Lipid-Lowering Efficacy of Ezetimibe in Patients with Atherosclerotic Cardiovascular Disease: A Systematic Review and Meta-Analyses

Patients with atherosclerotic cardiovascular disease (ASCVD), especially those with recent (< 1 year) acute coronary syndrome (ACS), are at high risk for recurrent cardiovascular events. This risk can be reduced by lowering low-density lipoprotein cholesterol (LDL-C) levels. A comprehensive meta-analysis on the LDL-C-lowering efficacy of ezetimibe is lacking. This study attempts to address this gap. A systematic literature review of randomized controlled trials evaluating the LDL-C-lowering efficacy of ezetimibe in the ASCVD population was conducted. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for publications from database inception to August 2018 and for conference abstracts from 2015 to August 2018. Meta-analyses were conducted to evaluate the LDL-C-lowering efficacy of ezetimibe in the ASCVD population and the recent ACS subgroup. In total, 12 studies were eligible for the meta-analyses. Treatment with combination ezetimibe plus statin therapy showed greater absolute LDL-C reduction than statin monotherapy (mean difference − 21.86 mg/dL; 95% confidence interval [CI] − 26.56 to − 17.17; p < 0.0001) after 6 months of treatment (or at a timepoint closest to 6 months). Similarly, in patients with recent ACS, combination ezetimibe plus statin therapy was favorable compared with statin monotherapy (mean treatment difference − 19.19 mg/dL; 95% CI − 25.22 to − 13.16; p < 0.0001). Ezetimibe, when added to statin therapy, provided a modest additional reduction in LDL-C compared with statin monotherapy. However, this may not be sufficient for some patients with ASCVD who have especially high LDL-C levels despite optimal statin therapy.     

Communicating with patients with inflammatory bowel disease

Ulcerative colitis and Crohn's disease, the two main forms of inflammatory bowel disease (IBD), are chronic illnesses that affect hundreds of thousands of Americans. Patients with IBD suffer chronically from diarrhea, abdominal pain, gastrointestinal bleeding, malabsorption, and weight loss requiring continuous medical and surgical attention. Despite recent advances in therapy, IBD follows a course of exacerbations and remissions with approximately 25-50% of patients relapsing annually. Hence, these diseases are readily encountered in primary care and gastroenterology clinics. Though medical and surgical treatment options have improved significantly, little has been written about the psychosocial aspects of IBD. Currently, there is a paucity of data concerning effective communication methods enabling physicians to develop stronger rapport with patients suffering from IBD, the care of whom requires a multidisciplinary approach involving primary care physicians, gastroenterologists, and colorectal surgeons. Because IBD has a high morbidity, it is worthwhile to further investigate those social factors that will improve patients' quality of life. In this paper, we summarize some of the common problems that emerge when taking care of patients with IBD and provide initial guidelines based on the world literature regarding the management and education of patients with IBD. Both primary care physicians and specialists (gastroenterologists, colorectal surgeons) need to be aware of the questions and concerns of IBD patients and to be capable of dispensing the information in a clear and concise manner. Using the case scenario format, we review the most common aspects of communication for health care professionals taking care of IBD patients and suggest ways to establish and maintain long-term doctor-patient relationships. The two most significant interventions that dramatically improve quality of life and patient-physician relationships are proper patient education and appropriate treatment of concurrent depression and anxiety. We hope that our review will form a framework by which different members of the medical team learn their roles in the complex management decisions affecting IBD patients.     

Procainamide-induced lupus erythematosus pericarditis encountered during coronary bypass sugery

Procainamide is probably the most common offending drug responsible for the drug-induced lupus erythematosus syndrome today. Pericarditis has been reported to occur in from 14 to 18 per cent of the cases of procainamide-induced lupus erythematosus, and occasional reports of massive pericardial effusion, pericardial tamponade and constrictive pericarditis have appeared in the literature. We describe a patient who presented with features of procainamide-induced lupus erythematosus without any clinical evidence of pericarditis. He underwent coronary bypass surgery 12 days after administration of the drug was stopped and was found to have a significant pericardial effusion at the time of surgery; histologic examination of pericardial tissue and pericardial fluid confirmed that the pericardial effusion was related to the procainamide-induced lupus syndrome. The incidence of pericarditis in procainamide-induced lupus erythematosus may be higher than presently accepted figures would indicate. Symptoms and signs related to procainamide-induced lupus pericarditis may cause diagnostic confusion with common postoperative bypass complications; the full implications of this disease entity to the patient undergoing coronary bypass are unknown.     

