Search

A rapid decline in self-renewability, viability and function, of isolated stem cells are major hurdles in developing cell based therapies. There has been an increasing interest towards identifying a support material for maintaining stem cell features of the isolated cells. Pioneering observations of the present paper, demonstrate functionally diverse potential of Solid Lipid Nanoparticles (SLNs) in deciding the fate & behavior of mouse mesenchymal stem cell. The evidences are provided to show the dual nature of the SLNs for being a scaffold for the stem cell attachment, to retain stemness, and as reagent for inducing stem cell differentiation. Scanning electron microscopic examinations together with expression analysis were used to conform to such observations. Results of the study thus suggest that Solid lipid nanoparticles can be used as a good support material when functionalized to achieve adhesive properties and as a molecular paradigm for studying the adipocytic differentiation. We envisage a new role of SLNs towards regulating stem cell character by orchestrating the structural alignment during preparation of Solid lipid nanoparticles.

AIM: To evaluate the association between the use of nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) with the development of bronchopulmonary dysplasia (BPD). METHODS: This is a single center retrospective cohort analysis of infants born at ≤1000 grams and ≤28 weeks gestation with respiratory distress treated with nCPAP or NIPPV. Groups were compared using Student's t test or chi-square, and associations estimated by logistic regression. RESULTS: Compared to nCPAP, infants who received NIPPV had a higher incidence of moderate to severe (M–S) BPD (84.2 vs 65.5%, p = 0.044) and death or severe BPD (75.0 vs 47.6%, p = 0.003). Each day on NIPPV was associated with an increased risk of M-S BPD (OR 1.08, p < 0.001) and an increased risk of death or severe BPD (OR 1.03, p = 0.006). After adjusting for days on oxygen, ventilator days, and days on all respiratory support, the odds of developing M-S BPD increased by 4.9% for each additional week on NIPPV (CI 2.1–7.7%, p =.0001). CONCLUSION: In this cohort, use of NIPPV was associated with an increased risk for developing BPD when compared to infants receiving nCPAP, and each additional day on NIPPV carried significant increased risk for developing BPD. [ABSTRACT FROM AUTHOR]

Objective: The objective of this program evaluation was to describe the outcomes of daily neonatologist telerounding with the onsite advanced practice provider (APP) in a Level II neonatal intensive care unit (NICU), before and during the coronavirus disease 2019 (COVID-19) pandemic., Study Design: Bedside telerounding occurred with an onsite APP using a telehealth cart and paired Bluetooth stethoscope. Data collected by longitudinal and cross-sectional surveys and chart review before (May 2019-February 2020) and during (March 2020-February 2021) the COVID-19 pandemic were analyzed using descriptive statistics and thematic analysis., Results: A total of 258 patients were admitted to the Level II NICU before (May 2019-February 2020) and during (March 2020-February 2021) the COVID-19 pandemic. Demographic characteristics and outcomes, including breastfeeding at discharge and length of stay were similar pre- and postonset of the COVID-19 pandemic. Postrounding surveys by 10 (response rate 83%) neonatologists indicated parents were present in 80 (77%) of rounds and video was at least somewhat helpful in 94% of cases. Cross-sectional survey responses of 23 neonatologists and APPs (response rate 62%) indicated satisfaction with the program. Common themes on qualitative analysis of open-ended survey responses were "need for goodness of fit" and "another set of eyes" and "opportunities for use.", Conclusion: Daily telerounding with neonatologists and APPs in a Level II NICU supported neonatal care. Quality metrics and clinical outcomes are described with no differences seen before and during the COVID-19 pandemic., Key Points: · Little is known about Level II NICU quality metrics and outcomes.. · Daily bedside telerounding with neonatologists and APPs is described.. · Telerounding supported neonatal care before and during the COVID-19 pandemic.. · Neonatologists found visual exam helpful in the majority of cases.. · No differences in NICU clinical outcomes were seen during the COVID-19 pandemic.., Competing Interests: None declared., (Thieme. All rights reserved.)

Compared to other techniques, poller screws with intramedullary nailing are technically simple, practical, and reproducible for the fixation of metaphyseal fractures. In addition, poller screws do not require special instruments or hardware and are minimally invasive. This review takes a historical perspective to evaluate poller screws holistically. A non-systematic search on PubMed was performed using 'Poller screw' or 'Blocking screw' to find early use of poller blocking screws. Relevant references from these primary studies were then followed up. In 1999, Krettek et al. first coined the term poller screws after the small metal bollards that block and direct traffic. Poller screws were introduced as an adjunct to aid the union of metaphyseal long bone fractures during intramedullary nailing. However, as more evidence was published, the true effectiveness of poller screws was not appreciated, leading to split opinions. Through our research, we have built upon our understanding of poller screws, and we present a novel classification of poller screws over the years while exploring our novel technique and what we believe to be the fourth generation of poller screws. Currently, there is a paucity of research focussing on poller screws. However, studying the original evidence regarding poller screws through the most recent articles has demonstrated a confusion of research in this field. Therefore, we suggest a more organised approach to classify the use of poller screws.

