Utility of F-15 diuretic MAG3 renography in assessment of paediatric hydronephrosis.

INTRODUCTION: Diuretic renography is crucial in evaluation of paediatric hydronephrosis. Furosemide is conventionally given 15-20 min after radiolabelled tracer (F+15/F+20 protocol), however this is equivocal in around 15% of patients. Giving furosemide 15 min prior to tracer (F-15 MAG3 protocol) has been suggested as an additional tool in the investigation of patients with suspected upper urinary tract obstruction. However, the role of this method in assessment and management of paediatric hydronephrosis is not widely reported. OBJECTIVE: To investigate utility of F-15 renograms in children with hydronephrosis being assessed for Pelvi-Ureteric Junction Obstruction (PUJO). STUDY DESIGN: Retrospective review of patients <16 years old undergoing F-15 MAG3 renogram between 2018 and 2021 in our tertiary paediatric surgical centre. Data collected included patient demographics, mode of presentation, investigations, management and outcomes. RESULTS: Eighteen patients were included. Median age at F-15 renogram was 7.3 years. Eleven patients presented with antenatal hydronephrosis, 5 with symptoms in childhood and 2 with incidental hydronephrosis on trauma imaging. Fourteen patients were symptomatic. Ten had a prior non-obstructed F+20 renogram but persisting symptoms suggestive of PUJO. Seven had previous equivocal F+20 renograms. One symptomatic patient directly underwent an F-15 renogram. A conclusive result was obtained in 16/18 (89%); 11 patients had obstructed curves and 5 non-obstructed. Two asymptomatic patients' scans were inconclusive. All symptomatic patients had conclusive scans. Of 11 patients with an obstructed F-15, 9 have undergone pyeloplasty to date. All have had post-operative resolution in symptoms and static or improved post-operative ultrasound. One patient with an inconclusive scan underwent pyeloplasty due to persisting hydronephrosis and parent preference. Three patients with non-obstructed F-15 renograms have been discharged. One symptomatic patient with a non-obstructive F-15 had a ureteric stent inserted due to persistent flank pain; 1 continues under surveillance. DISCUSSION: It is known that conventional F+20 MAG3 renograms can give equivocal results. Published experience suggests that F-15 renograms are conclusive in the majority of patients. Routine primary use is, however, discouraged as they can 'over diagnose' obstruction and limit the study of tracer transit under physiological flow rates. This study indicates that the F-15 renogram is a useful adjunct in the assessment of patients with symptoms suggestive of PUJO who have previously had an equivocal or a non-obstructed F+20 renogram. CONCLUSION: F-15 renogram was conclusive in 89% of patients. We recommend using F-15 renograms to aid surgical decision-making in children with equivocal F+20 renograms, especially in the presence of symptoms.

Low yield from imaging after non-E. coli urine tract infections in children treated in primary care and emergency department.

BACKGROUND: Imaging is recommended for selected children following urinary tract infections (UTIs) to look for actionable structural abnormalities. Non-E. coli is considered high risk in many national guidelines, but evidence is mainly drawn from small cohorts from tertiary centres. OBJECTIVE: To ascertain imaging yield from infants and children <12 years diagnosed with their first confirmed UTI (pure single growth >100 000 cfu per ml) in primary care or an emergency department without admission stratified by bacteria type. DESIGN, SETTING, PATIENTS: Data were collected from an administrative database of a UK citywide direct access UTI service between 2000 and 2021. Imaging policy mandated renal tract ultrasound and Technetium-99m dimercaptosuccinic acid scans in all children, plus micturating cystourethrogram in infants <12 months. RESULTS: 7730 children (79% girls, 16% aged <1 year, 55% 1-4 years) underwent imaging after first UTI diagnosed by primary care (81%) or emergency department without admission (13%). E. coli UTI yielded abnormal kidney imaging in 8.9% (566/6384). Enterococcus and KPP (Klebsiella, Proteus, Pseudomonas) yielded 5.6% (42/749) and 5.0% (24/483) with relative risks 0.63 (95% CI 0.47 to 0.86) and 0.56 (0.38 to 0.83)), respectively. No difference was found when stratified by age banding or imaging modality. CONCLUSION: In this largest published group of infants and children diagnosed in primary and emergency care not requiring admission, non-E. coli UTI was not associated with a higher yield from renal tract imaging.

