State Implementation of Congregate Care Reforms for Children in Foster Care.

OBJECTIVES: The Family First Prevention Services Act (FFPSA) allows states to use federal Title IV-E funds to provide time-limited, clinically appropriate use of congregate care, including Qualified Residential Treatment Programs (QRTPs), for youth in foster care. October 1, 2021 marked the deadline for states to begin implementing these FFPSA congregate care reforms. From June to September 2022, we conducted a mixed-methods study to obtain a baseline understanding of implementation barriers, successes, and recommendations to inform congregate care policy and practice. METHODS: We fielded a national survey with state child welfare agency directors and conducted focus groups with youth with QRTP experiences, child welfare agency administrators, and QRTP executive leaders. We integrated a descriptive analysis of survey data with focus group themes to summarize state implementation progress. RESULTS: A total of 47 states (90%) responded to the survey. Most states reported ongoing congregate care reforms aligned with FFPSA, reducing the use of congregate care and increasing kinship foster care. QRTPs have become the primary congregate care setting. Top implementation barriers concerned workforce resource and capacity constraints, funding, and access to therapeutic foster care models and foster families. Focus group themes converged on the lack of tailored treatment, quality staff, coordinated aftercare, and a need for QRTP outcome evidence. CONCLUSIONS: Early implementation lessons of FFPSA congregate care reforms call for additional funding and technical assistance, oversight of congregate care, professionalization and investment in QRTP staff, youth advisory boards to promote youth-driven treatment, and performance- and outcome-based monitoring of QRTPs.

Prenatal diagnosis of meningomyelocele resolves as a mature cystic teratoma in the thoracolumbar region.

A mature cystic teratoma is a mass with heterogeneous appearance, consisting of adult tissue with two or three layers: endoderm, mesoderm, and ectoderm. It is a rare, benign transformation of somatic tissue most commonly found in the sacrococcygeal region and may resemble an uncomplicated spina bifida on prenatal ultrasonography. In this case report, we describe a female newborn with an extremely rare mature cystic teratoma in the thoracolumbar region. She presented prenatally with a preliminary diagnosis of meningomyelocele, diastematomyelia, and Chiari II malformation and a possible teratoma. However, a mass containing solid glandular tissues and bony calcifications approximately 3 × 4 cm in size was observed in the thoracolumbar region upon birth. During surgical resection, no nerve roots were found in the associated meningocele. The patient retained full lower body function postoperatively following surgical excision of the thecal sac and teratoma.

Abdominal Pseudoaneurysms in Patients With High-Grade Traumatic Injuries.

Utilization of CT scans in the work-up of trauma patients has led to increasing diagnosis of traumatic pseudoaneurysms (PSAs). While rare, PSAs have devastating consequences if ruptured. Evidence for the benefit of early detection of PSAs is lacking. The objective of this case series was to determine the incidence of solid organ PSAs after trauma. A retrospective chart review of patients with AAST grade 3-5 traumatic solid organ injuries was performed. 47 patients were identified with PSAs. PSAs were most common in the spleen. A CT finding of contrast blush or extravasation was found in 33 patients. 36 patients underwent embolization. 12 patients had an abdominal CTA prior to discharge. Re-admission was required for 3 patients. 1 patient presented with PSA rupture. During the study, there was no consistency in surveillance for PSAs. Future studies are needed to develop evidence-based practice guidelines for PSA surveillance in high risk populations.

Nevoid basal cell carcinoma syndrome: a case report and literature review.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is a rare genetic disorder associated with basal cell carcinomas (BCC), skeletal anomalies, and jaw cysts, and a number of ocular abnormalities. We describe a case of a 12-year-old boy diagnosed with NBCCS found to have several ophthalmic manifestations including a myelinated retinal nerve fiber. We conducted a literature review targeting the ocular and systemic manifestations of NBCCS, with a focus on the ophthalmic findings that have not been well characterized. MATERIALS AND METHODS: We conducted a literature search from 1960 to 2021 utilizing specific keywords and criteria and excluded non-clinical articles. A total of 46 articles were ultimately used for the literature review. RESULTS: In NBCCS, BCCs typically present before the age of 30 and gradually become numerous. Certain ocular features, less common in the general population, are much more common with NBCCS. Depending on the study, prevalence of these features in patients with NBCCS ranges from 26-80% for hypertelorism and 7-36% for myelinated retinal nerve fiber layer. Prevalence of nystagmus in patients with NBCCS was found to be approximately 6%. Systemic findings such as bilamellar calcification of the falx cerebri, palmar pits, and odontogenic keratocysts (OKCs) are also prevalent. CONCLUSION: NBCCS may affect numerous organ systems, and thus requires a multidisciplinary team to manage. BCCs and jaw cysts are commonly occurring clinical features that have various surgical excisional options. The ocular anomalies of NBCCS are individually rare, and certain anomalies may present in the amblyogenic period of development and contribute to visual impairment.

