Hypothermia and Postconditioning after Cardiopulmonary Resuscitation Reduce Cardiac Dysfunction by Modulating Inflammation,Apoptosis and Remodeling

Background

Mild therapeutic hypothermia following cardiac arrest is neuroprotective, but its effect on myocardial dysfunction that is a critical issue following resuscitation is not clear. This study sought to examine whether hypothermia and the combination of hypothermia and pharmacological postconditioning are cardioprotective in a model of cardiopulmonary resuscitation following acute myocardial ischemia.

Methodology/Principal Findings

Thirty pigs (28–34 kg) were subjected to cardiac arrest following left anterior descending coronary artery ischemia. After 7 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started according to the current AHA guidelines. After successful return of spontaneous circulation (n = 21), coronary perfusion was reestablished after 60 minutes of occlusion, and animals were randomized to either normothermia at 38°C, hypothermia at 33°C or hypothermia at 33°C combined with sevoflurane (each group n = 7) for 24 hours. The effects on cardiac damage especially on inflammation, apoptosis, and remodeling were studied using cellular and molecular approaches. Five animals were sham operated. Animals treated with hypothermia had lower troponin T levels (p<0.01), reduced infarct size (34±7 versus 57±12%; p<0.05) and improved left ventricular function compared to normothermia (p<0.05). Hypothermia was associated with a reduction in: (i) immune cell infiltration, (ii) apoptosis, (iii) IL-1β and IL-6 mRNA up-regulation, and (iv) IL-1β protein expression (p<0.05). Moreover, decreased matrix metalloproteinase-9 activity was detected in the ischemic myocardium after treatment with mild hypothermia. Sevoflurane conferred additional protective effects although statistic significance was not reached.

Conclusions/Significance

Hypothermia reduced myocardial damage and dysfunction after cardiopulmonary resuscitation possible via a reduced rate of apoptosis and pro-inflammatory cytokine expression.     

Surgical Outcomes and Prognostic Factors of T4 Gastric Cancer Patients without Distant Metastasis

Objective

To evaluate surgical outcomes and prognostic factors for T4 gastric cancer treated with curative resection.

Methods

Between January 1994 and December 2008, 94 patients diagnosed with histological T4 gastric carcinoma and treated with curative resection were recruited. Patient characteristics, surgical complications, survival, and prognostic factors were analyzed.

Results

Postoperative morbidity and mortality were 18.1% and 2.1%, respectively. Multivariate analysis indicated lymph node metastasis (hazard ratio, 2.496; 95% confidence interval, 1.218–5.115; p = 0.012) was independent prognostic factor.

Conclusions

For patients with T4 gastric cancer, lymph node metastasis was associated with poorer survival. Neoadjuvant chemotherapy or aggressive adjuvant chemotherapy after radical resection was strongly recommended for these patients.     

Progesterone Receptor Status and Ki-67 Index May Predict Early Relapse in Luminal B/HER2 Negative Breast Cancer Patients: A Retrospective Study

Purpose

Few studies has documented early relapse in luminal B/HER2-negative breast cancer. We examined prognostic factors for early relapse among these patients to improve treatment decision-making.

Patients and Methods

A total 398 patients with luminal B/HER2-negative breast cancer were included. Kaplan-Meier curves were applied to estimate disease-free survival and Cox regression to identify prognostic factors.

Results

Progesterone receptor (PR) negative expression was associated with higher tumor grade (p<.001) and higher Ki-67 index (p = .010). PR-negative patients received more chemotherapy than the PR-positive group (p = .009). After a median follow-up of 28 months, 17 patients (4.3%) had early relapses and 8 patients (2.0%) died of breast cancer. The 2-year disease-free survival was 97.7% in the PR-positive and 90.4% in the PR-negative groups (Log-rank p = .002). Also, patients with a high Ki-67 index (defined as >30%) had a reduced disease-free survival (DFS) when compared with low Ki-67 index group (≤30%) (98.0% vs 92.4%, respectively, Log-rank p = .013). In multivariate analysis, PR negativity was significantly associated with a reduced DFS (HR = 3.91, 95% CI 1.29–11.88, p = .016).

