The prognostic significance of the prognostic nutritional index in cancer: a systematic review and meta-analysis

Purpose

The prognostic nutritional index (PNI) is a simple and effective parameter, initially created to evaluate preoperative nutritional conditions and surgical risk. It has been recently been found to be associated with short- and long-term outcomes of various malignancies. We performed a meta-analysis to determine the predictive significance of PNI in cancer, as a mean to assist in determining the optimal surgery timing and in improving the survival of cancer patients.

Methods

Data were retrieved from PubMed and ISI Web of Science to identify eligible studies. Odds ratios (ORs) and hazard ratios (HRs) were extracted and pooled to explore the relationships of PNI with patient survival and clinicopathological features.

Results

Fourteen studies with a total of 3,414 participants met the inclusion criteria. Low PNI was associated with poor overall survival (pooled OR 1.80, 95 % confidence interval [CI] 1.59–2.04) and the presence of post-operative complications (pooled OR 2.45, 95 % CI 1.31–4.58) in cancer patients, but not with cancer-specific survival (CSS) (pooled HR 1.81, 95 % CI 0.94–3.49). PNI was also found to be associated with invasion depth (pooled OR 5.07, 95 % CI 2.34–10.96) and lymph node metastasis (pooled OR 3.70, 95 % CI 2.32–5.92) in gastric cancer, whereas TNM stage was the only clinicopathological feature associated with PNI in colorectal carcinoma (pooled OR 1.81, 95 % CI 1.24–2.64).

Conclusions

PNI might be an effective predictive indicator for the prognosis of cancer, especially digestive system carcinomas. Further studies are required to verify the significance of PNI in clinical practice.     

Post-operative outcomes in adult obstructive sleep apnea patients undergoing non-upper airway surgery: a systematic review and meta-analysis

Background:

With the current obesity epidemic, obstructive sleep apnea (OSA) has become increasingly common. Several studies have reported on the risk of post-operative complications in OSA patients undergoing non-upper airway surgeries. The objective of our study was to systematically review the medical literature reporting the incidence of post-operative complications in patients with OSA.

Methods:

We conducted a systematic review using the Cochrane Collaboration Methodology. We searched Medline via Ovid, Pubmed, Embase, and Evidence-Based Medicine Reviews databases from 1950 to 2012. We rated the quality of evidence for each outcome using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Meta-analysis was done using Review Manager Version 5.0.20.

Results:

Our search resulted in 18 eligible studies. OSA was found to be associated with a significantly increased incidence of post-operative hypoxemia (odds ratio [OR]?=?3.06; 95 % confidence interval [CI] 2.35–3.97), respiratory complications (OR?=?2.77, 95 % CI 1.73–4.43), cardiac complications (OR?=?1.76 95 % CI 1.16–2.67), neurological complications (OR?=?2.65, 95 % CI 1.43–4.92), and unplanned intensive care unit (ICU) transfer (OR?=?2.97, 95 % CI 1.90–4.64). Re-intubation (OR?=?1.37, 95 % CI 0.65–2.91) was not significantly increased in patients with OSA. The association between OSA and post-operative outcomes remained unchanged with sub-group analysis including only studies that used polysomnography (PSG) for diagnosis.

Conclusions:

OSA patients are at increased risk of post-operative complications from non-upper airway surgeries. Early diagnosis and treatment of OSA might decrease post-operative complications in these patients. There is a need for further studies to assess the benefit of peri-operative treatment of OSA on post-operative outcomes.     

Improved oncologic outcomes with image-guided intensity-modulated radiation therapy using helical tomotherapy in locally advanced hepatocellular carcinoma

Aim

To investigate whether image-guided intensity-modulated radiation therapy (IG-IMRT) improves survival in hepatocellular carcinoma (HCC) relative to 3-dimensional conformal radiotherapy (3D-CRT).

