Abstract Background Large cohort studies provide conflicting evidence regarding the potential for oral macrolide antibiotics to increase the risk of serious cardiac events. Objectives This study ...performed a meta-analysis to examine the link between macrolides and risk of sudden cardiac death (SCD) or ventricular tachyarrhythmias (VTA), cardiovascular death, and death from any cause. Methods We performed a search of published reports by using MEDLINE (January 1, 1966, to April 30, 2015) and EMBASE (January 1, 1980, to April 30, 2015) with no restrictions. Studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of interest were included. Results Thirty-three studies involving 20,779,963 participants were identified. Patients taking macrolides, compared with those who took no macrolides, experienced an increased risk of developing SCD or VTA (RR: 2.42; 95% CI: 1.61 to 3.63), SCD (RR: 2.52; 95% CI: 1.91 to 3.31), and cardiovascular death (RR: 1.31; 95% CI: 1.06 to 1.62). No association was found between macrolides use and all-cause death or any cardiovascular events. The RRs associated with SCD or VTA were 3.40 for azithromycin, 2.16 for clarithromycin, and 3.61 for erythromycin, respectively. RRs for cardiovascular death were 1.54 for azithromycin and 1.48 for clarithromycin. No association was noted between roxithromycin and adverse cardiac outcomes. Treatment with macrolides is associated with an absolute risk increase of 118.1 additional SCDs or VTA, and 38.2 additional cardiovascular deaths per 1 million treatment courses. Conclusions Administration of macrolide antibiotics is associated with increased risk for SCD or VTA and cardiovascular death but not increased all-cause mortality.
To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC).
In all, ...185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS).
EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio HR 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020).
Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.
Abstract For the last 20 years, a great amount of evidence has accumulated through epidemiological studies that most of the dry eye disease encountered in daily life, especially in video display ...terminal (VDT) workers, involves short tear film breakup time (TFBUT) type dry eye, a category characterized by severe symptoms but minimal clinical signs. An unstable tear film also affects the visual function, possibly due to the increase of higher order aberrations. Based on the change in the understanding of the types, symptoms, and signs of dry eye disease, the Asia Dry Eye Society agreed to the following definition of dry eye: “Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage.” The definition stresses instability of the tear film as well as importance of visual impairment, highlighting an essential role for TFBUT assessment. This paper discusses the concept of Tear Film Oriented Therapy (TFOT), which evolved from the definition of dry eye, emphasizing the importance of a stable tear film.
Currently available echocardiographic reference values are derived mainly from North American and European population studies, and no echocardiographic reference values are available for the Chinese ...population. The aim of this study was to establish normal values of echocardiographic measurements of the cardiac chambers and great arteries in a nationwide, population-based cohort of healthy Han Chinese adults.
A total of 1,586 healthy Han Chinese volunteers aged 18 to 79 years were screened at 43 collaborating laboratories throughout China. Standard M-mode and two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries. The impacts of gender and age on all echocardiographic measurements were analyzed.
A total of 1,394 qualified healthy subjects (mean age, 47.3 ± 16.0 years; 678 men) were ultimately enrolled. Except for left ventricular ejection fraction, values of cardiac chamber and great arterial dimensions were significantly higher in men than in women. Most measurements of the atrial and great arterial dimensions, left ventricular wall thickness, and left ventricular mass increased with age in both men and women.
Normal reference values of cardiac dimensional parameters were established for the first time in a nationwide, population-based cohort of healthy Han Chinese adults. Because most of these parameters were found to vary with gender and age, reference values stratified for gender and age should be used in clinical practice.
