Siegfried Kropf

Detection and characterisation of focal liver lesions in colorectal carcinoma patients: comparison of diffusion-weighted and Gd-EOB-DTPA enhanced MR imaging

ObjectiveTo compare diffusion-weighted imaging (DWI) and Gd-EOB-DTPA-enhanced magnetic resonance (MR) imaging for the detection and characterisation of focal liver lesions (FLLs) in patients with colorectal carcinoma.MethodsSeventy-three patients underwent MR imaging including echoplanar DWI (MR-DWI) and dynamic (MR-Dyn) and hepatobiliary phase (MR-Late) Gd-EOB-DTPA-enhanced images. Two blinded readers independently reviewed 5 different image sets using a 5-point confidence scale. Accuracy was assessed by the area (Az) under the receiver operating characteristic curve, and sensitivity and specificity were calculated.ResultsA total of 332 FLLs were evaluated. Detection rates were significantly higher for MR-Late images (94.4% for benign and 100% for malignant lesions) compared with MR-DWI (78.3% and 97.5%) and MR-Dyn images (81.5% and 89.9%). Accuracy was 0.82, 0.76 and 0.89 for MR-DWI, MR-Dyn and MR-Late images while sensitivity was 0.98, 0.87 and 0.95, respectively. For characterisation of subcentimetre lesions sensitivity was highest for MR-DWI (0.92). Combined reading of unenhanced and contrast-enhanced images had an identical high accuracy of 0.98.ConclusionLate-phase Gd-EOB-DTPA-enhanced images were superior for the detection of FLLs, while DWIs were most valuable for the identification of particularly small metastases. Combined interpretation of unenhanced images resulted in precise characterisation of FLLs.

B Vitamins and the Risk of Total Mortality and Cardiovascular Disease in End-Stage Renal Disease Results of a Randomized Controlled Trial

Background— In observational studies, hyperhomocysteinemia has been found to be a risk factor for total mortality and cardiovascular events in patients with end-stage renal disease. These patients have grossly elevated homocysteine levels that can be lowered by supplementation with folic acid and vitamin B12. We conducted a randomized clinical trial with B vitamins to reduce homocysteine levels and therefore cardiovascular events and total mortality. Methods and Results— This randomized, double-blind multicenter study was conducted in 33 dialysis centers in north and east Germany between July 2002 and July 2008. We randomly assigned 650 patients with end-stage renal disease who were undergoing hemodialysis to 2 postdialysis treatments: 5 mg folic acid, 50 &mgr;g vitamin B12, and 20 mg vitamin B6 (active treatment) or 0.2 mg folic acid, 4 &mgr;g vitamin B12, and 1.0 mg vitamin B6 (placebo) given 3 times per week for an average of 2 years. The primary outcome was total mortality; the secondary outcome was fatal and nonfatal cardiovascular events. The primary outcome occurred in 102 patients (31%) receiving the active treatment and in 92 (28%) receiving placebo (hazard ratio, 1.13; 95% confidence interval, 0.85 to 1.50; P=0.51). The secondary outcome occurred in 83 patients (25%) receiving the active treatment and in 98 (30%) receiving placebo (hazard ratio, 0.80; 95% confidence interval, 0.60 to 1.07; P=0.13). Conclusions— Increased intake of folic acid, vitamin B12, and vitamin B6 did not reduce total mortality and had no significant effect on the risk of cardiovascular events in patients with end-stage renal disease. Clinical Trial Registration— URL: www.anzctr.org.au. Unique identifier: ACTRN12609000911291. URL: www.cochrane-renal.org. Unique identifier: CRG010600027.

Impact of Multiphase 68Ga-DOTATOC-PET/CT on therapy management in patients with neuroendocrine tumors.