Methods

Between 2006 and 2011, 187 HCC patients treated with definitive RT were reviewed. Median age was 53(range 51–83). All patients were stage III or IV-A. Concurrent chemoradiation was received by 178 patients (95.2 %). Overall actuarial survival (OS), progression-free survival (PFS), and infield-failure-free survival (IFFS) analyses were performed by Kaplan–Meier method. A Cox proportional hazards model was used for univariate and multivariate analysis. Pearson’s chi-square test or Fisher’s exact test was used to compare patient characteristics and treatment-related toxicity between the groups.

Results

Sixty-five patients were treated with IG-IMRT and 122 patients with 3D-CRT. No significant differences were seen between the groups for all patient characteristics. IG-IMRT delivered higher doses than 3D-CRT (median biological effective dose 62.5 vs 53.1 Gy, P < 0.001). IG-IMRT showed significantly higher 3-year OS (33.4 vs 13.5 %, P < 0.001), PFS (11.1 vs 6.0 %, P = 0.004), and IFFS (46.8 vs 28.2 %, P = 0.007) than 3D-CRT. On univariate and multivariate analysis, RT modality was significant prognostic factor for OS (HR 2.18; 95 % CI 1.45–3.25; P < 0.001), PFS (HR 1.64; 95 % CI 1.17–2.29; P = 0.004). There was no significant difference between the two modalities for radiation-induced liver disease (P = 0.716).

Conclusion

Our findings suggest that IG-IMRT could be an effective treatment that provides survival benefit without increasing severe toxicity in locally advanced HCC.     

Maintenance treatment with the immunomodulator MGN1703, a Toll-like receptor 9 (TLR9) agonist,in patients with metastatic colorectal carcinoma and disease control after chemotherapy: a randomised,double-blind,placebo-controlled trial

Purpose

This phase II study evaluated the synthetic DNA-based immunomodulator and Toll-like receptor 9 agonist MGN1703 as maintenance treatment in metastatic colorectal carcinoma (mCRC).

Methods

Fifty-nine patients with mCRC and disease control after standard first-line chemotherapy were randomised to MGN1703 60 mg (N = 43) or placebo (N = 16).

Results

The hazard ratio (HR) for the primary endpoint [progression-free survival (PFS) from the start of maintenance] was 0.56 (95 % CI 0.29–1.08; P = 0.07) and 0.55 (95 % CI 0.3–1.0; P = 0.04) by independent and investigator review, respectively. MGN1703 significantly improved PFS measured from the start of induction therapy versus placebo on independent (HR 0.49; 95 % CI 0.26–0.94; P = 0.03) and investigator review (HR 0.50; 95 % CI 0.31–1.02; P = 0.02). Overall survival (OS) data remain immature (HR 95 %; 95 % CI 0.3–1.5; P = 0.29) with 28/43 patients alive after a medium follow-up of >17 months. Retrospective subgroup analysis showed a significant effect of MGN1703 on PFS versus placebo in patients with greater than median tumour size reduction and normalised carcinoembryonic antigen concentrations following induction therapy, and in patients with elevated activated NKT cells ≥3.08 %. Adverse events were mild to moderate and limited to injection-site reactions or linked to general immune system activation.

Conclusions

MGN1703 maintenance treatment was well tolerated and appears to induce durable and prolonged PFS and disease control in a subgroup of patients with mCRC following induction therapy. Activated NKT cells may be a predictive biomarker for selecting patients likely to benefit more from MGN1703.     

Clinical outcomes of spontaneous bacterial peritonitis due to extended-spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumoniae: a retrospective cohort study

Purpose

The aim of this study was to (1) evaluate the clinical outcomes of spontaneous bacterial peritonitis (SBP) due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli or Klebsiella pneumoniae (EK) and (2) investigate the relationship between the adequacy of initial antibiotic treatments and patient outcomes.

Methods

We conducted a retrospective cohort study of cirrhotic patients with SBP caused by EK. We evaluated the 30-day mortality rate and used Cox proportional hazard models to identify risk factors for mortality.

