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.
Type 2 diabetes is a major threat to human health in the 21st century. More than half a billion people may suffer from this pandemic disease in 2030, leading to a huge burden of cardiovascular ...complications. Recently, 2 novel antidiabetic agents, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, reduced cardiovascular complications in a number of randomized control trials. To integrate new information and to achieve a streamlined process for better patient care, a working group was appointed by the Taiwan Society of Cardiology to formulate a stepwise consensus pathway for these therapies to reduce cardiovascular events in patients with type 2 diabetes. This consensus pathway is complementary to clinical guidelines, acting as a reference to improve patient care.
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•SGLT2 inhibitors and GLP-1 RAs decreased cardiovascular endpoints in a majority of clinical trials.•SGLT2 inhibitors are more effective in preventing and reducing renal endpoints and heart failure, while GLP-1 RAs are more effective in preventing and reducing stroke.We have developed a stepwise algorithm, using 5 clinical parameters, to prioritize specific medication in different clinical settings, including patients with ASCVD or risk factors alone.
Background Recurrent hepatocellular carcinoma (RHCC) after curative resection is a major challenge for hepatic surgeons. A better understanding of the clonal origin of RHCC will help clinicians ...design personalized therapy and assess postoperative outcomes. The current study was performed to determine the clonal origin of RHCC and its clinical significance. Study Design Fifteen high-frequency of loss of heterozygosity of DNA microsatellites were determined on 100 tumor nodules in 60 matched pairs of RHCC from 40 patients who underwent liver re-resections. The relationships among the origin of clonal patterns of RHCC and the surgicopathologic features and clinical outcomes were analyzed. Results Of 60 pairs of RHCC, there were 2 clonal patterns with 6 subclonal types. Pattern I was multicentric occurrence (MO type) in 14 pairs (23.3%) and pattern II was intrahepatic metastasis (IM type) in 46 pairs (76.7%). The clinicopathologic features, including recurrence time, tumor size, vascular invasion, histological grading, and associated chronic liver diseases in patients with the MO type of RHCC were significantly different from those with the IM type of RHCC (p < 0.05 to 0.001). Compared with patients in the IM group, patients in the MO group had significantly better overall survival (130.8 ± 8.5 months vs 80.8 ± 8.5 months; p < 0.05) and recurrence-free survival (33.8 ± 4.5 months vs 14.2 ± 2.5 months; p < 0.001). Conclusions The MO-type RHCC was closely associated with better postoperative outcomes when compared with the IM-type RHCC. Generally, we recommend liver re-resection for MO-type RHCC, and interventional therapy for IM-type RHCC. Microdissection-based microsatellite loss of heterozygosity protocol has advantages in assessing the clonal origin, modes of personalized treatment, and clinical outcomes of RHCC.
Background Recruitment and entrapment of bone marrow-derived endothelial progenitor cells (EPCs) is important in vascular endothelial growth factor (VEGF)-induced angiogenesis. EPC mobilization and ...differentiation are modulated by stromal-derived factor-1α (SDF-1α/CXCL12), another important chemokine. In this study, we investigated the hypothesis that SDF-1α and VEGF might act synergistically on EPC-mediated vasculogenesis. Methods EPCs were isolated and cultured from human peripheral blood, then transduced with retroviral vectors pBabe containing human VEGF165 complimentary DNA (Td/V-EPCs) and pBabe wild-type (Td/p-EPCs). EPC migration activity was investigated with a modified Boyden chamber assay. EPC apoptosis induced by serum starvation was studied by annexin V assays. The combined effect of local administration of SDF-1α and Td/V-EPC transplantation on neovascularization was investigated in a murine model of hind limb ischemia. Results Over-expression of hVEGF165 increased SDF-1α–mediated EPC migration. SDF-1α–mediated migration was significantly increased when EPCs were modified with VEGF (Td/V-EPCs) vs when VEGF was not present (Td/p-EPCs) or when VEGF alone was present (Td/V-EPCs; 196.8 ± 15.2, 81.2 ± 9.8, and 67.4 ± 7.4/mm2 , respectively P < .001). SDF-1α combined with VEGF reduced serum starvation-induced apoptosis of EPCs more than SDF-1α or VEGF alone ( P < .001). To determine the effect of this combination in vivo, SDF-1α was locally injected alone into the ischemic hind limb muscle of nude mice or combined with systemically injected Td/V-EPCs. The SDF-1α plus VEGF group showed significantly increased local accumulation of EPCs, blood-flow recovery, and capillary density compared with the other groups. The ratio of ischemic/normal blood flow in Td/V-EPCs plus SDF-1α group was significantly higher ( P < .01), as was capillary density (capillaries/mm2 ), an index of neovascularization (Td/V-EPCs plus SDF-1α group, 863 ± 31; no treatment, 395 ±13; SDF-1α, 520 ± 29; Td/p-EPCs, 448 ± 28; Td/p-EPCs plus SDF-1α, 620 ± 29; Td/V-EPCs, 570 ± 30; P < .01). To investigate a possible mechanistic basis, we showed that VEGF up-regulated the receptor for SDF-1α, CXCR4, on EPCs in vitro. Conclusion The combination of SDF-1α and VEGF greatly increases EPC-mediated angiogenesis. The use VEGF and SDF-1α together, rather than alone, will be a novel and efficient angiogenesis strategy to provide therapeutic neovascularization.
