Ureteropelvic junction obstruction and renal calculi: Simultaneous treatment by robot-assisted laparoscopic pyeloplasty and transcutaneous retrograde flexible ureteroscopy. Technique description and early outcomes.

BACKGROUND: Ureteropelvic junction obstruction (UPJO) and renal calculi are associated in 20 to 30% of cases and treatment is mandatory. The simultaneous surgical management is a therapeutic challenge that is still a source of controversy. We describe our technique combining robot-assisted laparoscopic pyeloplasty and transcutaneous retrograde flexible ureteroscopy (fURS), assessing the feasibility of simultaneous treatment through an original technique. METHODS: This single centre series reports our initial experience with 12 patients. From January 2014 to September 2018, 12 patients underwent robot-assisted laparoscopic pyeloplasty with simultaneous fURS for UPJO and renal calculi. Mean age was 46 years (24-68). 92% had multiple renal stones and the mean cumulative stone diameter was 31,3mm. Robot-assisted pyeloplasty was performed with peroperative transcutaneous retrograde fURS through a ureteral access sheath introduced in an incision on the bassinet through a subcostal trocar. Stone extraction was performed using a basket. RESULTS: All patients underwent surgery successfully, achieving UPJ repair and complete stone extraction. Mean operating time was 92,5min (85-110). All reported Clavien-Dindo complications were grade 1. Non-contrast enhanced abdominal CT performed 1 month after surgery confirmed the absence of residual stones in all patients. Mean follow-up time was 10 months with no recurrence of UPJO. CONCLUSION: This small series confirms the feasibility with good surgical results of concomitant robot-assisted laparoscopic pyeloplasty and transcutaneous retrograde fURS stone extraction. No major complications were observed. This technique is easily reproducible but requires 2 experienced urologists to be achieved in a contained operative time.

A 3D printed pulmonary mock loop for hemodynamic studies in congenital heart disease.

Background. With the increasing survival of the congenital heart disease population, there is a growing need for in-depth understanding of blood circulation in these patients. Mock loops provide the opportunity for comprehensive hemodynamic studies without burden and risks for patients. This study aimed to evaluate the ability of the presented mock loop to mimic the hemodynamics of the pulmonary circulation with and without stenosis and the MR compatibility of the system.Methods. A pulsatile pump with two chambers, separated by a flexible membrane, was designed and 3D printed. A cough assist device applied an alternating positive and negative pressure on the membrane. One adult, and three pediatric pulmonary bifurcations were 3D printed and incorporated in the setup. Two pediatric models had a 50% stenosis of the left branch. Bilateral compliance chambers allowed for individual compliance tuning. A reservoir determined the diastolic pressure. Two carbon heart valves guaranteed unidirectional flow. The positive pressure on the cough assist device was tuned until an adequate stroke volume was reached with a frequency of 60 bpm. Flow and pressure measurements were performed on the main pulmonary artery and the two branches. The MR compatibility of the setup was evaluated.Results. A stroke volume with a cardiac index of 2 l min-1m-2was achieved in all models. Physiological pressure curves were generated in both normal and stenotic models. The mock loop was MR compatible.Conclusion.This MR compatible mock loop, closely resembles the pulmonary circulation thereby providing a controllable environment for hemodynamic studies.

Treatment Efficacy Score-continuous residual cancer burden-based metric to compare neoadjuvant chemotherapy efficacy between randomized trial arms in breast cancer trials.