Conclusion

In this study, PR negativity was a prognostic factor for early relapse in luminal B/HER2-negative breast cancer, while a high Ki-67 index suggested a higher risk of early relapse.     

Prognostic Factors for Survival in Patients with High-Grade Meningioma and Recurrence-Risk Stratification for Application of Radiotherapy

Background

Radiotherapy for high-grade meningioma (HGM) is one of the essential treatment options for disease control. However, appropriate irradiation timing remains under debate. The object of this study is to discern which prognostic factors impact recurrence in HGM patients and to propose a risk-stratification system for the application of postoperative radiotherapy.

Methods

We retrospectively reviewed 55 adult patients who were diagnosed with Grade II and III intracranial meningioma. Cox regression models were applied to the analysis for impact on early recurrence in HGM patients without postoperative radiotherapy.

Results

Grade III malignancy (P = 0.0073) and transformed histology (P = 0.047) proved to be significantly poor prognostic factors of early recurrence by multivariate analysis. The other candidates for recurrence factors were Simpson Grade 3–5 resection, preoperative Karnofsky Performance status < = 70%, and MIB-1 labeling index > = 15%. According to these prognostic factors, postoperative HGM patients could be stratified into three recurrence-risk groups. The prognoses were significantly different between each group, as the 3-year actual recurrence-free rates were 90% in low-risk group, 31% in intermediate-risk group, and 15% in high-risk group.

Conclusion

We propose recurrence-risk stratification for postoperative HGM patients using clinically available factors. Our results suggest that the prognosis for patients with high-risk HGMs is dismal, whereas HGM patients belonging to the low-risk group could have favorable prognoses. This stratification provides us with the criteria necessary to determine whether to apply adjuvant radiotherapy to postoperative HGM patients, and to also help identify potentially curable HGMs without adjuvant radiotherapy.     

Urgent Ultrasound Guided Hemodynamic Assessments by a Pediatric Medical Emergency Team: A Pilot Study

Purpose

To determine the feasibility of using the Ultrasound Cardiac Output Monitor (USCOM) as an adjunct during hemodynamic assessments by a pediatric medical emergency team (PMET).

Methods

Pediatric in-patients at McMaster Children’s Hospital aged under 18 years requiring urgent PMET consultation, were eligible. Patients with known cardiac outflow valve defects, Pediatric Critical Care Unit in-patients, and those in cardiorespiratory arrest, were excluded. The primary outcome was feasibility, and the ease of USCOM transport and application as assessed by a self-administered user questionnaire. Secondary outcomes included the quality of USCOM measurements, and agreement in clinical versus USCOM-derived assessments.

Results

Forty-one patients from 85 eligible PMET consultations were enrolled between March and August 2011. A total of 55 USCOM assessments were performed on 36 of 41 (87.8%) participants. USCOM could not be completed in 5 (12.2%) participants due to patient agitation (n = 4) and emergent care (n = 1). USCOM was reported as easy to transport and apply by 97.4% and 94.7% of respondents respectively, not obstructive to patient care by 94.7%, and yielded timely measurements by 84.2% respondents. USCOM tracings were of good quality in 41 (75.9%) assessments. Agreement between clinical and USCOM-derived hemodynamic assessments by two independent raters was poor (Rater 1: κ = 0.094; Rater 2: κ = 0.146).

Conclusion

USCOM can be applied by a PMET during urgent hemodynamic assessments in children. While USCOM has been validated in stable children, its role in guiding hemodynamic resuscitation and informing therapeutic goals in a hemodynamically unstable pediatric population requires further investigation.     

Do Optimal Prognostic Thresholds in Continuous Physiological Variables Really Exist? Analysis of Origin of Apparent Thresholds,with Systematic Review for Peak Oxygen Consumption,Ejection Fraction and BNP

Background

Clinicians are sometimes advised to make decisions using thresholds in measured variables, derived from prognostic studies.