The prevalence of familial vesicoureteric reflux in infants with normal antenatal scans.

AIM: To determine the prevalence of familial vesicoureteric reflux (VUR) by studying the outcomes of screening in a contemporary cohort of newborns with normal antenatal kidney scans. METHODS: A review of screening outcomes in newborns with a first degree relative with VUR, normal antenatal scans and no prior urine infections between 2014-2019 at three maternity units in the North East of England was conducted. Imaging consisted of micturating cystourethrogram (MCUG) in all and renal tract ultrasound scan (RUS) routinely in two units and by clinician preference in one unit. RESULTS: At a median age of 59 days, 265 infants underwent MCUG. High-grade VUR (Grades 3-5) was detected in 13 (4.9%) and low-grade VUR (Grades 1-2) in 24 (9.1%). In the 152 infants who had a RUS, abnormalities were detected in 21 (13.8%). An abnormal postnatal RUS has a low positive predictive value (14.3%) for high-grade VUR, but a normal RUS has a high negative predictive value (95.4%). CONCLUSION: Compared to historical cohorts from two decades ago, the yield from familial VUR screening is low and unjustifiable in the setting of normal antenatal anomaly scans.

Diagnosing and treating occult vesicoureteric reflux using PIC cystography: Is it influenced by abnormalities on DMSA?

BACKGROUND: Positioning the Instillation of Contrast cystography (PICc) is used to identify occult vesicoureteric reflux (VUR) in patients with recurrent urinary tract infections (UTI) despite optimized bladder and bowel function and without VUR demonstrated on conventional imaging. AIM: To determine the incidence of finding occult VUR in such patients usingPICc and the benefit, if any, of treating it. We also assessed if this was influenced by abnormalities on the pre-operative DMSA. PATIENTS AND METHODS: This was a retrospective review of PICc in our hospital between 2016 and 2018 and involved three paediatric urologists. The primary indication for PICc was two or more culture proven UTIs despite optimized bladder and bowel function and no reflux on voiding cystourethrography (VCUG) or indirect radionuclide cystography (I-RNC). All children had a preoperative DMSA scan to document any abnormalities. PICc was performed in a standardized way to each ureteric orifice. If occult reflux was found, it was treated concomitantly by cystoscopic injection of Deflux®. To assess the influence of the pre-operative DMSA status, the cohort was subdivided into two groups based on the DMSA scan: Group 1-abnormal DMSA, Group 2-normal DMSA. The median follow-up was 26 months (range 3-39 months). RESULTS: PICc was performed in 25 patients [23 females and 2 males; median age: 7 years (range 2-16 years; IQR = 4)]; 17 from Group 1 and 8 from Group 2. Occult VUR was identified in 22 patients (88%); 15/17 (88.2%) in Group 1 and 7/8 (87.5%) in Group 2 (p = 0.9). After cystoscopic treatment, 21/25 (84%) became infection free and this was not influenced by the preoperative DMSA status (p = 0.6). Fig 1. DISCUSSION: In this challenging group of patients, looking for and treating occult reflux appears to be clinically useful and beneficial. The ability to test and treat at the same sitting is an added advantage of PICc. The DMSA results did not influence the diagnostic or therapeutic aspect of the process. Our results concur with other published literature. CONCLUSION: There is a high incidence of finding occult reflux using PICc in this cohort of patients. Concomitant cystoscopic treatment led to 84% of children becoming infection free on follow up. Abnormalities on DMSA did not influence either the likelihood of finding occult reflux or the likelihood of successful treatment.

Ratiology and a Complementary Class of Metrics for Cardiovascular Investigations.

Cardiovascular investigations often involve ratio-based metrics or differences: ejection fraction, arterial pressure augmentation index, coronary fractional flow reserve, pulse pressure. Focusing on a single number (ratio or difference) implies that information is lost. The lost companions constitute a well-defined but thus far unrecognized class, having additive value, a physical dimension, and often a physiological meaning. Physiologists should play a prominent role in exploring these complementary avenues and also define alternatives.

