Elimination of fosfomycin during dialysis with the Genius system in septic patients.

To assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily SLEDD sessions of eight hours. FOS was applied i.v. at doses of 3 × 5 g per day. FOS serum levels were measured pre- and post hemofilter before, during, and after SLEDD sessions, and instantaneous clearance was calculated. In five of the patients, we analyzed FOS levels after the first dose, in the other five patients serum levels were measured during ongoing therapy. FOS was eliminated rapidly via the hemofilter. FOS clearance decreased from 152 ± 10 mL/min (start of SLEED session) to 43 ± 38 mL/min (end of SLEDD session). In 3/5 first-dose patients after 4-6 h of SLEDD the FOS serum level fell below the EUCAST breakpoint of 32 mg/L for Enterobacterales and Staphylococcus species. In all patients with ongoing fosfomycin therapy serum levels were high and above the breakpoint at all times. FOS toxicity or adverse effects were not observed. FOS serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI. FOS is eliminated rapidly during SLEDD. A loading dose of 5 g is not sufficient to achieve serum levels above the EUCAST breakpoint for common bacteria in all patients, considering that T > MIC > 70% of the dosing interval indicates sufficient plasma levels. We thus recommend a loading dose of 8 g followed by a maintenance dose of 5 g after a SLEDD session in anuric patients. We strongly recommend therapeutic drug monitoring of FOS levels in critically ill patients with AKI and dialysis therapy.

Being Born Large for Gestational Age is Associated with Increased Global Placental DNA Methylation.

Being born small (SGA) or large for gestational age (LGA) is associated with adverse birth outcomes and metabolic diseases in later life of the offspring. It is known that aberrations in growth during gestation are related to altered placental function. Placental function is regulated by epigenetic mechanisms such as DNA methylation. Several studies in recent years have demonstrated associations between altered patterns of DNA methylation and adverse birth outcomes. However, larger studies that reliably investigated global DNA methylation are lacking. The aim of this study was to characterize global placental DNA methylation in relationship to size for gestational age. Global DNA methylation was assessed in 1023 placental samples by LC-MS/MS. LGA offspring displayed significantly higher global placental DNA methylation compared to appropriate for gestational age (AGA; p < 0.001). ANCOVA analyses adjusted for known factors impacting on DNA methylation demonstrated an independent association between placental global DNA methylation and LGA births (p < 0.001). Tertile stratification according to global placental DNA methylation levels revealed a significantly higher frequency of LGA births in the third tertile. Furthermore, a multiple logistic regression analysis corrected for known factors influencing birth weight highlighted an independent positive association between global placental DNA methylation and the frequency of LGA births (p = 0.001).

[New kidney function tests: Renal functional reserve and furosemide stress test]. / Neue Nierenfunktionstests: Renal-funktionelle Reserve und Furosemidstresstest.

Acute kidney injury (AKI) occurs in 30-50% of all intensive care patients. Renal replacement therapy (RRT) has to be initiated in 10-15%. The early in-hospital mortality is about 50%. Up to 20% of all survivors develop chronic kidney disease after intensive care discharge and progress to end-stage kidney disease within the next 10 years. For timely initiation of prophylactic or therapeutic interventions, it is crucial to exactly determine the actual kidney function, i. e., glomerular filtration rate (GFR), and to gain insight into the further development of kidney function. Traditionally, renal function has been estimated using serum levels of creatinine or urea. Unfortunately, both are notoriously unreliable and insensitive in intensive care patients. Cystatin C has fewer non-GFR determinants when compared to creatinine and is more sensitive and accurate to detect early decreases of GFR. At present, new functional tests are discussed, namely the furosemide stress test (FST) and renal functional reserve (RFR). The FST consists of an intravenous infusion of 1.0-1.5 mg/kgBW furosemide to critically ill patients with AKI. An increase in urine output to >100 ml/h is indicative of a GFR >20 ml/min and almost certainly excludes progression to AKI stage III and need for RRT. Estimation of RFR can be made by short-term oral or intravenous administration of a high protein load. A subsequent increase in GFR defines the presence and the magnitude of functional reserve which can be activated. Loss of RFR is an indicator of loss of functioning nephron mass and incomplete recovery following AKI. Both FST and RFR can help to improve diagnosis and care of high-risk patients with acute and chronic kidney disease.

