Non-motor symptom burden is strongly correlated to motor complications in patients with Parkinson's disease.

BACKGROUND AND PURPOSE: The objective of this study was to analyze the relationship between motor complications and non-motor symptom (NMS) burden in a population of patients with Parkinson's disease (PD) and also in a subgroup of patients with early PD. METHODS: Patients with PD from the COPPADIS cohort were included in this cross-sectional study. NMS burden was defined according to the Non-Motor Symptoms Scale (NMSS) total score. Unified Parkinson's Disease Rating Scale (UPDRS) part IV was used to establish motor complication types and their severity. Patients with ≤5 years of symptoms from onset were included as patients with early PD. RESULTS: Of 690 patients with PD (62.6 ± 8.9 years old, 60.1% males), 33.9% and 18.1% presented motor fluctuations and dyskinesia, respectively. The NMS total score was higher in patients with motor fluctuations (59.2 ± 43.1 vs. 38.3 ± 33.1; P < 0.0001) and dyskinesia (63.5 ± 40.7 vs. 41.4 ± 36.3; P < 0.0001). In a multiple linear regression model and after adjustment for age, sex, disease duration, Hoehn & Yahr stage, UPDRS-III score and levodopa equivalent daily dose, UPDRS-IV score was significantly related to a higher NMSS total score (ß = 0.27; 95% confidence intervals, 2.81-5.61; P < 0.0001), as it was in a logistic regression model on dichotomous NMSS total score (≤40, mild or moderate vs. >40, severe or very severe) (odds ratio, 1.31; 95% confidence intervals, 1.17-1.47; P < 0.0001). In the subgroup of patients with early PD (n = 396; mean disease duration 2.7 ± 1.5 years), motor fluctuations were frequent (18.1%) and similar results were obtained. CONCLUSIONS: Motor complications were frequent and were associated with a greater NMS burden in patients with PD even during the first 5 years of disease duration.

Systemic high-dose intravenous methotrexate in patients with central nervous system metastatic breast cancer.

BACKGROUND: Infusion of high-dose intravenous methotrexate (MTX) has been demonstrating to penetrate the blood-brain barrier. The aim of this present study was to assess the efficacy and safety of high dose MTX in patients with central nervous system (CNS) metastases of breast cancer. METHODS: Twenty-two patients with CNS metastases treated by MTX (3 g/m2) between April 2004 and October 2009 were enrolled. Clinical response rate, time to progression (TTP), overall survival (OS), and safety were assessed. RESULTS: In terms of brain metastases, 2 patients (9%) achieved a partial response, 10 patients (45%) had disease stabilization, and 10 patients (45%) had disease progression. In others metastatic sites, 7 patients (39%) achieved a disease stabilization, and 11 patients (61%) had disease progression. TTP and OS were 2.1 (95%CI 1.4-2.9) and 6.3 (95%CI 1.8-10) months, respectively. CONCLUSION: High-dose MTX demonstrated a moderate activity at 3 g/m2. Nonetheless, the favorable toxicity profile should suggest the possibility to increase the dosage and further study are planned.

Economic impact of prescribing error prevention with computerized physician order entry of injectable antineoplastic drugs.

UNLABELLED: A cost-benefit analysis was carried out to determine the potential economic costs and benefits of pharmaceutical analysis in preventing prescribing errors for full standardized injectable antineoplastic drugs computerized physician order entry, in a pharmaceutical unit (University teaching hospital), compared with theoretical setting with no pharmaceutical analysis. The viewpoint is that of the payer or the French national Public Health Insurance system, and is limited to hospital cost (only direct medical costs related to net cost and net benefit. A decision analysis model was performed to compare two strategies: with pharmaceutical analysis (± pharmacy intervention) and without pharmaceutical analysis. RESULTS: are expressed in terms of benefit-to-cost ratio and total benefit. The robustness of the results was assessed through a series of one-way sensitivity analyses. Over 1 year, prescribing error incidence was estimated at 1.5% [1.3-1.7], i.e. 218 avoided prescribing errors. Potential avoidance of hospital stay was estimated at 419 days or 1.9 ± 0.3 days per prescribing error. Cost-benefit analysis could estimate a net benefit-to-cost ratio of 33.3 (€17.34/€0.52) and a total benefit at €16.82 per pharmaceutical analysis or €249,844 per year. The sensitivity analysis showed robustness of results. Our study shows a substantial economic benefit of pharmaceutical analysis and intervention in the prevention of prescribing errors. The clinical pharmacist adds both value and economic benefit, making it possible to avoid additional use of expensive antineoplastic drugs and hospitalization. Computerized physician order entry of antineoplastic drugs improves the relevance of clinical pharmacist interventions, expanding pharmaceutical analysis and also the role of the pharmacist.

