A single blinded randomized controlled trial comparing semi-mechanical with hand-sewn cervical anastomosis after esophagectomy for cancer (SHARE-study).

OBJECTIVE: The aim was to compare leak rate between hand-sewn end-to-end anastomosis (ETE) and semi-mechanical anastomosis (SMA) after esophagectomy with gastric tube reconstruction. BACKGROUND DATA: The optimal surgical technique for creation of an anastomosis in the neck after esophagectomy is unclear. METHODS: Patients with esophageal cancer undergoing esophagectomy with gastric tube reconstruction and cervical anastomosis were eligible for participation after written informed consent. Patients were randomized in 1:1 ratio. Primary endpoint was anastomotic leak rate defined as external drainage of saliva from the site of the anastomosis or intra-thoracic manifestation of leak. Secondary endpoints included anastomotic stricture rate at one year follow up, number of endoscopic dilatations, dysphagia-score, hospital stay, morbidity, and mortality. Patients were blinded for intervention. RESULTS: Between August 2011 and July 2014, 174 patients with esophageal cancer underwent esophagectomy. Ninety-three patients were randomized to ETE (n = 44) or SMA (n = 49). Anastomotic leak occurred in 9 of 44 patients (20%) in the ETE group and 12 of 49 patients (24%) in the SMA group (absolute difference 4%, 95% CI -13% to +21%; p = .804). There was no significant difference in dysphagia at 1 year postoperatively (ETE 25% vs. SMA 20%; p = .628), in stricture rate (ETE 25% vs. 19% in SMA, p = .46), nor in median hospital stay (17 days in the ETE group, 13 days in the SMA group), morbidity (82% vs. 73%, p = .460) or mortality (0% vs. 4%, p = .175) between the groups.

Watchful Waiting Versus Surgery of Mildly Symptomatic or Asymptomatic Inguinal Hernia in Men Aged 50 Years and Older: A Randomized Controlled Trial.

OBJECTIVE: To compare if watchful waiting is noninferior to elective repair in men aged 50 years and older with mildly symptomatic or asymptomatic inguinal hernia. BACKGROUND: The role of watchful waiting in older male patients with mildly symptomatic or asymptomatic inguinal hernia is still not well-established. METHODS: In this noninferiority trial, we randomly assigned men aged 50 years and older with mildly symptomatic or asymptomatic inguinal hernia to either elective inguinal hernia repair or watchful waiting. Primary endpoint was the mean difference in a 4-point pain/discomfort score at 24 months of follow-up. Using a 0.20-point difference as a clinically relevant margin, it was hypothesized that watchful waiting was noninferior to elective repair. Secondary endpoints included quality of life, event-free survival, and crossover rates. RESULTS: Between January 2006 and August 2012, 528 patients were enrolled, of whom 496 met the inclusion criteria: 234 were assigned to elective repair and 262 to watchful waiting. The mean pain/discomfort score at 24 months was 0.35 [95% confidence interval (CI) 0.28-0.41)] in the elective repair group and 0.58 (95% CI 0.52-0.64) in the watchful waiting group. The difference of these means (MD) was -0.23 (95% CI -0.32 to -0.14). In the watchful waiting group, 93 patients (35·4%) eventually underwent elective surgery and 6 patients (2·3%) received emergent surgery for strangulation/incarceration. Postoperative complication rates and recurrence rates in these 99 operated individuals were comparable with individuals originally assigned to the elective repair group (8.1% vs 15.0%; P = 0.106, 7.1% vs 8.9%; P = 0.668, respectively). CONCLUSIONS: Our data could not rule out a relevant difference in favor of elective repair with regard to the primary endpoint. Nevertheless, in view of all other findings, we feel that our results justify watchful waiting as a reasonable alternative compared with surgery in men aged 50 years and older.

A prospective study on drug monitoring of PEGasparaginase and Erwinia asparaginase and asparaginase antibodies in pediatric acute lymphoblastic leukemia.

