Short versus long duration of dual antiplatelet therapy following drug-eluting stents: a meta-analysis of randomised trials

Background

Dual antiplatelet therapy (DAPT) remains the cornerstone therapy in the prevention of ischaemic events following drug-eluting stent (DES) implantation. Mandatory duration of DAPT after DES however, is a matter of debate. We aimed to evaluate safety and efficacy of short-term (up to 6 months) versus long-term (12 months) DAPT after DES implantation.

Methods

We searched PubMed, EMBASE, Cochrane databases, and international meetings for randomised clinical trials (RCTs) comparing short with long DAPT. We performed a systematic review and meta-analysis of major trials with primary outcomes: all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding event.

Results

Nine RCTs with a total number of 19,099 patients were pooled in the present meta-analysis. When compared with long DAPT, short DAPT was associated with a significant reduction in major bleeding events (0.62% vs. 1.10%, risk ratio (RR) 0.58, 95% confidence interval (CI) 0.39 to 0.86, p?<?0.007, I²?=?21%), whereas all-cause death (1.65% vs. 1.84%, RR 0.90, 95% CI 0.73 to 1.11, p?=?0.34, I2?=?0%), myocardial infarction (1.91% vs. 1.68%, RR 1.14, 95% CI 0.92 to 1.40, p?=?0.23, I2?=?0%), definite or probable stent thrombosis (0.62% vs. 0.47%, RR 1.25, 95% CI 0.84 to 1.86, p?=?0.27, I2?=?0%), and stroke (0.60% vs. 0.67%, RR 0.91, 95% CI 0.63 to 1.31, p?=?0.61, I2?=?0%) were similar.

Conclusions

Short DAPT following DES implantation results in a significant reduction of major bleeding events with no apparent increase in all-cause death, myocardial infarction, stent thrombosis, or stroke. Future dedicated trials should investigate the optimal strategies for patient-tailored DAPT in various subgroups.

     

Adjuvant zoledronic acid therapy for patients with early stage breast cancer: an updated systematic review and meta-analysis

Background

Zoledronic acid is a potent inhibitor of osteoclast-mediated bone resorption and has been widely used in bone metastasis malignancies and postmenopausal osteoporosis as a preventive therapy against skeletal-related events. The purpose of this study was to evaluate the clinical outcome of zoledronic acid as an adjuvant therapy for patients with early stage breast cancer.

Patients and methods

Entries in the PubMed and EMBASE databases up to 12 July 2013 were systematically reviewed. Online abstracts from the proceedings of the Annual Meetings of the American Society of Clinical Oncology (ASCO) (1992–2013) and the San Antonio Breast Cancer Symposium (SABCS) (2004–2013) were also reviewed. Primary endpoints included overall survival (OS) and disease-free survival (DFS), while secondary endpoints included bone metastasis-free survival (BMFS), distant metastasis-free survival (DMFS), and fracture-free rate (FFR).

Results

A total of eight studies including 3,866 subjects and 3,864 controls met our search criteria and were evaluated. The use of zoledronic acid was found to improve OS (relative risk (RR), 0.88; 95% confidence interval (CI), 0.77–1.01; p- value?=?0.06) and DMFS (RR, 0.77; 95% CI, 0.60–1.00; p- value?=?0.05). Furthermore, statistically significant benefits were associated with BMFS (RR, 0.81; 95% CI, 0.66–0.99; p- value?=?0.04) and FFRs (RR, 0.75; 95% CI, 0.61–0.92; p- value?=?0.007). In contrast, there was no significant difference in DFS with the application of zoledronic acid (RR, 0.88; 95% CI, 0.72–1.09; p- value?=?0.24). Sensitivity analysis further identified the improvement of 5-year OS for the adjuvant zoledronic acid therapy in early stage breast cancer patients (RR, 0.86; 95% CI, 0.75–0.99; p- value?=?0.03), while a borderline statistically significant benefit was observed for 5-year DFS (RR, 0.90; 95% CI, 0.81–1.00; p- value?=?0.06).

Conclusion

Zoledronic acid as an adjuvant therapy appears to improve the 5-year OS rate for early stage breast cancer patients, and was associated with a protective effect for the bone metastases and fractures evaluated in more than 7,000 patients. However, further research is needed to confirm our findings, and sub-group analyses according to menopause status or hormone status may provide further insight.

