A questionnaire survey of radiological diagnosis and management of renal dysplasia in children

Background: The condition called renal dysplasia is considered to be a frequent cause of chronic kidney disease in children. Formally, it is defined by histological parameters. In current nephrology practice, however, the appearance of the kidneys on ultrasound scanning is often used as a basis for the diagnosis. Methods: The European Society for Pediatric Nephrology Working Group on Congenital Anomalies of the Kidney and Urinary Tract hypothesized that the current diagnostic approach with regard to renal dysplasia was not homogeneous. Accordingly, we here report the results of a survey targeting pediatric nephrologists with 12 questions regarding their perceptions of the ultrasonographic characteristics of renal dysplasia and further tests that they might undertake. Results: Of almost 1200 physicians who successfully received the invitation, 248 from 54 countries completed the survey. There was a notable lack of homogeneity regarding the ultrasonographic diagnosis of renal dysplasia and also of follow-up tests, including genetic testing and further radiology. Conclusions: Based on the responses to this large survey, a picture emerges of nephrologists' current clinical practice with regard to renal dysplasia. The Working Group considers that these results serve as an important sounding board which can provide the basis for more definitive recommendations regarding the challenges to clinical diagnosis and diagnostic follow-up of this important condition

Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial

BACKGROUND: Tumor ablation is often employed for unresectable colorectal liver metastases. However, no survival benefit has ever been demonstrated in prospective randomized studies. Here, we investigate the long-term benefits of such an aggressive approach. METHODS: In this randomized phase II trial, 119 patients with unresectable colorectal liver metastases (n  38%) was met. We now report on long-term OS results. All statistical tests were two-sided. The analyses were according to intention to treat. RESULTS: At a median follow up of 9.7 years, 92 of 119 (77.3%) patients had died: 39 of 60 (65.0%) in the combined modality arm and 53 of 59 (89.8%) in the systemic treatment arm. Almost all patients died of progressive disease (35 patients in the combined modality arm, 49 patients in the systemic treatment arm). There was a statistically significant difference in OS in favor of the combined modality arm (hazard ratio [HR] = 0.58, 95% confidence interval [CI] = 0.38 to 0.88, P = .01). Three-, five-, and eight-year OS were 56.9% (95% CI = 43.3% to 68.5%), 43.1% (95% CI = 30.3% to 55.3%), 35.9% (95% CI = 23.8% to 48.2%), respectively, in the combined modality arm and 55.2% (95% CI = 41.6% to 66.9%), 30.3% (95% CI = 19.0% to 42.4%), 8.9% (95% CI = 3.3% to 18.1%), respectively, in the systemic treatment arm. Median OS was 45.6 months (95% CI = 30.3 to 67.8 months) in the combined modality arm vs 40.5 months (95% CI = 27.5 to 47.7 months) in the systemic treatment arm. CONCLUSIONS: This phase II trial is the first randomized study demonstrating that aggressive local treatment can prolong OS in patients with unresectable colorectal liver metastases

Transfusion Volume for Children with Severe Anemia in Africa

Background Severe anemia (hemoglobin level, 37.5°C) at screening (P=0.001 after Sidak correction). Among the 1943 children (60.8%) without fever, mortality was lower with a transfusion volume of 30 ml per kilogram than with a volume of 20 ml per kilogram (hazard ratio, 0.43; 95% CI, 0.27 to 0.69). Among the 1253 children (39.2%) with fever, mortality was higher with 30 ml per kilogram than with 20 ml per kilogram (hazard ratio, 1.91; 95% CI, 1.04 to 3.49). There was no evidence of differences between the randomized groups in readmissions, serious adverse events, or hemoglobin recovery at 180 days. Conclusions Overall mortality did not differ between the two transfusion strategies. (Funded by the Medical Research Council and Department for International Development, United Kingdom; TRACT Current Controlled Trials number, ISRCTN84086586. opens in new tab.