Influence of fetal glutathione S-transferase copy number variants on adverse reproductive outcomes.

A nested case-control association study was designed to investigate the influence of maternal and fetal copy number variants (CNVs) on reproductive outcomes. Genotypes of ten CNVs encompassing GST and CYP genes were assessed. Significant associations were only found for child CNV genotypes. In particular, the child GSTM1 insertion allele was associated with prematurity protection (odds ratio, 95% CI: 0.67, 0.51-0.89; P < 0.01), whereas the child GSTT2B insertion allele was associated with an increased risk of being small for gestational age (odds ratio, 95% CI: 1.33, 1.07-1.67; P = 0.01). The study highlights the role of the fetal genome in prenatal development and also the need to analyse CNVs in a systematic manner.

Bullous hemorrhagic dermatosis at distant sites: a report of 2 new cases due to enoxaparin injection and a review of the literature.

Enoxaparin is a low-molecular-weight heparin used in the prevention and treatment of pulmonary thromboembolism and other thrombotic disorders. The most common adverse reactions to enoxaparin are ecchymosis, skin necrosis, urticaria, angioedema, and eczema. The first 2 cases of bullous hemorrhagic dermatosis in areas distant from heparin injection sites were described in 2006. We present the cases of 2 men, aged 68 and 78 years, with progressive, advanced-stage lung cancer, who consulted with bullous hemorrhagic lesions without associated symptoms. Both patients reported that the lesions had appeared after initiation of heparin therapy at therapeutic doses. In our review of the literature, we found just 7 cases of heparin-induced bullous hemorrhagic dermatosis. We report a further 2 cases, caused by enoxaparin, in which treatment was continued and in which the lesions resolved in 2 to 3 weeks.

Traumatic tricuspid valve regurgitation: A two case series.

Traumatic tricuspid valve injury is rare, accounting for 0.02% of traumatic injuries. The majority of cases result from blunt force trauma to the chest, however penetrating injuries have been documented in literature. Patients' can be in the full spectrum of disease, from asymptomatic to cardiogenic shock. Indications for surgery include right heart failure or evidence of right heart volume overload in the setting of significant tricuspid regurgitation. Early surgical repair is warranted to preserve right ventricular function. Surgery also needs to be planned in conjunction with the patients' other injuries. In some cases, it may be beneficial for surgery to be delayed whilst the patient is closely observed, in order for the patient to recover from concomitant injuries. We report two cases of tricuspid regurgitation in the context of blunt trauma, and our approach to the management of these patients.

Penetrating cardiac trauma caused by a nail-gun: A case report and narrative review.

Introduction: Penetrating cardiac injuries are emergencies that require prompt surgical management. Most of these injuries are caused by gunshots or stab wounds however the incidence of nail-gun injuries is rising due to their availability and widespread use. Cardiac injuries caused by nail-guns are often self-inflicted. These injuries almost always require operative management with a sternotomy or thoracotomy. Case report: This case report describes a 47-year-old male with two self-inflicted nail-gun wounds to the chest. He presented in a stable condition and subsequently underwent an emergency sternotomy to repair a penetrating cardiac injury. We highlight our diagnostic and operative approach to this injury and present a contemporary narrative review of similar cases. Conclusion: Almost all cases of penetrating trauma caused by nail-gun injuries require urgent surgery. Some cases require the use of cardiopulmonary bypass. In this case, the use of the Medtronic® urchin apical suction device, usually reserved for off pump cardiac surgery, facilitated exposure and repair of the lateral wall of the left ventricle.

