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Lung involvement in children with congenital cytomegalovirus infection has been scarcely described. We describe three new cases of persistent pulmonary hypertension in children with congenital cytomegalovirus and review the other seven cases reported in the literature since 1988. All children had a symptomatic infection, including severe central nervous system or visceral findings. Morbidity and mortality were high. Persistent pulmonary hypertension may be a rare complication in severely symptomatic congenital cytomegalovirus infants. It is important to screen for congenital cytomegalovirus in cases of idiopathic refractory persistent pulmonary hypertension. Intensive treatment should be undertaken to treat this potentially rare lung involvement in combination with antiviral treatment., (© 2024 Japanese Teratology Society.)

Purpose: To provide a comprehensive report of the experience gained in the prenatal treatment of congenital diaphragmatic hernia (CDH) using fetoscopic endoluminal tracheal occlusion (FETO) following its implementation at a newly established specialized fetal medicine center., Methods: Mothers of fetuses with severe CDH were offered prenatal treatment by FETO., Results: Between 2018 and 2021, 16 cases of severe CDH underwent FETO. The median gestational age (GA) at balloon insertion was 28.4 weeks (IQR 27.8-28.6). The median GA at delivery was 37 weeks (IQR 34.4-37.8). The survival rate was 8/16 cases (50%). None of the survivors required home oxygen therapy at 6 months of age. Comparison between the survivors and deceased showed that survivors had balloon insertion 1 week earlier (27.8 vs. 28.4 weeks, p = 0.007), a higher amniotic fluid level change between pre- to post-FETO (3.4 vs 1.3, p = 0.024), a higher O/E LHR change between pre- to post-FETO (50.8 vs. 37.5, p = 0.047), and a GA at delivery that was 2 weeks later (37.6 vs. 35.4 weeks, p = 0.032)., Conclusions: The survival rate at 6 months of age in cases of severe CDH treated with FETO in our center was 50%. Our new fetal medicine center matches the performance of other leading international centers., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Although extremely premature birth disrupts lung development, adolescent survivors of extreme prematurity show good clinical and physiologic outcomes. Cardiopulmonary limitations may not be clinically evident at rest. Data regarding exercise limitation in adolescents following preterm birth in the postsurfactant era are limited., Research Question: What are the long-term effects of bronchopulmonary dysplasia (BPD) and extreme prematurity (<29 weeks) on ventilatory response during exercise in adolescents in the postsurfactant era?, Study Design and Methods: We followed a longitudinally recruited cohort of children aged 13-19 years who were born at a gestational age of <29 weeks (study group - SG). We compared the cardiopulmonary exercise testing (CPET) results of those with and without BPD, to their own CPET results from elementary school age (mean 9.09 ± 1.05 years)., Results: Thirty-seven children aged 15.73 ± 1.31 years, mean gestational age 26 weeks ( ± 1.19), completed the study. CPET parameters in adolescence were within the normal range for age, including mean V̇O 2 peak of 91% predicted. The BPD and non-BPD subgroups had similar results. In the longitudinal analysis of the SG, improvement was observed in adolescence, compared with elementary school age, in breathing reserve (36.37 ± 18.99 vs. 26.58 ± 17.92, p = 0.044), tidal volume as a fraction of vital capacity achieved at maximal load (0.51 ± 0.13 vs. 0.37 ± 0.08, p < 0.001), and respiratory exchange ratio at maximal load (1.18 ± 0.13 vs. 1.11 ± 0.10, p = 0.021)., Interpretation: In the current cohort, adolescents born extremely premature have essentially normal ventilatory response during exercise, unrelated to BPD diagnosis. CPET results in this population improve over time., (© 2024 The Authors. Pediatric Pulmonology published by Wiley Periodicals LLC.)