This study prospectively analyzed the efficacy of very prolonged courses of pegylated Escherichia coli asparaginase (PEGasparaginase) and Erwinia asparaginase in pediatric acute lymphoblastic leukemia (ALL) patients. Patients received 15 PEGasparaginase infusions (2500 IU/m(2) every 2 weeks) in intensification after receiving native E coli asparaginase in induction. In case of allergy to or silent inactivation of PEGasparaginase, Erwinia asparaginase (20 000 IU/m(2) 2-3 times weekly) was given. Eighty-nine patients were enrolled in the PEGasparaginase study. Twenty (22%) of the PEGasparaginase-treated patients developed an allergy; 7 (8%) showed silent inactivation. The PEGasparaginase level was 0 in all allergic patients (grade 1-4). Patients without hypersensitivity to PEGasparaginase had serum mean trough levels of 899 U/L. Fifty-nine patients were included in the Erwinia asparaginase study; 2 (3%) developed an allergy and none silent inactivation. Ninety-six percent had at least 1 trough level ≥100 U/L. The serum asparagine level was not always completely depleted with Erwinia asparaginase in contrast to PEGasparaginase. The presence of asparaginase antibodies was related to allergies and silent inactivation, but with low specificity (64%). Use of native E coli asparaginase in induction leads to high hypersensitivity rates to PEGasparaginase in intensification. Therefore, PEGasparaginase should be used upfront in induction, and we suggest that the dose could be lowered. Switching to Erwinia asparaginase leads to effective asparaginase levels in most patients. Therapeutic drug monitoring has been added to our ALL-11 protocol to individualize asparaginase therapy.

Insulin therapy in hyperglycemic children with severe acute asthma.

OBJECTIVES: The aim of this study was to assess the effect of intravenous (IV) insulin administration in children with severe acute asthma (SAA) and hyperglycemia on IV salbutamol consumption and length of stay (LOS) in a pediatric intensive care unit (PICU). METHODS: Retrospective, descriptive study of the clinical course before and after implementation of an insulin protocol for the treatment of hyperglycemia (i.e. blood glucose >8 mmol/L or 144 mg/dL, respectively) in the PICU of a tertiary care university hospital. Admissions between 1994 and 2010 were reviewed. The insulin protocol was introduced in 2006. RESULTS: A total of 131 pediatric patients with SAA complicated by hyperglycemia requiring IV salbutamol were included. Severity of illness before and after implementation of the insulin protocol did not significantly differ. The insulin-treated patient group had significantly higher maximum blood glucose levels and higher cumulative IV salbutamol dose than the non-treated group. There were no differences between these groups in the duration of IV salbutamol administration and LOS. CONCLUSIONS: In view of the lack of difference in outcomes and considering that the insulin protocol is labor-intensive, the question is whether this protocol is efficacious for the treatment of pediatric SAA associated with hyperglycemia.

The toxicity of very prolonged courses of PEGasparaginase or Erwinia asparaginase in relation to asparaginase activity, with a special focus on dyslipidemia.

We prospectively studied the incidence and clinical course of hypertriglyceridemia and hypercholesterolemia during very prolonged use of asparaginase in relation to levels of asparaginase activity in children with acute lymphoblastic leukemia. We also evaluated the incidence of pancreatitis, thrombosis, hyperammonemia and central neurotoxicity and their association with asparaginase activity levels. Eighty-nine patients were treated according to the Dutch Childhood Oncology Group Acute Lymphoblastic Leukemia 10 medium-risk intensification protocol, which includes 15 doses of PEGasparaginase (2,500 IU/m(2)) over 30 weeks. Erwinia asparaginase (20,000 IU/m(2)) was administered when allergy to or silent inactivation of PEGasparaginase occurred. Triglyceride, cholesterol and ammonia levels increased rapidly in children treated with PEGasparaginase and remained temporarily elevated, but normalized after administration of the last asparaginase dose. Among the patients treated with PEGasparaginase, hypertriglyceridemia and hypercholesterolemia (grade 3/4) were found in 47% and 25%, respectively. The correlation between PEGasparaginase activity levels and triglyceride levels was strongest at week 5 (Spearman correlation coefficient = 0.36, P = 0.005). The triglyceride levels were higher in children ≥ 10 years old than in younger patients (<10 years old) after adjustment for type of asparaginase preparation: median 4.9 mmol/L versus 1.6 mmol/L (P<0.001). In patients receiving Erwinia asparaginase, triglyceride levels increased in the first weeks as well, but no grade 3/4 dyslipidemia was found. Hyperammonemia (grade 3/4) was only found in patients treated with Erwinia asparaginase (9%). Thrombosis occurred in 4.5%, pancreatitis in 7%, and central neurotoxicity in 9% of patients using either of the two agents; these toxicities were not related to levels of asparaginase activity or to triglyceride levels. In conclusion, severe dyslipidemia occurred frequently, but was temporary and was not associated with relevant clinical events and should not, therefore, be considered a reason for modifying asparaginase treatment. Dyslipidemia was the only toxicity related to levels of asparaginase activity.

