Machine Perfusion versus Cold Storage of Kidneys Derived from Donation after Cardiac Death: A Meta-Analysis

Background

In response to the increased organ shortage, organs derived from donation after cardiac death (DCD) donors are becoming an acceptable option once again for clinical use in transplantation. However, transplant outcomes in cases where DCD organs are used are not as favorable as those from donation after brain death or living donors. Different methods of organ preservation are a key factor that may influence the outcomes of DCD kidney transplantation.

Methods

We compared the transplant outcomes in patients receiving DCD kidneys preserved by machine perfusion (MP) or by static cold storage (CS) preservation by conducting a meta-analysis. The MEDLINE, EMBASE and Cochrane Library databases were searched. All studies reporting outcomes for MP versus CS preserved DCD kidneys were further considered for inclusion in this meta-analysis. Odds ratios and 95% confidence intervals (CI) were calculated to compare the pooled data between groups that were transplanted with kidneys that were preserved by MP or CS.

Results

Four prospective, randomized, controlled trials, involving 175 MP and 176 CS preserved DCD kidney transplant recipients, were included. MP preserved DCD kidney transplant recipients had a decreased incidence of delayed graft function (DGF) with an odd ration of 0.56 (95% CI = 0.36–0.86, P = 0.008) compared to CS. However, no significant differences were seen between the two technologies in incidence of primary non-function, one year graft survival, or one year patient survival.

Conclusions

MP preservation of DCD kidneys is superior to CS in terms of reducing DGF rate post-transplant. However, primary non-function, one year graft survival, and one year patient survival were not affected by the use of MP or CS for preservation.     

High-Dose Statin Pretreatment Decreases Periprocedural Myocardial Infarction and Cardiovascular Events in Patients Undergoing Elective Percutaneous Coronary Intervention: A Meta-Analysis of Twenty-Four Randomized Controlled Trials

Background

Evidence suggests that high-dose statin pretreatment may reduce the risk of periprocedural myocardial infarction (PMI) and major adverse cardiac events (MACE) for certain patients; however, previous analyses have not considered patients with a history of statin maintenance treatment. In this meta-analysis of randomized controlled trials (RCTs), we reevaluated the efficacy of short-term high-dose statin pretreatment to prevent PMI and MACE in an expanded set of patients undergoing elective percutaneous coronary intervention.

Methods

We searched the PubMed/Medline database for RCTs that compared high-dose statin pretreatment with no statin or low-dose statin pretreatment as a prevention of PMI and MACE. We evaluated the incidence of PMI and MACE, including death, spontaneous myocardial infarction, and target vessel revascularization at the longest follow-up for each study for subgroups stratified by disease classification and prior low-dose statin treatment.

Results

Twenty-four RCTs with a total of 5,526 patients were identified. High-dose statin pretreatment was associated with 59% relative reduction in PMI (odds ratio [OR]: 0.41; 95% confidence interval [CI]: 0.34–0.49; P<0.00001) and 39% relative reduction in MACE (OR: 0.61; 95% CI: 0.45–0.83; P = 0.002). The benefit of high-dose statin pretreatment on MACE was significant for statin-naive patients (OR: 0.69; 95% CI: 0.50–0.95; P = 0.02) and prior low dose statin-treated patients (OR: 0.28; 95% CI: 0.12–0.65; P = 0.003); and for patients with acute coronary syndrome (OR: 0.52; 95% CI: 0.34–0.79; P = 0.003), but not for patients with stable angina (OR: 0.71; 95% CI 0.45–1.10; P = 0.12). Long-term effects on survival were less obvious.

Conclusions

High-dose statin pretreatment can result in a significant reduction in PMI and MACE for patients undergoing elective PCI. The positive effect of high-dose statin pretreatment on PMI and MACE is significant for statin-naïve patients and patients with prior treatment. The positive effect of high-dose statin pretreatment on MACE is significant for patients with acute coronary syndrome.     

Corticosteroids in the Treatment of Community-Acquired Pneumonia in Adults: A Meta-Analysis

Background

The benefit of corticosteroids in community-acquired pneumonia (CAP) remains controversial. We did a meta-analysis to include all the randomized controlled trials (RCTs) which used corticosteroids as adjunctive therapy, to examine the benefits and risks of corticosteroids in the treatment of CAP in adults.

Methods

Databases including Pubmed, EMBASE, the Cochrane controlled trials register, and Google Scholar were searched to find relevant trials. Randomized and quasi-randomized trials of corticosteroids treatment in adult patients with CAP were included. Effects on primary outcome (mortality) and secondary outcomes (adverse events) were accessed in this meta-analysis.

