bluuebunny/crossref_metadata_2025 huggingface dataset:
Contemporary management of renal cell carcinoma (RCC) in Victoria: implications for longer term outcomes and costs
Authors: Ta Anthony D. , Bolton Damien M. , Dimech Margaret K. , White Victoria , Davis Ian D. , Coory Michael , Millar Jeremy , Giles Graham
Published: October 2013

Objective

To describe the contemporary patterns of care for renal cell carcinoma (RCC) using a whole of population series from Victoria.

Patients and methods

Retrospective review of medical records of all patients diagnosed and treated for RCC in Victoria in 2009.

Patients were identified via the State‐wide Victorian Cancer Registry.

Patient demographic characteristics, symptoms, stage, and first‐line treatment were assessed.

Associations between case residential location (metropolitan or rural) and treatment were examined using multivariate logistic regression after adjusting for age, sex, socioeconomic status, treatment in private or public hospital and comorbidity.

Results

Data were obtained for 499 of 577 eligible patients.

In all, 413 patients (83%) underwent surgery.

Laparoscopic radical nephrectomy (RN) was the most common procedure for Stage I pT1a/pT1b tumours (51.2%); partial nephrectomy (PN) was performed for 27% of Stage I RCC

In multivariate analysis, regional patients were less likely to receive PN (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.18–0.85) for Stage I RCC, and less likely to receive systemic therapy for Stage IV RCC (OR 0.06, 95% CI 0.01–0.41).

Multidisciplinary team meetings were recorded for only 25% of patients and 3% were enrolled in a clinical trial.

Conclusion

Most contemporary patients diagnosed with RCC are still treated with RN, including those with smaller tumours amenable to PN.

This may impact future outcomes, including increased risk of chronic kidney disease and its potential financial healthcare burden.

Patterns of treatment also appear to differ between metropolitan and regional populations.
Non‐invasive urodynamics predicts outcome prior to surgery for prostatic obstruction
Authors: Losco Giovanni , Keedle Lucy , King Quinten
Published: October 2013

Objective

To assess whether the penile cuff non‐invasive urodynamic test serves as an effective diagnostic tool for predicting outcomes prior to disobstructive surgery for men presenting with voiding lower urinary tract symptoms.

Patients with proven urodynamic obstruction do better after surgery. The current gold standard, invasive pressure‐flow studies, imposes cost, resource demand, discomfort and inconvenience to patients.

Patients and Methods

Patients undergoing surgery for prostatic obstruction at Palmerston North Hospital had pre‐operative non‐invasive urodynamics and completed an International Prostate Symptom Score (IPSS). Catheterised patients were excluded.

Two months post‐operatively they completed a further IPSS score.

An improvement of seven or greater was defined as a clinically successful outcome.

Results were compared with the outcome predicted by the nomogram supplied with the urodynamic device.

Results

Data was obtained for 62 patients with mean age 70 years (range 49 to 86 years; SD 9 years). Follow‐up was complete for all patients.

Thirty‐eight patients underwent transurethral resection and 24 holmium laser enucleation of the prostate. Mean IPSS score was 21 (range 5 to 35; SD 6) pre‐operatively and 11 (range 1 to 31; SD 9) post‐operatively.

Thirty‐five patients were predicted obstructed and 27 not obstructed.

94% of those predicted obstructed had a successful outcome (p < 0.01).

70% predicted as not obstructed did not have a successful outcome after surgery (p < 0.01).

Conclusion

The penile cuff test is an exciting adjunct in the decision to proceed to surgery for prostatic obstruction.

Patients predicted to be obstructed have an excellent likelihood of a good surgical outcome, yet 30% of those shown not to be obstructed will still do well.

Whilst numbers in our study are small, outcomes compare favourably with published results on invasive urodynamic methods.
Investigation of poorer bladder cancer survival in women in NSW, Australia: a data linkage study
Authors: Tracey Elizabeth , Watt Hunter , Currow David , Young Jane , Armstrong Bruce
Published: October 2013

Objective

To investigate the associations of a range of personal and clinical variables with bladder cancer survival in men and women in NSW to see if we could explain why bladder cancer survival is consistently poorer in women than in men.

Patients and Methods

All 6880 cases of bladder cancers diagnosed in NSW between 2000 and 2008 were linked to hospital separation data and to deaths.

Separate Cox proportional hazards regression models of hazard of bladder cancer death were constructed for those who did or did not undergo cystectomy.

Results

A total of 16% of patients with bladder cancer underwent cystectomy (16% of men and 15% of women). Women who underwent cystectomy were 26% more likely to die than men (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.00–1.59) after adjustment for age, stage, time from diagnosis to cystectomy, distance from treatment facility and country of birth.

None of the above covariates had a material effect on the difference in hazard between women and men; however, when stratified by a history of cystitis, the adjusted hazard was 55% higher in women (HR 1.55, 95% CI 1.15–2.10) than in men with a history of cystitis while, in the absence of this history, there was no difference in the hazard between men and women (HR 0.99, 95% CI 0.57–1.70).

This apparent modification of the effect of sex on bladder cancer outcome was not seen in patients treated only by resection: the adjusted HRs in women relative to men were 1.10 (95% CI 0.92–1.31) in those with a history of cystitis and 1.21 (95% CI 0.98–1.50) in those without.

A history of haematuria did not modify appreciably the association of sex with bladder cancer outcome.