Objectives

We studied why there are conflicting apparently-optimal prognostic thresholds, for example in exercise peak oxygen uptake (pVO₂), ejection fraction (EF), and Brain Natriuretic Peptide (BNP) in heart failure (HF).

Data Sources and Eligibility Criteria

Studies testing pVO₂, EF or BNP prognostic thresholds in heart failure, published between 1990 and 2010, listed on Pubmed.

Methods

First, we examined studies testing pVO₂, EF or BNP prognostic thresholds. Second, we created repeated simulations of 1500 patients to identify whether an apparently-optimal prognostic threshold indicates step change in risk.

Results

33 studies (8946 patients) tested a pVO₂ threshold. 18 found it prognostically significant: the actual reported threshold ranged widely (10–18 ml/kg/min) but was overwhelmingly controlled by the individual study population''s mean pVO₂ (r = 0.86, p<0.00001). In contrast, the 15 negative publications were testing thresholds 199% further from their means (p = 0.0001). Likewise, of 35 EF studies (10220 patients), the thresholds in the 22 positive reports were strongly determined by study means (r = 0.90, p<0.0001). Similarly, in the 19 positives of 20 BNP studies (9725 patients): r = 0.86 (p<0.0001).Second, survival simulations always discovered a “most significant” threshold, even when there was definitely no step change in mortality. With linear increase in risk, the apparently-optimal threshold was always near the sample mean (r = 0.99, p<0.001).

Limitations

This study cannot report the best threshold for any of these variables; instead it explains how common clinical research procedures routinely produce false thresholds.

Key Findings

First, shifting (and/or disappearance) of an apparently-optimal prognostic threshold is strongly determined by studies'' average pVO₂, EF or BNP. Second, apparently-optimal thresholds always appear, even with no step in prognosis.

Conclusions

Emphatic therapeutic guidance based on thresholds from observational studies may be ill-founded. We should not assume that optimal thresholds, or any thresholds, exist.     

The Prognostic Value of SOX2 Expression in Non-Small Cell Lung Cancer: A Meta-Analysis

Objective

To investigate the association of SOX2 expression in tumor with clinicopathological features and survival of non-small-cell lung carcinoma (NSCLC) patients.

Methods

Publications assessing the clinicopathological characteristics and prognostic significance of SOX2 in NSCLC were identified up to May 2013. A meta-analysis of eligible studies was performed using standard statistical methods to clarify the association between SOX2 expression and these clinical parameters.

Results

A total of eight studies met the inclusion criteria. Analysis of these data showed that SOX2 expression was positively associated with squamous histology, (pooled OR = 5.26, 95% CI: 1.08–25.6, P = 0.040). Simultaneously, we also found that SOX2 expression was positively associated with overall survival (pooled HR = 0.65, 95% CI: 0.47–0.89, P = 0.007, random-effect).

Conclusions

SOX2 expression in tumor is a candidate positive prognostic biomarker for NSCLC patients.     

Epidemiology and Outcome of Severe Sepsis and Septic Shock in Intensive Care Units in Mainland China

Introduction

Information about sepsis in mainland China remains scarce and incomplete. The purpose of this study was to describe the epidemiology and outcome of severe sepsis and septic shock in mixed ICU in mainland China, as well as the independent predictors of mortality.

Methods

We performed a 2-month prospective, observational cohort study in 22 closed multi-disciplinary intensive care units (ICUs). All admissions into those ICUs during the study period were screened and patients with severe sepsis or septic shock were included.