Results

Nine trials involving 1001 patients were included. Use of corticosteroids did not significantly reduce mortality (Peto odds ratio [OR] 0.62, 95% confidence interval [CI] 0.37–1.04; P = 0.07). In the subgroup analysis by the severity, a survival benefit was found among severe CAP patients (Peto OR 0.26, 95% CI 0.11–0.64; P = 0.003). In subgroup analysis by duration of corticosteroids treatment, significant reduced mortality was found among patients with prolonged corticosteroids treatment (Peto OR 0.51, 95% CI 0.26–0.97; P = 0.04; I ² = 37%). Corticosteroids increased the risk of hyperglycemia (Peto OR 2.64, 95% CI 1.68–4.15; P<0.0001), but without increasing the risk of gastroduodenal bleeding (Peto OR 1.67, 95% CI 0.41–6.80; P = 0.47) and superinfection (Peto OR 1.36, 95% CI 0.65–2.84; P = 0.41).

Conclusion

Results from this meta-analysis did not suggest a benefit for corticosteroids treatment in patients with CAP. However, the use of corticosteroids was associated with improved mortality in severe CAP. In addition, prolonged corticosteroids therapy suggested a beneficial effect on mortality. These results should be confirmed by future adequately powered randomized trials.     

The Increased Risk for Autoimmune Diseases in Patients with Eating Disorders

Objective

Research suggests autoimmune processes to be involved in psychiatric disorders. We aimed to address the prevalence and incidence of autoimmune diseases in a large Finnish patient cohort with anorexia nervosa, bulimia nervosa, and binge eating disorder.

Methods

Patients (N = 2342) treated at the Eating Disorder Unit of Helsinki University Central Hospital between 1995 and 2010 were compared with general population controls (N = 9368) matched for age, sex, and place of residence. Data of 30 autoimmune diseases from the Hospital Discharge Register from 1969 to 2010 were analyzed using conditional and Poisson regression models.

Results

Of patients, 8.9% vs. 5.4% of control individuals had been diagnosed with one or more autoimmune disease (OR 1.7, 95% CI 1.5–2.0, P<0.001). The increase in endocrinological diseases (OR 2.4, 95% CI 1.8–3.2, P<0.001) was explained by type 1 diabetes, whereas Crohn''s disease contributed most to the risk of gastroenterological diseases (OR 1.8, 95% CI 1.4–2.5, P<0.001). Higher prevalence of autoimmune diseases among patients with eating disorders was not exclusively due to endocrinological and gastroenterological diseases; when the two categories were excluded, the increase in prevalence was seen in the patients both before the onset of the eating disorder treatment (OR 1.5, 95% CI 1.1–2.1, P = 0.02) and at the end of the follow-up (OR 1.4, 95% CI 1.1–1.8, P = 0.01).

Conclusions

We observed an association between eating disorders and several autoimmune diseases with different genetic backgrounds. Our findings support the link between immune-mediated mechanisms and development of eating disorders. Future studies are needed to further explore the risk of autoimmune diseases and immunological mechanisms in individuals with eating disorders and their family members.     

Derivation and Validation of a Scoring System to Identify Patients with Bacteremia and Hematological Malignancies at Higher Risk for Mortality

Background

The aim of this study was to develop and validate a reliable clinical prediction rule that could be employed to identify patients at higher likelihood of mortality among those with hematological malignancies (HMs) and bacterial bloodstream infections (BBSIs).

Methods and Findings

We conducted a retrospective cohort study in nine Italian hematological units. The derivation cohort consisted of adult patients with BBSI and HMs admitted to the Catholic University Hospital (Rome) between January 2002 and December 2008. Survivors and nonsurvivors were compared to identify predictors of 30-day mortality. The validation cohort consisted of patients hospitalized with BBSI and HMs who were admitted in 8 other Italian hematological units between January 2009 and December 2010. The inclusion and exclusion criteria were identical for both cohorts, with type and stage of HMs used as matching criteria. In the derivation set (247 episodes), the multivariate analysis yielded the following significant mortality-related risk factors acute renal failure (Odds Ratio [OR] 6.44, Confidential Interval [CI], 2.36–17.57, P<0.001); severe neutropenia (absolute neutrophil count <100/mm³) (OR 4.38, CI, 2.04–9.43, P<0.001); nosocomial infection (OR, 3.73, CI, 1.36–10.22, P = 0.01); age ≥65 years (OR, 3.42, CI, 1.49–7.80, P = 0.003); and Charlson Comorbidity Index ≥4 (OR, 3.01, CI 1.36–6.65, P = 0.006). The variables unable to be evaluated at that time (for example, prolonged neutropenia) were not included in the final logistic model. The equal-weight risk score model, which assigned 1 point to each risk factor, yielded good-excellent discrimination in both cohorts, with areas under the receiver operating curve of 0.83 versus 0.93 (derivation versus validation) and good calibration (Hosmer-Lemshow P = 0.16 versus 0.75).