Incisional hernia after liver transplantation: risk factors and health-related quality of life.

The aim of this cross-sectional study was to analyze the incidence of incisional hernia after liver transplantation (LT), to determine potential risk factors for their development, and to assess their impact on health-related quality of life (HRQoL). Patients who underwent LT through a J-shaped incision with a minimum follow-up of three months were included. Follow-up was conducted at the outpatient clinic. Short Form 36 (SF-36) and body image questionnaire (BIQ) were used for the assessment of HRQoL. A total of 140 patients was evaluated. The mean follow-up period was 33 (SD 20) months. Sixty patients (43%) were diagnosed with an incisional hernia. Multivariate analysis revealed surgical site infection (OR 5.27, p = 0.001), advanced age (OR 1.05, p = 0.003), and prolonged ICU stay (OR 1.54, p = 0.022) to be independent risk factors for development of incisional hernia after LT. Patients with an incisional hernia experienced significantly diminished HRQoL with respect to physical, social, and mental aspects. In conclusion, patients who undergo LT exhibit a high incidence of incisional hernia, which has a considerable impact on HRQoL. Development of incisional hernia was shown to be related to surgical site infection, advanced age, and prolonged ICU stay.

Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome.

Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69 hospitals in The Netherlands. We randomly assigned 150 children (9 months to 17 years) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo (n=74) or 6 months of prednisolone (n=76), and median follow-up was 47 months. Both groups received equal cumulative doses of prednisolone (approximately 3360 mg/m(2)). Among the 126 children who started trial medication, relapses occurred in 48 (77%) of 62 patients who received 3 months of prednisolone and 51 (80%) of 64 patients who received 6 months of prednisolone. Frequent relapses, according to international criteria, occurred with similar frequency between groups as well (45% versus 50%). In addition, there were no statistically significant differences between groups with respect to the eventual initiation of prednisolone maintenance and/or other immunosuppressive therapy (50% versus 59%), steroid dependence, or adverse effects. In conclusion, in this trial, extending initial prednisolone treatment from 3 to 6 months without increasing cumulative dose did not benefit clinical outcome in children with nephrotic syndrome. Previous findings indicating that prolonged treatment regimens reduce relapses most likely resulted from increased cumulative dose rather than the treatment duration.

Real-life compliance and persistence among users of subcutaneous and sublingual allergen immunotherapy.

BACKGROUND: Subcutaneous allergen immunotherapy (SCIT) and sublingual allergen immunotherapy (SLIT) are safe and effective treatments of allergic rhinitis, but high levels of compliance and persistence are crucial to achieving the desired clinical effects. OBJECTIVE: Our objective was to assess levels and predictors of compliance and persistence among grass pollen, tree pollen, and house dust mite immunotherapy users in real life and to estimate the costs of premature discontinuation. METHODS: We performed a retrospective analysis of a community pharmacy database from The Netherlands containing data from 6486 patients starting immunotherapy for 1 or more of the allergens of interest between 1994 and 2009. Two thousand seven hundred ninety-six patients received SCIT, and 3690 received SLIT. Time to treatment discontinuation was analyzed and included Cox proportional hazard models with time-dependent covariates, where appropriate. RESULTS: Overall, only 18% of users reached the minimally required duration of treatment of 3 years (SCIT, 23%; SLIT, 7%). Median durations for SCIT and SLIT users were 1.7 and 0.6 years, respectively (P < .001). Other independent predictors of premature discontinuation were prescriber, with patients of general practitioners demonstrating longer persistence than those of allergologists and other medical specialists; single-allergen immunotherapy, lower socioeconomic status; and younger age. Of the persistent patients, 56% were never late in picking up their medication from the pharmacy. Direct medication costs per nonpersistent patient discontinuing in the third year of treatment were €3800, an amount that was largely misspent. CONCLUSION: Real-life persistence is better in SCIT users than in SLIT users, although it is low overall. There is an urgent need for further identification of potential barriers and measures that will enhance persistence and compliance.