Clinical, radiological, and molecular diagnosis of congenital pituitary diseases causing short stature.

Short stature in children can be caused by congenital pituitary disorders involving at least one form of growth hormone deficiency. Clinical and radiological evaluations of the index case and family history assessments are essential to guide genetic diagnostic testing and interpret results. The first-line approach is panel testing of genes involved in pituitary development with variants known to be pathogenic in this context. It identifies a genetic cause in less than 10% of cases, however. Whole-exome and whole-genome sequencing techniques may provide original information but also raise new questions regarding the pathophysiological role of identified variants. These new tools can make genetic counselling more complex. The role of clinicians in these interpretations is therefore important. © 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Women's mood at high altitude. sexual dimorphism in hypoxic stress modulation by the tryptophan-melatonin axis.

Sexual (and gender)-dimorphism in tolerance to hypobaric hypoxia increasingly matters for a differential surveillance of human activities at high altitude (HA). At low altitudes, the prevalence of anxiety and depression in women has already been found to double when compared with men; it could be expected to even increase on exposure to HA. In purposefully caring for the health of women at HA, the present work explores the potential involvement of the tryptophan (Trp)-melatonin axis in mood changes on exposure to hypobaric hypoxia. The present work highlights some already known anxiogenic effects of HA exposure. Hypoxia and insomnia reduce serotonin (5-HT) availability; the latter defect being expressed as failure of brown adipose tissue (BAT) activation and mood disorders. Rapid eye movement (REM) sleep organization and synapsis restoration that are additionally affected by hypoxia impair memory consolidation. Affective complaints may thus surge, evolving into anxiety and depression. Sex-related differences in neural network organization and hormonal changes during the menstrual cycle, and certainly also during the life cycle, underscore the possibility of 5-HT-related mood alterations, particularly in women on HA exposure. The mean brain rate of 5-HT synthesis at sea level is already 1.5-fold higher in males than in females. sexual dimorphism also evidences the overexpression effects of SERT, a 5-HT transporter protein. Gonadal and thyroid hormones, as influenced by HA exposure, further modulate 5-HT availability and its effects in women. Besides caring for adequate oxygenation and maintenance of one's body core temperature, special precautions concerning women sojourning at HA should include close observations of hormonal cycles and, perhaps, also trials with targeted antidepressants.

Water disinfection by-products and bladder cancer: is there a European specificity? A pooled and meta-analysis of European case-control studies.

Several epidemiological studies suggested an association between the risk of bladder cancer and the exposure to trihalomethanes (THMs), the main disinfection by-products (DBPs) of chlorinated water. A previous pooled analysis of case-control studies from North America and Europe estimated a summarized dose-response relation. For policy guidance of drinking water disinfection in Europe and because major differences exist in water disinfection practices and DBPs occurrence between both continents, specific risk estimates for bladder cancer in relation to DBPs exposure for European populations were needed. We conducted a pooled and a two-stage random-effect meta-analyses of three European case-control studies from France, Finland, and Spain (5467 individuals: 2381 cases and 3086 controls). Individual exposure to THMs was calculated combining information on residential history, estimates of the average total THMs (TTHM) level in tap water at the successive residences and personal water consumption. A significant odds-ratio was observed for men exposed to an average residential TTHM level > 50 µg/l (OR = 1.47 (1.05; 2.05)) when compared to men exposed to levels ≤ 5 µg/l. The linear trend of the exposure-risk association was significant (p = 0.01). Risks increased significantly for exposure levels above 25 µg/l and with more than 30 years of exposure to chlorinated water, but were mainly driven by the level rather than the duration of exposure. No significant association was found among women or with cumulative exposure through ingestion. There was no evidence of a differential exposure-response relation for TTHM and bladder cancer in Europe and North America. Consequently, a global exposure-risk relation based on 4351 cases and 7055 controls is now available.

Individualized antibiotic prophylaxis reduces surgical site infections by gram-negative bacteria in instrumented spinal surgery.