Results

Between January 2006 and December 2012, a total of 231 episodes of SBP due to EK were recorded. Among them, 52 were caused by ESBL-producing EK (ESBL-EK). The 30-day mortality rate was significantly higher in patients with SBP due to ESBL-EK than in those with non-ESBL-producing EK (non-ESBL-EK) (34.6 vs. 18.4 %, respectively; p = 0.013). Multivariate analysis revealed that ESBL production [adjusted HR (aHR) 1.82, 95 % confidence interval (CI) 1.00–3.31], nosocomial infection (aHR 2.24, 95 % CI 1.26–3.95), septic shock (aHR 4.84, 95 % CI 2.70–8.65), higher Child-Pugh score (aHR 1.57, 95 % CI 1.28–1.92), and higher Charlson comorbidity index (aHR 1.37, 95 % CI 1.15–1.64) were independent risk factors for 30-day mortality in the total cohort. When we analyzed patients with SBP due to ESBL-EK separately, septic shock (aHR 3.64, 95 % CI 1.40–9.77), accompanying bacteremia (aHR 3.71, 95 % CI 1.37–10.08), and hepatocellular carcinoma (aHR 3.21, 95 % CI 1.20–8.56) were independent risk factors.

Conclusions

Both 7- and 30-day mortalities for SBP due to ESBL-EK were significantly higher than for SBP due to non-ESBL-EK. Initial antibiotic choice was not associated with poor clinical outcomes in patients with SBP due to ESBL-EK.     

BRCA1 promoter methylation is a marker of better response to platinum–taxane-based therapy in sporadic epithelial ovarian cancer

Background

The aim of the current study was to investigate the role of BRCA1 promoter methylation as predictive factor of response to platinum–taxane-based therapy in sporadic ovarian cancer.

Patients and methods

BRCA1 promoter methylation was analyzed in 42 sporadic epithelial ovarian cancers. The results were validated in a second cohort of 137 ovarian cancer patients.

Results

BRCA1 promoter methylation was observed in 35.7 % of patients in the first group and in 33.6 % in the second group. BRCA1 promoter methylation was associated with significant increase in median progression-free survival (PFS) of ovarian cancer patients receiving adjuvant platinum–taxane-based chemotherapy (P = 0.008). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to PFS (HR 0.52; 95 % CI 0.32–0.85, P = 0.009) after adjustment for other prognostic factors. Under the patients with recurrent disease, BRCA1 promoter methylation was associated with significant longer median PFS of 18.5 months in comparison with 12.8 months PFS for patients without BRCA1 promoter methylation.

Conclusions

BRCA1 promoter methylation is predictive for better response to platinum–taxane-based therapy in EOC.     

Walking Cadence and Mortality Among Community-Dwelling Older Adults

BACKGROUND

Older adults are encouraged to walk ≥100 steps?minute^?1 for moderate-intensity physical activity (i.e., brisk walking). It is unknown if the ability to walk ≥100 steps?minute^?1 predicts mortality.

OBJECTIVE

To determine if the ability to walk ≥100 steps?minute^?1 predicts mortality among older adults.

DESIGN, SETTING, AND PATIENTS

A population-based cohort study among 5,000 older adults from the Third National Health and Nutrition Survey (NHANES III; 1988–1994). Vital status and cause of death were collected through December 31, 2006. Median follow-up was 13.4 years. Average participant age was 70.6 years.

MEASUREMENTS

Walking cadence (steps?minute^?1) was calculated using a timed 2.4-m walk. Walking cadence was dichotomized at 100 steps?minute^?1 (≥100 steps?minute^?1 versus <100 steps?minute^?1) to demarcate the lower threshold of absolutely defined moderate-intensity physical activity. Walking cadence was also analyzed as a continuous variable. Predicted survival was compared between walking cadence and gait speed. The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular-specific and cancer-specific mortality and mortality from other causes.