Introduction: A new, citrate-free ixekizumab formulation, which is bioequivalent to the original formulation, was associated with significant reduction in injection site pain. This study evaluates patient satisfaction with the first injection experience of citrate-free ixekizumab in a real-world setting., Methods: A non-interventional, observational, web-based survey of adults (≥ 18 years) with psoriasis, psoriatic arthritis, or axial spondyloarthritis was conducted between August 2022 and March 2023. Patients enrolled in the Taltz US Customer Support Program were identified as receiving either the original ixekizumab or initiating citrate-free ixekizumab. Patients receiving original ixekizumab completed one survey at baseline to assess satisfaction with the formulation and one survey after switching to assess satisfaction, willingness to continue using and recommending citrate-free ixekizumab, and formulation preference. Participants previously exposed to ixekizumab completed one survey to assess their satisfaction and willingness to continue using and recommending citrate-free ixekizumab. Descriptive and comparative statistics are reported for patients that switched from original to citrate-free ixekizumab (n = 361); and descriptive statistics are reported for patients not previously exposed to ixekizumab (n = 90)., Results: A total of 451 patients were included in the analysis. Significantly more patients were satisfied with their first injection with citrate-free ixekizumab compared to original ixekizumab (83.9% vs. 71.7% respectively; p = 0.0001). Almost all patients who switched from original ixekizumab were definitely or mostly willing to continue using and recommending citrate-free ixekizumab (93.9% and 93.4%, respectively). Additionally, 94.2% of patients who switched from original to citrate-free ixekizumab preferred citrate-free ixekizumab or had no preference. Three-fourths of patients not previously exposed to ixekizumab were satisfied with their first injection with citrate-free ixekizumab and 94.5% were definitely or mostly willing to continue using citrate-free ixekizumab., Conclusion: The citrate-free ixekizumab formulation was preferred and well accepted by most patients who switched from the original ixekizumab formulation. Similar findings were seen for those newly initiating citrate-free ixekizumab., (© 2024. The Author(s).)

Acute myeloid leukemia (AML) and myeloid neoplasms develop through acquisition of somatic mutations that confer mutation-specific fitness advantages to hematopoietic stem and progenitor cells. However, our understanding of mutational effects remains limited to the resolution attainable within immunophenotypically and clinically accessible bulk cell populations. To decipher heterogeneous cellular fitness to preleukemic mutational perturbations, we performed single-cell RNA sequencing of eight different mouse models with driver mutations of myeloid malignancies, generating 269,048 single-cell profiles. Our analysis infers mutation-driven perturbations in cell abundance, cellular lineage fate, cellular metabolism, and gene expression at the continuous resolution, pinpointing cell populations with transcriptional alterations associated with differentiation bias. We further develop an 11-gene scoring system (Stem11) on the basis of preleukemic transcriptional signatures that predicts AML patient outcomes. Our results demonstrate that a single-cell-resolution deep characterization of preleukemic biology has the potential to enhance our understanding of AML heterogeneity and inform more effective risk stratification strategies., Competing Interests: Aspects of this work are included in United Kingdom patent application 2312684.0., (© 2023 The Author(s).)

Recent studies of exosomes derived from mesenchymal stem cells (MSCs) have indicated high potential clinical applications in many diseases. However, the limited source of MSCs impedes their clinical research and application. Most recently, induced pluripotent stem cells (iPSCs) have become a promising source of MSCs. Exosome therapy based on iPSC-derived MSCs (iMSCs) is a novel technique with much of its therapeutic potential untapped. Compared to MSCs, iMSCs have proved superior in cell proliferation, immunomodulation, generation of exosomes capable of controlling the microenvironment, and bioactive paracrine factor secretion, while also theoretically eliminating the dependence on immunosuppression drugs. The therapeutic effects of iMSC-derived exosomes are explored in many diseases and are best studied in wound healing, cardiovascular disease, and musculoskeletal pathology. It is pertinent clinicians have a strong understanding of stem cell therapy and the latest advances that will eventually translate into clinical practice. In this review, we discuss the various applications of exosomes derived from iMSCs in clinical medicine., (© 2023. The Author(s).)

Objective: This study is to evaluate the effects of darbepoetin alfa (darbe) on neutrophil count in preterm neonates treated for anemia of prematurity., Methods: This was a retrospective chart review comparing the absolute neutrophil counts (ANCs) of neonates administered 2 doses of subcutaneous darbe 10 mcg/kg to that of a randomly selected comparator group of neonates not administered the drug. Neonates <34 weeks gestational age, gestational age between 23w1d and 33w4d, born between July 2016 and June 2019, were included in the study., Results: The ANCs of 45 darbe-treated neonates compared with those of 45 randomly selected comparator control neonates revealed no difference in the rate of occurrence of neutropenia (ANC ≤1000/μL) between the darbe-treated neonates (26.7%) and comparator neonates (24.4%) (p > 0.99). There was also no difference in the rate of occurrence of severe neutropenia (ANC ≤500/μL) between the darbe-treated neonates (11.1%) and comparator neonates (6.7%) (p = 0.70). Darbepoetin alfa did not lead to differences in rates of resolution of neutropenia or severe neutropenia., Conclusions: Short-term administration of darbe did not affect the ANCs of preterm neonates treated for anemia of prematurity. There was no difference in the rates of occurrence of neutropenia, severe neutropenia, or resolution of either between the darbe-treated neonates and comparator neonates., Competing Interests: Disclosures. The authors declare no conflicts. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis., (Copyright. Pediatric Pharmacy Association. All rights reserved. For permissions, email: membership@pediatricpharmacy.org 2023.)