Analysis of Pediatric Dog Bite Injuries at a Level 1 Trauma Center Over 10 Years.

BACKGROUND: Dog bite injuries cause significant preventable patient morbidity and health care expenditure in children. This study aimed to characterize the patient and healthcare burden related to pediatric dog bite injuries at a level 1 trauma center. METHODS: This is a retrospective review of 356 pediatric patients who presented to Virginia Commonwealth University Pediatric Emergency Department between July 2007 and August 2017 after sustaining dog bite injuries. Demographic information, injury details, management, outcomes, and financial information were analyzed. RESULTS: Most pediatric dog bite injuries afflicted male children (55.6%), ages 6 to 12 years (45.7%), by a household dog (36.2%). The most common offending breed was a pit bull or pit bull mix (53.0%). Infants and grade schoolers were more likely to sustain bites to the head/face (P = 0.001). Usual management consisted of primary repair (75.9%), whereas approximately 25% of the patients required advanced reconstructive techniques. Most patients healed uneventfully, but prolonged antibiotics, additional wound care, or procedures were necessary in 8.4% of the patients. Hospital charges per patient averaged US $8830.70 and tended to be higher in the younger age groups. Insurance status was statistically associated with use of conscious sedation, surgical consult placement, and surgical repair. CONCLUSIONS: Although most pediatric dog bite injuries in this study healed uneventfully from primary management in the emergency department, 25% required additional interventions. Furthermore, patient care for these injuries was associated with significant but potentially avoidable personal and financial burden to families. Our data reflect a need for safety education on animal care, behavior, and interaction.

Targeting effector pathways in RAC1P29S-driven malignant melanoma.

Malignant melanoma is characterized by mutations in a number of driver genes, most notably BRAF and NRAS. Recent genomic analyses revealed that 4-9% of sun-exposed melanomas bear activating mutations in RAC1, which encodes a small GTPase that is known to play key roles in cell proliferation, survival, and migration. The RAC1 protein activates several effector pathways, including Group A p21-activated kinases (PAKs), phosphoinositol-3-kinases (PI3Ks), in particular the beta isoform, and the serum-response factor/myocardin-related transcription factor (SRF/MRTF). Having previously shown that inhibition of Group A PAKs impedes oncogenic signalling from RAC1P29S, we here extend this analysis to examine the roles of PI3Ks and SRF/MRTF in melanocytes and/or in a zebrafish model. We demonstrate that a selective Group A PAK inhibitor (Frax-1036), a pan-PI3K (BKM120), and two PI3Kß inhibitors (TGX221, GSK2636771) impede the growth of melanoma cells driven by mutant RAC1 but not by mutant BRAF, while other PI3K selective inhibitors, including PI3Kα, δ and γ, are less effective. Using these compounds as well as an SRF/MRTF inhibitor (CCG-203,971), we observed similar results in vivo, using embryonic zebrafish development as a readout. These results suggest that targeting Group A PAKs, PI3Kß, and/or SRF/MRTF represent a promising approach to suppress RAC1 signalling in malignant melanoma.

Discordant Effects of Putative Lysine Acetyltransferase Inhibitors in Biochemical and Living Systems.