RESULTS

Among 5,000 participants, 3,039 (61 %) walked ≥100 steps?minute^?1. During follow-up, 3,171 subjects died. In multivariable-adjusted analysis, ability to walk ≥100 steps?minute^?1 predicted a 21 % reduction in all-cause mortality (hazard ratio [HR], 0.79; 95 % confidence interval [95 % CI], 0.71–0.89, p?p??1 predicted reductions in cardiovascular-specific mortality (HR, 0.79 [0.67–0.92], p?=?0.002), cancer-specific mortality (HR, 0.76 [0.58–0.99], p?=?0.050), and mortality from other causes (HR, 0.82 [0.68–0.97], p?=?0.025). Predicted survival, adjusted for age and sex, was not different using walking cadence versus gait speed.

LIMITATIONS

Walking cadence was a cross-sectional measurement.

CONCLUSIONS

The ability to walk ≥100 steps?minute^?1 predicts a reduction in mortality among a sample of community-dwelling older adults.     

Role for gender in colorectal cancer risk: a Taiwan population-based study

Background and aims

Gender differences in the prognosis of colorectal cancer (CRC) remain controversial. The aim of this study was to complete a comprehensive analysis of gender differences in CRC survival derived from population registries in Taiwan.

Materials and methods

We analyzed survival data for patients diagnosed with CRC between 1998 and 2005 derived from the Taiwan Cancer Registry database. During this time period, 65,113 patients were registered, and 62,060 patients were eligible. Gender differences in overall survival and cancer-specific survival were analyzed by use of the Kaplan–Meier method. We then modeled the risk in different genders by use of a multivariate proportional hazard (Cox) model adjusting for possible confounders of survival.

Results

The 5-year period overall and cancer-specific survivals were significantly higher in women than in men [51.84 % (95 % confidence interval (CI), 51.22–52.46) vs. 47.68 % (95 % CI, 47.14–48.22), log-rank p?<?0.001; and 56.44 % (95 % CI, 55.82–57.07) vs. 53.47 % (95 % CI, 52.92–54.01), log-rank p?<?0.001, respectively]. Subgroup analysis revealed higher overall and cancer-specific survivals in women between 50 and 80 years age and those with adenocarcinomas (p?<?0.001). By use of Cox modeling, we noted a decreased hazard ratio (HR) for death from CRC in women compared with men (HR, 0.820–0.971), especially in the 50–80-year age group. All estimated HRs, after adjusting for age, tumor histology, and tumor site, had significant trends of a decreasing risk of death from CRC in women.

Conclusions

Our findings suggest that overall and cancer-specific survival advantage was most evident in women between 50 and 80 years of age.     

Sirolimus-eluting versus paclitaxel-eluting stent in primary angioplasty: a pooled patient-level meta-analysis of randomized trials

Large interests have been focused on the role of drug-eluting stents in the setting of ST-segment elevation myocardial infarction (STEMI) and concerns have emerged regarding an higher risk of stent thrombosis. Aim of the current study was to perform a meta-analysis using individual patient data to evaluate the long-term safety and effectiveness of sirolimus-eluting stent (SES) as compared to paclitaxel-eluting stent (PES) in patients undergoing primary percutaneous coronary intervention (PCI) for STEMI. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of SES versus PES for STEMI. No language restriction was applied. Primary study endpoint was the occurrence of major adverse cardiac events (MACE). Secondary endpoints were the occurrence of death, reinfarction, stent thrombosis, target-vessel revascularization (TVR). Individual patient data were obtained from 4 out of 5 trials identified, including a total of 1,000 patients, 504 (50.4 %) randomized to SES and 496 (49.6 %) randomized to PES. At long-term follow-up (1,021 [372–1,351] days), no difference was observed between SES and PES in terms of TVR (10 vs 11.6 %, HR [95 % CI 0.73 [0.45–1.16], p = 0.18, p het = 0.92]) (primary endpoint) or death (9.4 vs 10.4 %, HR [95 % CI 0.95 [0.58–1.54], p = 0.82, p het = 0.89]), reinfarction (8.2 vs 10.4 %, HR [95 % CI 0.91 [0.53–1.57], p = 0.73, p het = 0.83]), stent thrombosis (7.4 vs 4.6 %, HR [95 % CI 1.04 [0.55–2.05], p = 0.92, p het = 0.65]), and MACE (10 vs 13.6 %, HR [95 % CI 0.86 [0.63–1.18], p = 0.36, p het = 0.84]) (secondary endpoints). The present pooled patient-level meta-analysis demonstrates that, among STEMI patients undergoing primary PCI, SES and PES are associated with a similar outcome at long-term follow-up, in terms of death, reinfarction, stent thrombosis, TVR and MACE.     