Late Steroid Withdrawal Following AB0-Incompatible Renal Transplantation.

BACKGROUND: Current evidence on steroid withdrawal following AB0-incompatible (AB0i) renal transplantation is low. We compared clinical outcomes of patients who agreed to late steroid withdrawal and patients who remained on steroid treatment. METHODS: Steroid withdrawal was carried out in 11 patients at ≥12 months after transplantation (group W). For comparison, we analyzed 19 patients who remained on triple immunosuppression including steroids (group M). Minimum follow-up was 24 months following transplantation and 12 months after steroid withdrawal. RESULTS: Baseline characteristics, including observation times, were not different between groups W and M. Graft survival was 100% in group W compared with 84% (16/19) in group M (P = .15). In group M, 1 patient experienced graft failure because of suspected antibody-mediated rejection (ABMR) following temporary cessation of mycophenolate treatment after a diagnosis of cryptococcal pneumonia. Two patients died with functioning graft because of sepsis. In group W, we observed 1 episode of ABMR following steroid withdrawal. At the end of follow-up, estimated glomerular filtration rates (eGFR) were 54 (19-91) versus 60 (15-85) mL/min/1.73 m2 in group W versus M, respectively (P = .67). CONCLUSIONS: Late steroid withdrawal following AB0i transplantation is feasible at a moderate risk of rejection. We recommend close monitoring of renal function and HLA antibodies during and after steroid withdrawal. On the other hand, the occurrence of severe infections causing death and graft loss in patients on triple maintenance immunosuppression including steroids should remind us to consider the overall immunosuppressive burden.

Increased global placental DNA methylation levels are associated with gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. It is known that GDM is associated with an altered placental function and changes in placental gene regulation. More recent studies demonstrated an involvement of epigenetic mechanisms. So far, the focus regarding placental epigenetic changes in GDM was set on gene-specific DNA methylation analyses. Studies that robustly investigated placental global DNA methylation are lacking. However, several studies showed that tissue-specific alterations in global DNA methylation are independently associated with type 2 diabetes. Thus, the aim of this study was to characterize global placental DNA methylation by robustly measuring placental DNA 5-methylcytosine (5mC) content and to examine whether differences in placental global DNA methylation are associated with GDM. METHODS: Global DNA methylation was quantified by the current gold standard method, LC-MS/MS. In total, 1030 placental samples were analyzed in this single-center birth cohort study. RESULTS: Mothers with GDM displayed a significantly increased global placental DNA methylation (3.22 ± 0.63 vs. 3.00 ± 0.46 %; p = 0.013; ±SD). Bivariate logistic regression showed a highly significant positive correlation between global placental DNA methylation and the presence of GDM (p = 0.0009). Quintile stratification according to placental DNA 5mC levels revealed that the frequency of GDM was evenly distributed in quintiles 1-4 (2.9-5.3 %), whereas the frequency in the fifth quintile was significantly higher (10.7 %; p = 0.003). Bivariate logistic models adjusted for maternal age, BMI, ethnicity, recurrent miscarriages, and familiar diabetes predisposition clearly demonstrated an independent association between global placental DNA hypermethylation and GDM. Furthermore, an ANCOVA model considering known predictors of DNA methylation substantiated an independent association between GDM and placental DNA methylation. CONCLUSIONS: This is the first study that employed a robust quantitative assessment of placental global DNA methylation in over a thousand placental samples. The study provides large scale evidence that placental global DNA hypermethylation is associated with GDM, independent of established risk factors.

The hyperechoic zone around breast lesions - an indirect parameter of malignancy.