The Pythagorean theorem reveals the inherent companion of cardiac ejection fraction.

BACKGROUND: Quantification of ventricular performance requires a comprehensive metric which is manageable for patient care and clinical trials. Ejection fraction (EF) has been embraced as an attractive candidate. However, being a dimensionless ratio, EF has serious limitations. METHODS: We aim to identify what information is not recognized when limiting the volume-related analysis by exclusively relying on EF. This investigation applies the volume domain concept, relating end-systolic volume (ESV) to end-diastolic volume (EDV). This approach allows graphical identification of the information not covered by EF. Implications for atria, left ventricle (LV) and right ventricle (RV) are investigated in healthy individuals, and cardiac patient groups using various imaging modalities. RESULTS: The Pythagorean theorem indicates that the hypotenuse which relates any {EDV, ESV} combination to EF corresponds with the information not covered by the single metric EF. The impact of the recovered EF companion (EFC) is illustrated in healthy adults (N = 410, LV 2D echocardiography), heart transplant patients (N = 101, LV CT), individuals with heart failure (N = 197, biplane angiocardiography), for the RV with corrected Fallot (N = 124, MRI), diameters for left atrium (N = 49, MRI) and area for right atrium (N = 51, MRI). For any limited EF range we find a spectrum of EFC values, showing that the two metrics contain (partly) independent information, and emphasizing that the sole use of EF only partially conveys the full information available. CONCLUSIONS: The EFC is a neglected companion, containing information which is additive to EF. Analysis based on ESV and EDV is preferred over the use of EF.

Heart Function Analysis in Cardiac Patients with Focus on Sex-Specific Aspects.

Cardiac function is best described by investigating the pressure-volume relationships. This information permits description in terms of the ventricular volume regulation graph (VRG), estimation of systolic elastance, evaluation of lusitropic properties, and assessment of ventriculo-arterial coupling. Current techniques yield noninvasive determination of cardiac compartmental volumes, along with systolic/diastolic arterial pressure, while ventricular end-diastolic pressure can be inferred from an echocardiography-based surrogate measure. Ventricular volume is known to vary with age, as well as to be affected by intrinsic cardiac disease and abnormalities of the vascular system. Moreover, 35 years ago it has been shown in healthy adults that left ventricular volume is significantly smaller in women compared to men. This important observation has serious implications for several metrics which are routinely used in clinical practice, e.g., ejection fraction. The remarkable difference between ventricular size in men and women is also a powerful starting point for the study of aging and the investigation of interventions such as exercise. In this review we evaluate sex-specific characteristics of the VRG and the implications for various cardiac patient populations, during basal conditions and intervention such as exercise.

Sex- and Age-Related Reference Values in Cardiology, with Annotations and Guidelines for Interpretation.

The definition of "abnormal" in clinical sciences is often based on so-called reference values which point to a range that experts by some sort of consensus consider as normal when looking at biological variables. Such a level is commonly calculated by taking (twice) the standard deviation from the mean, or considering certain percentiles. The suspicion or even confirmation of a disease is then established by demonstrating that the value measured exceeds the upper or lower reference value. As is often the case, the measurement accuracy may depend on the conditions and specific method employed to collect and analyze data. This implies that, for example, data assessed by 2D echocardiography possibly differ from those obtained by MRI and therefore require modality-specific reference values. In this review we summarize reference values for the electrocardiogram, cardiac compartmental volumes, and arterial vessel size in males and females for various age groups. These values may further depend on other variables such as body size, physical training status, and ethnicity. Additional variables relevant for cardiology such as those referring to the microcirculation and biomarkers are only mentioned with reference to the pertinent literature. In general, the sex- and age-specific differences observed are often remarkable and warrant consideration in clinical practice and basic biomedical sciences.

Ejection fraction as related to basic components in the left and right ventricular volume domains.

