Noninferiority of Monoparametric MRI Versus Multiparametric MRI for the Detection of Prostate Cancer: Diagnostic Accuracy of ADC Ratios Based on Advanced "Zoomed" Diffusion-Weighted Imaging.

OBJECTIVES: The aim of this study was to compare the diagnostic accuracy of apparent diffusion coefficient (ADC) ratios as a monoparametric magnetic resonance imaging (MRI) protocol for the detection of prostate cancer (PCa) with the established multiparametric (mp) MRI at 3.0 T. MATERIALS AND METHODS: According to power analysis, 52 male patients were included in this monocenter study with prospective data collection and retrospective, blinded multireader image analysis. The study was approved by the local ethics committee. Patients were recruited from January to December 2020. Based on mpMRI findings, patients underwent in-bore MR biopsy or prostatectomy for histopathologic correlation of suspicious lesions. Three readers, blinded to the histopathologic results and images of mpMRI, independently evaluated ADC maps for the detection of PCa. The ADC ratio was defined as the lowest signal intensity (SI) of lesions divided by the SI of normal tissue in the zone of origin. Predictive accuracy of multiparametric and monoparametric MRI were compared using logistic regression analysis. Moreover, both protocols were compared applying goodness-of-fit analysis with the Hosmer-Lemeshow test for continuous ADC ratios and Pearson χ2 test for binary decision calls, correlation analysis with Spearman ρ and intraclass correlation coefficients, as well as noninferiority assessment with a TOST ("two one-sided test"). RESULTS: Eighty-one histopathologically proven, unique PCa lesions (Gleason score [GS] ≥ 3 + 3) in 52 patients could be unequivocally correlated, with 57 clinically significant (cs) PCa lesions (GS ≥ 3 + 4). Multiparametric MRI detected 95%, and monoparametric ADC detected ratios 91% to 93% of csPCa. Noninferiority of monoparametric MRI was confirmed by TOST (P < 0.05 for all comparisons). Logistic regression analysis revealed comparable predictive diagnostic accuracy of ADC ratios (73.7%-87.8%) versus mpMRI (72.2%-84.7%). Spearman rank correlation coefficient for PCa aggressiveness revealed satisfactory correlation of ADC ratios (P < 0.013 for all correlations). The Hosmer-Lemeshow test for the logistic regression analysis for continuous ADC ratios indicated adequate predictive accuracy (P = 0.55-0.87), and the Pearson χ2 test showed satisfactory goodness of fit (P = 0.35-0.69, χ2 = 0.16-0.87). CONCLUSIONS: Normalized ADC ratios based on advanced DWI are noninferior to mpMRI at 3.0 T for the detection of csPCa in a preselected patient cohort and proved a fast and accurate assessment tool, thus showing a potential prospect of easing the development of future screening methods for PCa.

Propofol Versus 4-hydroxybutyric Acid in Pediatric Cardiac Catheterizations.

INTRODUCTION: Pediatric patients require deep sedation at least for cardiac catheterizations (CCs). Usually, we perform these CCs applying propofol, but we have seen several side effects of this sedative. We have had good experience with 4-hydroxybutyric acid for other sedations. To optimize our standardized CC procedure, we initiated a prospective, randomized trial to compare the two substances. METHODS: We analyzed our sedation protocols of all CCs within a period of 12 months. In addition to the primary endpoints, the feasibility of the CCs and the occurrence of severe complications, several other parameters were included in the analysis (vital parameters, blood gas analysis, intervention measures). The protocols were blinded for the first part of the evaluation. RESULTS: During the 12-month-period, 36 patients were included in each group. The propofol group showed lower blood pressure values towards the end of the sedations, while the blood gas analyses revealed lower pH levels and higher pCO2 values. The complication rate was low in both groups. CONCLUSION: Both procedures are suited for the safe performance of deep sedations for CCs. The application of 4-hydroxybutyric acid seems to have a few advantages with regard to spontaneous breathing, gas exchange, stability of cardiocirculatory parameters and sedation quality.

Bone marrow aspirations in oncological patients: experience from an in-house standard in paediatrics.