Objective Extracorporeal membrane oxygenation (ECMO) is used to support postcardiotomy cardiogenic shock patients. Elevated serum lactate levels might reflect hypoxia in the tissues, which is ...associated with mortality in critically ill patients. This study examined the association between the early dynamic behavior of lactate and mortality after ECMO support. Methods We included 123 adult patients who had undergone cardiac surgery and received venous-arterial ECMO implantation to treat refractory postcardiotomy cardiogenic shock. The dynamic behaviors of lactate within 6 hours and 12 hours after the beginning of the ECMO support were incorporated into 2 regression models. Results A total of 56% of the patients were successfully weaned from ECMO support. The in-hospital mortality was 65.9% overall. Univariate and multivariate analyses indicated that age (odds ratio OR: 1.1 in the 6-hour model; 1.1 in the 12-hour model), gender (female; OR: 5.6 in the 6-hour model; 7.7 in the 12-hour model), mean lactate concentration (OR: 1.1 in the 6-hour model; 1.2 in the 12-hour model) and lactate clearance (OR: 0.5 in the 6-hour model; 0.1 in the 12-hour model) were reliable predictors ( P < .05) of in-hospital mortality. The mean lactate concentration (C statistic: 0.71) and lactate clearance (C statistic: 0.72) 12 hours after the initiation of ECMO support provided better prognostic guidance. The mean lactate concentration (OR: 1.2) and lactate clearance (OR: 0.3) were able to predict successful weaning from ECMO in the 12-hour model only. Conclusions In addition to age and gender (female), early lactate behaviors, particularly lactate clearance, after ECMO support are highly associated with in-hospital mortality in postcardiotomy patients. Additionally, early lactate behavior is also predictive of successful weaning from ECMO.
Exposure to particulate matter (PM) has been a major public health threat, but the potentially differential effects on asthma of PM remain largely unknown in high altitude settings. We evaluated the ...effects of ambient PM on asthma in high altitude settings.
The study recruited a representative sample from high altitude settings using a multistage stratified sampling procedure. Asthma was defined by a self-reported history of diagnosis by a physician or by wheezing symptoms in the preceding 12 months. The annual mean PM2.5 and PM10 concentrations were calculated for each grid cell at 1-km spatial resolution based on the geographical coordinates.
We analyzed data for participants (mean age 39.1 years, 51.4% female) and 183 (3.7%, 95% confidence interval (CI): 3.2–4.2) of the participants had asthma. Prevalence was higher in women (4.3%, 95% CI 3.5–5.1) than in men (3.1%, 2.4–3.8) and increasing with higher concentration of PM exposures. For an interquartile range (IQR) difference (8.77 μg/m3) in PM2.5 exposure, the adjusted odds ratio (OR) was 1.64 (95% CI 1.46–1.83, P < 0.001) for risk of asthma. For PM10, there was evidence for an association with risk of asthma (OR 2.34, 95% CI: 1.75–3.15, P < 0.001 per IQR of 43.26 μg/m3). Further analyses showed that household mold or damp exposure may aggravate PM exposure associated risks of asthma.
This study identified that PM exposure could be a dominate environmental risk factor for asthma but largely unconsidered in the high-altitude areas. The association between PM exposure and asthma should be of interest for planners of national policies and encourage programs for prevention of asthma in residents living at high altitudes.
Abstract Objective The advantages and limitations of the endoscopy-assisted transoral approach(EATA) and external approaches(EAs) in resection of parapharyngeal space tumors(PSTs) remain unclear. ...Here, we compared the use of the EATA and EAs for the resection of large benign PSTs. Study design Forty-four patients with parapharyngeal space tumors were divided into the EATA and EA groups. The perioperative and postoperative outcomes of the patients were evaluated. Results All of the tumors were completely removed. However, the procedure was converted to an open procedurefor four patients in the EATA group, and six patients in the EA group required endoscopic assistance. The intraoperative blood loss, amount and duration of drainage, postoperative pain, total hospital stay and cosmetic outcomes were superior in the EATA group(P<0.05). Conclusion Use of the EATA for resection of large benign PSTs advantageously decreased the surgical invasiveness of the procedure and resulted in better aesthetic results. However, use of the combined surgical approach allowed for improved access for the resection of PSTs.