     

Predictors of thrombolysis in the telestroke and non telestroke settings for hypertensive acute ischemic stroke patients

Background

In acute ischemic stroke patients, telestroke technology provides sustainable approaches to improve the use of thrombolysis therapy. How this is achieved as it relates to inclusion or exclusion of clinical risk factors for thrombolysis is not fully understood. We investigated this in a population of hypertensive stroke patients.

Methods

Structured data from a regional stroke registry that contained telestroke and non telestroke patients with a primary diagnosis of acute ischemic stroke with history of hypertension were collected between January 2014 and June 2016. Clinical risk factors associated with inclusion or exclusion for recombinant tissue plasminogen activator (rtPA) in the telestroke and non telestroke were identified using multiple regression analysis. Associations between variables and rtPA in the regression models were determined using variance inflation factors while the fitness of each model was determined using the ROC curve to predict the power of each logistic regression model.

Results

The non telestroke admitted more patients (62% vs 38%), when compared with the telestroke. Although the telestroke admitted fewer patients, it excluded 11% and administered thrombolysis therapy to 89% of stroke patients with hypertension. In the non telestroke group, adjusted odd ratios showed significant associations of NIH stroke scale score (OR?=?1.059, 95% CI, 1.025–1.093, P <?0.001) and coronary artery disease (OR?=?2.003, 95% CI, 1.16–3.457, P?=?0.013) with inclusion, while increasing age (OR?=?0.979, 95% CI, 0.961–0.996, P?=?0.017), higher INR (OR?=?0.146, 95% CI, 0.032–0.665, P?=?0.013), history of previous stroke (OR?=?0.39, 95% CI, 0.223–0.68, P?=?0.001), and renal insufficiency (OR?=?0.153, 95% CI, 0.046–0.508, P?=?0.002) were associated with rtPA exclusion. In the telestroke, only direct admission to the telestroke was associated with rtPA administration, (OR?=?4.083, 95% CI, 1.322–12.611, P?=?0.014).

Conclusion

The direct admission of hypertensive stroke patients to the telestroke network was the only factor associated with inclusion for thrombolysis therapy even after adjustment for baseline variables. The telestroke technology provides less restrictive criteria for clinical risk factors associated with the inclusion of hypertensive stroke patients for thrombolysis.

     

The relationship between human leukocyte antigen-DP/DQ gene polymorphisms and the outcomes of HCV infection in a Chinese population

Background

Recently, human leukocyte antigen (HLA) class-II gene polymorphisms have been reported to be related to Hepatitis C virus (HCV) infection and chronicity. The objective of this study was to explore the relationship of HLA-DP rs9277535 and HLA-DQ rs7453920 with the outcomes of HCV infection.

Methods

The rs9277535 and rs7453920 were genotyped in 370 subjects with chronic HCV infection, 194 subjects with spontaneous HCV clearance, and 973 subjects with non-HCV infection from the Chinese population using the ABI TaqMan allelic discrimination assay.

Results

Logistic regression analyses showed that the minor allele A of rs7453920 significantly increased the susceptibility of HCV infection in dominant model (adjusted OR?=?1.33, 95% CI: 1.04–1.71, P?=?0.026) and additive models (adjusted OR?=?1.30, 95% CI: 1.06–1.60, P?=?0.012). Rs9277535 A allele significantly increased the risk of chronic HCV infection in dominant model (adjusted OR?=?1.52, 95% CI: 1.01–2.28, P?=?0.046). Haplotype AA showed a higher risk of HCV infection than the most frequent haplotype GG (adjusted OR?=?1.37, 95% CI: 1.05–1.78, P?=?0.018).

Conclusion

The HLA-DQ rs7453920 and -DP rs9277535 mutations were significantly associated with HCV infection susceptibility and chronicity, respectively.

     

Prognostic value of rising mean platelet volume during hospitalization in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Background

The prognostic significance of changes in mean platelet volume (MPV) during hospitalization in ST segment elevation myocardial infarction (STEMI) patients underwent primary percutaneous coronary intervention (pPCI) has not been previously evaluated. The aim of this study was to determine the association of in-hospital changes in MPV and mortality in these patients.

Methods

Four hundred eighty consecutive STEMI patients were enrolled in this retrospective study. The patients were grouped as survivors (n?=?370) or non-survivors (n?=?110). MPV at admission, and at 48–72?h was evaluated. Change in MPV (MPV at 48–72?h minus MPV on admission) was defined as ΔMPV.