BACKGROUND: Nearly all paediatric patients require deep sedation when undergoing bone marrow aspiration (BMA). We analyzed the data from our protocols documented in a standardised procedure for bone marrow puncture over a period of 2 years. METHODS: Our standard included the documentation of personal data as well as vital parameters. In addition, we documented all medications administered, potential complications and required intervention measures, as necessary. RESULTS: A total of 107 protocols were available for the evaluation. Our standard covered the usage of midazolam and S­ketamine and resulted in complications in just 9 patients, which could be remedied using simple measures. For both active substances, the dosage necessary to reach sufficient deep analgosedation was significantly higher for patients under 24 months of age. CONCLUSIONS: Our standard for BMA provides a practical and feasible procedure. In addition to good examination conditions, our standard also helps ensure the safety of our patients.

Predictive value of soluble ST2 in adolescent and adult patients with complex congenital heart disease.

BACKGROUND: Soluble suppression of tumorogenicity 2 (sST2) has been shown to be of prognostic value in patients with chronic and acute left heart failure. The present study aims to assess the predictive value of sST2 levels in adult patients with complex congenital heart disease (CHD). METHODS: In 169 consecutive patients with complex CHD and a mean age of 28.2 ± 12.0 years, sST2 levels were compared to 32 healthy controls and associated with clinical status as well as the occurrence of major adverse cardiac events (MACE). Mean follow-up time was 35.6 ± 24.9 months. RESULTS: In CHD patients, median sST2 levels were 29.7 ng/ml compared to 26.4 ng/ml in healthy controls (p = 0.007) and increased with different types of CHD and the severity of MACE. According to ROC analysis, the most important predictors of acute heart/Fontan failure were NYHA class III/IV (AUC 0.804, p<0.001, CI 0.668-0.941), NT-proBNP levels (AUC 0.794, p<0.001, CI 0.640-0.948), γGT levels (AUC 0.793, p<0.001, CI 0.678-0.909) and sST2 levels (AUC 0.742, p = 0.004, CI 0.626-0.858), with NYHA class III/IV as the strongest independent predictor (p<0.001). All-cause mortality was best predicted by sST2 levels (AUC 0.890, p<0.001, CI 0.741-1.000), NT-proBNP levels (AUC 0.875, p = 0.001, CI 0.766-0.984) and NYHA class III/IV (AUC 0.837, p = 0.003, CI 0.655-1.000) with sST2 as the strongest independent predictor (p<0.001). Moreover, AUC increased to 0.918 combining both biomarkers and net reclassification improved with the addition of sST2. CONCLUSION: In patients with complex CHD, sST2 may have additive value to natriuretic peptides for the prediction of all-cause mortality.

Acute appendicitis in children: can surgery be postponed? Short-term results in a cohort of 225 children.

PURPOSE: To our knowledge, there is no German study, which has examined the relationship between a postponement of surgery (from emergency service to standard working time) and the corresponding risk of postoperative complications in children and adolescents with acute appendicitis. The aim of this study is to examine if surgery of acute appendicitis in childhood can be postponed from night shift to the next working day without negative effects for the patient. METHODS: In a retrospective analysis (September 2001 to June 2007), the files of 225 paediatric surgical patients with acute appendicitis have been analysed concerning history, histology, course of treatment and development of complications. The cohort was divided into groups by their histology (common, "A", complicated appendicitis, "B") and by the median time (10 h) from admission to surgery (immediate, "C", delayed surgery, "D"). These groups have been analysed and compared. RESULTS: Groups A and B did not differ concerning time to admittance (p = 0.922). Seven patients developed complications (n = 7/225, 3.1%). Six complications were seen in group C (n = 6/113, 5.3%) compared to 1 in group D (n = 1/112, 0.9%), the difference was not significant (p = 0.119). None of the patients of group B developed complications after delayed surgery. Median follow-up was 10 days (IQR 7-15). CONCLUSIONS: In view of the development of complications, there was no evidence that the time between inpatient admission and surgery had any impact on the postoperative result. Thus, there is usually no need to perform surgery in common appendicitis during night shift.

Radiotherapy of painful heel spur with two fractionation regimens : Results of a randomized multicenter trial after 48 weeks' follow-up.