To evaluate the effectiveness of a novel protocol, adopted in our institution, as a quality improvement project for congenital diaphragmatic hernia (CDH). A maximal lung protection (MLP) protocol was implemented in 2019. This strategy included immediate use of high-frequency oscillatory ventilation (HFOV) after birth, during the stay at the Neonatal Intensive Care Unit (NICU), and during surgical repair. HFOV strategy included low distending pressures and higher frequencies (15 Hz) with subsequent lower tidal volumes. Surgical repair was performed early, within 24 h of birth, if possible. A retrospective study of all inborn neonates prenatally diagnosed with CDH and without major associated anomalies was performed at the NICU of Schneider Children's Medical Center of Israel between 2009 and 2022. Survival rates and pulmonary outcomes of neonates managed with MLP were compared to the historical standard care cohort. Thirty-three neonates were managed with the MLP protocol vs. 39 neonates that were not. Major adverse outcomes decreased including death rate from 46 to 18% (p = 0.012), extracorporeal membrane oxygenation from 39 to 0% (p < 0.001), and pneumothorax from 18 to 0% (p = 0.013)., Conclusion:  MLP with early surgery significantly improved survival and additional adverse outcomes of neonates with CDH. Prospective randomized studies are necessary to confirm the findings of the current study., What Is Known: • Ventilator-induced lung injury was reported as the main cause of mortality in neonates with congenital diaphragmatic hernia (CDH). • Conventional ventilation is recommended by the European CDH consortium as the first-line ventilation modality; timing of surgery is controversial., What Is New: • A maximal lung protection strategy based on 15-Hz high-frequency oscillatory ventilation with low distending pressures as initial modality and early surgery significantly reduced mortality and other outcomes., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Despite advances in neonatal care, late-onset sepsis remains an important cause of preventable morbidity and mortality. Neonatal late-onset sepsis rates have decreased in some countries, while in others they have not. Our objective was to compare trends in late-onset sepsis rates in 9 population-based networks from 10 countries and to assess the associated mortality within 7 days of late-onset sepsis., Methods: We performed a retrospective population-based cohort study. Infants born at 24-28 weeks' gestation between 2007 and 2019 were eligible for inclusion. Late-onset sepsis was defined as a positive blood or cerebrospinal fluid culture. Late-onset sepsis rates were calculated for 3 epochs (2007-11, 2012-15, and 2016-19). Adjusted risk ratios (aRRs) for late-onset sepsis were calculated for each network., Results: Of a total of 82,850 infants, 16,914 (20.4%) had late-onset sepsis, with Japan having the lowest rate (7.1%) and Spain the highest (44.6%). Late-onset sepsis rates decreased in most networks and remained unchanged in a few. Israel, Sweden, and Finland showed the largest decrease in late-onset sepsis rates. The aRRs for late-onset sepsis showed wide variations between networks. The rate of mortality temporally related to late-onset sepsis was 10.9%. The adjusted mean length of stay for infants with late-onset sepsis was increased by 5-18 days compared to infants with no late-onset sepsis., Conclusions: One in 5 neonates of 24-28 weeks' gestation develops late-onset sepsis. Wide variability in late-onset sepsis rates exists between networks with most networks exhibiting improvement. Late-onset sepsis was associated with increased mortality and length of stay., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background and Objectives: Late-onset sepsis is associated with significant morbidity and mortality among very low birth weight (VLBW) infants. Our objective was to determine risk factors associated with late-onset sepsis and to present temporal trends in overall and pathogen-specific rates., Methods: Population-based study by the Israel Neonatal Network on VLBW infants (≤1500 g) born between 1995 and 2019. Late-onset sepsis required clinical symptoms and microbiologic confirmation. Bivariate and multivariable analyses were performed to identify risk factors. The study period was divided into 4 epochs. Overall and pathogen-specific late-onset sepsis rates for each epoch were compared., Results: The study population comprised 31 612 VLBW infants, of whom 7423 (23.5%) had late-onset sepsis. An increased adjusted risk of late-onset sepsis was associated with gestational age <27 w (odds ratio [OR] 8.90, 95% confidence interval [CI] 7.85-10.09) and delivery room resuscitation (OR 1.43, 95% CI 1.34-1.52) and a decreased adjusted risk among infants born between 2013 and 2019 (OR 0.32, 95% CI 0.29-0.35). Late-onset sepsis rates declined from 29.5% in 1995 to 2000 to 13.0% in 2013 to 2019. Gram-negative and fungal rates decreased in all epochs, whereas gram-positive rates decreased only in the last epoch. The adjusted hazard ratios (95% CI) decreased in the 2013 to 2019 versus 1995 to 2000 epochs and were: all late-onset sepsis, 0.40 (0.37-0.43); gram-positive, 0.47 (0.37-0.59); gram- negative, 0.54 (0.48-0.61); fungal, 0.17 (0.12-0.22)., Conclusions: The strongest risk factor for late-onset sepsis was gestational age <27 w. Over a 25-year period, the pathogen-specific rates of late-onset sepsis among VLBW infants decreased approximately twofold for gram-positive and gram-negative bacterial infections and sixfold for fungal infections., (Copyright © 2023 by the American Academy of Pediatrics.)