Conclusion

Women's poorer survival from bladder cancer compared with that of men remains unexplained; however, the possibility that some factor associated with a history of cystitis may contribute to or explain the poorer outcome in women merits further investigation.
Impact of androgen suppression and zoledronic acid on bone mineral density and fractures in the Trans‐Tasman Radiation Oncology Group (TROG) 03.04 Randomised Androgen Deprivation and Radiotherapy (RADAR) randomized controlled trial for locally advanced prostate cancer
Authors: Denham James W. , Nowitz Michael , Joseph David , Duchesne Gillian , Spry Nigel A. , Lamb David S. , Matthews John , Turner Sandra , Atkinson Chris , Tai Keen‐Hun , Gogna Nirdosh Kumar , Kenny Lizbeth , Diamond Terry , Smart Richard , Rowan David , Moscato Pablo , Vimieiro Renato , Woodfield Richard , Lynch Kevin , Delahunt Brett , Murray Judy , D'Este Cate , McElduff Patrick , Steigler Allison , Kautto Allison , Ball Jean
Published: October 2013

Objective

To study the influence of adjuvant androgen suppression and bisphosphonates on incident vertebral and non‐spinal fracture rates and bone mineral density (BMD) in men with locally advanced prostate cancer.

Patients and Methods

Between 2003 and 2007, 1071 men with locally advanced prostate cancer were randomly allocated, using a 2 × 2 trial design, to 6 months i.m. leuprorelin (androgen suppression [AS]) before radiotherapy alone ± 12 months additional leuprorelin ± 18 months zoledronic acid (ZdA), commencing at randomization.

The main endpoint was incident thoraco‐lumbar vertebral fractures, which were assessed radiographically at randomization and at 3 years, then reassessed by centralized review.

Subsidiary endpoints included incident non‐spinal fractures, which were documented throughout follow‐up, andBMD, which was measured in 222 subjects at baseline, 2 years and 4 years.

Results

Incident vertebral fractures at 3 years were observed in 132 subjects. Their occurrence was not increased by 18 months’AS, nor reduced byZdA.

Incident non‐spinal fractures occurred in 72 subjects and were significantly related toASduration but not toZdA.

Osteopenia and osteoporosis prevalence rates at baseline were 23.4 and 1.4%, respectively, at the hip.

Treatment for 6 and 18 months withAScaused significant reductions in hipBMDat 2 and 4 years (P< 0.01) andZdAprevented these losses at both time points.

Conclusion

In anAS‐naïve population, 18 months ofZdAtreatment prevented the sustainedBMDlosses caused by 18 months ofAStreatment; however, the study power was insufficient to show thatASduration orZdAinfluenced vertebral fracture rates.
Penile vibratory stimulation in the recovery of urinary continence and erectile function after nerve‐sparing radical prostatectomy: a randomized, controlled trial
Authors: Fode Mikkel , Borre Michael , Ohl Dana A. , Lichtbach Jonas , Sønksen Jens
Published: October 2013

Objective

To examine the effect of penile vibratory stimulation (PVS) in the preservation and restoration of erectile function and urinary continence in conjunction with nerve‐sparing radical prostatectomy (RP).

Patients and Methods

The present study was conducted between July 2010 and March 2013 as a randomized prospective trial at two university hospitals. Eligible participants were continent men with an International Index of Erectile Function‐5 (IIEF‐5) score of at least 18, scheduled to undergo nerve‐sparing RP.

Patients were randomized to a PVS group or a control group. Patients in the PVS group were instructed in using a PVS device (FERTI CARE® vibrator).

Stimulation was performed at the frenulum once daily by the patients in their own homes for at least 1 week before surgery. After catheter removal, daily PVS was re‐initiated for a period of 6 weeks.

Participants were evaluated at 3, 6 and 12 months after surgery with the IIEF‐5 questionnaire and questions regarding urinary bother. Patients using up to one pad daily for security reasons only were considered continent. The study was registered at http://clinicaltrials.gov/ (NCT01067261).

Results

Data from 68 patients were available for analyses (30 patients randomized to PVS and 38 patients randomized to the control group).

The IIEF‐5 score was highest in the PVS group at all time points after surgery with a median score of 18 vs 7.5 in the control group at 12 months (P = 0.09), but the difference only reached borderline significance.

At 12 months, 16/30 (53%) patients in the PVS group had reached an IIEF‐5 score of at least 18, while this was the case for 12/38 (32%) patients in the control group (P = 0.07).

There were no significant differences in the proportions of continent patients between groups at 3, 6 or 12 months. At 12 months 90% of the PVS patients were continent, while 94.7% of the control patients were continent (P = 0.46).

Conclusion

The present study did not document a significant effect of PVS. However, the method proved to be acceptable for most patients and there was a trend towards better erectile function with PVS. More studies are needed to explore this possible effect further.
Are prophylactic antibiotics necessary in patients with preoperative sterile urine undergoing ureterorenoscopic lithotripsy?
Authors: Hsieh Cheng‐Hsing , Yang Stephen Shei‐Dei , Lin Chia‐Da , Chang Shang‐Jen
Published: October 2013

Objective

To compare the efficacy of prophylactic antibiotics in reducing post‐surgical infections in patients undergoing ureterorenoscopic lithotripsy (URSL).

Patients and Methods

The study was a double‐blind, prospective, randomized controlled trial.

Between 2009 and 2012, 212 patients with preoperative sterile urine undergoing URSL were randomly allocated, in a ratio of 1:1:1:1, to receive prophylactic antibiotics with single‐dose i.v. cefazolin (1 g), ceftriaxone (1 g) or oral levofloxacin (500 mg), or no treatment (control group), respectively.

Urine analysis and urine cultures were obtained between postoperative days 5 and 7.

Pyuria was defined as ≥10 white blood cells/high power field. Significant bacteriuria was defined as ≥100,000 colony‐forming units uropathogens/mL. Febrile urinary tract infection (fUTI) was defined as a body temperature of 38.5 °C with pyuria or significant bacteriuria ≤7 days after surgery.

Results

In total, 206 patients were eligible for analysis.