Introduction: Subcutaneous (SC) injection is a common route of drug administration; however, injection site pain (ISP) might create a negative patient experience. We evaluated ISP, bioequivalence, and overall safety of the citrate-free (CF) formulation of ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A., Methods: Two phase 1, single-blind studies were conducted in healthy participants. The crossover study A (NCT03848403) evaluated pain intensity on injection as measured by visual analog scale of pain (VAS) scores. Subjects (N = 70) were randomized 1:1:1 at the beginning to three possible treatment sequences and received a 1 mL SC injection of the three formulations sequentially in the abdomen on days 1, 8, and 15, respectively. A mixed-effects repeated measures analysis model was used to analyze VAS score by time post-injection. Study B (NCT04259346) evaluated the bioequivalence of a single 80 mg dose of CF formulation compared to the original commercial formulation. Subjects (N = 245) were randomized 1:1 to either commercial or CF formulation and received a single SC injection into the abdomen, arm, or thigh., Results: Primary endpoint was achieved in both studies. In study A, least-squares mean (LSM) difference of VAS scores immediately post injection between commercial (n = 61) and CF formulation (n = 63) was - 21.7 (p < 0.0001), indicating a lower degree of pain associated with CF formulation. In study B, bioequivalence of the CF formulation was established as 90% CIs for the ratio of geometric LSM AUC 0-tlast , AUC 0-∞ , and C max between treatments were contained within the prespecified limits of 0.8 and 1.25. Except for less ISP in the CF formulation, overall safety profile was comparable., Conclusion: Ixekizumab CF formulation proved to be bioequivalent, was associated with less ISP, and had no other notable differences in the safety profile compared to the original commercial formulation., Trail Registration: ClinicalTrials.gov identifier NCT03848403, NCT04259346., (© 2022. The Author(s).)

We report on a term infant with clinically significant hemolysis and hyperbilirubinemia. Testing revealed ABO incompatibility between maternal type A and infant type AB. The maternal alloantibody screen was negative. The infant's direct antiglobulin test was positive, and anti-B IgG was eluted off the infant's red blood cells (RBCs). Testing of the mother's plasma revealed a high anti-B titer. The infant was successfully treated with phototherapy and intravenous immunoglobulin. The bilirubin and hematocrit stabilized, and the infant was discharged home. This case was unusual because of its severity and unusual ABO constellation. Furthermore, this report is an exemplary educational case study on how effective collaboration between the clinical team and the blood bank laboratory is critical in reaching the correct diagnosis. In summary, the differential diagnosis of more unusual and atypical ABO-incompatible constellations must be considered when an infant presents with unexplained hemolysis., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The presentation of a hot swollen joint is common in the emergency department, general practice, rheumatology and orthopedic clinics. There is a wide set of differential diagnoses for a hot swollen joint, thus making it difficult to diagnose and manage, especially for junior doctors. Initially, it is pertinent to exclude/diagnose medical and surgical emergencies., Objective: This paper aims to summarize the key indications within the history, examination and investigations in order to quickly and effectively diagnose a hot swollen joint based on the original 2006 management guidelines and the papers discussing other possible indications and management strategies published since then., Results: Currently, the management of crystal and non-infectious arthropathies is well recognized with little disparity. However, the treatment of infectious arthritis is not concrete, and there are discrepancies in management between doctors., Conclusion: We have summarized the key indications and provided a diagnostic flow chart to aid with the management of a hot swollen joint., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: A vital element of the Next Accreditation System is measuring and reporting educational Milestones. Little is known about changes in Milestones levels during the transition from residency to fellowship training., Objective: Evaluate the Accreditation Council for Graduate Medical Education (ACGME) Milestones' ability to provide a linear trajectory of professional development from general pediatrics residency to neonatal-perinatal medicine (NPM) fellowship training., Methods: We identified 11 subcompetencies that were the same for general pediatrics residency and NPM fellowship. We then extracted the last residency Milestone level and the first fellowship Milestone level for each subcompetency from the ACGME's Accreditation Data System on 89 subjects who started fellowship training between 2014 and 2018 at 6 NPM fellowship programs. Mixed-effects models were used to examine the intra-individual changes in Milestone scores between residency and fellowship after adjusting for the effects of the individual programs., Results: A total of 1905 subcompetency Milestone levels were analyzed. The average first fellowship Milestone levels were significantly lower than the last residency Milestone levels (residency, mean 3.99 [SD = 0.48] vs fellowship 2.51 [SD = 0.56]; P < .001). Milestone levels decreased by an average of -1.49 (SD = 0.65) from the last residency to the first fellowship evaluation. Significant differences in Milestone levels were seen in both context-dependent subcompetencies (patient care and medical knowledge) and context-independent subcompetencies (professionalism)., Conclusions: Contrary to providing a linear trajectory of professional development, we found that Milestone levels were reset when trainees transitioned from general pediatrics residency to NPM fellowship., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