Left-sided primary tumors are associated with favorable prognosis in patients with KRAS codon 12/13 wild-type metastatic colorectal cancer treated with cetuximab plus chemotherapy: an analysis of the AIO KRK-0104 trial

Purpose

AIO KRK-0104 investigated first-line therapy of metastatic colorectal cancer (mCRC) with cetuximab, capecitabine and irinotecan versus cetuximab, capecitabine and oxaliplatin. This analysis investigated the impact of primary tumor location on outcome of patients.

Patients and methods

Left-sided primary tumors were defined as tumors from rectum to left flexure, while tumors in the remaining colon were regarded right sided. Overall survival (OS), progression-free survival (PFS) and response rate were correlated with primary tumor location. A Cox regression model was used to evaluate interaction between primary tumor location and KRAS mutation.

Results

Of 146 patients of the AIO KRK-0104 trial, 100 patients presented left-sided (of those 68 KRAS codon 12/13 wild-type) and 46 patients right-sided primary tumors (of those 27 KRAS codon 12/13 wild-type). Left-sided tumors were associated with significantly longer OS (p = 0.016, HR = 0.63) and PFS (p = 0.02, HR = 0.67) as compared to right-sided tumors. These effects were present in the KRAS codon 12/13 wild-type population (HR OS: 0.42; HR PFS: 0.54), while no impact of primary tumor location was evident in patients with KRAS codon 12/13 mutant tumors (HR OS: 1.3; HR PFS: 1.01). A significant interaction of KRAS status and primary tumor location concerning OS and PFS was observed.

Conclusion

Our findings suggest that primary tumor location and KRAS codon 12/13 mutational status interact on the outcome of patients with mCRC receiving cetuximab-based first-line therapy. Left-sided primary tumor location might be a predictor of cetuximab efficacy.     

Listeria monocytogenes meningoencephalitis in adults: analysis of factors related to unfavourable outcome

Purpose

To analyse the short-term outcome in patients with Listeria monocytogenes meningoencephalitis (LMME) to improve management and outcome.

Methods

Observational study with adult patients with LMME between 1977 and 2009 at a tertiary hospital in Barcelona, Spain. Parameters that predicted outcome were assessed with univariate and logistic regression analysis.

Results

Of 59 cases of LMME, 28 occurred in the last decade. Since 1987, a new protocol has been used and 29/45 patients (64 %) treated since then received adjuvant dexamethasone. In patients who received this treatment there was a trend towards fewer neurological sequelae (5 vs 33 %; p = 0.052). Antiseizure prophylaxis with phenytoin was administered in 13/45 (28 %) patients. Seizures occurred in 7/45 (16 %) patients, all in the group who did not receive phenytoin. Hydrocephalus presented in 8/59 (14 %). It was never present at admission and five patients needed neurosurgical procedures. Sequelae after 3 months were present in 8/45 (18 %), mostly cranial nerve palsy. Rhombencephalitis (RE) was related to the presence of neurologic sequelae (OR: 20.4, 95 % CI: 1.76–236). Overall mortality was 14/59 (24 %), 9/59 (15 %) due to neurological causes related to hydrocephalus or seizures. Mortality was defined as early in 36 % and late in 64 %. In the multivariate analysis, independent risk factors for mortality were presence of hydrocephalus (OR: 17.8, 95 % CI: 2.753–114) and inappropriate empirical antibiotic therapy (OR: 6.5, 95 % CI: 1.201–35).