Introduction: Perianal fistulizing Crohn's disease (CD) is a phenotype with a poor prognosis. There are no studies in our country. Our objective is to determine the clinical, sociodemographic and treatment characteristics of perianal fistulizing CD in a Colombian multicenter registry., Materials and Methods: A retrospective, multicenter observational study was carried out, with prospective data collection, in the main reference centers for inflammatory Bowel disease (IBD) in the country. Continuous variables were expressed as medians and interquartile ranges. The categorical outcome variables were compared by the Chi-square test., Results: Sixty-five patients with perianal fistulizing CD were documented, with a median age of appearance of perianal fistula of 31.0 years (range: 24-42), predominantly in men (61.5%; H:M ratio: 1.4:1). Complex perianal fistulas were more frequent than simple ones (75.35 vs. 24.6%). Regarding medical treatment, 66.2% of the patients received antibiotics, 64.6% steroids, 78.5% biological therapy, 47.7% non-cutting setons, and 46.2% required surgical management, other than seton placement. Only 29.2% achieved complete remission of the fistula, and 9.2% of the patients ended up in a definitive colostomy. CD patients with complex fistulas received more biological therapy, compared to CD patients with simple fistulas (84.8 vs. 56.3%; P: 0.038)., Conclusions: Perianal fistulizing CD has a poor prognosis in our setting, only 3 out of 10 patients achieve complete remission despite treatment. A multidisciplinary management is essential for the comprehensive management of this difficult pathology., (Copyright © 2022 Elsevier España, S.L.U. All rights reserved.)

To date, there is no overarching proposition for the ontogenetic-neurobiological basis of self-regulation. This paper suggests that the balanced self-regulatory reaction of the fetus, newborn and infant is based on a complex mechanism starting from early brainstem development and continuing to progressive control of the cortex over the brainstem. It is suggested that this balance occurs through the synchronous reactivity between the sympathetic and parasympathetic systems, both which originate from the brainstem. The paper presents an evidence-based approach in which molecular excitation-inhibition balance, interchanges between excitatory and inhibitory roles of neurotransmitters as well as cardiovascular and white matter development across gestational ages, are shown to create sympathetic-parasympathetic synchrony, including the postnatal development of electroencephalogram waves and vagal tone. These occur in developmental milestones detectable in the same time windows (sensitive periods of development) within a convergent systematic progress. This ontogenetic stepwise process is termed "the self-regulation clock" and suggest that this clock is located in the largest connection between the brainstem and the cortex, the corticospinal tract. This novel evidence-based new theory paves the way towards more accurate hypotheses and complex studies of self-regulation and its biological basis, as well as pointing to time windows for interventions in preterm infants. The paper also describes the developing indirect signaling between the suprachiasmatic nucleus and the corticospinal tract. Finally, the paper proposes novel hypotheses for molecular, structural and functional investigation of the "clock" circuitry, including its associations with other biological clocks. This complex circuitry is suggested to be responsible for the developing self-regulatory functions and their neurobehavioral correlates.

Preterm infants, age-corrected for prematurity, score on average, 10 points lower on IQ tests than full-term infants tested at comparable ages. This review focuses on the potential contribution of the hypothalamus to cognitive neuro-regulatory development in preterm infants through its bidirectional neural connections with the prefrontal cortex and its neuroendocrine activity. It aims to clarify the central role of the hypothalamus in preterm high stress situations and in influencing cognitive development via its connectivity to the cerebral cortex. The review further evaluates epigenomic sensitivity to environmental inputs. Recent results suggest that an optimal range of DNA methylations (via a continuous process of decreasing levels of receptor methylations that are too high, and increasing levels that are too low) appears necessary in order to reach an adaptive level of receptor availability. Several studies have demonstrated amelioration of preterm infants' stress while in the Newborn Intensive Care Unit (NICUs) and following discharge. The authors postulate that feedback mechanisms and correction signals are the basis for a hypothalamic homeostatic modulating function, a "hypothalamic resistance response", which may account for the stress reduction brought about by in- and post-NICU early interventions and their results of promoting self-regulation and cognition., Competing Interests: None., (© 2021 The Authors.)