CHRNB1 encodes the β subunit of the acetylcholine receptor (AChR) at the neuromuscular junction. Inherited defects in the neuromuscular junction can lead to congenital myasthenia syndrome (CMS), a clinically and genetically heterogeneous group of disorders which includes fetal akinesia deformation sequence (FADS) on the severe end of the spectrum. Here, we report two unrelated families with biallelic CHRNB1 variants, and in each family, one child presented with lethal FADS. We contrast the diagnostic odysseys in the two families, one of which lasted 16 years while the other, utilizing rapid exome sequencing, led to specific treatment in the first 2 weeks of life. Furthermore, we note that CHRNB1 variants may be under-recognized because in both families, one of the variants is a single exon deletion that has been previously described but may not easily be detected in clinically available genetic testing., (© 2020 Wiley Periodicals LLC.)

Background: Gastroschisis is an abdominal wall defect wherein the bowel is herniated into the amniotic fluid. Controversy exists regarding optimal prenatal surveillance strategies that predict fetal well-being and help guide timing of delivery. Our objective was to develop a clinical care pathway for prenatal management of uncomplicated gastroschisis at our institution., Methods: We performed a review of literature from January 1996 to May 2017 to evaluate prenatal ultrasound (US) markers and surveillance strategies that help determine timing of delivery and optimize outcomes in fetal gastroschisis., Results: A total 63 relevant articles were identified. We found that among the US markers, intraabdominal bowel dilatation, polyhydramnios, and gastric dilatation are potentially associated with postnatal complications. Prenatal surveillance strategy with monthly US starting at 28weeks of gestational age (wGA) and twice weekly non-stress testing beginning at 32wGA is recommended to optimize fetal wellbeing. Timing of delivery should be based on obstetric indications and elective preterm delivery prior to 37wGA is not indicated., Conclusions: Close prenatal surveillance of fetal gastroschisis is necessary due to the high risk for adverse outcomes including intrauterine fetal demise in the third trimester. Decisions regarding the timing of delivery should take into consideration the additional prematurity-associated morbidity.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Objectives: To evaluate the utility of the fetal thigh soft tissue thickness (STT) in calculating the estimated fetal weight (EFW) in fetuses with gastroschisis versus the standard formula of Hadlock et al (Am J Obstet Gynecol 1985; 151:333-337) compared to the actual birth weight (ABW)., Methods: A retrospective study of neonates born with gastroschisis delivered at our institution was performed. Two reviewers measured the fetal thigh STT on saved images. The estimated gestational age, fetal biometric measurements, and ABW were abstracted. In addition to the Hadlock formula, 3 STT-based formulas reported by Scioscia et al (Ultrasound Obstet Gynecol 2008; 31:314-320) and Kalantari et al (Iran J Reprod Med 2013; 11:933-938) were used to calculate the EFW., Results: Eighty-two patients with gastroschisis qualified for inclusion in our study. The mean STTs ± SD as measured by readers 1 and 2 were 10.9 ± 2.7 and 10.6 ± 2.7 mm, respectively. Seventeen (21%) fetuses were small for gestational age at birth. The Hadlock formula underestimated the EFW relative to the ABW, with an average difference of -97 g (-3.9%) and - 5.1% in terms of growth percentiles. All of the STT-based EFW formulas overestimated the EFW on average by 327 to 701 g (13%-24%) in terms of weight and 26% to 52% in terms of growth percentiles. The Hadlock formula classified 22 as having intrauterine growth restriction (sensitivity, 65%; specificity, 83%, based on the ABW). None of the STT-based formulas classified any fetuses as intrauterine growth restricted., Conclusions: In a group of patients with gastroschisis, we found that the EFW by the fetal thigh STT calculation overestimated the average fetal weight in all of our cases., (© 2020 by the American Institute of Ultrasound in Medicine.)

Objective: To evaluate the impact of nephrology integration in the NICU on acute kidney injury (AKI) incidence, provider reporting, and nephrology referral., Study Design: Cohort study in a single-center NICU from January 2012 to December 2017 (n = 1464). We assessed the impact of clinical practice changes including neonatal-nephrology rounds on the incidence of AKI., Results: AKI occurred in 318 neonates (22%). AKI occurred less frequently in those admitted after clinical practice changes (P < 0.001). After multivariable adjustment, clinical practice changes were associated with reduced odds of AKI (adjusted odds ratio, 0.31; 95% CI 0.22-0.44, P < 0.001). Provider reporting of AKI improved (P < 0.001) and more neonates were referred for nephrology follow-up (P < 0.001)., Conclusions: Increased nephrology integration in the NICU was associated with decreased AKI incidence. While recognition of AKI improved, AKI remained poorly reported and nephrology AKI follow-up did not routinely occur. This study supports the importance of increased nephrology involvement in the NICU.