PURPOSE: To evaluate an irregular perilesional hyperechoic zone as a potential criterion of malignancy on breast ultrasound and to test whether this zone correlates with perilesional T2 hyperintensity on magnetic resonance imaging (MRI). MATERIALS AND METHODS: A total of 137 patients (85 malignant lesions, 52 benign lesions) who underwent breast ultrasound with a 9 - 14 MHz linear broad-spectrum transducer and consecutive ultrasound-guided biopsy were included. All patients additionally underwent breast MR imaging with dedicated breast coils at 1.5 T. The protocol included a T2-weighted sequence. Perilesional hyperechoic and T2 hyperintense areas were measured by planimetry using the slice showing maximum extension of this area. The sensitivity and specificity of the perifocal area for identifying breast malignancy were determined using ROC analysis. Correlation was assessed using Pearson analysis. RESULTS: The presence of a hyperechoic zone identified malignancy with a sensitivity of 87% and a specificity of 81%. Additionally, there was a highly significant correlation of the size of the hyperechoic zone with the degree of tumor differentiation (p = 0.002) as well as with the mib-1 proliferation index (p = 0.006) and lymphangio-invasion (p = 0.02). No significant correlation was found between the hyperchoic zone and the T2 hyperintense zone on MRI (R2 = 0.16). CONCLUSION: A hyperechoic zone surrounding breast lesions may serve as an additional sonomorphologic criterion of malignancy. Yet, it does not seem to correlate with edema on MRI.

[Real-time MRI/US fusion-guided biopsy improves detection rates of prostate cancer in pre-biopsied patients]. / Die Echtzeit-MRT/US-Fusionsbiopsie verbessert die Detektionsrate des Prostatakarzinoms nach mehrfach negativen Vorbiopsien.

BACKGROUND: According to the guidelines of the European Association of Urology (EAU) on prostate cancer (PCa) in 2013, patients with increasing prostate-specific antigen (PSA) levels, suspicious digital rectal examination (DRE) or high-grade prostatic intraepithelial neoplasia after negative prostate biopsy (PB) should undergo a repeat biopsy. Low cancer detection rates in the repeat biopsy illuminate the dilemma of the international gold standard of transrectal ultrasound (TRUS) guided PB in the detection of PCa. Our study evaluated the combination of TRUS and prostate magnetic resonance imaging (MRI) and its reported high sensitivities and high specificities by using real-time MRI/US fusion-guided biopsy. The detection of clinically significant PCa was investigated. MATERIAL AND METHODS: 128 consecutive patients in the period of January 2012 to August 2013 were included. All patients had at least one TRUS-guided biopsy with negative findings and the clinical indication for a systematic re-biopsy. Prior to the MRI/US fusion all patients underwent a 3 Tesla prostate MRI without endorectal coil. The MRI data were uploaded to a modern US system. The B-mode, power-mode, elastography and CEUS imaging were used to classify the suspicious lesions from the MRI on a scale of 0-3 and a US sum score was calculated. The lesion was consecutively biopsied by real-time MRI/US fusion followed by a systematic 10 core biopsy. RESULTS: Among 128 patients 51 PCa could be detected (39.8%). From these 51 PCa cases, clinically significant PCa was detected by MRI/US fusion-guided biopsy as follows: Gleason score >7 in 9 of 10 patients; Gleason score=7 in 14 of 20 patients and Gleason score <7 in 13 of 21 patients. A positive correlation was shown between the US sum score and the associated PI-RADS score in 65 patients in whom lesions were classified by PI-RADS. A positive correlation was further shown between the US sum score and the Gleason score of all suspicious and biopsied lesions. MRI/US fusion and TRUS-guided biopsy combined, detected 30 of 51 PCa; 6 of 51 PCa were detected by MRI/US fusion alone and 15 of 51 PCa by conventional TRUS-guided biopsy alone. CONCLUSION: Real-time MR/US fusion increases detection rates of PCa in patients undergoing repeat biopsy. Especially, clinically significant PCa with a Gleason score ≥ 7 were almost exclusively detected by MR/US fusion-guided biopsy.

Detection of microcalcifications in women with dense breasts and hypoechoic focal lesions: comparison of mammography and ultrasound.