Objective: We aimed to determine the independent effect of maternal antepartum hemorrhage (APH) on mortality and major neonatal morbidities among very low birth weight (VLBW), very preterm infants., Study Design: A population-based cohort study of VLBW singleton infants born at 24 to 31 weeks of gestation between 1995 and 2016 was performed. Infants born with the following pregnancy associated complications were excluded: maternal hypertensive disorders, prolonged rupture of membranes, amnionitis, maternal diabetes, and small for gestational age. APH included hemorrhage due to either placenta previa or placental abruption. Univariate and multivariable logistic regression analyses were performed to assess the effect of maternal APH on mortality and major neonatal morbidities., Results: The initial cohort included 33,627 VLBW infants. Following exclusions, the final study population comprised 6,235 infants of whom 2,006 (32.2%) were born following APH and 4,229 (67.8%) without APH. In the APH versus no APH group, there were higher rates of extreme prematurity (24-27 weeks of gestation; 51.6% vs. 45.3%, p  < 0.0001), mortality (20.2 vs. 18.5%, p  = 0.011), bronchopulmonary dysplasia (BPD, 16.1 vs. 13.0%, p  = 0.004) and death or adverse neurologic outcome (37.4 vs. 34.5%, p  = 0.03). In the multivariable analyses, APH was associated with significantly increased odds ratio (OR) for BPD in the extremely preterm infants (OR: 1.31, 95% confidence interval: 1.05-1.65). The OR's for mortality, adverse neurological outcomes, and death or adverse neurological outcome were not significantly increased in the APH group., Conclusion: Among singleton, very preterm VLBW infants, maternal APH was associated with increased odds for BPD only in extremely premature infants, but was not associated with excess mortality or adverse neonatal neurological outcomes., Key Points: · Outcome of very low birth weight infants born after antepartum hemorrhage (APH) was assessed.. · APH was not associated with higher infant mortality.. · APH was not associated with adverse neurological outcome.. · APH was associated with increased bronchopulmonary dysplasia in extremely preterm infants.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objectives: Neonatal late-onset sepsis work-up is a frequent occurrence in every neonatal department. Blood cultures are the diagnostic gold standard, however, a negative culture prior to 48-72 h is often considered insufficient to exclude sepsis. We aimed to develop a decision tree which would enable exclusion of late-onset sepsis within 24 h using clinical and laboratory variables. Study Design: Infants evaluated for late-onset sepsis during the years 2016-2019, without major malformations, in a tertiary neonatal center were eligible for inclusion. Blood cultures and clinical and laboratory data were extracted at 0 and 24 h after sepsis work-up. Infants with bacteriologically confirmed late-onset sepsis were compared to matched control infants. Univariate logistic regression identified potential risk factors. A decision tree based on Chi-square automatic interaction detection methodology was developed and validated. Results: The study cohort was divided to a development cohort (105 patients) and a validation cohort (60 patients). At 24 h after initial evaluation, the best variables to identify sepsis were C-reactive protein > 0.75 mg/dl, neutrophil-to-lymphocyte ratio > 1.5 and sick-appearance at 24 h. Use of these 3 variables together with blood culture status at 24 h, enabled identification of all infants that eventually developed sepsis through the decision tree model. Our decision tree has an area under the receiver operating characteristic curve of 0.94 (95% CI: 0.90-0.98). Conclusions: In non-sick appearing infants with a negative blood culture at 24 h and normal laboratory values, sepsis is highly unlikely and discontinuing antibiotics after 24 h is a viable option., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Goldberg, Sokolover, Bromiker, Amitai, Chodick, Scheuerman, Ben-Zvi and Klinger.)

Introduction: Extraintestinal manifestations (EIMs) are frequent in patients with inflammatory bowel disease (IBD). Our objective is to characterize and determine the prevalence of MEIs in our cohort of patients with IBD., Patients and Methods: A retrospective study was carried out in adult patients with IBD at the Pablo Tobón Uribe Hospital in Medellín. Colombia. Articular MEIs, primary sclerosing cholangitis (PSC), both ophthalmological and dermatological, were considered. Absolute and relative frequencies were used. The Chi square test of independence was used to compare 2proportions and the odds ratio (OR) was estimated., Results: Our registry has 759 patients with IBD, 544 present UC (71.6%), 200 CD (26.3%) and 15 unclassifiable IBD (1.9%); 177 patients with IBD (23.3%) presented EIMs, 123 of 544 (22.6%) with UC and 53 of 200 (26.5%) with CD (OR: 0.81, 95% CI: 0.55-1.17, P=0.31). Regarding the type of EIMs, the articular ones were the most frequent (13.5%), more in CD than in UC (20.0 vs. 11.3%, OR 1.94, 95% CI: 1.25-3.00, P=0.0037). Patients with IBD and EIMs used more antibodies against tumor necrosis factor (anti-TNFs), compared to those without EIMs (43.5 vs. 18.5%, OR 3.38, 95% CI: 2.31-4.90, P=0.0001)., Conclusions: The prevalence of EIMs in our cohort is high (23.3%) and the most frequent type is joint. Anti-TNFs are most used when IBD and EIMs coexist. Our study provides valuable information on the association of EIMs and IBD in Latin America., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)