PURPOSE: Surgical site infection (SSI) can be a challenging complication after posterior spinal fusion and instrumentation (PSFI). An increasing rate of SSI by gram-negative bacteria (GNB) has been observed. Current guideline recommendations have not been effective for preventing infection by these microorganisms. METHODS: Retrospective cohort study comparing two consecutive groups of patients undergoing PSFI at a single institution. Cohort A includes 236 patients, operated between January 2006 and March 2007, receiving standard preoperative antibiotic prophylaxis with cefazolin (clindamycin in allergic patients). Cohort B includes 223 patients operated between January and December 2009, receiving individualized antibiotic prophylaxis and treatment based on preoperative urine culture. Cultures were done 3-5 days before surgery in patients meeting one of the following risk criteria for urinary tract colonization: hospitalization longer than 7 days, indwelling catheter, neurogenic bladder, history of urinary incontinence, or history of recurrent urinary tract infection. RESULTS: Twenty-two (9.3%) patients in cohort A developed SSI, 68.2% due to GNB. 38 (17%) patients in cohort B were considered at risk for GNB colonization; preoperative urine culture was positive in 14 (36%). After adjusted antibiotic prophylaxis, 15 (6.27%) patients in cohort B developed SSI, 33.4% due to GNB. A statistically significant reduction in GNB SSI was seen in cohort B (Fisher's exact test, p = 0.039). CONCLUSION: Higher preoperative GNB colonization rates were found in patients with neurogenic bladder or indwelling catheters. Preoperative bacteriological screening, treatment for bacteriuria, and individualized antibiotic prophylaxis were effective for reducing GNB SSI.

Population pharmacokinetics of the humanised monoclonal antibody, HuHMFG1 (AS1402), derived from a phase I study on breast cancer.

BACKGROUND: HuHMFG1 (AS1402) is a humanised monoclonal antibody that has undergone a phase I trial in metastatic breast cancer. The aim of this study was to characterise the pharmacokinetics (PKs) of HuHMFG1 using a population PK model. METHOD: Data were derived from a phase I study of 26 patients receiving HuHMFG1 at doses ranging from 1 to 16 mg kg(-1). Data were analysed using NONMEM software and covariates were included. A limited sampling strategy (LSS) was developed using training and a validation data set. RESULTS: A linear two-compartment model was shown to be adequate to describe data. Covariate analysis indicated that weight was not related to clearance. An LSS was successfully developed on the basis of the model, in which one sample is collected immediately before the start of an infusion and the second is taken at the end of infusion. CONCLUSION: A two-compartment population PK model successfully describes HuHMFG1 behaviour. The model suggests using a fixed dose of HuHMFG1, which would simplify dosing. The model could be used to optimise dose level and dosing schedule if more data on the correlation between exposure and efficacy become available from future studies. The derived LSS could optimise further PK assessment of this antibody.

COGENT (COlorectal cancer GENeTics): an international consortium to study the role of polymorphic variation on the risk of colorectal cancer.

It is now recognised that a part of the inherited risk of colorectal cancer (CRC) can be explained by the co-inheritance of low-penetrance genetic variants. The accumulated experience to date in identifying these variants has served to highlight difficulties in conducting statistically and methodologically rigorous studies and follow-up analyses. The COGENT (COlorectal cancer GENeTics) consortium includes 20 research groups in Europe, Australia, the Americas, China and Japan. The overarching goal of COGENT is to identify and characterise low-penetrance susceptibility variants for CRC through association-based analyses. In this study, we review the rationale for identifying low-penetrance variants for CRC and our proposed strategy for establishing COGENT.

Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of recurrent bleeding: a multicentre randomised controlled trial.

BACKGROUND AND AIMS: Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic band ligation (EBL) in the prevention of recurrent bleeding, but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate. The present study was aimed at evaluating this issue in a multicentre randomised controlled trial (RCT) and to correlate changes in hepatic venous pressure gradient (HVPG) during treatment with clinical outcomes METHODS: 158 patients with cirrhosis, admitted because of variceal bleeding, were randomised to receive nadolol+isosorbide-5-mononitrate alone (Drug: n = 78) or combined with EBL (Drug+EBL; n = 80). HVPG measurements were performed at randomisation and after 4-6 weeks on medical therapy. RESULTS: Median follow-up was 15 months. One-year probability of recurrent bleeding was similar in both groups (33% vs 26%: p = 0.3). There were no significant differences in survival or need of rescue shunts. Overall adverse events or those requiring hospital admission were significantly more frequent in the Drug+EBL group. Recurrent bleeding was significantly more frequent in HVPG non-responders than in responders (HVPG reduction >or=20% or

Treatment of balanitis xerotica obliterans in pediatric patients. / Tratamiento de la balanitis xerótica obliterante en pacientes pediátricos.

