Plasma exchange therapy for severe gastrointestinal involvement of Henoch Schönlein purpura in children.

OBJECTIVES: The aim of this report is to evaluate the plasma exchange as a choice for the management of life-threating gastrointestinal system (GIS) involvement in Henoch-Schönlein purpura (HSP) when refractory to conventional therapies. METHODS: We retrospectively reviewed the medical records of HSP patients who had plasma exchange therapy due to massive GIS involvement. We reported age, gender, initial HSP presentation, etiological or triggering factors and disease course. Treatment modalities, side effects and their outcomes were noted. RESULTS: We reported 7 cases of childhood HSP with severe gastrointestinal involvement refractory to common immunosuppression with systemic steroid and cytotoxic therapy. All patients gave inadequate response to pulse methyl prednisolone or oral prednisolone therapy with ongoing GIS bleeding and severe abdominal pain. Therefore, pulse cyclophosphamide was added to the treatment. Two patients received additional intravenous immunoglobulin (IVIG) therapy. Gastrointestinal manifestations continued and plasma exchange was performed. All patients improved after plasma exchange treatment. CONCLUSIONS: Treatment of GI involvement in HSP with plasma exchange has been mainly based on case reports. According to our data, we propose that, plasma exchange may be a safe and efficient management choice in paediatric HSP patients with massive GIS involvement that are refractory to other therapies.

Proton beam radiotherapy for choroidal and ciliary body melanoma in the UK-national audit of referral patterns of 1084 cases.

INTRODUCTION: Proton beam therapy has been utilised for the treatment of uveal melanoma in the UK for over 30 years, undertaken under a single centre. In the UK, all ocular tumours are treated at one of four centres. We aimed to understand the variation in referral patterns to the UK proton service, capturing all uveal melanoma patients treated with this modality. METHODS: Retrospective analysis of data regarding all patients treated at the Clatterbridge Proton service between January 2004 and December 2014. RESULTS: A total of 1084 patients with uveal melanoma were treated. The mean age was 57 years (range 9-90 years), basal diameter of 11.5 mm (range 2.0-23.4 mm) and tumour thickness of 3.9 mm (range 0.1-15.4 mm). The majority were TNM stage I (39%) or II (36%). The distance to the optic nerve varied from 0 to 24.5 mm with 148 (14%) of patients having ciliary body involvement. There were variations in the phenotypic characteristic of the tumours treated with protons from different centres, with London referring predominantly small tumours at the posterior pole, Glasgow referring large tumours often at the ciliary body and Liverpool sending a mix of these groups. DISCUSSION: In the UK, common indications for the use of proton treatment in uveal melanoma include small tumours in the posterior pole poorly accessible for plaque treatment (adjacent to the disc), tumours at the posterior pole affecting the fovea and large anterior tumours traditionally too large for brachytherapy. This is the first UK-wide audit enabling the capture of all patients treated at the single proton centre.

Clinical implication of pretreatment neutrophil to lymphocyte ratio in soft tissue sarcoma.

INTRODUCTION: Elevated neutrophil to lymphocyte ratio has been identified as a prognostic indicator in malignancies whereas; its association with extremity and trunk soft tissue sarcoma remain unclear. The aim of this study is to determine the utility of full blood neutrophil lymphocyte ratio (NLR) in preoperative diagnosis and its predictive value for survival in patients managed for soft tissue sarcoma of the trunk and extremities. METHOD: 223 patients who presented with a soft tissue tumor were retrospectively reviewed. The study period was from January 2002-December 2009. Preoperative NLR as well as demographics, clinical and histopathological data were analysed. RESULTS: Full blood NLR was significantly higher in patient with a soft tissue sarcoma compared to benign soft tissue tumors (p < 0.001). Cox regression analysis demonstrated that elevated NLR >5 (p < 0.05) may be an adverse prognostic factor for Overall Survival. CONCLUSION: The preoperative NLR is a simple, investigation predicting the preoperative diagnosis of a soft tissue sarcoma and a predictor of worse overall survival for patient with a soft tissue sarcoma.

Double-blind evaluation and benchmarking of survival models in a multi-centre study.