Results

At follow-up, long-term mortality was 23%. The non-survivors had a high ΔMPV than survivors (0.37 (??0.1–0.89) vs 0.79 (0.30–1.40) fL, p?<? 0.001). A high ΔMPV was an independent predictor of all cause mortality ((HR: 1.301 [1.070–1.582], p?=?0.008). Morever, for long-term mortality, the AUC of a multivariable model that included age, LVEF, Killip class, and history of stroke/TIA was 0.781 (95% CI:0.731–0.832, p?<? 0.001). When ΔMPV was added to a multivariable model, the AUC was 0.800 (95% CI: 0.750–0.848, z?=?2.256, difference p?=?0.0241, Fig. 1). Also, the addition of ΔMPV to a multivariable model was associated with a significant net reclassification improvement estimated at 24.5% (p?=?0.027) and an integrated discrimination improvement of 0.014 (p?=?0.0198).

Conclusions

Rising MPV during hospitalization in STEMI patients treated with pPCI was associated with long-term mortality.

     

Corticosteroid plus β<Subscript>2</Subscript>-agonist in a single inhaler as reliever therapy in intermittent and mild asthma: a proof-of-concept systematic review and meta-analysis

Background

Current guidelines recommend a single inhaler maintenance and reliever therapy (SMART) regimen for moderate to severe asthma. However, evidence for the inhaled corticosteroid plus fast-onset-acting β₂-agonist (ICS/FABA) as reliever therapy in management of intermittent and mild asthma patients is lacking.

Objective

To systematically explore efficacy and safety of the proof-of-concept of the ICS plus FABA regimen in a single inhaler as reliever therapy across children and adults with intermittent and mild persistent asthma.

Methods

We searched online bibliographic databases for randomized controlled trials (RCTs) involving the as-needed use of ICS/FABA as monotherapy in intermittent or mild asthma patients. The primary outcomes were exacerbations and the hazard ratio (HR) of the time to first exacerbation.

Results

Six RCTs (n?=?1300) met the inclusion criteria. Compared with the as-needed FABA regimen, the as-needed use of ICS/FABA as monotherapy statistically reduced exacerbations (RR?=?0.56, P?=?0.001). Compared with regular ICS regimen, the as-needed ICS/FABA therapy had slightly higher risk of exacerbations (RR?=?1.39, P?=?0.011). The HR for time to first exacerbations in the ICS/FABA regimen was significant lower when compared with FABA regimen (HR?=?0.52, P?=?0.002) but had no difference when compared with ICS regimen (HR?=?1.30, P?=?0.286). The corticosteroid exposure in the daily ICS regimen was 2- to 5-fold compared with as-needed use of ICS/FABA regimen.

Conclusions

Our analysis shows that the ICS/FABA as a symptom-driven therapy may be a promising alternative regimen for the patients with intermittent or mild asthma, but it needs further real-world RCTs to confirm these findings.

     

Association of Klotho gene polymorphism with hypertension and coronary artery disease in an Iranian population

Background

Klotho, possibly an age-regulating protein, is considered an important factor contributing to the lifespan and pathophysiology of hypertension and coronary artery disease (CAD). The present study was carried out aiming to investigate the association of Klotho-rs564481 (C1818T) gene polymorphism with hypertension and CAD.

Methods

A total of 286 CAD-suspicious subjects were entered into this case-control study. The polymorphism was investigated in hypertensive patients with no CAD (H-Tens, n?=?60); hypertensive patients with CAD (CAD?+?H-Tens, n?=?95); CAD patients with no hypertension (CAD, n?=?61); and non-hypertensive non-CAD subjects, which were regarded as the control group (Ctrl, n?=?70). Genotype and allele frequencies were assessed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

Results

A significant difference was found in allele frequency of Klotho C1818T among the four research groups (P?=?0.03). It was also found that wild-type homozygote subjects were negatively associated with hypertension as compared to heterozygote ones (OR?=?0.07 [95% CI: 0.008–0.69] P?=?0.02). Moreover, in the subgroups older than 57?years old, dominant genetic model demonstrated a negative association with CAD combined with hypertension (OR?=?0.31 [95% CI: 0.10–0.95] P?=?0.04).

Conclusions

In conclusion, Klotho C1818T variant may be associated with a decreased risk of hypertension. Moreover, aging enhanced positive effects of the Klotho polymorphism on CAD combined with hypertension, indicating the possibility that the KLOTHO gene might play a part in the age-related occurrence of CAD combined with hypertension.

