Multi-disciplinary care in patients with complex pediatric general and thoracic surgical pathology: lessons learned from a 20-year experience.

PURPOSE: Complex pediatric surgery patients with thoracic tumors invading the mediastinum and infradiaphragmatic tumors extending into the chest are at risk for surgical morbidity and mortality if the patient's care is not coordinated. We sought to identify areas of focus when managing these patients to improve care. METHODS: A 20-year, retrospective study of pediatric patients with complex surgical pathology was performed. Demographic data, pre-operative characteristics, intraoperative data, complications, and outcomes data were collected. Three index cases were highlighted to provide granularity in patient management. RESULTS: Twenty-six patients were identified. Common pathology included mediastinal teratomas, foregut duplications, advanced Wilms tumors, hepatoblastoma, and lung masses. All cases were performed in a multidisciplinary fashion. All cases were done with pediatric cardiothoracic surgery and three cases (11.5%) required pediatric otolaryngology. Eight patients (30.7%) required cardiopulmonary bypass. Operative and 30-day mortality was zero. CONCLUSIONS: Management of complex pediatric surgical patients requires a multidisciplinary approach throughout the patient's hospital course. This multidisciplinary team should meet in advance of a patient's procedure to create a customized care plan that may include pre-operative optimization. At the time of their procedure, all necessary and emergency equipment should available. This approach improves patient safety and has resulted in excellent outcomes. LEVEL OF EVIDENCE: IV.

Estimates of Treatable Deaths Within the First 20 Years of Life from Scaling Up Surgical Care at First-Level Hospitals in Low- and Middle-Income Countries.

BACKGROUND: Surgical care is an important, yet often neglected component of child health in low- and middle-income countries (LMICs). This study examines the potential impact of scaling up surgical care at first-level hospitals in LMICs within the first 20 years of life. METHODS: Epidemiological data from the global burden of disease 2019 Study and a counterfactual method developed for the disease control priorities; 3rd Edition were used to estimate the number of treatable deaths in the under 20 year age group if surgical care could be scaled up at first-level hospitals. Our model included three digestive diseases, four maternal and neonatal conditions, and seven common traumatic injuries. RESULTS: An estimated 314,609 (95% UI, 239,619-402,005) deaths per year in the under 20 year age group could be averted if surgical care were scaled up at first-level hospitals in LMICs. Most of the treatable deaths are in the under-5 year age group (80.9%) and relates to improved obstetrical care and its effect on reducing neonatal encephalopathy due to birth asphyxia and trauma. Injuries are the leading cause of treatable deaths after age 5 years. Sixty-one percent of the treatable deaths occur in lower middle-income countries. Overall, scaling up surgical care at first-level hospitals could avert 5·1% of the total deaths in children and adolescents under 20 years of age in LMICs per year. CONCLUSIONS: Improving the capacity of surgical services at first-level hospitals in LMICs has the potential to avert many deaths within the first 20 years of life.

Transformation of Ritonavir Nanocrystal Suspensions into a Redispersible Drug Product via Vacuum Drum Drying.

The present study explored vacuum drum drying (VDD) as potential drying technique for the solidification of crystalline ritonavir nanosuspensions prepared by wet-ball milling. In detail, the impact of drying protectants (mannitol, lactose, trehalose) added to the ritonavir nanosuspension was assessed in dependence of the drum temperature with respect to processibility via VDD, resulting intermediate powder properties, remaining nanoparticulate redispersibility and crystallinity. A clear impact of the glass transition temperature (Tg) of the drying protectant on the redispersibility/crystallinity of the VDD intermediate was observed. Increased Tg of the drying protectant was associated with improved redispersibility/crystallinity at a defined drum temperature. Consequently, the high Tg-substance trehalose and lactose showed a better performance than mannitol at higher drum temperatures. However, the processability and related powder properties were not in accordance with this observation. Mannitol containing formulations showed superior processibility to those containing trehalose/lactose. Moreover, the impact of the tableting and encapsulation process on the redispersibility of the VDD intermediate was studied for a selected formulation. Neither process demonstrated a negative impact on redispersibility. In conclusion, vacuum drum drying is a promising drying technique for the solidification of nanosuspensions to result in dried powder still containing ritonavir nanoparticles while demonstrating acceptable to good downstream processibility to tablets/capsules.