Accurate modelling of time-to-event data is of particular importance for both exploratory and predictive analysis in cancer, and can have a direct impact on clinical care. This study presents a detailed double-blind evaluation of the accuracy in out-of-sample prediction of mortality from two generic non-linear models, using artificial neural networks benchmarked against a partial logistic spline, log-normal and COX regression models. A data set containing 2880 samples was shared over the Internet using a purpose-built secure environment called GEOCONDA (www.geoconda.com). The evaluation was carried out in three parts. The first was a comparison between the predicted survival estimates for each of the four survival groups defined by the TNM staging system, against the empirical estimates derived by the Kaplan-Meier method. The second approach focused on the accurate prediction of survival over time, quantified with the time dependent C index (C(td)). Finally, calibration plots were obtained over the range of follow-up and tested using a generalization of the Hosmer-Lemeshow test. All models showed satisfactory performance, with values of C(td) of about 0.7. None of the models showed a systematic tendency towards over/under estimation of the observed survival at tau=3 and 5 years. At tau=10 years, all models underestimated the observed survival, except for COX regression which returned an overestimate. The study presents a robust and unbiased benchmarking methodology using a bespoke web facility. It was concluded that powerful, recent flexible modelling algorithms show a comparative predictive performance to that of more established methods from the medical and biological literature, for the reference data set.

[New approach to perimembranous ventricular septal defect by real-time 3D echocardiography]. / Nouvelle approche des communications interventriculaires périmembraneuses par échocardiographie 3D temps réel.

Perimembranous ventricular septal defects (VSD) have a close anatomical relationship to the aortic and tricuspid valve which may make percutaneous closure difficult. The authors' objective was to study the anatomy of perimembranous VSD by real-time 3D echocardiography. Fourteen patients aged 1 day to 3 years (mean 3 months) underwent transthoracic 2D and 3D echocardiography. Two patients (> 10 kg) underwent closure of the perimembranous VSD with an Amplatzer occluder. The other 12 patients were operated (surgical closure in 11 and circling suture with resorbable thread in 1 patient). The 3D echocardiography showed variations in the geometry of the perimembranous VSD (eccentric, oval, cleft). The maximal diameter of the septal defect by 3D echocardiography was on average 2 mm greater than the diameter by 2D echocardiography. The 3D echo enabled visualisation of the close relationship of the septal tricuspid leaflet, the aortic valve and the perimembranous VSD, showing the mechanism of its closure and the associated aortic regurgitant lesions. The profile of the prosthesis implanted percutaneously was well shown in the different 3D views. The authors conclude that real-time 3D echocardiography is a technique which allows accurate anatomic description of perimembranous VSD. As a complement to classical 2D methods, it gives a better appreciation of the maximal diameter of the septal defect and of its relationship to the aortic and tricuspid valves.

[Unusual outcome of mitral valve infectious endocarditis in a premature infant]. / Evolution inhabituelle d'une endocardite infectieuse mitrale chez un prématuré.

The authors report a case of Staphylococcus Aureus infectious endocarditis in a premature baby. Echocardiography on the 8th day of life showed a large vegetation on the anterior mitral leaflet without significant regurgitation. Intravenous antibiotics and platelet antiaggregant therapy were given. At three weeks of age the vegetation split into two, one part attached to the foramen ovale and the other to the anterior mitral leaflet. At one month, the development of severe mitral regurgitation led to surgical valvuloplasty in a 2 kg neonate, the vegetation on the foramen ovale having spontaneously fragmented. The ablation of the mitral vegetation associated with commissuroplasty reduced the mitral regurgitation. At 3 months after surgery, the child was asymptomatic with a minimal mitral regurgitation.

[A rare association of double discordance with aortic arch anomalies: value of multislice CT scan]. / Association exceptionnelle d'une double discordance avec anomalie des arcs aortiques: apport du scanner multicoupe.

The authors report the case of a 14 month old infant admitted for intermittent stridor. Routine echocardiography showed atrioventricular and ventriculo-arterial discordance with an intact septum and situs solitus with levocardia. Multislice CT scan showed tracheal compression due to a Neuhauser anomaly of the aortic arches. The paucity of symptoms led to surgical abstention.

[B-natriuretic peptide and cardiological emergencies in childhood]. / Peptide natriurétique de type B et urgences cardiologiques chez l'enfant.