Results

A total of 484 patients, 37.3 per 100 ICU admissions were diagnosed with severe sepsis (n = 365) or septic shock (n = 119) according to clinical criteria and included into this study. The most frequent sites of infection were the lung and abdomen. The overall ICU and hospital mortality rates were 28.7% (n = 139) and 33.5% (n = 162), respectively. In multivariate analyses, APACHE II score (odds ratio[OR], 1.068; 95% confidential interval[CI], 1.027–1.109), presence of ARDS (OR, 2.676; 95%CI, 1.691–4.235), bloodstream infection (OR, 2.520; 95%CI, 1.142–5.564) and comorbidity of cancer (OR, 2.246; 95%CI, 1.141–4.420) were significantly associated with mortality.

Conclusions

Our results indicated that severe sepsis and septic shock were common complications in ICU patients and with high mortality in China, and can be of help to know more about severe sepsis and septic shock in China and to improve characterization and risk stratification in these patients.     

Impact of Rescue-Thrombolysis during Cardiopulmonary Resuscitation in Patients with Pulmonary Embolism

Background

Cardiac arrest in patients with pulmonary embolism (PE) is associated with high morbidity and mortality. Thrombolysis is expected to improve the outcome in these patients. However studies evaluating rescue-thrombolysis in patients with PE are missing, mainly due to the difficulties of clinical diagnosis of PE. We aimed to determine the success influencing factors of thrombolysis during resuscitation in patients with PE.

Methodology/Principal Findings

We analyzed retrospectively the outcome of 104 consecutive patients with confirmed (n = 63) or highly suspected (n = 41) PE and monitored cardiac arrest. In all patients rtPA was administrated for thrombolysis during cardiopulmonary resuscitation. In 40 of the 104 patients (38.5%) a return of spontaneous circulation (ROSC) could be achieved successfully. Patients with ROSC received thrombolysis significantly earlier after CPR onset compared to patients without ROSC (13.6±1.2 min versus 24.6±0.8 min; p<0.001). 19 patients (47.5%) out of the 40 patients with initially successful resuscitation survived to hospital discharge. In patients with hospital discharge thrombolysis therapy was begun with a significantly shorter delay after cardiac arrest compared to all other patients (11.0±1.3 vs. 22.5±0.9 min; p<0.001).

Conclusion

Rescue-thrombolysis should be considered and started in patients with PE and cardiac arrest, as soon as possible after cardiac arrest onset.     

Fixed Effects Modelling for Provider Mortality Outcomes: Analysis of the Australia and New Zealand Intensive Care Society (ANZICS) Adult Patient Data-Base

Background

Risk adjusted mortality for intensive care units (ICU) is usually estimated via logistic regression. Random effects (RE) or hierarchical models have been advocated to estimate provider risk-adjusted mortality on the basis that standard estimators increase false outlier classification. The utility of fixed effects (FE) estimators (separate ICU-specific intercepts) has not been fully explored.

Methods

Using a cohort from the Australian and New Zealand Intensive Care Society Adult Patient Database, 2009–2010, the model fit of different logistic estimators (FE, random-intercept and random-coefficient) was characterised: Bayesian Information Criterion (BIC; lower values better), receiver-operator characteristic curve area (AUC) and Hosmer-Lemeshow (H-L) statistic. ICU standardised hospital mortality ratios (SMR) and 95%CI were compared between models. ICU site performance (FE), relative to the grand observation-weighted mean (GO-WM) on odds ratio (OR), risk ratio (RR) and probability scales were assessed using model-based average marginal effects (AME).

Results

The data set consisted of 145355 patients in 128 ICUs, years 2009 (47.5%) & 2010 (52.5%), with mean(SD) age 60.9(18.8) years, 56% male and ICU and hospital mortalities of 7.0% and 10.9% respectively. The FE model had a BIC = 64058, AUC = 0.90 and an H-L statistic P-value = 0.22. The best-fitting random-intercept model had a BIC = 64457, AUC = 0.90 and H-L statistic P-value = 0.32 and random-coefficient model, BIC = 64556, AUC = 0.90 and H-L statistic P-value = 0.28. Across ICUs and over years no outliers (SMR 95% CI excluding null-value = 1) were identified and no model difference in SMR spread or 95%CI span was demonstrated. Using AME (OR and RR scale), ICU site-specific estimates diverged from the GO-WM, and the effect spread decreased over calendar years. On the probability scale, a majority of ICUs demonstrated calendar year decrease, but in the for-profit sector, this trend was reversed.