Conclusions

Outcome of LMME may be improved by appropriate empirical antibiotic therapy, suspicion and careful management of hydrocephalus. Use of adjuvant dexamethasone or phenytoin in a subgroup of these patients might have a benefit.     

Duodenal Adenomas Coincide with Colorectal Neoplasia

Background and Aim

Small case series have alluded to an association between sporadic duodenal adenomas and colorectal neoplasia. The strength of the association remains uncertain. This case–control study was designed to test this association in a large national pathology database.

Methods

This study, performed at Miraca Life Sciences, a specialized pathology laboratory that receives gastrointestinal biopsy specimens from outpatient centers throughout the US, included all subjects who underwent a bidirectional endoscopy with biopsy results from both procedures between January 2008 and December 2011. The association between duodenal and colonic neoplasms was investigated using odds ratios (OR) and their 95 % confidence intervals (CIs) derived from univariate and multivariate analyses.

Results

There were 203,277 patients who underwent bidirectional procedures within the study period (mean age 58 years, 58 % females). Duodenal adenomas were present in 537 patients (median age 65 years, 51 % females; OR for male sex 1.34, 95 % CI 1.13–1.59). Hyperplastic colon polyps were present in 30,205 and colon adenomas in 85,801 patients. Hyperplastic polyps were more common in patients with duodenal adenomas (1.45, 1.07–1.95). Patients with duodenal adenomas also had a significantly greater prevalence of all types of colonic adenomas (2.65, 2.16–3.25), particularly of advanced adenomas (4.30, 3.24–5.70) and colorectal cancer (3.13, 1.38–7.12). Duodenal adenomas were associated with an equally increased risk for left and right colon adenomas.

Conclusions

Patients with duodenal adenomas harbor an increased risk for any type of colonic neoplasm. This association may provide new insights into the general mechanisms underlying mucosal proliferation in the gastrointestinal tract.     

Implanted endocardial lead characteristics and risk of stroke or transient ischemic attack

Introduction

Patent foramen ovale (PFO) has been recently implicated as a strong predictor of stroke or transient ischemic attack (TIA) in patients with implanted pacemaker or defibrillation leads. Leads in the right heart can form thrombi that embolize to the pulmonary circulation and raise pulmonary pressure. This increases right-to-left shunting through PFO or intrapulmonary shunts and can result in paradoxical embolism. We sought to determine whether certain lead characteristics confer a higher thrombogenic risk resulting in stroke/TIAs in patients either with or without a PFO.

Methods

We retrospectively analyzed 5,646 patients (mean age 67.3?±?16.3 years, 64 % male) who had endocardial device leads implanted in 2000–2010. We performed univariate and multivariate-adjusted proportional hazards models to determine association of lead characteristics with stroke/TIA during follow-up.

Results

On univariate analysis, passively fixated tined leads were associated with more stroke/TIAs (HR 1.77, 95 % CI 1.27, 2.47; p?p?=?0.003). Number of leads per patient, presence of atrial lead, maximum lead size, tip shape, and type of insulating material were not associated with stoke/TIA. On multivariate analyses adjusting for age, sex, diagnosis of PFO, and prior history of stroke/TIA, the presence of tined leads was associated with stroke/TIA (HR 1.41, 95 % CI 1.00–1.97; p?=?0.049). Defibrillation coils were no longer associated with lower stroke/TIA on multivariate analysis.

Conclusions

Most physical characteristics of contemporary leads do not impact rate of stroke/TIA among patients receiving implantable devices. The presence of a PFO is a major risk factor for stroke/TIA in patients with endovascular leads.     