The rates of postoperative pyuria were significantly lower in patients with prophylaxis than in the control group (48.4 vs 64.7%, P = 0.04).

Patients receiving prophylaxis with levofloxacin and ceftriaxone had a significantly lower risk of pyuria compared with the control group (52.0 and 36.5 vs 64.7%, respectively; P < 0.05).

The rates of bacteriuria and fUTI tended to be lower in patients with prophylaxis, although the difference was not significant (4.5 vs 11.8%, P = 0.09, 1.3 vs 5.9%, P = 0.09).

There was no significant difference in rates of bacteriuria and fUTI between the four groups. Patients with proximal stones had a higher risk of developing postoperative fUTI (odds ratio 9.35; P = 0.03).

Conclusion

Antibiotic prophylaxis significantly reduces the incidence of pyuria after URSL and tends to diminish the risk of bacteriuria and fUTI.
Cyclooxygenase‐2 inhibitor suppresses tumour progression of prostate cancer bone metastases in nude mice
Authors: Garcia Marta , Velez Roberto , Romagosa Cleofé , Majem Blanca , Pedrola Núria , Olivan Mireia , Rigau Marina , Guiu Marc , Gomis Roger R. , Morote Juan , Reventós Jaume , Doll Andreas
Published: October 2013

Objective

To assess whether celecoxib, a selective cyclooxygenase‐2 (COX‐2) inhibitor with anti‐cancer properties, has an inhibitory effect on tumour establishment and progression of prostate cancer (PCa) bone metastases.

Materials and Methods

PC‐3 stable luciferase‐expressing cells were injected into male nude mice by intracardiac (i.c.) and intratibial (i.t.) injections, and the effect of celecoxib on bone metastases was then recorded using bioluminescence image analysis.

In cases of chemoprevention, mice received 3 mg/kg celecoxib from 1 week before cell implantation until the end of the study, and to test the therapeutic effect, mice received celecoxib 1 week after cell implantation until the end of the study.

Tumour tissue samples were histologically examined and COX‐2 expression was quantified at the protein level.

Results

Celecoxib significantly decreased cell viability and the proliferation of human PCa cells in vitro in a dose‐dependent manner.

Bone metastases were detected after i.c. injection in nude mice.

Celecoxib (15 ppm) administered before i.c. injection did not inhibit the cellular metastatic potential, as the numbers of bone metastases were similar in both groups. However, celecoxib did decrease metastatic progression in the osseous environment when cells were injected directly into the tibia (P < 0.05).

At the protein level, COX‐2 expression was significantly decreased in the celecoxib treatment group (P < 0.01).

Conclusion

In a preclinical mice model, celecoxib administered orally at the standard human dose inhibits the progression of established PCa bone metastases.
Open and robot‐assisted radical retropubic prostatectomy in men receiving ongoing low‐dose aspirin medication: revisiting an old paradigm?
Authors: Leyh‐Bannurah Sami‐Ramzi , Hansen Jens , Isbarn Hendrik , Steuber Thomas , Tennstedt Pierre , Michl Uwe , Schlomm Thorsten , Haese Alexander , Heinzer Hans , Huland Hartwig , Graefen Markus , Budäus Lars
Published: October 2013

Objective

To assess blood loss, transfusion rates and 90‐day complication rates in patients receiving ongoing 100 mg/day aspirin medication and undergoing open radical prostatectomy (RP) or robot‐assisted RP (RARP).

Patients and Methods

Between February 2010 and August 2011, 2061 open RPs and 400 RARPs were performed. All patients received low‐molecular‐weight heparin for thrombembolism prophylaxis. Aspirin intake during surgery was recorded in 137 patients (5.5%).

Descriptive statistics and multivariable analyses after propensity‐score matching for balancing potential differences in patients with and without aspirin medication were used to assess the risk of blood loss above the median in patients undergoing open RP or RARP.

Results

The median blood loss in the open RP cohort with and without aspirin medication was 750 and 700 mL, respectively, and in the RARP cohort it was 200 and 150 mL, respectively. Within the same cohorts, transfusions were administered in 21 and 8% and 0 and 1% of patients, respectively.

The 90‐day complication rates in patients with ongoing aspirin medication were 5.8, 4.4, 7.3 and 0% for Clavien grades I, II, III and IV complications, respectively.

In multivariable analyses and after propensity‐score matching, prostate volume (odds ratio 1.03; 95% CI 1.02–1.04; P < 0.01) but not ongoing aspirin medication achieved independent predictor status for the risk of blood loss above the median.

Conclusions

Major surgery such as open RP and RARP can be safely performed in patients with ongoing aspirin medication without greater blood loss.

Higher 90‐day complication rates were not detected in such patients.

Differences in transfusion rates between the groups receiving and not receiving ongoing aspirin medication may be explained by a higher proportion of patients with coronary artery disease in the group receiving ongoing aspirin mediciation. This comorbidity may result in a higher peri‐operative threshold for allogenic blood transfusion.
A critical appraisal of complications of percutaneous nephrolithotomy in paediatric patients using adult instruments
Authors: Goyal Neeraj Kumar , Goel Apul , Sankhwar Satya Narayan , Singh Vishwajeet , Singh Bhupendra Pal , Sinha Rahul Janak , Dalela Divakar , Yadav Rahul
Published: October 2013

Objective

To evaluate the complications (using the CROES Clavien scoring system) and various factors affecting them in children undergoing percutaneous nephrolithotomy (PCNL).

Patients and Methods

We analysed prospectively maintained data of paediatric PCNL (patients ≤17 years) from January 2008 to December 2012.