BACKGROUND: In this randomized multicenter trial, we compared the effect of a lower single dose of 0.5 Gy vs. a standard single dose of 1 Gy concerning pain relief and quality of life, while maintaining a uniform total dose of 6 Gy. On the basis of laboratory observations, the lower single dose would be expected to be more effective. PATIENTS AND METHODS: A total of 127 patients suffering from painful heel spur were randomized: Patients in the standard group were treated with single fractions of 6 × 1 Gy twice a week, while the experimental group was treated with single fractions of 12 × 0.5 Gy three times a week. Patients who did not show satisfactory pain relief after 12 weeks were offered re-irradiation with the standard dose. The study's primary endpoints were pain relief and quality of life. Therapy results were evaluated and compared based on follow-up examinations after 12 and 48 weeks. RESULTS: The data of 117 patients could be evaluated. There was no significant difference between the groups concerning the results of a visual analogue scale (VAS), Calcaneodynia Score (CS), and the somatic scale of the 12-Item Short-Form Health Survey(SF-12). Patients undergoing re-irradiation showed a significant benefit concerning pain relief. Their total outcome was comparable to patients showing a good response from the beginning. No relevant acute or chronic side effects were recorded. CONCLUSION: Both patient groups showed good results concerning pain relief. A fractionation schedule of 12 × 0.5 Gy was not superior to the current standard dose of 6 × 1 Gy. Further trials are necessary to explore the best fractionation schedule.

Plasma trimethylamine-N-oxide following supplementation with vitamin D or D plus B vitamins.

SCOPE: We compared the effect of supplementation with vitamin D + B or vitamin D on plasma trimethylamine N-oxide (TMAO) and choline metabolites. METHODS AND RESULTS: This is a randomized single-blinded nonplacebo-controlled study. Twenty-seven participants received 1200 IU vitamin D3 and 800 mg calcium, and 25 participants received additionally 0.5 mg folic acid, 50 mg B6, and 0.5 mg B12 for 1 year. Plasma homocysteine (Hcy), TMAO, and choline metabolites were measured at baseline and 12 months later. TMAO declined in the vitamin D arm by 0.5 versus 2.8 µmol/L in the D + B arm (p = 0.005). Hcy decreased and betaine increased in the D + B compared to the D arm. Within-subject levels of plasma choline and dimethylglycine and urine betaine increased in both arms and changes did not differ between the arms. TMAO reduction was predicted by higher baseline TMAO and lowering Hcy in stepwise regression analysis. The test-retest variations of TMAO were greater in the D + B arm compared to vitamin D arm. CONCLUSION: B vitamins plus vitamin D lowered plasma fasting TMAO compared to vitamin D. Vitamin D caused alterations in choline metabolism, which may reflect the metabolic flexibility of C1-metabolism. The molecular mechanisms and health implications of these changes are currently unknown.

Influence of Respiratory Position on Contrast Attenuation in Pulmonary CT Angiography: A Prospective Randomized Clinical Trial.

OBJECTIVE: The purpose of this study was to prospectively compare the effect of inspiration and resting expiratory position on contrast enhancement in pulmonary CT angiography (CTA) in a randomized clinical trial. SUBJECTS AND METHODS: In accordance with a power analysis performed before the study, we included 28 consecutive patients referred for evaluation of suspected pulmonary embolism in this prospective study. Patients were randomly assigned to perform either inspiration (n = 14; six men, eight women; mean age [SD], 38.1 ± 9.8 years) or resting expiratory position (n = 14; six men, eight women; mean age: 42.1 ± 9.2 years). All patients were scanned in a standardized supine position and scanning parameters were kept constant. Contrast medium was injected automatically with bolus tracking. Objective pulmonary vessel attenuation was quantified with digital measurement. Results were analyzed by using the unpaired t test and chi-square test. RESULTS: Patients in the resting expiratory position showed significantly higher contrast attenuation than those who performed inspiration (302.9 ± 11.9 HU vs 221.5 ± 20.9 HU; p < 0.01). There were no significant differences in applied total volume of contrast agent (76.8 ± 1.9 mL vs 75.7 ± 1.6 mL; p = 0.6765), total volume including normal saline bolus (116.8 mL ± 2.8 mL vs 121.8 mL ± 2.3 mL; p = 0.1724) or flow rate (3.1 mL/s ± 0.1 mL/s vs 3.2 mL/s ± 0.1 mL/s). CONCLUSION: Pulmonary CTA should be performed in the resting expiratory position, and patients should be instructed to avoid inspiration to achieve the highest possible attenuation in the pulmonary arteries.

