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.
Early repolarization pattern (ERP) has been proved to increase risk of arrhythmia death in the general population, but its prognostic significance in patients with structural heart disease (SHD) is ...controversial.
The purpose of this study was to conduct a meta-analysis of studies assessing the association between ERP and risk of ventricular arrhythmias (VTAs) and sudden cardiac death (SCD) in patients with SHD.
We performed a literature search using MEDLINE (January 1, 1966, to September 25, 2016) and EMBASE (January 1, 1980, to September 25, 2016) with no restrictions. Studies that reported odds ratio (OR) estimates with 95% confidence intervals (CIs) for the associations of interest were included.
The search yielded 19 observational studies, involving 7268 patients that reported 1127 cases of VTAs or SCD. In the selected studies, the point estimates of the ORs were consistently greater than 1. Compared with those without ERP, patients with ERP experienced a significantly increased risk of developing VTAs or SCD (OR 4.76; 95% CI 3.62-6.26), ventricular fibrillation (OR 7.14; 95% CI 4.31-11.82), and SCD (OR 4.07; 95% CI 1.58-10.51). The results were consistent and statistically significant in all subgroups. ERP with J-point elevation in inferior leads, notching configuration, and horizontal or descending ST segment connote higher risk.
ERP is associated with a significant increased risk of VTAs or SCD in patients with SHD. Future research should attempt to understand the exact mechanisms for the arrhythmia risk and to introduce ERP in the risk stratification in this patient group.
Summary Background Endoscopically assisted selective neck dissection (SND) has recently been applied in clinical N0 cases of oral squamous cell carcinoma (OSCC). However, nothing is known of the ...immune response after surgery. Methods A total of 60 patients with cT1-2N0 OSCC randomly underwent endoscopically assisted SND and open operations. The serum levels of IL-6, IL-8, IL-10, IL-1b, TNF-a, CRP, cortisol, ACTH, and growth hormone were analyzed before the start of the surgery(T0) and at 2(T1), 6(T2), 24(T3), and 72 hours (T4) after surgery. Results A total of 31 patients were randomized for endoscopic SND, whereas 29 underwent open procedures. The release of IL-6, IL-10 and CRP was significantly lower in the endoscopic group than in the open surgery group (p<0.05), and cortisol levels were also lower in the endoscopic group (p<0.05). Conclusions Endoscopic SND could effectively provide lower inflammatory responses and surgical stress, reducing peri-operative trauma and accelerating recovery.
Objectives A meta-analysis was performed to determine the risk and incidence rate of arrhythmia death, cardiac death, and all-cause death in the general population with the early repolarization ...pattern (ERP). Background The ERP has recently been associated with vulnerability to ventricular fibrillation in case-control studies. However, the prognostic significance of the ERP in the general population is controversial. Methods Relevant studies published through July 31, 2012, were searched and identified in the MEDLINE and Embase databases. Studies that reported risk ratio estimates with 95% confidence intervals (CIs) for the associations of interest were included. Data were extracted, and summary estimates of association were obtained using a random-effects model. Results Of the 9 studies included, 3 studies reported on arrhythmia death (31,981 subjects, 1,108 incident cases during 726,741 person-years of follow-up), 6 studies reported on cardiac death (126,583 subjects, 10,010 incident cases during 2,054,674 person-years of follow-up), and 6 studies reported on all-cause death (112,443 subjects, 22,165 incident cases during 2,089,535 person-years of follow-up). The risk ratios of the ERP were 1.70 (95% CI: 1.19 to 2.42; p = 0.003) for arrhythmia death, 0.78 (95% CI: 0.27 to 2.25; p = 0.63) for cardiac death, and 1.06 (95% CI: 0.87 to 1.28; p = 0.57) for all-cause death. The estimated absolute risk differences of subjects with the ERP were 70 cases of arrhythmia death per 100,000 subjects per year. J-point elevation ≥ 0.1 mV in the inferior leads and notching configuration had an increased risk for arrhythmia death in subgroup studies. Conclusions The ERP was associated with increased risk and a low to intermediate absolute incidence rate of arrhythmia death. Further study is needed to clarify which subgroups of subjects with the ERP are at higher risk for arrhythmia death.