Conclusions

The risk index accurately identifies patients with HMs and BBSIs at high risk for mortality; a better initial predictive approach may yield better therapeutic decisions for these patients, with an eventual reduction in mortality.     

CpG Island Methylator Phenotype,Helicobacter pylori,Epstein-Barr Virus,and Microsatellite Instability and Prognosis in Gastric Cancer: A Systematic Review and Meta-Analysis

Background

The controversy of CpG island methylator phenotype (CIMP) in gastric cancer persists, despite the fact that many studies have been conducted on its relation with helicobacter pylori (H. pylori), Epstein-Barr virus (EBV), and microsatellite instability (MSI) and prognosis. To drive a more precise estimate of this postulated relationship, a meta-analysis was performed based on existing relevant studies.

Methods

We combined individual patient data from 12 studies which involved 1000 patients with gastric cancer, which met the criteria. We tabulated and analyzed parameters from each study, including H. pylori, EBV, MSI, and clinical information of patients.

Results

The overall OR for H. pylori infection in CIMP positive group vs. negative group revealed that significantly elevated risks of positive H. pylori infection in the former were achieved (OR 2.23 95% CI, 1.25–4.00; P = 0.007, P_{heterogeneity} = 0.05). Similarly, strong relation between EBV infection and CIMP was achieved by OR 51.27 (95% CI, 9.39–279.86; P<0.00001, P_{heterogeneity} = 0.39). The overall OR for MSI in CIMP positive group vs. negative group was 4.44 (95% CI, 1.17–16.88; P = 0.03, P_{heterogeneity} = 0.01). However, there did not appear to be any correlations with clinical parameters such as tumor site, pathological type, cell differentiation, TNM stage, distant metastasis, lymph node metastasis, and 5-year survival.

Conclusions

The meta-analysis highlights the strong relation of CIMP with H. pylori, EBV, and MSI, but CIMP can not be used as a prognostic marker for gastric cancer.     

Cardioembolic and Small Vessel Disease Stroke Show Differences in Associations between Systemic C3 Levels and Outcome

Background

Activation of the complement system has been proposed to play a role in the pathophysiology of stroke. As the specific involvement of the complement proteins may be influenced by stroke etiology, we compared plasma C3 and C3a levels in patients with cardioembolic (CE) and small vessel disease (SVD) subtypes of ischemic stroke and control subjects and evaluated their association to outcome at three months and two years.

Methodology/Principal Findings

Plasma C3 and C3a levels in 79 CE and 79 SVD stroke patients, sampled within 10 days and at three months after stroke, and age- and sex-matched control subjects from The Sahlgrenska Academy Study on Ischemic Stroke were measured by ELISA. Functional outcome was assesed with modified Rankin Scale. In the CE group, plasma C3 levels were elevated only in the acute phase, whereas C3a was elevated at both time points. The follow-up phase plasma C3 levels in the upper third were associated with an increased risk of unfavorable outcome at three months (OR 7.12, CI 1.72–29.46, P = 0.007) as well as after two years (OR 8.25, CI 1.61–42.28, P = 0.011) after stroke. These associations withstand adjustment for age and sex. Conversely, three-month follow-up plasma C3a/C3 level ratios in the middle third were associated with favorable outcome after two years both in the univariate analysis (OR 0.19, CI 0.05–0.82, P = 0.026) and after adjustment for age and sex (OR 0.19, CI 0.04–0.88, P = 0.033). In the SVD group, plasma C3 and C3a levels were elevated at both time points but showed no significant associations with outcome.

Conclusions

Plasma C3 and C3a levels are elevated after CE and SVD stroke but show associations with outcome only in CE stroke.     

Impact of Early Reoperation following Living-Donor Liver Transplantation on Graft Survival

Background

The reoperation rate remains high after liver transplantation and the impact of reoperation on graft and recipient outcome is unclear. The aim of our study is to evaluate the impact of early reoperation following living-donor liver transplantation (LDLT) on graft and recipient survival.

Methods

Recipients that underwent LDLT (n = 111) at the University of Tokyo Hospital between January 2007 and December 2012 were divided into two groups, a reoperation group (n = 27) and a non-reoperation group (n = 84), and case-control study was conducted.