Plasma trimethylamine N-oxide concentration is associated with choline, phospholipids, and methyl metabolism.

BACKGROUND: Elevated plasma concentrations of the gut bacteria choline metabolite trimethylamine N-oxide (TMAO) are associated with atherosclerosis. However, the determinants of TMAO in humans require additional assessment. OBJECTIVE: We examined cardiometabolic risk factors and pathways associated with TMAO concentrations in humans. DESIGN: A total of 283 individuals (mean ± SD age: 66.7 ± 9.0 y) were included in this observational study. Plasma concentrations of trimethylamine, TMAO, choline, lipids, phospholipids, and methyl metabolites were measured. RESULTS: Study participants were divided into 4 groups by median concentrations of TMAO and choline (4.36 and 9.7 µmol/L, respectively). Compared with the group with TMAO and choline concentrations that were less than the median (n = 82), the group with TMAO and choline concentrations that were at least the median (n = 83) was older and had lower high-density lipoprotein (HDL) cholesterol, phospholipids, and methylation potential, higher creatinine, betaine, S-adenosylhomocysteine (SAH), and S-adenosylmethionine (SAM), and higher percentages of men and subjects with diabetes. The difference in plasma TMAO concentrations between men and women (7.3 ± 10.0 compared with 5.4 ± 5.6 µmol/L, respectively) was NS after adjustment for age and creatinine (P = 0.455). The TMAO:trimethylamine ratio was higher in men (P < 0.001). Diabetes was associated with significantly higher plasma TMAO concentration (8.6 ± 12.2 compared with 5.4 ± 5.2 µmol/L) even after adjustments. Sex and diabetes showed an interactive effect on trimethylamine concentrations (P = 0.010) but not on TMAO concentrations (P = 0.950). Positive determinants of TMAO in a stepwise regression model that applied to the whole group were SAH, trimethylamine, choline, and female sex, whereas plasma phosphatidylcholine was a negative determinant. CONCLUSIONS: High TMAO and choline concentrations are associated with an advanced cardiometabolic risk profile. Diabetes is related to higher plasma TMAO concentrations but also to alterations in interrelated pathways such as lipids, phospholipids, and methylation. Elevated plasma TMAO concentrations likely reflect a specific metabolic pattern characterized by low HDL and phospholipids in addition to hypomethylation. This trial was registered at clinicaltrials.gov as NCT02586181 and NCT02588898.

Randomized multicenter follow-up trial on the effect of radiotherapy on painful heel spur (plantar fasciitis) comparing two fractionation schedules with uniform total dose: first results after three months' follow-up.

BACKGROUND: Our first trial on radiotherapy for painful heel spur published in 2012 comparing the analgesic effect of a standard dose (6 × 1.0 Gy within three weeks) to that of a very low one (6 × 0.1 Gy within three weeks) resulted in a highly significant superiority of the standard dose arm. In the meantime, experimental data have shown that lower single doses in the range of 0.5 - 0.7 Gy might be even more effective than the current standard dose of 1.0 Gy. Therefore, we conducted a second trial comparing the analgesic effect of standard single doses of 1.0 Gy to that of low single doses of 0.5 Gy using uniform total doses of 6 Gy. PATIENTS AND METHODS: One hundred twenty-seven patients were randomized to receive radiation therapy either with a total dose of 6.0 Gy applied in 6 fractions of 1.0 Gy twice weekly (standard dose) or with the same total dose applied in 12 fractions of 0.5 Gy three times weekly (experimental dose). In all patients lateral opposing 6MV photon beams were used. The results were measured using Visual analogue scale (VAS), Calcaneodynia score (CS) and SF-12 health survey. The first phase of this trial ended after a three months' follow-up; it will be continued up to 48 weeks. RESULTS: Nine patients had to be excluded after randomization either due to the withdrawal of informed consent to radiotherapy by the patients or radiotherapy with an incorrect dosage. The groups were comparable concerning biographical and disease data. The mean calcaneodynia score (CS) was higher in the experimental group (p = 0.002). After three months' follow-up, we saw a very favorable pain relief in both arms (decline of VAS score: standard arm 42 points, experimental arm 44 points (n.s.), but we did not notice any statistically significant difference between the arms neither concerning the pain parameters nor the quality of life parameters. No relevant acute side effects were recorded. CONCLUSIONS: Favorable laboratory results could not be translated into an enhanced pain relief in our patients. This trial was terminated after the interim analysis (127 patients randomized). Further trials will be necessary to explore the best fractionation schedule. This trial has been approved by the expert panel of the DEGRO as well as by the Ethics committee of the Saarland Physicians' chamber. TRIAL REGISTRATION: Current trial registration at German Clinical Trials Register with the number DRKS00004458.