Gastroesophageal reflux is the involuntary retrograde passage of gastric contents into the esophagus with or without regurgitation and is considered a normal physiologic process, occurring daily in greater than one-third of all infants. Gastroesophageal reflux disease (GERD) is pathologic reflux associated with poor weight gain, irritability, dysphagia and often requires evaluation and treatment. No gold-standard testing for GERD exists. Measurements made by pH probe or multichannel intraesophageal impedance may provide insight into the quantity and character of reflux. Those events do not correlate well with clinical symptoms. Most cases of GERD can be treated conservatively with alterations in the infant's environment and/or feeding pattern. Proton pump inhibitors remain the mainstay for pharmacotherapy of GERD, although these have been associated with increased rates of infection, especially in the preterm population. Neonatal GERD remains a difficult entity to define and manage, and additional studies to aid in the clinical diagnosis and management are needed. [Pediatr Ann. 2020;49(2):e77-e81.]., (Copyright 2020, SLACK Incorporated.)

Procoagulant platelets promote thrombin generation during thrombosis. Platelets become procoagulant in an all-or-nothing manner. We investigated how distinct Ca2+ signaling between platelet subpopulations commits some platelets to become procoagulant, using the high-affinity Ca2+ indicator Fluo-4, which may become saturated during platelet stimulation, or low-affinity Fluo-5N, which reports only very high cytosolic Ca2+ concentrations. All activated platelets had high Fluo-4 fluorescence. However, in Fluo-5N-loaded platelets, only the procoagulant platelets had high fluorescence, indicating very high cytosolic Ca2+. This finding indicates a novel, "supramaximal" Ca2+ signal in procoagulant platelets (ie, much higher than normally considered maximal). Supramaximal Ca2+ signaling and the percentage of procoagulant platelets were inhibited by cyclosporin A, a mitochondrial permeability transition pore blocker, and Ru360, an inhibitor of the mitochondrial Ca2+ uniporter, with no effect on Fluo-4 fluorescence. In contrast, Synta-66, an Orai1 blocker, reduced Fluo-4 fluorescence but did not directly inhibit generation of the supramaximal Ca2+ signal. Our findings show a distinct pattern of Ca2+ signaling in procoagulant platelets and provide a new framework to interpret the role of platelet signaling pathways in procoagulant platelets. This requires reassessment of the role of different Ca2+ channels and may provide new targets to prevent formation of procoagulant platelets and limit thrombosis., (© 2020 by The American Society of Hematology.)

Objective: To determine 1-year survival in a cohort of newborns with an Apgar score of 0 at 5 and 10 min of age., Study Design: A retrospective cohort study of the Washington State Comprehensive Hospital Abstract Reporting System from 2005 to 2014., Results: Of 879,340 births, 199 (0.02%) had an Apgar score of 0 at 5 min, and 109 (0.01%) also had a score of 0 at 10 min. One-year survival was 46% for newborns with Apgar score of 0 at 5 and 10 min. One-year survival by gestational age was 4% for newborns <30 weeks, 38% for 30-35 weeks, and 67% for ≥36 weeks., Conclusion: Survival at 1 year of age for newborns with an Apgar score of 0 at 5 and 10 min has improved, as compared with historic cohorts. Cautious optimism is warranted since morbidity-free survival could not be assessed.

Objective To assess the feasibility and accuracy of point-of-care ultrasound (POCUS) in monitoring peripherally inserted central catheter (PICC) location in neonates by non-radiologist physicians. Methods A prospective cohort study compared PICC localization by ultrasound in neonates with a recent radiograph. The ultrasound exam was performed using a standardized protocol with 13-6 MHz linear and 8-4 MHz phased array transducers by a neonatal-perinatal fellow who was blinded to PICC location on the radiograph. Results Of the 30 neonates included, 96.6% (n = 29) were preterm, with 63.3% (n = 19) weighing <1500 g. Nighty-four percent (n = 94) of ultrasound scans matched the radiograph report. The protocol had a sensitivity of 0.97, specificity of 0.66 and positive predictive value of 0.98. Conclusion Limited ultrasound exams to monitor PICC position in neonates using a standardized protocol by non-radiologist physicians are feasible and accurate in a single ultrasound user. Further study in multiple providers is needed before widespread use.

