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Background: Immature gut motility in preterm neonates may be a risk factor for necrotizing enterocolitis (NEC). Using preterm pigs as a model for infants, we hypothesized that intestinal dysmotility precedes NEC development. Methods: Eighty-five preterm pigs were fed increasing amounts of milk diets to induce NEC lesions, as detected at autopsy on day 5. Gut transit time was determined on day 4 by x-ray imaging after oral intake of contrast solution. Results: No clinical or radiological signs of NEC were detected on day 4, but macroscopic NEC lesions were recorded in 59% of pigs (n = 50) on day 5. Relative to pigs without NEC (noNEC, n = 35), pigs with small intestinal lesions (siNEC, n = 18) showed delayed stomach emptying time (StEmpty) and time for contrast to reach cecum (ToCecum) already on day 4. Pigs with lesions only in colon (coNEC, n = 20) showed more diarrhea, shorter ToCecum time, but longer small intestinal emptying time (SiEmpty). ToCecum time predicted siNEC and coNEC lesions with a receiver-operator characteristic area under the curve of 78–81%. Conclusions: Region-dependent changes in gut transit time is associated with early NEC development in preterm pigs. How gut dysmotility is related to NEC in preterm infants requires further investigations. Impact: Using preterm pigs as a model for preterm infants, we show that gut transit time, using serial x-ray contrast imaging, was changed in individuals with NEC-like lesions before they showed the typical radiological signs of NEC. Thus prolonged transit time across the entire gut was recorded when NEC lesions appeared in the small intestine but not when lesions were detected only in the colon.Until now, recordings of food transit have mainly investigated changes in the upper gut. Using serial x-rays, this study describes food transit across the entire gut and documents a region-dependent effect of NEC lesions on gut transit changes in preterm individuals.The findings provide proof of concept for use of x-ray contrast imaging as a tool to monitor gut transit in preterm pigs as models for infants. Delayed passage across the entire gut may be an early sign of small intestinal NEC, at least in pigs. More studies are needed to confirm relations in infants. In the future, it might be possible to use x-ray contrast imaging in preterm infants to better understand gut motility in relation to early NEC progression and need for medical NEC treatment.

Immature gut motility in preterm neonates may be a risk factor for necrotizing enterocolitis (NEC). Using preterm pigs as a model for infants, we hypothesized that intestinal dysmotility precedes NEC development.Eighty-five preterm pigs were fed increasing amounts of milk diets to induce NEC lesions, as detected at autopsy on day 5. Gut transit time was determined on day 4 by x-ray imaging after oral intake of contrast solution.No clinical or radiological signs of NEC were detected on day 4, but macroscopic NEC lesions were recorded in 59% of pigs (n = 50) on day 5. Relative to pigs without NEC (noNEC, n = 35), pigs with small intestinal lesions (siNEC, n = 18) showed delayed stomach emptying time (StEmpty) and time for contrast to reach cecum (ToCecum) already on day 4. Pigs with lesions only in colon (coNEC, n = 20) showed more diarrhea, shorter ToCecum time, but longer small intestinal emptying time (SiEmpty). ToCecum time predicted siNEC and coNEC lesions with a receiver-operator characteristic area under the curve of 78-81%.Region-dependent changes in gut transit time is associated with early NEC development in preterm pigs. How gut dysmotility is related to NEC in preterm infants requires further investigations.Using preterm pigs as a model for preterm infants, we show that gut transit time, using serial x-ray contrast imaging, was changed in individuals with NEC-like lesions before they showed the typical radiological signs of NEC. Thus prolonged transit time across the entire gut was recorded when NEC lesions appeared in the small intestine but not when lesions were detected only in the colon. Until now, recordings of food transit have mainly investigated changes in the upper gut. Using serial x-rays, this study describes food transit across the entire gut and documents a region-dependent effect of NEC lesions on gut transit changes in preterm individuals. The findings provide proof of concept for use of x-ray contrast imaging as a tool to monitor gut transit in preterm pigs as models for infants. Delayed passage across the entire gut may be an early sign of small intestinal NEC, at least in pigs. More studies are needed to confirm relations in infants. In the future, it might be possible to use x-ray contrast imaging in preterm infants to better understand gut motility in relation to early NEC progression and need for medical NEC treatment.