BACKGROUND: Ejection fraction (EF) is commonly applied as a clinically relevant metric to assess ventricular function. The numerical value of EF depends on the interplay between end-systolic volume (ESV) and end-diastolic volume (EDV). Remarkably, the relative impact of the two constitutive components on EF received little attention. METHODS: Three patient groups not using beta-blockers were analyzed for a robust investigation into the relative contribution of ESV and EDV when assessing EF: cardiac patients (N=155) with left ventricular (LV) data obtained by biplane ventriculography, near-normals (N=276) by gated SPECT investigation, and an MRI-based post Fallot repair study including right ventricular (RV) data (N=124), besides LV. We compared various routes to evaluate EF via linear and several types of nonlinear regression with ESV as independent variable. Advanced statistics was applied to evaluate sex-specific differences. RESULTS: In all cases ESV emerges as the dominant component of EF, with less (P<0.0001) impact of EDV. The relationship for EF versus ESV is nonlinear (P<0.0001), and similar for both sexes. A linear approach may be inadequate and generate erroneous statistical outcomes when comparing subgroups of patients. CONCLUSIONS: Values for EF primarily depend on ESV, both for LV and RV. This relationship is essentially nonlinear, and similar for both sexes. A logarithmic approximation is convenient and often acceptable. However, application of linear regression for EF vs ESV may lead to incorrect conclusions, particularly when comparing males and females.

Radioactive seed localization compared with wire-guided localization of non-palpable breast carcinoma in breast conservation surgery- the first experience in the United Kingdom.

OBJECTIVE: In the UK, guidewires have traditionally been used for localization of non-palpable breast lesions in patients undergoing breast conservation surgery (BCS). Radioactive seed localization (RSL) using Iodine-125 seeds is an alternative localization method and involves inserting a titanium capsule, containing radioactive Iodine-125, into the breast lesion. We aim to demonstrate feasibility of RSL compared with guidewire-localization (GWL) for BCS in the UK. METHODS: Data were collected on 100 patients with non-palpable unifocal invasive carcinoma of the breast undergoing GWL WLE prior to the introduction of RSL and the first 100 patients treated with RSL WLE. Statistical comparisons were made using Χ2-squared analysis or unpaired two-sample t-test. Significance was determined to be at p ≤ 0.05. RESULTS: Mean total tumour size was 19.44 mm (range: 5-55) in the GWL group and 18.61 mm (range: 3.8-59) in the RSL group (p = 0.548), while mean total specimen excision weight was significantly lower in the RSL group; 31.55 g (range: 4.5-112) vs 37.42 g (range: 7.8-157.1) (p = 0.018). Although 15 patients had inadequate surgical resection margins in the GWL group compared the 13 in the RSL group (15 vs 13%, respectively, p = 0.684), 10 of the patients in the GWL group had invasive carcinoma present resulting in at least one positive margin compared with only 3 patients in the RSL group (10 vs 3%, respectively, p = 0.045). CONCLUSION: In this study, RSL is shown to be non-inferior to the use of GWL for non-palpable carcinoma in patients undergoing BCS and we suggest that it could be introduced successfully in other breast units. Advances in knowledge: Here we have demonstrated the use of RSL localization results in significant lower weight resection specimens of breast carcinoma when compared with a matched group using GWL, without any significant differences in oncological outcome between the groups.

Monte Carlo method applied to the evaluation of the relationship between ejection fraction and its constituent components.

Ventricular function is routinely assessed by applying the clinically accepted metric ejection fraction (EF). The numerical value of EF depends on the interplay between end-systolic volume (ESV) and end-diastolic volume (EDV). The relative impact of the two constitutive components has received little attention. Pediatric cardiologists are interested in EF vs ESV when evaluating various congenital abnormalities. Following successful surgical intervention of Fallot tetralogy, many of these patients receive follow-up, not only during childhood, but also when being adults. Cardiologists diagnosing and treating elderly patients often analyze EF vs EDV, notably for phenotyping heart failure patients. Therefore, we study EF vs ESV as well as EF vs EDV in more detail. We explore the fundamentals of EF while analyzing a Fallot patient group. Three routes were followed, namely nonlinear regression, by implementing a Monte Carlo approach to generate EDV on the basis of known ESV values, and by using a theoretical graphical derivation. Our MRI-based post Fallot repair study includes left (LV) and right ventricular (RV) data (N=124). Using a robust approach we employed nonlinear regression with ESV as an independent variable. EDV was also assessed by Monte Carlo generated values for stroke volume within a physiological range. In all cases ESV emerges as the dominant component of EF, with less (P<;0.0001) impact of EDV. Using three independent routes we demonstrate that values for EF primarily depend on the corresponding ESV. This relationship is nonlinear, and correlation is always better with ESV compared to EDV in these patients, and confirmed in random number modeling studies.