Imaging standardization in metastatic colorectal cancer : a joint EORTC-ESOI-ESGAR expert consensus recommendation

Background: Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumor burden. Response Evaluation Criteria in Solid Tumors (RECIST) provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardized imaging protocol tailored to mCRC patients. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging endpoints and is an obstacle for research on novel imaging endpoints. Patients and methods: Acknowledging the recently highlighted potential of radiomics and artificial intelligence (AI) tools as decision support for patient care in mCRC, a multidisciplinary, international, and expert panel of imaging specialists was formed to find consensus on mCRC imaging protocols using the Delphi method. Results: Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups, the European Society of Oncologic Imaging (ESOI) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the EORTC-ESOI-ESGAR core imaging protocol was identified. Conclusion: This consensus protocol attempts to promote standardization and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardization will increase reproducibility of radiomics and AI studies and serve as a catalyst for future research on imaging endpoints. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these imaging standards across recruiting centers.peer-reviewe

The Diagnosis of Urinary Tract infection in Young children (DUTY): a diagnostic prospective observational study to derive and validate a clinical algorithm for the diagnosis of urinary tract infection in children presenting to primary care with an acute illness

Background It is not clear which young children presenting acutely unwell to primary care should be investigated for urinary tract infection (UTI) and whether or not dipstick testing should be used to inform antibiotic treatment. Objectives To develop algorithms to accurately identify pre-school children in whom urine should be obtained; assess whether or not dipstick urinalysis provides additional diagnostic information; and model algorithm cost-effectiveness. Design Multicentre, prospective diagnostic cohort study. Setting and participants Children < 5 years old presenting to primary care with an acute illness and/or new urinary symptoms. Methods One hundred and seven clinical characteristics (index tests) were recorded from the child’s past medical history, symptoms, physical examination signs and urine dipstick test. Prior to dipstick results clinician opinion of UTI likelihood (‘clinical diagnosis’) and urine sampling and treatment intentions (‘clinical judgement’) were recorded. All index tests were measured blind to the reference standard, defined as a pure or predominant uropathogen cultured at ≥ 105 colony-forming units (CFU)/ml in a single research laboratory. Urine was collected by clean catch (preferred) or nappy pad. Index tests were sequentially evaluated in two groups, stratified by urine collection method: parent-reported symptoms with clinician-reported signs, and urine dipstick results. Diagnostic accuracy was quantified using area under receiver operating characteristic curve (AUROC) with 95% confidence interval (CI) and bootstrap-validated AUROC, and compared with the ‘clinician diagnosis’ AUROC. Decision-analytic models were used to identify optimal urine sampling strategy compared with ‘clinical judgement’. Results A total of 7163 children were recruited, of whom 50% were female and 49% were < 2 years old. Culture results were available for 5017 (70%); 2740 children provided clean-catch samples, 94% of whom were ≥ 2 years old, with 2.2% meeting the UTI definition. Among these, ‘clinical diagnosis’ correctly identified 46.6% of positive cultures, with 94.7% specificity and an AUROC of 0.77 (95% CI 0.71 to 0.83). Four symptoms, three signs and three dipstick results were independently associated with UTI with an AUROC (95% CI; bootstrap-validated AUROC) of 0.89 (0.85 to 0.95; validated 0.88) for symptoms and signs, increasing to 0.93 (0.90 to 0.97; validated 0.90) with dipstick results. Nappy pad samples were provided from the other 2277 children, of whom 82% were < 2 years old and 1.3% met the UTI definition. ‘Clinical diagnosis’ correctly identified 13.3% positive cultures, with 98.5% specificity and an AUROC of 0.63 (95% CI 0.53 to 0.72). Four symptoms and two dipstick results were independently associated with UTI, with an AUROC of 0.81 (0.72 to 0.90; validated 0.78) for symptoms, increasing to 0.87 (0.80 to 0.94; validated 0.82) with the dipstick findings. A high specificity threshold for the clean-catch model was more accurate and less costly than, and as effective as, clinical judgement. The additional diagnostic utility of dipstick testing was offset by its costs. The cost-effectiveness of the nappy pad model was not clear-cut. Conclusions Clinicians should prioritise the use of clean-catch sampling as symptoms and signs can cost-effectively improve the identification of UTI in young children where clean catch is possible. Dipstick testing can improve targeting of antibiotic treatment, but at a higher cost than waiting for a laboratory result. Future research is needed to distinguish pathogens from contaminants, assess the impact of the clean-catch algorithm on patient outcomes, and the cost-effectiveness of presumptive versus dipstick versus laboratory-guided antibiotic treatment

