Does the kidney actually swell during an acute urinary tract obstruction?

BACKGROUND: The appearance of renal swelling during an acute obstruction of the urinary tract could be caused by hydronephrosis or an increase of the parenchymal volume. To the best of our knowledge no studies have been performed regarding renal parenchymal volume change during an acute urinary tract obstruction. PURPOSE: To investigate the change in renal parenchymal volume during an acute urinary tract obstruction and to correlate any such volume change to the degree of secondary signs of obstruction. MATERIAL AND METHODS: In total, 20 patients with obstructive ureterolithiasis were retrospectively and randomly included. Two observers measured the parenchymal volume of the obstructed and the contralateral kidney in CT examinations before, during, and after obstruction. Hydronephrosis, hydroureter, perirenal stranding, and thickening of the renal fascia were graded and correlated to volume change. RESULTS: A decreased volume was noted after obstruction in the obstructed kidneys (-24%) (P < 0.0001) and in the contralateral kidneys (-5%) (P = 0.0110) with a positive correlation of change in volume (P = 0.011). The volume of the obstructed kidneys was larger than the contralateral kidneys during obstruction (P < 0.0001) but not after obstruction (P = 0.559). No significant difference in volume was found before compared to after obstruction. Secondary signs of obstruction did not correlate to volume change. CONCLUSION: The parenchymal volume increases in the obstructed kidneys as well as in the contralateral kidneys during obstruction. The increase in volume was larger in the obstructed kidneys compared to the contralateral kidneys. After obstruction the kidneys regained their original volume. Secondary signs did not correlate to volume change.

Patient compliance with Twin Block appliance during treatment of Class II malocclusion: a randomized controlled trial on two check-up prescriptions.

BACKGROUND: Compliance is crucial for the treatment outcome with removable appliances. Previous studies on treatment with the Twin Block appliance have focused on effectiveness in relation to other treatment methods or wear-time. Studies on different check-up intervals to improve compliance seem to be lacking. OBJECTIVES: To compare the impact of two different check-up prescriptions on patient compliance and treatment outcome during treatment with Twin Block. TRIAL DESIGN: Two-arm parallel group, single-centre, randomized controlled trial. MATERIALS AND METHODS: Seventy-three patients, 38 boys, and 35 girls, mean age 11.2 years, were included and block-randomized into two groups treated with a Twin Block appliance. Group 1 was called for check-up visit every sixth week and group 2 every fourth week. Compliance was evaluated with a TheraMon® microsensor, moulded into the appliance, measuring wear-time. Overjet, overbite, and molar relationships were assessed on study casts before and after treatment. The treatment outcomes were analysed on an intention-to-treat basis. RESULTS: In group 1, the reduction of overjet was 5.2 mm and the mean wear-time was 6.9 hours. In group 2, the reduction was 4.7 mm and the wear-time was 6.1 hours. Seventy-four per cent of the patients presented an overjet of 4 mm or less. Wear-time did not correlate to age, gender, or severity of malocclusion. HARMS: No harm was observed in any patient. Lateral open bites were registered during treatment but were normalized at the end of the treatment. LIMITATIONS: The trial was a single-centre study and long-term effects were not evaluated. CONCLUSIONS: During treatment with the Twin Block appliance, a 4-week check-up interval did not improve treatment outcome or increase wear-time, compared to a 6-week check-up interval. The mean wear-time was 6.5 hours per day, even if the recommendation was 12 hours. CLINICAL TRIAL REGISTRATION: NCT05155774.

Accuracy of iodine quantification using dual-energy computed tomography with focus on low concentrations.