Results

Early reoperation was performed in 27 recipients (24.3%). Mean time [standard deviation] from LDLT to reoperation was 10 [9.4] days. Female sex, Child-Pugh class C, Non-HCV etiology, fulminant hepatitis, and the amount of intraoperative fresh frozen plasma administered were identified as possibly predictive variables, among which females and the amount of FFP were identified as independent risk factors for early reoperation by multivariable analysis. The 3-, and 6- month graft survival rates were 88.9% (95%confidential intervals [CI], 70.7–96.4), and 85.2% (95%CI, 66.5–94.3), respectively, in the reoperation group (n = 27), and 95.2% (95%CI, 88.0–98.2), and 92.9% (95%CI, 85.0–96.8), respectively, in the non-reoperation group (n = 84) (the log-rank test, p = 0.31). The 12- and 36- month overall survival rates were 96.3% (95%CI, 77.9–99.5), and 88.3% (95%CI, 69.3–96.2), respectively, in the reoperation group, and 89.3% (95%CI, 80.7–94.3) and 88.0% (95%CI, 79.2–93.4), respectively, in the non-reoperation group (the log-rank test, p = 0.59).

Conclusions

Observed graft survival for the recipients who underwent reoperation was lower compared to those who did not undergo reoperation, though the result was not significantly different. Recipient overall survival with reoperation was comparable to that without reoperation. The present findings enhance the importance of vigilant surveillance for postoperative complication and surgical rescue at an early postoperative stage in the LDLT setting.     

The Association between the Pro12Ala Variant in the PPARγ2 Gene and Type 2 Diabetes Mellitus and Obesity in a Chinese Population

Background

Conflicting results have been reported on the association of the Pro12Ala polymorphism of the PPARγ2 gene with the risk of type 2 diabetes or obesity.

Methods and Findings

A total of 3146 subjects with 1145 cases of type 2 diabetes and 2001 healthy controls were included in the study. Genomic DNA was obtained from blood samples and the screening for the gene polymorphisms was done using an allelic discrimination assay-by-design TaqMan method. Overall, the Ala allele frequency was 5.6% in control subjects and 3.9% in diabetes subjects (P = 0.023). We found a statistically significant association of carriers of the Ala allele with greater homoeostasis model assessment of beta cell function index in all subjects (P = 0.046). After controlling for confounders, carriers of the Ala allele had a decreased risk of diabetes compared with noncarriers [odds ratio (OR) 0.64, 95% confidence interval (CI) 0.49–0.83; P = 0.001]. A beneficial effect of the Ala allele was also observed for obesity (OR 0.64, 95% CI 0.42–0.96; P = 0.030).

Conclusion

Our results suggested that the presence of the Ala allele may contribute to improved insulin secretory capacity and may confer protection from type 2 diabetes and obesity in the Chinese population.     

Stent-Assisted Coiling versus Coiling in Treatment of Intracranial Aneurysm: A Systematic Review and Meta-Analysis

Background and Purpose

Stent-assisted coiling was initially invented for wide-neck aneurysms, but is now used for smaller berry aneurysms. The aim of this study was to compare the safety and efficiency of stent-assisted coiling with conventional coiling in treatment of intracranial aneurysms.

Methods

A meta-analysis of studies that compared stent-assisted coiling with coiling only was conducted by searching English literatures via Pubmed, Medline and Cochrane Library databases without restricting the publication year. The primary outcomes in this study were immediate occlusion, progressive thrombosis rate, all-complication rate and angiographic recurrence. The secondary outcomes examined were packing density, mortality, permanent complication and thromboembolic complication rate.

Results

Ten retrospective cohort studies were included. There is currently only one unfinished randomized study. Although the stent-assisted coiling group tended to show a lower initial occlusion rate than that of the coiling-only group (57.6% versus 68.7%; OR, 0.66; 95% CI, 0.30–1.44; P = 0.30), it achieved a significantly higher progressive thrombosis rate during follow up compared to that of the coiling only group (37.5% versus 19.4%; OR, 2.75; 95% CI, 1.95–3.86; P<0.00001) and a significantly lower recurrence rate (16.2% versus 34.4%; OR, 0.35; 95% CI, 0.25–0.49; P<0.00001). With respect to safety concerns, the all-complication rate (17.6% versus 15.9%; OR, 1.12; 95% CI, 0.77–1.62; P = 0.56), mortality rate (9.1% versus 2.6%; OR, 2.31; 95% CI, 0.68–7.82; P = 0.18), permanent complication rate (5.6% versus 3.9%; OR, 1.52; 95% CI, 0.96–2.41; P = 0.08) and thromboembolic complication rate (4.2% versus 4.9%; OR, 0.99; 95% CI, 0.41–2.38; P = 0.97) did not show significant difference between the two groups.

Conclusions

Stent-assisted coiling has a lower recurrence rate than conventional coiling. Analysis of complication events did not show any significant difference between the two methods. Despite the findings reported herein, further validation by well-designed prospective studies is needed.     

Prediction of Long-Term Mortality by Preoperative Health-Related Quality-of-Life in Elderly Onco-Surgical Patients

Objective

Aim of this study was to evaluate the association between preoperative health-related quality of life (HRQoL) and mortality in a cohort of elderly patients (>65 years) with gastrointestinal, gynecological and genitourinary carcinomas.