Our primary objective was to examine external hip joint moments during walking in people with mild radiographic hip osteoarthritis (OA) with and without symptoms and disease-free controls. Three groups were compared (symptomatic with mild radiographic hip OA, n = 12; asymptomatic with mild radiographic hip OA, n = 13; OA-free controls, n = 20). Measures of the external moment (peak and impulse) in the sagittal, frontal and transverse plane during walking were determined. Variables were compared according to group allocation using mixed linear regression models that included individual gait trials, with group allocation as fixed effect and walking speed as a random effect. Participants with evidence of radiographic disease irrespective of symptoms walked 14-16% slower compared to disease-free controls (p = 0.002). Radiographic disease without symptoms was not associated with any altered measures of hip joint moment compared to asymptomatic OA-free controls once speed was taken into account (p ≥ 0.099). People with both mild radiographic disease and symptoms had lower external peak hip adduction moment (p = 0.005) and lower external peak internal rotation moment (p < 0.001) accounting for walking speed. Among angular impulses, only the presence of symptoms was associated with a reduced hip internal rotation impulse (p = 0.002) in the symptomatic group. Collectively, our observations suggest that symptoms have additional mechanical associations from radiographic disease alone, and provide insight into potential early markers of hip OA. Future research is required to understand the implications of modifying walking speed and/or the external hip adduction and internal rotation moment in people with mild hip OA., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: The risk of neonatal early-onset sepsis (EOS) is traditionally assessed on maternal signs of clinical chorioamnionitis. Recently, an online EOS risk calculator was developed by Kaiser Permanente using maternal and neonatal clinical parameters. We were interested in whether an increased Kaiser sepsis risk score correlates with histologic acute chorioamnionitis or acute funisitis., Design: Included in this retrospective review are 119 chorioamnionitis-exposed term neonates from January 1, 2015 and December 31, 2016. Clinical charts from mother-baby pairs were reviewed. An EOS risk score was obtained using the online Kaiser Sepsis Calculator. The presence and severity of acute chorioamnionitis and acute funisitis were recorded. A SPSS software was used for statistical analysis (IBM, New Jersey, USA)., Results: The Kaiser Sepsis Calculator could identify 97 of 119 (81.5%) neonates without increased risk for sepsis. Histologic acute chorioamnionitis was present in 100 of 119 cases (84%), in which 44 cases (44%) show severe acute chorioamnionitis. Acute funisitis was recognized in 87 of 119 (73.1%) cases, all of which had concurrent acute chorioamnionitis. Severe funisitis was seen in 38 of the 87 cases (43.7%). The Kaiser Sepsis risk score correlates with the presence and severity of acute funisitis ( P  = .037 and P  = .044, respectively) but not with the presence or the severity of acute chorioamnionitis ( P  = .105 and P  = .672, respectively)., Conclusion: Our study provides histological evidence to support that the Kaiser Sepsis Calculator may help to effectively reduce unwarranted blood culture, antibiotics exposure, and neonatal intensive care unit admission in term neonates.

Competing Interests: Both Dr. Strand and Dr. Sawyer are members of the American Academy of Pediatrics Neonatal Resuscitation Program Steering Committee. The other authors have no conflict of interest to disclose.

Importance: The developmental origins of mental illness are incompletely understood. Although the development of autism and schizophrenia are linked to infections during fetal life, it is unknown whether more common psychiatric conditions such as depression might begin in utero., Objective: To estimate the risk of psychopathologic conditions imparted from fetal exposure to any maternal infection while hospitalized during pregnancy., Design, Setting, and Participants: A total of 1 791 520 Swedish children born between January 1, 1973, and December 31, 2014, were observed for up to 41 years using linked population-based registries. Children were excluded if they were born too late to contribute person-time, died before being at risk for the outcome, or were missing particular model data. Infection and psychiatric diagnoses were derived using codes from hospitalizations. Directed acyclic graphs were developed from a systematic literature review to determine Cox proportional hazards regression models for risk of psychopathologic conditions in the children. Results were evaluated using probabilistic and simple bias analyses. Statistical analysis was conducted from February 10 to October 17, 2018., Exposures: Hospitalization during pregnancy with any maternal infection, severe maternal infection, and urinary tract infection., Main Outcomes and Measures: Inpatient diagnosis of autism, depression, bipolar disorder, or psychosis among offspring., Results: A total of 1 791 520 Swedish-born children (48.6% females and 51.4% males) were observed from birth up to age 41 years, with a total of 32 125 813 person-years. Within the directed acyclic graph framework of assumptions, fetal exposure to any maternal infection increased the risk of an inpatient diagnosis in the child of autism (hazard ratio [HR], 1.79; 95% CI, 1.34-2.40) or depression (HR, 1.24; 95% CI, 1.08-1.42). Effect estimates for autism and depression were similar following a severe maternal infection (autism: HR, 1.81; 95% CI, 1.18-2.78; depression: HR, 1.24; 95% CI, 0.88-1.73) or urinary tract infection (autism: HR, 1.89; 95% CI, 1.23-2.90; depression: HR, 1.30; 95% CI, 1.04-1.61) and were robust to moderate unknown confounding. Within the directed acyclic graph framework of assumptions, the relationship between infection and depression was vulnerable to bias from loss to follow-up, but separate data from the Swedish Death Registry demonstrated increased risk of suicide among individuals exposed to pregnancy infection. No evidence was found for increased risk of bipolar disorder or psychosis among children exposed to infection in utero., Conclusions and Relevance: These findings suggest that fetal exposure to a maternal infection while hospitalized increased the risk for autism and depression, but not bipolar or psychosis, during the child's life. These results emphasize the importance of avoiding infections during pregnancy, which may impart subtle fetal brain injuries contributing to development of autism and depression.