BACKGROUND: Iodine quantification using dual-energy computed tomography (DECT) is helpful in characterizing, and follow-up after treatment of tumors. Some malignant masses, for instance papillary renal cell carcinomas (p-RCC), are hard to differentiate from benign lesions because of very low contrast enhancement. In these cases, iodine concentrations might be very low, and it is therefore important that iodine quantification is reliable even at low concentrations if this technique is used. PURPOSE: To examine the accuracy of iodine quantification and to determine whether it is also accurate for low iodine concentrations. MATERIAL AND METHODS: Twenty-six syringes with different iodine concentrations (0-30 mg I/mL) were scanned in a phantom model using a DECT scanner with two different kilovoltage and image reconstruction settings. Iodine concentrations were measured and compared to known concentration. Absolute and relative errors were calculated. RESULTS: For concentrations of 1 mg I/mL or higher, there was an excellent correlation between true and measured iodine concentrations for all settings (R = 0.999-1.000; P < 0.001). For concentrations <1.0 mg I/mL, the relative error was greater. Absolute and relative errors were smaller using tube voltages of 80/Sn140 kV than 100/Sn140 kV (P < 0.01). Reconstructions using a 3.0-mm slice thickness had less variance between repeated acquisitions versus 0.6 mm (P < 0.001). CONCLUSION: Iodine quantification using DECT was in general very accurate, but for concentrations < 1.0 mg I/mL the technique was less reliable. Using a tube voltage with larger spectral separation was more accurate and the result was more reproducible using thicker image reconstructions.

In vitro CT visualization of the biopsy location by filling the core biopsy needle with contrast media.

BACKGROUND: When performing computed tomography (CT)-guided biopsy procedures with non-disposable, automatic biopsy instruments, the actual course of the biopsy needle is not registered. PURPOSE: To evaluate the ability to visualize the sampling location after CT-guided biopsy in vitro using a novel method, where the space between the inner needle and the outer cannula in a core biopsy needle is filled with contrast media; and to compare the grade of visibility for two different concentrations of contrast media. MATERIAL AND METHODS: Core needle biopsies were performed in a tissue phantom using biopsy needles primed with two different iodine contrast media concentrations (140 mg I/mL and 400 mg I/mL). Commercially available needle-filling contraptions with sealing membranes were used to fill the needles. Each biopsy was imaged with CT, and the visibility was evaluated twice by three senior radiologists in a randomized order. RESULTS: The presence of traces was confirmed after biopsy, almost without exception for both concentrations. The visibility was sufficient to determine the biopsy location in all observations with the 400 mg I/mL filling, and in 7/10 observations with the 140 mg I/mL filling. The grade of visibility of the trace and the proportion of the biopsy needle course outlined were higher with the 400 mg I/mL filling. CONCLUSION: With CT-guided biopsy in vitro, the sampling location can be visualized using a novel method of priming the biopsy needle with iodine contrast media, specifically highly concentrated contrast media.

Addition of benzylpenicillin to antibiotic prophylaxis reduces deep sternal wound infection after cardiac surgery.

OBJECTIVES: In Sweden, cloxacillin is recommended as the sole antibiotic prophylaxis for prevention of surgical site infections after cardiac surgery. Cutibacterium acnes, formerly Propionibacterium acnes, has been shown to be present in the surgical wound. Formerly an overlooked pathogen, there are increasing reports that C acnes can cause surgical site infections, including sternal wound infections. Cloxacillin may not be optimal for prevention of C acnes infection, therefore benzylpenicillin was added to our routine intraoperative prophylaxis in 2015. The aim of this study was to investigate the effect of benzylpenicillin on incidence of sternal wound infection. METHODS: We included 3920 consecutive patients that underwent cardiac surgery via median sternotomy at our centre from 2009 thru 2018. All patients were followed up two months postoperatively. The rate of sternal wound infection before and after 2015 were compared. Logistic multivariable analysis was used to adjust for potential confounders. RESULTS: The mean incidence of sternal wound infection that required surgical revision decreased from 4.7% to 1.7% after addition of benzylpenicillin (p < 0.001). Significant decrease was seen in sternal wound infections caused by Coagulase negative staphylococci, either alone (p<0.001) or concomitant with C acnes (p=0.008). Addition of benzylpenicillin remained independently associated with the reduction of sternal wound infections in the multivariable analysis (OR=0.36 CI=0.23-0.56, p<0.001). CONCLUSIONS: Addition of benzylpenicillin was associated with a reduction in surgically treated infections and might be effective against infection caused by CoNS with and without co-infection by C acnes, although the exact underlying mechanism is unknown.

Open vs closed surgical exposure of palatally displaced canines: a comparison of clinical and patient-reported outcomes-a multicentre, randomized controlled trial.