Neuroprotective effect of placenta-derived mesenchymal stromal cells: role of exosomes.

We have established early-gestation chorionic villus-derived placenta mesenchymal stromal cells (PMSCs) as a potential treatment for spina bifida (SB), a neural tube defect. Our preclinical studies demonstrated that PMSCs have the potential to cure hind limb paralysis in the fetal lamb model of SB via a paracrine mechanism. PMSCs exhibit neuroprotective function by increasing cell number and neurites, as shown by indirect coculture and direct addition of PMSC-conditioned medium to the staurosporine-induced apoptotic human neuroblastoma cell line, SH-SY5Y. PMSC-conditioned medium suppressed caspase activity in apoptotic SH-SY5Y cells, suggesting that PMSC secretome contributes to neuronal survival after injury. As a part of PMSC secretome, PMSC exosomes were isolated and extensively characterized; their addition to apoptotic SH-SY5Y cells mediated an increase in neurites, suggesting that they exhibit neuroprotective function. Proteomic and RNA sequencing analysis revealed that PMSC exosomes contain several proteins and RNAs involved in neuronal survival and development. Galectin 1 was highly expressed on the surface of PMSCs and PMSC exosomes. Preincubation of exosomes with anti-galectin 1 antibody decreased their neuroprotective effect, suggesting that PMSC exosomes likely impart their effect via binding of galectin 1 to cells. Future studies will include in-depth analyses of the role of PMSC exosomes on neuroprotection and their clinical applications.-Kumar, P., Becker, J. C., Gao, K., Carney, R. P., Lankford, L., Keller, B. A., Herout, K., Lam, K. S., Farmer, D. L., Wang, A. Neuroprotective effect of placenta-derived mesenchymal stromal cells: role of exosomes.

Surviving Lambs with Myelomeningocele Repaired in utero with Placental Mesenchymal Stromal Cells for 6 Months: A Pilot Study.

BACKGROUND: Fetal repair of myelomeningocele (MMC) with placental mesenchymal stromal cells (PMSCs) rescues ambulation in the ovine model up to 48 h postnatally. Outcomes past 48 h are unknown as MMC lambs have not been survived past this timepoint. OBJECTIVE: We aimed to survive lambs for 6 months following the fetal repair of MMC with PMSCs. METHODS: Fetal MMC lambs were repaired with PMSCs. Lambs received either no additional treatment or postnatal bracing and physical therapy (B/PT). Motor function was assessed with the sheep locomotor rating (SLR). Lambs with an SLR of 15 at birth were survived for 6 months or until a decline in SLR less than 15, whichever came first. All lambs underwent a perimortem MRI. RESULTS: The lambs with no postnatal treatment (n = 2) had SLR declines to 7 and 13 at 29 and 65 days, respectively, and were euthanized. These lambs had a spinal angulation of 57° and 47°, respectively. The B/PT lamb (n = 1) survived for 6 months with a sustained SLR of 15 and a lumbar angulation of 42°. CONCLUSION: Postnatal physical therapy and bracing counteracted the inherent morbidity of the absent paraspinal muscles in the ovine MMC model allowing for survival and maintenance of rescued motor function of the prenatally treated lamb up to 6 months.

A Decade of Experience with the Ovine Model of Myelomeningocele: Risk Factors for Fetal Loss.