Design

Prospective cohort pilot study.

Setting

Tertiary university hospital in Germany.

Patients

Between June 2008 and July 2010 and after ethical committee approval and written informed consent, 126 patients scheduled for onco-surgery were included. Prior to surgery as well as 3 and 12 months postoperatively all participants completed the EORTC-QLQ-C30 questionnaire (measuring self-reported health-related quality of life). Additionally, demographic and clinical data including the Mini Mental State Examination (MMSE) were collected. Surgery and anesthesia were conducted according to the standard operating procedures. Primary endpoint was the cumulative mortality rate over 12 months after one year. Changes in Quality of life were considered as secondary outcome.

Results

Mortality after one year was 28%. In univariable and multivariable logistic regression analysis baseline HRQoL self-reported cognitive function (OR per point: 0.98; CI 95% 0.96–0.99; p = 0.024) and higher symptom burden for appetite loss (per point: OR 1.02; CI 95% 1.00–1.03; p = 0.014) were predictive for long-term mortality. Additionally the MMSE as an objective measure of cognitive impairment (per point: OR 0.69; CI 95% 0.51–0.96; p = 0.026) as well as severity of surgery (OR 0.31; CI 95% 0.11–0.93; p = 0.036) were predictive for long-term mortality. Global health status 12 months after surgery was comparable to the baseline levels in survivors despite moderate impairments in other domains.

Conclusion

This study showed that objective and self-reported cognitive functioning together with appetite loss were prognostic for mortality in elderly cancer patients. In addition, impaired cognitive dysfunction and severity of surgery were predictive for one-year mortality whereas in this selected population scheduled for surgery age, gender, cancer site and metastases were not.     

The Association of Homocysteine with Metabolic Syndrome in a Community-Dwelling Population: Homocysteine Might Be Concomitant with Metabolic Syndrome

Objective

Elevated plasma total homocysteine (tHcy) and metabolic syndrome (MetS) are both associated with cardiovascular disease, but the association between tHcy and MetS is not well characterized. The aim of this study was to determine the relationship between tHcy and MetS.

Methods

To further estimate the time-dependent association of tHcy and MetS, we analyzed the tHcy level and MetS in 1499 subjects from a 4.8-year longitudinal study in Beijing, People’s Republic of China.

Results

In multiple linear regression analysis, baseline tHcy levels associated with age, BMI, SBP, DBP, LDL-C and Cr independently over 4.8-years follow-up; age, BMI, SBP, DBP and Cr were found to be associated with tHcy levels independently at the end of follow-up. Logistic regression analysis showed that there was no association between the baseline tHcy level and MetS over the 4.8-year follow-up (odds ratio (OR), 1.32; 95% confidence interval (CI), 0.79–2.19; P = 0.282); rather, there was an association only with hypertension as a MetS component (OR, 1.53; 95% CI, 1.06–2.21; P = 0.024). tHcy levels were associated with MetS at both cross-sectional baseline (OR, 1.38; 95% CI, 1.02–1.88; P = 0.038) and cross-sectional follow-up (OR, 1.60; 95% CI, 1.02–2.50; P = 0.041). The tHcy levels of MetS subjects were higher than those of non-MetS subjects at both cross-sectional baseline (19.35±7.92 µmol/L vs. 17.45±6.70 µmol/L, respectively; P = 0.001) and cross-sectional follow-up (18.95±7.15 µmol/L vs. 17.11±5.98 µmol/L, respectively; P = 0.02).

Conclusion

The tHcy level was not predictive of the incidence of MetS; however, it may be a risk factor for hypertension as a MetS component. Furthermore, tHcy levels were associated with MetS at cross-sectional baseline and follow-up, which suggests that a higher level of tHcy might be concomitant with MetS.     

Prognostic Significance of Circulating Tumor Cells in Non-Small-Cell Lung Cancer Patients: A Meta-Analysis

Background

The prognostic significance of circulating tumor cells (CTCs) detected in patients with non-small-cell lung cancer (NSCLC) is still inconsistent. We aimed to assess the prognostic relevance of CTCs using a meta-analysis.

Methods

We searched PubMed, Web of Science and EMBASE for relevant studies that assessed the prognostic relevance of CTCs in NSCLC. Statistical analyses were conducted to calculate the summary incidence, odds ratio, relative risks (RRs) and 95% confidence intervals (CIs) using fixed or random-effects models according to the heterogeneity of included studies.