Introduction: The small bowel capsule endoscopy (SBCE) has revolutionised the study of small bowel diseases. The objective of this study is to determine the indications, findings and diagnostic yield of SBCE in a national registry., Patients and Methods: An observational, analytical cross-sectional study was carried out, analysing the SBCE records at seven centres in the country, where different variables were collected., Results: 1,883 SBCEs were evaluated. The average age was 55.4 years (5.6-94.2). The most frequent indications were suspicion of small bowel bleeding (SBB) (64.4%), study of Crohn's disease (15.2%) and chronic diarrhoea (11.2%). 54.3% were prepared with laxatives. The most frequent lesions found were erosions/ulcers (31.6%), angioectasias (25.7%) and parasitosis (2.7%). The diagnostic yield (P1+P2, Saurin classification) of SBCE in SBB was 60.6%, being higher in overt SBB (66.0%) compared to occult SBB (56.0%) (P=.003). The studies with better preparation showed higher detection of lesions (93.8% vs. 89.4%) (OR=1.8, CI: 95%: 1.2-2.6; P=.004). The SBCE complication rate was 3.1%, with complete SB visualisation at 96.6% and SB retention rate of 0.7%. 81.5% of SBCEs were performed on an outpatient basis, and presented a greater complete SB visualisation than hospital ones (97.1% vs. 94.3%) (OR=2.1, CI: 95%, 1.2-3.5; P=.008)., Conclusions: The indications, findings and diagnostic performance of SBCEs in Colombia are similar to those reported in the literature, with a high percentage of complete studies and a low rate of complications., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)

Introduction: gastric varices hemorrhage is a severe complication of portal hypertension, with high mortality rates and few management alternatives, especially when there is a contraindication to transjugular intrahepatic portosystemic shunts (TIPS). The usual therapeutic options are the injection of cyanoacrylate, the insertion of coils or both. Hydrocoils are special coils coated with different types of expandable hydrogel polymers conventionally used in neurovascular interventionism. They allow rapid occlusion of vessel, forming a mesh that favors the local formation of thrombus and the development of a neointima on the gel cover. We consider the use of endoscopic ultrasound (EUS) guided hydrocoil insertion in gastric varices, without using cyanoacrylate., Objective: this study aimed to evaluate the safety and effectivity of the application of EUS-guided hydrocoils in patients with gastric varices hemorrhage with TIPS contraindication., Material and Methods: this was a retrospective case series of four patients with TIPS contraindication after interventional radiologist evaluation. Linear echoendoscopes, fluoroscopy, 19G needles and hydrocoils (Azur®, Terumo) and Progreat® 3 Fr microcatheters were used. An interventional radiologist expert advised the procedures and endoscopic ultrasound confirmed the varix obliteration., Results: technical and clinical success occurred in all patients involved in this study. There were no adverse effects related to the procedure or endoscopic equipment damage., Conclusions: the application of EUS-guided hydrocoils can be a safe and effective method in the short term for gastric varices bleeding in patients who are not candidates for TIPS. Besides, a complete obliteration of the vascular lumen could occur and thus, dispense with the use of cyanoacrylate. Further studies are needed to corroborate these preliminary results.

Objective: To compare the efficacy and reliability of two pulse-oximeters (POx) (Masimo Radical-7 and Nellcor ™ Oxymax Bedside) and evaluate the feasibility of routine ECG monitoring during delivery room transition., Study Design: Prospective observational comparative study. Sixty newborns were connected simultaneously to both POxs and ECG monitor (as a gold standard for HR). Times to achieve a stable signal were compared. Heart rates were compared to simultaneous ECG., Results: A significant difference in times to stable signal was found: Mean, Median (Interquartile range) for Nellcor and Masimo, were 15, 8.5 (6-18) and 27, 12 (9-34) seconds, respectively. Compared to ECG, false bradycardia was displayed in 18 of 55 (35%) newborns by the Masimo POx and in no newborns by the Nellcor POx. Attaching the ECG monitor was feasible but consumed additional resources., Conclusions: The time for achievement of a stable saturation reading in an uncomplicated resuscitation setting differed significantly between POxs.

Introduction: pancreatic insulinoma is a sporadic, usually benign, frequently solitary tumor that is smaller than 20 mm. When it is functioning, patients present with symptoms of hypoglycemia secondary to insulin hypersecretion. The diagnosis is clinical, with biochemical and radiological confirmation. Surgery is the management of choice, although endoscopic ultrasound-guided ablation is currently being developed., Material and Methods: we present a prospective case series of pancreatic insulinoma patients with symptoms of severe hypoglycemia, who were treated with endoscopic ultrasound-guided ethanol ablation as an alternative to surgical management., Results: technical and clinical success was achieved in all cases and there were no complications associated with the procedure., Conclusion: the treatment of symptomatic insulinoma by endoscopic ultrasound-guided ethanol ablation could be a safe and effective alternative to surgical management in non-surgical patients or those who refuse surgery.