INTRODUCTION: The ovine model is the gold standard large animal model of myelomeningocele (MMC); however, it has a high rate of fetal loss. We reviewed our experience with the model to determine risk factors for fetal loss. METHODS: We performed a retrospective review from 2009 to 2018 to identify operative factors associated with fetal loss (early fetal demise, abortion, or stillbirth). Operative risk factors included gestational age at operation, operative time, reduction of multiple gestations, amount of replaced amniotic fluid, ambient temperature, and method of delivery. RESULTS: MMC defects were created in 232 lambs with an overall survival rate of 43%. Of the 128 fetuses that died, 53 (42%) had demise prior to repair, 61 (48%) aborted, and 14 (11%) were stillborn. Selective reduction of multiple gestations in the same uterine horn was associated with increased fetal demise (OR 3.03 [95% CI 1.29-7.05], p = 0.01). Later gestational age at MMC repair and Cesarean delivery were associated with decreased abortion/stillbirth (OR 0.90 [95% CI 0.83-0.90], p = 0.03, and OR 0.37 [95% CI 0.16-0.31], p = 0.02), respectively. CONCLUSION: Avoiding selective reduction, repairing MMC later in gestation, and performing Cesarean delivery decreases the rate of fetal loss in the ovine MMC model.

Genome-Wide Association and Trans-ethnic Meta-Analysis for Advanced Diabetic Kidney Disease: Family Investigation of Nephropathy and Diabetes (FIND).

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

Age Does Matter: A Pilot Comparison of Placenta-Derived Stromal Cells for in utero Repair of Myelomeningocele Using a Lamb Model.

INTRODUCTION: Fetal amniotic membranes (FM) have been shown to preserve spinal cord histology in the fetal sheep model of myelomeningocele (MMC). This study compares the effectiveness of placenta-derived mesenchymal stromal cells (PMSCs) from early-gestation versus term-gestation placenta to augment FM repair to improve distal motor function in a sheep model. METHODS: Fetal lambs (n = 4) underwent surgical MMC creation followed by repair with FM patch with term-gestation PMSCs (n = 1), FM with early-gestation PMSCs (n = 1), FM only (n = 1), and skin closure only (n = 1). Histopathology and motor assessment was performed. RESULTS: Histopathologic analysis demonstrated increased preservation of spinal cord architecture and large neurons in the lamb repaired with early-gestation cells compared to all others. Lambs repaired with skin closure only, FM alone, and term-gestation PMSCs exhibited extremely limited distal motor function; the lamb repaired with early-gestation PMSCs was capable of normal ambulation. DISCUSSION: This pilot study is the first in vivo comparison of different gestational-age placenta-derived stromal cells for repair in the fetal sheep MMC model. The preservation of large neurons and markedly improved motor function in the lamb repaired with early-gestation cells suggest that early-gestation placental stromal cells may exhibit unique properties that augment in utero MMC repair to improve paralysis.

New susceptibility loci associated with kidney disease in type 1 diabetes.

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genome-wide association studies (GWAS) of T1D DN comprising ~2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2 × 10(-8)) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0 × 10(-9)). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-ß1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1 × 10(-7)), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.

Integrative biology identifies shared transcriptional networks in CKD.

A previous meta-analysis of genome-wide association data by the Cohorts for Heart and Aging Research in Genomic Epidemiology and CKDGen consortia identified 16 loci associated with eGFR. To define how each of these single-nucleotide polymorphisms (SNPs) could affect renal function, we integrated GFR-associated loci with regulatory pathways, producing a molecular map of CKD. In kidney biopsy specimens from 157 European subjects representing nine different CKDs, renal transcript levels for 18 genes in proximity to the SNPs significantly correlated with GFR. These 18 genes were mapped into their biologic context by testing coregulated transcripts for enriched pathways. A network of 97 pathways linked by shared genes was constructed and characterized. Of these pathways, 56 pathways were reported previously to be associated with CKD; 41 pathways without prior association with CKD were ranked on the basis of the number of candidate genes connected to the respective pathways. All pathways aggregated into a network of two main clusters comprising inflammation- and metabolism-related pathways, with the NRF2-mediated oxidative stress response pathway serving as the hub between the two clusters. In all, 78 pathways and 95% of the connections among those pathways were verified in an independent North American biopsy cohort. Disease-specific analyses showed that most pathways are shared between sets of three diseases, with closest interconnection between lupus nephritis, IgA nephritis, and diabetic nephropathy. Taken together, the network integrates candidate genes from genome-wide association studies into their functional context, revealing interactions and defining established and novel biologic mechanisms of renal impairment in renal diseases.