Aim: Retrospective evaluation of the impact of integrated positron emission tomography/computed tomography (PET/CT) using 68Ga-DOTA(0)-Phe(1)-Tyr(3)-octreotide (68Ga-DOTATOC) on the therapeutic management of patients with neuroendocrine tumors (NET). Methods: The 68Ga-DOTATOC-PET/CT data of 66 patients (31 male, 35 female; age: 29–79, mean age: 56 years) with known or suspected NET were included. Imaging data (PET and triple-phase contrast-enhanced CT) were evaluated in consensus by two readers for the visualization of NET manifestations. Combined PET/CT, clinical and imaging follow-up as well as histopathology (if available) served as the reference standard. In order to assess the impact of the respective submodalities on the therapeutic strategy chosen, the results were compared to the treatment decision made by the interdisciplinary NET tumor board of our institution. Results: Two of the initial 66 patients included did not suffer from NET according to further immunohistopathological examination. In 50 of the remaining 64 (78%) NET patients, a total of 181 NET manifestations were detected by PET/CT. 59/181 (32.6%) were detected by one submodality only (CT 17.1%, PET 15.5%, p for comparison of both = 0.459). Combined PET/CT reading had an impact on the therapeutic management in 24 of 64 (38%) NET patients: primary resection (n = 5), curative lymph node resection (n = 1), initiation/switch of chemotherapy (CTx) due to progressive disease (n = 10), no surgery due to systemic disease (n = 2), radiopeptide receptor therapy instead of CTx (n = 1), additional bisphosphonate therapy (n = 4), and hepatic brachytherapy (n = 1). In 12 of 24 (50%) of these patients, relevant findings were detected by a single submodality only: CT (n = 5), PET (n = 7); p for comparison = 0.774). Conclusion:68Ga-DOTATOC-PET/CT influences therapeutic management in about one third of patients examined. CT and PET are comparably sensitive, deliver complementary information and equally contribute to therapeutic decision-making. Thus, despite the merits of the PET modality, the CT component must not be neglected and an optimized multiphase CT protocol is recommended.

Increased pregnancy rates after ultralong postoperative therapy with gonadotropin-releasing hormone analogs in patients with endometriosis ☆

OBJECTIVE To examine whether ultralong GnRH analog (GnRH-a) therapy after surgical treatment of endometriosis and before ART influences the pregnancy rate. DESIGN Prospective, randomized, controlled study. SETTING University clinic for reproductive medicine and gynecologic endocrinology. PATIENT(S) One hundred ten patients with stage II to IV endometriosis according to ASRM criteria. INTERVENTION(S) Fifty-five patients received GnRH-a for 6 months after surgery and subsequently underwent up to 3 cycles of ART, and 55 patients received 3 cycles of ART alone immediately after surgery. MAIN OUTCOME MEASURE(S) Clinical pregnancy rates. RESULTS The pregnancy rate per patient was higher among patients who received follow-up treatment with GnRH-a. The same results were found in patients with stage III or IV endometriosis who were undergoing IUI or IVF/ICSI. CONCLUSION(S) Ultralong GnRH-a therapy increases the pregnancy rate of ART in patients with severe endometriosis.

Skin-to-Skin Contact Improves Gas Exchange in Premature Infants

OBJECTIVE:Skin-to-skin contact (kangarooing) is regarded as an important method to improve intensive care in premature infants. There is still demand for investigations of its impact on physiological parameters.STUDY DESIGN:We examined 53 preterm infants of <1800 gm in a prospective, pretest-test-posttest design study during incubator care (60 minutes), skin-to-skin contact (90 minutes), and incubator care again (90 minutes). Heart rate, respiratory rate, oxygen saturation (SaO2), transcutaneous pO2 (tcpO2), transcutaneous pCO2, rectal temperature, and fraction of inspired oxygen were measured.RESULTS:The heart rate increased during skin-to-skin contact by 5 beats per minute (p < 0.001), the respiratory rate dropped by 5/minute (p < 0.01), the SaO2 improved by 0.4% (p < 0.05) accompanied by an increase of tcpO2 of 4.8 mm Hg (p < 0.001), the tcpCO2 dropped by 1.2 mm Hg (p < 0.001), and the rectal temperature increased by 0.3 ° C (p < 0.001). Analyzing three groups separately by postnatal weight, we observed the smallest increase in heart rate and the highest decrease in respiratory rate in infants of <1000 gm (p < 0.001). The increase in SaO2 and in the tcpO2 doubles in infants of <1000 gm compared with infants of >1000 gm (p < 0.001). All changes were independent of postnatal age.CONCLUSION: During skin-to-skin contact, preterm infants not only remain clinically stable but also show a more efficient gas exchange. Although the patient is removed (transferred) from the incubator, there is no risk of hypothermia even in infants of <1000 gm.