Randomized multicenter follow-up trial on the effect of radiotherapy for plantar fasciitis (painful heels spur) depending on dose and fractionation - a study protocol.

BACKGROUND: An actual clinical trial showed the effect of low dose radiotherapy in painful heel spur (plantar fasciitis) with single doses of 1.0 Gy and total doses of 6.0 Gy applied twice weekly. Furthermore, a lot of animal experimental and in vitro data reveals the effect of lower single doses of 0.5 Gy which may be superior in order to ease pain and reduce inflammation in patients with painful heel spur. Our goal is therefore to transfer this experimentally found effect into a randomized multicenter trial. STUDY DESIGN/METHODS: This was a controlled, prospective, two-arm phase III-multicenter trial. The standard arm consisted of single fractions of 1.0 Gy applied two times a week, for a total dose of 6.0 Gy (total therapy time: 3 weeks). The experimental arm consisted of single fractions of 0.5 Gy applied 3 times a week, for a total dose of 6.0 Gy (total therapy time: 4 weeks). Following a statistical power calculation, there were 120 patients for each investigation arm. The main inclusion criteria were: age > = 40 years, clinical and radiologically diagnosed painful heel spur (plantar fasciitis), and current symptoms for at least 6 months. The main exclusion criteria were: former local trauma, surgery or radiotherapy of the heel; pregnant or breastfeeding women; and a pre-existing severe psychiatric or psychosomatic disorder. METHODS: After approving a written informed consent the patients are randomized by a statistician into one of the trial arms. After radiotherapy, the patients are seen after six weeks, after twelve weeks and then every twelve weeks up to 48 weeks. Additionally, they receive a questionnaire every six weeks after the follow-up examinations up to 48 weeks. The effect is measured using the visual analogue scale of pain (VAS), the calcaneodynia score according to Rowe and the SF-12 score. The primary endpoint is the pain relief three months after therapy. Patients of both therapy arms with an insufficient result are offered a second radiotherapy series applying the standard dose (equally in both arms). This trial protocol has been approved by the expert panel of the DEGRO as well as by the Ethics committee of the Saarland Physicians' chamber. TRIAL REGISTRATION: Current trial registration at German Clinical Trials Register with the number DRKS00004458.

A scoring-system for angiographic findings in nonocclusive mesenteric ischemia (NOMI): correlation with clinical risk factors and its predictive value.

PURPOSE: This study was designed to evaluate the clinical value of a standardized angiographic scoring system in patients with nonocclusive mesenteric ischemia (NOMI). METHODS: Sixty-three consecutive patients (mean age: 73 ± 8 years) with suspect of NOMI after cardiac or major thoracic vessel surgery underwent catheter angiography of the superior mesenteric artery. Images were assessed by two experienced radiologists on consensus basis using a scoring system consisting of five categories, namely vessel morphology, reflux of contrast medium into the aorta, contrasting and distension of the intestine, as well as the time to portal vein filling. These were correlated to previously published risk factors of NOMI and outcome data. RESULTS: The most significant correlation was found between the vessel morphology and death (p < 0.001) as well as reflux of contrast medium into the aorta and death (p = 0.005). Significant correlation was found between delayed portal vein filling and preoperative statin administration (p = 0.011), previous stroke (p = 0.033), and renal insufficiency (p = 0.043). Reflux of contrast medium correlated significantly with serum lactate >10 mmol/L (p = 0.046). The overall angiographic score correlated with death (p = 0.017) and renal insufficiency (p = 0.02). The ROC-analysis revealed that a score of ≥3.5 allows for identifying patients with increased perioperative mortality with a sensitivity of 85.7 % and a specificity of 49 %. With the use of a simplified score (vessel morphology, reflux of contrast medium into the aorta, and time to portal vein filling), specificity was increased to 71.4 %. CONCLUSIONS: The applied scoring system allows standardized interpretation of angiographic findings in NOMI patients. Beyond that the score seems to correlate well with risk factors of NOMI and outcome.