Transformation of ABT-199 Nanocrystal Suspensions into a Redispersible Drug Product-Impact of Vacuum Drum Drying, Spray Drying and Tableting on Re-Nanodispersibility.

The present study compared vacuum drum drying (VDD) and conventional spray drying (SD) for solidifying crystalline ABT-199 nanosuspensions into redispersible oral drug products. The aim was to optimize formulation compositions and process conditions to maintain nanoparticle size after tablet redispersion. The impact of drug load (22%, 33%, 44%) and type of drying protectant (mannitol, mannitol/trehalose mix (1:1), trehalose) on redispersibility and material powder properties were investigated. Moreover, compression analysis was performed assessing the influence of compaction pressure on primary nanocrystal redispersibility and tablet disintegration. Higher drug loads and lower drying protectant levels resulted in particle growth, confirming a drug load dependence on redispersibility behavior. Notably, all drying protectants showed similar protection properties at properly chosen drying process parameters (Tg-dependent), except when VDD was used for mannitol formulations. Differences between the applied drying processes were observed in terms of downstream processing and tabletability: mannitol-containing formulations solidified via VDD showed an improved processability compared to formulations with trehalose. In conclusion, VDD is a promising drying technique that offers advantageous downstream processability compared to SD and represents an attractive novel processing technology for the pharmaceutical industry. As demonstrated in the present study, VDD combines higher yields with a leaner manufacturing process flow. The improved bulk properties provide enhanced tabletability and enable direct compression.

Sex-specific role of high-fat diet and stress on behavior, energy metabolism, and the ventromedial hypothalamus.

BACKGROUND: Scientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contribute to metabolic dysregulation in both males and females. Our study aimed to investigate the combined effects of high-fat diet (HFD) induced obesity and repeated stress on fear-related behaviors, metabolic, immune, and hypothalamic outcomes in male and female mice. METHODS: To investigate this, we used a highly reliable rodent behavioral model that faithfully recapitulates key aspects of post-traumatic stress disorder (PTSD)-like fear. We subjected mice to footshock stressor followed by a weekly singular footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. At weeks 10 and 14 we conducted glucose tolerance and insulin sensitivity measurements. Additionally, we placed the mice in metabolic chambers to perform indirect calorimetric measurements. Finally, we collected brain and peripheral tissues for cellular analysis. RESULTS: We observed that HFD-induced obesity disrupted fear memory extinction, increased glucose intolerance, and affected energy expenditure specifically in male mice. Conversely, female mice on HFD exhibited reduced respiratory exchange ratio (RER), and a significant defect in glucose tolerance only when subjected to repeated stress. Furthermore, the combination of repeated stress and HFD led to sex-specific alterations in proinflammatory markers and hematopoietic stem cells across various peripheral metabolic tissues. Single-nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus (VMH) revealed microglial activation in female mice on HFD, while male mice on HFD exhibited astrocytic activation under repeated stress. CONCLUSIONS: Overall, our findings provide insights into complex interplay between repeated stress, high-fat diet regimen, and their cumulative effects on health, including their potential contribution to the development of PTSD-like stress and metabolic dysfunctions, emphasizing the need for further research to fully understand these interconnected pathways and their implications for health.

In our study, we attempted to investigate how the combination of diet, stress, and sex can affect various aspects of health in mice. Specifically, we aimed to elucidate the neurobiology of underlying stress and metabolic dysfunction with a focus on sex-specific differences. We recognize that stress and metabolic disorders often co-occur and exhibit distinct patterns between sexes. In the present study, we observed that male mice fed a high-fat diet exhibited an inability to extinguish fear memory, mirroring a hallmark symptom observed in PTSD patients. We also observed sex-specific differences in metabolic and immune function in response to the diet and stress challenge. We uncovered that both repeated stress and a HFD can induce alterations in the quantity and types of immune cells present in various peripheral tissues, suggesting potential pathways through which metabolic diseases may develop. Our investigation further revealed that the ventromedial hypothalamus, responsible for regulating metabolism and stress behavior, exhibited distinct transcriptomic activity patterns in males and females. These findings shed light on the complex connections between high fat diet, stress levels, and overall health, emphasizing the importance of continued research in this area.

