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Re: Imaging Strategy for Infants With Urinary Tract Infection: A New Algorithm
2506
LETTERS TO THE EDITOR/ERRATA
Reply by Authors: As stated in the article, the absence of data regarding the reasons for delayed treatment is a limitation of the study. We also agree with Klotz that upgrading at radical prostatectomy in the delayed group likely reflects grade progression as well as some higher grade tumors that were missed on the initial staging evaluation. Although it is unclear why sampling error on the initial biopsy would be different between the immediate and delayed groups, we cannot rule out the potential influence of unmeasured confounders on our results. Regardless, the findings in our study highlight the limitations of current clinical staging modalities to characterize accurately the biological aggressiveness of prostate cancers at diagnosis. While this fact may not prove to be clinically relevant for older men with significant comorbidities, these uncertainties are particularly critical for young men with a long life expectancy who are otherwise candidates for definitive therapy. In this regard many prior studies have evaluated the pathological outcomes of radical prostatectomy among men who would have met various criteria for active surveillance.1,2 For example Suardi et al reported aggressive pathology features in the radical prostatectomy specimen in 28% of men who would have met 2 of the most strict criteria for active surveillance.1 Nevertheless, prostatectomy tumor features are admittedly an imperfect proxy for survival outcomes. Our study takes this issue to the next level by actually showing significantly higher rates of biochemical recurrence in men who initially met low risk criteria but had a delay of more than 6 months before undergoing definitive therapy. Certainly we agree with Klotz that association is not equivalent to causation, and by no means do we suggest that our study establishes causality. Some of the key criteria to establish actual causality are strength and consistency of the evidence. In a recent update of the Scandinavian Prostate Cancer Group-4 randomized trial Bill-Axelson et al reported significant reductions in metastasis (RR 0.43, p ⫽ 0.008) and all cause mortality (RR 0.62, p ⫽ 0.02) with radical prostatectomy compared to watchful waiting at 15 years for men with low risk disease (PSA less than 10 ng/ml, Gleason less than 7 or WHO grade 1).3 Future prospective studies are needed to evaluate critically the long-term outcomes following definitive treatment compared to active surveillance in a contemporary population with screen detected disease. 1. Suardi N, Capitanio U, Chun FK et al: Currently used criteria for active surveillance in men with low-risk prostate cancer: an analysis of pathologic features. Cancer 2008; 113: 2068.
3. Bill-Axelson A, Holmberg L, Ruutu M et al: Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2011; 364: 1708.
2. Griffin CR, Yu X, Loeb S et al: Pathological features after radical prostatectomy in potential candidates for active monitoring. J Urol 2007; 178: 860.
Re: Imaging Strategy for Infants With Urinary Tract Infection: A New Algorithm I. Preda, U. Jodal, R. Sixt, E. Stokl and S. Hansson J Urol 2011; 185: 1046 –1052.
To the Editor: We appreciated the study by Preda et al, and their effort to provide an evidencebased evaluation of imaging techniques after urinary tract infection (UTI) in the current debate and controversies regarding the respective roles of ultrasound (US), cystography and dimercaptosuccinic acid scintigraphy. Briefly in a cohort of 270 children this prospective study demonstrated that C-reactive protein (CRP) could be a predictor of renal scarring. The first part of the analysis was nicely conducted, based only on variables available at the time of UTI diagnosis, and ended up in a reliable logistic regression model, including CRP and urinary tract dilatation on renal US. However, it would have been interesting to study the input of each of the significant variables into the model,1 running some maximum likelihood estimates to add weight and confidence to the choice of keeping only CRP and renal US for the next steps. Moreover, it is unclear why the authors chose to derive the practical decision rule by defining the best cutoff for CRP and renal anteroposterior diameter without weighting the 2 variables with any coefficient. This approach would give additional reliability and accuracy to the analysis, potentially making the rule more reproducible when it comes to external validation.
