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.

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.

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.

Endothelial function and mechanical arterial properties in children born small for gestational age: comparison with obese children.

BACKGROUND: Early cardiovascular events preceding atherosclerosis have been reported in children born small for gestational age (SGA). AIMS: To describe in detail the mechanical and functional arterial properties of SGA children and to compare the data to those of obese children in order to gain a better understanding of the severity of the dysfunction. A control group was required to overcome the lack of normal values. METHODS: Three groups of 7- to 15-year-old children were included. Sixty children born SGA without obesity, 49 children with obesity and not SGA, and 55 controls underwent complete carotid and brachial arterial measurements using ultrasound and flow-mediated dilation. Biological measurements were performed in the obese and SGA groups. RESULTS: Mean blood pressure and intima-media thickness were lower in SGA children than in the obese group (p < 0.001 and p = 0.004, respectively), but not different from the control group. Flow-mediated dilation was lower in SGA than in obese children and in controls (p < 0.001). CONCLUSION: These data show that children born SGA have endothelial dysfunction with normal intima-media thickness.

Oxygen saturation profile in healthy preterm infants.

AIM: To establish a reference range for oxygen saturation (SpO(2)) in well preterm infants to guide home oxygen therapy using a pulse oximeter and Pulse Oximetry Data Analysis Software (PODS). METHODS: SpO(2) and heart-rate profiles of healthy preterm infants receiving mechanical ventilation for less than 6 h and supplemental oxygen for less than 48 h were monitored using a pulse oximeter. The stored data were downloaded from the monitor to a personal computer as individual files. Each infant's files of SpO(2) were subsequently displayed in graphic form, and a reference range was constructed using dedicated software, PODS. RESULTS: 43 infants were studied. The median value of all infants mean SpO(2) values was 95% (range 92-99%). The median duration of saturations less than 85% and between 85% and 90 % were 1% and 2% respectively. Using the study group median, 5th and 95th percentiles, a cumulative frequency curve of time against SpO(2) value was constructed (representing the reference range of SpO(2) profiles in healthy preterm infants). CONCLUSION: The SpO(2) reference range can be used as an easy and practical guide to compare SpO(2) profiles of infants on home oxygen therapy and guide their oxygen therapy.

Furnished cages for laying hens: study of the effects of group size and litter provision on laying location, zootechnical performance and egg quality.

The furnished cage is a new housing system for layers. A current trend in furnished cage design is to increase group size and replace the litter box with a mat provided with litter. An experiment was set up to determine the effects of group size and litter provision on laying performance and egg quality of beak-trimmed ISA Brown hens housed in large furnished cages with more than 12 hens. Six treatments, each of 18 furnished cages (768 cm(2)/hen including nest and litter area) were compared in a 3 × 2 experimental trial: three group sizes (S20 (20 hens per cage), S40 (40) and S60 (60)), with or without feed as litter distributed on the mat of the litter area. The provision of facilities per hen was equal in all treatments. Mortality, laying rate, mean egg weight, feed intake and feed conversion ratio were unaffected by group size over the 53-week laying period, and performance exceeded the ISA production standards. The overall percentage of eggs laid in the nest exceeded 95% except that it was slightly lower in group S20 (92.0% ± 6.4% v. S40: 96.0% ± 3.3% and S60: 96.2% ± 2.7%) leading to a higher proportion of dirty eggs (S20: 1.6% ± 2.2%, S40: 1.4% ± 1.5%, S60: 1.0% ± 1.0%). At 66 to 70 weeks, eggs laid outside the nest had a slightly higher count of mesophilic bacteria on the eggshell (5.0 log CFU/egg ± 0.4) than those laid in the nest (4.8 log CFU/egg ± 0.5) but no difference in contamination was observed between group sizes. Litter provision had no effect on mortality, egg weight or egg quality traits except for a higher proportion of broken eggs in cages with litter (5.3% ± 6.2% v. 4.6% ± 5.7%). Providing hens with feed for litter was associated with a higher laying rate (97.3% ± 3.2% v. 94.8% ± 4.4% at 23 weeks) and an apparent improvement in feed efficiency at the beginning of the laying period (feed conversion ratio based on feed consumption at the trough: 2.18 ± 0.06 with litter v. 2.28 ± 0.09 without litter at 25 weeks). The results of this study showed that a high level of productivity and good egg quality could be obtained in large furnished cages. Further research is needed to assess the impact on hens' welfare and performance of using more economically competitive substrates than feed for litter.

Continuous and discrete time survival analysis: neural network approaches.

In this paper we describe and compare two neural network models aimed at survival analysis modeling, based on formulations in continuous and discrete time. Learning in both models is approached in a Bayesian inference framework. We test the models on a real survival analysis problem, and we show that both models exhibit good discrimination and calibration capabilities. The C index of discrimination varied from 0.8 (SE=0.093) at year 1, to 0.75 (SE=0.034) at year 7 for the continuous time model; from 0.81 (SE=0.07) at year 1, to 0.75 (SE=0.033) at year 7 for the discrete time model. For both models the calibration was good (p<0.05) up to 7 years.

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.

[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.

[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.

[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.

[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.

[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.

Double-blind comparison of survival analysis models using a bespoke web system.

The aim of this study was to carry out a comparison of different linear and non-linear models from different centres on a common dataset in a double-blind manner to eliminate bias. The dataset was shared over the Internet using a secure bespoke environment called geoconda. Models evaluated included: (1) Cox model, (2) Log Normal model, (3) Partial Logistic Spline, (4) Partial Logistic Artificial Neural Network and (5) Radial Basis Function Networks. Graphical analysis of the various models with the Kaplan-Meier values were carried out in 3 survival groups in the test set classified according to the TNM staging system. The discrimination value for each model was determined using the area under the ROC curve. Results showed that the Cox model tended towards optimism whereas the partial logistic Neural Networks showed slight pessimism.

Evidence-based analysis of field testing of medical electrical equipment.

Field testing of medical electrical equipment remains a topic of debate amongst biomedical engineers. A questionnaire was circulated among members of the main professional body for Medical Engineering Departments in the UK and Ireland and in the Medical Physics and Engineering Mailbase Server. The aim of the questionnaire was to establish consensus on common practice on the frequency and type of safety tests carried out in the field and common sources of hazards and risk management. Twenty-six replies were received in total. A clear majority of 54% of the respondents reported that they carried out safety tests on hospital-based medical equipment on a yearly basis. For other equipment, regular tests were carried out by 58% on loan equipment and by 69% on medical electrical systems. Laboratory equipment on the other hand were not tested in 42% of the cases. Domiciliary and research equipment were only tested in 11% and 15% of the cases respectively. A clear majority of 93% said that they label equipment after tests, 34% said that they always record the actual values (as opposed to pass or fail) and 54% said they carry out functional test as part of the safety test. Although 61% of failures were attributed to the mains lead, only 50% of the respondents said that they had a management system in place for detachable mains leads.

[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.

[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.

[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.