Stone complexity was defined according to validated Guy's stone score (GSS). Procedures were performed in the prone position by experienced urologists. The tract was dilated (24–30F) under fluoroscopic guidance, and an adult rigid nephroscope complemented with a cystoscope/ureteroscope were used.

Complications were recorded according to the CROES‐Clavien score, recently defined by the Clinical Research Office of the Endourological Society (CROES) Study Group.

Results

The study group comprised 158 procedures performed in 153 children (98 boys and 55 girls), with a mean (range) age 10.03 ± 4.51 (2–17) years.

The mean (range) stone burden was 376.68 ± 265.23 (150–2400) mm2. The distribution of cases according to the GSS was 31% grade I, 35.4% grade II, 19% grade III, and 14.6% grade IV.

The stone‐free rate of PCNL monotherapy was 85.4%, which increased to 93.7% after relook PCNL/extracorporeal shock wave lithotripsy. In all, 62 children (39.2%) had operative complications; 84% were minor, i.e. Clavien grade 1/2, and managed conservatively.

Stone size, GSS, tract size, number of punctures and operation duration were significantly associated with complications on univariate analysis (P < 0.05). However, on multivariate logistic regression analysis, operation duration was the only independent risk factor associated with complications (95% confidence interval: 1.013–1.065, odds ratio = 1.04; P = 0.038).

Conclusions

Percutaneous nephrolithotomy in children using adult instruments is an effective and safe procedure for managing simple as well as complex renal calculi.

Assignment of specific Clavien scores to all possible PCNL complications by the CROES PCNL Study Group have improved precision in reporting complications in a standard objective format, including the minor ones. Such models are very useful for making inter‐observer comparisons to obtain clinically relevant inferences.

Mean operation duration is the only independent factor affecting complications of the procedure.
Comparison of high‐dose (86.4 Gy) IMRT vs combined brachytherapy plus IMRT for intermediate‐risk prostate cancer
Authors: Spratt Daniel E. , Zumsteg Zachary S. , Ghadjar Pirus , Kollmeier Marisa A. , Pei Xin , Cohen Gilad , Polkinghorn William , Yamada Yoshiya , Zelefsky Michael J.
Published: October 2013

Objective

To compare tumour control and toxicity outcomes with the use of high‐dose intensity‐modulated radiation therapy (IMRT) alone or brachytherapy combined with IMRT (combo‐RT) for patients with intermediate‐risk prostate cancer.

Patients and Methods

Between 1997 and 2010, 870 consecutive patients with intermediate‐risk prostate cancer were treated at our institution with either 86.4 Gy of IMRT alone (n = 470) or combo‐RT consisting of brachytherapy combined with 50.4 Gy of IMRT (n = 400).

Brachytherapy consisted of low‐dose‐rate permanent interstitial implantation in 260 patients and high‐dose‐rate temporary implantation in 140 patients.

The median (range) follow‐up for the entire cohort was 5.3 (1–14) years.

Results

For IMRT alone vs combo‐RT, 7‐year actuarial prostate‐specific antigen (PSA)‐relapse‐free survival (PSA‐RFS) rates were 81.4 vs 92.0% (P < 0.001), and distant metastases‐free survival (DMFS) rates were 93.0 vs 97.2% (P = 0.04), respectively.

Multivariate analysis showed that combo‐RT was associated with better PSA‐RFS (hazard ratio [HR], 0.40 [95% confidence interval, 0.24–0.66], P < 0.001), and better DMFS (HR, 0.41 [0.18–0.92], P = 0.03).

A higher incidence of acute genitourinary (GU) grade 2 (35.8 vs 18.9%; P < 0.01) and acute GU grade 3 (2.3 vs 0.4%; P = 0.03) toxicities occurred in the combo‐RT group than in the IMRT‐alone group. Most acute toxicity resolved. Late toxicity outcomes were similar between the treatment groups. The 7‐year actuarial late toxicity rates for grade 2 gastrointestinal (GI) toxicity were 4.6 vs 4.1% (P = 0.89), for grade 3 GI toxicity 0.4 vs 1.4% (P = 0.36), for grade 2 GU toxicity 19.4 vs 21.2% (P = 0.14), and grade 3 GU toxicity 3.1 vs 1.4% (P = 0.74) for the IMRT vs the combo‐RT group, respectively.

Conclusions

Enhanced dose escalation using combo‐RT was associated with superior PSA‐RFS and DMFS outcomes for patients with intermediate‐risk prostate cancer compared with high‐dose IMRT alone at a dose of 86.4 Gy.

While acute GU toxicities were more prevalent in the combo‐RT group, the incidence of late GI and GU toxicities was similar between the treatment groups.
Positive vascular wall margins have minimal impact on cancer outcomes in patients with non‐metastatic renal cell carcinoma (RCC) with tumour thrombus
Authors: Abel E. Jason , Carrasco Alonso , Karam Jose , Tamboli Pheroze , Delacroix Scott , Vaporciyan Ara A. , Wood Christopher G.
Published: October 2013

Objective

To evaluate the impact of microscopically positive vascular margins on recurrence and cancer‐specific survival (CSS) in patients with renal cell carcinoma (RCC) with venous thrombus

Patients and Methods

We reviewed the records from the period 1993 to 2009 of consecutive patients treated surgically for RCC with venous tumour thrombus at the University of Texas MD Anderson Cancer Center.

Patients with metastatic disease, positive soft tissue margins or gross residual disease at time of thrombectomy were excluded.

The primary outcome measures were local or systemic disease recurrence, and CSS.

Univariate and multivariate analysis were used to evaluate whether microscopically positive vascular margins were associated with RCC recurrence or CSS after nephrectomy with thrombectomy.

Results

A total of 256 patients with RCC were identified with a median (interquartile range) follow‐up of 36.7 (18.4–63.5) months. Microscopic tumour was present at the margin of resection in 47 patients (18.4%).