Results

A total of 20 studies, comprising 1576 patients, met the inclusion criteria. In identified studies, CTCs were not correlated with histology (adenocarcinoma vs squamous cell carcinoma) (odds ratio [OR]  =  0.88; 95% confidence interval [CI]: 0.59–1.33; Z = –0.61; P = 0.545). However, pooled analyses showed that CTCs were associated with lymph node metastasis (OR = 2.06; 95% CI: 1.18–3.62; Z = 2.20; P = 0.027) and tumor stage (OR  = 1.95; 95% CI: 1.08–3.54; Z = 2.53; P = 0.011). Moreover, CTCs were significantly associated with shorter overall survival (relative risk [RR]  = 2.19; 95% CI: 1.53–3.12; Z = 4.32; P<0.0001) and progression-free/disease-free survival (RR  = 2.14; 95% CI: 1.36–3.38; Z = 3.28; P<0.0001).

Conclusion

The presence of CTCs indicates a poor prognosis in patients with NSCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in lung cancer.     

Duration of Chemotherapy for Small Cell Lung Cancer: A Meta-Analysis

Background

Maintenance chemotherapy is widely provided to patients with small cell lung cancer (SCLC). However, the benefits of maintenance chemotherapy compared with observation are a subject of debate.

Methodology and Principal Findings

To identify relevant literature, we systematically searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. Eligible trials included patients with SCLC who either received maintenance chemotherapy (administered according to a continuous or switch strategy) or underwent observation. The primary outcome was 1-year mortality, and secondary outcomes were 2-year mortality, overall survival (OS), and progression-free survival (PFS). Of the 665 studies found in our search, we identified 14 relevant trials, which together reported data on 1806 patients with SCLC. When compared with observation, maintenance chemotherapy had no effect on 1-year mortality (odds ratio [OR]: 0.88; 95% confidence interval [CI]: 0.66–1.19; P = 0.414), 2-year mortality (OR: 0.82; 95% CI: 0.57–1.19; P = 0.302), OS (hazard ratio [HR]: 0.87; 95% CI: 0.71–1.06; P = 0.172), or PFS (HR: 0.87; 95% CI: 0.62–1.22; P = 0.432). However, subgroup analyses indicated that maintenance chemotherapy was associated with significantly longer PFS than observation in patients with extensive SCLC (HR, 0.72; 95% CI: 0.58–0.89; P = 0.003). Additionally, patients who were managed using the continuous strategy of maintenance chemotherapy appeared to be at a disadvantage in terms of PFS compared with patients who only underwent observation (HR, 1.27; 95% CI: 1.04–1.54; P = 0.018).

Conclusions/Significance

Maintenance chemotherapy failed to improve survival outcomes in patients with SCLC. However, a significant advantage in terms of PFS was observed for maintenance chemotherapy in patients with extensive disease. Additionally, our results suggest that the continuous strategy is inferior to observation; its clinical value needs to be investigated in additional trials.     

A Large Cohort Study Reveals the Association of Elevated Peripheral Blood Lymphocyte-to-Monocyte Ratio with Favorable Prognosis in Nasopharyngeal Carcinoma

Background

Nasopharyngeal carcinoma (NPC) is an endemic neoplasm in southern China. Although NPC sufferers are sensitive to radiotherapy, 20–30% of patients finally progress with recurrence and metastases. Elevated lymphocyte-to-monocyte ratio (LMR) has been reported to be associated with favorable prognosis in some hematology malignancies, but has not been studied in NPC. The aim of this study was to evaluate whether LMR could predict the prognosis of NPC patients.

Methods

A retrospective cohort of 1,547 non-metastatic NPC patients was recruited between January 2005 and June 2008. The counts for peripheral lymphocyte and monocyte were retrieved, and the LMR was calculated. Receiver operating characteristic curve analysis, univariate and multivariate COX proportional hazards analyses were applied to evaluate the associations of LMR with overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and loco-regional recurrence-free survival (LRRFS), respectively.

Results

Univariate analysis revealed that higher LMR level (≥5.220) was significantly associated with superior OS, DFS and DMFS (P values <0.001). The higher lymphocyte count (≥2.145×10⁹/L) was significantly associated with better OS (P = 0.002) and DMFS (P = 0.031), respectively, while the lower monocyte count (<0.475×10⁹/L) was associated with better OS (P = 0.012), DFS (P = 0.011) and DMFS (P = 0.003), respectively. Multivariate Cox proportional hazard analysis showed that higher LMR level was a significantly independent predictor for superior OS (hazard ratio or HR  = 0.558, 95% confidence interval or 95% CI  = 0.417–0.748; P<0.001), DFS (HR  = 0.669, 95% CI  = 0.535–0.838; P<0.001) and DMFS (HR = 0.543, 95% CI  = 0.403–0.732; P<0.001), respectively. The advanced T and N stages were also independent indicators for worse OS, DFS, and DMFS, except that T stage showed borderline statistical significance for DFS (P = 0.053) and DMFS (P = 0.080).

