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Distal femoral fractures are uncommon in the newborn period, and conventional radiographs can miss the diagnosis in infants born prematurely due to delayed ossification. Hence, modalities like ultrasound may have a role in diagnosis. Herein, we report a male infant born preterm with a swollen knee due to a distal femoral fracture after a non‐traumatic Caesarean section. The fracture was not present on the conventional radiograph. Instead, it was detected on a repeat sonogram and healed spontaneously with no complications. This case describes the importance of musculoskeletal radiographic expertise for diagnosis of this uncommon newborn fracture. [ABSTRACT FROM AUTHOR]

Objective: To determine the sex‐specific diaphragm thickness in infants with bronchopulmonary dysplasia (BPD) as well as in healthy term and near‐term infants. Methods: We performed a secondary analysis of an observational study to compare the sonographic diaphragm thickness at end expiration (DTexp) in female and male infants. The study included infants with BPD and healthy near‐term and term infants. To account for differences in anthropometric measurements, we calculated the DTexp as a ratio of body surface area (BSA). Statistical analysis was performed using R statistical software. Results: Of the 111 infants included, 54 (48.6%) were female. There were no significant differences in mean (SD) birth gestation [26.2 (2.1) vs 26.3 (2.1) weeks] and mean study age [38.0 (2.0) vs 37.4 (1.1) weeks] of male vs female infants with BPD. The mean (SD) DTexp [1.5 (0.4) mm vs 1.2 (0.3) mm, P =.02] and DTexp/BSA [8.3 (2.3) mm/m2 vs 6.7 (1.6) mm/m2, P <.01] were significantly thicker in female than male infants with BPD. In contrast, there were no significant differences in DTexp between sexes [1.5 (0.4) mm vs 1.5 (0.3) mm, P =.89] within the healthy control group. Moreover, there were no differences in inspiratory diaphragm thickness, diaphragm thickness fraction, or excursion between males and females in the BPD or healthy groups. Conclusions: Male infants with BPD exhibit thinner diaphragm thickness compared with female infants. Its implication on higher rates of BPD in preterm males is unclear, but this finding highlights the need for further investigation. [ABSTRACT FROM AUTHOR]

Objective: Surfactant administration via a thin catheter (STC) is an alternative to surfactant administration post endotracheal intubation in preterm infants with respiratory distress syndrome (RDS); however, the benefits particularly in infants <29 weeks' gestation and the neurodevelopmental outcomes remain unclear. Thus, our objective was to systematically review and meta-analyze the efficacy and safety of STC compared to intubation for surfactant or nasal continuous positive airway pressure (nCPAP) in preterm infants with RDS. Methods: Medical databases were searched until December 2022 for randomized controlled trials (RCTs) assessing STC compared to controls that included intubation for surfactant or nCPAP in preterm infants with RDS. The primary outcome was bronchopulmonary dysplasia (BPD) at 36 weeks gestation in survivors. Subgroup analysis was conducted comparing STC to controls in infants < 29 weeks' gestation. The Cochrane risk of bias (ROB) tool was used and certainty of evidence (CoE) was rated according to GRADE. Results: Twenty-six RCTs of 3349 preterm infants, in which half of the studies had low risk of bias, were included. STC decreased the risk of BPD in survivors compared to controls (17 RCTs; N = 2408; relative risk (RR) = 0.66; 95% confidence interval (CI) 0.51 to 0.85; number needed to treat for an additional beneficial outcome (NNTB) = 13; CoE: moderate). In infants < 29 weeks' gestation, STC significantly reduced the risk of BPD compared to controls (6 RCTs, N = 980; RR 0.63; 95% CI 0.47 to 0.85; NNTB = 8; CoE: moderate). Conclusions: Compared to controls, STC may be a more efficacious and safe method of surfactant delivery in preterm infants with RDS, including infants < 29 weeks' gestation. [ABSTRACT FROM AUTHOR]

