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.
Abstract Objectives This study aimed to investigate sympathetic nerve (SN) ultrastructural changes and hemodynamic and pulmonary artery (PA) pathological improvements by pulmonary arterial ...denervation (PADN) in animals with pulmonary arterial hypertension (PAH), as well as the underlying mechanisms. Background SN overactivity plays a role in PAH. Previous studies have reported short-term improvements in pulmonary arterial pressure (PAP) and cardiac function by PADN, but PA remodeling and the associated mechanisms remain unclear. Methods Forty dogs were randomly (ratio of 1:3) assigned to the control (intra-atrial injection of N-dimethylacetamide, 3 mg/kg) and test (intra-atrial injection of dehydrogenized-monocrotaline, 3 mg/kg) groups. After 8 weeks, the animals in the test group with a mean PAP >25 mm Hg (n = 20) were randomized (ratio of 1:1) into the sham and PADN groups. At 14 weeks, the hemodynamics, medial wall thickness and PA muscularization, and messenger ribonucleic acid expression of genes in lung tissues were measured. Another 35 PAH dogs were used to measure the SN conduction velocity, electron microscopic assessment, and nerve distribution. Results PADN induced significant SN demyelination and axon loss and slowed SN conduction velocity over time, with resulting profound reductions in the mean PAP (23.5 ± 2.3 mm Hg vs. 33.7 ± 5.8 mm Hg), pulmonary vessel resistance (3.5 ± 2.3 Wood units vs. 7.7 ± 1.7 Wood units), medial wall thickness (22.3 ± 3.3% vs. 30.4 ± 4.1%), and full muscularization (40.3 ± 9.3% vs. 57.1 ± 5.7%) and increased nonmuscularization (29.8 ± 6.1% vs. 12.9 ± 4.9%) compared with the Sham group (all p < 0.001). PADN inhibited the messenger ribonucleic acid expression of genes correlated with inflammation, proliferation, and vasoconstriction. Conclusions PADN induces permanent SN injury and subsequent improvements in hemodynamics and PA remodeling in animals with PAH through mechanisms that may be experimentally and clinically beneficial.
Summary Spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal metaplasia (IM) have been recognized as neoplastic precursors in gastric carcinogenesis. We explored the relationship ...between SPEM and IM in Epstein-Barr virus–associated (EBVaGC) and Epstein-Barr virus–negative (EBVnGC) gastric cancer. Sixty-four EBVaGC and one hundred and fifty-four EBVnGC patients were included. EBV positivity was identified using Epstein-Barr virus–encoded RNA-1 in situ hybridization. SPEM was subclassified into absent, early, and advanced SPEM. Acute and chronic inflammation was graded as absent, mild, moderate, and marked. Univariate and multivariate logistic regression analyses were conducted to analyze the correlation between SPEM, IM, and inflammation. Our study revealed that SPEM was detected in 87.5% EBVaGC and 85.1% EBVnGC patients. Distribution of patients according to the SPEM classification was significantly different between EBVaGC and EBVnGC groups ( P = .038). IM was observed less frequently in EBVaGC when compared with EBVnGC patients ( P < .001). No difference was observed between EBVaGC and EBVnGC in the levels of acute and chronic inflammation. A positive correlation between IM and SPEM status was observed in both EBVaGC and EBVnGC patients. Furthermore, advanced SPEM was an independent influential factor to IM in EBVnGC ( P = .013). In conclusion, SPEM was associated with both EBVaGC and EBVnGC more frequently than IM. Moreover, advanced SPEM had a stronger association with IM than early SPEM in EBVnGC. These results suggest that identification of SPEM should be used as a high-risk indicator for detecting early gastric carcinoma, and should be brought to the attention of pathologists and clinicians.
Objective
To introduce the clinical features of and surgical techniques for a rare type of irreducible pertrochanteric femur fracture pattern with bisection of the lesser trochanter.
Methods
From ...January 2017 to December 2019, 357 patients with per/intertrochanteric femur fractures underwent surgery by closed reduction and internal fixation, of whom 12 patients were identified with rare preoperative imaging features, the lesser trochanter was almost equally bisected. The main fracture pathoanatomy of these cases included: The anterior fracture line passed along the intertrochanteric line to the medial lesser trochanter and bisected it into 2 equal parts from mid-level of the lesser trochanteric protrusion. The proximal part of the lesser trochanter connected to the head-neck fragment and attached by the psoas major tendon, while the distal part of the lesser trochanter connected to the femoral shaft and attached by the tendon of the iliac muscle. These fractures were irreducible by a closed maneuver and were reduced with limited assistance by some devices, and short intramedullary nails were used for fixation of these fractures.