Conclusions

The elevated pretreatment peripheral LMR level was a significant favorable factor for NPC prognosis and this easily accessed variable may serve as a potent marker to predict the outcomes of NPC patients.     

Meta-Analysis on the Associations of TLR2 Gene Polymorphisms with Pulmonary Tuberculosis Susceptibility among Asian Populations

Background

Publications regarding the associations of toll-like receptor 2 (TLR2) G2258A and T597C polymorphisms with pulmonary tuberculosis (PTB) susceptibility are inconsistent. A meta-analysis was conducted to investigate the relationship between TLR2 G2258A and T597C polymorphisms with PTB susceptibility.

Methods

A systematic search was performed for published studies on the relationship between TLR2 polymorphisms and PTB susceptibility. Information was gathered from each eligible study, and statistically analyzed.

Results

6 eligible studies, totaling 1301 cases and 1217 controls on G2258A genotypes, and 8 studies, totaling 2175 cases and 2069 controls on T597C genotypes, were included in the analysis. TLR2 2258G allele and 2258GG genotype were found to be associated with decreased PTB susceptibility (A vs. G: OR  = 3.02, 95% CI: 2.22–4.12, P<0.001, GA+AA vs. GG: OR  = 2.69, 95% CI = 1.49–4.87, P = 0.001). In the subgroup analyses, the 2258G allele and 2258GG genotype also exhibited a protective effect of PTB risk in Asians (A vs. G: OR  = 2.95, 95% CI: 1.91–4.55, P<0.001; GA+AA vs. GG: OR  = 3.59, 95% CI: 2.23–5.78, P<0.001), while no associations were observed in Caucasians. No significant associations between T597C polymorphism and PTB were found in the allele model (C vs. T: OR  = 0.95, 95% CI: 0.86–1.04, P = 0.28), co-dominant model (CC vs. TT: OR  = 0.88, 95% CI = 0.92–1.40, P = 0.25; CT vs. TT: OR  = 0.92, 95% CI = 0.80–1.06, P = 0.28), recessive model (CC vs. TT+TC: OR  = 0.96, 95% CI: 0.80–1.16, P = 0.69), or dominant model (TC+CC vs. TT: OR  = 0.93, 95% CI = 0.76–1.15, P = 0.51). The associations of T597C polymorphism with PTB susceptibility, in the ethnic-specific analyses, were still not significant.

Conclusion

TLR2 2258G allele may provide protective effects against PTB susceptibility, particularly among Asians, whereas TLR2 T597C polymorphism might not be associated with PTB susceptibility.     

External Suction versus Water Seal after Selective Pulmonary Resection for Lung Neoplasm: A Systematic Review

Objective

To evaluate whether external suction is more advantageous than water seal in patients undergoing selective pulmonary resection (SPR) for lung neoplasm.

Summary of Background Data

Whether external suction should be routinely applied in postoperative chest drainage is still unclear, particularly for lung neoplasm patients. To most surgeons, the decision is based on their clinical experience.

Methods

Randomized control trials were selected. The participants were patients undergoing SPR with lung neoplasm. Lung volume reduction surgery and pneumothorax were excluded. Suction versus non-suction for the intervention. The primary outcome was the incidence of persistent air leak (PAL). The definition of PAL was air leak for more than 3–7 days. The secondary outcomes included air leak duration, time of drainage, postoperative hospital stay and the incidence of postoperative pneumothorax. Studies were identified from literature collections through screening. Bias was analyzed and meta-analysis was used.

Results

From the 1824 potentially relevant trials, 6 randomized control trials involving 676 patients were included. There was no difference between external suction and water seal in decreasing the incidence of PAL [95% confidence interval (CI) 0.81−2.16; z = 1.10; P = 0.27]. Regarding secondary outcomes, there were no differences in time of drainage (95% CI−0.36−1.56, P = 0.22), postoperative hospital stay (95% CI -.31−.54, P = 0.87) or incidence of postoperative pneumothorax (95% CI 0.18−.02, P = 0.05) between external suction and water seal.

Conclusions

For participants, no differences are identified in terms of PAL incidence, drainage time, length of postoperative hospital stay or incidence of postoperative pneumothorax between external suction and water seal. The bias analysis should be emphasized. To the limitations of the bias and methodological differences among the included studies, we have no recommendation on whether external suction should be routinely applied after lung neoplasm SPR. More high-quality randomized controlled trials are needed.

Systematic Review Registration

None.     

Immediate Postmastectomy Breast Reconstruction Showed Limited Advantage in Patient Survival after Stratifying by Family Income

Background

Postmastectomy breast reconstruction is widely used in breast cancer patients for its aesthetic effect. Although several studies have casted suspicion upon the oncological safety of immediate breast reconstruction after mastectomy, the potential impact of different reconstruction methods on patient survival remains unclear.