Carriage of Mycoplasma pneumoniae in the upper respiratory tract of symptomatic and asymptomatic children: an observational study.

BACKGROUND: Mycoplasma pneumoniae is thought to be a common cause of respiratory tract infections (RTIs) in children. The diagnosis of M. pneumoniae RTIs currently relies on serological methods and/or the detection of bacterial DNA in the upper respiratory tract (URT). It is conceivable, however, that these diagnostic methods also yield positive results if M. pneumoniae is carried asymptomatically in the URT. Positive results from these tests may therefore not always be indicative of a symptomatic infection. The existence of asymptomatic carriage of M. pneumoniae has not been established. We hypothesized that asymptomatic carriage in children exists and investigated whether colonization and symptomatic infection could be differentiated by current diagnostic methods. METHODS AND FINDINGS: This study was conducted at the Erasmus MC-Sophia Children's Hospital and the after-hours General Practitioners Cooperative in Rotterdam, The Netherlands. Asymptomatic children (n = 405) and children with RTI symptoms (n = 321) aged 3 mo to 16 y were enrolled in a cross-sectional study from July 1, 2008, to November 30, 2011. Clinical data, pharyngeal and nasopharyngeal specimens, and serum samples were collected. The primary objective was to differentiate between colonization and symptomatic infection with M. pneumoniae by current diagnostic methods, especially real-time PCR. M. pneumoniae DNA was detected in 21.2% (95% CI 17.2%-25.2%) of the asymptomatic children and in 16.2% (95% CI 12.2%-20.2%) of the symptomatic children (p = 0.11). Neither serology nor quantitative PCR nor culture differentiated asymptomatic carriage from infection. A total of 202 children were tested for the presence of other bacterial and viral pathogens. Two or more pathogens were found in 56% (63/112) of the asymptomatic children and in 55.5% (50/90) of the symptomatic children. Finally, longitudinal sampling showed persistence of M. pneumoniae in the URT for up to 4 mo. Fifteen of the 21 asymptomatic children with M. pneumoniae and 19 of the 22 symptomatic children with M. pneumoniae in this longitudinal follow-up tested negative after 1 mo. CONCLUSIONS: Although our study has limitations, such as a single study site and limited sample size, our data indicate that the presence of M. pneumoniae in the URT is common in asymptomatic children. The current diagnostic tests for M. pneumoniae are unable to differentiate between asymptomatic carriage and symptomatic infection.

Up to five years experience with 11 mucopolysaccharidosis type VI patients.

Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI, MPS VI) is a rare progressive metabolic disorder characterized by coarse facial features, hepatosplenomegaly, restrictive pulmonary function, cardiac abnormalities and stiff joints. The disease is caused by a deficiency of the lysosomal enzyme N-acetyl galactosamine 4-sulfatase which leads to glycosaminoglycan (GAG) storage in various tissues. It presents as a clinical spectrum with varying disease progressions and severities. While the phases I/II/III studies proved the effectiveness of enzyme-replacement therapy (ERT) with recombinant human arylsulfatase B, long-term data are still scarce. Over treatment periods ranging from 1.3 to 5.4 years, this prospective open-label follow-up study in 11 Dutch mucopolysaccharidosis type VI patients (age 2-18 years) showed that ERT had significant positive effects on cardiac-wall diameters (IVSd and LVMI), left and right shoulder flexions (p<0.001), liver size and spleen size (p<0.001), urinary GAG excretion (p<0.001), and the scales of quality of life (motor functioning and body functioning). ERT did not affect cardiac valve regurgitation or hearing function; HRQoL decreased slightly in two domains ('anxiety' and 'negative emotions'), and patients with the rapid and slow progressive forms of the disease differed with regard to baseline GAG excretion and GAG decrease during treatment. In conclusion, ERT had an effect on several clinical parameters. This effect was established in an open cohort of young mucopolysaccharidosis type VI patients.

Enzyme replacement therapy and fatigue in adults with Pompe disease.