Ingestion of foreign bodies is common in the pediatric population. Most foreign bodies have a benign behavior and are usually eliminated without generating greater morbidity and mortality. In relation to the intake of magnets, its frequency has increased to the point that it currently represents a public health problem in the pediatric population. The ingestion of a single magnet does not generate any risk, but the ingestion of 2 or more of these, or even of magnets and metals in succession is considered an emergency since they can attract each other and can cause serious symptoms of intestinal obstruction, bleeding, fistulas, perforation and even intestinal necrosis. We present 2 pediatric patients, who ingested multiple magnets, in these cases we highlight the variety in the clinical presentation, as well as the complications presented in relation to a late diagnosis.

Introduction: Cystic diseases of the lung are a rare spectrum of anomalies, commonly diagnosed prenatally. We present a case of a newborn twin, born at 29 weeks gestational. The infant was diagnosed with respiratory distress syndrome shortly after birth, treated with surfactant by the INSURE method (intubation, surfactant administration, extubation) and required only short-term non-invasive ventilation. On the 40th day of life an extensive single lung cystic disease was identified after respiratory deterioration occurred. The diagnostic approach is presented. The differential diagnosis of neonatal cystic lung disease includes congenital and acquired diseases. The most common cystic lesions presenting in the neonatal period include congenital pulmonary airway malformation (CPAM), pulmonary sequestration, bronchogenic cysts, congenital lobar emphysema and acquired lung damage resulting in cyst formation including pulmonary interstitial emphysema, damage secondary to infection disease. Follow-up showed gradual resolution of the cystic disease, supporting an acquired lung disease. The cystic lung disease may be due to barotrauma from non-invasive ventilation, unequal surfactant distribution, genetic susceptibility to the relatively mild barotrauma associated with non-invasive ventilation or a combination of these factors. The case report demonstrates that procedures considered "safe" such as non-invasive ventilation and surfactant administration may result in extensive lung damage.

To conduct a survey of the local prevalent bacteria and antibiotic resistance in a referral tertiary neonatal intensive care unit (NICU), in order to assess the efficacy of local antibiotic policies. We reviewed all positive blood and cerebrospinal fluid cultures obtained between January 2007 and December 2017 in the NICU of Schneider Children's Medical Center of Israel. Early and late-onset bacteremia were defined as episodes occurring within or after the first 3 calendar days of life respectively. Empiric treatment included ampicillin and gentamicin or piperacillin-tazobactam and amikacin for early or late-onset bacteremia respectively. The prevalence and antibiotic resistance of the bacteria were described and compared over time. Eight hundred and twenty nine of 15,947 (5.2%) newborns had at least one episode of bacteremia; 81 had multiple episodes. The most common bacteria were Escherichia coli (32.35%) and group B Streptococcus (19.11%) or coagulase negative Staphylococcus (CoNS) (60.5%) and Klebsiella sp. (12.4%) in early or late-onset bacteremia respectively. Overall, all Gram-positive bacteria were susceptible to vancomycin and most non-CoNS to ampicillin. Nosocomial vs. vertical bacteremia had increased resistance to ampicillin and cephalosporins. Resistance of nosocomial bacteria to piperacillin-tazobactam was 22.4%, to amikacin 3.3%, and to meropenem 1.8%. Changes over time: Gram-negative bacteria had a significant increase in resistance to cotrimoxazole and piperacillin. The resistance to gentamicin doubled. Our empiric antibiotic regimen covers the most frequent isolates. Amikacin may replace gentamicin for selected sick patients in early-onset bacteremia. Piperacillin-tazobactam should be combined with amikacin until susceptibility is available.

We appreciate the interest shown in our article "Endoscopic ultrasound-guided fine-needle aspiration for splenomegaly and focal splenic lesion: is it safe, effective and necessary?", as well as the academic discussion raised by gastroenterology-ultrasound experts in the letter to the editor. In the discussion of our article, we mention that EUS-FNA is necessary and/or the first option in splenomegaly and/or small focal splenic lesions where percutaneous biopsy are limited, when difficulty accessing the focal splenic lesions, in obese patients and in those with ascites, recent abdominal surgery or a poor acoustic window.