Conclusions

The FE estimator had model advantage compared with conventional RE models. Using AME, between and over-year ICU site-effects were easily characterised.     

High survival rate of 43% in out-of-hospital cardiac arrest patients in an optimised chain of survival

Aims

Survival to hospital discharge after out-of-hospital cardiac arrest (OHCA) varies widely. This study describes short-term survival after OHCA in a region with an extensive care path and a follow-up of 1 year.

Methods

Consecutive patients ≥16 years admitted to the emergency department between April 2011 and December 2012 were included. In July 2014 a follow-up took place. Socio-demographic data, characteristics of the OHCA and interventions were described and associations with survival were determined.

Results

Two hundred forty-two patients were included (73 % male, median age 65 years). In 76 % the cardiac arrest was of cardiac origin and 52 % had a shockable rhythm. In 74 % the cardiac arrest was witnessed, 76 % received bystander cardiopulmonary resuscitation and in 39 % an automatic external defibrillator (AED) was used. Of the 168 hospitalised patients, 144 underwent therapeutic procedures. A total of 105 patients survived until hospital discharge. Younger age, cardiac arrest in public area, witnessed cardiac arrest, cardiac origin with a shockable rhythm, the use of an AED, shorter time until return of spontaneous circulation, Glasgow Coma Scale (GCS) ≥13 during transport and longer length of hospital stay were associated with survival. Of the 105 survivors 72 survived for at least 1 year after cardiac arrest and 6 patients died.

Conclusion

A survival rate of 43 % after OHCA is achievable. Witnessed cardiac arrest, cardiac cause of arrest, initial cardiac rhythm and GCS ≥13 were associated with higher survival.     

Prognostic Nomograms for Predicting Survival and Distant Metastases in Locally Advanced Rectal Cancers

Aim

To develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment.

Materials and Methods

A total of 883 patients with stage II–III rectal cancers were retrospectively collected from a single institution. Survival analyses were performed to assess each variable for overall survival (OS), local recurrence (LR) and distant metastases (DM). Cox models were performed to develop a predictive model for each endpoint. The performance of model prediction was validated by cross validation and on an independent group of patients.

Results

The 5-year LR, DM and OS rates were 22.3%, 32.7% and 63.8%, respectively. Two prognostic nomograms were successfully developed to predict 5-year OS and DM-free survival rates, with c-index of 0.70 (95% CI = [0.66, 0.73]) and 0.68 (95% CI = [0.64, 0.72]) on the original dataset, and 0.76 (95% CI = [0.67, 0.86]) and 0.73 (95% CI = [0.63, 0.83]) on the validation dataset, respectively. Factors in our models included age, gender, carcinoembryonic antigen value, tumor location, T stage, N stage, metastatic lymph nodes ratio, adjuvant chemotherapy and chemoradiotherapy. Predicted by our nomogram, substantial variability in terms of 5-year OS and DM-free survival was observed within each TNM stage category.

Conclusions

The prognostic nomograms integrated demographic and clinicopathological factors to account for tumor and patient heterogeneity, and thereby provided a more individualized outcome prognostication. Our individualized prediction nomograms could help patients with preoperatively under-staged rectal cancer about their postoperative treatment strategies and follow-up protocols.     

Risk and Prognostic Factors of Inpatient Mortality Associated with Unintentional Insecticide and Herbicide Poisonings: A Retrospective Cohort Study

Introduction

Pesticide poisoning is an important public health problem worldwide. The study aimed to determine the risk of all-cause and cause-specific inpatient mortality and to identify prognostic factors for inpatient mortality associated with unintentional insecticide and herbicide pesticide poisonings.

