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Objective: Decrease: 1) time from tracheostomy or gastrostomy tube placement to discharge home, and 2) avoidable readmissions within 7 days post-discharge, for medically complex infants., Study Design: Five neonatology units and representatives from Medicaid and Managed Care Organizations participated. Measures included length of stay (LOS) from surgery to discharge, readmissions, and time from surgery to identifying home nursing. We used statistical process control (SPC) methods and bivariate tests for post-hoc before-after comparisons., Result: Among 421 infants, no avoidable readmissions occurred in the final 25 months. LOS and all-cause readmissions were unchanged (SPC). LOS changes were variable, ranging from -39.5 days (tracheostomy and ventilator) to +30.8 days (tracheostomy without ventilator) and not significant. Median time to identify home nursing was 70.1 days (range 2-428)., Conclusion: Although lack of skilled home nursing precluded improving transitions from NICU to home in medically complex infants, all avoidable readmissions were eliminated for 25 months., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Infections caused by the Gram-negative pathogen Pseudomonas aeruginosa are emerging worldwide as a major threat to human health. Conventional antibiotic monotherapy suffers from rapid resistance development, underlining urgent need for novel treatment concepts. Here, we report on a nontraditional approach to combat P. aeruginosa -derived infections by targeting its main virulence factor, the elastase LasB. We discovered a new chemical class of phosphonates with an outstanding in vitro ADMET and PK profile, auspicious activity both in vitro and in vivo . We established the mode of action through a cocrystal structure of our lead compound with LasB and in several in vitro and ex vivo models. The proof of concept of a combination of our pathoblocker with levofloxacin in a murine neutropenic lung infection model and the reduction of LasB protein levels in blood as a proof of target engagement demonstrate the great potential for use as an adjunctive treatment of lung infections in humans., Competing Interests: The authors declare the following competing financial interest(s): J.K., K.V., A.S.A., A.M.K., J.H., C.D., A.K.H.H., and R.W.H. are co-inventors on the international patent application (PCT/EP2021/073381) that incorporates methods outlined in this manuscript., (© 2023 The Authors. Published by American Chemical Society.)

Background: A paucity of studies describes the prevalence of family-centered care (FCC) practices and resources in US neonatal units., Purpose: To identify US prevalence of FCC practices and resources and to identify the largest gaps in resource provision., Methods: Neonatal nurses completed an online survey through national conferences (eg, NANN educational conference), neonatal organization Web sites (eg, NANN research survey), and social media (eg, NANN and NPA Facebook). Nurses provided demographics and the National Perinatal Association Self-Assessment on Comprehensive Family Support, a 61-item checklist of FCC practices and resources from 6 categories: family-centered developmental care, staff education/support, peer support, palliative care, discharge education, and mental health support., Results: Nurses (n = 103) reported lowest resources for Peer Support and Mental Health Support. About a third had a neonatal intensive care unit parent advisory committee (n = 39; 37.9%). Only 43.7% (n = 45) had necessary amenities for families to stay with their infants. Less than a third felt that mental health professionals were adequately staffed to provide counseling to parents (n = 28; 27.5%). Very few nurses had adequate training on providing parents psychological support (n = 16; 15.8%). More than half (n = 58; 56.3%) stated that all staff receive training in family-centered developmental care. Finally, less than half (n = 42; 40.8%) stated that staff see parents as equal members of the care team., Implications for Practice: We demonstrate a consistent and widespread lack of training provided to neonatal staff in nearly every aspect of comprehensive FCC support., Implications for Research: Researchers need to identify unit/organizational interventions that increase adoption and implementation of FCC practices and resources., (Copyright © 2021 by The National Association of Neonatal Nurses.)

Despite the progress in surgical techniques and antibiotic prophylaxis, opportunistic wound infections with Bacillus cereus remain a public health problem. Secreted toxins are one of the main factors contributing to B . cereus pathogenicity. A promising strategy to treat such infections is to target these toxins and not the bacteria. Although the exoenzymes produced by B . cereus are thoroughly investigated, little is known about the role of B . cereus collagenases in wound infections. In this report, the collagenolytic activity of secreted collagenases (Col) is characterized in the B . cereus culture supernatant (csn) and its isolated recombinantly produced ColQ1 is characterized. The data reveals that ColQ1 causes damage on dermal collagen (COL). This results in gaps in the tissue, which might facilitate the spread of bacteria. The importance of B . cereus collagenases is also demonstrated in disease promotion using two inhibitors. Compound 2 shows high efficacy in peptidolytic, gelatinolytic, and COL degradation assays. It also preserves the fibrillar COLs in skin tissue challenged with ColQ1, as well as the viability of skin cells treated with B . cereus csn. A Galleria mellonella model highlights the significance of collagenase inhibition in vivo., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