OBJECTIVES: To compare treatment time, patients' perceptions during orthodontic treatment, dental fear and side effects, between open and closed surgical exposures in patients with palatally displaced canines (PDCs). TRIAL DESIGN: Multicentre, randomized controlled trial, with random 1:1 allocation of two parallel groups. MATERIALS AND METHODS: One hundred and twenty patients from three different orthodontic centres were randomized into one of the two intervention arms, open or closed surgical exposure. Both techniques had mucoperiosteal flaps raised and bone removed above the PDCs. In open exposure, tissue was removed above the canine, and glass ionomer - reaching above soft tissue - was built on the crown. The canine was then left to erupt spontaneously, prior to orthodontic alignment. At closed exposure, a chain was bonded to the canine and orthodontic traction was applied under the mucosa until eruption. Orthodontic alignment of the canines was undertaken after eruption into the oral cavity, with fixed appliances in both groups. All participants were treated according to intention to treat (ITT). BLINDING: Due to the nature of this trial, only outcome assessors could be blinded to the intervention group. RESULTS: One hundred and seventeen patients completed the trial. All PDCs were successfully aligned. Total treatment time was equal in the two techniques, mean difference -0.1 months (95% CI -3.2 to 2.9, P = 0.93). The closed group experienced more pain and discomfort during the active orthodontic traction. Dental fear, root resorption and periodontal status did not show any clinically significant differences between the groups. GENERALIZABILITY: Results of this randomized controlled trial (RCT) can be generalized only to a similar population aged 9-16 years, if exclusion criteria are met. CONCLUSION: The closed exposure group experienced more pain and discomfort mostly during active orthodontic traction. All other studied outcomes were similar between the two exposure groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02186548 and Researchweb.org, ID: 127201.

Translation and validation of the English-language instrument Orthognathic Quality of Life Questionair into Swedish.

INTRODUCTION: In orthognathic surgery, understanding the patient's motives for treatment is a key factor for postoperative patient satisfaction and treatment success. In countries/systems where orthognathic surgery is funded by public means, patients are referred mainly due to functional problems, although studies of quality of life related changes after treatment indicate that psychosocial and aesthetic reasons might be equal or more important for the patient. There is no available validated condition specific instruments in the Swedish language for quality of life evaluation of patients with dentofacial deformities. Aims/objectives: Cross cultural translation and adaptation of the English-language instrument 'Orthognathic Quality of Life Questionnaire' (OQLQ) into Swedish. Methods: OQLQ was translated into Swedish. A total of 121 patients in four groups were recruited and the Swedish version of the OQLQ (OQLQ-S) was tested by psychometric methods. Reliability was assessed by internal consistency and test-retest reliability. Validity was evaluated by face, convergent and discriminant validity. Results/findings and conclusions: OQLQ-S is reliable and showed good construct validity and internal consistency and can be used in a Swedish speaking population as a complement to clinical variables to evaluate patients with dentofacial deformity.

Split renal function after treatment of small renal masses: comparison between radiofrequency ablation and laparoscopic partial nephrectomy.

BACKGROUND: Radiofrequency ablation (RFA) and laparoscopic partial nephrectomy (LPN) are used to treat small renal masses (SRM; ≤4 cm), although there are conflicting results in the changes in creatinine and estimated glomerular filtration rate (eGFR) after treatment. On contrast-enhanced computed tomography (CE-CT) images, the quantity and quality of renal function can be evaluated by calculating the split renal function (SRF). PURPOSE: To compare renal function after RFA or LPN treatment of SRMs through evaluation of the SRF in the affected kidney. MATERIAL AND METHODS: Single T1a renal tumors successfully treated with RFA (n = 60) or LPN (n = 31) were retrospectively compared. The SRF was calculated on pre-treatment CE-CT images and the first follow-up exam after completed treatment. Serum creatinine and eGFR values were collected simultaneously. To compare renal function outcomes, Student's t-test and multivariable linear regression models (adjusted to RFA/LPN treatment, pre-treatment SRF/eGFR, BMI, age, tumor characteristics, and Charlson Comorbidity Index) were used. RESULTS: SRF was reduced in both groups, although reduction was greater in the LPN group (LPN -5.7%) than in the RFA group (RFA -3.5%; P = 0.013). After adjusted analysis, the LPN group still had greater SRF reduction (difference 3.2%, 95% confidence interval 1.3-1.5; P = 0.001). There was no difference between groups in the change of creatinine/eGFR after treatment. CONCLUSION: Both RFA and LPN are nephron-sparing when treating SRMs. However, in this series, reduction of SRF in the affected kidney was smaller after RFA, having a more favorable preservation of renal function than LPN.