Neonatal sepsis is a major cause of worldwide morbidity and mortality. Blood cultures are considered the gold standard for diagnosis, but results are often delayed for 24 to 48 hours, and sensitivity, although improved by modern techniques, such as automated blood cultures, is variable and affected by the bacterial load. For these reasons, empiric antibiotics are frequently administered to avoid potential devastating consequences of untreated sepsis. Unnecessary antibiotic treatment has been associated with increased mortality and other adverse outcomes; therefore, antibiotics should be discontinued as soon as sepsis has been ruled out. Negative cultures pose a challenge to clinicians, who must distinguish between real sepsis and sepsis-like conditions (noninfectious or viral) which do not require antibiotics. Focal infections with negative blood cultures do require antibiotic treatment. Ultra-low bacteremia, primary or secondary to recent antibiotic exposure, is often associated with negative cultures, and some consider a short course of empiric antibiotics sufficient for clearing of bacteremia. Biomarkers and molecular methods based on polymerase chain reaction are important add-ons to clinical signs or symptoms for establishing the diagnosis of sepsis. Other promising future potential adjuvants are metabolomics. Antibiotic stewardship should be implemented to avoid or discontinue unnecessary treatment. Prevention of infection still remains the most important step for dealing with neonatal sepsis. KEY POINTS: · Blood cultures are the gold standard diagnosis of neonatal sepsis but sometimes may be negative.. · Other bacterial, viral, and noninfectious conditions may mimic sepsis, prompting initiation of empiric antibiotic treatments.. · Since a definition of neonatal sepsis is lacking, recognizing real septic episodes may be challenging.., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Objective: No single test can accurately identify neonatal late-onset sepsis (LOS). Our aim was to use clinical evaluation with laboratory tests to rapidly assess sepsis risk., Study Design: A retrospective case-control study was performed in a tertiary Neonatal Center during the years 2016-2019. Infants with bacteriologically confirmed LOS were compared with control infants. A clinical health evaluation score was assigned to each infant. A prediction model was developed and validated by multivariable analysis., Results: The study included 145 infants, 48 with sepsis, and 97 controls. LOS was independently associated with: sick appearance (OR: 5.7, 95% CI: 1.1-29.1), C-reactive protein > 0.75 (OR: 5.4, 95% CI: 1.1-26.3), and neutrophil-to-lymphocyte ratio > 1.5 (OR: 6.7, 95% CI: 1.2-38.5). Our model had an area under the receiver operating characteristic curve of 0.92 (95% CI: 0.86-0.97)., Conclusions: Clinical evaluation with neutrophil-to-lymphocyte ratio and C-reactive protein can rapidly identify LOS enabling decreased health costs and antibiotic use.

Background: Prematurity is a risk factor for impaired lung function. We sought to assess the long-term effect of palivizumab immunization and extreme prematurity (<29 weeks gestation) on respiratory symptoms and pulmonary function in adolescence., Research Question: What is the long-term effect of palivizumab immunization and extreme prematurity (<29 weeks) on respiratory symptoms and pulmonary function in adolescence?, Study Design and Methods: We examined survivors of extreme prematurity (<29 weeks gestation) at 13 to 18 years of age (study group). Study group babies who were born immediately before palivizumab immunization (nonpalivizumab group [NPG]) were compared with those babies who were born just after implementation (PG) and with a control group. For study group patients, lung function in adolescence was further compared longitudinally with that at primary school age., Results: Sixty-four adolescents aged 15.76 ± 1.52 years were included: 46 in the study group (17 PG and 29 NPG) and 18 in the control group. For the study group, wheezing episodes, inhaler use, and hospitalizations were uncommon. For the study group compared with the control group, FEV 1 percent predicted was 82.60% ± 13.54% vs 105.83% ± 13.12% (P < .001), and the lung clearance index was 7.67 ± 1.02 vs 7.46 ± 0.70 (P = .48), respectively. Study group adolescents with bronchopulmonary dysplasia had a higher lung clearance index than did adolescents with no bronchopulmonary dysplasia (7.94 ± 1.11 vs 7.20 ± 0.60; P = .002). PG and NPG adolescents were not significantly different. Comparing the study group in adolescence with primary school age, we found improvement in mean FEV 1 percent predicted bronchodilator response (0.37% ± 9.98% vs 5.67% ± 9.87%; P = .036) and mean provocative concentration causing 20% decline in FEV 1 (12.16 ± 4.71 mg/mL vs 4.14 ± 4.51 mg/mL, respectively; P < .001)., Interpretation: Palivizumab did not provide any discernable long-term protective effect. Nevertheless, adolescent survivors of extreme prematurity showed good clinical and physiologic outcomes, except for mildly raised lung clearance index in patients with bronchopulmonary dysplasia. Airway hyperreactivity detected at primary school age, decreased by adolescence., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: splenomegaly and/or focal splenic lesions (FSL) have limited histopathologic studies due to the risk posed by splenic punctures. Percutaneous biopsies with a fine needle are difficult, especially due to interposition of gases, ascites, obesity or a history of abdominal surgery. On the other hand, endoscopic ultrasound (EUS) takes advantage of the proximity of the gastric wall to the spleen in order to puncture and visualize the needle and its movements in real time., Objective: to describe the initial experience and results obtained with EUS-FNA in patients with splenomegaly or FSL., Materials and Methods: this was a descriptive observational study. EUS-FNA of the spleen was performed with a slow-pull technique, which avoided fanning with an average of 3 needle passes. Biopsies were sent in Cytorich RedTM solution for analysis by cytology and cell block., Results: punctures were performed in 15 patients (9 females) and the median age was 67 years (range 44-86). Patients studied due to an enlarged spleen or splenic FSL, in the context of fever of an unknown origin, adenopathies and abnormal weight loss were included. A conclusive diagnosis was achieved by EUS-FNA in 10 patients (66.7 %), 4 were large cell type B non-Hodgkin's lymphoma and one Hodgkin's lymphoma. There were no immediate or delayed complications related to the procedure., Conclusions: EUS-guided splenic punctures appear to be safe, effective and may be necessary in some clinical settings in order to complete the etiologic filiation of splenomegaly of an uncertain origin or FSL and to rule out malignancy.