Increasing antimicrobial resistance is evolving to be one of the major threats to public health. To reduce the selection pressure and thus to avoid a fast development of resistance, novel approaches aim to target bacterial virulence instead of growth. Another strategy is to restore the activity of antibiotics already in clinical use. This can be achieved by the inhibition of resistance factors such as metallo-β-lactamases (MBLs). Since MBLs can cleave almost all β-lactam antibiotics, including the "last resort" carbapenems, their inhibition is of utmost importance. Here, we report on the synthesis and in vitro evaluation of N -aryl mercaptoacetamides as inhibitors of both clinically relevant MBLs and the virulence factor LasB from Pseudomonas aeruginosa . All tested N -aryl mercaptoacetamides showed low micromolar to submicromolar activities on the tested enzymes IMP-7, NDM-1 and VIM-1. The two most promising compounds were further examined in NDM-1 expressing Klebsiella pneumoniae isolates, where they restored the full activity of imipenem. Together with their LasB-inhibitory activity in the micromolar range, this class of compounds can now serve as a starting point for a multi-target inhibitor approach against both bacterial resistance and virulence, which is unprecedented in antibacterial drug discovery., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objectives: Determine if antenatal counseling delivered in the outpatient setting improves parental knowledge and satisfaction without contributing to anxiety., Study Design: Randomized control trial at a large academic institution. Mothers at risk for preterm delivery were enrolled following routine maternal-fetal medicine (MFM) visits and randomized to early antenatal counseling of prematurity or standard counseling by MFM providers. The primary outcome was parental knowledge of prematurity. Secondary outcomes included parental satisfaction, anxiety scores, and compliance with recommended follow-up., Results: Seventy-six women were enrolled, 38 in each group. Early counseling group had higher knowledge scores (86.3 vs 64.3, p = <0.001) and parental satisfaction (p = 0.003). Anxiety scores were similar between the two groups (38.2 vs 40.4, p = 0.53). No difference was noted in compliance with follow-up., Conclusions: Antenatal counseling in the high-risk outpatient setting improved parental knowledge and satisfaction without leading to increased anxiety., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Microbial infections are a significant threat to public health, and resistance is on the rise, so new antibiotics with novel modes of action are urgently needed. The extracellular zinc metalloprotease collagenase H (ColH) from Clostridium histolyticum is a virulence factor that catalyses tissue damage, leading to improved host invasion and colonisation. Besides the major role of ColH in pathogenicity, its extracellular localisation makes it a highly attractive target for the development of new antivirulence agents. Previously, we had found that a highly selective and potent thiol prodrug (with a hydrolytically cleavable thiocarbamate unit) provided efficient ColH inhibition. We now report the synthesis and biological evaluation of a range of zinc-binding group (ZBG) variants of this thiol-derived inhibitor, with the mercapto unit being replaced by other zinc ligands. Among these, an analogue with a phosphonate motif as ZBG showed promising activity against ColH, an improved selectivity profile, and significantly higher stability than the thiol reference compound, thus making it an attractive candidate for future drug development., (© 2021 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

Objective: The objective of this study is to determine the resuscitation choices at 22-24 weeks gestation, related to whether mothers received antenatal counseling and the timing relative to delivery., Study Design: A retrospective chart review was performed of infants inborn at 22-24 weeks, over a 5-year period. Infants were excluded if they had major birth defects, were still hospitalized, or the consult occurred before 22 weeks., Result: Of 121 infants born at 22 0 -24 6 weeks, 91 were born to mothers who received a neonatology consult. For 80 infants resuscitated after consult, the median time between consult and delivery was 51.7 h (range: 0.1-366.3 h). For 11 infants who received comfort care after consult, the median time between consult and delivery was 20.0 h (range: 0.8-64.4 h)., Conclusions: After receiving counseling on the morbidity and mortality of delivery at 22-24 weeks, most parents chose resuscitation. Overall, 12-24 h between consult and delivery, parents were more likely to choose comfort care.