OBJECTIVES: Balanitis xerotica obliterans (BXO) is a chronic inflammatory disease with a little known incidence in pediatric population. The objective of this work was to describe our experience in the treatment of BXO. MATERIALS AND METHODS: Retrospective study carried out in 419 patients undergoing circumcision surgery between January 2014 and January 2017. Demographic, clinical, therapeutic, and anatomical and pathological variables, as well as complications during follow-up, were analyzed. RESULTS: Of the 419 patients, 41 (9.78%) were diagnosed with BXO. 6 patients were excluded owing to lack of follow-up, so 35 patients were analyzed. Mean age at diagnosis was 8.6 years. Suspicion diagnosis was clinical at physical exploration in 17 patients (48.6%), and at surgery in 18 patients (51.4%). Anatomical and pathological confirmation was performed in a total 35 patients (100%). During follow-up, 6 patients (17.14%) had lesions in the glans, 3 (8.57%) in the urethra, and 9 (25.71%) in both. 6 meatotomies (17.14%) and 5 new circumcisions (14.28%) had to be carried out. Mean recurrence time was 32.43 months. In 19 patients (54.28%), topical corticoids - ointment - were applied, and 1 patient (2.85%) received topical immunosuppressants. CONCLUSIONS: A close follow-up of patients with clinical or anatomical and pathological diagnosis of BXO is required given its high morbidity. The complications described in pediatric population include meatal and urethral stenosis, as well as recurrent phimosis, unless a sufficient amount of foreskin is resected.

OBJETIVOS: La balanitis xerótica obliterante (BXO) es una enfermedad crónica inflamatoria de incidencia poco conocida en la población pediátrica. El objetivo de este trabajo es describir nuestra experiencia en el tratamiento de las BXO. MATERIAL Y METODOS: Estudio retrospectivo de 419 pacientes intervenidos de circuncisión en el periodo comprendido entre enero de 2014 y enero de 2017. Analizamos variables demográficas, clínicas, anatomopatológicas, terapéuticas y complicaciones durante el seguimiento. RESULTADOS: De los 419 pacientes, 41 fueron diagnosticados de BXO (9,78%). Seis pacientes fueron excluidos por falta de seguimiento, por lo que se analizaron 35 pacientes. La media de edad al diagnóstico fue de 8,6 años. El diagnóstico de sospecha fue clínico durante la exploración física en 17 pacientes (48,6%) y durante la intervención en 18 (51,4%), realizando la confirmación anatomopatológica en un total de 35 pacientes (100%). Durante el seguimiento 6 pacientes (17,14%) presentaron lesiones en glande, 3 (8,57%) en uretra y 9 (25,71%) en ambas localizaciones, siendo necesaria la realización de 6 meatotomías (17,14%) y de nueva circuncisión en 5 (14,28%). El tiempo medio de recidiva fue de 32,43 meses. En 19 pacientes (54,28%) se aplicaron corticoides tópicos en pomada y en 1 paciente inmunosupresores tópicos (2,85%). CONCLUSIONES: Es necesario un seguimiento estrecho de los pacientes con diagnóstico clínico o anatomopatológico de BXO dada su elevada morbilidad. Las principales complicaciones descritas en la población pediátrica son la estenosis meatal y uretral, así como la recidiva de la fimosis si no se reseca el prepucio suficientemente.

Swimming pool attendance and risk of asthma and allergic symptoms in children.