Methods

We performed a retrospective cohort study of 3,986 inpatients recruited at hospitalization between 1999 and 2008 in Taiwan. We used the International Classification of Disease, 9th ed., Clinical Modification external causes of injury codes to classify poisoning agents into accidental poisoning by insecticides and herbicides. Comparisons in mortality rates were made between insecticide poisoning patients and herbicide poisoning patients by using the Cox proportional hazards models to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs).

Results

There were 168 deaths during 21,583 person-days of follow-up evaluation (7.8 per 1,000 person-days). The major causes of mortality for insecticide poisonings were the toxic effect of organophosphate and coma, and the major causes of mortality for herbicide poisonings were the toxic effect of other pesticides and the toxic effect of organophosphate. The mortality for herbicide exposure was fourfold higher than that for insecticide exposure. The factors associated with inpatient mortality were herbicide poisonings (HR = 4.58, 95% CI 3.29 to 6.37) and receiving mechanical ventilation treatment (HR = 3.85, 95% CI 2.73 to 5.42).

Conclusions

We demonstrated that herbicides stand out as the dominant agent for poisoning-related fatalities. The control of and limiting access to herbicide agents and developing appropriate therapeutic regimens, including emergency care, should be priorities.     

Risk Factors in Chronic Subdural Hematoma: Comparison of Irrigation with Artificial Cerebrospinal Fluid and Normal Saline in a Cohort Analysis

Background

Chronic subdural hematoma (CSDH) is known to have a substantial recurrence rate. Artificial cerebrospinal fluid (ACF) is an effective irrigation solution in general open craniotomy and endoneurosurgery, but no evidence of its use in burr-hole surgery exists.

Objective

To identify the potential of ACF irrigation to prevent CSDH recurrence. More specifically, to investigate the perioperative and intraoperative prognostic factors, and to identify controllable ones.

Methods

To examine various prognostic factors, 120 consecutive patients with unilateral CSDH treated with burr-hole drainage between September 2007 and March 2013 were analyzed. Intraoperative irrigation was performed with one of two irrigation solutions: normal saline (NS; n = 60) or ACF (n = 60). All patients were followed-up for at least 6 months postoperatively. We also examined the morphological alternations of the hematoma outer membranes after incubation with different solutions.

Results

Eleven patients (9.2%) had recurrence. Nine patients (15%) required additional surgery in the NS group, whereas only 2 patients (3.3%) in the ACF group required additional surgery. Among preoperative and intraoperative data, age (<80 years old, P = .044), thrombocyte (>22.0, P = .037), laterality (right, P = .03), and irrigation solution (ACF, P = .027) were related to smaller recurrence rates by log-rank tests. Only the type of irrigation solution used significantly correlated with recurrence in favor of ACF in both Cox proportional hazards (relative hazard: 0.20, 95% confidence interval (CI): 0.04–0.99; P = .049) and logistic regression models (odds ratio, 0.17, 95% CI: 0.03–0.92; P = .04) using these factors. Histological examinations of the hematoma membranes showed that the membranes incubated with NS were loose and infiltrated by inflammatory cells compared with those incubated with ACF.

Conclusion

Irrigation with ACF decreased the rate of CSDH recurrence.     

Prognostic Value of Histological Response to Chemotherapy in Osteosarcoma Patients Receiving Tumor-Bearing Frozen Autograft

Background

A variety of surgical procedures are now available for tissue reconstruction after osteosarcoma excision, and an important prognostic factor is the evaluation of response to chemotherapy using histology. Although tumor-bearing autografts are useful tools for reconstruction, re-use of the primary tumor may make it difficult to assess the histological response to chemotherapy, since the entire tumor cannot be analyzed. Here, we analyzed the prognostic value of the histological response in the patients who received frozen tumor-bearing autografts for reconstruction.

Method

Retrospective analysis of the medical records of 51 patients with high-grade osteosarcoma of the extremities was performed. All patients received reconstruction using frozen tumor-bearing autografts. Tumor necrosis was evaluated in extraskeletal masses and cancellous bone.