PURPOSE: Microcalcifications in the breasts can point to breast cancer. However, there is great morphologic variety, and microcalcifications do not always correlate with malignancy. We conducted a prospective study to compare ultrasound and mammography in the detection of microcalcifications following sonographic diagnosis of a hypoechoic focal lesion in women with dense breast composition. MATERIALS AND METHODS: A total of 104 lesions potentially associated with microcalcifications (82 malignant and 23 benign lesions) were included in the study. The breast was examined by ultrasound (9 MHz, Aplio XG/500) with additional use of MicroPure imaging for the demonstration and evaluation of microcalcifications. The presence of a focal lesion was verified and microcalcifications were counted at ultrasound and mammography by blinded readers. The sensitivity and specificity were determined, and ROC analysis and AUC analysis were performed. RESULTS: The women had a median age of 51 years. The average number of microcalcifications detected by sonography (2.12 ±â€Š2.77) and mammography (3.59 ±â€Š6.35) was not significantly different (p > 0.05). Correlation of the techniques was adequate (Pearson's r = 0.616, p < 0.0001; Spearman's rho = 0.654, p < 0.0001). The intraclass correlation coefficient was K = 0.382 ±â€Š0.072 (p < 0.0001), also indicating adequate agreement of both techniques. The sensitivity and specificity were 70%/30% for MicroPure and 45%/55% for mammography. The positive predictive value of mammography was superior to that of MicroPure (88% vs. 78%). CONCLUSION: The sonographic detection of microcalcifications with MicroPure imaging in breasts with a hypoechoic focal lesion correlates well with digital mammography.

[Detection of prostate cancer by real-time MR/ultrasound fusion-guided biopsy: 3T MRI and state of the art sonography]. / Detektion des Prostatakarzinoms durch Echtzeit-MRT/US-Fusionsbiopsie: 3T MRT und moderne Ultraschalltechnik.

PURPOSE: Multiparametric MRI of the prostate is a noninvasive diagnostic method with high sensitivity and specificity for prostate cancer. The aim of this study is to evaluate whether prostate cancer detection rates of transrectal ultrasound (TRUS)-guided biopsy may be improved by an image fusion of state-of-the-art ultrasound (CEUS, elastography) and MR (T2w, DWI) imaging. MATERIALS AND METHODS: 32 consecutive patients with a history of elevated PSA levels and at least one negative TRUS-guided biopsy with clinical indication for a systematic re-biopsy underwent multiparametric 3 T MRI without endorectal coil. MR data (T2w) were uploaded to a modern sonography system and image fusion was performed in real-time mode during biopsy. B-mode, Doppler, elastography and CEUS imaging were applied to characterize suspicious lesions detected by MRI. Targeted biopsies were performed in MR/US fusion mode followed by a systematic standard TRUS-guided biopsy. Detection rates for both methods were calculated and compared using the Chi²-test. RESULTS: Patient age was not significantly different in patients with and without histologically confirmed prostate cancer (65.2 ± 8.0 and 64.1 ± 7.3 age [p = 0.93]). The PSA value was significantly higher in patients with prostate cancer (15.5 ± 9.3 ng/ml) compared to patients without cancer (PSA 10.4 ± 9.6 ng/ml; p = 0.02). The proportion of histologically confirmed cancers in the study group (n = 32) of the MR/US fusion biopsy (11/12; 34.4 %) was significantly higher (p = 0.01) in comparison to the TRUS systematic biopsy (6/12; 18.8 %). CONCLUSION: Real-time MR/US image fusion may enhance cancer detection rates of TRUS-guided biopsies and should therefore be studied in further larger studies.

Outcome of expanded criteria donor kidneys that were transplanted at other Eurotransplant centers after being rejected by our institution.