Genetic polymorphism of the OPG gene associated with breast cancer.

BACKGROUND: The receptor activator of NF-κB (RANK), its ligand (RANKL) and osteoprotegerin (OPG) have been reported to play a role in the pathophysiological bone turnover and in the pathogenesis of breast cancer. Based on this we investigated the role of single nucleotide polymorphisms (SNPs) within RANK, RANKL and OPG and their possible association to breast cancer risk. METHODS: Genomic DNA was obtained from Caucasian participants consisting of 307 female breast cancer patients and 396 gender-matched healthy controls. We studied seven SNPs in the genes of OPG (rs3102735, rs2073618), RANK (rs1805034, rs35211496) and RANKL (rs9533156, rs2277438, rs1054016) using TaqMan genotyping assays. Statistical analyses were performed using the χ2-tests for 2 x 2 and 2 x 3 tables. RESULTS: The allelic frequencies (OR: 1.508 CI: 1.127-2.018, p=0.006) and the genotype distribution (p=0.019) of the OPG SNP rs3102735 differed significantly between breast cancer patients and healthy controls. The minor allele C and the corresponding homo- and heterozygous genotypes are more common in breast cancer patients (minor allele C: 18.4% vs. 13.0%; genotype CC: 3.3% vs. 1.3%; genotype CT: 30.3% vs. 23.5%). No significantly changed risk was detected in the other investigated SNPs. Additional analysis showed significant differences when comparing patients with invasive vs. non-invasive tumors (OPG rs2073618) as well as in terms of tumor localization (RANK rs35211496) and body mass index (RANKL rs9533156 and rs1054016). CONCLUSIONS: This is the first study reporting a significant association of the SNP rs3102735 (OPG) with the susceptibility to develop breast cancer in the Caucasian population.

Randomized, multicenter trial on the effect of radiation therapy on plantar fasciitis (painful heel spur) comparing a standard dose with a very low dose: mature results after 12 months' follow-up.

PURPOSE: To conduct a randomized trial of radiation therapy for painful heel spur, comparing a standard dose with a very low dose. METHODS AND MATERIALS: Sixty-six patients were randomized to receive radiation therapy either with a total dose of 6.0 Gy applied in 6 fractions of 1.0 Gy twice weekly (standard dose) or with a total dose of 0.6 Gy applied in 6 fractions of 0.1 Gy twice weekly (low dose). In all patients lateral opposing 4- to 6-MV photon beams were used. The results were measured using a visual analogue scale, the Calcaneodynia score, and the SF12 health survey. The fundamental phase of the study ended after 3 months, and the follow-up was continued up to 1 year. Patients with insufficient pain relief after 3 months were offered reirradiation with the standard dosage at any time afterward. RESULTS: Of 66 patients, 4 were excluded because of withdrawal of consent or screening failures. After 3 months the results in the standard arm were highly significantly superior compared with those in the low-dose arm (visual analogue scale, P=.001; Calcaneodynia score, P=.027; SF12, P=.045). The accrual of patients was stopped at this point. Further evaluation after 12 months' follow-up showed the following results: (1) highly significant fewer patients were reirradiated in the standard arm compared with the low-dose arm (P<.001); (2) the results of patients in the low-dose arm who were reirradiated were identical to those in the standard arm not reirradiated (reirradiation as a salvage therapy if the lower dose was ineffective); (3) patients experiencing a favorable result after 3 months showed this even after 12 months, and some results even improved further between 3 and 12 months. CONCLUSIONS: This study confirms the superior analgesic effect of radiation therapy with 6-Gy doses on painful heel spur even for a longer time period of at least 1 year.

