Risk factors for mortality in preterm infants with necrotizing enterocolitis: a retrospective multicenter analysis.

It is difficult to predict the risk of mortality in necrotizing enterocolitis (NEC). This study aimed at identifying risk factors for severe NEC (Bell stage III) and mortality in preterm children with NEC. In this multicenter retrospective study, we analyzed multiple data from 157 premature children with confirmed NEC in the period from January 2007 to October 2018. We performed univariate, multivariate, stepwise logistic regression, and receiver operator characteristics (ROC) analyses. We were able to demonstrate that low Apgar scores (notably at 1' and 5'), low hemoglobin concentration (Hgb), and high lactate level at disease onset and during disease correlated with NEC severity and mortality (P < 0.05, respectively). Severe NEC was related to congenital heart disease (CHD - OR 2.6, CI95% 1.2-5.8, P 0.015) and patent ductus arteriosus (PDA - OR 3.3, CI95% 1.6-6.9, P 0.0012), whereas death was related to the presence of PDA (OR 5.5, CI95% 2.3-14, P < 0.001).Conclusion: Low Apgar scores, low Hgb, high lactate levels, and the presence of CHD or PDA correlated with severe NEC or mortality in children with NEC. What is Known: • It remains difficult to predict which infant that suffers from necrotizing enterocolitis at risk of death. • Several clinical and laboratory parameters tools to predict fatal outcome in NEC. What is New: • The following laboratory parameters were associated with the risk of death from NEC: Hemoglobin concentration, base excess and lactate level. • The following clinical variables were associated with the risk of death from NEC: Apgar scores, as well as the presence of congenital heart disease and patent ductus arteriosus.

Parental satisfaction with waiting time in a Swiss tertiary paediatric emergency department.

INTRODUCTION: Patient numbers in paediatric emergency departments (PED) are steadily increasing. Parental perception of waiting time and reasons for attending a PED with non-emergencies have been investigated in the UK, Australia, Korea, Canada and the USA. We sought to examine which factors influence parental satisfaction with waiting time in a tertiary Swiss PED and whether these differed from other countries. METHODS: Paper surveys were administered to parents of children presenting to our interdisciplinary PED from February to May 2015. Primary outcome was parental satisfaction with waiting time, secondary outcomes were satisfaction with treatment, parental reasons for presentation with non-emergencies, parental perception of times to triage, first physician contact and disposition from ED, level of physician training, understanding of various anticrowding strategies and comparison of perceived and true waiting times to triage and physician contact. RESULTS: 739 out of 750 surveys were returned (57 complete, 298 with 1 or 2 missing answers). Satisfaction with waiting time (on a 5-point-Likert-scale; 1 being the best possible answer) was higher in groups with shorter waiting time until triage (+0.41, p=0.001), first physician contact (+1.43, p<0.001) and discharge (+0.71, p<0.001), higher triage category urgency (+0.47, p=0.044) and available entertainment (+0.82, p<0.001). Early first physician contact (+0.33, p=0.008) and time to discharge less than 4 hours (+0.37, p<0.001) was associated with greater satisfaction with treatment (p<0.05). The most frequent reasons for presentation were parental impression that the child had an emergency (n=265, 35.9%) and referral by the family doctor (n=245, 33.2%). CONCLUSION: To counteract parental dissatisfaction associated with waiting time, we suggest the implementation of feasible measures including entertainment while waiting, early first medical review and timely discharge from the PED.

Risk of digestive cancers in a cohort of 69 460 five-year survivors of childhood cancer in Europe: the PanCareSurFup study.

BACKGROUND: Survivors of childhood cancer are at risk of subsequent primary neoplasms (SPNs), but the risk of developing specific digestive SPNs beyond age 40 years remains uncertain. We investigated risks of specific digestive SPNs within the largest available cohort worldwide. METHODS: The PanCareSurFup cohort includes 69 460 five-year survivors of childhood cancer from 12 countries in Europe. Risks of digestive SPNs were quantified using standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. RESULTS: 427 digestive SPNs (214 colorectal, 62 liver, 48 stomach, 44 pancreas, 59 other) were diagnosed in 413 survivors. Wilms tumour (WT) and Hodgkin lymphoma (HL) survivors were at greatest risk (SIR 12.1; 95% CI 9.6 to 15.1; SIR 7.3; 95% CI 5.9 to 9.0, respectively). The cumulative incidence increased the most steeply with increasing age for WT survivors, reaching 7.4% by age 55% and 9.6% by age 60 years (1.0% expected based on general population rates). Regarding colorectal SPNs, WT and HL survivors were at greatest risk; both seven times that expected. By age 55 years, 2.3% of both WT (95% CI 1.4 to 3.9) and HL (95% CI 1.6 to 3.2) survivors had developed a colorectal SPN-comparable to the risk among members of the general population with at least two first-degree relatives affected. CONCLUSIONS: Colonoscopy surveillance before age 55 is recommended in many European countries for individuals with a family history of colorectal cancer, but not for WT and HL survivors despite a comparable risk profile. Clinically, serious consideration should be given to the implementation of colonoscopy surveillance while further evaluation of its benefits, harms and cost-effectiveness in WT and HL survivors is undertaken.