Results
All patients were followed up for an average of 14.2 ± 2.1 months. Clinical fracture union occurred at an average of 10.8 ± 1.5 weeks, while radiographic union occurred at an average of 12.7 ± 1.2 weeks. No cut out of the helical blade was visible on radiographs. The average Parker-Palmer score was 6.9 ± 1.3 (range, 5-9) at the last follow up, including 8 cases rated as excellent, 2 as good and 2 as fair.
Conclusion
Two-part pertrochanteric femur fractures with bisection of the lesser trochanter have an irreducible fracture pattern with cortical locking and soft tissue incarceration. Soft tissue release and short cephalomedullary nail fixation for this fracture pattern provide stable fixation and allow early exercise. This treatment appears to have excellent outcomes in the short and medium terms.
Objective Pregnancy-associated plasma protein A (PAPP-A) may play an important role in the development of acute coronary syndrome. This study aimed to investigate the relationship between the levels ...of circulating PAPP-A and the mid-term outcomes of percutaneous coronary intervention (PCI) in patients with non–ST-elevation acute coronary syndrome. Methods The circulating PAPP-A levels and high-sensitivity C-reactive protein before PCI were measured in 129 patients with single coronary artery stenosis. The end point of clinical follow-up was cardiac death, nonfatal myocardial infarction, target vessel revascularization, and rehospitalization for angina. Results During the follow-up of an average of 20.3 ± 5.2 months, a cardiac event was recorded in 25 patients (19.4%). The levels of PAPP-A (29.85 ± 19.51 mIu/L vs 20.47 ± 14.33 mIu/L, P = . 007) and high-sensitivity C-reactive protein (5.63 ± 2.13 mg/L vs 4.11 ± 1.28 mg/L, P = . 014) in patients with cardiac events were higher than in those without cardiac events. PAPP-A ≥ 11.33 mIu/L has a strong predictive value for a combined end point (risk ratio = 4.1; 95% confidence interval, 1.0-16.2; P = . 037). Patients with lower PAPP-A levels (<11.33 mIu/L) had higher event-free survivals than patients with higher PAPP-A levels (log rank = 9.334, P = . 025). Conclusion Circulating PAPP-A levels predict the mid-term outcomes of PCI in patients with non–ST-elevation acute coronary syndrome and single-vessel stenosis.
Summary Lysyl oxidase family members have various roles in cancer progression. The aim of this study was to investigate their expression and clinical significance in esophageal squamous cell ...carcinoma. We examined messenger RNA expression of lysyl oxidase family members including lysyl oxidase and lysyl oxidase–like proteins (lysyl oxidase L) in 10 esophageal squamous cell carcinoma cell lines and 83 pairs of tumor samples by quantitative real-time polymerase chain reaction. All except lysyl oxidase L3 were expressed at high levels in esophageal squamous cell carcinoma, but only lysyl oxidase L2 was associated with lymph node metastasis ( P = .034). We examined lysyl oxidase L2 protein further by immunohistochemistry staining in 178 surgically resected esophageal squamous cell carcinoma tissue samples. The protein manifested decreased nuclear expression and increased cytoplasmic expression. Moreover, these 2 events both had significant correlation with the presence of lymph node metastasis ( P = .001 and P < .001). Overall survival rates of the patients with esophageal squamous cell carcinoma with decreased nuclear expression or increased cytoplasmic expression of lysyl oxidase L2 were significantly lower than those of the patients with esophageal squamous cell carcinoma with the reverse expression pattern ( P = .040 or P = .022). Multivariate analyses revealed that nuclear expression of lysyl oxidase L2 was an independent prognostic factor for esophageal squamous cell carcinoma. These results suggest that lysyl oxidase L2 exerts a critical effect on esophageal squamous cell carcinoma progression and can be a predictive marker of lymph node metastasis and outcome.
Highlights • The aim of this study is to determine the molecular mechanisms behind stereotactic body radiation therapy (SBRT) stimulating mesenchymal stem cell (MSC) migration and differentiation. • ...Bone-marrow derived MSCs migrate to the tumor parenchyma and differentiate into pericytes, inducing tumor vasculogenesis after SBRT, and promoting tumor recurrence. • MSC migration and maturation may be abrogated with AMD3100 and imatinib. • This novel treatment strategy warrants clinical investigation.