Increased asthma risk has been associated with pool attendance in children but evidence is inconsistent and inconclusive. A survey was conducted of 3,223 9-12-yr-old children in Sabadell (Spain) to evaluate association between swimming pool attendance and prevalence of asthma and allergic conditions and symptoms. Parents completed a questionnaire on lifetime frequency of pool attendance and symptoms in the last 12 months (wheezing, asthma medication, rhinitis and allergic rhinitis), ever having asthma and eczema, and potential confounders. Indicators of indoor and outdoor swimming pool attendance early in life, cumulatively and currently were calculated. Swimming pool attendance before the age of 2 yrs was associated with slightly lower prevalence of current asthma (OR 0.79, 95% CI 0.43-1.46), rhinitis (OR 0.86, 95% CI 0.68-1.08) and allergic rhinitis symptoms (OR 0.72, 95% CI 0.54-0.96) compared to those who started attending swimming pools after 4 yrs of age. An increased prevalence of eczema was associated with duration of lifetime pool attendance (OR 1.71, 95%CI 1.38-2.12 for >5 yrs versus 0 yrs). Swimming pool attendance in Spanish children was associated with slightly less upper and lower respiratory tract symptoms and with more eczema. Longitudinal studies are required to confirm these findings and avoid potential reverse causation.

The detection of brain ischaemia in rats by inductive phase shift spectroscopy.

Ischaemia in the brain is an important clinical problem that is often monitored and studied with expensive devices such as MRI and PET, which are not readily available in low economical resource parts of the world. We have developed a new less expensive tool for non-invasive monitoring of ischaemia in the brain. This is a first feasibility study describing the concept. The system is based on the hypothesis that electromagnetic properties of the tissue change during ischaemia and that measuring the electromagnetic properties of the bulk of the brain with non-contact means can detect these changes. The apparatus we have built and whose design we describe here consists of two electromagnetic coils placed around the head. The system measures the bulk change in time of the phase difference between the electromagnetic signal on the two coils in a range of frequencies. A mathematical model simulating the device and the measurement is also introduced. Ischaemia was induced in the brain of rats by occlusion of the right cerebral and carotid arteries. Experimental subjects were monitored for 24 h. Inductive phase shift measurements were made at five frequencies in the range of 0.1-50 MHz eight times during the observation period. An ex vivo estimation of the percentage of necrosis in the ischemic subjects at t = 24 h was done. The mathematical model was also applied to the experimental tested situation. The results of both experiments and theory show significant phase shifts increase as a function of frequency and ischaemia time. The theoretical and experimental results suggest that the tested technique has the potential to detect the processes and level of ischaemia in the brain by non-invasive, continuous, bulk volumetric monitoring with a simple and inexpensive apparatus.

Open vs robotic infant ureteroureterostomy.

INTRODUCTION: A ureteroureterostomy (UU) is often used to manage some duplication anomalies. The operation is commonly performed through a Pfannenstiel incision, but other minimally invasive approaches have been described. The objective of this study is to compare open vs robotic infant UU with regards to operative time, complications, and operative success. METHODS AND MATERIALS: This is a retrospective institutional review board approved study of all infant UUs performed from July 2013 to January 2019. Before the DaVinci Xi became available (November 2017), UUs were primarily done open. All UUs after November 2017 were robotic. Surgery was recommended electively at 6 months in suspected cases of ectopic ureters or earlier for history of febrile UTI's or worsening hydronephrosis. Both open and robotic cases were started with cystoscopy and lower pole ureteral stent placement. A 5-0 polypropylene suture was tied in between in the stent and the Foley catheter. Foley and stent were removed 3-7 days after surgery in the clinic or at home by the parents. For both open and robotic approaches, patients were discharged on postoperative day (POD) 1 with the Foley draining into a double diaper on antibiotic prophylaxis. RESULTS: From July 2013 to January 2019, 12 open and eight robotic infant UUs were performed. One patient in each group had a ureterocele, and the rest had ectopic ureters. Median age was 7 months for both the open and robotic groups. All patients except one had a 3.7 Fr by 10-12 cm stent placed attached to an 8-10 Fr silicone Foley catheter. The exception was the first robotic case who had a 3 Fr stent with no dangler placed after failed attempts with a 4.7 Fr stent (there were no 3.7 Fr stents that day). Median surgery time was 129 min (range 100-188, mean 133 min) for open and 130 min (range 79-226 min, mean 137 min) for robotic (P-value 0.8). In addition to the robotic case who had a 3 Fr stent placed with no dangler, an additional robotic case had to have her stent removed under anesthesia because the dangler broke or the knot got undone when the Foley was removed. One patient in the robotic arm who had the surgery done for a ureterocele had two postoperative febrile UTI's. Evaluation with VCUG and renal ultrasound (US) did not reveal hydronephrosis or reflux. She was managed conservatively. Other than the two cystoscopy and stent removals, no patient required a reoperation. DISCUSSION: These data indicate that the laparoscopic robotic-assisted UU can be safely performed in infants with similar operative time compared with the traditional open Pfannenstiel approach. The two complications in the robotic arm were not related to the approach itself but to issues with the stents, which would have not been prevented by an open approach. There were no complications specific to the robotic approach. CONCLUSIONS: Laparoscopic robotic-assisted infant UUs are safe, effective, and can be done in a similar time compared with the traditional open Pfannenstiel approach.