The median recurrence‐free interval was significantly shorter in patients with positive vascular margins: 22.1 vs 70.2 months (P = 0.009).

The rate of local recurrence was higher in patients with positive vein margins: 12.8 vs 4.3% (P < 0.01). Local recurrence without concomitant systemic recurrence was identified in only two of 256 (0.8%) patients.

Patients with positive vascular margins had significantly worse CSS times compared with patients with negative vascular margins: 37.7 vs 93.0 months (P = 0.004).

In multivariable analysis, positive vascular margins were found to be independently predictive of local recurrence but not of systemic recurrence or CSS.

Conclusions

Complete surgical excision should always be attempted because positive vascular wall margins increase local recurrence rates.

Invasion of RCC into the vein wall at the resection margin is associated with aggressive tumour biology, and the majority of patients with positive vascular wall margins experience systemic recurrence.
Reflex fluorescence in situ hybridization assay for suspicious urinary cytology in patients with bladder cancer with negative surveillance cystoscopy
Authors: Kim Philip H. , Sukhu Ranjit , Cordon Billy H. , Sfakianos John P. , Sjoberg Daniel D. , Hakimi A. Ari , Dalbagni Guido , Lin Oscar , Herr Harry W.
Published: October 2013

Objective

To assess the ability of reflex UroVysion fluorescence in situ hybridization (FISH) testing to predict recurrence and progression in patients with non‐muscle‐invasive bladder cancer (NMIBC) with suspicious cytology but negative cystoscopy.

Patients and Methods

Patients under NMIBC surveillance were followed with office cystoscopy and urinary cytology every 3–6 months.

Between March 2007 and February 2012, 500 consecutive patients with suspicious cytology underwent reflex FISH analysis.

Clinical and pathological data were reviewed retrospectively.

Predictors for recurrence, progression and findings on subsequent cystoscopy (within 2–6 months after FISH) were evaluated using univariate and multivariate Cox regression.

Results

In all, 243 patients with suspicious cytology also had negative surveillance cystoscopy.

Positive FISH was a significant predictor of recurrence (hazard ratio [HR] = 2.35, 95% confidence interval [CI]: 1.42–3.90, P = 0.001) in multivariate analysis and for progression (HR = 3.01, 95% CI: 1.10–8.21, P = 0.03) in univariate analysis, compared with negative FISH.

However, positive FISH was not significantly associated with evidence of tumour on subsequent surveillance cystoscopy compared with negative FISH (odds ratio = 0.8, 95% CI: 0.26–2.74, P = 1).

Conclusions

Positive FISH predicts recurrence and progression in patients under NMIBC surveillance with suspicious cytology but negative cystoscopy.

However, there was no association between the FISH result and tumour recurrence in the immediate follow‐up period.

Reflex FISH testing for suspicious cytology might have limited ability to modify surveillance strategies in NMIBC.
Incremental detection rate of prostate cancer by real‐time elastography targeted biopsies in combination with a conventional 10‐core biopsy in 1024 consecutive patients
Authors: Salomon Georg , Drews Nils , Autier Philippe , Beckmann Ann , Heinzer Hans , Hansen Jens , Michl Uwe , Schlomm Thorsten , Haese Alex , Steuber Thomas , Graefen Markus , Becker Andreas
Published: October 2013

Objective

To quantify the incremental detection rate (DR) of a targeted biopsy in addition to a randomized 10‐core biopsy.

Patients and Methods

This retrospective study analysed 1024 patients who consecutively underwent a four‐core real‐time elastography (RTE) targeted biopsies in addition to a randomized 10‐core transrectal ultrasonography (TRUS)‐guided biopsy in a primary or rebiopsy setting.

The overall DR, the DR of a 10‐core randomized, RTE targeted biopsy and the incremental DR were calculated.

Results

Overall, randomized and RTE targeted biopsy DRs (for the combination, the 10‐core and the four‐core RTE biopsy scheme) were 46.2% (n = 473), 39.1% (n = 400) and 29.0% (n = 297), respectively.

Four‐core RTE targeted biopsies detected an additional 73 patients not detected by the 10‐core randomized biopsies (increase in the overall DR of 7.1%). This represented a relative increase in DR of 18.3%. The incremental DR was better in rebiopsy patients (24.8%) than in patients having their first biopsy (14.7%).

Within all patients diagnosed by RTE targeted biopsy only, 34 patients harboured significant Gleason 4 or 5 prostate cancer (PCa), diagnosed by four‐core RTE biopsy only. Moreover, PCa with a Gleason grade of 4 or 5 was detected by four‐core RTE biopsies in 30 patients, who showed low‐grade PCa ≤ Gleason 3 only in the systematic 10‐core biopsy.

Conclusions

Real‐time elastography targeted biopsy seems to be an appropriate method for increasing the DR of PCa.

Nevertheless, RTE targeted biopsies missed a high proportion of patients with PCa and should therefore be considered as an addition to randomized biopsies.
Japanese Adolescents' Disclosure and Information Management With Parents
Authors: Nucci Larry , Smetana Judith , Araki Noriyuki , Nakaue Masataka , Comer Jessamy
Published: October 2013

Adolescents' obligation to disclose and their actual disclosure about their activities to parents, justifications for nondisclosure, and strategies for information management were examined in different domains in 460 middle adolescents (Mage = 16.6 years) from working and middle‐class families in Japan. Adolescents felt most obligated to disclose prudential issues, but disclosed most about personal issues. Adolescents primarily justified nondisclosure with claims to personal choice and for prudential issues, concerns with parental disapproval. They rarely lied and mostly told parents if asked or avoided the issue. Findings revealed consistencies with prior work on disclosure with European and U.S. adolescents, as well as patterns specific to the Japanese cultural setting.
Prophylactic and therapeutic vaccination with carrier‐bound Bet v 1 peptides lacking allergen‐specific T cell epitopes reduces Bet v 1‐specific T cell responses via blocking antibodies in a murine model for birch pollen allergy
Authors: Linhart B. , Narayanan M. , Focke‐Tejkl M. , Wrba F. , Vrtala S. , Valenta R.
Published: October 2013

Background

Vaccines consisting of allergen‐derived peptides lacking IgE reactivity and allergen‐specific T cell epitopes bound to allergen‐unrelated carrier molecules have been suggested as candidates for allergen‐specific immunotherapy.