The majority of patients who experience cutaneous adverse drug reactions (cADRs) concurrently receive multiple medications, meaning that the causative drug remains unidentified. We explored the ...association between human leukocyte antigen (HLA) alleles and cADRs, regardless of the allergenic drug, to investigate whether different drug-induced cADRs were associated with the same or similar risk alleles in a Han Chinese population. We genotyped a sample of 146 cADR patients and 230 population controls from the same hospital and systematically analyzed the association between HLA Class I genes and cADRs. The carrier frequency of HLA-B∗46:01 in cADR patients was found to be significantly higher than that in population controls (P = .0021, odds ratio OR = 2.18, 95% confidence interval CI: 1.33–2.58). Subgroup analysis showed that HLA-B∗46:01 was significantly associated with urticaria and erythema multiforme (P = .0077, OR = 2.53, 95% CI: 1.30–4.91; and P = .0049, OR = 2.77, 95% CI: 1.39–5.50, respectively). Furthermore, a significant association was also detected between HLA-A∗02:01 and erythema multiforme (P = .0038, OR = 2.65, 95% CI: 1.31–5.33). This study is the first to demonstrate that HLA-B∗46:01 is a risk allele for cADRs in a Han Chinese population, indicating that screening for HLA-B∗46:01 prior to the administration of medication may predict the risk of developing cADRs.
Background Abelmoschus manihot , a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess ...its efficacy and safety in patients with primary glomerular disease. Study Design Prospective, open-label, multicenter, randomized, controlled, clinical trial. Setting & Participants From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. Interventions A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50 mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50 mg/d. The duration of intervention was 24 weeks. Outcomes & Measurements The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. Results Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot , losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2 , respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of −508, −376, and −545 mg/d, respectively ( P = 0.003 for A manihot vs losartan and P < 0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups ( P > 0.05), and there were no severe adverse events in any group. Limitations Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. Conclusions A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.
Summary Background The ability of circulating microRNAs (miRNAs) to detect preclinical hepatocellular carcinoma has not yet been reported. We aimed to identify and assess a serum miRNA combination ...that could detect the presence of clinical and preclinical hepatocellular carcinoma in at-risk patients. Methods We did a three-stage study that included healthy controls, inactive HBsAg carriers, individuals with chronic hepatitis B, individuals with hepatitis B-induced liver cirrhosis, and patients with diagnosed hepatocellular carcinoma from four hospitals in China. We used array analysis and quantitative PCR to identify 19 candidate serum miRNAs that were increased in six patients with hepatocellular carcinoma compared with eight control patients with chronic hepatitis B. Using a training cohort of patients with hepatocellular carcinoma and controls, we built a serum miRNA classifier to detect hepatocellular carcinoma. We then validated the classifiers' ability in two independent cohorts of patients and controls. We also established the classifiers' ability to predict preclinical hepatocellular carcinoma in a nested case-control study with sera prospectively collected from patients with hepatocellular carcinoma before clinical diagnosis and from matched individuals with hepatitis B who did not develop cancer from the same surveillance programme. We used the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) to evaluate diagnostic performance, and compared the miRNA classifier with α-fetoprotein at a cutoff of 20 ng/mL (AFP20). Findings Between Aug 1, 2009, and Aug 31, 2013, we recruited 257 participants to the training cohort, and 352 and 139 participants to the two independent validation cohorts. In the third validation cohort, 27 patients with hepatocellular carcinoma