Barriers to Transitional Care in Spina Bifida.

The health care needs children with spina bifida evolve over their lifetime; continued, regular contact with appropraitely trained, multidisciplinary providers is crucial to a patient's health and quality of life. Substantial research has been conducted to improve the transition process starting at an early age; however, there continue to be strong barriers to successful transition. This article reviews key aspects of the care of patients with spina bifida, the impact of inadequate transition to adult care, barriers to transition, and offers a potential vision for the future.

Management of pediatric renal trauma - Results from the American Association for Surgery and Trauma Multi-Institutional Pediatric Acute Renal Trauma Study (Mi-PARTS).

BACKGROUND: Pediatric renal trauma is rare and lacks sufficient population-specific data to generate evidence-based management guidelines. A non-operative approach is preferred and has been shown to be safe. However, bleeding risk assessment and management of collecting system injury is not well understood. We introduce the Multi-institutional Pediatric Acute Renal Trauma Study (Mi-PARTS), a retrospective cohort study designed to address these questions. This manuscript describes the demographics and contemporary management of pediatric renal trauma at Level I trauma centers in the United States. METHODS: Retrospective data were collected at 13 participating Level I trauma centers on pediatric patients presenting with renal trauma between 2010-2019. Data were gathered on demographics, injury characteristics, management, and short-term outcomes. Descriptive statistics were used to report on demographics, acute management and outcomes. RESULTS: In total 1216 cases were included in this study. 67.2% were male, and 93.8% had a blunt injury mechanism. 29.3% had isolated renal injuries. 65.6% were high-grade (AAST Grade III-V) injuries. The mean Injury Severity Score (ISS) was 20.5. Most patients were managed non-operatively (86.4%) 3.9% had an open surgical intervention, including 2.7% having nephrectomy. Angioembolization was performed in 0.9%. Collecting system intervention was performed in 7.9%. Overall mortality was 3.3% and was only observed in polytrauma. The rate of avoidable transfer was 28.2%. CONCLUSION: The management and outcomes of pediatric renal trauma lacks data to inform evidence-based guidelines. Non-operative management of bleeding following renal injury is a well-established practice. Intervention for renal trauma is rare. Our findings reinforce differences from the adult population, and highlights opportunities for further investigation. With data made available through Mi-PARTS we aim to answer pediatric specific questions, including a pediatric-specific bleeding risk nomogram, and better understanding indications for interventions for collecting system injuries. LEVEL OF EVIDENCE: IV, Epidemiological (prognostic/epidemiological, therapeutic/care management, diagnostic test/criteria, economic/value-based evaluations, and Systematic Review and Meta-Analysis).

Blunt traumatic female urethral and bladder neck injuries: a 15-year single-institution experience.

PURPOSE: To describe our experience in the management and outcomes of female patients with urethral or bladder neck (BN) injury at a high-volume Level 1 trauma center. METHODS: A retrospective chart review of all female patients with urethral or BN injury by blunt trauma mechanism admitted to a Level 1 trauma center between 2005 and 2019 was performed. RESULTS: Ten patients met study criteria with median age 36.5 years. All had concomitant pelvic fractures. All injuries were confirmed operatively, with no delayed diagnoses. Two patients were lost to follow up. One patient was not eligible for early repair of urethral injury and had two repairs of a urethrovaginal fistula. Two of seven (29%) patients who underwent early repair of their injury had an early Clavien grade > 2 complication, with none reporting long-term complications at median follow-up of 15.2 months. CONCLUSIONS: Intraoperative evaluation is critical in the diagnosis of female urethral and BN injury. In our experience, acute surgical complications are not uncommon after the management of such injuries. However, there were no reported long-term complications in those patients who had prompt management of their injury. This aggressive diagnostic and surgical strategy is instrumental in attaining excellent surgical outcomes.

Ureteral Injuries Secondary to Blunt Abdominal Trauma: A 15-Year Review of Presentation, Management, and Outcomes at a Level 1 Trauma Center.