BACKGROUND: Difference in pathologic complete response (pCR) rate after neoadjuvant chemotherapy does not capture the impact of treatment on downstaging of residual cancer in the experimental arm. We developed a method to compare the entire distribution of residual cancer burden (RCB) values between clinical trial arms to better quantify the differences in cytotoxic efficacy of treatments. PATIENTS AND METHODS: The Treatment Efficacy Score (TES) reflects the area between the weighted cumulative distribution functions of RCB values from two trial arms. TES is based on a modified Kolmogorov-Smirnov test with added weight function to capture the importance of high RCB values and uses the area under the difference between two distribution functions as a statistical metric. The higher the TES the greater the shift to lower RCB values in the experimental arm. We developed TES from the durvalumab + olaparib arm (n = 72) and corresponding controls (n = 282) of the I-SPY2 trial. The 11 other experimental arms and control cohorts (n = 947) were used as validation sets to assess the performance of TES. We compared TES to Kolmogorov-Smirnov, Mann-Whitney, and Fisher's exact tests to identify trial arms with higher cytotoxic efficacy and assessed associations with trial arm level survival differences. Significance was assessed with a permutation test. RESULTS: In the validation set, TES identified arms with a higher pCR rate but was more accurate to identify regimens as less effective if treatment did not reduce the frequency of high RCB values, even if the pCR rate improved. The correlation between TES and survival was higher than the correlation between the pCR rate difference and survival. CONCLUSIONS: TES quantifies the difference between the entire distribution of pathologic responses observed in trial arms and could serve as a better early surrogate to predict trial arm level survival differences than pCR rate difference alone.

Computational Analysis of the Pulmonary Arteries in Congenital Heart Disease: A Review of the Methods and Results.

With the help of computational fluid dynamics (CFD), hemodynamics of the pulmonary arteries (PA's) can be studied in detail and varying physiological circumstances and treatment options can be simulated. This offers the opportunity to improve the diagnostics and treatment of PA stenosis in biventricular congenital heart disease (CHD). The aim of this review was to evaluate the methods of computational studies for PA's in biventricular CHD and the level of validation of the numerical outcomes. A total of 34 original research papers were selected. The literature showed a great variety in the used methods for (re) construction of the geometry as well as definition of the boundary conditions and numerical setup. There were 10 different methods identified to define inlet boundary conditions and 17 for outlet boundary conditions. A total of nine papers verified their CFD outcomes by comparing results to clinical data or by an experimental mock loop. The diversity in used methods and the low level of validation of the outcomes result in uncertainties regarding the reliability of numerical studies. This limits the current clinical utility of CFD for the study of PA flow in CHD. Standardization and validation of the methods are therefore recommended.

Predicted sensitivity to endocrine therapy for stage II-III hormone receptor-positive and HER2-negative (HR+/HER2-) breast cancer before chemo-endocrine therapy.

BACKGROUND: We proposed that a test for sensitivity to the adjuvant endocrine therapy component of treatment for patients with stage II-III breast cancer (SET2,3) should measure transcription related to estrogen and progesterone receptors (SETER/PR index) adjusted for a baseline prognostic index (BPI) combining clinical tumor and nodal stage with molecular subtype by RNA4 (ESR1, PGR, ERBB2, and AURKA). PATIENTS AND METHODS: Patients with clinically high-risk, hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) breast cancer received neoadjuvant taxane-anthracycline chemotherapy, surgery with measurement of residual cancer burden (RCB), and then adjuvant endocrine therapy. SET2,3 was measured from pre-treatment tumor biopsies, evaluated first in an MD Anderson Cancer Center (MDACC) cohort (n = 307, 11 years' follow-up, U133A microarrays), cut point was determined, and then independent, blinded evaluation was carried out in the I-SPY2 trial (n = 268, high-risk MammaPrint result, 3.8 years' follow-up, Agilent-44K microarrays, NCI Clinical Trials ID: NCT01042379). Primary outcome measure was distant relapse-free survival. Multivariate Cox regression models tested prognostic independence of SET2,3 relative to RCB and other molecular prognostic signatures, and whether other prognostic signatures could substitute for SETER/PR or RNA4 components of SET2,3. RESULTS: SET2,3 added independent prognostic information to RCB in the MDACC cohort: SET2,3 [hazard ratio (HR) 0.23, P = 0.004] and RCB (HR 1.77, P < 0.001); and the I-SPY2 trial: SET2,3 (HR 0.27, P = 0.031) and RCB (HR 1.68, P = 0.008). SET2,3 provided similar prognostic information irrespective of whether RCB-II or RCB-III after chemotherapy, and in both luminal subtypes. Conversely, RCB was most strongly prognostic in cancers with low SET2,3 status (MDACC P < 0.001, I-SPY2 P < 0.001). Other molecular signatures were not independently prognostic; they could effectively substitute for RNA4 subtype within the BPI component of SET2,3, but they could not effectively substitute for SETER/PR index. CONCLUSIONS: SET2,3 added independent prognostic information to chemotherapy response (RCB) and baseline prognostic score or subtype. Approximately 40% of patients with clinically high-risk HR+/HER2- disease had high SET2,3 and could be considered for clinical trials of neoadjuvant endocrine-based treatment.