Cardiac function by MRI in congenital heart disease: Impact of consensus training on interinstitutional variance

To investigate the impact of interinstitutional variance (=interobserver variance between institutions) for volumetric and flow cardiac MR (CMR) data and if training on image reading could improve bias.

Different Activation of Mitogen-Activated Protein Kinase and Akt Signaling Is Associated with Aggressive Phenotype of Human Meningiomas

Purpose: Activation of intracellular signaling cascades has been implicated in the growth control of benign meningiomas, but their role for meningioma progression and outcome is unknown. Here we determined the expression and function of proteins involved in mitogen-activated protein kinase (MAPK) and phosphinositol-3 kinase (PI3K)/Akt signaling in benign, atypical, and malignant meningiomas and studied their association with clinicopathologic data including meningioma recurrence. Experimental Design: Expression of various MAPK and PI3K signaling proteins was determined in 70 primary meningiomas and, if present, in recurrent tumors by immunohistochemistry and Western blotting. The expression patterns in primary and recurrent tumors were related to clinical data. The effect of MAPK and PI3K pathway inhibition on cell proliferation and apoptosis was determined using a primary malignant meningioma cell culture. Results: Atypical and malignant meningiomas showed higher levels of phospho-Akt compared with benign tumors, and their proliferation could be inhibited by PI3K blocking using wortmannin. PI3K inhibition did not induce apoptosis in malignant meningioma cells. In contrast, expression of phospho-Raf and phospho-MAPK was decreased in aggressive meningiomas compared with benign tumors, but MAPK inhibition by PD98059 resulted in tumor cell apoptosis and decreased proliferation. Reduced MAPK activation was associated with meningioma recurrence, and PI3K activation was associated with poor preclinical condition and brain invasion of malignant meningiomas. Conclusions: Both MAPK and PI3K/Akt pathways are activated at different levels in benign and malignant meningiomas. Activation of PI3K/Akt signaling contributes to the aggressive behavior of malignant meningiomas, whereas MAPK activation is involved in both proliferation and apoptosis of malignant meningiomas.

Effect of the soil type on the microbiome in the rhizosphere of field-grown lettuce

The complex and enormous diversity of microorganisms associated with plant roots is important for plant health and growth and is shaped by numerous factors. This study aimed to unravel the effects of the soil type on bacterial communities in the rhizosphere of field-grown lettuce. We used an experimental plot system with three different soil types that were stored at the same site for 10 years under the same agricultural management to reveal differences directly linked to the soil type and not influenced by other factors such as climate or cropping history. Bulk soil and rhizosphere samples were collected 3 and 7 weeks after planting. The analysis of 16S rRNA gene fragments amplified from total community DNA by denaturing gradient gel electrophoresis and pyrosequencing revealed soil type dependent differences in the bacterial community structure of the bulk soils and the corresponding rhizospheres. The rhizosphere effect differed depending on the soil type and the plant growth developmental stage. Despite the soil type dependent differences in the bacterial community composition several genera such as Sphingomonas, Rhizobium, Pseudomonas, and Variovorax were significantly increased in the rhizosphere of lettuce grown in all three soils. The number of rhizosphere responders was highest 3 weeks after planting. Interestingly, in the soil with the highest numbers of responders the highest shoot dry weights were observed. Heatmap analysis revealed that many dominant operational taxonomic units were shared among rhizosphere samples of lettuce grown in diluvial sand, alluvial loam, and loess loam and that only a subset was increased in relative abundance in the rhizosphere compared to the corresponding bulk soil. The findings of the study provide insights into the effect of soil types on the rhizosphere microbiome of lettuce.

Functional analysis of the components of the right ventricle in the setting of tetralogy of Fallot.