Validation of self-reported cardiovascular problems in childhood cancer survivors by contacting general practitioners: feasibility and results.

BACKGROUND: Epidemiological studies often rely on self-reported health problems and validation greatly improves study quality. In a study of late effects after childhood cancer, we validated self-reported cardiovascular problems by contacting general practitioners (GPs). This paper describes: (a) the feasibility of this approach; and (b) the agreement between survivor-reports and reports from their GP. METHODS: The Swiss Childhood Cancer Survivor Study (SCCSS) contacts all childhood cancer survivors registered in the Swiss Childhood Cancer Registry since 1976 who survived at least 5 years from cancer diagnosis. We validated answers of all survivors who reported a cardiovascular problem in the questionnaire. Reported cardiovascular problems were hypertension, arrhythmia, congestive heart failure, myocardial infarction, angina pectoris, stroke, thrombosis, and valvular problems. In the questionnaire, we further asked survivors to provide a valid address of their GP and a consent for contact. We sent case-report forms to survivors' GPs and requested information on cardiovascular diagnoses of their patients. To determine agreement between information reported by survivors and GPs, we calculated Cohen's kappa (κ) coefficients for each category of cardiovascular problems. RESULTS: We used questionnaires from 2172 respondents of the SCCSS. Of 290 survivors (13% of 2172) who reported cardiovascular problems, 166 gave consent to contact their GP and provided a valid address. Of those, 135 GPs (81%) replied, and 128 returned the completed case-report form. Survivor-reports were confirmed by 54/128 GPs (42%). Of the 54 GPs, 36 (28% of 128) confirmed the problems as reported by the survivors; 11 (9% of 128) confirmed the reported problem(s) and gave additional information on more cardiovascular outcomes; and seven GPs (5% of 128) confirmed some, but not all cardiovascular problems. Agreement between GPs and survivors was good for stroke (κ = 0.79), moderate for hypertension (κ = 0.51), arrhythmias (κ = 0.41), valvular problems (κ = 0.41) and thrombosis (κ = 0.56), and poor for coronary heart disease (κ = 0.15) and heart failure (κ = 0.32). CONCLUSIONS: Despite excellent GP compliance, it was found unfeasible to validate self-reported cardiovascular problems via GPs because they do not serve as gatekeepers in the Swiss health care system. It is thus necessary to develop other validation methods to improve the quality of patient-reported outcomes.

Risk Factors for Necrotizing Enterocolitis in Infants With Patent Arterial Duct. A Retrospective Matched Paired Analysis.

Background: The development of necrotizing enterocolitis (NEC) in neonates with patent ductus arteriosus (PDA) is not well-understood. Our aim was to find risk factors for NEC in children with a significant PDA and to assess differences in mortality and duration of hospital stay between patients with PDA and those with PDA and NEC. Methods: We performed a retrospective single center case control study including infants with PDA scheduled for treatment. We compared multiple patient data between patients with PDA and those with PDA and NEC from 2004 to 2018 using 1:2 and 1:1 matching. Results: We used 1:2 matching with 26 NEC patients (cases) and 52 PDA patients without NEC (controls) and 1:1 matching with 5 NEC patients and 5 PDA patients without NEC. NEC patients had lower Apgar score (1'), more congenital malformations, more suspected sepsis, less hypotension, higher minimum platelet count and higher CRP-values during the week before NEC (P < 0.05, respectively). The mortality was higher in NEC cases [29% (9/31)] compared to the control patients [2% (1/57), P < 0.001]. Lower Apgar score (1') was correlated with an increased risk of NEC stage III. Hypotension was inversely correlated with the odds of NEC (OR 0.3). Conclusions: NEC increased mortality in infants with PDA. Hypotension did not increase the risk of NEC in infants with PDA. Routine clinical parameters were not able to predict NEC in infants who suffer from PDA.

Gastrointestinal sequelae after surgery for necrotising enterocolitis: a systematic review and meta-analysis.