Thioredoxin-Interacting Protein Deficiency Protects against Diabetic Nephropathy

Expression of thioredoxin-interacting protein (TxNIP), an endogenous inhibitor of the thiol oxidoreductase thioredoxin, is augmented by high glucose (HG) and promotes oxidative stress. We previously reported that TxNIP-deficient mesangial cells showed protection from HG-induced reactive oxygen species, mitogen-activated protein kinase phosphorylation, and collagen expression. Here, we investigated the potential role of TxNIP in the pathogenesis of diabetic nephropathy (DN) in vivo. Wild-type (WT) control, TxNIP^−/−, and TxNIP^+/− mice were rendered equally diabetic with low-dose streptozotocin. In contrast to effects in WT mice, diabetes did not increase albuminuria, proteinuria, serum cystatin C, or serum creatinine levels in TxNIP^−/− mice. Whereas morphometric studies of kidneys revealed a thickened glomerular basement membrane and effaced podocytes in the diabetic WT mice, these changes were absent in the diabetic TxNIP^−/− mice. Immunohistochemical analysis revealed significant increases in the levels of glomerular TGF-β1, collagen IV, and fibrosis only in WT diabetic mice. Additionally, only WT diabetic mice showed significant increases in oxidative stress (nitrotyrosine, urinary 8-hydroxy-2-deoxy-guanosine) and inflammation (IL-1β mRNA, F4/80 immunohistochemistry). Expression levels of Nox4-encoded mRNA and protein increased only in the diabetic WT animals. A significant loss of podocytes, assessed by Wilms’ tumor 1 and nephrin staining and urinary nephrin concentration, was found in diabetic WT but not TxNIP^−/− mice. Furthermore, in cultured human podocytes exposed to HG, TxNIP knockdown with siRNA abolished the increased mitochondrial O₂⁻ generation and apoptosis. These data indicate that TxNIP has a critical role in the progression of DN and may be a promising therapeutic target.     

Large multicystic pulmonary chondroid hamartoma in a child presenting as pneumothorax

We describe a 10-year-old boy with a rare large multicystic pulmonary chondroid hamartoma in the right lower lobe presenting with severe respiratory distress. The radiological evaluation showed a large multicystic lesion in the right lower lobe with pneumothorax. Commonly, pulmonary hamartomas are asymptomatic, small in size, and are diagnosed incidentally in adults. Our case is highly unusual due to its young age, prominent clinical symptoms of severe respiratory distress with pneumothorax at presentation, very large size, and prominent cystic change. The lesion was surgically excised, and histopathological features were compatible with a multicystic chondroid hamartoma.Hamartomas are an abnormal proliferation of a mixture of tissue elements that are normally present in that organ. Pulmonary hamartomas (PH), also known as chondroid hamartomas, are the most common benign tumors of the lung in adults.1 They are slow growing, non-infiltrative, and nodular. Histologically, they show a mixture of mature mesenchymal tissue like adipose tissue, cartilage, bone, smooth muscle bundles, and fibromyxoid tissue in varying proportions.2 In addition, cleft-like spaces lined by respiratory epithelium are common. Males are 4 times more affected than females. The PHs are common in the fifth and sixth decade of life, and they tend to occur in the peripheral lung fields. Radiologically, they are typically described as coin lesions due to their smooth, sharply demarcated outline, and round shape. Identification of ‘popcorn-like’ calcification on plain radiograph is diagnostic when present. The PHs are mostly asymptomatic, diagnosed incidentally, measuring less than 4 cms in diameter, and they rarely show extensive cyst formation. We report a case of a large multilocular cystic chondroid pulmonary hamartoma in a 10-year-old boy. Our objective in presenting this particular case is to highlight the highly unusual pediatric age group, unique clinical and radiological findings, prominent cystic change, and very large size.     

Reversible regional wall motion abnormalities on exercise technetium-99m-gated cardiac single photon emission computed tomography predict high-grade angiographic stenoses

OBJECTIVES: We sought to determine the level of angiographic stenosis at which reversible regional wall motion abnormalities (RWMA) are present on exercise stress technetium-99m (Tc-99m)- gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI), and whether assessments of stress and rest RWMA add incremental diagnostic information. BACKGROUND: Stress and rest gated SPECT MPI enables the detection of post-exercise stunning. Although some studies have correlated RWMA to the severity of MPI defects, only one previous study correlated RWMA on gated MPI to angiographic findings. However, this correlation excluded patients with rest perfusion defects and did not involve gating of rest images. METHODS: One hundred patients undergoing angiography within six months of exercise stress Tc-99m (sestamibi)-gated SPECT MPI (in the absence of interim cardiac events or revascularization) were recruited. Images were acquired 15 to 30 min after stress and interpreted without knowledge of the Duke treadmill score, left ventricular ejection fraction and angiographic data. RESULTS: The sensitivity of reversible RWMA for angiographic stenoses >70% was 53%, with a specificity of 100%. The presence of reversible RWMA was able to stratify patients with angiographic stenoses of 50% to 79% and 80% to 99% with a high positive predictive value. A good correlation was noted between the presence of reversible RWMA and the coronary artery jeopardy score (R = 0.49, p < 0.0001). Multivariate analysis showed that the post-stress RWMA, Duke treadmill and reversible RWMA scores were significant predictors of angiographic severity. CONCLUSIONS: Post-stress and reversible RWMA, as shown by exercise stress Tc-99m-gated SPECT MPI, are significant predictors of angiographic disease and add incremental value to MPI for the assessment of angiographic severity.