Mycoplasma hominis (M hominis) is a rare cause of neonatal bacterial meningitis. Treatment can be challenging because of M hominis' intrinsic antibiotic resistance and the difficulty in accessing antimicrobial susceptibility testing. In this report, we describe an extremely preterm male infant with seizures who had a subsequent diagnosis of M hominis meningitis. Because of severity of illness, doxycycline (4 mg/kg IV every 24 hours) and moxifloxacin (5 mg/kg IV every 24 hours) were started empirically. Repeat cerebrospinal fluid cultures were negative and showed decreasing pleiocytosis. Given the concentration-dependent killing of moxifloxacin and concern for endovascular infection from a concomitant cerebral venous sinus thrombosis, serum concentrations of moxifloxacin were obtained to estimate pharmacokinetic and pharmacodynamic parameters. These were compared to the targets described in other case reports of M hominis meningitis. The maximum serum concentration (Cmax) was 2.5 mg/L, volume of distribution was 2.2 L/kg, clearance was 0.18 L/kg/hr, terminal half-life was 8.6 hours, and area-under-the-concentration-time curve (AUC) was 28.1 mg•hr/L. Using the range of minimum inhibitory concentrations (MICs) reported in the literature, the estimated Cmax/MIC for this patient was 21 to 158 (target Cmax/MIC: >10) and AUC/MIC was 234 to 1757 (target AUC/MIC: =100). Doxycycline and moxifloxacin were continued for 6 weeks. No adverse events to moxifloxacin or doxycycline were observed in the NICU. This report describes the successful treatment of M hominis neonatal meningitis and adds to the knowledge of pharmacokinetic and pharmacodynamic parameters of moxifloxacin in neonates. Additional data will help to confirm the role for routine therapeutic drug monitoring of moxifloxacin in neonates. ABBREVIATIONS AUC, area under the concentration time curve; Cmax, maximum serum concentration; CSF, cerebrospinal fluid; IV, intravenous; MIC, minimum inhibitory concentration; NICU, neonatal intensive care unit; PHVD, posthemorrhagic ventricular dilation. [ABSTRACT FROM AUTHOR]

Objective: To describe the trend in costs over 10 years for tertiary-level neonatal care of infants born 220/7-286/7 weeks of gestation during an ongoing Canadian national quality improvement project.Study Design: Clinical characteristics, outcomes, and third-party payor costs for the tertiary neonatal care of infants born 220/7-286/7 weeks of gestation between the years 2010 and 2019 were analyzed from the Canadian Neonatal Network database. Costs were estimated using resource use data from the Canadian Neonatal Network and cost inputs from hospitals, physician billing, and administrative databases in Ontario, Canada. Cost estimates were adjusted to 2017 Canadian dollars (CAD). A generalized linear mixed-effects model with gamma regression was used to estimate trends in costs.Results: Between 2010 and 2019, the number of infants born <24 weeks of gestation increased from 4.4% to 7.7%. The average length of stay increased from 68 days to 75 days. Unadjusted average ± SD total costs per neonate were $120 717 ± $93 062 CAD in 2010 and $132 774 ± $93 161 CAD in 2019. After adjustment for year, center, and gestation, total costs and length of stay increased significantly, by $13 612 CAD (P < .01) and 8.1 days (P < .01) over 10 years, respectively; whereas costs accounting for LOS remained stable.Conclusions: The total costs and length of stay for infants 220/7-286/7 weeks of gestation have increased over the past decade in Canada during an ongoing national quality improvement initiative; however, there was an increase in the number and survival of neonates at the age of periviability. [ABSTRACT FROM AUTHOR]

Transplantation of human islets is an attractive alternative to daily insulin injections for patients with type 1 diabetes. However, the majority of islet recipients lose graft function within five years. Inflammation is a primary contributor to graft loss, and inhibiting pro-inflammatory cytokine activity can reverse inflammation mediated dysfunction of islet grafts. As mesenchymal stem cells (MSCs) possess numerous immunoregulatory properties, we hypothesized that MSCs could protect human islets from pro-inflammatory cytokines. Five hundred human islets were co-cultured with 0.5 or 1.0×106 human MSCs derived from bone marrow or pancreas for 24 hours followed by 48 hour exposure to interferon-c, tumor necrosis factor-α and interleukin 1β. Controls include islets cultured alone (± cytokines) and with human dermal fibroblasts (6 cytokines). For all conditions, glucose stimulated insulin secretion (GSIS), total islet cellular insulin content, islet b cell apoptosis, and potential cytoprotective factors secreted in the culture media were determined. Cytokine exposure disrupted human islet GSIS based on stimulation index and percentage insulin secretion. Conversely, culture with 1.0×106 bMSCs preserved GSIS from cytokine treated islets. Protective effects were not observed with fibroblasts, indicating that preservation of human islet GSIS after exposure to pro-inflammatory cytokines is MSC dependent. Islet b cell apoptosis was observed in the presence of cytokines; however, culture of bMSCs with islets prevented b cell apoptosis after cytokine treatment. Hepatocyte growth factor (HGF) as well as matrix metalloproteinases 2 and 9 were also identified as putative secreted cytoprotective factors; however, other secreted factors likely play a role in protection. This study, therefore, demonstrates that MSCs may be beneficial for islet engraftment by promoting cell survival and reduced inflammation. [ABSTRACT FROM AUTHOR]

Competing Interests: Competing interests: None declared.