Lysine acetyltransferases (KATs) are exquisitely fine-tuned to target specific lysine residues on many proteins, including histones, with aberrant acetylation at distinct lysines implicated in different pathologies. However, researchers face a lack of molecular tools to probe the importance of site-specific acetylation events in vivo. Because of this, there can be a disconnect between the predicted in silico or in vitro effects of a drug and the actual observable in vivo response. We have previously reported on how an in vitro biochemical analysis of the site-specific effects of the compound C646 in combination with the KAT p300 can accurately predict changes in histone acetylation induced by the same compound in cells. Here, we build on this effort by further analyzing a number of reported p300 modulators, while also extending the analysis to correlate the effects of these drugs to developmental and phenotypical changes, utilizing cellular and zebrafish model systems. While this study demonstrates the utility of biochemical models as a starting point for predicting in vivo activity of multi-site targeting KATs, it also highlights the need for the development of new enzyme inhibitors that are more specific to the regulation of KAT activity in vivo.

Expanding the phenotype for the recurrent p.Ala391Glu variant in FGFR3: Beyond crouzon syndrome and acanthosis nigricans.

BACKGROUND: Craniosynostosis, or premature fusion of the skull sutures, is a group of disorders that can present in isolation (nonsyndromic) or be associated with other anomalies (syndromic). Delineation of syndromic craniosynostosis is confounded due to phenotypic overlap, variable expression as well as molecular heterogeneity. We report on an infant who presented at birth with multisuture synostosis, turribrachycephaly, midface hypoplasia, beaked nose, low set ears, a high palate and short squat appearing thumbs, and great toes without deviation. The additional MRI findings of choanal stenosis and a Chiari I malformation suggested a diagnosis of Pfeiffer syndrome. First tier molecular testing did not reveal a pathogenic variant. METHODS: Whole exome sequencing on DNA samples from the proband and her unaffected parents was utilized to delineate the variant causative for the Pfeiffer syndrome diagnosis. RESULTS: On whole exome sequencing, a de novo NM_000142.4:c.1428C>A missense variant causing a p.Ala391Glu amino acid change in FGFR3 has been identified. The p.Ala391Glu change has been predominantly identified in patients with Crouzon syndrome with acanthosis nigricans. CONCLUSIONS: This finding illustrates the first reported case of a child with an overlap with Pfeiffer syndrome to have the p.Ala391Glu variant.

Genomic analyses in African populations identify novel risk loci for cleft palate.

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.

The Use of a Novel Local Flap Trainer in Plastic Surgery Education.

With the limitations of work hour restrictions and legal liability surgical resident's operative experience is declining. We sought to find other methods of training using tactile surgical simulations for plastic surgery. With the collaborative efforts of a local artist, a local flap trainer was designed to simulate the natural properties, layers, and interaction between layers of tissue. A session was held with Plastic Surgery faculty, residents, and students to review and practice local flaps using the trainer. Afterward, the participants filled out a survey evaluating the simulated skin and tissue model and the effectiveness of the class as a teaching model. The survey given had multiple questions asking the participant to provide a ranking from 1 to 10. The results show that the class utilizing the new suture pad was an effective teaching tool with an average score of 9.56. The suture pad was given a score of 6.77 for simulating realistic skin. Overall, the group rated increased understanding and confidence of local flaps after the class. Surgical skill simulations are becoming increasingly more important with the decline of resident operative experience. There are limited options for surgical simulations that provide a realistic experience. We designed a suture pad that is effective at simulating human tissue. The surveys show that using this suture pad in flap workshops provides a valuable teaching tool.

Microvascular Replantation Following Facial Dog Bites in Children: Systematic Review and Management Algorithm.

BACKGROUND: Pediatric dog bite injuries account for 1% of emergency department visits per year and represent an underrecognized and underreported public health problem. Reconstructive surgery is frequently utilized, and in the most extreme injuries, microvascular replantation may be considered. We sought to systematically review the available literature on microvascular replantation after facial dog bite injuries in children, with particular attention to perioperative morbidity and long-term follow-up. METHODS: We reviewed a case of microvascular replantation after a facial dog bite injury in a child from our own institution and conducted a systematic literature search to identify other similar reports. Clinical variables were collected from the reported cases, and descriptive statistics were calculated. A management algorithm was developed from the reviewed published experience. RESULTS: We report the youngest child to date in the literature to undergo replantation after a facial dog bite injury. Nineteen other cases were found involving children aged 18 months to 17 years, with follow-up ranging from 2 weeks to 28 years. Anastomosis techniques varied considerably and included both an artery and vein in only 9 (47%) of 19 cases. Venous congestion was nearly universal, and multimodal techniques were used until native venous outflow was reestablished. Blood transfusion was common, but intensive care unit utilization was not frequently reported. Long-term outcomes were excellent, with growth of the replanted part and recovery of function; however, minor revision procedures were common. CONCLUSIONS: Microvascular replantation following facial dog bite amputation injuries in the pediatric population is the ultimate step in the reconstructive ladder. Strong consideration should be given to microvascular exploration with involvement of large or whole segments of the lip, nose, or ear; however, parents should be counseled extensively regarding the known morbidity of replantation surgery. With meticulous surgical technique and careful postoperative care, replantation after facial dog bite amputation injuries may successfully achieve dramatic and lasting results for pediatric patients.