Safety and efficacy of stenting for aortic arch hypoplasia in patients with coarctation of the aorta.

BACKGROUND: Despite a successful repair procedure for coarctation of the aorta (CoA), up to two-thirds of patients remain hypertensive. CoA is often seen in combination with abnormal aortic arch anatomy and morphology. This might be a substrate for persistent hypertension. Therefore, we performed endovascular aortic arch stent placement in patients with CoA and concomitant aortic arch hypoplasia or gothic arch morphology. The goal of this retrospective analysis was to investigate the safety and efficacy of aortic arch stenting. METHODS: A retrospective analysis was performed in patients who underwent stenting of the aortic arch at the University Medical Center Utrecht. Measurements collected included office blood pressure, use of antihypertensive medication, invasive peak-to-peak systolic pressure over the arch, and aortic diameters on three-dimensional angiography. Data on follow-up were obtained at the date of most recent outpatient visit. RESULTS: Twelve patients underwent stenting of the aortic arch. Mean follow-up duration was 14 ± 11 months. Mean peak-to-peak gradient across the arch decreased from 39 ± 13 mm Hg to 7 ± 8 mm Hg directly after stenting (p < 0.001). There were no major procedural complications. Mean systolic blood pressure decreased from 145 ± 16 mm Hg at baseline to 128 ± 9 mm Hg at latest follow-up (p = 0.014). CONCLUSION: This retrospective study shows that stenting of the aortic arch is successful when carried out in a state-of-the-art manner. A direct optimal angiographic and haemodynamic result was shown. No major complications occurred during or after the procedure. At short- to medium-term follow-up a decrease in mean systolic blood pressure was observed.

Assessing cardiac function from total-variation-regularized 4D C-arm CT in the presence of angular undersampling.

Time-resolved tomographic cardiac imaging using an angiographic C-arm device may support clinicians during minimally invasive therapy by enabling a thorough analysis of the heart function directly in the catheter laboratory. However, clinically feasible acquisition protocols entail a highly challenging reconstruction problem which suffers from sparse angular sampling of the trajectory. Compressed sensing theory promises that useful images can be recovered despite massive undersampling by means of sparsity-based regularization. For a multitude of reasons-most notably the desired reduction of scan time, dose and contrast agent required-it is of great interest to know just how little data is actually sufficient for a certain task. In this work, we apply a convex optimization approach based on primal-dual splitting to 4D cardiac C-arm computed tomography. We examine how the quality of spatially and temporally total-variation-regularized reconstruction degrades when using as few as [Formula: see text] projection views per heart phase. First, feasible regularization weights are determined in a numerical phantom study, demonstrating the individual benefits of both regularizers. Secondly, a task-based evaluation is performed in eight clinical patients. Semi-automatic segmentation-based volume measurements of the left ventricular blood pool performed on strongly undersampled images show a correlation of close to 99% with measurements obtained from less sparsely sampled data.

Three-dimensional rotational angiography in children with an aortic coarctation.

BACKGROUND: Children with aortic coarctations (CoA) are increasingly percutaneously treated. Good visualisation of the CoA is mandatory and can be obtained with three-dimensional rotational angiography (3DRA). This study aims to compare the diagnostic and therapeutic additional value of 3DRA with conventional biplane angiography (CA) in children with a CoA. METHODS: Patients undergoing percutaneous treatment of CoA with balloon angioplasty (BA) or stent between 2003 and 2015, were retrospectively reviewed on success rate, complications, radiation and technical settings. Diagnostic quality of CA and 3DRA and additional value of 3DRA were scored. RESULTS: In total, 134 patients underwent 183 catheterisations, 121 CA and 62 3DRA-guided. Median age was 0.52 years in the BA group and 11.19 years in the stent group. 3DRA was superior to CA in displaying the left ventricle (p = 0.008), ascending aorta (p < 0.001), aortic arch (p = 0.005) and coronary arteries (p < 0.001). In the BA group, 3DRA had a significantly higher success rate than CA (100.0 % versus 68.9 %, p = 0.016). All stent interventions were successful. Complication rates did not differ significantly. The median total dose area product did not significantly differ between CA and 3DRA in the BA (27.88 µGym2/kg versus 15.81 µGym2/kg, p = 0.275) or stent group (37.34 µGym2/kg versus 45.24 µGym2/kg, p = 0.090). 3DRA was of additional value in 96.8 % of the interventions. CONCLUSIONS: 3DRA is superior to CA in diagnostic quality and not associated with increased radiation exposure. It provides high additional value in guiding CoA related interventions.