Objectives We aimed to identify risk factors for recurrent syncope in children and adolescents with congenital long QT syndrome (LQTS). Background Data regarding risk assessment in LQTS after the ...occurrence of the first syncope episode are limited. Methods The Prentice-Williams-Peterson conditional gap time model was used to identify risk factors for recurrent syncope from birth through age 20 years among 1,648 patients from the International Long QT Syndrome Registry. Results Multivariate analysis demonstrated that corrected QT interval (QTc) duration (≥500 ms) was a significant predictor of a first syncope episode (hazard ratio: 2.16), whereas QTc effect was attenuated when the end points of the second, third, and fourth syncope episodes were evaluated (hazard ratios: 1.29, 0.99, 0.90, respectively; p < 0.001 for the null hypothesis that all 4 hazard ratios are identical). A genotype-specific subanalysis showed that during childhood (0 to 12 years), males with LQTS type 1 had the highest rate of a first syncope episode (p = 0.001) but exhibited similar rates of subsequent events as other genotype-sex subsets (p = 0.63). In contrast, in the age range of 13 to 20 years, long QT syndrome type 2 females experienced the highest rate of both first and subsequent syncope events (p < 0.001 and p = 0.01, respectively). Patients who experienced ≥1 episodes of syncope had a 6- to 12-fold (p < 0.001 for all) increase in the risk of subsequent fatal/near-fatal events independently of QTc duration. Beta-blocker therapy was associated with a significant reduction in the risk of recurrent syncope and subsequent fatal/near-fatal events. Conclusions Children and adolescents who present after an episode of syncope should be considered to be at a high risk of the development of subsequent syncope episodes and fatal/near-fatal events regardless of QTc duration.
Abstract Background Acute rejection (AR), initiated by alloreactive CD4+ T cells, hampers allograft survival. Soluble fibrinogen-like protein 2 (sFGL2) is a novel effector of CD4+ T cells. We ...previously found that serum sFGL2 significantly increased in renal allograft recipients with AR. In this study, sFGL2 secretion by CD4+ T cells and its mechanism were further explored both in vivo and in vitro. Materials and methods Forty cases of living-related renal transplant recipients with biopsy-proven AR or stable renal function were collected and detected serum sFGL2, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, and peripheral CD4+ T cells. In vitro , the isolated human CD4+ T cells were stimulated by TNF-α or IFN-γ. sFGL2 in the supernatant and mitogen-activated protein kinase (MAPK) proteins in the CD4+ T cells were investigated. Approval for this study was obtained from the Ethics Committee of Fudan University. Results sFGL2, TNF-α, IFN-γ, and CD4+ T cells were significantly increased in the peripheral blood of renal allograft recipients with AR. Stimulation with 1000 U/mL TNF-α or 62.5 U/mL IFN-γ for 48 h provided an optimal condition for CD4+ T cells to secrete sFGL2 in vitro . Phosphorylated (p-) c-Jun N-terminal kinase was remarkably upregulated in the activated CD4+ T cells, whereas no significant changes were found in p-p38 MAPK or p-ERK1/2 expression. Furthermore, inhibition of c-Jun N-terminal kinase significantly reduced sFGL2 secretion by CD4+ T cells. Conclusions sFGL2 secretion by CD4+ T cells can be induced with TNF-α and IFN-γ stimulation through MAPK signaling in renal allograft AR. Our study suggests that sFGL2 is a potential mediator in the pathogenesis of allograft rejection.
Objective We investigated the effect of recombinant human bone morphogenetic protein 2 (rhBMP-2) on new bone formation during rapid-rate mandibular distraction osteogenesis. We also explored the ...feasibility of using local BMP-2 gene therapy to compensate for bad callus formation caused by a rapid distraction rate. Study design Bone marrow mesenchymal stem cells (MSCs) from Japanese rabbits were transfected with adenovirus (adv)–BMP-2. The right mandibles of the rabbits were distracted after corticotomy. The distraction rate in group A was 0.8 mm/d. The distraction rate in group B was 2.4 mm/d, and the distraction gap was injected with adv- lacZ –transfected bone marrow MSCs. The distraction rate in group C was 2.4 mm/d, and the distraction gap was injected with adv–BMP-2–transfected bone marrow MSCs. New generation bone tissue in the distraction gap was analyzed by plain radiograph examinations, microfocus computerized tomography (micro-CT) examinations, and biomechanical tests at weeks 2, 4, and 8 of the consolidation period. Results Radiographic and micro-CT examinations showed a better bone quality in group C compared with group A at weeks 2 and 4 of the consolidation period. There was no obvious new bone formation in group B. The trabecular parameters (trabecular thickness, trabecular number, volumetric bone mineral density at tissue, and bone volume fraction) were significantly higher in group C than in group A at weeks 2 and 4. At week 8, no significant difference were detected for all parameters except trabecular number between groups A and C. All biomechanical stress parameters were significantly higher in group C than in group A at week 4, and only peak stress was significantly different at week 8. Conclusions Gene therapy using rhBMP-2–modified MSCs promoted new bone formation during mandibular distraction osteogenesis, and effectively compensated for the detrimental effect of rapid distraction rate on new bone formation.
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