BACKGROUND: Pompe disease is a hereditary metabolic myopathy, for which enzyme replacement therapy (ERT) has been available since 2006. We investigated whether ERT reduces fatigue in adult patients with Pompe disease. METHODS: In this prospective international observational survey, we used the Fatigue Severity Scale (FSS) to measure fatigue. Repeated measures ANOVA was used to analyze the data over time. In a subgroup of patients, we also evaluated muscle strength using the Medical Research Council Scale, measured pulmonary function as Forced Vital Capacity, and assessed depression using the Hospital Anxiety and Depression Scale. RESULTS: We followed 163 patients for a median period of 4 years before ERT and for 3 years during ERT. Before ERT, the mean FSS score remained stable at around 5.3 score points; during ERT, scores improved significantly by 0.13 score points per year (p < 0.001). Fatigue decreased mainly in women, in older patients and in those with shorter disease duration. Patients' improvements in fatigue were moderately correlated with the effect of ERT on depression (r 0.55; CI 95% 0.07 to 0.70) but not with the effect of ERT on muscle strength or pulmonary function. CONCLUSIONS: Fatigue is a common and disabling problem in patients with early and advanced stages of Pompe disease. Our finding that ERT helps to reduce fatigue is therefore important for this patient population, irrespective of the mechanisms underlying this effect.

The relevance of patient-reported outcomes in a grass pollen immunotherapy trial in children and adolescents with rhinoconjunctivitis.

BACKGROUND: Patient-reported outcomes (PROs) are the only instruments available to assess the efficacy of an intervention in patients with allergic rhinoconjunctivitis. As allergic rhinoconjunctivitis is a systemic disease, it is now recommended to use not only PROs focusing at classical symptoms, but also health-related quality of life (HRQL) instruments in immunotherapy trials. METHODS: A previously published immunotherapy trial in children and adolescents (6-18 yr) with hay fever provided us with data to assess the relevance of two of these additional outcome measures, the disease-specific rhinoconjunctivitis quality of life questionnaire (RQLQ) and the generic COOP/WONCA-charts (CWC). A PRO was considered relevant if it was responsive to pollen exposure and at least had a moderate correlation with the classical symptoms of allergic rhinoconjunctivitis. Furthermore, we evaluated a post-season PRO, that is, a global assessment of symptoms (GAS). This assessment is used in clinical trials as a tool for selecting participants with sufficient symptoms and in daily practice to evaluate the patient's complaints during the preceding season. We assessed the correlation of this retrospective score with the actual symptoms during the previous pollen season. RESULTS: Data from 36 children and 63 adolescents were analysed. On the basis of the total scores of the paediatric and adolescent version of the RQLQ, both questionnaires were considered relevant as they were responsive to exposure and showed a moderate to strong correlation with the rhinoconjunctivitis symptoms. However, in both children and adolescents, 40% of the RQLQ items were not relevant according to our definition. The CWC as a whole and the separate charts appear less relevant because of the weak correlations with the daily symptom score from the diary. The correlation between our post-season GAS and the in season daily symptom score was weak. CONCLUSION: The paediatric and adolescent RQLQ are relevant, but could be shortened as they contain a substantial number of irrelevant items. The CWC are not relevant in the monitoring of children and adolescents with allergic rhinoconjunctivitis caused by grass pollen. The retrospective GAS does not sufficiently reflect the actual symptoms during the preceding season.

Mucopolysaccharidosis: cardiologic features and effects of enzyme-replacement therapy in 24 children with MPS I, II and VI.

We determined the cardiologic features of children with MPS I, II and VI, and evaluated the effect of enzyme-replacement therapy (ERT) on cardiac disease. Twenty-four children aged 1-18 years with MPS I, II or VI were prospectively evaluated with echocardiogram and electrocardiogram from the start of enzyme-replacement therapy up to 6 years of treatment. At start of therapy, 66% had abnormal cardiac geometric features. Left-ventricular mass index (LVMI) was increased in half of the patients, due mainly to concentric hypertrophy in MPS I and II and to eccentric hypertrophy in MPS VI. Regurgitation was most severe in a subgroup of young MPS VI patients (<5 years) at the mitral valve. At baseline, all patients had abnormal valves. The ECG showed no clear rhythm or conduction abnormalities; neither, in most patients, did it reflect the hypertrophy. After ERT, the LVMI Z-score normalized in 70% of the patients who had a Z-score > 2. LVMI Z-scores decreased significantly in patients with MPS I and MPS II (p = 0.04 and p = 0.032). Despite ERT, valve regurgitation increased in 60% of the patients. We conclude that all our MPS patients have cardiac abnormalities. The most severe cardiac disease was observed in a subgroup of young MPS VI patients. While ERT had an effect on LVMI and IVSd, it apparently had little or none on valve regurgitation.