Objective

To study whether prophylactic and therapeutic vaccination with carrier‐bound peptides from the major birch pollen allergen Bet v 1 lacking allergen‐specific T cell epitopes has influence on Bet v 1‐specific T cell responses.

Methods

Three Bet v 1‐derived peptides, devoid of Bet v 1‐specific T cell epitopes, were coupled to KLH and adsorbed to aluminium hydroxide to obtain a Bet v 1‐specific allergy vaccine. Groups of BALB/c mice were immunized with the peptide vaccine before or after sensitization to Bet v 1. Bet v 1‐ and peptide‐specific antibody responses were analysed by ELISA. T cell and cytokine responses to Bet v 1, KLH, and the peptides were studied in proliferation assays. The effects of peptide‐specific and allergen‐specific antibodies on T cell responses and allergic lung inflammation were studied using specific antibodies.

Results

Prophylactic and therapeutic vaccination with carrier‐bound Bet v 1 peptides induced a Bet v 1‐specific IgG antibody response without priming/boosting of Bet v 1‐specific T cells. Prophylactic and therapeutic vaccination of mice with the peptide vaccine induced Bet v 1‐specific antibodies which suppressed Bet v 1‐specific T cell responses and allergic lung inflammation.

Conclusion and Clinical Relevance

Vaccination with carrier‐bound allergen‐derived peptides lacking allergen‐specific T cell epitopes induces allergen‐specific IgG antibodies which suppress allergen‐specific T cell responses and allergic lung inflammation.
Managing generalized interferon‐induced eruptions and the effectiveness of desensitization
Authors: Poreaux C. , Bronowicki J.‐P. , Debouverie M. , Schmutz J.‐L. , Waton J. , Barbaud A.
Published: October 2013

Background

We evaluated the value of skin tests and the efficacy of a 12‐step desensitization protocol to pegylated interferon (IFN) in patients with generalized drug eruptions due toIFNs.

Methods

A retrospective study (1998–2009) was followed by a cross‐sectional clinical study conducted prospectively (2009–2011). All patients received a dermatological clinical examination and skin tests. Twelve‐stepIFNdesensitization was proposed for patient with active hepatitis C and no alternative therapy.

Results

Twenty‐six patients (13 males, mean age, 53.5 years) had generalized reactions toIFNs; 21 were treated withIFN‐α and 5 withIFN‐β. Moreover, 21 patients had skin tests. Intradermal tests (IDTs) were positive after an average of 72 h. Cross‐reactivity between peg‐IFN‐α2a and peg‐IFN‐α2b was observed in 5/10 cases in the prospective study. In 16 of 26 cases,IFNtreatment was stopped. In 8 of 16 cases of diffuse eczematous drug eruption, treatment was continued. The corticosteroid and antihistamine were sufficient in 4/8 cases. In three other cases, topical tacrolimus was highly effective. In 3 of 16 cases in which treatment were stopped, patients underwent the early resumption of peg‐IFN‐α. These three patients had positive tests with peg‐IFN‐α2a and peg‐IFN‐α2b and successfully completed the tolerance induction protocol for peg‐IFN‐α2b. Tolerance induction involved a weekly dose of peg‐IFNand a gradual increase in the recovery of an antiviral C. Clinical tolerance was excellent, and the patients' viral load C became negative.

Conclusions

Our study demonstrates the benefit of allergy testing in cases of generalized drug reactions toIFN, cross‐reactivities in a single class ofIFNs and the importance of delayedIDTreading. We report for the first time the effectiveness of 12‐step desensitization with peg‐IFN.
Intravascular immunity as a key to systemic vasculitis: a work in progress, gaining momentum
Authors: Ramirez G A , Maugeri N , Sabbadini M G , Rovere-Querini P , Manfredi A A
Published: October 2013

Vascular inflammation contributes to the defence against invading microbes and to the repair of injured tissues. In most cases it resolves before becoming apparent. Vasculitis comprises heterogeneous clinical entities that are characterized by the persistence of vascular inflammation after it has served its homeostatic function. Most underlying mechanisms have so far remained elusive. Intravascular immunity refers to the surveillance of the vasculature by leucocytes that sense microbial or sterile threats to vessel integrity and initiate protective responses that entail most events that determine the clinical manifestations of vasculitis, such as end-organ ischaemia, neutrophil extracellular traps generation and thrombosis, leucocyte extravasation and degranulation. Understanding how the resolution of vascular inflammation goes awry in patients with systemic vasculitis will facilitate the identification of novel pharmacological targets and bring us a step closer in each patient to the selection of more effective and less toxic treatments.
Exome sequencing identifies mutations in KIF14 as a novel cause of an autosomal recessive lethal fetal ciliopathy phenotype
Authors: Filges I. , Nosova E. , Bruder E. , Tercanli S. , Townsend K. , Gibson W.T. , Röthlisberger B. , Heinimann K. , Hall J.G. , Gregory‐Evans C.Y. , Wasserman W.W. , Miny P. , Friedman J.M.
Published: October 2013