Background Carbohydrate antigen (CA19-9) is a well-established marker to monitor disease status after resection of pancreatic cancer. However, few serum markers have been reported to improve the ...prognostic ability of postoperative CA19-9, especially in patients with normal postoperative CA19-9. Methods A total of 353 patients with pancreatic ductal adenocarcinoma treated by radical resection were reviewed retrospectively, and a prospective cohort including 142 patients with resectable pancreatic head carcinoma was analyzed as a validation cohort. Perioperative CA19-9 and postoperative serum markers (CEA, CA242, CA72-4, CA50, CA125, CA153, and AFP) were investigated. Results Patients with postoperative normalization of CA19-9 had improved survival times (recurrence-free survival: 11.9 months; overall survival: 22.5 months) compared with those with decreased but still elevated postoperative CA19-9 (recurrence-free survival: 6.8 months, P < .001; overall survival: 13.5 months, P < .001) or those with increased postoperative CA19-9 (recurrence-free survival: 3.5 months, P < .001; overall survival: 7.9 months, P < .001), which was similar to those with consistently normal CA19-9 during perioperative periods (recurrence-free survival: 10.6 months, P = .799; overall survival: 24.1 months, P = .756). Normal postoperative CA19-9 levels were an independent indicator for a positive outcome after operation, regardless of preoperative CA19-9 levels. Elevated postoperative CEA and CA125 were identified further as independent risk factors for patients with normal postoperative CA19-9, while elevated postoperative CA125 and nondecreased postoperative CA19-9 were independent prognostic markers for patients with elevated postoperative CA19-9. Conclusion The postoperative monitoring of CEA and CA125 provided prognostic significance to the measurement of CA19-9 in pancreatic cancer after resection.
Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular ...(LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
Saphenous vein grafts continue to be the backbone of daily coronary revascularization practice, but controversy still exists about whether to use them as an individual or sequential graft. We ...undertook a systematic review and meta-analysis of cohort studies to compare the midterm or long-term patency of sequential vein coronary bypass grafts with those of vein grafts.
A comprehensive search strategy was run in PubMed, Embase, the Cochrane Library, and the Chinese Biomedical Literature Database. Inclusion criteria were the following: (1) two cohorts of patients received sequential and single saphenous vein coronary bypass grafting, respectively; (2) prospective or retrospective cohort design; and (3) graft patency examined by angiography or ultrafast computed tomography. Two researchers independently performed the literature search, data extraction, and quality assessment.
We identified 1,385 titles, reviewed 38 articles for inclusion criteria, and included 12 studies in the meta-analysis. The risk of occlusion in sequential grafts was lower (risk ratio RR = 0.67, 95% confidence interval CI 0.60 to 0.74) than that in single grafts. The risk of occlusion in side-to-side anastomoses was lower (RR = 0.52; 95% CI, 0.34 to 0.80) than that of end-to-side anastomoses for sequential vein grafts. There was no difference in occlusion between the distal end-to-side anastomoses of sequential vein grafts and those of single vein grafts (RR = 0.85; 95% CI, 0.68 to 1.06).
The midterm and long-term patency of sequential vein grafts appears to be better than that of single vein grafts and the patency of side-to-side anastomoses appears to be better than that of end-to-side anastomoses for sequential vein grafts.
Background Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) is reported to be different in inflammatory patterns of the sinonasal mucosa in white patients. ...Studies in nonwhite populations may further be helpful to understand the pathogenic mechanisms of CRS. Objective To investigate the immunopathologic profiles of CRSwNP and CRSsNP in adult Chinese. Methods Histologic characteristics of surgical samples were analyzed in 50 controls, 94 CRSsNP patients, and 151 CRSwNP patients. Tissue samples from 17 controls, 36 CRSsNP patients, and 45 CRSwNP patients were stained for CD3, CD4, CD8, CD20, CD68, myeloperoxidase, and dendritic cell lysosome-associated membrane protein. Expression profiles of transcription factors of T-cell subsets in relation to cytokines and a marker of natural killer T cell (Vα24) were examined by means of quantitative RT-PCR. Results Over half of CRSwNP patients presented noneosinophilic inflammation. CRSwNP had a higher number of eosinophils, plasma cells, and CD3+ , CD8+ , CD20+ , and CD68+ cells and a lower myeloperoxidase expression rate than CRSsNP. Expression levels of transcription factors and cytokines of TH 1/TH 2/TH 17 were increased, whereas the expression rate of Forkhead box p3 and TGF-β1 was decreased in both CRSsNP and CRSwNP compared with controls. Comparing CRSsNP and CRSwNP, CRSsNP had higher levels of IFN-γ expression, whereas only eosinophilic CRSwNP demonstrated an enhanced expression of GATA-3 and IL-5. Compared with noneosinophilic CRSwNP, an exaggerated TH 2/TH 17 reaction and Vα24 expression were found in eosinophilic CRSwNP. Conclusion Both Chinese CRSsNP and CRSwNP patients demonstrate impaired regulatory T cell function and enhanced TH 1/TH 2/TH 17 responses. CRSsNP is confirmed to be a predominant TH 1 milieu, whereas TH 2 skewed inflammation with predominant TH 17 reactions, and infiltration of natural killer T cells can be demonstrated only in eosinophilic CRSwNP, but not in noneosinophilic CRSwNP.