Patients and Methods

We identified 35,126 female patients diagnosed with breast cancer from January 1, 1998 to December 31, 2002 in the Surveillance, Epidemiology, and End Results database. Breast cancer-specific survival (BCSS) and overall survival (OS) were compared among patients who underwent mastectomy with or without immediate breast reconstruction (autologous reconstruction or implant reconstruction) using Cox proportional hazard regression models.

Results

In multivariate analysis unadjusted for family income, patients undergoing immediate postmastectomy reconstruction exhibited improved BCSS [pooled reconstruction (any types of reconstruction): hazard ratio (HR)  =  0.87, 95% confidence interval (CI) 0.80–0.95, P = 0.001] and OS (pooled reconstruction: HR = 0.70, 95% CI 0.65–0.75, P<0.001) compared to patients who underwent mastectomy alone. However, after stratifying by family income, patients receiving reconstruction showed limited advantage in BCSS and OS compared with those undergoing mastectomy alone. When comparing between the two reconstruction methods, no significant differences were observed in either BCSS (implant versus autologous reconstruction: HR = 1.11, 95%CI 0.90–1.35, P = 0.330) or OS (implant versus autologous reconstruction: HR = 1.07, 95% 0.90–1.28, P = 0.424).

Conclusions

Compared to mastectomy alone, immediate postmastectomy reconstruction had limited advantage in survival after adjusting for confounding factor of family income. Our findings, if validated in other large databases, may help to illustrate the actual effect of immediate postmastectomy reconstruction on patient survival.     

Monocarboxylate Transporters 1–4 in NSCLC: MCT1 Is an Independent Prognostic Marker for Survival

Introduction

Monocarboxylate transporters (MCTs) 1–4 are lactate transporters crucial for cancers cells adaption to upregulated glycolysis. Herein, we aimed to explore their prognostic impact on disease-specific survival (DSS) in both cancer and tumor stromal cells in NSCLC.

Methods

Tissue micro arrays (TMAs) were constructed, representing both cancer and stromal tumor tissue from 335 unselected patients diagnosed with stage I–IIIA NSCLC. Immunohistochemistry was used to evaluate the expression of MCT1-4.

Results

In univariate analyses; ↓MCT1 (P = 0.021) and ↑MCT4 (P = 0.027) expression in cancer cells, and ↑MCT1 (P = 0.003), ↓MCT2 (P = 0.006), ↓MCT3 (P = 0.020) expression in stromal cells correlated significantly with a poor DSS. In multivariate analyses; ↓MCT1 expression in cancer cells (HR: 1.9, CI 95%: 1.3–2.8, P = 0.001), ↓MCT2 (HR: 2.4, CI 95%: 1.5–3.9, P<0.001), ↓MCT3 (HR: 1.9, CI 95%: 1.1–3.5, P = 0.031) and ↑MCT1 expression in stromal cells (HR: 1.7, CI 95%: 1.1–2.7, P = 0.016) were significant independent poor prognostic markers for DSS.

Conclusions

We provide novel information of MCT1 as a candidate marker for prognostic stratification in NSCLC. Interestingly, MCT1 shows diverging, independent prognostic impact in the cancer cell and stromal cell compartments.     

TNF-Alpha rs1800629 Polymorphism Is Not Associated with HPV Infection or Cervical Cancer in the Chinese Population

Background

While HPV infection is the main cause of cervical cancer, genetic susceptibility to HPV infection is not well understood. Tumor necrosis factor alpha (TNF-alpha), involved in the defense against HPV infection, plays an important role in cervical cancer progression and regression. The aim of this study was to investigate the relationship between the TNF-alpha rs1800629 polymorphism and risk of HPV infection or cervical cancer.

Methods

Three groups were involved in this study of Chinese women. Group 1 consisted of 285 high risk HPV positive cervical cancer patients, Group 2, 225 high risk HPV positive patients without cervical cancer, and Group 3, 318 HPV negative women with no cervical cancer. Blood samples were obtained from all patients and genotyped by PCR-RLFP. Fifty randomly selected samples were further sequenced.

Results

The allele and genotype distributions of the TNF-alpha rs1800629 polymorphism were not significantly different between each of the groups (P>0.05). There are no significant relationship between rs1800629 polymorphism and high risk HPV infection (OR  = 0.649, 95% CI: 0.253–1.670, P = 0.371), cervical cancer (OR  = 0.993, 95% CI: 0.376–2.618, P = 0.988), or cervical cancer with HPV infection (OR  = 0.663, 95% CI: 0.250–1.758, P = 0.409).

Conclusions

We demonstrated that there is no association between TNF rs1800629 polymorphism and the HPV infection, or cervical cancer with HPV infection.