Significant scales in community structure.

Many complex networks show signs of modular structure, uncovered by community detection. Although many methods succeed in revealing various partitions, it remains difficult to detect at what scale some partition is significant. This problem shows foremost in multi-resolution methods. We here introduce an efficient method for scanning for resolutions in one such method. Additionally, we introduce the notion of "significance" of a partition, based on subgraph probabilities. Significance is independent of the exact method used, so could also be applied in other methods, and can be interpreted as the gain in encoding a graph by making use of a partition. Using significance, we can determine "good" resolution parameters, which we demonstrate on benchmark networks. Moreover, optimizing significance itself also shows excellent performance. We demonstrate our method on voting data from the European Parliament. Our analysis suggests the European Parliament has become increasingly ideologically divided and that nationality plays no role.

Role of second trials in cascades of information over networks.

We study the propagation of information in social networks. To do so, we focus on a cascade model where nodes are infected with probability p_{1} after their first contact with the information and with probability p_{2} at all subsequent contacts. The diffusion starts from one random node and leads to a cascade of infection. It is shown that first and subsequent trials play different roles in the propagation and that the size of the cascade depends in a nontrivial way on p_{1} , p_{2} , and on the network structure. Second trials are shown to amplify the propagation in dense parts of the network while first trials are dominant for the exploration of new parts of the network and launching new seeds of infection.

Diagnostic catheterization and balloon sizing of atrial septal defects by echocardiographic guidance without fluoroscopy.

To avoid x-ray exposure prior to interventional closure of atrial septal defects (ASDs), we recently developed a technique for diagnostic catheterization and balloon sizing of the defect by echocardiographic guidance without fluoroscopy. We report on our first experiences with this technique. Fourteen patients with atrial septal perforations (mean age, 23 years; range, 1-66 years) underwent diagnostic catheterization and balloon sizing prior to possible interventional defect closure. Mean size of the defects was 16 mm (7-29 mm). Mean left-to-right shunt was Qp/Qs = 2.0 (range, 1.0-4.0). Without fluoroscopy, the procedures were performed in two children by transthoracic echocardiography (TTE) and in 12 patients by both TTE and transesophageal echocardiography (TEE). Mean procedure time was 59 minutes (range, 35-90 minutes). We conclude that oxymetry, pressure recordings, and the estimation of the balloon-stretched size of atrial septal perforations can be performed safely by echocardiographic guidance without fluoroscopy. The x-ray exposure for patient selection prior to a transcatheter closure of an ASD can be avoided with this technique.

Immunochemical characterization of purified human oxidized low-density lipoprotein antibodies.