Background IL-25 is thought to participate in allergic inflammation by propagating T h 2-type responses. Objective To address the hypothesis that allergen provocation increases expression of IL-25 ...and its receptor IL-25R in the asthmatic bronchial mucosa and skin dermis of atopic subjects. Methods Sequential single and double immunostaining was used to evaluate the numbers and phenotypes of IL-25 and IL-25R immunoreactive cells in bronchial biopsies from mild atopic subjects with asthma (n = 10) before and 24 hours after allergen inhalation challenge and skin biopsies from atopic subjects (n = 10) up to 72 hours after allergen subepidermal injection. Results IL-25 immunoreactivity was expressed by a majority of epidermal cells in both organs at baseline and was not further augmented by challenge. IL-25R immunoreactive cells were rare in the epidermis before or after challenge. Allergen challenge was associated with significantly ( P < .01) increased expression of IL-25 and IL-25R immunoreactivity in the submucosa of both organs. IL-25 immunoreactivity colocalized with eosinophils, mast cells, and endothelial cells, whereas IL-25R immunoreactivity colocalized with eosinophils, mast cells, endothelial cells, and T lymphocytes. In both organs, correlations were observed between increases in IL-25 expression and the magnitudes of the late-phase allergen-induced clinical responses. Conclusion Allergen provocation induces functionally relevant, increased expression of IL-25 and its receptor in the asthmatic bronchial mucosa and dermis of sensitized atopic subjects. In addition to T cells, eosinophils, mast cells, and endothelial cells are potential sources and targets of IL-25 in the course of allergic inflammation.
Abstract Background Although current osteoporosis management guidelines recommend use of pharmacologic treatment after hip fracture, the care of such patients has been suboptimal. The objective of ...this cross-national study was to quantify the use of and adherence to osteoporosis medication after hip fracture in 3 countries with different healthcare systems—the United States, Korea, and Spain. Methods In 3 cohorts of patients aged ≥65 years hospitalized for hip fracture, we calculated the proportion receiving ≥1 osteoporosis drug after discharge. Adherence to osteoporosis treatment was measured as the proportion of days covered (PDC) during the first year after the hip fracture. Results We identified 86,202 patients with a hip fracture: 4704 (US Medicare), 6700 (US commercial), 57,631 (Korea), and 17,167 (Spain). The mean age was 77-83 years, and 74%-78% were women. In the year before the index hip fracture, 16%-18% were taking an osteoporosis medication. Within 3 months after the index hip fracture, 11% (US Medicare), 13% (US commercial), 39% (Korea), and 25% (Spain) of patients filled ≥1 prescription for osteoporosis medication. For those who filled ≥1 prescriptions for an osteoporosis medication, the mean PDC in the year after the fracture was 0.70 (US Medicare), 0.67 (US commercial), 0.43 (Korea), and 0.66 (Spain). Conclusions Regardless of differences in healthcare delivery systems and medication reimbursement plans, the use of osteoporosis medications for the secondary prevention of osteoporotic fracture was low. Adherence to osteoporosis treatment was also suboptimal, with the PDC <0.70 in all 3 countries.
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