Background: In recent years, interest in universal newborn screening for congenital cytomegalovirus (cCMV) has intensified. consequently, reliable and simple methods of mass screening for cCMV, are essential. Herein, we present a novel approach of using polymerase chain reaction (PCR) in saliva with direct inoculation onto Guthrie paper. Our aim was to determine the diagnostic accuracy of real- time PCR in saliva rolled directly onto Guthrie paper in diagnosing cCMV infection., Objectives: To evaluate the diagnostic accuracy of real-time PCR analysis of dried saliva on Guthrie paper as a future approach for mass screening of newborns in diagnosing cCMV infection., Study Design: This prospective, blinded study was performed in a tertiary cytomegalovirus (CMV) clinic from May 2018 through January 2019. Forty-two cCMV positive newborns and 41 without cCMV, were enrolled and tested for CMV using PCR from their saliva placed onto Guthrie paper and from their saliva using standard methods. Specificity and sensitivity of dried saliva PCR versus gold-standard methods were analyzed., Results: Forty-two out of 42 (100 %) CMV positive infants showed positive PCR in the dried saliva on the Guthrie paper. All (100 %) controls exhibited negative PCR results. Congenital CMV infection was identified with a sensitivity of 100 % (95 % C.I. = 91.4%-100.00%) and specificity of 100 % (95 % C.I. = 91.4%-100.00%)., Discussion: CMV testing with saliva real-time PCR on Guthrie paper displayed a high sensitivity and specificity, rendering it a powerful screening test. The accuracy, simplicity of sampling, storage and transportation and the potential reliance on existing logistic resources, establishes this method as a candidate for cCMV universal screening programs., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: The objective of this study is to determine the true incidence of early neonatal hypoglycemia and to confirm potential risk factors., Study Design: The study was conducted at tertiary Medical Center in Israel, between June and September 2014. First blood glucose concentrations of all infants admitted to the nursery were measured using a "point of care" analyzer (Accu-Chek). We recorded risk factors for hypoglycemia such as birth weight, gestational age, maternal diabetes and demographics and analyzed their association with two hypoglycemia cutoffs: 40 and 47 mg/dl., Results: Of 4000 newborns admitted during that period, 3595 were analyzed after excluding 405 who had missing data. Glucose level was obtained at a mean age of 74 ± 30 min. One hundred and twenty-four newborns (3.4%) had blood glucose levels below 40 mg/dl and 435 (12.1%) below 47 mg/dl. Univariate analyses revealed that gestational age, maternal diabetes, low birth weight (<2500 g), and twin delivery were associated with early neonatal hypoglycemia. Other risk factors (e.g. large or small for gestational age, birth weight >3800 g) were not. In multivariate analysis, gestational age remained the strongest association, while maternal diabetes and low birth weight became non-significant., Conclusions: We showed a high occurrence of early hypoglycemia in normal newborns using universal screening. The strongest risk factor was early gestational age. Surprisingly, incidence of early hypoglycemia in the presence of other classical risk factors was like that of the general population.