The goal of this study was to characterize the isotypes and reactivity of human autoantibodies to copper oxidized LDL (oxLDL). Forty-six purified oxLDL antibodies contained immunoglobulins of the three major isotypes, with a predominance of IgG, subclasses 1 and 3. These IgG isotypes are known to interact with FcRgammaI and to activate the complement system and thus are potentially able to activate macrophages and cause foam cell formation. The same purified antibodies were tested for cross-reactivity with malondialdehyde (MDA)-, glycated (Glyc)-, and native (n)LDL and cardiolipin. Absorption with oxLDL resulted in a decrease of reactivity of 77.2 +/- 4.7%. Absorption with MDA-LDL resulted in a wider range of reduction of reactivity values, ranging from 50 to 87%, possibly reflecting differences in the degree of MDA modification. Absorption with Glyc- and nLDL caused a minor decrease in the reactivity of antibodies to oxLDL (5.9 +/- 7.1 and 6.8 +/- 6. 4%, respectively), comparable to the reduction of reactivity (2.1 +/- 4.0%) measured after absorption with transferrin, an irrelevant protein used as a negative control. These results suggest that oxLDL antibodies recognize primarily MDA epitopes. To determine whether purified oxLDL antibodies also recognize other epitopes known to be generated during copper oxidation of LDL, such as 4-hydroxynonenal (HNE)- and N(epsilon)(carboxymethyl)-lysine (CML), two additional sets of experiments were carried out. First, we monitored the formation of CML-, MDA-lysine, and HNE-lysine at different times during copper oxidation of two LDL pools. Both pools showed simultaneous increases in protein modification, as indicated by increasing fluorescence emission at 430 nm, and in immunoreactivity with oxLDL antibodies, coinciding closely with MDA modification of lysine groups. Second, we assessed whether the reactivity of oxLDL antibodies could be blocked by absorption with CML- or HNE-LDL. HNE-LDL did not react with isolated oxLDL antibodies. Highly modified CML-LDL (>90% of lysine residues modified) reduced the reactivity of oxLDL antibodies, but only by 25.5%. Finally, we investigated the possible cross-reactivity of oxLDL antibodies with cardiolipin. Seventeen purified oxLDL antibodies were used in this study, which showed that absorption with oxLDL or nLDL did not affect their reactivity with immobilized cardiolipin.

Transcatheter closure as standard treatment for most interatrial defects: experience in 200 patients treated with the Amplatzer Septal Occluder.

To judge whether an Amplatzer Septal Occluder can be used as standard therapy instead of surgery for closure of atrial septal defects we report our experiences in 200 patients. Of these patients, 127 had an atrial septal defect with haemodynamically significant left-to-right shunt, 68 patients a persistent oval foramen after presumed paradoxical embolism, and 5 had a fenestration after Fontan-repair. Mean age was 29.8 years (0.8 to 77.7 years). Body weight ranged from 6.9 to 120.0 kg (mean 51.5 kg). After diagnostic cardiac catheterization, and balloon-sizing of the defect, we implanted Amplatzer Septal Occluders with stents of 4 to 28 mm diameter. Follow-up studies were obtained after 48 hours, and one, six, and twelve months. Transcatheter closure of the atrial septal defect proved successful in all without any relevant residual shunts. In particular, complete closure was achieved in all patients after presumed paradoxical embolism. The mean period of follow-up is 9.5 months, with a range from 0.4 to 23.5 months, giving a total of 1898 patient months. The occlusion rate after three month was 98.1%. A trivial haemodynamically insignificant residual shunt remained in 1.9% of the patients. Fluoroscopy times ranged from 0 to 43.5 minutes, with a median of 8.7 minutes. The excellent results in the short and medium term in children and adults have resulted in using this device routinely at the present time for closure of central atrial septal defects up to a diameter of 28 mm. Final judgement, however, is only possible after long-term follow-up.

[Arrhythmias in patients with congenital heart disease and their impact on prognosis]. / Arrhythmien bei Patienten mit angeborenen Herzfehlern und Bedeutung für die Prognose.

Patients with congenital heart disease have an increased chance to suffer from brady- as well as tachyarrhythmias. The impact of these on quality of life, morbidity and mortality is more often imperative as compared to heart-healthy individuals. The substrate for these may be either congenital or acquired. Improvements of the surgical management of these patients have led, on the one hand, to improved survival rates with prolonged life expectancy within the last 2 decades, which on the other hand provided the basis for a higher rate of acquired cardiac arrhythmias. Together, this not only challenges diagnostics and therapy but also the prognostic relevance of these arrhythmias. The therapeutic strategies and prognostic markers have until now mostly been based on retrospective studies limited by the low number of patients and inhomogeneous patient selection. Despite these limitations, an increased risk of sudden cardiac death has been substantiated for certain patient groups, e.g., those operated on by the Mustard- or Senning procedures in patients with transposition of the great arteries and patients operated on with correction of the tetralogy of Fallot. However, until now it has not been possible to identify reliable markers for establishing the risk on an individual basis within these patient cohorts. For achieving reliable data on the symptomatic and prognostic effects of present-day--as well as new-coming--therapeutic strategies, it is mandatory to perform prospectively based, randomized multicenter studies. Furthermore, the well-appreciated synergism of hemodynamically and primarily of arrhythmia-based effects on prognosis could potentially be divided into their relative weight to better guide appropriate, substrate-related therapy. In addition, this should help to get better estimates of the risk for sudden cardiac death in different, etiologically homogeneous, groups of patients with congenital heart disease.