Microwave ablation of 105 T1 renal tumors: technique efficacy with a mean follow-up of two years.

BACKGROUND: Thermal ablation (TA) with radiofrequency (RFA) or cryoablation (CA) are established treatments for small renal masses (≤4 cm). Microwave ablation (MWA) has several potential benefits (decreased ablation time, less susceptibility to heat-sink, higher lesion temperatures than RFA) but is still considered experimental considering the available small-sample studies with short follow-up. PURPOSE: To evaluate technique efficacy and complications of our initial experience of renal tumors treated using percutaneous MWA with a curative intent. MATERIAL AND METHODS: A total of 105 renal tumors (in 93 patients) were treated between April 2014 and August 2017. MWA was performed percutaneously with computed tomography (CT) guidance under conscious sedation (n=82) or full anesthesia. Patients were followed with contrast-enhanced CT scans at six months and yearly thereafter for a minimum of five years. The mean follow-up time was 2.1 years. The percentage of tumors completely ablated in a single session (primary efficacy rate) and those successfully treated after repeat ablation (secondary efficacy rate) were recorded. Patient and tumor characteristics as well as complications were collected retrospectively. RESULTS: The median patient age was 70 years and median tumor size was 25 mm. Primary efficacy rate was 96.2% (101/105 tumors). After including two residual tumors for a second ablation session, secondary efficacy was 97.1% (102/105). Periprocedural complications were found in 5.2% (5/95) sessions: four Clavien-Dindo I and one Clavien-Dindo IIIa. One postprocedural Clavien-Dindo II complication was found. CONCLUSION: MWA has high efficacy rates and few complications compared to other TA methods at a mean follow-up of two years.

Consultation on UTUC, Stockholm 2018 aspects of diagnosis of upper tract urothelial carcinoma.

PURPOSE: To summarize knowledge on upper urinary tract carcinoma (UTUC) regarding diagnostic procedures, risk factors and prognostic markers. METHODS: A scoping review approach was applied to search literature in Pubmed, Web of Science, and Embase. Consensus was reached through discussions at Consultation on UTUC in Stockholm, September 2018. RESULTS: Tumor stage and grade are the most important prognostic factors. CT urography (CTU) including corticomedullary phase is the preferred imaging modality. A clear tumor on CTU in combination with high-grade UTUC in urine cytology identifies high-risk UTUC, and in some cases indirect staging can be obtained. Bladder urine cytology has limited sensitivity, and in most cases ureterorenoscopy (URS) with in situ samples for cytology and histopathology are mandatory for exact diagnosis. Image-enhancing techniques, Image S1 and narrow-band imaging, may improve tumor detection at URS. Direct confocal laser endomicroscopy may help to define grade during URS. There is strong correlation between stage and grade, accordingly correct grading is crucial. The correlation is more pronounced using the 1999 WHO than the 2004 classification: however, the 1999 system risks greater interobserver variability. Using both systems is advisable. A number of tissue-based molecular markers have been studied. None has proven ready for use in clinical practice. CONCLUSIONS: Correct grading and staging of UTUC are mandatory for adequate treatment decisions. Optimal diagnostic workup should include CTU with corticomedullary phase, URS with in situ cytology and biopsies. Both WHO classification systems (1999 and 2004) should be used to decrease risk of undergrading or overtreatment.

Periprocedural outcome after laparoscopic partial nephrectomy versus radiofrequency ablation for T1 renal tumors: a modified R.E.N.A.L nephrometry score adjusted comparison.