Results

Five-year overall survival of patients with good and poor response to chemotherapy was 82.9% and 46.4%, respectively (P = 0.044), and 5-year event-free survival was 57.7% and 36.0%, respectively (P = 0.329). Multivariate analysis revealed that a poor histological response to chemotherapy was a significant prognostic factor for overall survival (P = 0.033).

Conclusion

Histological response is an important and reliable prognostic factor in patients undergoing reconstruction using frozen tumor-bearing autografts.     

Cardiopulmonary Bypass during Cardiac Surgery Modulates Systemic Inflammation by Affecting Different Steps of the Leukocyte Recruitment Cascade

Background

It is known that the use of a cardiopulmonary bypass (CPB) during cardiac surgery leads to leukocyte activation and may, among other causes, induce organ dysfunction due to increased leukocyte recruitment into different organs. Leukocyte extravasation occurs in a cascade-like fashion, including capturing, rolling, adhesion, and transmigration. However, the molecular mechanisms of increased leukocyte recruitment caused by CPB are not known. This clinical study was undertaken in order to investigate which steps of the leukocyte recruitment cascade are affected by the systemic inflammation during CPB.

Methods

We investigated the effects of CPB on the different steps of the leukocyte recruitment cascade in whole blood from healthy volunteers (n = 9) and patients undergoing cardiac surgery with the use of cardiopulmonary bypass (n = 7) or in off-pump coronary artery bypass-technique (OPCAB, n = 9) by using flow chamber experiments, transmigration assays, and biochemical analysis.

Results

CPB abrogated selectin-induced slow leukocyte rolling on E-selectin/ICAM-1 and P-selectin/ICAM-1. In contrast, chemokine-induced arrest and transmigration was significantly increased by CPB. Mechanistically, the abolishment of slow leukocyte rolling was due to disturbances in intracellular signaling with reduced phosphorylation of phospholipase C (PLC) γ2, Akt, and p38 MAP kinase. Furthermore, CPB induced an elevated transmigration which was caused by upregulation of Mac-1 on neutrophils.

Conclusion

These data suggest that CPB abrogates selectin-mediated slow leukocyte rolling by disturbing intracellular signaling, but that the clinically observed increased leukocyte recruitment caused by CPB is due to increased chemokine-induced arrest and transmigration. A better understanding of the underlying molecular mechanisms causing systemic inflammation after CPB may aid in the development of new therapeutic approaches.     

Significance of Pulmonary Arterial Pressure as a Prognostic Indicator in Lung-Dominant Connective Tissue Disease

Background

Lung-dominant connective tissue disease (LD-CTD) is a new concept for classifying the subset of patients with interstitial pneumonia who have clinical features suggesting an associated CTD, but whose features fall short of a clear diagnosis of CTD under the current rheumatologic classification systems. The impact of mean pulmonary arterial pressure (MPAP) in LD-CTD has not been sufficiently elucidated.

Objectives

To evaluate the survival impact of MPAP measured during the initial evaluation in patients with LD-CTD.

Methods

We retrospectively analyzed the initial evaluation data of 100 LD-CTD patients undergoing pulmonary function test, 6-min walk test (6MWT), and right heart catheterization (RHC).

Results

The mean MPAP was 16.2±4.4 mm Hg, and 18 patients had MPAP≥20 mm Hg. A univariate Cox proportional hazard model showed that MPAP and several variables have a statistically significant impact on survival. With stepwise, multivariate Cox proportional analysis, MPAP (HR  = 1.293; 95% CI 1.130–1.480; p<0.001) and mean forced vital capacity (FVC) % predicted (HR = 0.958; 95% CI 0.930–0.986; p = 0.004) were shown to be independent determinants of survival.

Conclusions

Higher MPAP and lower %FVC at the initial evaluation were significant independent prognostic factors of LD-CTD. MPAP evaluation provides additional information of disease status and will help physicians to predict mortality in LD-CTD.     