Evaluating the Benefits of Ventriculostomy Compared to Intracranial Pressure Monitoring for Severe Pediatric Traumatic Brain Injury.

BACKGROUND: In this study, we compared outcomes between intracranial pressure monitoring (ICP) only versus ventriculostomy (VT) using a nationwide database of pediatric trauma patients. METHODS: Pediatric patients (<18 years) with severe blunt TBI who underwent ICP monitoring with or without VT were identified from the 2017-2021 ACS Trauma Quality Programs. We excluded patients who experienced death or craniotomy/craniectomy within 48 h. The primary outcome was discharge disposition. Secondary outcomes were subsequent intracranial surgery, length of stay (LOS), and infectious complications. Competing risks survival analysis was used to evaluate the multivariable association between ICP vs. VT and outcomes. RESULTS: Of 1719 eligible patients, 65.9% were male and 54.1% had VT. Between the ICP and VT groups, there were no differences in mean age (11.4 vs. 11.0 years, p = 0.145), injury severity score (30.9 vs. 30.9, p = 0.937), or median GCS (3 vs. 3, p = 0.120). Multivariable analysis showed a robust association between VT and discharge home (compared to rehabilitation center; sHR 0.85, 95% CI 0.74-0.97, p = 0.017). VT use was not associated with increased mortality compared to ICP (p = 0.342). Finally, VT patients had longer median LOS (20.5 vs. 18.0 days, p < 0.001) but there was no difference in subsequent craniotomy/craniectomy (8.6 vs. 6.5%, p = 0.096) or infectious complications (1.2 vs. 0.9%, p = 0.549). CONCLUSION: VT was associated with greater discharge to home. Although VT patients had a greater LOS, the risk for other secondary outcomes did not vary, suggesting that VT may have benefits for the treatment of severe TBI with respect to discharge disposition. LEVEL OF EVIDENCE: III.

Up and over: Consequences of raising the United States-Mexico border wall height.

OBJECTIVES: San Diego County's geographic location lends a unique demographic of migrant patients injured by falls at the United States-Mexico border. To prevent migrant crossings, a 2017 Executive Order allocated funds to increase the southern California border wall height from 10 ft to 30 ft, which was completed in December 2019. We hypothesized that the elevated border wall height is associated with increased major trauma, resource utilization, and health care costs. METHODS: Retrospective trauma registry review of border wall falls was performed by the two Level I trauma centers that admit border fall patients from the southern California border from January 2016 to June 2022. Patients were assigned to either "pre-2020" or "post-2020" subgroups based upon timing of completion of the heightened border wall. Total number of admissions, operating room utilization, hospital charges, and hospital costs were compared. RESULTS: Injuries from border wall falls grew 967% from 2016 to 2021 (39 vs. 377 admissions); this percentage is expected to be supplanted in 2022. When comparing the two subgroups, operating room utilization (175 vs. 734 total operations) and median hospital charges per patient ($95,229 vs. $168,795) have risen dramatically over the same time period. Hospital costs increased 636% in the post-2020 subgroup ($11,351,216 versus $72,172,123). The majority (97%) of these patients are uninsured at admission, with costs largely subsidized by federal government entities (57%) or through state Medicaid enrollment postadmission (31%). CONCLUSION: The increased height of the United States-Mexico border wall has resulted in record numbers of injured migrant patients, placing novel financial and resource burdens on already stressed trauma systems. To address this public health crisis, legislators and health care providers must conduct collaborative, apolitical discussions regarding the border wall's efficacy as a means of deterrence and its impact on traumatic injury and disability. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Evaluating pediatric car safety compliance in motor vehicle collisions: Identifying high-risk groups for improper restraint usage.