The increase in B-natiuretic peptide (BNP) is well correlated with cardiovascular symptoms in adults. Its use in children is recent and only partially evaluated. The authors undertook a prospective study of BNP concentrations and its kinetics in 54 children with an average age of 15 months (5 days to 11 years) admitted as paediatric emergencies. The symptoms were dyspnoea (60%), shock (15%), suspicion of Kawasaki disease (15%) and other (10%). Twenty children had BNP levels of more than 100 pg/ml related to decompensation of known congenital heart disease in 7 patients (average BNP 462 +/- 323 pg/ml), due to neonatal coarctation in 2 patients (BNP > 3000 pg/ml), due to cardiomyopathy in 6 patients (BNP= 2576 +/- 1215 pg/ml), due to an arrhythmia in 1 patient (BNP= 3754 pg/ml) and to Kawasaki disease in 4 patients (BNP= 521 +/- 448 pg/ml). Thirty-four children had BNP values of less than 100 pg/ml; 29 had no cardiac disease and 5 had known congenital heart disease with other symptoms. Measuring BNP is quick and economical and is a valuable aid in the diagnosis of cardiac dysfunction in symptomatic children in the emergency room. High BNP values seem to be correlated with the severity of the cardiac disease. Low BNP values seem to have a good negative predictive value in children without underlying cardiac disease. The interpretation of intermediary values, especially when there is previous cardiac disease, is more difficult in view of the absence of known threshold values for different haemodynamic situations. Further studies are required to determine the value of this test for the follow-up and setting up of prognostic values in children with congenital heart disease.

[Very large cardiac tumor revealed by ventricular arrhythmia in a 18-month-old infant]. / Volumineuse tumeur cardiaque révélée par un trouble du rythme ventriculaire chez un nourrisson de 18 mois.

Cardiac tumors are rare in childhood and can be revealed by arrhythmias. We report the observation of an 18-month-old infant who had an episode of ventricular tachycardia (VT) which resulted in a large intramyocardic tumour diagnosis evocating a left ventricular fibroma. A treatment by amiodarone allowed a stable reduction of the VT. The presence of an intracardiac obstruction or uncontrollable arrhythmias would lead to a surgical resection.

[Cor triatriatum sinister: unusual cause of neonatal respiratory distress]. / Coeur triatrial gauche: une cause inhabituelle de détresse respiratoire néonatale.

We report the case of a newborn presenting with neonatal respiratory distress due to acute pulmonary edema, the underlying diagnosis being cor triatriatum sinister. This rare anomaly can be lethal in the short term. However, it can be completely cured surgically provided that diagnosis is made on time.

[A new approach to the tricuspid valve in Ebstein's anomaly by real time 3D echocardiography]. / Nouvelle approche de la valve tricuspide par échocardiographie 3D temps réel dans la maladie d'Ebstein.

Ebstein's anomaly affects the tricuspid valve with a large range of anatomical forms. Successful tricuspid valvuloplasty depends mainly on the ability to mobilise the leaflets. Evaluation of the leaflet surface is difficult with 2D echocardiography whereas 3D echocardiography provides intracardiac views of the valve. The authors used this method in 10 patients with 3 modes of imaging: biplane, real time and total volume. The study population (age: 1 day to 30 years) included: 1 prenatal diagnosis, 1 neonate with refractory cyanosis, 5 patients with mild tricuspid regurgitation, 3 patients with severe tricuspid regurgitation, 2 of whom underwent valvuloplasty. 3D echocardiography was disappointing in the foetus and neonate because of poor spatial resolution. The ventricular view of the tricuspid valve in older children and adults allowed analysis of tricuspid leaflet coaptation and of the mechanism of regurgitation. The commissures and leaflet surfaces were assessed. The results of surgical valvuloplasty could be evaluated by 3D echocardiography. 3D echocardiography is now transthoracic and a real time investigation. Technical advances are required before it comes into routine usage: a more manoeuvrable matricial probe (integrating pulsed and continuous wave Doppler) and larger volume real time 3D imaging with better resolution. Its role in the assessment of Ebstein's anomaly should be evaluated in a larger series of patients.

[Spiral CT scan imaging of the coronary vessels six years after complete repair of a Taussig-Bing malformation]. / Imagerie coronaire par scanner spiralé 6 ans après correction complete d'une malformation de Taussig-Bing.