Preresection transarterial chemoembolization for hepatocellular carcinoma: An experience with 23 patients

Purpose

The routine use of transarterial chemoembolization (TACE) prior to resection for hepatocellular carcinoma (HCC) is not recommended, although its use in the transplant setting is gaining popularity. In the absence of other effective neoadjuvant or adjuvant treatment options, TACE may benefit selected patients. The aim was to evaluate the feasibility and outcomes of preoperative TACE for selected patients with HCC.

Methods

From November 2010 to October 2012, 23 patients of HCC were selected by a multidisciplinary team to undergo TACE prior to resection.

Results

TACE was successful in all patients with no intraprocedural complications. TACE reduced the mean maximum tumor diameter from 9.2 to 8.2 cm and increased the mean future liver remnant (FLR) from 37.7 % to 49.1 %. Nineteen resections were completed with negative margins, of which only three patients (15.8 %) had cirrhosis. Two patients (10.5 %) experienced postoperative bile leaks and six patients (31.5 %) developed postoperative liver failure, two (10.5 %) of which succumbed to grade C liver failure. From the date of surgery, the median follow up time was 17.1 months. Four patients (17 %) did not undergo curative resection due to disease progression in three patients and severe TACE toxicity in one patient. None of the resected patients developed disease recurrence and the overall survival was 21 months.

Conclusion

Encouraging outcomes in terms of disease recurrence and overall survival need to be balanced with the risk of surgical drop out and perioperative complications when selecting patients for TACE prior to resection.     

Transthoracic echocardiographic and cardiopulmonary exercise testing parameters in Eisenmenger’s syndrome

Objective

The six-minute walk test (6MWT) evaluates the functional exercise capacity in patients with cardiopulmonary disease. We aimed to investigate the association between 6MWT distance and transthoracic echocardiographic (TTE) findings as well as cardiopulmonary exercise testing (CPET) parameters in Eisenmenger’s syndrome (ES) patients waiting for heart–lung transplantation on their initial admission to our center.

Patients and methods

A total of 23 patients with ES (12 women, 11 men; mean age, 28.2?±?8.1 years) were included in the study. The correlation between 6MWT distance and CPET and TTE findings was retrospectively analyzed.

Results

The most frequent underlying heart diseases were ventricular septal defect (VSD) with complex congenital heart disease (n?=?10, 43?%) and isolated VSD (n?=?7, 30?%). The 6MWT distance was 349.7?±?77.4 m in the study group. An inverse correlation was found between 6MWT distance and systolic pulmonary arterial pressure (SPAP) measured with TTE (r?=???0.445; p?=?0.03). All patients underwent CPET at the first visit. Mean VO₂ max was 14.9?±?3.3 ml/kg/min and the VE/VCO₂ rate was 50.4?±?9.2?%. No significant correlation was observed between 6MWT and CPET findings. SPAP, which did not display any correlation with CPET findings, was the only independent predictor of 6MWT distance.

Conclusion

We suggest that 6MWT distance may be more suitable than CPET in the follow-up of ES patients. Further prospective, randomized, controlled trials are necessary to make more robust interpretations of this issue.     

Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study

Aims/hypothesis

Only a few longitudinal molecular studies of enterovirus and islet autoimmunity have been reported, and positive results seem to be limited to Finland. We aimed to investigate an association between enterovirus RNA in blood and islet autoimmunity in the MIDIA study from Norway, a country which largely shares environmental and economic features with Finland.

Methods

We analysed serial blood samples collected at ages 3, 6, and 9 months and then annually from 45 children who developed confirmed positivity for at least two autoantibodies (against insulin, GAD65 and IA-2) and 92 matched controls, all from a cohort of children with a single high-risk HLA-DQ-DR genotype. Enterovirus was tested in RNA extracted from frozen blood cell pellets, using real-time RT-PCR with stringent performance control.