Gene discovery using massively parallel sequencing has focused on phenotypes diagnosed postnatally such as well‐characterized syndromes or intellectual disability, but is rarely reported for fetal disorders. We used family‐based whole‐exome sequencing in order to identify causal variants for a recurrent pattern of an undescribed lethal fetal congenital anomaly syndrome. The clinical signs included intrauterine growth restriction (IUGR), severe microcephaly, renal cystic dysplasia/agenesis and complex brain and genitourinary malformations. The phenotype was compatible with a ciliopathy, but not diagnostic of any known condition. We hypothesized biallelic disruption of a gene leading to a defect related to the primary cilium. We identified novel autosomal recessive truncating mutations in KIF14 that segregated with the phenotype. Mice with autosomal recessive mutations in the same gene have recently been shown to have a strikingly similar phenotype. Genotype–phenotype correlations indicate that the function of KIF14 in cell division and cytokinesis can be linked to a role in primary cilia, supported by previous cellular and model organism studies of proteins that interact with KIF14. We describe the first human phenotype, a novel lethal ciliary disorder, associated with biallelic inactivating mutations in KIF14. KIF14 may also be considered a candidate gene for allelic viable ciliary and/or microcephaly phenotypes.
The relationship of distance from the surgical centre on attendance and weight loss after laparoscopic gastric bypass surgery in the United Kingdom
Authors: Jennings N. , Boyle M. , Mahawar K. , Balupuri S. , Small P.
Published: October 2013

Obesity remains a significant worldwide health problem and is currently increasing. Surgery remains the only proven long‐term intervention and has been shown to be cost‐effective. Evidence suggests that regular follow‐up following laparoscopic adjustable gastric banding is related to improved outcome, such evidence is lacking for laparoscopic gastric bypass surgery (laparoscopic Roux‐en‐Y gastric bypass [LRYGB]). This study examines the effect of distance on attendance at post‐operative clinics and subsequent weight loss following surgery. A prospectively maintained database was interrogated to analyze patients undergoing LRYGB before August 2010. Patient demographics, percentage excess weight loss (%EWL), compliance with out‐patient clinic attendances and the distance the patients lived from the hospital were examined. Perfect clinic attendees were compared with non‐attendees and the distances patients lived from the hospital evaluated. There was a significantly greater %EWL at 1 year post‐op observed in the perfect attendees group (65.5 vs. 59.5, P = 0.01). Increased %EWL was also evident at 2 years post‐op but did not reach statistical significance (66.9 vs. 59.5, P = 0.06). There was a negative correlation observed between post‐operative weight loss and distance from the bariatric centre (R = −0.21, P = 0.04). Close follow‐up following LRYGB is essential to optimize outcomes. Increased frequency of out‐patient clinic visits was associated with improved post‐operative weight loss. Increasing distance between the patient's home and the bariatric centre was associated with worse post‐operative weight loss.
A systematic review of ordinal scales used to classify the eating and drinking abilities of individuals with cerebral palsy
Authors: Sellers Diane , Pennington Lindsay , Mandy Anne , Morris Christopher
Published: October 2013

Aim

The aim of this review was to examine systematically the scope, validity, and reliability of ordinal scales used to classify the eating and drinking ability of people with cerebral palsy (CP).

Method

Six electronic databases were searched to identify measures used to classify eating and drinking ability; in addition, two databases were used to track citations of key texts. The constructs assessed by each measure were examined in relation to the World Health Organization International Classification of Functioning, Disability and Health. Evidence of validity and reliability of the identified scales was appraised from peer‐reviewed studies using standard criteria.

Results

Fifteen scales were identified in 23 papers. Clinician or researcher assessment was required for 13 scales; nine scales made use of information from parents and carers through interviews or questionnaires. Eight scales used the terms mild, moderate, and severe (with varying definitions) to describe different aspects of eating and drinking impairment. There was an assessment of either content validity and/or reliability for five scales; however, none met the recommended psychometric quality standards.

Interpretation

Currently, there is a lack of evidence of the validity and reliability of ordinal scales of functional eating and drinking abilities of people with CP.
Prognostic Value of Treadmill Stress Echocardiography at Extremes of Exercise Performance: Submaximal <85% Maximum Predicted Heart Rate versus High Exercise Capacity ≥10 Metabolic Equivalents
Authors: Yao Siu‐Sun , Agarwal Vikram , Chaudhry Farooq A.
Published: October 2013

Background

Submaximal stress testing or achieving <85% maximum predicted heart rate (MPHR) may lead to nondiagnostic results and indeterminate outcomes. High exercise capacity (≥10 metabolic equivalents, METS) is a predictor of favorable prognosis. The purpose of this study was to evaluate the prognostic value of submaximal or high exercise capacity stress echocardiography.

Methods

We evaluated 1781 patients (55 ± 13 years; 59% male) undergoing treadmill stress echocardiography divided into 811 patients with submaximal (<85% MPHR) and 970 patients with high exercise capacity (≥10 METS). Resting left ventricular ejection fraction and regional wall motion were assessed. The left ventricle was divided into 16 segments and scored on 5‐point scale of wall motion. Abnormal stress echocardiography was defined as stress‐induced ischemia (wall‐motion score of ≥1 grade). Follow‐up (3.3 ± 1.5 years) for nonfatal myocardial infarction (MI) (n = 40) and cardiac death (n = 52) were obtained.

Results

By univariate analysis, echocardiographic variables of ejection fraction, peak wall‐motion score index (WMSI) and number of new ischemic wall‐motion abnormalities were significant predictors of cardiac events. Cumulative survival was significantly worse in patients with abnormal (ischemic) versus normal (nonischemic) stress echocardiography in submaximal (4.4%/year vs. 1.3%/year, P < 0.0001) and high exercise capacity (1.5%/year vs. 0.2%/year, P < 0.0001) studies. Multivariate Cox proportional hazards analysis identified number of new ischemic wall‐motion abnormalities as the strongest predictor of cardiac events (P < 0.05) in both groups.