PURPOSE: There is a growing discrepancy between the demand for renal transplants and the number of transplants conducted. For the many patients on the renal transplant waiting list, this means increased dialysis-associated morbidity, mortality and a reduced quality of life. The aim of this study was to ascertain whether it is justifiable for transplant centers to reject cadaveric donor organs on hand of marginal organ quality. METHODS: We identified 110 kidneys that were primarily rejected for transplantation at Charité Universitätsmedizin Berlin, Campus Mitte, and later transplanted at another center within the Eurotransplant zone. Using data from the Collaborative Transplant Study, we analyzed various demographic donor data including cold ischemia times, as well as graft and recipient outcomes. RESULTS: The median follow-up was 54 months. The cold ischemia time averaged 16 h. The organs that were primarily rejected by our center and then transplanted at other Eurotransplant centers showed 31 % of recipients had creatinine levels under 1.47 mg/dl and 94 % had levels under 2.97 mg/dl at 3-year follow-up. The mean death-censored graft survival was 71.4 months. The mean renal transplant recipient survival was 87.5 months. CONCLUSIONS: Based on our findings, we propose that acceptance criteria for marginal donor kidneys need to be widened.

[Sonographic detection of microcalcifications - potential of new method]. / Sonografische Mikrokalkdetektion - Potenzial einer neuen Methode.

PURPOSE: Does the easier microcalcification detection (EMD) method enable sonographic visualization of microcalcifications in breast core biopsy specimens compared with mammography? MATERIALS AND METHODS: In a prospective randomized study, 105 core biopsy specimens obtained with stereotactic guidance were examined by mammography and ultrasound. EMD is integrated in a high-end ultrasound system and uses three level settings (0 - 2 blue, 3 - 5 violet, and 6 - 8 black-and-white; 14 MHz). Detection of microcalcifications per core specimen was determined for ultrasound and mammography. EMD image quality was rated on a scale of 1 - 9. ANOVA and Sidak post-hoc testing, Pearson regression analysis (r), and Spearman rank correlation (rho) were performed. The intraclass correlation coefficient (ICC) was calculated, and an ROC analysis was conducted. RESULTS: The blue color map 1 was assigned the highest mean score of 1.5 ± 0.7 (p< 0.05 compared with black-and-white and violet). There was good correlation between the two modalities (r= 0.708 and rho= 0.694) with detection of 3.5 ± 3.1 microcalcifications per specimen by ultrasound versus 4.3 ± 4.8 by mammography (p> 0.05). The ICC of 0.773 indicates little disagreement between the two modalities. ROC analysis showed mammography to be superior to ultrasound compared with histological detection of microcalcifications (AUC= 0.837 vs. AUC= 0.728). CONCLUSION: Sonographic detection of microcalcifications in stereotactic biopsy specimens using the EMD method correlates well with digital mammography. Mammography is slightly superior.

Significant differentiation of focal breast lesions: raw data-based calculation of strain ratio.

PURPOSE: We compared elastography, B-mode ultrasound and mammography to determine whether raw data calculation of strain ratios (SRs) can further improve the differentiation of focal breast lesions. MATERIALS AND METHODS: 201 women with histologically proven focal breast lesions (85 benign, 116 malignant) were included at two German breast centers. Patients underwent a standardized ultrasound procedure using high-end ultrasound system with a 9-MHz broadband linear transducer. Two experienced readers analyzed the B-mode scans and mammograms using the BI-RADS criteria, while elastograms were analyzed using the Tsukuba score. SRs were calculated from a tumor-adjusted ROI and a comparable ROI placed in the lateral fatty tissue. The sensitivity, specificity, and cutoff values were calculated for SRs (ROC analysis). RESULTS: The median age was 53 years. The sensitivity and specificity were 85 %/ 60 % for B-mode scanning, 85 %/ 68 % for elastography, 78 %/ 62 % for mammography, and 95 %/ 74 % for SRs. An SR cutoff value of 2.27 (AUC 0.907) allowed significant differentiation (p < 0.001) between malignant and benign lesions. The quantitative SR calculation was superior to subjective interpretation of B-mode scans and sonoelastograms with a positive predictive value of 83 % versus 78 % and 74 %, and equal to mammograms. CONCLUSION: Strain ratio calculation contributes to the standardization of sonoelastography with high sensitivity and allows significant differentiation between benign and malignant breast lesions with a higher specificity compared to B-mode, subjective evaluation of elastography and mammography.