     

Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC

Background

Graft-versus-host disease (GVHD) is one of the leading causes of non-relapse mortality and morbidity after allogeneic hematopoietic stem cell transplantation (allo-HCT).

Methods

We evaluated the outcomes of two well-established strategies used for GVHD prevention: in vivo T cell depletion using antithymocyte globulin (ATG) and ex vivo T cell depletion using a CD34-selected (CD34+) graft. A total of 525 adult patients (363 ATG, 162 CD34+) with intermediate or high-risk cytogenetics acute myeloid leukemia (AML) in first complete remission (CR1) were included. Patients underwent myeloablative allo-HCT using matched related or unrelated donors.

Results

Two-year overall survival estimate was 69.9% (95% CI, 58.5–69.4) in the ATG group and 67.6% (95% CI, 60.3–74.9) in the CD34+ group (p?=?0.31). The cumulative incidence of grade II–IV acute GVHD and chronic GVHD was higher in the ATG cohort [HR 2.0 (95% CI 1.1–3.7), p?=?0.02; HR 15.1 (95% CI 5.3–42.2), p?<?0.0001]. Parameters associated with a lower GVHD-free relapse-free survival (GRFS) were ATG [HR 1.6 (95% CI 1.1–2.2), p?=?0.006], adverse cytogenetic [HR 1.7 (95% CI 1.3–2.2), p?=?0.0004], and the use of an unrelated donor [HR 1.4 (95% CI 1.0–1.9), p?=?0.02]. There were no statistical differences between ATG and CD34+ in terms of relapse [HR 1.52 (95% CI 0.96–2.42), p?=?0.07], non-relapse mortality [HR 0.96 (95% CI 0.54–1.74), p?=?0.90], overall survival [HR 1.43 (95% CI 0.97–2.11), p?=?0.07], and leukemia-free survival [HR 1.25 (95% CI 0.88–1.78), p?=?0.21]. Significantly, more deaths related to infection occurred in the CD34+ group (16/52 vs. 19/112, p?=?0.04).

Conclusions

These data suggest that both ex vivo CD34-selected and in vivo ATG T cell depletion are associated with a rather high OS and should be compared in a prospective randomized trial.

     

Open versus closed vitrification system of human oocytes and embryos: a systematic review and meta-analysis of embryologic and clinical outcomes

Background

The objective of this study was to carry out a systematic review and meta-analysis of embryologic and clinical outcomes following open versus closed vitrification of human oocytes and embryos.

Methods

An electronic literature search was conducted in main electronic databases up to June 30, 2018 using the following key terms: ‘oocyte’, ‘embryo’, ‘blastocyst’, ‘vitrification’, ‘cryopreservation’, ‘device’, ‘survival rate’, ‘pregnancy rate’, etc. A meta-analysis was performed using a random effect model to estimate the value of risk ratios (RRs) and 95% confidence interval (CI). Subgroup analyses and sensitivity analyses were carried out to further confirm the results.

Results

Twelve (Eight prospective and four retrospective) studies comparing open versus closed vitrification of human oocytes or embryos were included. For prospective studies on oocytes, no evidence for a significant difference in cryosurvival rate (RR?=?0.91, 95% CI: 0.80–1.03, P?=?0.14; n?=?2048) or clinical pregnancy rate (RR?=?1.29, 95% CI: 0.80–2.06, P?=?0.30; n?=?150) was observed. Additionally, there were no significant differences between the two methods concerning secondary endpoints included positive βHCG rate, implantation rate, miscarriage rate, ongoing pregnancy rate, live birth rate, cancellation rate, babies born per transferred blastocysts, or multiple birth rate (P?>?0.05). The results of the retrospective studies were similar as the prospective studies.

Conclusions

It is still impossible to conclude that closed vitrification system could be a substitution for open system in human oocyte and embryo cryopreservation based on current evidence. Therefore, more well-designed prospective studies addressing these issues are still warranted.

     

Safety and efficacy of inspiratory muscle training for preventing adverse outcomes in patients at risk of prolonged hospitalisation

Background

The early institution of inspiratory muscle training on hospitalised patients with no established respiratory deficits could prevent in-hospital adverse outcomes that are directly or indirectly associated to the loss of respiratory muscle mass inherent to a prolonged hospital stay. The objective of the clinical trial is to assess the impact of inspiratory muscle training on hospital inpatient complications.