Conclusions

Despite normal stress echocardiography, the inability to achieve 85% MPHR conferred a higher, intermediate cardiac event rate of 2.9%/year. The ability to achieve 9 minutes (≥10 metabolic equivalents, METS) conferred an overall low cardiac event rate of 0.4%/year. However, the absence or presence of ischemia by stress echocardiography was able to further risk stratify patients with either submaximal or high exercise capacity studies.
Papillary Fibroelastoma of the Pulmonary Valve – A Systematic Review
Authors: Hakim Fayaz A. , Aryal Madan Raj , Pandit Anil , Pandit Aashrayata Aryal , Alegria Jorge R. , Kendall Christopher B. , Click Roger L.
Published: October 2013

The pulmonary valve is the least affected site for valvular papillary fibroelastoma. With increasing use of routine echocardiography and other modalities of imaging, pulmonary valve papillary fibroelastomas (PVPFE) are being recognized more frequently. PVPFE is more often an incidental diagnosis and symptomatic patients usually present with shortness of breath. Embolic phenomena and right ventricular outflow tract obstruction are the most serious complications of PVPFE. Since PVPFE is rare, the purpose of this systematic review is to address demographic characteristics, the clinical presentation, management, and outcome of this benign tumor of the pulmonary valve.
Cause of death in mild cognitive impairment: a prospective study (NEDICES)
Authors: Contador I. , Bermejo‐Pareja F. , Mitchell A. J. , Trincado R. , Villarejo A. , Sánchez‐Ferro Á. , Benito‐León J.
Published: October 2013

Background and purpose

Previous studies have reported the occurrence of increased mortality rates among individuals with mild cognitive impairment (MCI), but possible links between MCI subtypes and cause‐specific mortality need to be explored. To examine short‐term mortality (5 years), long‐term mortality (13 years) and cause‐specific mortality of individuals over 65 years of age suffering from MCI compared with cognitively unimpaired individuals in the Neurological Disorders in Central Spain (NEDICES) cohort.

Methods

Mild cognitive impairment was classified using standardized psychometric and functional assessment in accordance with diagnostic convention. Cox's proportional hazards models, adjusted by sociodemographics and comorbidity factors, were used to assess the risk of death at 5 and 13 years of MCI subtypes compared with a reference group of older people without cognitive impairment (N = 2329). Causes of death were obtained from the National Population Register of Spain.

Results

There were 1484 deceased individuals at 13 years. MCI subtypes were defined as amnestic single domain (N = 259), amnestic multiple domain (N = 197) and non‐amnestic (N = 641). After adjusting for covariates, only the amnestic multiple domain MCI subtype showed an increased hazard ratio (HR) for mortality at 5 years versus the reference group. However, the HR for mortality at 13 years was increased for all MCI subtypes. The HR by MCI subtype was 1.19 in the non‐amnestic subtype (95% CI 1.05–1.36), 1.31 in the amnestic single domain subtype (95% CI 1.10–1.56) and 1.67 in the amnestic multiple domain subtype (95% CI 1.38–2.02). In terms of cause‐specific mortality, the chance of death from dementia was statistically higher in all MCI subtypes.

Conclusion

Amnestic multiple domain MCI showed the greatest risk of mortality in comparison with other MCI subtypes at different intervals. Dementia was the only cause‐specific mortality that was increased in MCI individuals.
An Interpretive Argument for Blended Course Design
Authors: Gleason Jesse
Published: October 2013

As courses that once regularly met face‐to‐face are increasingly offered in blended or fully online formats, questions have been raised about the comparability of instruction, teacher and student roles, and overall quality of the learning experience. The present study offers a five‐inference interpretive argument (Chapelle, Enright & Jamieson, 2008a; Kane, 2006) that may be used to guide the design and implementation of blended language curriculum and instruction in which tasks are viewed as micro‐formative assessments. An example compares the language practiced and produced by students during three language tasks that were carried out both online and in a classroom setting. Finally, suggestions to guide the gathering of validity evidence for blended language course design are offered.
Trends in seedling growth and carbon‐use efficiency vary among broadleaf tree species along a latitudinal transect in eastern North America
Authors: Dillaway Dylan N. , Kruger Eric L.
Published: October 2013

Factors constraining the geographic ranges of broadleaf tree species in eastern North America were examined in common gardens along a ~1500 km latitudinal transect travers in grange boundaries of four target species: trembling aspen (Populus tremuloides) and paper birch (Betula papyrifera) to the north vs. eastern cottonwood (Populus deltoides) and sweet gum (Liquidambar styraciflua) to the south. In 2006 and 2007, carbon‐use efficiency (CUE), the proportion of assimilated carbon retained in biomass, was estimated for seedlings of the four species as the quotient of relative growth rate (RGR) and photosynthesis per unit tree mass (Atree). In aspen and birch, CUE and RGR declined significantly with increasing growth temperature, which spanned 9 °C across gardens and years. The 37% (relative) CUE decrease from coolest to warmest garden correlated with increases in leaf nighttime respiration (Rleaf) and the ratio of Rleaf to leaf photosynthesis (R%A). For cottonwood and sweet gum, however, similar increases in Rleaf and R%A accompanied modest CUE declines, implying that processes other than Rleaf were responsible for species differences in CUE's temperature response. Our findings illustrate marked taxonomic variation, at least among young trees, in the thermal sensitivity of CUE, and point to potentially negative consequences of climate warming for the carbon balance, competitive ability, and persistence of two foundation species in northern temperate and boreal forests.