BACKGROUND: Comparable oncological outcomes have been seen after surgical nephrectomy and thermal ablation of renal tumors recently. However, periprocedural outcome needs to be assessed for aiding treatment decision. PURPOSE: To compare efficacy rates and periprocedural outcome (technical success, session time, hospitalization time, and complications) after renal tumor treatment with laparoscopic partial nephrectomy (LPN) or radiofrequency ablation (RFA). MATERIAL AND METHODS: The initial experience with 49 (treated with LPN) and 84 (treated with RFA) consecutive patients for a single renal tumor (diameter ≤ 5 cm, limited to the kidney) during 2007-2014 was evaluated. Patient and tumor characteristics, efficacy rates, and periprocedural outcome were collected retrospectively. The stratified Mantel Haenzel and Van Elteren tests, adjusted for tumor complexity (with the modified R.E.N.A.L nephrometry score [m-RNS]), were used to assess differences in treatment outcomes. RESULTS: Primary efficacy rate was 98% for LPN and 85.7% for RFA; secondary efficacy rate was 93.9% for LPN and 95.2% for RFA; and technical success rate was 87.8% for LPN and 100% for RFA. Median session (m-RNS adjusted P < 0.001; LPN 215 min, RFA 137 min) and median hospitalization time were longer after LPN (m-RNS adjusted P < 0.001; LPN 5 days, RFA 2 days). Side effects were uncommon (LPN 2%, RFA 4.8%). Complications were more frequent after LPN (m-RNS adjusted P < 0.001; LPN 42.9%, RFA 10.7%). CONCLUSION: Both methods achieved equivalent secondary efficacy rates. RFA included several treatment sessions, but session and hospitalization times were shorter, and complications were less frequent than for LPN. The differences remained after adjustment for renal tumor complexity.

nanoDSF as screening tool for enzyme libraries and biotechnology development.

Enzymes are attractive tools for synthetic applications. To be viable for industrial use, enzymes need sufficient stability towards the desired reaction conditions such as high substrate and cosolvent concentration, non-neutral pH and elevated temperatures. Thermal stability is an attractive feature not only because it allows for protein purification by thermal treatment and higher process temperatures but also due to the associated higher stability against other destabilising factors. Therefore, high-throughput screening (HTS) methods are desirable for the identification of thermostable biocatalysts by discovery from nature or by protein engineering but current methods have low throughput and require time-demanding purification of protein samples. We found that nanoscale differential scanning fluorimetry (nanoDSF) is a valuable tool to rapidly and reliably determine melting points of native proteins. To avoid intrinsic problems posed by crude protein extracts, hypotonic extraction of overexpressed protein from bacterial host cells resulted in higher sample quality and accurate manual determination of several hundred melting temperatures per day. We have probed the use of nanoDSF for HTS of a phylogenetically diverse aldolase library to identify novel thermostable enzymes from metagenomic sources and for the rapid measurements of variants from saturation mutagenesis. The feasibility of nanoDSF for the screening of synthetic reaction conditions was proved by studies of cosolvent tolerance, which showed protein melting temperature to decrease linearly with increasing cosolvent concentration for all combinations of six enzymes and eight water-miscible cosolvents investigated, and of substrate affinity, which showed stabilisation of hexokinase by sugars in the absence of ATP cofactor. ENZYMES: Alcohol dehydrogenase (NADP+ ) (EC 1.1.1.2), transketolase (EC 2.2.1.1), hexokinase (EC 2.7.1.1), 2-deoxyribose-5-phosphate aldolase (EC 4.1.2.4), fructose-6-phosphate aldolase (EC 4.1.2.n).

Closed vs open surgical exposure of palatally displaced canines: surgery time, postoperative complications, and patients' perceptions: a multicentre, randomized, controlled trial.

Background: Closed and open surgical techniques are two different main approaches to surgical exposure of palatally displaced canines (PDCs). Because there is insufficient evidence to support one technique over the other, there is a need for randomized controlled trials. Objectives: To compare surgery time, complications and patients' perceptions between closed and open surgical techniques in PDCs. Trial design: The trial was a multicentre, randomized, controlled trial with two parallel groups randomly allocated in a 1:1 ratio. Material and methods: Study participants were 119 consecutive patients from 3 orthodontic centres, with PDCs planned for surgical exposure, randomly allocated according to a computer-generated randomization list, using concealed allocation. Full-thickness mucoperiosteal flap was raised, and bone covering the canine was removed in both interventions. In closed exposure, an attachment with a chain was bonded to the canine and the flap was sutured back with the chain penetrating the mucosa. In open exposure, a window of tissue around the tooth was removed and glass ionomer cement placed on the canine crown, to prevent gingival overgrowth during spontaneous eruption. Patient perceptions were assessed with two questionnaires, for the evening on the day of operation and 7 days post-surgery. Blinding: It was not possible to blind either patients or care providers to the interventions. The outcome assessors were blinded and were unaware of patients' intervention group. Results: Seventy-five girls and 44 boys, mean age 13.4 years (SD 1.46) participated in the study and got either of the interventions (closed exposure, n = 60; open exposure, n = 59). Surgery time did not differ significantly between the interventions. Complications though were more severe in bilateral cases and the patients experienced more pain and impairment in the open group. Conclusion: There were no statistically significant differences regarding surgery time between the groups. Postoperative complications were similar between the groups in unilateral PDCs, but more common in the open group in bilateral cases. More patients in the open group experienced pain and impairment compared to the closed group. Trial registration: Trial registration: ClinicalTrials.gov, ID: NCT02186548 and Researchweb.org, ID: 127201.