No evidence of increased asparagine levels in the bone marrow of patients with acute lymphoblastic leukemia during asparaginase therapy.

BACKGROUND: Mesenchymal cells (MSCs) in bone marrow (BM) may produce asparagine and form protective niches for leukemic cells. In vitro, this led to high levels of asparagine and conferred asparaginase resistance to acute lymphoblastic leukemia (ALL) cells. The aim of this study was to investigate whether MSCs or other cells in BM indeed produce such significant amounts of asparagine in vivo as to result in clinical asparaginase resistance. PROCEDURE: Twenty-six patients with newly diagnosed ALL were enrolled. All children received induction chemotherapy according to the Dutch Childhood Oncology Group (DCOG) ALL-10 protocol. Asparaginase was administered from days 12-33. Asparaginase, asparagine, aspartic acid, glutamine, and glutamic acid levels were measured in BM and blood at diagnosis, days 15, 33, and 79. RESULTS: Median asparaginase trough levels were not significantly different at days 15 and 33. Only at diagnosis, asparagine level was significantly higher in BM than in blood (P = 0.001). Asparagine levels were all below the lower limit of quantification in BM and blood at days 15 and 33. However, aspartic acid level in BM was significantly higher than in blood (P < 0.001) at diagnosis, and also at days 15, 33, and 79. CONCLUSIONS: We demonstrate higher aspartic acid levels in BM compared to blood; however, no increased asparagine levels were seen during induction therapy containing asparaginase in BM when compared to blood. Therefore, increased asparagine synthesis by MSCs is of relevance for resistance to asparaginase of leukemic cells in vitro, but it is questionable whether this leads to asparaginase resistance in childhood ALL patients.

Chronic anal and perianal pain resolved with MRI.

OBJECTIVE: The purpose of this study was to assess the diagnostic value of anorectal MRI in the care of patients with chronic anal and perianal pain but without findings of abnormalities in the clinical workup. MATERIALS AND METHODS: Patients referred from a tertiary department of colorectal surgery to the MRI unit with clinically occult chronic anal and perianal pain were included. MRI of the anorectum was performed with an endoanal or pelvic phased-array coil. The images from all examinations were read by two radiologists. MRI findings were correlated with clinical follow-up data. RESULTS: The study group (103 patients) was stratified into patients with no history of anorectal disease (n = 60) and those who had a history of surgery for anorectal disease (n = 43). MRI findings suggested the final diagnoses in 40 patients (39%). These diagnoses were 28 cases of suppurative lesions (27%), 11 cases of painful scarring of the anus (11%), and one case of metastasis to the sacrum (1%). Suppurative lesions were surgically proved with marked relief of pain after surgery. In the other patients the final diagnoses were 37 cases of levator ani syndrome (36%) and 26 cases of unspecified functional anorectal pain (25%). No MRI abnormalities were found in 33 of the patients with levator ani syndrome and 26 of the patients with unspecified anorectal pain. The two readers had very good agreement (κ = 0.92). The patients with a history of anorectal disease had significantly more MRI findings of abnormalities (60%) than did patients without a history of anorectal disease (23%). The positive predictive value of MRI was 91%, and the negative predictive value was 100%. CONCLUSION: In 39% of patients, MRI showed abnormalities that were clinically confirmed as the final diagnosis. Surgical treatment will especially benefit patients with suppurative lesions, resulting in relief of pain.

Acute kidney injury is a frequent complication in critically ill neonates receiving extracorporeal membrane oxygenation: a 14-year cohort study.