Concomitant Tumor Expression of EGFR and TATI/SPINK1 Associates with Better Prognosis in Colorectal Cancer

Background

Epidermal growth factor receptor (EGFR) activation plays a role in colorectal cancer (CRC) carcinogenesis, and anti-EGFR drugs are used in treatment of advanced CRC. One of the EGFR ligands is tumor-associated trypsinogen inhibitor TATI, also called serine protease inhibitor Kazal type1 (SPINK 1), which we recently showed to be an independent prognostic marker in CRC.

Methods

We studied the prognostic value of immunohistochemical expression of EGFR and concomitant expression of EGFR and TATI/SPINK1 in a series of 619 colorectal cancer patients.

Results

Of the samples, 92% were positive for EGFR. EGFR+/TATI+ was seen in 62.8%, EGFR+/TATI− in 29.5%, EGFR−/TATI+ in 4.9%, and EGFR−/TATI− in 2.7% of patients. EGFR expression correlated with WHO grade (p = 0.040). In univariate analysis, EGFR expression correlated with favourable survival (p = 0.006). EGFR+/TATI+ patients showed better survival than did those with other combinations (p<0.001). In multivariate analysis, EGFR+/TATI+ was an independent prognostic factor of favourable prognosis (p<0.001).

Conclusion

Concomitant positivity of EGFR and TATI/SPINK1 predicts favourable prognosis in CRC.     

C-Reactive Protein as a Prognostic Factor for Human Osteosarcoma: A Meta-Analysis and Literature Review

Background

Osteosarcoma is the most common primary bone cancer in growing adolescents and young adults. The prognostic role of C-reactive protein (CRP) in patients with osteosarcoma is not fully investigated. The purpose of this study is to perform a meta-analysis and literature review on the role of CRP in osteosarcoma and to assess the potential role of serum CRP as a prognostic factor for patients with osteosarcoma.

Methods

A detailed literature search was made in Medline for related research publications written in English. Methodological quality of the studies was also evaluated. The data were extracted and assessed by two reviewers independently. Analysis of pooled data were performed, risk ratio (RR) and corresponding confidence intervals (CIs) were calculated and summarized respectively.

Results

Final analysis of 397 patients from 2 eligible studies was performed. Combined RR of CRP expression suggested that the raised serum CRP level had an adverse prognostic effect on overall survival of patients with osteosarcoma (n = 397 in 2 studies; RR = 0.35; 95% CI: 0.18–0.68; p = 0.002). In the uni- and multivariate survival analysis, response rate and CRP levels were the only independent prognostic variables.

Conclusions

The results of this meta-analysis suggest that CRP expression confers a worse prognosis in patients with osteosarcoma. Large prospective studies are necessary to provide solid data to confirm the prognostic significance of CRP.     

Prognostic Value of Epidermal Growth Factor Receptor Mutations in Resected Non-Small Cell Lung Cancer: A Systematic Review with Meta-Analysis

Background

The prognostic value of epidermal growth factor receptor (EGFR) mutations in resected non-small cell lung cancer (NSCLC) remains controversial. We performed a systematic review with meta-analysis to assess its role.

Methods

Studies were identified via an electronic search on PubMed, Embase and Cochrane Library databases. Pooled hazard ratio (HR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis.

Results

There were 16 evaluated studies (n = 3337) in the meta-analysis. The combined HR evaluating EGFR mutations on disease free survival was 0.96 (95% CI [0.79–1.16] P = 0.65). The combined HR evaluating EGFR mutations on overall survival was 0.86 (95% CI [0.72–1.04] P = 0.12). The subgroup analysis based on univariate and multivariate analyses in DFS and OS showed no statistically significant difference. There was also no statistically significant difference in DFS and OS of stage I NSCLC patients.

Conclusion

The systematic review with meta-analysis showed that EGFR mutations were not a prognostic factor in patients with surgically resected non-small cell lung cancer. Well designed prospective study is needed to confirm the result.