Predictive value of secondary signs of obstruction in follow-up computed tomography of ureteral stones: a study with dynamic computed tomography.

OBJECTIVES: This study aimed to determine the ratio of obstruction and predictive values of secondary signs in follow-up computed tomography (CT) of ureterolithiasis patients; to correlate stone characteristics with obstruction; to compare enhancement of obstructed and non-obstructed kidneys; and to compare radiation dose of the dynamic CT protocol to an excretory-phase protocol. MATERIALS AND METHODS: This retrospective study assessed 49 follow-up CT scans of patients with remaining ureterolithiasis after a renal colic episode. Obstruction was measured as time taken to excretion of contrast medium in dynamic CT. Degree of secondary signs of obstruction was evaluated from the unenhanced CT. Data were collected on patients' gender and age, stone size and location, time from renal colic to follow-up, attenuation of the renal cortex and radiation dose. RESULTS: Obstruction was present in 28% (n = 14) at follow-up. Predictive values (sensitivity, specificity, positive predictive value, negative predictive value) were calculated for hydronephrosis (1.0, 0.63, 0.52, 1.0), hydroureter (1.0, 0.4, 0.4, 1.0), perirenal stranding (0.21, 0.94, 0.6, 0.75), Gerota's fascia (0.21, 0.97, 0.75, 0.76) and renal swelling (0.21, 0.97, 0.75, 0.76). Obstruction was not correlated with stone characteristics. Enhancement was lower in obstructed kidneys (p < 0.01). Radiation dose was reduced by 43% (1.8 mSv). CONCLUSIONS: Obstruction was found in 28% of patients. Secondary signs were scarce and of indeterminate value to the diagnosis of obstruction. The absence of hydronephrosis and hydroureter contradicted obstruction. Stone characteristics were not correlated with obstruction. Enhancement of the renal cortex was lower in obstructed kidneys. The dynamic protocol reduced the radiation dose.

Intratumorally injected pro-inflammatory allogeneic dendritic cells as immune enhancers: a first-in-human study in unfavourable risk patients with metastatic renal cell carcinoma.

BACKGROUND: Accumulating pre-clinical data indicate that the efficient induction of antigen-specific cytotoxic CD8+ T cells characterizing viral infections is caused by cross-priming where initially infected DCs produce an unique set of inflammatory factors that recruit and activate non-infected bystander DCs. Our DC-based immunotherapy concept is guided by such bystander view and accordingly, we have developed a cellular adjuvant consisting of pre-activated allogeneic DCs producing high levels of DC-recruiting and DC-activating factors. This concept doesn't require MHC-compatibility between injected cells and the patient and therefore introduces the possibility of using pre-produced and freeze-stored DCs from healthy blood donors as an off- the-shelf immune enhancer. The use of MHC-incompatible allogeneic DCs will further induce a local rejection process at the injection site that is expected to further enhance recruitment and maturation of endogenous bystander DCs. METHODS: Twelve intermediate and poor risk patients with newly diagnosed metastatic renal cell carcinoma (mRCC) where included in a phase I/II study. Pro-inflammatory allogeneic DCs were produced from a leukapheresis product collected from one healthy blood donor and subsequently deep-frozen. A dose of 5-20 × 106 DCs (INTUVAX) was injected into the renal tumor twice with 2 weeks interval before planned nephrectomy and subsequent standard of care. RESULTS: No INTUVAX-related severe adverse events were observed. A massive infiltration of CD8+ T cells was found in 5 out of 12 removed kidney tumors. No objective tumor response was observed and 6 out of 11 evaluable patients have subsequently received additional treatment with standard tyrosine kinase inhibitors (TKI). Three of these 6 patients experienced an objective tumor response including one sunitinib-treated patient who responded with a complete and durable regression of 4 brain metastases. Median overall survival (mOS) is still not reached (currently 42.5 months) but has already passed historical mOS in patients with unfavourable risk mRCC on standard TKI therapy. CONCLUSIONS: Our findings indicate that intratumoral administration of proinflammatory allogeneic DCs induces an anti-tumor immune response that may prolong survival in unfavourable risk mRCC-patients given subsequent standard of care. A randomized, multi-center, phase II mRCC trial (MERECA) with INTUVAX in conjuction with sunitinib has been initiated. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01525017.