Methods

This is a double-blind randomised controlled trial. Subjects in the intervention group underwent an inspiratory muscle training loaded with 50% maximum inspiratory pressure twice daily for 4 weeks from study enrolment. Patients were randomly assigned to an inspiratory muscle training group or a sham inspiratory muscle training group. All patients received conventional physiotherapy interventions. Baseline and post-intervention respiratory and peripheral muscle strength, functionality (performance of activities of daily living), length of hospital stay, and death were evaluated. Clinical outcomes were assessed until hospital discharge. This study was approved by the Institutional Hospital Ethics Committee (03/2014).

Results

Thirty-one patients assigned to the inspiratory muscle training group and 34 to the sham inspiratory muscle training group were analysed. Patients in the inspiratory muscle training group had a shorter mean length of hospital stay (35.3?±?2.7 vs. 41.8?±?3.5 days, p?<?0.01) and a lower risk of endotracheal intubation (relative risk (RR)?=?0.36; 95% confidence interval (CI) 0.27–0.97; p?=?0.03) as well as muscle weakness (RR?=?0.36; 95% CI 0.19–0.98; p?=?0.02) and mortality (RR?=?0.23; 95% CI 0.2–0.94; p?=?0.04). The risk of adverse events did not differ significantly between groups.

Conclusion

Inspiratory muscle training was a protective factor against endotracheal intubation, muscle weakness, and mortality.

Trial registration

ClinicalTrials.gov, ID: NCT02459444. Registered on 19 May 2015.

     

Adjunctive corticosteroid therapy for inpatients with <Emphasis Type="Italic">Mycoplasma pneumoniae</Emphasis> pneumonia

Background

There is conflicting evidence regarding the benefit of adjunctive corticosteroid therapy in patients with Mycoplasma pneumoniae pneumonia. We hypothesised that corticosteroid therapy could reduce mortality and length of stay (LOS) in such patients.

Methods

Adult patients with M. pneumoniae pneumonia from January 2010 to December 2013 were identified from the Japanese Diagnosis Procedure Combination inpatient database. The effects of low-dose and high-dose corticosteroid therapies on mortality, LOS, drug costs and hyperglycaemia requiring insulin treatment were evaluated using propensity score analyses.

Results

Eligible patients (n?=?2228) from 630 hospitals were divided into no-corticosteroid (n?=?1829), low-dose corticosteroid (n?=?267) and high-dose corticosteroid (n?=?132) groups. The propensity score-matched pairs were generated from no-corticoid and low-dose corticoid groups (251 pairs), or no-corticoid and high-dose corticosteroid groups (120 pairs). Adjunctive corticosteroid therapy did not decrease 30-day mortality. In addition, both low-dose and high-dose corticosteroid therapies were associated with increases in LOS. Furthermore, hyperglycaemia requiring insulin treatment and drug cost increased with corticosteroid use.

Conclusions

Adjunctive treatment with low-dose or high-dose corticosteroids may not be beneficial in M. pneumoniae pneumonia.

     

Tumor-infiltrating CD8+ and FOXP3+ lymphocytes before and after neoadjuvant chemotherapy in cervical cancer

Background

Neoadjuvant chemotherapy (NACT) has been recently accepted as an effective alternative in patients with locally advanced cervical cancer. However, little is known about the effects of NACT on the immunological microenvironment in cervical cancers. In this study, we analyzed the alterations of tumor infiltrating lymphocytes (TILs) before and after NACT and analyzed their prognostic significance in advanced cervical cancer patients treated with platinum-based NACT.

Methods

We recruited 137 patients with stage Ib2 and IIa2 cervical cancer retrospectively. Pretreatment biopsy and surgical specimens after NACT were immunostained with CD8 and Foxp3. The densities of intratumoral and peritumoral immunopositive TILs were analyzed separately.

Results

Foxp3+ T cells density significantly decreased in both intratumoral (median 28.49 vs. 19.97; Z?=???8.635, p?<?0.001) and peritumoral (median 113.53 vs. 82.48; Z?=???3.741, p?<?0.001) areas after NACT, whereas CD8+ T cell counts remained stable in both intratumoral (median 121.32 vs. 109.59; Z?=???0.817,p?=?0.414) and peritumoral (median 402.56 vs. 390.84; Z?=???1.138,p?=?0.255) areas. Patients with pathological complete response (pCR) had significantly lower number of Foxp3+ T cell density after NACT than non-pCR cases in both intratumoral (median16.12 vs. 22.00; Z?=???2.009, p?=?0.045) and peritumoral areas(median 63.31 vs. 98.48; Z?=???2.469, p?=?0.014). Multivariate analyses demonstrated that high ratio of intratumoral CD8/peritumoral Foxp3 in residual tumors was independent prognostic factor for both progression-free survival (HR?=?0.297; 95% CI, 0.109–0.810, p?=?0.018) and overall survival (HR?=?0.078; 95% CI, 0.010–0.598, p?=?0.014).