OBJECTIVES: To document what types of gastrointestinal sequelae were described after surgery for necrotising enterocolitis (NEC) and to analyse their frequency. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline, EMBASE and the Cochrane library (CENTRAL) from 1990 to October 2016. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included studies, which provided original data on the occurrence of gastrointestinal sequelae in patients surviving surgery for NEC. Meta-analysis and metaregression to assess heterogeneity were performed for studies including 10 or more patients with gastrointestinal strictures, recurrence of NEC, intestinal failure (IF) and adhesion ileus. RESULTS: Altogether 58 studies, including 4260 patients, met the inclusion criteria. Strictures were reported to occur in 24% (95% CI 17% to 31%) of surviving patients, recurrence of NEC in 8% (95% CI 3% to 15%), IF in 13% (95% CI 7% to 19%) and adhesion ileus in 6% (95% CI 4% to 9%). Strictures were more common following enterostomy (30%; 95% CI 23% to 37%) than after primary anastomosis (8%; 95% CI 0% to 23%) and occurred more often after enterostomy without bowel resection than with bowel resection. We found considerable heterogeneity in the weighted average frequency of all sequelae (I2 range: 38%-90%). Intestinal outcomes were poorly defined, there were important differences in study populations and designs, and the reported findings bear a substantial risk of bias. CONCLUSIONS: Gastrointestinal sequelae in neonates surviving surgery for NEC are frequent. Long-term follow-up assessing defined gastrointestinal outcomes is warranted.

Risk of subsequent primary leukaemias among 69,460 five-year survivors of childhood cancer diagnosed from 1940 to 2008 in Europe: A cohort study within PanCareSurFup.

BACKGROUND: Survivors of childhood cancers are at risk of developing subsequent primary leukaemias (SPLs), but the long-term risks beyond 20 years of treatment are still unclear. We investigated the risk of SPLs in five-year childhood cancer survivors using a large-scale pan-European (PanCareSurFup) cohort and evaluated variations in the risk by cancer and demographic factors. METHODS: This largest-ever assembled cohort comprises 69,460 five-year childhood cancer survivors from 12 European countries. Standardised incidence ratios (SIRs) and absolute excess risks (AERs) were calculated. RESULTS: One hundred fifteen survivors developed an SPL including 86 myeloid leukaemias (subsequent primary myeloid leukaemias [SPMLs]), 17 lymphoid leukaemias and 12 other types of leukaemias; of these SPLs, 31 (27%) occurred beyond 20 years from the first childhood cancer diagnosis. Compared with the general population, childhood cancer survivors had a fourfold increased risk (SIR = 3.7, 95% confidence interval [CI]: 3.1 to 4.5) of developing leukaemia, and eight leukaemias per 100,000 person-years (AER = 7.5, 95% CI: 6.0 to 9.2) occurred in excess of that expected. The risks remained significantly elevated beyond 20 years from the first primary malignancy (SIR = 2.4, 95% CI: 1.6 to 3.4). Overall, the risk ratio for SPML (SIR = 5.8, 95% CI: 4.6 to 7.1) was higher than that for other SPLs. CONCLUSIONS: We demonstrate that beyond 20 years after childhood cancer diagnosis, survivors experience an increased risk for SPLs compared with that expected from the general population. Our findings highlight the need for awareness by survivors and their healthcare providers for potential risk related to SPL.

Congenital Heart Disease Increases Mortality in Neonates With Necrotizing Enterocolitis.

Background: Studies on the influence of congenital heart disease (CHD) on neonates with necrotizing enterocolitis (NEC) have produced varied results. We therefore examined the influence of CHD on NEC outcomes. Methods: We carried out a retrospective single-center study including infants with confirmed NEC, treated between 2004 and 2017. We excluded patients with isolated patent ductus arteriosus or pulmonary hypertension (n = 45) and compared outcomes of patients with hemodynamically relevant CHD (n = 38) and those without CHD (n = 91). Results: Patients with CHD were more mature than those without CHD [gestational age, median, 95% confidence interval (CI95), 37.1, 34.5-37.2w, vs. 32.6, 31.9-33.3w; P < 0.01]. The presence of CHD did not influence the frequencies of severe disease (overall 21% Bell stage III), nor surgical interventions (overall 30%), the occurrence of intestinal complications (overall 13%), nor the duration of hospitalization (overall 38 days in survivors). The overall mortality as well as NEC-related mortality was increased with the presence of CHD, being 50% (19 out of 38) and 13% (5 out of 38), respectively, when compared to patients without CHD, being 8% (7 out of 91) and 3% (3 out of 91). The presence of CHD and of advanced NEC stage III were independent predictors of NEC-associated fatalities with multivariable odds ratios (CI95) of 7.0, 1.3-39.5 for CHD, and of 3.4, 1.6-7.5 for stage III disease. Conclusions: While some outcome parameters in neonates with NEC remained unaffected by the presence of CHD, the mortality risk for patients with CHD was seven times higher than without CHD.