Directed evolution of P450cin for mediated electron transfer.

Directed evolution is a powerful method to optimize enzyme properties for application demands. Interesting targets are P450 monooxygenases which catalyze the stereo- and regiospecific hydroxylation of chemically inert C-H bonds. Synthesis employing P450s under cell-free reaction conditions is limited by low total turnover numbers, enzyme instability, low product yields and the requirement of the expensive co-factor NADPH. Bioelectrocatalysis is an alternative to replace NADPH in cell-free P450-catalyzed reactions. However, natural enzymes are often not suitable for using non-natural electron delivery systems. Here we report the directed evolution of a previously engineered P450 CinA-10aa-CinC fusion protein (named P450cin-ADD-CinC) to use zinc/cobalt(III)sepulchrate as electron delivery system for an increased hydroxylation activity of 1,8-cineole. Two rounds of Sequence Saturation Mutagenesis (SeSaM) each followed by one round of multiple site-saturation mutagenesis of the P450 CinA-10aa-CinC fusion protein generated a variant (Gln385His, Val386Ser, Thr77Asn, Leu88Arg; named KB8) with a 3.8-fold increase in catalytic efficiency (28 µM-1 min-1) compared to P450cin-ADD-CinC (7 µM-1 min-1). Furthermore, variant KB8 exhibited a 1.5-fold higher product formation (500 µM µM-1 P450) compared to the equimolar mixture of CinA, CinC and Fpr using NADPH as co-factor (315 µM µM-1 P450). In addition, electrochemical experiments with the electron delivery system platinum/cobalt(III)sepulchrate showed that the KB8 variant had a 4-fold higher product formation rate (0.16 nmol (nmol) P450-1 min-1 cm-2) than the P450cin-ADD-CinC (0.04 nmol (nmol) P450-1 min-1 cm-2). In summary, the current work shows prospects of using directed evolution to generate P450 enzymes suitable for use with alternative electron delivery systems.

Predictive factors for complete renal tumor ablation using RFA.

BACKGROUND: Radiofrequency ablation (RFA) can be used to treat renal masses in patients where surgery is preferably avoided. As tumor size and location can affect ablation results, procedural planning needs to identify these factors to limit treatment to a single session and increase ablation success. PURPOSE: To identify factors that may affect the primary efficacy of complete renal tumor ablation with radiofrequency after a single session. MATERIAL AND METHODS: Percutaneous RFA (using an impedance based system) was performed using computed tomography (CT) guidance. Fifty-two renal tumors (in 44 patients) were retrospectively studied (median follow-up, 7 months). Data collection included patient demographics, tumor data (modified Renal Nephrometry Score, histopathological diagnosis), RFA treatment data (electrode placement), and follow-up results (tumor relapse). Data were analyzed through generalized estimating equations. RESULTS: Primary efficacy rate was 83%. Predictors for complete ablation were optimal electrode placement (P = 0.002, OR = 16.67) and increasing distance to the collecting system (P = 0.02, OR = 1.18). Tumor size was not a predictor for complete ablation (median size, 24 mm; P = 0.069, OR = 0.47), but all tumors ≤2 cm were completely ablated. All papillary tumors and oncocytomas were completely ablated in a single session; the most common incompletely ablated tumor type was clear cell carcinoma (6 of 9). CONCLUSION: Optimal electrode placement and a long distance from the collecting system are associated with an increased primary efficacy of renal tumor RFA. These variables need to be considered to increase primary ablation success. Further studies are needed to evaluate the effect of RFA on histopathologically different renal tumors.

Comparison of post contrast CT urography phases in bladder cancer detection.