Advances in neonatal care have led to increased survival of infants with complex medical needs and technology dependence. Transition of the ventilator-dependent infant from hospital to home is a complex process that requires extensive coordination between the medical team and family. Home caregivers must be prepared to provide routine care for the ventilator-dependent child and respond to life-threatening emergencies. Families should be counseled on the need for home nursing, medical equipment and an adequate home environment to ensure a safe transition to home. Throughout the process, the family may require financial, social and psychological support. A structured education and transition process that is clearly communicated to parents is necessary to have an effective partnership with families., (© 2019 Published by Elsevier Ltd.)

Objective: To determine whether the use of family members as educators in a structured educational intervention would increase neonatology fellows' confidence in performing core communication skills targeted to guide family decision-making., Study Design: Neonatology fellows at two centers participated in simulation-based training utilizing formally trained family members of former patients. Fellows completed self-assessment surveys before participating, immediately following participation, and 1-month following the training. Family members also evaluated fellow communication., Results: For each core competency assessed, there was a statistically significant increase in self-perceived preparedness from pre-course to post-course assessments. Fellows additionally endorsed using skills learned in the curriculum in daily clinical practice. Family educators rated fellow communication highest in empathetic listening and nonverbal communication., Conclusions: Participation in a communication skills curriculum utilizing formally trained family members as educators for medical trainees successfully increased fellows' self-perceived preparedness in selected core competencies in communication. Family educators provided useful, generalizable feedback.

Essentials The self-inhibitory mechanism of von Willebrand factor (VWF) remains unclear. Residues flanking the A1 domain of VWF form a discontinuous autoinhibitory module (AIM). rVWF 1238-1493 exhibited greater thermostability and inactivity than its shorter counterparts. The cooperative coupling between the N- and C- AIM regions are required for inhibiting A1., Summary: Background The hierarchical hemostasis response involves a self-inhibitory feature of von Willebrand factor (VWF) that has not been fully characterized. The residues flanking the A1 domain of VWF are important in this self-inhibition by forming an autoinhibitory module (AIM) that masks the A1 domain. Objectives To delimit the AIM sequence and to evaluate the cooperative interplay between the discontinuous AIM regions. Methods ELISA, flow cytometry, a thermal stability assay and hydrogen-deuterium exchange (HDX) mass spectrometry were used to characterize recombinant VWF A1 fragments varying in length. Results The longest A1 fragment (rVWF 1238-1493 ) showed higher inactivity in binding the platelet receptor glycoprotein (GP) Ibα and greater thermostability than its shorter counterparts. The HDX results showed that most of the N-terminal residues and residues 1459-1478 at the C-terminus of rVWF 1238-1493 have slower deuterium uptake than the residues in its denatured counterpart, implying that these residues may interact with the A1 domain. In contrast, residues 1479-1493 showed less difference from the denatured form, indicating that these residues are unlikely to be involved in binding the A1 domain. The A1 fragment that lacks either the entire C-terminal flanking region of the AIM (C-AIM), i.e. rVWF 1238-1461 , or the entire N-terminal flanking region of the AIM (N-AIM), i.e. rVWF 1271-1493 , showed high GPIbα-binding affinity and low thermostability, suggesting that removal of either N-terminal or C-terminal residues resulted in loss of AIM inhibition of the A1 domain. Conclusion The AIM is probably composed of residues 1238-1271 (N-AIM) and 1459-1478 (C-AIM). Neither the N-AIM nor the C-AIM alone could fully inhibit binding of the A1 domain to GPIbα., (© 2018 International Society on Thrombosis and Haemostasis.)

Diprosopus is a rare congenital malformation associated with high mortality. Here, we describe a patient with diprosopus, multiple life-threatening anomalies, and genetic mutations. Prenatal diagnosis and counseling made a beneficial impact on the family and medical providers in the care of this case.

Introduction. Neonatal hydrocolpos is a rare condition. Hydrocolpos is cystic dilatation of the vagina with fluid accumulation due to a combination of stimulation of secretary glands of the reproductive tract and vaginal obstruction. The differential for a neonatal presentation of lower abdominal mass includes urogenital anomalies, Hirschsprung's, disease or sacrococcygeal teratoma. Prenatal diagnosis and early newborn imaging studies leads to early detection and treatment of these cases. Case. We report here two cases of neonatal hydrocolpos with prenatal diagnosis of lower abdominal mass. Postnatally, ultrasound, MRI imaging, and cystoscopy confirmed large cystic mass as hydrocolpos with distal vaginal obstruction. Both patients had enlarged renal system secondary to mass effect. Conclusion. High index of suspicion for hydrocolpos in a newborn presenting with fetal diagnosis of infraumbilical abdominal mass will facilitate timely intervention and prevention of complications.