AIM Necrotising enterocolitis (NEC) is often staged according to Bell's 1978 system, but today's NEC cases are more immature than the ones that were used to develop Bell's stages. Our aim was to explore the clinical and radiographic findings of contemporary cases of NEC and spontaneous intestinal perforation. METHODS We coded the clinical records of all cases of NEC stages I-III and spontaneous intestinal perforation born in 2006-2015 at the tertiary department of neonatology at Rigshospitalet, Denmark, for 16 clinical and radiographic symptoms and signs at disease onset and at climax. These variables were explored using principal component analysis, which can detect patterns in large datasets. RESULTS We reviewed 640 clinical records and included 158 cases of NEC or spontaneous intestinal perforation. When we entered the clinical and radiographic signs at disease climax, the cases were roughly grouped according to Bell's stages, except for a small group of NEC III cases, who were grouped with the cases of spontaneous intestinal perforation. CONCLUSION An analysis of the pattern of clinical and radiographic findings in a 2006-2015 population of NEC cases supported Bell's 1978 staging system. However, the separation between NEC and spontaneous intestinal perforation still poses a difficult task.

A newborn presents with marked swelling and discoloration around the right hip and thigh (Figure 1). Figure 1. Newborn with marked swelling and discoloration around the right hip and thigh. ### Prenatal and Birth Histories ### Presentation Infant was discharged home and did well during the first week; she was well-appearing and feeding by demand every 3 to 4 hours. On day 8 a health visitor found a significant weight loss of 650 g. The infant was admitted to a local neonatal ward. She was moderately dehydrated with a sodium level of 160 mEq/L (160 mmol/L). There were no other significant clinical or laboratory findings, and the dehydration was thought to be caused by difficulties with breastfeeding. Oral rehydration was performed via nasogastric tube, and the infant was subsequently successfully transitioned to breastfeeding and discharged on day 15. On day 20 the parents noticed swelling and bluish discoloration of the infant’s right thigh, but she remained otherwise well. Four days later she held her leg in a fixed flexed position and she was crying during diaper changes. They consulted their general practitioner, who referred the infant to a neonatal intensive care unit. ### Vital Signs

Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies, such as cryptogenic organizing pneumonia, diffuse alveolar damage, interstitial pneumonia, and nonspecific interstitial fibrosis. Compared with patients with other noninfectious pulmonary pathologies, BO patients had significantly lower values of forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients with other noninfectious pulmonary pathology fulfilled the BOS criteria. Pathological BO diagnosis was not superior to BOS criteria in predicting decrease in pulmonary function beyond the time of biopsy. A lung biopsy may provide a characterization of pathological patterns that can extend our knowledge on the pathophysiology of HSCT-related lung diseases.

Aim Necrotising enterocolitis contributes considerably to the mortality of preterm infants, but most questions remain unsolved after decades of extensive research. This Danish study investigated the validity of necrotising enterocolitis diagnoses at discharge according to Bell's staging system. Methods We conducted a retrospective single-centre cohort study of 714 preterm infants with a gestational age of less than 30 weeks born in 2006–2013. The infants were diagnosed with necrotising enterocolitis according to Bell's stages 2–3 at discharge and in retrospect by an expert panel, which served as our gold standard. Results The sensitivity of necrotising enterocolitis diagnosed at discharge was 0.72–0.75 depending on whether spontaneous intestinal perforation was included as necrotising enterocolitis or not. The positive predictive value of the diagnosis was 0.49–0.61. The incidence was significantly higher when diagnosed at discharge than when diagnosed by the expert panel (11.1 versus 9.0%, p = 0.03). The mortality rate for infants who were underdiagnosed at discharge was 50.0%, and it was 25.8% for infants who were overdiagnosed (p = 0.10). Conclusion We found poor validity for the discharge diagnosis of necrotising enterocolitis. In future, a better way of defining the disease is needed for large-scale epidemiologic research.