A questionnaire survey of radiological diagnosis and management of renal dysplasia in children

Background: The condition called renal dysplasia is considered to be a frequent cause of chronic kidney disease in children. Formally, it is defined by histological parameters. In current nephrology practice, however, the appearance of the kidneys on ultrasound scanning is often used as a basis for the diagnosis. Methods: The European Society for Pediatric Nephrology Working Group on Congenital Anomalies of the Kidney and Urinary Tract hypothesized that the current diagnostic approach with regard to renal dysplasia was not homogeneous. Accordingly, we here report the results of a survey targeting pediatric nephrologists with 12 questions regarding their perceptions of the ultrasonographic characteristics of renal dysplasia and further tests that they might undertake. Results: Of almost 1200 physicians who successfully received the invitation, 248 from 54 countries completed the survey. There was a notable lack of homogeneity regarding the ultrasonographic diagnosis of renal dysplasia and also of follow-up tests, including genetic testing and further radiology. Conclusions: Based on the responses to this large survey, a picture emerges of nephrologists’ current clinical practice with regard to renal dysplasia. The Working Group considers that these results serve as an important sounding board which can provide the basis for more definitive recommendations regarding the challenges to clinical diagnosis and diagnostic follow-up of this important condition

Cetuximab plus gemcitabine and cisplatin compared with gemcitabine and cisplatin alone in patients with advanced pancreatic cancer: a randomised, multicentre, phase II trial

Background: Preclinical data have suggested a synergistic effect of cetuximab combined with gemcitabine and cisplatin and clinical data have shown a substantial improvement in response and survival when gemcitabine is combined with a platinum analogue compared with gemcitabine alone. The aim of this study was to assess the activity and feasibility of a combination of cetuximab with gemcitabine and cisplatin compared with use of gemcitabine and cisplatin alone for the treatment of advanced pancreatic cancer. Methods: In a multicentre, randomised phase II trial, 84 patients with advanced pancreatic cancer were randomly assigned to either 250 mg/m2 cetuximab weekly, after a loading dose of 400 mg/m2, plus 1000 mg/m2 gemcitabine and 35 mg/m2 cisplatin on days 1 and 8 of a 21-day cycle or to the same chemotherapeutic regimen without cetuximab. The primary endpoint was objective response (defined as the proportion of patients whose best response was either partial response or complete response). Secondary endpoints included disease control (defined as the proportion of patients whose best response was either partial response, complete response, or stable disease), progression-free survival, and overall survival. All assessments of response at each site were done blindly by a local experienced radiologist who was not directly involved in the trial. Responses were measured according to an intention-to-treat analysis. This trial is registered with the Clinical Trial registry, number NCT00536614. Findings: 29 men and 13 women were randomly assigned to cetuximab plus gemcitabine and cisplatin (median age 61 years [range 38-78]) and 22 men and 20 women were randomly assigned to gemcitabine and cisplatin (median age 64 years [range 40-76]). Seven of 40 (17·5%) patients had an objective response in the cetuximab group (95% CI 7·3-32·8) and five of 41 (12·2%) patients had an objective response in the non-cetuximab group (95% CI 4·1-26·2). No significant difference was noted between the groups both for objective response (5·3% higher in the cetuximab group [95% CI -16·5 to 27·1]; χ2 test=0·360; p=0·549) or for disease control (3·5% higher in the non-cetuximab group [-34·0% to 27·0%]; 0·446; p=0·504). Overall median follow-up was 11·8 months (range 2·5-18·5). No significant differences between the groups were noted in median progression-free survival (hazard ratio 0·96, 95% CI 0·60-1·52, p=0·847) or in median overall survival (0·91, 0·54-1·55, p=0·739): median progression-free survival was 3·4 months (95% CI 2·4-5·1) in the cetuximab group and 4·2 months (2·6-5·4) in the non-cetuximab group; median overall survival was 7·5 months (5·1-8·8) and 7·8 months (5·3-15·0), respectively. 33 patients from both groups had at least one grade 3-4 toxic effect. Interpretation: The addition of cetuximab to a combination of gemcitabine and cisplatin does not increase response or survival for patients with advanced pancreatic cancer. Although toxic effects were not increased by cetuximab, this combination should not be further assessed in phase III trials