Results

Out of 807 blood samples, 72 (8.9%) were positive for enterovirus. There was no association between enterovirus RNA and islet autoimmunity in samples obtained strictly before (7.6% cases, 10.0% controls, OR 0.75 [95% CI 0.36, 1.57]), or strictly after the first detection of islet autoantibodies (10.5% case, 5.8% controls, OR 2.00 [95% CI 0.64, 6.27]). However, there was a tendency towards a higher frequency of enterovirus detection in the first islet autoantibody-positive sample (15.8%) compared with the corresponding time point in matched controls (3.2%, OR 8.7 [95% CI 0.97, 77]). Neither of these results was changed by adjusting for potential confounders, restricting to various time intervals or employing various definitions of enterovirus positivity.

Conclusions/interpretation

Positivity for enterovirus RNA in blood did not predict the later induction of islet autoantibodies, but enterovirus tended to be detected more often at the islet autoantibody seroconversion stage.     

Temporal and Spatial Dependence of Inflammatory Biomarkers and Suppression by Fluvastatin in Dextran Sodium Sulfate-Induced Rat Colitis Model

Background

Dextran sodium sulfate (DSS)-induced colitis in rats is widely used as an experimental model for elucidating the etiology of ulcerative colitis (UC) and developing its novel remedy. We investigated the temporal and spatial changes in inflammatory mediators such as tumor necrosis factor (TNF)-α and inducible nitric oxide synthase (iNOS) in the regions of rectum and distal colon and examined whether statins, which were designed to lower plasma cholesterol levels, influenced those mediators.

Methods

Colitis was induced in rats by oral administration of 5 % DSS for 5 days, followed by 2 % DSS for 10 days. 5 % DSS rats were treated with fluvastatin (20 mg/kg) concomitantly for 5 days. The expression of inflammatory mediators of a sequence of four regions in rectum (R) and distal colon (D0, D1, and D2) was determined by quantitative RT-PCR.

Results

The peak of colitic damage, which was confirmed clinically and histopathologically, was found on days 4–6. The expression of TNF-α, iNOS, cytokine-induced neutrophil chemoattractant-1, interleukin (IL)-1β, and IL-6 mRNA increased in R time dependently, showing the peak on days 4–6, and then decreased thereafter. The levels of mRNAs reduced from R to D0, D1, and D2 region dependently. Fluvastatin decreased the expression of these markers in addition to the prevention of DSS-induced damage.

Conclusions

Results demonstrated that the expression of inflammatory biomarkers had time and region specificity and was markedly inhibited by fluvastatin. To obtain a precise drug effect for UC, it is important to elucidate the temporal and spatial dependence of inflammatory biomarkers in DSS colitis model.     

Improved survival for older patients undergoing surgery for colorectal cancer between 2008 and 2011

Introduction

Older colorectal cancer patients have a higher risk of postoperative complications, and the impact of adverse events on survival is also significantly higher. Innovations like laparoscopic surgery which improve short-term outcome for older patients can also benefit their overall prognosis. We set out to analyse the impact of an increased utilisation of laparoscopic surgery for colorectal cancer in the Netherlands on overall survival.

Methods

All patients diagnosed with stages I–III colorectal cancer in the Netherlands between 2008 and 2011 were selected from the Netherlands Cancer Registry. Changes in perioperative mortality, 3-month mortality and 1-year mortality rates were analysed using year of diagnosis as an instrumental variable.

Results

Over 33,000 patients were included in the analyses. Data on surgical approach were not precisely known for 2008 and 2009; in 2010, 36.6 % of definitive surgical procedures were performed laparoscopically and 45.9 % in 2011. A laparoscopic approach was used less frequently in the patients aged ≥75 years (in 2011, 40.3 versus 49.2 % of younger patients; p?p?=?0.02), 3-month mortality from 4.8 to 3.9 % (p?=?0.01) and 1-year mortality from 9.6 to 8.3 % (p?Conclusion Between 2008 and 2011, the utilisation of a laparoscopic approach increases significantly, resulting in reduced mortality rates, particularly for the elderly. Therefore, a laparoscopic approach should be used whenever possible, which may allow for further improvement of outcomes.