Objectives: To assess whether a limited ultrasound (US) scanning protocol to monitor the upper extremity peripherally inserted central catheter (PICC) location in neonates is feasible for experienced US operators., Methods: A radiologist, who was blinded to the PICC location on chest radiography, performed 14 US scans on 11 neonates with upper extremity PICCs. A US machine with 13-6-MHz linear and 8-4-MHz phased array transducers was used for the examinations., Results: The study population included 54% (n = 6) preterm infants, with 72% (n = 8) weighing less than 1500 g. The US location of the PICC was the same as the chest radiographic report in all 14 scans. A subclavicular long-axis view of the anterior chest visualized all PICCs in the subclavian or brachiocephalic veins. A parasternal long-axis right ventricular inflow view was able to visualize PICCs in the superior vena cava (SVC), and a subcostal long-axis view evaluated PICCs in the lower SVC and heart. The scanning time was location dependent: less than 5 minutes for PICCs in the brachiocephalic or subclavian vein and 5 to 10 minutes for PICCs in the SVC or heart. There were no desaturations below 90%, increases in the fraction of inspired oxygen need, or hypotension episodes during scanning., Conclusions: A limited US scanning protocol to determine the upper extremity PICC location is feasible. Our protocol needs to be tested in neonatal providers before further dissemination., (© 2018 by the American Institute of Ultrasound in Medicine.)

Objective: To evaluate the effects of use of the Kaiser Neonatal Early-Onset Sepsis Calculator (NEOSC) on NICU admissions, laboratory testing, antibiotic exposure, and exclusive breastfeeding (EBF) rates in full-term neonates exposed to chorioamnionitis., Design: Quality improvement project with review of retrospective data., Setting/local Problem: In this single-site, community hospital with approximately 4,000 births per year, all neonates exposed to chorioamnionitis required NICU admission, laboratory evaluation, and empiric antibiotics., Participants: Term neonates born to mothers diagnosed with chorioamnionitis identified through the International Classification of Diseases, Tenth Revision codes based on the discharge diagnosis., Intervention/measurements: The baseline retrospective analysis included calculation of sepsis risk with the Kaiser NEOSC through a chart review of neonates exposed to chorioamnionitis from January 1, 2015, to December 31, 2016. We compared the risk for sepsis with actual laboratory testing and antibiotic use and examined EBF before implementation of the use of the NEOSC. Implementation began January 2017; postintervention data were examined at 6 months and 1 year. All cases of neonates exposed to chorioamnionitis after the intervention were reviewed for use of the NEOSC, NICU admission/readmission for sepsis, laboratory testing, use of antibiotics, and EBF., Results: In the 12 months after NEOSC use was implemented, NICU admissions, laboratory testing, and antibiotic use decreased. Among all neonates exposed to chorioamnionitis after implementation (N = 74), 68 (93%) were not admitted to the NICU, and only 8 (11%) required laboratory evaluation. Rates of EBF in neonates exposed to chorioamnionitis increased from less than 10% to greater than 50% after implementation. The length of the NICU stay for neonates exposed to chorioamnionitis decreased from an average of 138 to 12 days with no negative consequences., Conclusion: Most neonates exposed to chorioamnionitis appeared well and did not require NICU admission, laboratory testing, or antibiotic therapy. Rates of EBF improved after use of NEOSC was implemented. The practice change helped prevent adverse consequences, such as painful interventions and separation of the mother and neonate. No neonates were readmitted for sepsis., (Copyright © 2019 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

We describe a neonate with severe respiratory failure due to acinar dysplasia found by rapid exome sequencing (rES), to have a deletion containing the TBX4 gene. rES can affect patient management in the intensive care unit and should be considered in concert with lung biopsy in neonates with undifferentiated respiratory failure., (© 2019 Wiley Periodicals, Inc.)