and 135 matched controls were included in the nested case-control study, which ran from Aug 1, 2009, to Aug 31, 2014. We identified a miRNA classifier (Cmi ) containing seven differentially expressed miRNAs (miR-29a, miR-29c, miR-133a, miR-143, miR-145, miR-192, and miR-505) that could detect hepatocellular carcinoma. Cmi showed higher accuracy than AFP20 to distinguish individuals with hepatocellular carcinoma from controls in the validation cohorts, but not in the training cohort (AUC 0·826 95% CI 0·771–0·880 vs 0·814 0·756–0·872, p=0·72 in the training cohort; 0·817 0·769–0·865 vs 0·709 0·653–0·765, p=0·00076 in validation cohort 1; and 0·884 0·818–0·951 vs 0·796 0·706–0·886, p=0·042 for validation cohort 2). In all four cohorts, Cmi had higher sensitivity (range 70·4–85·7%) than did AFP20 (40·7–69·4%) to detect hepatocellular carcinoma at the time of diagnosis, whereas its specificity (80·0–91·1%) was similar to that of AFP20 (84·9–100%). In the nested case-control study, sensitivity of Cmi to detect hepatocellular carcinoma was 29·6% (eight of 27 cases) 12 months before clinical diagnosis, 48·1% (n=13) 9 months before clinical diagnosis, 48·1% (n=13) 6 months before clinical diagnosis, and 55·6% (n=15) 3 months before clinical diagnosis, whereas sensitivity of AFP20 was only 7·4% (n=2), 11·1% (n=3), 18·5% (n=5), and 22·2% (n=6) at the corresponding timepoints (p=0·036, p=0·0030, p=0·021, p=0·012, respectively). Cmi had a larger AUC than did AFP20 to identify small-size (AUC 0·833 0·782–0·883 vs 0·727 0·664–0·792, p=0·0018) and early-stage (AUC 0·824 0·781–0·868 vs 0·754 0·702–0·806, p=0·015) hepatocellular carcinoma and could also detect α-fetoprotein-negative (AUC 0·825 0·779–0·871) hepatocellular carcinoma. Interpretation Cmi is a potential biomarker for hepatocellular carcinoma, and can identify small-size, early-stage, and α-fetoprotein-negative hepatocellular carcinoma in patients at risk. The miRNA classifier could be valuable to detect preclinical hepatocellular carcinoma, providing patients with a chance of curative resection and longer survival. Funding National Key Basic Research Program, National Science and Technology Major Project, National Natural Science Foundation of China.
Percutaneous microwave ablation and radiofrequency ablation are two commonly used modalities for the treatment of hepatocellular carcinoma; however, comparisons of them have not been documented ...adequately.
Of 102 patients with biopsy-proved hepatocellular carcinoma, 49 (98 nodules) were treated percutaneously with microwave ablation and 53 (72 nodules) with radiofrequency ablation. The local tumor control, complications related to treatment, and long-term results of the two modalities were compared retrospectively.
The complete ablation rates were 94.9% (93/98) using microwave ablation vs 93.1% (67/72) using radiofrequency ablation (P = 0.75), and no significant differences were found either in the ablation of tumors of 3.0 cm or less (P = 1.00) or in those of more than 3.0 cm (P = 1.00) between the two modalities. The local recurrence rates were 11.8% (11/93) using microwave ablation vs 20.9% (14/67) using radiofrequency ablation (P = 0.12), and there were no significant differences between the two modalities either in tumors of 3.0 cm or less (P = 0.36) or in those of more than 3.0 cm (P = 0.82). The rates of major complications associated with microwave ablation and radiofrequency ablation were 8.2% (4/49) vs 5.7% (3/53; P = 0.71). The disease-free survival rates in the microwave ablation group were 45.9%, 26.9%, 26.9%, and 13.4% at 1, 2, 3, and 4 years, respectively, and those in the radiofrequency ablation group were 37.2%, 20.7%, and 15.5% at 1, 2 and 3 years, respectively (P = 0.53). The 1-, 2-, 3-, and 4-year cumulative survival rates for patients who underwent microwave ablation were 81.6%, 61.2%, 50.5%, and 36.8%, respectively, and for patients who underwent radiofrequency ablation the rates were 71.7%, 47.2%, 37.6%, and 24.2%, respectively (P = 0.12).
Percutaneous microwave ablation and radiofrequency ablation are both effective methods in treating hepatocellular carcinomas. The local tumor control, complications related to treatment, and long-term survivals were equivalent for the two modalities.
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