Conclusions

NACT in cervical cancers can induce anti-cancer immunity by altering TILs subsets. An elevated intratumoral CD8/peritumoral Foxp3 ratio after NACT may confer a favorable clinical outcome.

     

Apolipoprotein E polymorphism and the risk of aneurysmal subarachnoid hemorrhage in a South Indian population

Background

The rupture of a brain aneurysm causes bleeding in the subarachnoid space. This is known as aneurysmal subarachnoid hemorrhage (aSAH). We evaluated the association of apolipoprotein E (APOE) polymorphism and the risk of aSAH in a South Indian population.

Methods

The study was performed on 200 subjects with aSAH and 253 healthy control subjects. Blood samples (5 ml) were used to isolate DNA and genotyping was performed for rs7412 and rs429358 using a Taqman allelic discrimination assay. Statistical software R.3.0.11 was used to statistically analyze the data and a p value <?0.05 was considered as statistically significant.

Results

We found a significant association with the risk of aSAH in ε3/ ε4 genetic model (OR?=?1.91, 95% CI?=?1.16–3.14, p?=?0.01). However, in the other genetic models and allele frequency, there was no significant association with the risk of aSAH. In subtyping, we found a significant association of ε2 allele frequency with posterior communicating artery (PCOM) aneurysm (OR?=?3.59, 95% CI?=?1.11–11.64, p?=?0.03).

Conclusion

Our results suggest that APOE polymorphism has an influence on the risk of aSAH in this South Indian population, specifically in the PCOM subtype.

     

The relationship between epicardial adipose tissue and coronary artery stenosis by sex and menopausal status in patients with suspected angina

Background

Evidence suggests that epicardial adipose tissue (EAT) is closely related to coronary artery stenosis (CAS). However, sexual dimorphism may be present in adipose tissue, and its influence on CAS between men and women is controversial. We assessed the relationship between EAT and CAS by sex and menopausal status in patients with suspected angina.

Methods

Six hundred twenty-eight consecutive patients (men/women n?=?257/371; mean age = 59.9?±?10.2?years) who had chest pain for angina and underwent coronary angiography were included. CAS was defined as >?50% luminal narrowing of at least one epicardial coronary artery. EAT thickness was measured by transthoracic echocardiography.

Results

Of the 628 patients, 52.1% (n?=?134) of men and 35.3% (n?=?131) of women had CAS. The mean EAT thickness was not different between men and women and was larger in patients with CAS (8.04?±?2.39 vs 6.58?±?1.88?mm, P?<?0.001). EAT thickness was independently associated with CAS in both sexes (P?<?0.001). The odds ratio (OR) of EAT for the presence of CAS was higher in men (OR?=?1.43, 95% confidence interval [CI] 1.21–1.69) than in women (OR?=?1.24, 95% CI 1.10–1.40). EAT thickness was larger in postmenopausal women than in premenopausal women (7.59?±?2.25 vs 5.80?±?1.57?mm, P?<?0.001) and was independently related with CAS (OR?=?1.24, 95% CI 1.09–1.41). This was not the case in premenopausal women.

Conclusion

In patients with suspected angina, an increase in EAT thickness was independently related to the presence of CAS in both men and women, with it being stronger in men. According to menopausal status in women, EAT thickness is significantly associated with CAS only in postmenopausal women.

     

Association between <Emphasis Type="Italic">ATM</Emphasis> gene polymorphisms,lung cancer susceptibility and radiation-induced pneumonitis: a meta-analysis

Background

Previous studies have suggested that DNA double-strand break (DSB) repair is an important protective pathway after damage. The ataxia telangiectasia mutated (ATM) gene plays an important role in the DNA DSB repair pathway. DNA damage is a major cytotoxic effect that can be caused by radiation, and the ability to repair DNA after damage varies among different tissues. Impaired DNA repair pathways are associated with high sensitivity to radiation exposure. Hence, ATM gene polymorphisms are thought to influence the risk of cancer and radiation-induced pneumonitis (RP) risk in cancer patients treated with radiotherapy. However, the results of previous studies are inconsistent. We therefore conducted this comprehensive meta-analysis.