Plasma pharmacokinetics of daptomycin in critically ill patients with renal failure and undergoing CVVHD.

BACKGROUND: Daptomycin is a novel antibiotic with primarily renal elimination. METHODS: In an open-label, prospective trial, the pharmacokinetics of daptomycin after single (8 mg/kg BW) and multiple intravenous doses (4 mg/kg BW) at steady state were determined in critically ill, dialysis-dependent patients treated with continuous veno-venous hemodialysis (CVVHD). Daptomycin levels were determined by HPLC. Subjects with normal renal function received one dose of 4 mg/kg BW of daptomycin. RESULTS: In the normal controls, daptomycin administration resulted in a mean maximum concentration (Cmax) of 60.7 ± 10.7 mg/l and an area under the time-versus-concentration curve from 0 to 24 h (AUC0-24) of 402 ± 56 mg × h/l. In the CVVHD-treated patients, a loading dose of 8 mg/kg lead to Cmax of 87.5 ± 15.0 mg/l, AUC0-24 of 537 ± 97 mg × h/l and AUC24-48 of 193 ± 69 mg × h/l, respectively. After multiple doses of 4 mg/kg every 48 h, Cmax was 41.8 ± 5.0 mg/l, AUC0-24 302 ± 43 mg × h/l and AUC 24-48 h 102 ± 24 mg × h/l, respectively. Approximately 40% of the daptomycin dose administered was removed by CVVHD. Mean plasma half-lives of daptomycin in patients were 2 - 3 times longer than in healthy controls. CONCLUSIONS: The dosing regimen of 4 mg/kg TBW of daptomycin administered to CVVHD patients every 48 h is inappropriate to achieve effective antimicrobial plasma concentrations of daptomycin in the second half of the dosing interval (24 - 48 h). Doses of ≥ 4 mg/kg TBW administered intravenously every 24 h are necessary in CVVHD patients to assure that plasma daptomycin levels are comparably high to subjects with normal renal function and to avoid underdosing.

Relationship between fetal head station established using an open magnetic resonance imaging scanner and the angle of progression determined by transperineal ultrasound.

OBJECTIVE: We investigated the correlation between the angle of progression measured by transperineal ultrasound and fetal head station measured by open magnetic resonance imaging (MRI), the gold standard, in pregnant women at full term. METHODS: Thirty-one pregnant women at full term with a fetus in the occipitoanterior position were enrolled. First, the distance between the leading part of the skull and the interspinal plane was obtained using an open MRI system with the patient in a supine position. Immediately after MRI, the angle of progression was obtained by transperineal ultrasound without changing the woman's posture. RESULTS: There was a significant correlation between the angle of progression determined by transperineal sonography and the distance between the presenting fetal part and the level of the maternal ischial spines (y = - 0.51x + 60.8, r(2) = 0.38, P < 0.001). None of the fetal heads was engaged at the time of MRI and ultrasound examinations. CONCLUSIONS: The present study demonstrated a predictable relationship between the angle of progression obtained by transperineal ultrasound and the traditional scale used to quantify fetal head descent. Based on our results, station 0 would correspond to a 120° angle of progression. However, this correlation is based on statistical assumptions only and has to be proven in future studies.

Multicenter study of ultrasound real-time tissue elastography in 779 cases for the assessment of breast lesions: improved diagnostic performance by combining the BI-RADS®-US classification system with sonoelastography.