OBJECTIVE: To report our contemporary experience with ureteral injuries secondary to blunt trauma, with diagnostic methods and management stratified according to injury severity. MATERIALS AND METHODS: We performed a retrospective 15-year study (4/2005-4/2020) at a regional level I trauma center. Patients were categorized as having a partial or complete transection injury. Treatment success was defined as the absence of hydronephrosis or obstruction on follow-up imaging. RESULTS: Eighteen patients suffered 10 partial and 9 complete ureteral transections. All 16 patients who underwent initial evaluation with computed tomography were correctly graded as having partial or complete transections, and there were no missed injuries. Treatment of partial transections included observation (3/9), retrograde double-J stent placement (4/9), and Heineke-Mikulicz pyeloplasty (2/9). At a median follow-up of 9 (IQR 2-59) months, 8/9 (89%) partial transections were treated successfully. Treatment of complete transections included pyeloplasty (3/9), ureteroureterostomy (4/9), and ureteroneocystostomy (1/9). One patient who underwent attempted reconstruction 6 days after trauma required nephrectomy. At a median follow-up of 32 (IQR 4-82) months, 7/8 (89%) reconstructed complete transections were treated successfully. CONCLUSION: Computed tomography with delayed phase imaging is a sensitive test to detect ureteral injuries after blunt trauma, and computed tomography can distinguish between partial and complete transections. Partial transection injuries secondary to blunt trauma may be amenable to ureteral stent placement or close observation in select cases. Good intermediate-term outcomes can be achieved with early surgical intervention in the case of complete transections.

Computed tomography-based volume calculations of renal ischemia predicts post-traumatic renal function after renal infarction injury.

OBJECTIVES: To describe a systematic method to quantify the severity of renal infarction injury and assess its association with post-traumatic renal function after blunt trauma. METHODS: We retrospectively reviewed all patients who suffered an AAST grade IV renal infarction injury without active bleeding secondary to blunt trauma between 1/2010 and 10/2020. Only patients with a pre-traumatic eGFR within 12 months of injury and post-traumatic eGFR within 3-12 months were included. Percentage of renal ischemia was defined as: (ischemic volume/total volume) × 100%. Two radiologists reviewed computed tomography images to determine ischemic and overall cross-sectional areas using the polygon region of interest tool. These areas were multiplied by slice thickness to obtain ischemic and total volumes. Intraclass correlation coefficient was used to assess consistency between radiologists. Linear regression analyses were used to assess the association between percentage of renal ischemia and post-traumatic renal function. RESULTS: Thirty-five of 140 (25.0%) patients met inclusion criteria. The median (IQR) pre-trauma eGFR was 107.7 ml/min/1.73m2 (90.6-121.8), percentage of renal ischemia was 8.4% (2.9-30.1), and decrease in eGFR after trauma was 12.9 ml/min/1.73m2 (0.4-32.6). There was excellent reliability in calculating ischemic volume (ICC = 0.987) and total kidney volume (ICC = 0.995) between two radiologists. When adjusting for pre-traumatic eGFR, patient age, and injury severity score, a 10% increase in ischemic volume was associated with a post-injury eGFR value that was 8.0 ml/min/1.73 m2 (95% CI - 11.2, - 4.7) lower. CONCLUSIONS: CT-based volume calculation of renal ischemia may be utilized to quantify kidney injury and be associated with post-traumatic renal function loss.

Long-term urological and gynecological outcomes following complete primary repair in females with bladder exstrophy.

INTRODUCTION: Long-term continence outcomes in patients undergoing complete primary repair of exstrophy (CPRE) have shown that a subset of patients do not achieve continence until after puberty. We aim to update the continence outcomes as well as describe gynecological outcomes for females having undergone CPRE. MATERIALS AND METHODS: This was a retrospective review between 1989 and 2019 at a single institution. Inclusion criteria were females with classic bladder exstrophy who underwent CPRE. Exclusion criteria were variant diagnoses and age <4 years. Continence was defined as dry for ≥3 h (volitional voiding or clean intermittent catheterization (CIC)). Partial continence was defined as minor stress incontinence or enuresis. Vaginal stenosis was evaluated in post-pubertal patients. RESULTS: Eighteen patients met inclusion criteria. Median age at last follow-up was 15.9 years (IQR 13.1, 18.4). All patients underwent primary closure <30 days of life (n = 18). Subsequent procedures included bladder augmentation (n = 4), continent catheterizable channel (n = 7), bladder neck injections (n = 12) and bladder neck reconstruction (n = 12). Continence and partial continence were achieved in 6/18 (33.3%) and 9/18 (50.0%), respectively, with mean 3.2 ± 2.5 continence procedures at 9.6 years (IQR 7.3, 15.2). Volitional voiding was seen in 11/18 (61.1%) and 7/18 (38.9%) performed CIC, with no significant difference in continence. Mean bladder capacity was 199 ml ± 96 versus 90 ml ± 29 in the volitional voiding versus CIC group (P = 0.0047). Eleven women with median age of 18.0 years (IQR 15.2, 21.4) had recorded menarche: 6/11 (54.5%) patients reported painful/irregular menses, controlled with hormonal therapy. Six of 11 (54.5%) women had vaginal stenosis managed with vaginal dilation (n = 2) or vaginoplasty (n = 4). Three (27.3%) reported tampon use and penetrative intercourse. CONCLUSION: Overall, the majority of women who have undergone CPRE achieved complete or partial continence, though most required additional procedures and time to attain it. Additionally, volitional voiding was achievable. Bladder capacity was significantly lower in patients dependent on CIC. Most required medical or surgical interventions for gynecologic concerns post menarche. This study underscores the unique needs of girls and young women with bladder exstrophy and further supports the importance of close long-term urologic and gynecologic management throughout development.