LETTERS TO THE EDITOR/ERRATA
2507
We would also like to comment on the predictive ability of other biomarkers regarding renal scarring, such as procalcitonin. Indeed, about 12 different teams have shown that procalcitonin provides a good predictive ability for diagnosing renal parenchymal involvement. These findings have also been confirmed in meta-analyses of studies and individual patient data.2,3 Moreover, procalcitonin was confirmed to offer diagnostic accuracy for late renal scarring in 9 cohort studies also summarized in a meta-analysis.3 Pooling individual patient data allowed us to perform a comparison of CRP, white blood cell count and procalcitonin, which revealed that procalcitonin was a better predictor than CRP or white blood cell count regarding acute pyelonephritis and later renal damage, with an area under the ROC curve that was significantly higher for both conditions.3 However, procalcitonin is not often used in daily clinical practice because of its poor availability in the context of emergency care. Nevertheless, given the growing evidence regarding the usefulness of procalcitonin in the infectious diseases field, this biomarker may translate into wider use and may overtake CRP in the coming years, as it looks promising for earlier diagnosis and prediction of severe infectious outcome. One example is deriving an imaging/examination evidence-based evaluation for children after a first UTI.4 In conclusion, the current debate on which imaging to prescribe after a pediatric UTI and the relaxing recommendations on vesicoureteral reflux assessment bring opportunities to produce, validate and evaluate in the future new algorithms that could consider population diversity on one hand and geographic differences in the management of such cases worldwide on the other. Respectfully, Sandrine Leroy and Justine Bacchetta Epidemiology of Emerging Diseases Unit Institut Pasteur Paris and Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant Bron, France 1. Royston P, Moons KG, Altman DG et al: Developing a prognostic model. BMJ 2009; 338: 604. 2. Mantadakis E, Plessa E, Vouloumanou EK et al: Serum procalcitonin for prediction of renal parenchymal involvement in children with urinary tract infections: a meta-analysis of prospective clinical studies. J Pediatr 2009; 155: 875. 3. Leroy S, Fernandez-Lopez A, Nifkar R et al: Predictive ability of procalcitonin for acute pyelonephritis and late renal scars in children
with urinary tract infection: systematic review and meta-analysis on individual patient data. Presented at 15th Congress of International Pediatric Nephrology Association, New York, August 29-September 2, 2010. 4. Leroy S and Gervaix A: Procalcitonin: a key marker in children with urinary tract infection. Adv Urol 2011: 2011; 397618.
Reply by Authors: We appreciate the comments by Leroy and Bacchetta. The main goal of our work with infants with urinary tract infections was to construct a clinical decision tool that is easy to use and can be applied at the bedside. The use of coefficients for CRP and renal anteroposterior diameter would complicate the formula with little additional effect on sensitivity and specificity, as illustrated by the ROC curve. The area under the curve increases from 0.77 for CRP alone to 0.81 for CRP in combination with anteroposterior diameter 10 mm or greater. The addition of serum creatinine, leukocyturia and non-Escherichia coli bacteria increases the area under the curve slightly to 0.84. Concerning other biomarkers for renal damage, procalcitonin is of great interest, although its availability for rapid analysis is restricted. Several other biomarkers are interesting, especially when urine samples can be used.1 1. Andersson L, Preda I, Hahn-Zoric M et al: Urinary proteins in children with urinary tract infection. Pediatr Nephrol 2009; 24: 1533.
LETTERS TO THE EDITOR/ERRATA
Reply by Authors: As stated in the article, the absence of data regarding the reasons for delayed treatment is a limitation of the study. We also agree with Klotz that upgrading at radical prostatectomy in the delayed group likely reflects grade progression as well as some higher grade tumors that were missed on the initial staging evaluation. Although it is unclear why sampling error on the initial biopsy would be different between the immediate and delayed groups, we cannot rule out the potential influence of unmeasured confounders on our results. Regardless, the findings in our study highlight the limitations of current clinical staging modalities to characterize accurately the biological aggressiveness of prostate cancers at diagnosis. While this fact may not prove to be clinically relevant for older men with significant comorbidities, these uncertainties are particularly critical for young men with a long life expectancy who are otherwise candidates for definitive therapy. In this regard many prior studies have evaluated the pathological outcomes of radical prostatectomy among men who would have met various criteria for active surveillance.1,2 For example Suardi et al reported aggressive pathology features in the radical prostatectomy specimen in 28% of men who would have met 2 of the most strict criteria for active surveillance.1 Nevertheless, prostatectomy tumor features are admittedly an imperfect proxy for survival outcomes. Our study takes this issue to the next level by actually showing significantly higher rates of biochemical recurrence in men who initially met low risk criteria but had a delay of more than 6 months before undergoing definitive therapy. Certainly we agree with Klotz that association is not equivalent to causation, and by no means do we suggest that our study establishes causality. Some of the key criteria to establish actual causality are strength and consistency of the evidence. In a recent update of the Scandinavian Prostate Cancer Group-4 randomized trial Bill-Axelson et al reported significant reductions in metastasis (RR 0.43, p ⫽ 0.008) and all cause mortality (RR 0.62, p ⫽ 0.02) with radical prostatectomy compared to watchful waiting at 15 years for men with low risk disease (PSA less than 10 ng/ml, Gleason less than 7 or WHO grade 1).3 Future prospective studies are needed to evaluate critically the long-term outcomes following definitive treatment compared to active surveillance in a contemporary population with screen detected disease. 1. Suardi N, Capitanio U, Chun FK et al: Currently used criteria for active surveillance in men with low-risk prostate cancer: an analysis of pathologic features. Cancer 2008; 113: 2068.
3. Bill-Axelson A, Holmberg L, Ruutu M et al: Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med 2011; 364: 1708.
2. Griffin CR, Yu X, Loeb S et al: Pathological features after radical prostatectomy in potential candidates for active monitoring. J Urol 2007; 178: 860.