Transcatheter closure of atrial septal defects under echocardiographic guidance without X-ray: initial experiences.

BACKGROUND: Transcatheter closure of atrial septal defects is performed under fluoroscopy, but echocardiography has gained an important role in the procedure. With the new Amplatzer Septal Occluder a device has become available which is easy to implant with minimal fluoroscopy time. We developed an interventional procedure with this device under transesophageal echocardiography alone without fluoroscopy. METHODS AND RESULTS: Four patients (3 to 16 years of age, bodyweight 14 to 60 kg) with atrial septal defects centrally located in the oval fossa were elected for transcatheter closure. After sedation with midazolam and propofol a diagnostic and interventional catheterization was performed in all cases without fluoroscopy. Oxymetric shunt was Qp: Qs = 1.7 (1.5 to 2.1). Under transesophageal echocardiography, the defects were sized over the wire with a balloon catheter. Mean balloon stretched diameter was 10 mm (7 to 14 mm). Under transesophageal echocardiography an Amplatzer Septal Occluder was placed into the defect. In two patients this was achieved with a 5 MHz monoplane pediatric transducer, in two patients a 10mm 5 MHz multiplane probe was used. Complete closure was achieved in all patients and no complications were encountered. CONCLUSION: We conclude that in selected cases with an atrial septal defect located in the oval fossa and clear-cut echocardiographic findings, an Amplatzer Septal Occluder can be safely deployed under echocardiographic guidance alone.

[Initial clinical results with the Amplatzer septal occluder--a self-centering double disc for occlusion of atrial septal defects]. / Initiale klinische Ergebnisse mit dem Amplatzer Septal Occluder--ein selbstzentrierender Doppelschirm zum Verschluss von Vorhofseptumdefekten.

UNLABELLED: In recent years many different systems for transcatheter closure of an atrial septal defect (ASD) have been developed and tested. However, all systems presently available have some special disadvantages. The recently introduced Amplatzer Septal Occluder (ASO), though, appears promising. It is a self-expanding and self-centering double disc made from a Nitinol mesh, which is tightly woven to give mechanical strength. Both discs are separated by a connecting cylindrical portion. Its diameter may be chosen, so that it corresponds to that of the ASD. Discs of polyester patches are sewn into the retention discs as well as into the cylindrical portion of the device in order to augment thrombogenicity. After measuring the diameter of the ASD with a balloon, an appropriate ASO is selected and advanced into the left atrium through a 7 or 8 French sheath. Then the distal disc and part of the connecting cylindrical portion is developed in the left atrium and pulled against the atrial septum, so that the cylindrical portion is occluding the ASD. Thereafter, proximal disc is deployed and the delivery cable disconnected. As long as the cable is connected to the device repositioning is easily achieved by pulling the device back into the sheath. Within a time period of 4 months in 29 out of 31 patients (median age: 12.1 years, median weight: 45.0 kg) complete closure of the ASD with a mean diameter of 11.0 mm (6-20 mm) was achieved without complications, the average fluoroscopy time being 8.3 min (2.9-21.5 min). Mean Qp:Qs was 1.5 (0.9-2.2). During a mean follow-up period of 2.1 months post implantation fixed seating of the ASO without residual shunt, arrhythmias, thrombembolic events and impairment of A-V valves was observed in all patients. CONCLUSION: The Amplatzer septal occluder allows quick, safe, and complete closure of atrial septal defects without complications if one adheres to strict implantation criteria. For a final judgement, however, long-term follow-up studies are necessary.