BackgroundIn cystic fibrosis (CF), chronic infection of the airways with Achromobacter xylosoxidans have become more frequent. The pathogenic role of this is yet unclear.MethodsA retrospective case-control study of all patients chronically infected with A. xylosoxidans for at least 3 years. 15 patients (6 males) with chronic A. xylosoxidans infection were matched by age, FEV1 and body mass index z-score to 15 controls (7 males) at the time of establishment of chronic infection. Clinical parameters of the groups were compared from the time of establishment of chronic infection until spring 2006, giving a follow-up time of 3–11 years. Chest X-rays taken 3 years prior to establishment of chronic infection and after 3 years of chronic infection were compared using a modified Brasfield score. Finally, strains from individual patients were analysed using PFGE to investigate possible cross-infection.ResultsThe median slope of decline of FEV1 in the case group changed from +3.1% to −0.5% predicted/year (p

Ultrasonically guided biopsy was performed in 11 patients with lytic bone lesions suspected for metastases and primary detected by conventional X-ray and CT. The lesions were localized in the ribs, scapula and sacrum. The material obtained by fine needle aspiration biopsies and cutting biopsies confirmed malignancy in all patients. We conclude that US-guided biopsy from osteolytic bone lesions is a rapid and useful procedure to obtain the diagnosis. The only limitation in the applicability of US-guided biopsy was the clear visualization of the lesion by the ultrasound examination which depend on the localization of the lesion.

Background and Aims: Retrospectivestudies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Hypothetically, this could be due to selection bias. The aim of this study was to determine age at reaching pubertal milestones in healthy internationally adopted girls in a prospective, clinical study. Methods: A longitudinal cohort study including 276 randomly recruited internationally adopted girls. At baseline, age ranged from 4 to 13 years. Participants were followed with biannual examinations over a period of 2 years. Examinations included height, weight, Tanner staging, blood sampling and bone age assessment. Age distribution at entering pubertal stages B2–B5 (breast development), PH1–PH5 (pubic hair development) and menarche was estimated by probit analysis. Data were compared to a reference population of Danish-born girls, studied cross-sectionally. Results: Mean age at B2+ was 9.5 years (95% prediction interval 7.1–12.0 years) and mean age at menarche was 12.1 (10.2–14.0) years in adopted girls, which was significantly lower compared to the reference group (p < 0.0003). 16% of adopted girls entered stage B2 before 8 years of age. The puberty-related rise in LH, FSH and estradiol was detected at earlier ages in adopted girls compared to the reference group. Conclusion: Internationally adopted girls have a significantly higher risk of precocious pubertal maturation compared to Danish-born girls.

Context: Recent studies have indicated that internationally adopted girls are at high risk of developing precocious puberty. Clinical studies including a contemporary control group are lacking. Objective: The objective was to study clinical, biochemical, and ultrasonographic markers of pituitary-gonadal activation in prepubertal adopted girls and a control group in the same age categories. Setting: The study took place at University Hospital, Copenhagen, Denmark. Design and Participants: The study included randomly selected internationally adopted girls [(n = 99; mean age, 6.9 (5.1–8.5) yr] and controls of Danish origin [n = 93; mean age, 6.8 (5.2–8.5) yr] who were studied cross-sectionally. Methods: Height, weight, and pubertal stage were assessed with serum levels of reproductive hormones. Size and morphology of internal genitals were evaluated by ultrasonography. Bone age was evaluated by x-ray of the left hand. Results: Serum values of FSH were significantly higher in prepubertal adopted girls compared with controls [median, 1.4 (95% confidence interval, 0.4–3.6) vs. 1.0 (0.4–2.4) IU/liter; P 18 pmol/liter) in 46.5% of prepubertal adopted girls and 20.7% of controls (P = 0.001). In prepubertal adopted girls, the proportion of measurable samples increased significantly with age [odds ratio, 2.5 (95% confidence interval, 1.3–5.0; P = 0.009]. In controls, the odds ratio was 1.0 (0.6–1.7) (P = 0.9). Serum SHBG levels were significantly lower in prepubertal adopted girls compared with controls [99.0 (50.4–153.0) vs. 115.0 (53.1–202.1); P < 0.001]. Conclusion: Five- to 8-yr-old adopted girls showed signs of increased pituitary as well as gonadal activity despite prepubertal phenotype in the majority of girls. Our findings suggest that early onset of puberty in adopted girls is centrally driven.