Objective: To describe the trend in costs over 10 years for tertiary-level neonatal care of infants born 22 0/7 -28 6/7  weeks of gestation during an ongoing Canadian national quality improvement project., Study Design: Clinical characteristics, outcomes, and third-party payor costs for the tertiary neonatal care of infants born 22 0/7 -28 6/7  weeks of gestation between the years 2010 and 2019 were analyzed from the Canadian Neonatal Network database. Costs were estimated using resource use data from the Canadian Neonatal Network and cost inputs from hospitals, physician billing, and administrative databases in Ontario, Canada. Cost estimates were adjusted to 2017 Canadian dollars (CAD). A generalized linear mixed-effects model with gamma regression was used to estimate trends in costs., Results: Between 2010 and 2019, the number of infants born <24 weeks of gestation increased from 4.4% to 7.7%. The average length of stay increased from 68 days to 75 days. Unadjusted average ± SD total costs per neonate were $120 717 ± $93 062 CAD in 2010 and $132 774 ± $93 161 CAD in 2019. After adjustment for year, center, and gestation, total costs and length of stay increased significantly, by $13 612 CAD (P < .01) and 8.1 days (P < .01) over 10 years, respectively; whereas costs accounting for LOS remained stable., Conclusions: The total costs and length of stay for infants 22 0/7 -28 6/7  weeks of gestation have increased over the past decade in Canada during an ongoing national quality improvement initiative; however, there was an increase in the number and survival of neonates at the age of periviability., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aim: To minimize the expansion of pancreatic mesenchymal cells in vitro and confirm that β-cell progenitors reside within the pancreatic epithelium., Methods: Due to mesenchymal stem cell (MSC) expansion and overgrowth, progenitor cells within the pancreatic epithelium cannot be characterized in vitro, though β-cell dedifferentiation and expansion of MSC intermediates via epithelial-mesenchymal transition (EMT) may generate β-cell progenitors. Pancreatic epithelial cells from endocrine and non-endocrine tissue were expanded and differentiated in a novel pancreatic epithelial expansion medium supplemented with growth factors known to support epithelial cell growth (dexamethasone, epidermal growth factor, 3,5,3'-triiodo-l-thyronine, bovine brain extract). Cells were also infected with a single and dual lentiviral reporter prior to cell differentiation. Enhanced green fluorescent protein was controlled by the rat Insulin 1 promoter and the monomeric red fluorescent protein was controlled by the mouse PDX1 promoter. In combination with lentiviral tracing, cells expanded and differentiated in the pancreatic medium were characterized by flow cytometry (BD fluorescence activated cell sorting), immunostaining and real-time polymerase chain reaction (PCR) (7900HT Fast Realtime PCR System)., Results: In the presence of 10% serum MSCs rapidly expand in vitro while the epithelial cell population declines. The percentage of vimentin(+) cells increased from 22% ± 5.83% to 80.43% ± 3.24% (14 d) and 99.00% ± 0.0% (21 d), and the percentage of epithelial cells decreased from 74.71% ± 8.34% to 26.57% ± 9.75% (14 d) and 4.00% ± 1.53% (21 d), P < 0.01 for all time points. Our novel pancreatic epithelial expansion medium preserved the epithelial cell phenotype and minimized epithelial cell dedifferentiation and EMT. Cells expanded in our epithelial medium contained significantly less mesenchymal cells (vimentin(+)) compared to controls (44.87% ± 4.93% vs 95.67% ± 1.36%; P < 0.01). During cell differentiation lentiviral reporting demonstrated that, PDX1(+) and insulin(+) cells were localized within adherent epithelial cell aggregates compared to controls. Compared to starting islets differentiated cells had at least two fold higher gene expression of PDX1, insulin, PAX4 and RFX (P < 0.05)., Conclusion: PDX1(+) cells were confined to adherent epithelial cell aggregates and not vimentin(+) cells (mesenchymal), suggesting that EMT is not a mechanism for generating pancreatic progenitor cells.

Genetic screening of the breast and ovarian cancer susceptibility gene BRCA1 has uncovered a large number of variants of uncertain clinical significance. Here, we use biochemical and cell-based transcriptional assays to assess the structural and functional defects associated with a large set of 117 distinct BRCA1 missense variants within the essential BRCT domain of the BRCA1 protein that have been documented in individuals with a family history of breast or ovarian cancer. In the first method, we used limited proteolysis to assess the protein folding stability of each of the mutants compared with the wild-type. In the second method, we used a phosphopeptide pull-down assay to assess the ability of each of the variants to specifically interact with a peptide containing a pSer-X-X-Phe motif, a known functional target of the BRCA1 BRCT domain. Finally, we used transcriptional assays to assess the ability of each BRCT variant to act as a transcriptional activation domain in human cells. Through a correlation of the assay results with available family history and clinical data, we define limits to predict the disease risk associated with each variant. Forty-two of the variants show little effect on function and are likely to represent variants with little or no clinical significance; 50 display a clear functional effect and are likely to represent pathogenic variants; and the remaining 25 variants display intermediate activities. The excellent agreement between the structure/function effects of these mutations and available clinical data supports the notion that functional and structure information can be useful in the development of models to assess cancer risk.