PURPOSE: Hitachi real-time tissue elastography (HI-RTE) is an ultrasound technique that facilitates the estimation of tissue elasticity. Our study evaluates whether sonoelastography improves the differentiation of benign and malignant breast lesions. MATERIALS AND METHODS: In a multicenter approach sonoelastography of focal breast lesions was carried out in 779 patients with subsequent histological confirmation. We present data from 3 study centers (Berlin, Bielefeld, Homburg/Saar) focusing on the sensitivity (SE), specificity (SP) and the positive (PPV) and negative predictive value (NPV) of sonoelastography. In addition we performed an analysis of the diagnostic performance, expressed by the pretest and posttest probability of disease (POD), in BI-RADS®-US 3 or 4 lesions as these categories can imply both malignant and benign lesions and a more precise prediction would be a preferable aim. RESULTS: Sonoelastography demonstrated an improved SP (89.5 %) and an excellent PPV (86.8 %) compared to B-mode ultrasound (76.1 % and 77.2 %). Especially in dense breasts ACR III-IV, the SP was even higher (92.8 %). In BI-RADS-US 3 lesions, a suspicious elastogram significantly modified the POD from 8.3 % to a posttest POD of 45.5 %. In BI-RADS-US 4 lesions, we found a pretest POD of 56.6 %. The posttest POD changed significantly to 24.2 % with a normal elastogram and to 81.5 % with a suspicious elastogram. CONCLUSION: Our data demonstrates that the complementary use of sonoelastography definitely improves the performance in breast diagnostics. Finally we present a protocol of how sonoelastography can be integrated into our daily practice.

Differentiation of parotid gland tumors with contrast-enhanced ultrasound.

PURPOSE: Pilot study to evaluate a new ultrasound (US) technique for differentiating parotid cystadenolymphoma (CL) from pleomorphic adenoma (PA). MATERIALS AND METHODS: 27 patients presenting with a palpable lesion of the parotid gland were examined by B-mode US. All patients underwent US examination with administration of 2.4 ml US contrast medium (USCM). The intratumoral time-to-peak was determined. The contrast medium inflow curves from the tumor and parotid parenchyma were compared by using AUC analysis and compared with histology. RESULTS: Histology demonstrated cystadenolymphoma in 9 cases (CL group) and pleomorphic adenoma in 9 (PA group). The intratumoral time-to-peak in the PA group was markedly longer than in the CL group (26.8 +/- 11.1 sec versus 22.6 +/- 5.1 sec, p < 0.05). AUC analysis for the tumor area demonstrated a significant difference between the PA group (30.3 +/- 24.3 dB/area) and the CL group (77.4 +/- 45.6 dB/area, p < 0.05). CONCLUSION: The standardized analysis of USCM inflow curves has the potential to differentiate cystadenolymphoma and pleomorphic adenoma. More patient numbers, perhaps with blinded readers, would allow reliable diagnostic determination for future studies.

Impact of maternal endothelial nitric oxide synthase gene polymorphisms on blood pressure, protein excretion and fetal outcome in pregnancy.

A genetic association study was conducted to assess whether genetically determined alterations of the nitric oxide system are associated with clinical markers of pre-eclampsia. A large number of Caucasian women were consecutively included after delivery and genotyped for the endothelial nitric oxide synthase gene (NOS3) polymorphisms G894T, T789C (n=1502) and intron 4a/b (n=2186). There are no significant differences in mean blood pressure (BP), protein excretion or new-onset peripheral oedema between any of the genotypes over the course of pregnancy. Neither particular haplotypes nor the combined presence of any two alleles is associated with those markers of pre-eclampsia. The maternal polymorphisms do not seem to influence fetal growth, birth weight or the incidence of congenital malformations. We demonstrate in a large Caucasian population that maternal polymorphisms of the NOS3 gene are not related to clinical markers of pre-eclampsia. The functional relevance of the NOS3 variants alone does not seem to be strong enough to affect BP regulation during pregnancy.

Citrate anticoagulation protocol for slow extended hemodialysis with the Genius dialysis system in acute renal failure.

BACKGROUND: The Genius dialysis system is increasingly used as an intermittent hemodialysis device in the setting of acute renal failure. Slow extended hemodialysis is preferred in the case of critical ill patients. In this study we established a safe and feasible citrate anticoagulation protocol for slow extended hemodialysis (SLED) with the Genius system. METHODS: We compared six anticoagulation protocols using SLED in 34 critically ill patients with acute renal failure. One group (A) received only citrate anticoagulation. Four groups (B - D) were treated with citrate and different additional systemic anticoagulation. Patients in the last group (F) were anticoagulated with heparin and were free of citrate anticoagulation. The total number of treatments was 103. A 4% sodium citrate solution was infused into the arterial line of the dialysis device for citrate anticoagulation. The dialysis solution contained one mmol/L of calcium. No additional calcium supplementation was done. We monitored electrolyte, acid-base and cardiovascular status prospectively. RESULTS: Hemodialysis was well tolerated hemodynamically. Electrolytes remained stable throughout hemodialysis in all groups. The decrease in ionized and total calcium was within the expected, clinically acceptable range. Bicarbonate and pH levels increased during dialysis, especially if citrate was used. CONCLUSIONS: Slow extended Genius hemodialysis with citrate is well tolerated and offers a safe and effective alternative to systemic anticoagulation.