Background—Anatomic and functional observations suggest that the right ventricle (RV) can be analyzed in terms of its inlet, apical trabecular, and outlet components. Our study was designed to evaluate the regional adaptation of these components to different conditions of loading, with additional analysis of the surgical techniques used for primary repair. Methods and Results—We studied prospectively 45 patients with tetralogy of Fallot (age, 20.5±8.1 years) and 24 control subjects (age, 20.1±5.8 years). All subjects were studied by using cardiac MRI. End-diastolic (EDV), end-systolic (ESV), stroke volumes (SV), and ejection fraction (EF) were determined for the overall RV and separately for its inlet, apical trabecular, and outlet components. The patients had pulmonary regurgitant fractions of 33.2±11.1%, and RV peak-systolic pressures of 40.7±16.1 mm Hg. In controls, the apical trabecular component EDV was 51.5±11.1 mL/m2 (54.3±6.8% of the total RV EDV), ESV was 19.2±6.3 mL/m2 (47.6±10.5% of RV ESV), and SV was 32.3±6.9 mL/m2 (58.9±6.6% of RV SV), resulting in an EF of 63.1±7.7%. When considering all patients, the apical trabecular component took up the greatest part of the overload, having an EDV of 76.5±18.1 mL/m2, and an ESV of 31.6±12.8 mL/m2, reflecting an increase of 49 and 67% over controls, respectively (P<0.001). EF was 59.7±10.7%, and was maintained at control levels (P=0.132). In controls, the outlet had considerable ejecting force, with an EF of 54.8±9.1%, whereas it was decreased in the patients with tetralogy (EF=28.5±11.9%). There was significant increase of ESV (P<0.001), but not of EDV, with EF decreased by 45% (P<0.001). The inlet was not significantly affected by overload. The surgical technique did not significantly affect any measured parameter for any component. Conclusions—In patients with tetralogy of Fallot, subsequent to surgical correction, the individual components of the RV respond in characteristic fashion to RV overload.

Homocysteine as a Risk Factor for Cardiovascular Disease in Patients Treated by Dialysis: A Meta–analysis

BACKGROUND In the general population, increased homocysteine concentrations are a risk factor for cardiovascular disease and mortality. However, it is not known whether this also applies to patients with end-stage renal disease. STUDY DESIGN Meta-analysis of retrospective (11 studies including 1,506 individuals), prospective observational studies (12 studies including 1,975 individuals), and intervention trials (5 studies including 1,642 dialysis patients). Analyses were carried out separately, according to the study design. SETTING & POPULATION Studies of patients with end-stage renal disease treated by means of hemodialysis or peritoneal dialysis. SELECTION CRITERIA FOR STUDIES Studies investigating the association between total homocysteine level and cardiovascular disease or total mortality or the influence of vitamin supplementation on cardiovascular or mortality risk. INTERVENTION In intervention studies, vitamin preparations with folic acid alone or in combination with other vitamins, such as vitamin B(12) and B(6), were used. OUTCOMES In retrospective studies, cases are patients with cardiovascular diseases. Outcomes for prospective observational and intervention studies are cardiovascular events and total mortality. RESULTS In retrospective studies, there was no significant overall difference in homocysteine concentrations between cases and controls (weighted mean difference in homocysteine, 2.82 micromol/L; 95% confidence interval [CI], -2.22 to 7.86; P = 0.3). The pooled overall risk estimate for prospective observational studies suggests no association between homocysteine level (5-micromol/L increase) and total mortality (hazard ratio [HR], 1.02; 95% CI, 0.93 to 1.12; P = 0.7), but there was an association with cardiovascular events (HR, 1.09; 95% CI, 1.03 to 1.14; P = 0.001). In subgroup analysis of patients not receiving vitamins, an increase in homocysteine level was associated with increased mortality (HR, 1.07; 95% CI, 1.02 to 1.13; P = 0.01). For intervention trials with B vitamins, there was a significant risk reduction for cardiovascular disease (relative risk, 0.73; 95% CI, 0.56 to 0.94; P = 0.02), but no risk reduction for total mortality or the composite end point including total mortality (relative risk, 1.01; 95% CI, 0.88 to 1.15; P = 0.9). LIMITATIONS Many studies are small, which may lead to the observed heterogeneity. Some intervention trials are neither placebo controlled nor randomized. Separate analyses for specific end points and patients treated by means of hemodialysis or peritoneal dialysis were not possible. CONCLUSION Total homocysteine level may be a risk factor for cardiovascular events and total mortality in patients with end-stage renal disease not receiving vitamin supplementation or folic acid food fortification. There may be a potential for reducing cardiovascular disease in this population by folic acid supplementation.