Methods

A systematic literature search was performed in the PubMed, Embase, China National Knowledge Internet (CNKI) and Wanfang databases to identify studies that investigated the association between the ATM gene polymorphisms and both lung cancer and RP radiotherapy-treated lung cancer (the last search was conducted on Dec.10, 2015). The odds ratio (OR) and 95% confidence interval (CI) were used to investigate the strength of these relationships. Funnel plots and Begg’s and Egger’s tests were conducted to assess the publication bias. All analyses were performed in STATA 13.0 software.

Results

Ten eligible case-control studies (4731 cases and 5142 controls) on lung cancer susceptibility and four (192 cases and 772 controls) on RP risk were included. The results of the overall and subgroup analyses indicated that in the ATM gene, the rs189037 (?111G?>?A, ?4519G?>?A), rs664677 (44831C?>?T, 49238C?>?T) and rs664143 (131,717 T?>?G) polymorphisms were significantly associated with lung cancer susceptibility (OR?=?1.21, 95% CI?=?1.04–1.39, P?=?0.01; OR?=?1.26, 95% CI?=?1.06–1.49, P?=?0.01; OR?=?1.43, 95% CI?=?1.15–1.78, P?<?0.01). Additionally, the rs189037 variant was significantly associated with RP risk (OR?=?1.74, 95% CI?=?1.02–2.97, P?=?0.04). No publication bias was found in the funnel plots, Begg’s tests or Egger’s tests.

Conclusions

The results indicate that the ATM rs189037, rs664677 and rs664143 gene polymorphisms are risk factors for lung cancer, while the ATM rs189037 variant was significantly associated with RP risk.

     

Prognostic impact of pretreatment lymphocyte-to-monocyte ratio in advanced epithelial cancers: a meta-analysis

Background

There is increasing evidence that inflammation-based biomarkers are associated with tumor microenvironment which plays important roles in cancer progression. A high lymphocyte-to-monocyte ratio (LMR), has been suggested to indicate favorable prognoses in various epithelial cancers. We performed a meta-analysis to quantify the prognostic value of LMR in advanced-stage epithelial cancers undergoing various treatment.

Methods

We searched PubMed, EMBASE, Web of science and Cochrane Library up to July 2018 for relevant studies. We included studies assessing the prognostic impact of pretreatment LMR on clinical outcomes in patients with advanced-stage epithelial cancers. The primary outcome was overall survival (OS) and the secondary outcome was progression free survival (PFS). The summary hazard ratio (HR) and 95% confidence interval (CI) were calculated.

Results

A total of 8984 patients from 35 studies were included. A high pretreatment LMR was associated with favorable OS (HR?=?0.578, 95% CI 0.522–0.641, P?<?0.001) and PFS (HR?=?0.598, 95% CI 0.465–0.768, P?<?0.001). The effect of LMR on OS was observed among various tumor types. A higher pretreatment LMR was associated with improved OS in chemotherapy (n?=?10, HR?=?0.592, 95% CI 0.518–0.676, P?<?0.001), surgery (n?=?10, HR?=?0.683, 95% CI 0.579–0.807, P?<?0.001) and combined therapy (n?=?11, HR?=?0.507, 95% CI 0.442–0.582, P?<?0.001) in the subgroup analysis by different therapeutic strategies. The cut-off value for LMR was 3.0 (range?=?2.35–5.46). Subgroup analysis according to the cut-off value showed a significant prognostic value of LMR on OS and PFS in both subgroups.

Conclusions

A high pretreatment LMR is associated with favorable clinical outcomes in advanced-stage epithelial cancers undergoing different therapeutic strategies. LMR could be used to improve clinical decision-making regarding treatment in advanced epithelial cancers.

     

Association between viscoelastic tests-guided therapy with synthetic factor concentrates and allogenic blood transfusion in liver transplantation: a before-after study

Background

Perioperative bleeding and transfusion are important causes of morbidity and mortality in patients undergoing liver transplantation. The aim of this study is to assess whether viscoelastic tests-guided therapy with the use of synthetic factor concentrates impact transfusion rates of hemocomponents in adult patients undergoing liver transplantation.

