < 0.001). The PCI group was significantly associated with older age, dyslipidemia, history of cancer, high Euroscore, elevated creatininemia, single‐vessel disease, fewer chronic occlusions of the left anterior descending artery, and more LMCA stenosis ≥70%. The multivariate logistic regression analysis was adjusted for age, diabetes, left ventricular ejection fraction, Euroscore, and plasma creatininemia and stratified on the score of propensity to be treated with PCI. In the subgroup below median propensity score, the adjusted odds ratio for 1‐year MACCE was OR = 0.91 (95% confidence interval: 0.14 to 5.98; P = 0.924) whereas OR was 0.16 (0.04–0.69; P = 0.013) in the subgroup above median propensity score. Conclusions: In patients with a high probability of being treated with PCI (older age, high Euroscore, high creatininemia, single‐vessel disease, …), the 1‐year risk of MACCE was significantly lower in PCI‐ than in CABG‐treated subjects. No significant difference was found in other cases.     

Natural killer-like T-cell lymphomas: aggressive lymphomas of T-large granular lymphocytes [see comments]

Natural killer (NK)-like T cells are major histocompatibility complex- unrestricted cytotoxic T cells that are surface CD3-positive, express NK-cell antigens, and rearrange their T-cell receptor. Most neoplasms arising from this T-cell subpopulation have been a chronic lymphoproliferative disease referred to as T-large granular lymphocyte (LGL) leukemia. Only 10 NK-like T-cell lymphomas have been described in detail previously; this study presents the clinicopathologic features of six others and distinguishes these lymphomas from T-LGL leukemia. All patients presented with B-symptoms and often had marked hepatosplenomegaly without significant peripheral lymphadenopathy. Four of the six patients were immunosuppressed. All had CD3, CD8, CD56- positive tumors, presumably of hepatosplenic (n = 3), intestinal (n = 1), pulmonary (n = 1), or nodal (n = 1) origin. Three patients had lymphomatous bone marrow infiltrates, and four had peripheral blood involvement by neoplastic large lymphocytes, some of which had a blastic appearance or resembled virocytes. Azurophilic granules, ultrastructurally corresponding to cytoplasmic dense core and/or double density granules, were seen in all cases. T-cell clonality was shown in five tumors by Southern blot analysis, and three had abnormal karyotypes. Two untreated patients died 20 days after presentation, and three patients who received combination chemotherapy died within 5 months of presentation. One patient remains in complete remission 22 months after treatment. These findings suggest NK-like T-cell lymphomas are aggressive, are clinicopathologically distinct from T-LGL leukemia, and should be in the differential diagnosis of extranodal T-cell lymphoproliferations, including those in immunosuppressed patients. Furthermore, the LGL morphology, phenotype, and tissue distribution of some NK-like T-cell lymphomas suggest they arise from thymic- independent T cells of the hepatic sinusoids and intestinal mucosa.     

Deubiquitinating enzyme CYLD negatively regulates the ubiquitin-dependent kinase Tak1 and prevents abnormal T cell responses

The deubiquitinating enzyme CYLD has recently been implicated in the regulation of signal transduction, but its physiological function and mechanism of action are still elusive. In this study, we show that CYLD plays a pivotal role in regulating T cell activation and homeostasis. T cells derived from Cyld knockout mice display a hyperresponsive phenotype and mediate the spontaneous development of intestinal inflammation. Interestingly, CYLD targets a ubiquitin-dependent kinase, transforming growth factor-beta-activated kinase 1 (Tak1), and inhibits its ubiquitination and autoactivation. Cyld-deficient T cells exhibit constitutively active Tak1 and its downstream kinases c-Jun N-terminal kinase and IkappaB kinase beta. These results emphasize a critical role for CYLD in preventing spontaneous activation of the Tak1 axis of T cell signaling and, thereby, maintaining normal T cell function.     

Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity

Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.