Effect of sex, age, and weight on ejection fraction and end-systolic volume reference limits in gated myocardial perfusion SPECT.

BACKGROUND: The left-ventricular ejection fraction (EF) and end-systolic volume (ESV) are strong predictors of prognosis for cardiac death. Gated myocardial perfusion single-photon emission computed tomography (gSPECT) may be used to measure ESV and EF. However, systematic differences may exist between referred populations. Our aim was to derive male and female reference limits for left-ventricular functional parameters, and determine the effect of age, weight, and body surface area (BSA). METHODS AND RESULTS: The ejection fraction and ESV were derived using QGS software for 127 patients with normal gSPECT studies. The lower reference limits of EF were 46.2% and 55.6% for men and women, respectively. The upper reference limits of ESV were 30.4 mL and 21.4 mL, and 15.7 mL/m(2) and 11.1 mL/m(2), when indexed to BSA for men and women, respectively. There was no correlation between EF and age, weight, or BSA (P > .05). There was a small decrease in ESV with age, and an increase with weight and BSA (P < .05). The sex-specific differences remained after adjusting for confounding variables. CONCLUSIONS: We demonstrated a significant sex difference for all functional parameters measured, and we established the influence of patient age and weight. Local reference limits for ESV and EF have been established, and the latter are transferable to other departments operating similar protocols.

The effect of imaging time, radiopharmaceutical, full fat milk and water on interfering extra-cardiac activity in myocardial perfusion single photon emission computed tomography.

BACKGROUND AND AIM: Extra-cardiac activity can interfere with observer interpretation of myocardial perfusion single photon emission computed tomography (SPECT) images. Fatty meals and drinks to reduce interference have been tested; however, a simple study of delayed imaging with (99m)Tc-tetrofosmin and (99m)Tc-sestamibi has not been specifically addressed. The aim was to quantify the effects of imaging time, radiopharmaceutical and oral administration of full fat milk and water on interfering activity. METHODS: Myocardial perfusion SPECT images were acquired using either tetrofosmin or sestamibi. Patients were imaged at 0.5, 1 or 2 h post-injection (tetrofosmin, 59; sestamibi, 72). Additional groups of patients were imaged either with or without milk (tetrofosmin, 54; sestamibi, 45) and with milk and water (sestamibi, 30). A myocardial region was drawn on the anterior projection and a thin adjacent extra-cardiac region was generated automatically. The count density ratio was calculated and validated with a trial of five observers. A decreasing ratio correlated significantly with observer rank of increasing interference with SPECT image interpretation (r=0.95, P=0.001). RESULTS: The ratio improved significantly as the imaging time increased for both tetrofosmin and sestamibi groups (P<0.05). The groups given milk or milk plus water showed no significant improvement against control groups (P > or = 0.2). There was no significant difference between tetrofosmin and sestamibi at any time point (P > or = 0.4). CONCLUSIONS: Image interpretation may be improved by delayed imaging for tetrofosmin and sestamibi. However, in contrast with common practice, the administration of milk or water appears to be of no clinical value compared with delayed imaging, and there is no significant difference between interfering activity from tetrofosmin and sestamibi.

Exo-pi-bonding to an ortho-carborane hypercarbon atom: systematic icosahedral cage distortions reflected in the structures of the fluoro-, hydroxy- and amino-carboranes, 1-X-2-Ph-1,2-C2B10H10 (X=F, OH or NH2) and related anions.

The structures of derivatives of phenyl-ortho-carborane bearing on the second cage hypercarbon atom a pi-donor substituent (F, OH, O-, NH2, NH- and CH2-) were investigated by NMR, X-ray crystallography and computational studies. The molecular structures of these compounds, notably their cage C1-C2 distances and the orientations of their pi-donor substituents (OH, NH2, NH- and CH2-) show remarkable and systematic variations with the degree of exo pi-bonding, which varies as expected with the pi-donor characteristics of the substituent.