Methods

This is an interventional before-after comparative study. Patients undergoing liver transplantation before the implementation of a protocol using thromboelastometry and synthetic factor concentrates were compared to patients after the implementation. Primary outcome was transfusion of any hemocomponents. Secondary outcomes included: transfusion of red blood cells (RBC), fresh frozen plasma (FFP), cryoprecipitate or platelets, clinical complications, length of stay and in-hospital mortality.

Results

A total of 183 patients were included in the control and 54 in the intervention phase. After propensity score matching, the proportion of patients receiving any transfusion of hemocomponents was lower in the intervention phase (37.0 vs 58.4%; OR, 0.42; 95% CI, 0.20–0.87; p?=?0.019). Patients in the intervention phase received less RBC (30.2 vs 52.5%; OR, 0.21; 95% CI, 0.08–0.56; p?=?0.002) and FFP (5.7 vs 27.3%; OR, 0.11; 95% CI, 0.03–0.43; p?=?0.002). There was no difference regarding transfusion of cryoprecipitate and platelets, complications related to the procedure, hospital length of stay and mortality.

Conclusions

Use of a viscoelastic test-guided transfusion algorithm with the use of synthetic factor concentrates reduces the transfusion rates of allogenic blood in patients submitted to liver transplantation.

Trial registration

This trial was registered retrospectively on November 15th, 2018 – clinicaltrials.gov – Identifier: NCT03756948.

     

Long-duration general anesthesia influences the intelligence of school age children

Background

General anesthesia has been linked to impaired brain development in immature animals and young children. In this study the influence of orthopedic surgery under general anesthesia on the intelligence of school age children has been evaluated.

Methods

A total of 209 subjects aged 6–12 years were recruited and allocated into 4 groups according to the duration of general anesthesia, including a control group (n?=?30), short (< 1 h, n?=?49), moderate- (1–3 h, n?=?51) and long-duration groups (> 3 h, n?=?79), respectively. The intelligence quotient (IQ) of the subjects was measured by the Raven’s Standard Progressive Matrices (RSPM) before and after orthopedic surgery under general anesthesia of various durations (vide supra).

Results

The IQ score decreased significantly in the long-duration group at 1 month post-operation compared with the pre-operation score (P?<?0.001), and IQ did not recover completely at 3 months postoperatively (P?<?0.05), but had recovered when measured at the 1-year follow-up. Moreover, this study showed that the development of children’s intelligence was affected by the exposure time to anesthetics at a younger age (OR?=?5.26, 95% CI:2.70–8.41, P?<?0.001), having a mother with a low education level (OR?=?2.71, 95% CI:1.24–6.14, P?=?0.014) and premature birth (OR?=?2.76, 95% CI:1.34–5.46, P?=?0.005).

Conclusions

More than 3 h general anesthesia influenced the IQ of school age children for up to 3 months after orthopedic surgery. Beside extended exposure time to anesthetics additional factors for post-operative IQ reduction were younger children age, mothers with low educational levels and premature birth.

Trial registration

Chinese Clinical Trial Registry with registration number ChiCTR-OOC-17013497 retrospectively registered on 11/23/2017.

     

Double product reflects the association of heart rate with MACEs in acute coronary syndrome patients treated with percutaneous coronary intervention

Background

There is little information about the prognostic value of double product (DP) for acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). The aim of this study was to investigate whether DP reflects the predictive power of heart rate (HR) or systolic blood pressure (SBP) in ACS patients treated with PCI.

Methods

A total of 7590 ACS patients who had undergone PCI, free from cardiac shock, were included. The follow-up duration was two years. The main adverse cardiovascular events (MACEs) included all-cause death, recurrent myocardial infarction and stroke.

Results

In the unadjusted model, significantly higher rates of MACEs were recorded in the high DP group (relative risk 1.41, 95%CI 1.08 to 1.83, p?=?0.012). However, in the full adjusted models, after including HR and SBP, the predictive value of DP was not significant (relative risk 0.86, 95%CI 0.55 to1.33, p?=?0.499). The predictive value of HR for MACEs was statistically significant (relative risk 1.74, 95% CI 1.33–2.28, p?<?0.001). It was worth noting that the history of hypertension was strongly associated with MACEs (relative risk 1.53, 95% CI 1.11–2.11, p?=?0.009).

Conclusion

High DP is associated with MACEs for ACS patients treated with PCI. However, the predictive value of DP weakened when adjusted for HR. Therefore, we have shown that DP may reflect the predictive power of HR for ACS patients treated with PCI.