Arrival time parametric imaging: a new ultrasound technique for quantifying perfusion of kidney grafts.

PURPOSE: Evaluation of a new standardised ultrasound (US) technique for diagnosis of acute rejection of kidney grafts. MATERIALS AND METHODS: Twenty-two kidney recipients underwent US examination following administration of 1.6 ml US contrast medium (USCM, SonoVue) 6 days after kidney transplantation. The examinations were performed with the Aplio US system (Toshiba). The difference in time to the first increase in signal intensity between the renal artery and the renal cortex was determined. Subsequently, the temporal course of contrast enhancement in the area of the renal artery following the first peak was recorded over 10 sec and depicted in colour using a Windows-based software. The resulting colour-time-images were evaluated by three readers who rated the images on an analogue scale from 1 (normal) to 5 (abnormal). RESULTS: 12 of the 22 patients had an uneventful clinical course. US demonstrated rapid inflow of the USCM into the renal cortex. The calculated time difference was 1.0 +/- 0.4 sec. The score assigned to the parametric images was 1.7 +/- 0.8. 8 of the 22 patients underwent biopsy and showed histologically proven rejection. The time difference in the rejection group was twice as high as in the normal group (2.2 +/- 0.7 sec, p < 0.05). The scores were in the abnormal range (3.7 +/- 1.6, p < 0.05). Two patients with perirenal haematoma also had high scores, without rejection. CONCLUSIONS: Acute rejection and perirenal haematoma are associated with a delayed signal increase in the renal cortex. This information can be provided with a single image with standardised colour display of the temporal course of USCM inflow.

[Image quality and characterisation of sonographically detected breast lesions: comparison of tissue harmonic imaging alone and in combination with frequency compounding]. / Steigerung der Bildqualität bei der Dignitätsbeurteilung mammasonografischer Herde mittels Frequenz-Compounding.

PURPOSE: To determine the accuracy of frequency compounding (FC) in detection and characterisation of breast lesions by ultrasound (US) and to assess the image quality in direct comparison with tissue harmonic imaging (THI). MATERIALS AND METHODS: A total of 60 breast lesions were examined; these were malignant in 39 cases and benign in 21 as confirmed by histology of core biopsy specimens (Aplio 80, Toshiba, Otawara, Japan). A total of 120 freeze frames, 60 B-mode scans with THI and 60 scans with FC were assessed by three independent examiners, who determined the presence of pathology on a scale of 1 to 5 using established criteria (BI-RADS classification). Image quality of each technique was rated on a ranking scale of - 2 (FC clearly superior to THI), - 1 (FC slightly superior to THI), 0 (identical), + 1 (THI slightly superior to FC), to + 2 (THI clearly superior to FC). The different US techniques were compared in terms of image quality and diagnostic accuracy using Mann Whitney U test and ROC analysis. RESULTS: The results for image quality were as follows: - 0.56 +/- 0.71. In 56 % of the images FC was superior to THI, both techniques were identical in 37 % of cases, and in only 7 % THI was superior to FC. The following AUCs (Area under Curve, presence of pathology) were calculated: 0.945 and 0.969 for THI and FC, respectively (not significant). The two US techniques had comparable sensitivity (FC/THI 100/98 %) and specificity (FC/THI 76/74 %). CONCLUSION: Altogether, the diagnostic value of FC was comparable to that of THI with only slight differences. For ultrasound examinations of breast lesions, FC improves the image quality and conspicuity of pathology.