PURPOSE: To identify patient factors associated with improper restraint usage and worse trauma outcomes for pediatric patients involved in motor vehicle collisions (MVCs). METHODS: Retrospective study performed at a Level I pediatric trauma center for patients (≤18 yr) evaluated after MVC between 2008 and 2018. The Area Deprivation Index (ADI) was used to measure neighborhood socioeconomic disadvantage (NSD) levels based on the patient's home address. Trauma registry data was correlated to ADI and used to analyze appropriate restraint usage by NSD. Proper restraint practices were defined based on national guidelines and state laws. Demographics and clinical outcomes were also analyzed. Chi-square analysis with Bonferroni corrections was used to assess the association of ADI, race, and ethnicity with proper restraint usage. RESULTS: Among 1152 patients included, approximately 50% were male, the median age was 7 years [IQR 4-10], and 53% were of Hispanic ethnicity. Hispanic patients comprised 73% of children in ADI quintile 5 (greatest NSD), yet only 26% of children in ADI quintile 1 (least NSD). No differences were observed across clinical data and outcomes. Hispanic children <8 yr were significantly less likely to be in a car seat/booster seat compared to non-Hispanic children (OR 0.69, 95% CI 0.50-0.95, p = 0.025). Furthermore, those with greatest NSD (ADI quintile 5) had the largest proportion of unrestrained patients (21%, see Fig. 1). CONCLUSION: Hispanic children, especially those who require infant or booster seats (<8 yr), and children living in areas with greater neighborhood socioeconomic disadvantage demonstrated poorer restraint practices. ADI can successfully identify high-risk groups for targeted injury prevention programs and improved compliance in the most vulnerable neighborhoods. TYPE OF STUDY: Retrospective Study.

Understanding the burden of traumatic injuries at the United States-Mexico border: A scoping review of the literature.

ABSTRACT: The US-Mexico border is the busiest land crossing in the world and faces continuously increasing numbers of undocumented border crossers. Significant barriers to crossing are present in many regions of the border, including walls, bridges, rivers, canals, and the desert, each with unique features that can cause traumatic injury. The number of patients injured attempting to cross the border is also increasing, but significant knowledge gaps regarding these injuries and their impacts remain. The purpose of this scoping literature review is to describe the current state of trauma related to the US-Mexico border to draw attention to the problem, identify knowledge gaps in the existing literature, and introduce the creation of a consortium made up of representatives from border trauma centers in the Southwestern United States, the Border Region Doing Research on Trauma Consortium. Consortium members will collaborate to produce multicenter up-to-date data on the medical impact of the US-Mexico border, helping to elucidate the true magnitude of the problem and shed light on the impact cross-border trauma has on migrants, their families, and the US health care system. Only once the problem is fully described can meaningful solutions be provided.

A systems view of genetics in chronic kidney disease.

A tight interplay of genetic predisposition and environmental factors define the onset and the rate of progression of chronic renal disease. We are seeing a rapid expansion of information about genetic loci associated with kidney function and complex renal disease. However, discovering the functional links that bridge the gap from genetic risk loci to disease phenotype is one of the main challenges ahead. Risk loci are currently assigned to a putative context using the functional annotation of the closest genes via a guilt-by-proximity approach. These approaches can be extended by strategies integrating genetic risk loci with kidney-specific, genome-wide gene expression. Risk loci-associated transcripts can be assigned a putative disease-specific function using gene expression coregulation networks. Ultimately, genotype-phenotype dependencies postulated from these associative approaches in humans need to be tested via genetic modification in model organisms. In this review, we survey strategies that employ human tissue-specific expression and the use of model organisms to identify and validate the functional relationship between genotype and phenotype in renal disease. Strategies to unravel how genetic risk and environmental factors orchestrate renal disease manifestation can be the first steps toward a more integrated, holistic approach urgently needed for chronic renal diseases.

Synthesis and Characterization of Biodegradable Poly(butyl cyanoacrylate) for Drug Delivery Applications.