Disruption of Thrombocyte and T Lymphocyte Development by a Mutation in ARPC1B.

Regulation of the actin cytoskeleton is crucial for normal development and function of the immune system, as evidenced by the severe immune abnormalities exhibited by patients bearing inactivating mutations in the Wiskott-Aldrich syndrome protein (WASP), a key regulator of actin dynamics. WASP exerts its effects on actin dynamics through a multisubunit complex termed Arp2/3. Despite the critical role played by Arp2/3 as an effector of WASP-mediated control over actin polymerization, mutations in protein components of the Arp2/3 complex had not previously been identified as a cause of immunodeficiency. Here, we describe two brothers with hematopoietic and immunologic symptoms reminiscent of Wiskott-Aldrich syndrome (WAS). However, these patients lacked mutations in any of the genes previously associated with WAS. Whole-exome sequencing revealed a homozygous 2 bp deletion, n.c.G623DEL-TC (p.V208VfsX20), in Arp2/3 complex component ARPC1B that causes a frame shift resulting in premature termination. Modeling of the disease in zebrafish revealed that ARPC1B plays a critical role in supporting T cell and thrombocyte development. Moreover, the defects in development caused by ARPC1B loss could be rescued by the intact human ARPC1B ortholog, but not by the p.V208VfsX20 variant identified in the patients. Moreover, we found that the expression of ARPC1B is restricted to hematopoietic cells, potentially explaining why a mutation in ARPC1B has now been observed as a cause of WAS, whereas mutations in other, more widely expressed, components of the Arp2/3 complex have not been observed.

Zebrafish B Cell Development without a Pre-B Cell Stage, Revealed by CD79 Fluorescence Reporter Transgenes.

CD79a and CD79b proteins associate with Ig receptors as integral signaling components of the B cell Ag receptor complex. To study B cell development in zebrafish, we isolated orthologs of these genes and performed in situ hybridization, finding that their expression colocalized with IgH-µ in the kidney, which is the site of B cell development. CD79 transgenic lines were made by linking the promoter and upstream regulatory segments of CD79a and CD79b to enhanced GFP to identify B cells, as demonstrated by PCR analysis of IgH-µ expression in sorted cells. We crossed these CD79-GFP lines to a recombination activating gene (Rag)2:mCherry transgenic line to identify B cell development stages in kidney marrow. Initiation of CD79:GFP expression in Rag2:mCherry+ cells and the timing of Ig H and L chain expression revealed simultaneous expression of both IgH-µ- and IgL-κ-chains, without progressing through the stage of IgH-µ-chain alone. Rag2:mCherry+ cells without CD79:GFP showed the highest Rag1 and Rag2 mRNAs compared with CD79a and CD79b:GFP+ B cells, which showed strongly reduced Rag mRNAs. Thus, B cell development in zebrafish does not go through a Raghi CD79+IgH-µ+ pre-B cell stage, different from mammals. After the generation of CD79:GFP+ B cells, decreased CD79 expression occurred upon differentiation to Ig secretion, as detected by alteration from membrane to secreted IgH-µ exon usage, similar to in mammals. This confirmed a conserved role for CD79 in B cell development and differentiation, without the requirement of a pre-B cell stage in zebrafish.

Ribosomal Proteins Rpl22 and Rpl22l1 Control Morphogenesis by Regulating Pre-mRNA Splicing.