Do Clopidogrel Nonresponders Have an Increased Risk of Adverse Events during Supra-Aortal Angioplasty and Stenting?

Objective. The aim of the present study was to correlate new periprocedural diffusion-weighted imaging (DWI) lesions during stenting of supra-aortal arteries with the level of platelet inhibition using point-of-care analysis. Background. Cardiological studies have shown that patients undergoing coronary PTA have a significantly elevated risk of severe thrombotic complications if patients show insufficient inhibition of platelet function. Methods. From August 2008 to June 2009, 44 patients with an indication of supra-aortal angioplasty and/or stenting were prospectively enrolled. Platelet reactivity was tested using a Multiplate device (Dynabyte). These patients underwent MRI before and after the intervention to determine the prevalence of new DWI lesions. The primary endpoint was the prevalence of DWI lesions; the secondary endpoint was clinical status until discharge from hospital. Results. There was no significant relationship between the primary endpoint and the degree of platelet function. Patients with high platelet reactivity showed the same amount of periprocedural complications as patients with sufficient inhibition of platelets. Conclusions. Clopidogrel did not have a protective effect on periprocedural complications, nor did it decrease the number of silent DWI lesions after the procedure. The predescribed strong relationship between high platelet reactivity and early post-procedural adverse events was not observed in our cohort.

Thoracotomy procedures effect cytokine levels after thoracoabdominal esophagectomy.

Pulmonary complications together with surgical complications are the most frequent causes for morbidity and mortality after thoracoabdominal esophagectomy. The con-tinuous improvement of surgical techniques has led to a decrease in surgical complications, whereas up to 30% of the patients develop postoperative pulmonary complications such as acute lung injury (ALI) or even the more severe acute respiratory distress syndrome (ARDS), which are characterized by an acute inflammation in the lung parenchyma and the airspace. Evidence from several studies indicates that a complex network of inflammatory cytokines and mediators play a key role in mediation, amplification, and perpetuation of the process of lung injury and that the thoracotomy itself is a risk factor for developing ALI or ARDS. In this trial, the cytokine levels of IL6, IL8 and IL10 were measured and compared in 30 patients who had undergone an extended radical thoracoabdominal esophagectomy for esophageal cancer, via anterolateral thoracotomy (n=17) or posterolateral thoracotomy (n=13). Patients of both groups were similar in terms of age, sex and preoperative pulmonary function as well as in the anesthetic procedures they have undergone. All patients displayed significantly increased serum levels of IL6 and IL8 after thoracoabdominal esophagectomy. However, patients who were subjected to an anterolateral thoracotomy were reported with significantly higher serum levels of IL6 and IL8 compared to patients who had received a posterolateral thoracotomy. Thus, the choice of the thoracotomy method during the thoracoabdominal esophagectomy and the resultant cytokine levels may contribute to the occurrence of postoperative pulmonary complications and may have an impact on the extent and severity of the surgical stress.

miR-21 functionally interacts with the 3'UTR of chemokine CCL20 and down-regulates CCL20 expression in miR-21 transfected colorectal cancer cells.

As deregulation of miRNAs and chemokine CCL20 was shown to play a role in colorectal cancer (CRC) pathogenesis, we analyzed the functional interactions of candidate miRNAs with CCL20 mRNA. After target prediction software programs indicated a role for miR-21 in CCL20 regulation, we applied the luciferase reporter assay system to demonstrate that miR-21 functionally interacts with the 3'UTR of CCL20 mRNA and down-regulates CCL20 in miR-21 mimic transfected CRC cell lines (Caco-2, SW480 and SW620). Thus, regulation of CCL20 expression by miR-21 might be a regulatory mechanism involved in progression of CRC.

Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases.