Poly(butyl cyanoacrylate) (PBCA) is a biodegradable and biocompatible homopolymer which is used as a carrier matrix for drug delivery systems in the pharmaceutical industry. Typically, polymerization is carried out under aqueous conditions and results in molecular weights are mostly lower than 3000 g/mol due to the instability of the high molecular weight PBCA. However, the stability of polymer excipients is a major prerequisite for drug product development in the pharmaceutical industry. In this work, a reliable polymer synthesis strategy for PBCA was designed to control the molecular weight in a nonaqueous polymerization environment. The anionic polymerization process and the impact of key synthesis parameters were investigated. The results confirmed that the previously postulated depolymerization-repolymerization process (DPRP) in the literature can be used to tailor the molecular weight of PBCA. The amount of sodium methoxide present during the polymerization proved to be the key parameter to control the DPRP and the molecular weight as desired. In addition, it was discovered that end-capping the PBCA chain suppressed the DPRP and prevented monomer release by depriving the PBCA of its living character. Thus, neat PBCA polymer with varying molecular weights determined by Advanced Polymer Chromatography™ as well as end-capped PBCA were synthesized, and the improvement of the chemical and shelf-life stability were confirmed using NMR.

Modified laparoscopic gastrostomy tube placement in children: Does subcutaneous suture type matter?

BACKGROUND: Laparoscopic gastrostomy tube (GT) placement carries the risk of early tube dislodgement and is often modified with absorbable subcutaneously-tunneled transabdominal tacking sutures that can aid in tube replacement. However, these buried sutures may increase the risk of surgical site infection (SSI). This study sought to evaluate SSI rates associated with different types of transabdominal tacking sutures used in modified laparoscopic GT placement. METHODS: A single-institution, retrospective review was performed of all patients ≤18 years-old undergoing modified laparoscopic GT placement between September 2016 and March 2020. Patients were stratified into three groups by suture type used, and the primary outcome was SSI within six weeks of surgery. Demographic and perioperative data were analyzed by chi-square or Fisher's exact test. RESULTS: A total of 113 modified laparoscopic GT placements were performed at a median age of 9 months (interquartile range 3 months to 3 years). Prophylactic antibiotic use was similar between groups. Eleven patients (10%) developed an SSI, and all were treated with antibiotics alone. No SSIs were observed with the use of poliglecaprone suture (n = 46), and higher SSI rates were observed with use of polyglactin (n = 17) and polydioxanone (n = 51) suture (18% polyglactin vs. 16% polydioxanone vs. 0% poliglecaprone, p<0.05). No differences were observed in rates of early postoperative dislodgement, leakage, or granulation tissue. CONCLUSION: Absorbable braided and long-lasting monofilament transabdominal tacking sutures may increase risk of SSI following modified laparoscopic gastrostomy tube placement. In this cohort, the use of poliglecaprone (Monocryl) suture was associated with no SSIs and similar rates of postoperative dislodgement, leakage, and granulation tissue. LEVEL OF EVIDENCE: Treatment Study, Level III.

Complete Absence of the Extrahepatic Biliary Tree in a Newborn With Pigmented Stools.

"Yellow stools in neonatal cholestasis exclude biliary atresia." This conventional wisdom led to the development of the infant stool color card, which alerts parents to seek medical referral when pale stools are observed, a strategy that has been shown to improve survival in infants with biliary atresia (BA). Here, we present a case of a newborn with significant direct hyperbilirubinemia (direct bilirubin level of up to 9.2 mg/dL on day of life 10) who continued to produce colored stools. Whole-genome sequencing results were negative for genetic causes of cholestasis. Hepatobiliary scintigraphy findings were nonexcretory. A liver biopsy specimen revealed cholestasis, ductular hyperplasia, giant cell formation, minimal inflammation, minimal portal or periportal fibrosis, and no evidence of viral changes. On day of life 38, during the exploratory laparotomy, the patient was found to have complete absence of the extrahepatic biliary tree, or biliary aplasia, possibly a rare, severe form of BA. This report aims to increase our vigilance and help prevent diagnostic error in patients with signs and symptoms of BA who may produce pigmented stools. Primary care physicians should hence refer an infant (early and urgently) to a pediatric gastroenterologist for further workup for a direct bilirubin level >1.0 mg/dL with any total bilirubin level, irrespective of the color of the infant's stools.