Most ribosomal proteins (RP) are regarded as essential, static components that contribute only to ribosome biogenesis and protein synthesis. However, emerging evidence suggests that RNA-binding RP are dynamic and can influence cellular processes by performing "extraribosomal," regulatory functions involving binding to select critical target mRNAs. We report here that the RP, Rpl22, and its highly homologous paralog Rpl22-Like1 (Rpl22l1 or Like1) play critical, extraribosomal roles in embryogenesis. Indeed, they antagonistically control morphogenesis through developmentally regulated localization to the nucleus, where they modulate splicing of the pre-mRNA encoding smad2, an essential transcriptional effector of Nodal/TGF-ß signaling. During gastrulation, Rpl22 binds to intronic sequences of smad2 pre-mRNA and induces exon 9 skipping in cooperation with hnRNP-A1. This action is opposed by its paralog, Like1, which promotes exon 9 inclusion in the mature transcript. The nuclear roles of these RP in controlling morphogenesis represent a fundamentally different and paradigm-shifting mode of action for RP.

Neonatal Soft Tissue Reconstruction Using a Bioengineered Skin Substitute.

Total parenteral nutrition (TPN) can be a lifesaving intervention for premature neonates and it is often delivered through peripheral access in this unique population. However, extravasation and tissue damage can result. Current literature lacks strong evidence regarding the treatment and reconstruction of such injuries in this age group. The authors present a patient with a 30-week gestational age premature newborn whom suffered an extravasation injury with peripherally administered TPN leading to full thickness skin and soft tissue necrosis of the dorsum of the right hand. This was serially debrided and ultimately repaired using Apligraf (Graftskin, Living Skin Equivalent, LSE; Organogenesis Inc, Canton, MA), which rapidly facilitated secondary healing.

Hypophosphatemic rickets and craniosynostosis: a multicenter case series.

OBJECTIVE This study examines a series of patients with hypophosphatemic rickets and craniosynostosis to characterize the clinical course and associated craniofacial anomalies. METHODS A 20-year retrospective review identified patients with hypophosphatemic rickets and secondary craniosynostosis at 3 major craniofacial centers. Parameters examined included sex, age at diagnosis of head shape anomaly, affected sutures, etiology of rickets, presenting symptoms, number and type of surgical interventions, and associated diagnoses. A review of the literature was performed to optimize treatment recommendations. RESULTS Ten patients were identified (8 males, 2 females). Age at presentation ranged from 1 to 9 years. The most commonly affected suture was the sagittal (6/10 patients). Etiologies included antacid-induced rickets, autosomal dominant hypophosphatemic rickets, and X-linked hypophosphatemic (XLH) rickets. Nine patients had undergone at least 1 cranial vault remodeling (CVR) surgery. Three patients underwent subsequent surgeries in later years. Four patients underwent formal intracranial pressure (ICP) monitoring, 3 of which revealed elevated ICP. Three patients were diagnosed with a Chiari Type I malformation. CONCLUSIONS Secondary craniosynostosis develops postnatally due to metabolic or mechanical factors. The most common metabolic cause is hypophosphatemic rickets, which has a variety of etiologies. Head shape changes occur later and with a more heterogeneous presentation compared with that of primary craniosynostosis. CVR may be required to prevent or relieve elevated ICP and abnormalities of the cranial vault. Children with hypophosphatemic rickets who develop head shape abnormalities should be promptly referred to a craniofacial specialist.

Atypical Spitz Nevi: A Case Report and Review of the Literature.

A case of atypical ("pagetoid") compound Spitz nevus on the face of a 2-year-old girl is reported with a review of the literature. The nevus was composed of broad but laterally demarcated compound proliferation of enlarged fusiform and epithelioid melanocytes, with florid pagetoid scatter above the junction. Immunohistochemical analyses revealed the Ki-67 proliferation index to be relatively low. Given the histomorphological overlap with melanoma, an array-based comparative genomic hybridization approach revealed a subthreshold gain in chromosome 1q and gain in distal chromosome 17q, with no other associated chromosomal gains or losses. These molecular aberrations suggested a partially transformed tumor, without adequate evidence for a molecular diagnosis of melanoma. Because of the diagnostic dilemma posed by these lesions, recent research has focused on molecular alterations that may help differentiate Spitz tumors from malignant melanomas.