The Taussig-Bing malformation is a rare form of transposition of the great arteries with a ventricular septal defect. Associated cardiac abnormalities are common: hypoplasia of the aorta and especially coronary anomalies which may complicate surgical repair. The authors report the case of a patient with this malformation diagnosed in utero and who underwent anatomical repair on the 11th day of life. The coronary anatomy described by the surgeon was type E of Yacoub and Radley-Smith's classification. The postoperative course was uncomplicated. At the age of 6, a spiral CT scan was performed routinely under betablocker therapy. The coronary trajectory with a double loop, the patency of the coronary ostia and of the aortic isthmus were accurately demonstrated by this form of imaging.

[3D echocardiography of the ascending aorta in Marfan's syndrome]. / Echocardiographie 3D de l'aorte ascendante dans le syndrome de Marfan.

Marfan's syndrome is a cause of dilatation of the aorta, the main complication of which is dissection of the aorta. 2D echocardiography is the reference investigation for measuring the ascending aorta. Asymmetry of sinus dilatation makes a 3D approach necessary. Real time 3D echocardiography is a simple, non-invasive method which, by a biplane mode, allows measurement of the 3 sinuses of Valsalva. The aim of the study was to compare the 2D and 3D echocardiographic methods for measuring the ascending aorta. Fifteen patients (average age 12 +/- 8 years) with Marfan's syndrome were studied prospectively. The maximal 3D diameter was significantly greater than the 2D measurement (31.7 +/- 6.8 mm vs 29.9 +/- 6.6 mm, p< 0.005). In 4 patients, the difference was over 3 mm. The diameter between the right coronary and left coronary sinus was greater than the two others (right coronary-non coronary and left coronary-non coronary). The oldest 5 patients had an MRI aortic measurement very similar to that of 3D echocardiography (36.6 vs 36.7 mm). Real time 3D echocardiography in the biplane mode enables reliable and reproducible measurement of the aortic root in patients with Marfan's syndrome. Larger and multicenter studies are required to allow confirmation of the value of 3D echocardiography in the follow-up of these patients.

[Unusual association of chylopericardium and aortic hypoplasia in a neonate]. / Association inhabituelle chez un nouveau-né d'un chylopéricarde et d'une hypoplasie aortique.

We report the case of a neonate with two very rare anomalies: primary chylopericardium and diffuse hypoplasia of the thoraco-abdominal aorta. The presentation on the 16th post-natal day was with dyspnoea and refusal to feed. The initial clinical examination revealed hepatomegaly and weak femoral pulses. 2D ultrasound gave a diagnosis of a large compressive pericardial effusion combined with moderate hypoplasia of the aortic isthmus. Emergency pericardial drainage removed 80ml of chylous liquid. Following prolonged parenteral nutrition, the pericardial effusion stabilised. A mechanism of diffuse vascular disease affecting the aorta and the lymphatic system is suggested.

[Unusual diagnosis of partial left abnormal pulmonary venous return in neonate]. / Découverte inhabituelle d'un retour veineux anormal partiel du poumon gauche chez un nouveau-né.

The authors report on a case of a newborn with partial anomalous pulmonary venous return of the lower left pulmonary vein. Diagnosis was performed during the introduction of a central venous catheter. The complications of partial anomalous pulmonary venous rely principally in the risk of endothelium damage and subsequent pulmonary arterial hypertension.

Feasibility of neonatal lung imaging using electrical impedance tomography.

The feasibility of detecting the lungs in preterm babies using electrical impedance tomography (EIT) was investigated. A single frequency instrument using 16 electrodes to apply current and detect peripheral voltages was constructed. The instrument applied AC current of 1.5 mA peak-peak at a carrier frequency of 20 kHz. Images were reconstructed using a sensitivity-regions backprojection method. A 9-day-old preterm baby was tested and data were collected at a speed of 10 frames/s. A dynamic image showing the lungs at full inspiration referenced to expiration is illustrated in this paper. Impedance measurements taken across the chest during the first 2 s did not show a clear pattern thus demonstrating irregular breathing. Region of interest analysis were carried out on the reconstructed images and tracked with time. Fourier transforms were then performed on these signals and a fundamental frequency at 1 Hz, corresponding to normal breathing rate of 60 breaths/min, was detected. Harmonics of the signal caused distortion especially on the left lung where the effects of cardiac events were more dominant.