INTRODUCTION: Newborns in need of extracorporeal membrane oxygenation (ECMO) support are at high risk of developing acute kidney injury (AKI). AKI may occur as part of multiple organ failure and can be aggravated by exposure to components of the extracorporeal circuit. AKI necessitates adjustment of dosage of renally eliminated drugs and avoidance of nephrotoxic drugs. We aimed to define systematically the incidence and clinical course of AKI in critically ill neonates receiving ECMO support. METHODS: This study reviewed prospectively collected clinical data (including age, diagnosis, ECMO course, and serum creatinine (SCr)) of all ECMO-treated neonates within our institution spanning a 14-year period. AKI was defined by using the Risk, Injury, Failure, Loss of renal function, and End-stage renal disease (RIFLE) classification. SCr data were reviewed per ECMO day and compared with age-specific SCr reference values. Accordingly, patients were assigned to RIFLE categories (Risk, Injury, or Failure as 150%, 200%, or 300% of median SCr reference values). Data are presented as median and interquartile range (IQR) or number and percentage. RESULTS: Of 242 patients included, 179 (74%) survived. Median age at the start of ECMO was 39 hours (IQR, 26 to 63); median ECMO duration was 5.8 days (IQR, 3.9 to 9.4). In total, 153 (64%) patients had evidence of AKI, with 72 (30%) qualifying as Risk, 55 (23%) as Injury, and 26 (11%) as Failure. At the end of the study period, only 71 (46%) patients of all 153 AKI patients improved by at least one RIFLE category. With regression analysis, it was found that nitric oxide ventilation (P = 0.04) and younger age at the start of ECMO (P = 0.004) were significant predictors of AKI. Survival until intensive care unit discharge was significantly lower for patients in the Failure category (35%) as compared with the Non-AKI (78%), Risk (82%), and Injury category (76%), with all P < 0.001, whereas no significant differences were found between the three latter RIFLE categories. CONCLUSIONS: Two thirds of neonates receiving ECMO had AKI, with a significantly increased mortality risk for patients in the Failure category. As AKI during childhood may predispose to chronic kidney disease in adulthood, long-term monitoring of kidney function after ECMO is warranted.

Perception of bronchoconstriction: a complementary disease marker in children with asthma.

INTRODUCTION: Asthma guidelines use symptoms as the most important aspect of asthma control. Symptom perception varies widely between individuals. Over-perception as well as underperception of bronchoconstriction could have a negative effect on asthma management. We hypothesized that perception of bronchoconstriction in childhood asthma is not related to common measures of disease control. For that reason, we examined the clinical determinants of the perception of bronchoconstriction and the repeatability of perception measurements. PATIENTS AND METHODS: In school-age children with moderately severe atopic asthma, we measured the perception of bronchoconstriction (decrease in forced expiratory volume in 1 second (FEV(1)) during methacholine bronchoprovocation challenges. The perception of bronchoconstriction was assessed as the slope of the relation between FEV(1) and Borg score, and as the Borg score at a 20% decrease in FEV(1) from baseline during the provocation test (PS(20)). Data from subjects who had a 20% or more decrease in FEV(1) (n = 112) were used for the analysis. Fifty-four children repeated the test after 3 months. Symptoms, use of rescue medication, and peak expiratory flows were scored in diaries during the 2 weeks before testing. RESULTS: Symptom perception was significantly better in children without (PD(20) > 1570 µg, n = 28) than in children with airway hyperresponsiveness (PD(20) ≤ 1570 µg, n = 112), slope 0.22 versus 0.13 respectively (p < .001). Borg scores correlated with PD(20) (p = .01), baseline FEV(1) (only for slope, p = .04), and use of rescue beta agonist (p = .01), but not with other aspects of asthma control. Repeatability of Borg scores was good (slope: R = 0.59, PS(20): R = 0.52). CONCLUSION: Poorer symptom perception in asthmatic children correlated with hyperresponsiveness, and was associated with lower baseline FEV(1) and less use of rescue bronchodilators. This suggests that the measurement of symptom perception should be taken into account in individual management plans for children with asthma.

Emotional distress in 652 Dutch very long-term survivors of childhood cancer, using the hospital anxiety and depression scale (HADS).