'Mini' extravesical reimplant with 'mini' tapering for infants younger than 6 months.

INTRODUCTION: Some infants with obstructed megaureters or ectopic ureters requiring surgery undergo a cutaneous ureterostomy followed by definitive repair after 12 months of age. Since 2013, a 'mini' extravesical reimplant with or without 'mini' tapering (MER) was performed instead of cutaneous ureterostomy in such infants. OBJECTIVE: To describe the technique and outcomes for MER. STUDY DESIGN: This is a retrospective review of infants younger than 6 months who underwent MER. MER consists of a 2- to 3-cm extravesical tunnel, regardless of the ureter diameter. 'Mini' tapering consisted of an adventitial sparing technique involving only the distal 2-3 cm of the ureter. Details of the technique are included in the video. The main outcomes were postoperative symptomatic urinary tract infections (UTI's) and reoperations. Voiding function was assessed at the last contact with the family. RESULTS: Nine consecutive infants underwent MER from July 2013 to March 2018. Four patients had ectopic ureters and five had primary obstructed megaureters. The median ureteral diameter was 1.5 cm. Indications for surgery were as per the British Association of Pediatric Urologists guidelines on megaureters. All patients had 3-month postoperative renal ultrasound, and seven of the nine patients had postoperative voiding cystourethrogram (VCUG). One patient with a normal postoperative VCUG and MAG 3, as well as resolved hydroureteronephrosis had a few postoperative febrile UTIs but no more for >1 year at the last follow-up. At a median time from surgery of 44 months, there have been no reoperations (except cystoscopy with stent removal). With regard to voiding function, six patients were successfully potty trained, one has bowel and bladder incontinence at the age of 4 years - with stable renal ulstraound -, and two are younger than 2 years. DISCUSSION: MER has been the only surgery needed for the cohort of nine infants younger than 6 months with distal ureteral obstruction at a median time from surgery of 44 months. Voiding function does not appear to be affected by the operation. CONCLUSIONS: For babies younger than 6 months of age in need of surgery for obstructed distal ureter, MER appears to be a feasible and effective option, associated with reduced morbidity and reoperation rate compared to the alternatives.

The relation between paracetamol use and asthma: a GA2LEN European case-control study.

Studies from the UK and USA suggest that frequent use of paracetamol (acetaminophen) may increase the risk of asthma, but data across Europe are lacking. As part of a multicentric case-control study organised by the Global Allergy and Asthma European Network (GA(2)LEN), it was examined whether or not frequent paracetamol use is associated with adult asthma across Europe. The network compared 521 cases with a diagnosis of asthma and reporting of asthma symptoms within the last 12 months with 507 controls with no diagnosis of asthma and no asthmatic symptoms within the last 12 months across 12 European centres. All cases and controls were selected from the same population, defined by age (20-45 yrs) and place of residence. In a random effects meta-analysis, weekly use of paracetamol, compared with less frequent use, was strongly positively associated with asthma after controlling for confounders. There was no evidence for heterogeneity across centres. No association was seen between use of other analgesics and asthma. These data add to the increasing and consistent epidemiological evidence implicating frequent paracetamol use in asthma in diverse populations.