OBJECTIVES: The aim of this study was to investigate which post-contrast phase(s) in a four-phase CT urography protocol is (are) most suitable for bladder cancer detection. METHODS: The medical records of 106 patients with visible haematuria who underwent a CT urography examination, including unenhanced, enhancement-triggered corticomedullary (CMP), nephrographic (NP) and excretory (EP) phases, were reviewed. The post-contrast phases (n = 318 different phases) were randomized into an evaluation order and blindly reviewed by two uroradiologists. RESULTS: Twenty-one patients were diagnosed with bladder cancer. Sensitivity for bladder cancer detection was 0.95 in CMP, 0.83 in NP and 0.81 in EP. Negative predictive value (NPV) was 0.99 in CMP, 0.96 in NP and 0.95 in EP. The sensitivity was higher in CMP than in both NP (p-value 0.016) and EP (p-value 0.0003). NPV was higher in CMP than in NP (p-value 0.024) and EP (p-value 0.002). CONCLUSIONS: In the CT urography protocol with enhancement-triggered scan, sensitivity and NPV were highest in the corticomedullary phase, and this phase should be used for bladder assessment. KEY POINTS: • More bladder tumours are detected during the corticomedullary phase than during other phases. • Sensitivity and NPV for bladder cancer detection were highest in corticomedullary phase. • The corticomedullary phase in CT urography should be used for bladder assessment.

The effect of preheated versus room-temperature skin disinfection on bacterial colonization during pacemaker device implantation: a randomized controlled non-inferiority trial.

BACKGROUND: In clinical practice, patients who are awake often comment that cold surgical skin disinfectant is unpleasant. This is not only a problem of patients' experience; heat loss during the disinfection process is a problem that can result in hypothermia. Evidence for the efficacy of preheated disinfection is scarce. We tested whether preheated skin disinfectant was non-inferior to room-temperature skin disinfectant on reducing bacterial colonization during pacemaker implantation. METHODS: This randomized, controlled, non-inferiority trial included 220 patients allocated to skin disinfection with preheated (36 °C) or room-temperature (20 °C) chlorhexidine solution in 70 % ethanol. Cultures were obtained by swabbing at 4 time-points; 1) before skin disinfection (skin surface), 2) after skin disinfection (skin surface), 3) after the incision (subcutaneously in the wound), and 4) before suturing (subcutaneously in the wound). RESULTS: The absolute difference in growth between patients treated with preheated versus room-temperature skin disinfectant was zero (90 % CI -0.101 to 0.101; preheated: 30 of 105 [28.6 %] vs. room-temperature: 32 of 112 [28.6 %]). The pre-specified margin for statistical non-inferiority in the protocol was set at 10 % for the preheated disinfectant. There were no significant differences between groups regarding SSIs three month postoperatively, which occurred in 0.9 % (1 of 108) treated with preheated and 1.8 % (2 of 112) treated with room-temperature skin disinfectant. CONCLUSION: Preheated skin disinfection is non-inferior to room-temperature disinfection in bacterial reduction. We therefore suggest that preheated skin disinfection become routine in clean surgery. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov (NCTO2260479).

Bladder cancer detection in patients with gross haematuria: Computed tomography urography with enhancement-triggered scan versus flexible cystoscopy.

OBJECTIVE: Computed tomography urography (CTU) can be used to direct further investigation of patients if the bladder tumour detection rate is high. The aim of this study was to compare a CTU protocol including an enhancement-triggered scan and flexible cystoscopy for detecting bladder tumours. MATERIALS AND METHODS: Patients with gross haematuria undergoing CTU during 2005-2008 were included. For patients younger than 50 years the CTU protocol included unenhanced, enhancement-triggered corticomedullary, and excretory phases. Patients older than 50 years followed the same protocol plus a nephrographic phase. The entire urinary tract was examined in all phases. RESULTS: Of 435 patients, 55 patients were diagnosed with bladder tumour. CTU detected bladder tumour in 48 patients (87%). Five CTU examination reports were false positive. With CTU, sensitivity for finding bladder tumour was 0.87, specificity 0.99, positive predictive value (PPV) 0.91 and negative predictive value (NPV) 0.98. Cystoscopy detected bladder tumour in 48 patients (87%) and had one false-positive finding, resulting in sensitivity of 0.87, specificity 1.0, PPV 0.98 and NPV 0.98. CONCLUSIONS: The detection rate of bladder tumours for the CTU protocol including an enhancement-triggered scan was high and comparable to flexible cystoscopy. Hence, this protocol could be used to assess the bladder as the primary investigation and direct further investigation of the patient.