BACKGROUND: After a more successful treatment of pediatric cancer, the number of childhood cancer survivors is progressively increasing. Consequently, awareness of psychological late sequelae is important. PROCEDURE: The Hospital Anxiety and Depression Scale (HADS) was used as a screening tool for emotional distress in a single center cohort of 652 childhood cancer survivors (median age 23 y [range, 15 to 46 y], median follow-up time 15 y [range, 5 to 42 y]). Results were compared with a control group of 440 Dutch subjects. A higher HADS score linearly reflect a higher level of emotional distress, and a score ≥15 is indicative of clinically significant emotional distress. RESULTS: Mean HADS score of the childhood cancer survivors was not different from the control group (P=0.38). Survivors exposed to global central nervous system (CNS) irradiation had a significantly higher HADS score than the control group (8.3±6.6; P=0.05) as well as other survivors (P=0.01). Forty-three survivors (7%) had a HADS score ≥15. Survivors with a HADS score ≥15 were variously spread over the diagnostic-related and treatment-related subgroups. Linear regression analysis showed that high educational achievement (ß=-1.28; P<0.01) and age at the time of the study (ß=0.08; P=0.03) were both significantly associated with the HADS score. CONCLUSIONS: Emotional distress does not occur more often in childhood cancer survivors than in the normal population. No disease-related or treatment-related variable was independently associated with emotional distress.

The current state of active third stage management to prevent postpartum hemorrhage: a cross-sectional study.

OBJECTIVE: To investigate the implementation of the International Confederation of Midwives/International Federation of Gynecology and Obstetrics (ICM/FIGO) guideline on active third stage management in vaginal deliveries in daily clinical practice. DESIGN: Observational, cross-sectional study. SETTING: One tertiary and one teaching hospital in the Netherlands. POPULATION: Women undergoing vaginal deliveries. METHODS: A case record form was completed after every vaginal delivery. Primary outcome was adequate guideline adherence, defined as initial administration of 10 IU oxytocin, performance of controlled cord traction and uterine massage. Adequate guideline adherence was a priori estimated to be 10%. With a sample size of 600, i.e. 300 women per hospital, the standard error of the resulting percentage would be less than 2% for each hospital. RESULTS: Six hundred and twenty six women were included. Guideline adherence was adequately performed in 48% of vaginal deliveries. Oxytocin was administered after birth in 98% of deliveries and in 80% the correct dose was used. Controlled cord traction was performed in 63% and uterine massage in 93%; however, the latter was performed as advised (at least eight times) in only 8%. The amount of blood loss was not associated with the use of either 5 or 10 IU oxytocin (p = 0.818). Controlled cord traction and uterine massage were more frequently performed when blood loss exceeded 500 mL (p < 0.001). CONCLUSIONS: Active third stage management according to the ICM/FIGO guideline is adequately performed in only 48% of all vaginal deliveries. Results of this study call for training programs to increase adherence to the ICM/FIGO guideline.

Chest computed tomography scores are predictive of survival in patients with cystic fibrosis awaiting lung transplantation.

RATIONALE: Up to one-third of patients with cystic fibrosis (CF) awaiting lung transplantation (LTX) die while waiting. Inclusion of computed tomography (CT) scores may improve survival prediction models such as the lung allocation score (LAS). OBJECTIVES: This study investigated the association between CT and survival in patients with CF screened for LTX. METHODS: Clinical data and chest CTs of 411 patients with CF screened for LTX between 1990 and 2005 were collected from 17 centers. CTs were scored with the Severe Advanced Lung Disease (SALD) four-category scoring system, including the components infection/inflammation (INF), air trapping/hypoperfusion (AT), normal/hyperperfusion (NOR), and bulla/cysts (BUL). The volume of each component was computed using semiautomated software. Survival analysis included Kaplan-Meier curves and Cox regression models. MEASUREMENTS AND MAIN RESULTS: Three hundred and sixty-six (186 males) of 411 patients entered the waiting list (median age, 23 yr; range, 5-58 yr). Subsequently, 67 of 366 (18%) died while waiting, 263 of 366 (72%) underwent LTX, and 36 of 366 (10%) were awaiting LTX at the census date. INF and LAS were significantly associated with waiting list mortality in univariate analyses. The multivariate Cox model including INF and LAS grouped in tertiles, and comparing tertiles 2 and 3 with tertile 1, showed waiting list mortality hazard ratios of 1.62 (95% confidence interval [95% CI], 0.78-3.36; P = 0.19) and 2.65 (95% CI, 1.35-5.20; P = 0.005) for INF, and 1.42 (95% CI, 0.63-3.24; P = 0.40), and 2.32 (95% CI, 1.17-4.60; P = 0.016) for LAS, respectively. These results indicated that INF and LAS had significant, independent predictive value for survival. CONCLUSIONS: CT score INF correlates with survival, and adds to the predictive value of LAS.