A premature twin infant girl was transferred to a level IV neonatal intensive care unit for recurrent bloody stools, anaemia and discomfort with feeds; without radiographic evidence of necrotising enterocolitis. Additional imaging after transfer revealed a large retroperitoneal mass in the region of the pancreas compressing the inferior vena cava and abdominal aorta, raising suspicion for neuroblastoma. Abdominal exploration and biopsy unexpectedly revealed that the lesion was an infantile capillary haemangioma involving the small bowel, omentum, mesentery and pancreas. The infant was subsequently treated with propranolol, with a decrease in the size of the lesion over the first year of her life and a drastic improvement in feeding tolerance. While cutaneous infantile haemangiomas are common, visceral infantile haemangiomas are less so and may present a significant diagnostic challenge for clinicians. This interesting case demonstrates that such lesions should be considered in the differential diagnosis for unexplained gastrointestinal bleeding or abdominal symptoms in newborns., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal alloimmune neutropenia (NAN) are two rare complications of newborns caused by antibodies against paternal inherited antigens. Human platelet (HPA) and neutrophil antigens (HNA) are the common targets. Human leukocyte antigen (HLA) class I proteins are also expressed on platelets and neutrophils and anti-HLA antibodies have occasionally been implicated in these complications. We report a premature twin infant who presented with severe thrombocytopenia and neutropenia clinically compatible with FNAIT and NAN, from a mother with no identifiable HPA or HNA antibodies, but with very high levels of complement-fixing antibodies against paternal inherited HLA. These antibodies were also detected in the infant. HLA antibodies are commonly present in multiparous women who deliver healthy infants. They can, however, be cytotoxic and cause clinical complications after blood products transfusion (TRALI and becoming refractory to platelets transfusion) and after organ transplantation (allogeneic organ rejection)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The transformation of a general pediatrician into a neonatologist requires rigorous training in a diverse range of core skills during neonatal-perinatal medicine fellowship. This training includes the care of high-risk newborn infants, as well as interdisciplinary communication with care team members and families in the neonatal intensive care unit. In addition, neonatal-perinatal medicine fellows need to acquire competency in key procedurals skills, including neonatal resuscitation techniques, to be able to safely practice neonatology without direct supervision on graduation. Although there is much general advice available to help residents and fellows navigate training, there is little specific advice or guidance for neonatal fellows. In this Perspective , we present 10 commandments for neonatal fellows. The commandments include (1) cherish your patients and their families, (2) know your limits and seek help when needed, (3) understand competency-based medical education, (4) remember the 6 core competencies, (5) review your specialty milestones, (6) have an individualized learning plan, (7) seek out feedback, (8) honor your attendings and nurses, (9) appreciate the importance of teamwork, and (10) do not take thyself in vain. These commandments were developed based on the experience of the authors, working closely with neonatal fellows over several decades. The commandments are present not as unbreakable rules, but rather as words of advice from 2 neonatologists who, having completed their neonatal fellowship, want to help guide others do the same. We believe that this resource will be useful to fellowship programs and neonatal-perinatal fellows., Competing Interests: Declaration of conflicting interests:The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Gastroschisis is a severe congenital anomaly associated with a significant morbidity and mortality. There are limited temporal trend data on incidence, mortality, length of stay, and hospital cost of gastroschisis. Our aim was to study these temporal trends using the National Inpatient Sample (NIS)., Methods: We identified all neonatal admissions with a diagnosis of gastroschisis within the NIS from 2010 through 2014. We limited admission age to ≤ 28 days and excluded all those transferred to other hospitals. We estimated gastroschisis incidence, mortality, length of hospital stay, and cost of hospitalization. For continuous variables, trends were analyzed using survey regression. Cochrane-Armitage trend test was used to analyze trends for categorical variables. P < 0.05 was considered as significant., Results: The incidence of gastroschisis increased from 4.5 to 4.9/10,000 live births from 2010 through 2014 (P = 0.01). Overall mortality was 3.5%, median length of stay was 35 days (95% CI 26-55 days), and median cost of hospitalization was $75,859 (95% CI $50,231-$122,000). After adjusting for covariates, there was no statistically significant change in mortality (OR = 1.13; 95% CI 0.87-1.48), LOS (β = - 2.1 ± 3.5; 95% CI - 9.0 to 4.8) and hospital cost (β = - 2.137 ± 10.813; 95% CI - 23,331 to 19,056) with each calendar year increase on multivariate logistic regression analysis., Conclusion: The incidence of neonates with gastroschisis increased between 2010 and 2014. Incidence was highest in the West. No difference in mortality and resource utilization was observed.

Background: The approach to intrapartum and postnatal management of an infant born through meconium-stained amniotic fluid (MSAF) in the delivery room (DR) has changed several times over the last few decades, leading to confusion and anxiety among health care providers (nurses, nurse practitioners, respiratory therapists, midwives, and physicians). This article provides state-of-the-art insight into the evidence or lack thereof for the changes in guidelines., Purpose: To discuss the evidence for evolution of DR management of vigorous and nonvigorous infants born through any type of MSAF., Methods: Review of guidelines from the Neonatal Resuscitation Program of the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists, the International Liaison Committee on Resuscitation, Consensus on Science and Treatment Recommendations, and textbooks of neonatal resuscitation and research using MEDLINE via PubMed., Findings: In pregnancies complicated by MSAF, intrapartum suctioning of the oro- and nasopharynx and postnatal intubation with tracheal suctioning of infants have been traditionally used to clear the airway and decrease meconium aspiration syndrome. The recommendations for these perinatal practices have changed several times due to some evidence that the procedures are not beneficial and may even be harmful., Implications for Practice: Intrapartum suctioning and postnatal tracheal suctioning of infants (vigorous or nonvigorous) born through MSAF are not recommended. This is a "high-risk" delivery requiring 2 team members to be present at birth-one with full resuscitation skills including tracheal intubation., Implications for Research: Need to evaluate effects of discontinuing the practice of tracheal suctioning in nonvigorous infants on the incidence of meconium aspiration syndrome and neonatal mortality.