GNA11 Q209L Mouse Model Reveals RasGRP3 as an Essential Signaling Node in Uveal Melanoma.

Uveal melanoma (UM) is characterized by mutually exclusive activating mutations in GNAQ, GNA11, CYSLTR2, and PLCB4, four genes in a linear pathway to activation of PLCß in almost all tumors and loss of BAP1 in the aggressive subset. We generated mice with melanocyte-specific expression of GNA11Q209L with and without homozygous Bap1 loss. The GNA11Q209L mice recapitulated human Gq-associated melanomas, and they developed pigmented neoplastic lesions from melanocytes of the skin and non-cutaneous organs, including the eye and leptomeninges, as well as at atypical sites, including the lymph nodes and lungs. The addition of Bap1 loss increased tumor proliferation and cutaneous melanoma size. Integrative transcriptome analysis of human and murine melanomas identified RasGRP3 to be specifically expressed in GNAQ/GNA11-driven melanomas. In human UM cell lines and murine models, RasGRP3 is specifically required for GNAQ/GNA11-driven Ras activation and tumorigenesis. This implicates RasGRP3 as a critical node and a potential target in UM.

Microbiological evaluation of infected pelvic lymphocele after robotic prostatectomy: potential predictors for culture positivity and selection of the best empirical antimicrobial therapy.

OBJECTIVES: To examine symptomatology and microbiology of infected lymphocele (LC) post-robotic-assisted radical prostatectomy and pelvic lymph node dissection (PLND) and to assess for potential predictors for LC fluid culture positivity. Secondly, to provide general recommendations about use of select antimicrobial therapy. METHODS: This was a single-center, IRB-approved, retrospective, case series review conducted between October 2008 and October 2014. Data included symptomatology, microbiology of symptomatic LC in men post-robotic prostatectomy and PLND. Those with infected LC were compared to those men with symptomatic LC in the absence of infection. RESULTS: Symptomatic LC was seen in 7% of men, and among those, infected LC was seen in 42%. Infected LC cultures showed predominance of G+ cocci such as S. aureus, coagulase-negative Staphylococcus species, S. pyogenes, S. fecalis and S. viridans. Monomicrobial infection was seen in 85%. Multivariate logistic regression showed leukocytosis [Odds: 12.3, p = 0.03, 95% CI (1.2-125)] was significant predictor for culture positivity, whereas trend toward significance for factors such CT findings of thickened walls around the LC +/- air. CONCLUSIONS: LC infection following PLND for prostate cancer is usually monomicrobial and caused by Gram+ cocci. GI tract and skin flora are the main habitat. High index of suspicion of infected LC is undertaken in the presence of leukocytosis, fever and abnormal CT findings. Based upon our local hospital antibiogram, combination of IV ampicillin/sulbactam and vancomycin is suggested as the best initial empiric therapy in treating these patients.

Transposable elements have rewired the core regulatory network of human embryonic stem cells.

Detection of new genomic control elements is critical in understanding transcriptional regulatory networks in their entirety. We studied the genome-wide binding locations of three key regulatory proteins (POU5F1, also known as OCT4; NANOG; and CTCF) in human and mouse embryonic stem cells. In contrast to CTCF, we found that the binding profiles of OCT4 and NANOG are markedly different, with only approximately 5% of the regions being homologously occupied. We show that transposable elements contributed up to 25% of the bound sites in humans and mice and have wired new genes into the core regulatory network of embryonic stem cells. These data indicate that species-specific transposable elements have substantially altered the transcriptional circuitry of pluripotent stem cells.