Neural network analysis of oxygenation signals in infants during sleep.

The use of artificial neural networks (ANNs) to interpret sleep monitoring signals is described. Recordings from ten infants with apparent life threatening episodes were assigned into training feedforward R-PROP networks. In order to separate good signal from artefact, 60 second time frames of SaO2 and TcPO2 signals were processed and the mean and standard deviation values were used as inputs to the networks. Intra-human errors were minimized using this method whilst inter-human errors remained significant. To decrease the latter, the number of hidden units was increased to eight. Sensitivity figures of the SaO2 network were 0.93 and 0.9 for the training and test sets respectively whilst the specificity figures were 0.7 and 0.65 respectively. For the TcPO2 signals the above figures were 0.92, 0.85, 0.77 and 0.61 respectively.

A fuzzy system for detecting distorted plethysmogram pulses in neonates and paediatric patients.

Pulse oximetry is a useful, quick, non-invasive and widely used technology for monitoring oxygen saturation (SaO2) for neonates and paediatric patients. However, pulse oximetry is fraught with artefacts, causing false alarms resulting from patient or probe movement. The shape of the plethysmogram is a useful visual indicator for determining the reliability of SaO2 numerical readings. If certain features could be defined that tag valid plethysmogram pulses, then automatic recognition of valid SaO2 values can be attained. We observed that the systolic upstroke time (t1), the diastolic time (t2) and heart rate (HR) extracted from the plethysmogram pulse constitute features which can be used for detecting normal and distorted plethysmogram pulses. Therefore, we developed a knowledge-based system using fuzzy logic for classifying plethysmogram pulses into two categories: valid and artefact. A total of 22,497 pulse waveforms were used to define the system parameters. These were obtained from 13 patients with heart rates ranging between 62 and 209 beats min-1. A further 1420 waveforms obtained from another four patients were used for testing the system, and visually classified into 833 (59%) valid and 587 (41%) distorted segments. The system was able to classify 679 (82%) valid segments and 543 (93%) distorted segments correctly. The calculations of the system's performance showed 82% sensitivity, 86% accuracy and 93% specificity. We, therefore, conclude that the algorithm used in this system can be implemented in its present from for real-time SaO2 monitoring in intensive care for detecting valid and distorted plethysmogram pulses.

Data recovery from reduced electrode connection in electrical impedance tomography.

In electrical impedance tomography, a single channel failure causes distortion to the overall image. Mathematical modelling and curve-fitting techniques were used to recover corrupted data. A single channel was disconnected in two experiments on a saline-filled dish with one and two objects, respectively. Voltage gradient data were then synthesized from the overall shape of the curve and reconstructed. The technique demonstrated a considerable improvement in the image quality. We conclude that the technique can be adapted in applications where channel failure can occur regularly such as neonatal monitoring.

[Real time 3D echocardiography in congenital heart disease]. / Echocardiographie 3D temps réel des cardiopathies congénitales.

The introduction of the 3D mode in echocardiography has led to its use in everyday clinical practice. One hundred and fifty real time 3D echocardiographic examinations were performed in 20 foetus, 110 children and 20 adults with various congenital heart lesions (shunts, valvular lesions, aortic diseases). The 4x matricial probe enables the instantaneous acquisition of transthoracic volumes. Four modes of 3D imaging were used: real time, total volume, colour Doppler and biplane. Quantitative measurements were performed at an outlying station. The feasibility of the method in the foetus, the child and the adult was respectively 90%, 99% and 85%. Real time 3D echocardiography did not affect the diagnoses made by standard echocardiography. The 3D imaging gave a more accurate description of atrial septal defects and congenital valvular lesions. Biplane imaging was decisive in the quantitative approach to aortic dilatation of Marfan's syndrome and in segmental analysis of the foetal heart. 3D colour Doppler imaging has been disappointing but the possibilities of volumic quantification of blood flow are very promising. The present limitations of the method are the inadequate resolution in the small child and the absence of quantitative measurement on the echograph. The facility of utilisation of the matricial probe should lead to routine usage of 3D echocardiography as with 2D and the Doppler modes. Its value should be decisive in many congenital cardiac lesions requiring surgery or interventional catheterisation.