Soft strain sensors are needed for a variety of applications including human motion and health monitoring, soft robotics, and human/machine interactions. Capacitive-type strain sensors are excellent ...candidates for practical applications due to their great linearity and low hysteresis; however, a big limitation of this sensor is its inherent property of low sensitivity when it comes to detecting various levels of applied strain. This limitation is due to the structural properties of the parallel plate capacitor structure during applied stretching operations. According to this model, at best the maximum gauge factor (sensitivity) that can be achieved is 1. Here, we report the highest gauge factor ever achieved in capacitive-type strain sensors utilizing an ultrathin wrinkled gold film electrode. Our strain sensor achieved a gauge factor slightly above 3 and exhibited high linearity with negligible hysteresis over a maximum applied strain of 140%. We further demonstrated this highly sensitive strain sensor in a wearable application. This work opens up the possibility of engineering even higher sensitivity in capacitive-type strain sensors for practical and reliable wearable applications.
Summary The alteration of DNA methylation is one of the most common epigenetic changes in human cancers. Three genes, namely, DNA methyltransferase 1, 3a, and 3b, which code for DNA ...methyltransferases that affect promoter methylation status, are thought to play an important role in the development of cancers and may be good anticancer therapy targets. The methylation of tumor suppressor genes has been reported in gastroenteropancreatic neuroendocrine tumors; however, there have been no studies about DNA methyltransferase protein expression and its clinical significance in gastroenteropancreatic neuroendocrine tumors. In this study, the expression of DNA methyltransferase 1, 3a, and 3b was studied in 63 gastroenteropancreatic neuroendocrine tumors by immunohistochemistry. The expression of DNA methyltransferase 1, 3a, and 3b was frequently detected in gastroenteropancreatic neuroendocrine tumors (87%, 81%, and 75%, respectively). The DNA methyltransferase 3a expression level was significantly higher in poorly differentiated neuroendocrine carcinomas than in well-differentiated neuroendocrine tumors or well-differentiated neuroendocrine carcinomas ( P < .01 and P < .05, respectively). The expression of DNA methyltransferase 1, 3a, and 3b showed significantly higher levels in stage IV tumors than in stage I or II tumors. In addition, the expression levels of DNA methyltransferase 1, 3a, and 3b were positively correlated with the MIB-1 labeling index in gastroenteropancreatic neuroendocrine tumors ( R = 0.293, P = .019; R = 0.457, P = .001; and R = 0.249, P = .049; respectively). In addition, the expression levels and positive immunostaining frequencies of DNA methyltransferase 3a and 3b were significantly lower in midgut neuroendocrine tumors than in foregut or hindgut neuroendocrine tumors. Our findings suggest that the overexpression of DNA methyltransferase 1, 3a, and 3b is related to tumorigenesis and the progression of gastroenteropancreatic neuroendocrine tumors.
Abstract Background Shikonin, a natural naphthoquinone pigment extracted from the root of Lithospermum erythrorhizon , has shown a variety of pharmacologic properties including anti-inflammatory ...effect. In the present study, we analyzed the role of shikonin in acute lung injury induced by lipopolysaccharide (LPS) in mice. Materials and methods Sixty male BALB/C mice were randomly allocated into six groups ( n = 10, each): control group, shikonin group (50 mg/kg), LPS group, and three different doses (12.5, 25, and 50 mg/kg) for shikonin-treated groups. Shikonin or vehicle was given with an intragastric administration 1 h before an intratracheal instillation of LPS (5 mg/kg). The severity of pulmonary injury was evaluated 6 h after LPS challenge. Results Shikonin pretreatment significantly attenuated LPS-induced pulmonary histopathologic changes, alveolar hemorrhage, and neutrophil infiltration. The lung wet-to-dry weight ratios, as the index of pulmonary edema, were markedly decreased by shikonin pretreatment. Moreover, shikonin decreased the productions of the proinflammatory cytokines including tumor necrosis factor alpha and interleukin 1β and the concentration of total proteins in the bronchoalveolar lavage fluid. Shikonin pretreatment also reduced the concentrations of myeloperoxidase and nitric oxide in lung tissues. In addition, shikonin pretreatment significantly suppressed LPS-induced activation of cyclooxygenase 2 and inducible nitric oxide synthase and the nuclear factor κB DNA-binding activity in lung tissues. Conclusions This study indicates that shikonin may have a protective effect against LPS-induced acute lung injury, and the potential mechanism of this action may attribute partly to the inhibition of inducible nitric oxide synthase and cyclooxygenase 2 expression by downregulating nuclear factor κB activation.
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