AIM: To evaluate the influence of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in liver metastases of stage IV colorectal cancer (CRC) patients. METHODS: Using Real Time-PCR, enzyme-linked immunosorbent assay, Western Blots and immunohistochemistry, we have analyzed the expression of CCL20, CCR6 and proliferation marker Ki-67 in colorectal liver metastasis (CRLM) specimens from stage IV CRC patients who received preoperative FOLFOX chemotherapy (n = 53) and in patients who did not receive FOLFOX chemotherapy prior to liver surgery (n = 29). RESULTS: Of the 53 patients who received FOLFOX, time to liver surgery was ≤ 1 mo in 14 patients, ≤ 1 year in 22 patients and > 1 year in 17 patients, respectively. In addition, we investigated the proliferation rate of CRC cells in liver metastases in the different patient groups. Both CCL20 and CCR6 mRNA and protein expression levels were significantly increased in patients who received preoperative FOLFOX chemotherapy ≤ 12 mo before liver surgery (P < 0.001) in comparison to patients who did not undergo FOLFOX treatment. Further, proliferation of CRLM cells as measured by Ki-67 was increased in patients who underwent FOLFOX treatment. CCL20 and CCR6 expression levels were significantly increased in CRLM patients who had undergone preoperative FOLFOX chemotherapy. CONCLUSION: This chemokine/receptor up-regulation could lead to increased proliferation/migration through an autocrine mechanism which might be used by surviving metastatic cells to escape cell death caused by FOLFOX.

CCL20/CCR6 expression profile in pancreatic cancer.

BACKGROUND: CCL20 and its receptor CCR6 have been shown to play a role in the onset, development and metastatic spread of various gastrointestinal malignancies. In this study, the expression profile and clinical significance of the CCL20/CCR6 system in distinct benign, pre-malignant and malignant pancreatic tissues was investigated. METHODS: Using RealTime-PCR, enzyme-linked immunosorbent assay (ELISA), Western Blot and immunohistochemistry, we have analyzed the expression profile of CCL20/CCR6 in resection specimens from patients with chronic pancreatitis (CP) (n = 22), pancreatic cystadenoma (PA) (n = 11) and pancreatic carcinoma (PCA) (n = 25) as well as in the respective matched normal pancreatic tissues. RESULTS: CCL20 mRNA and protein was weakly expressed in normal pancreatic tissues and CP and PA specimens but significantly up-regulated in PCA (8-fold) as compared to the matched normal tissue (P < 0.05). Moreover, CCL20 mRNA and protein expression was significantly associated with advanced T-category in patients with PCA (P < 0.05). CCR6 mRNA showed a significant up-regulation in all three disease entities as compared to normal tissues (P < 0.05, respectively). CONCLUSION: CCL20 and CCR6 were significantly up-regulated in PCA as compared to the normal pancreatic tissue and CCL20 was significantly associated with advanced T-category in PCA patients. This suggests that CCL20 and CCR6 play a role in the development and progression of PCA and may constitute potential targets for novel treatment strategies.

Low serum folate and vitamin B-6 are associated with an altered cancellous bone structure in humans.

BACKGROUND: Several clinical trials have reported B vitamins to be associated with osteoporosis. OBJECTIVE: Our objective was to investigate whether low serum B vitamins are associated with altered structural and biomechanical properties of human bone. DESIGN: Femoral heads of 94 men and women who underwent hip arthroplasty were analyzed by using dual-energy X-ray absorptiometry (DXA), biomechanical testing (indentation method), and histomorphometry. In addition, blood was collected to measure serum concentrations of homocysteine, folate, vitamin B-6, vitamin B-12, the bone formation marker osteocalcin, and the bone resorption marker tartrate-resistant acid phosphatase (TRAP). Measurement outcomes were grouped according to subjects with high and low serum concentrations, respectively, of folate, vitamin B-6, and vitamin B-12 (n = 47 for each group). RESULTS: Histomorphometric analysis showed a significantly lower trabecular thickness and trabecular area in subjects with low serum folate concentrations than in those with high serum folate concentrations and a significantly lower trabecular number in subjects with low serum vitamin B-6 concentrations than in those with high serum vitamin B-6 concentrations. In contrast, we found a comparable trabecular structure in subjects with high and low serum vitamin B-12 concentrations. DXA and biomechanical testing did not show significant differences between subjects with high and low serum B vitamin concentrations. Osteocalcin was significantly lowered in subjects with a low serum B vitamin concentration, whereas there was no association between serum B vitamins and TRAP. CONCLUSION: The results of the present study indicate that low serum folate and vitamin B-6 concentrations, but not low serum vitamin B-12 concentrations, are associated with an altered morphology of human bone.