Re: Imaging Strategy for Infants With Urinary Tract Infection: A New Algorithm I. Preda, U. Jodal, R. Sixt, E. Stokl and S. Hansson J Urol 2011; 185: 1046 –1052.
To the Editor: We appreciated the study by Preda et al, and their effort to provide an evidencebased evaluation of imaging techniques after urinary tract infection (UTI) in the current debate and controversies regarding the respective roles of ultrasound (US), cystography and dimercaptosuccinic acid scintigraphy. Briefly in a cohort of 270 children this prospective study demonstrated that C-reactive protein (CRP) could be a predictor of renal scarring. The first part of the analysis was nicely conducted, based only on variables available at the time of UTI diagnosis, and ended up in a reliable logistic regression model, including CRP and urinary tract dilatation on renal US. However, it would have been interesting to study the input of each of the significant variables into the model,1 running some maximum likelihood estimates to add weight and confidence to the choice of keeping only CRP and renal US for the next steps. Moreover, it is unclear why the authors chose to derive the practical decision rule by defining the best cutoff for CRP and renal anteroposterior diameter without weighting the 2 variables with any coefficient. This approach would give additional reliability and accuracy to the analysis, potentially making the rule more reproducible when it comes to external validation.
LETTERS TO THE EDITOR/ERRATA
2507
We would also like to comment on the predictive ability of other biomarkers regarding renal scarring, such as procalcitonin. Indeed, about 12 different teams have shown that procalcitonin provides a good predictive ability for diagnosing renal parenchymal involvement. These findings have also been confirmed in meta-analyses of studies and individual patient data.2,3 Moreover, procalcitonin was confirmed to offer diagnostic accuracy for late renal scarring in 9 cohort studies also summarized in a meta-analysis.3 Pooling individual patient data allowed us to perform a comparison of CRP, white blood cell count and procalcitonin, which revealed that procalcitonin was a better predictor than CRP or white blood cell count regarding acute pyelonephritis and later renal damage, with an area under the ROC curve that was significantly higher for both conditions.3 However, procalcitonin is not often used in daily clinical practice because of its poor availability in the context of emergency care. Nevertheless, given the growing evidence regarding the usefulness of procalcitonin in the infectious diseases field, this biomarker may translate into wider use and may overtake CRP in the coming years, as it looks promising for earlier diagnosis and prediction of severe infectious outcome. One example is deriving an imaging/examination evidence-based evaluation for children after a first UTI.4 In conclusion, the current debate on which imaging to prescribe after a pediatric UTI and the relaxing recommendations on vesicoureteral reflux assessment bring opportunities to produce, validate and evaluate in the future new algorithms that could consider population diversity on one hand and geographic differences in the management of such cases worldwide on the other. Respectfully, Sandrine Leroy and Justine Bacchetta Epidemiology of Emerging Diseases Unit Institut Pasteur Paris and Centre de Référence des Maladies Rénales Rares, Hôpital Femme Mère Enfant Bron, France 1. Royston P, Moons KG, Altman DG et al: Developing a prognostic model. BMJ 2009; 338: 604. 2. Mantadakis E, Plessa E, Vouloumanou EK et al: Serum procalcitonin for prediction of renal parenchymal involvement in children with urinary tract infections: a meta-analysis of prospective clinical studies. J Pediatr 2009; 155: 875. 3. Leroy S, Fernandez-Lopez A, Nifkar R et al: Predictive ability of procalcitonin for acute pyelonephritis and late renal scars in children
with urinary tract infection: systematic review and meta-analysis on individual patient data. Presented at 15th Congress of International Pediatric Nephrology Association, New York, August 29-September 2, 2010. 4. Leroy S and Gervaix A: Procalcitonin: a key marker in children with urinary tract infection. Adv Urol 2011: 2011; 397618.
Reply by Authors: We appreciate the comments by Leroy and Bacchetta. The main goal of our work with infants with urinary tract infections was to construct a clinical decision tool that is easy to use and can be applied at the bedside. The use of coefficients for CRP and renal anteroposterior diameter would complicate the formula with little additional effect on sensitivity and specificity, as illustrated by the ROC curve. The area under the curve increases from 0.77 for CRP alone to 0.81 for CRP in combination with anteroposterior diameter 10 mm or greater. The addition of serum creatinine, leukocyturia and non-Escherichia coli bacteria increases the area under the curve slightly to 0.84. Concerning other biomarkers for renal damage, procalcitonin is of great interest, although its availability for rapid analysis is restricted. Several other biomarkers are interesting, especially when urine samples can be used.1 1. Andersson L, Preda I, Hahn-Zoric M et al: Urinary proteins in children with urinary tract infection. Pediatr Nephrol 2009; 24: 1533.