Prenatal treprostinil reduces the pulmonary hypertension phenotype in the rat model of congenital diaphragmatic hernia.

BACKGROUND: Persistent pulmonary hypertension (PH) causes significant mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Since pulmonary vascular abnormalities in CDH develop early during foetal development, we hypothesized that prenatal maternal administration of treprostinil, through its anti-remodelling effect, would improve the PH-phenotype in the nitrofen rat model of CDH. METHODS: In a dose-finding study in normal, healthy pregnant rats, we demonstrated target-range foetal plasma treprostinil concentrations without signs of toxicity. Next, an efficacy study was performed assessing the effects of treprostinil administration at 900 and 1500ng/kg/min from gestational day (GD) 16 until term (GD 21) in CDH and control pups. Pulmonary vascular and airway morphometry, lung mechanics, and expression patterns of genes implicated in the prostaglandin vasoactive pathway were studied. FINDINGS: In rats maternal administration of 1500ng/kg/min treprostinil reached target foetal concentrations, with no detrimental maternal or foetal side-effects. Prenatal exposure to 900 and 1500 ng/kg/min treprostinil reduced the medial wall thickness (%MWT) (CDH·900, 38.5± 8·4%; CDH.1500, 40·2±9·7%; CDH, 46·6±8·2%; both p < 0·0001) in rat pups with CDH, however increased the %MWT in normal foetuses (C.T.900, 36·6±11·1%; C.T.1500, 36·9±9·3%; C.P., 26·9±6·2%; both p < 0·001). Pulmonary airway development, lung hypoplasia and pulmonary function were unaffected by drug exposure. INTERPRETATION: In pregnant rats maternally administered treprostinil crosses the placenta, attains foetal target concentrations, and is well tolerated by both mother and foetuses. This report shows a significant reduction of pulmonary arteriole muscularization with prenatal treprostinil in a nitrofen rat model, supporting the promise of this treatment approach for PH of CDH. FUNDING: United Therapeutics Corporation provided treprostinil and financial support (ISS-2020-10879).

Left Atrial Dissection Secondary to Retrograde Coronary Sinus Cannulation During a Stanford Acute Type-A Aortic Dissection Repair: A Case Report.

Left atrial (LA) dissections are rare phenomena, often iatrogenic, caused by blood flow into a false lumen, potentially obstructing the pulmonary veins or flow into the left ventricle. Severity can range from an incidental observation or complete circulatory collapse. While LA dissections are often associated with mitral valve repair, there are 2 reported cases of LA dissections associated with retrograde cardioplegia cannula insertion through the coronary sinus. Here, we present a large LA dissection that was directly visualized and tracked to a coronary sinus injury from the retrograde cardioplegia cannula. The clinical presentation and echocardiography findings informed our subsequent management.

An Examination of General Surgery Residency Programs with a Rural Track.

BACKGROUND: There is a steady decline in the general surgery workforce in rural areas of the United States. In response, some surgery residency programs have developed rural tracks to encourage rural practice and adequately prepare trainees for this setting. OBJECTIVE: To compare the practice type and location of graduates from general surgery residency programs with and without a dedicated rural track between 2011-2020. METHODS: General surgery residency programs with and without a rural track were identified using the American Medical Association Residency and Fellowship Electronic Interactive Database and the Rural Surgery Program list from the American College of Surgeons. Graduates of these programs who entered general surgery practice between 2011-2020 were subsequently identified from individual residency program websites and tracked to their current practice setting using a Google search of first and last name and residency affiliation. Practice location was identified by zip code or county name and coded by Rural-Urban Continuum Codes (RUCC, Economic Research Service, USDA). RESULTS: We identified 2,582 general surgery residency graduates from 2011 to 2020 across 66 residency programs. Of these graduates from programs without a rural track, 23.6% entered general surgery practice without additional fellowship training, compared to 34.0% from residency programs with a rural track (p = 0.019). Community or University-based program designation was not associated with decision to enter general surgery practice over fellowship training (p = 0.420). Proportion of graduates entering rural practice as defined by RUCC groups 7-9 was not associated with having a rural program track or with community or university-based program status. CONCLUSION: Residency programs with a rural track produce a higher proportion of graduates entering general surgery compared to fellowship, though they are no more likely than programs without a rural track to produce graduates who ultimately practice in rural areas.

Integrated Ultrasound With Urodynamics Illustrates Effect of Bladder Volume on Upper Tract Dilation: Should we Trust Surveillance Ultrasounds?

OBJECTIVE: To evaluate if ultrasound during urodynamics (uUS) will show that traditional ultrasound (tUS) routinely underestimates the potential magnitude of upper tract dilation (UTD). METHODS: Prospective pilot study of 10 consecutive patients ≥ 5 years of age undergoing same day uUS and tUS. Using randomized images, the study pediatric radiologist determined anterior-posterior renal pelvic diameter (APD), bladder volume, vesicoureteral reflux (VUR) and UTD grades. A single pediatric urologist determined urodynamic bladder capacity and assigned either hostile, intermediate, abnormal but safe, or normal national spina bifida patient registry classification (NSBPR). RESULTS: Bladder volume on tUS was significantly smaller than final bladder volume on uUS (180 vs 363 ml: P<.001). On average, patient reported maximum catheterized/voided volumes were also 82 ml greater than final bladder capacity on uUS. UTD was upgraded in 25% of kidneys and APD increased by 0.6 cm on uUS over that seen on tUS (P=.001). Units with VUR had greater increases in APD (1.2 P=.007 vs. 0.3 cm P=0.06). Changes in APD stratified by NSBPR revealed average increases of up to 1.3 cm. CONCLUSION: Despite instructions to the contrary, patients come for tUS with a relatively empty bladder as compared to either their urodynamic or patient-reported capacity. This translates to a significant underestimation of UTD with tUS, most notably in those with VUR. Alternatives to traditional protocols include insisting patients wait until their bladder is truly full for tUS, retrograde filling their bladder, or performing uUS. Accurate assessment of UTD severity may help guide long term management.

Reassessing the utility of routine urine culture with urodynamics: UTI incidence and risk factors.

INTRODUCTION: There is no consensus regarding use of periprocedural antibiotics or routine urine cultures during urodynamics study (UDS) in children. At our hospital, we historically have obtained urine cultures during UDS. However, even with positive cultures, few patients require treatment. Most are successfully managed with increased hydration and frequent bladder emptying. PURPOSE: To evaluate clinical characteristics, antibiotic treatment, and outcomes in patients undergoing UDS to identify (1) risk factors for urinary tract infection (UTI) after UDS, and (2) patients who may benefit from routine urine culture. STUDY DESIGN: Retrospective review of 769 patients who underwent 1057 UDS between January 2013 and January 2015. Positive urine culture was defined as ≥104 colony forming units/ml. Afebrile UTI was defined as new symptoms within 7 days. Febrile UTI was new symptoms with fever (≥38.5 °C). Fisher's exact test was used for comparative analyses. RESULTS: Nearly all patients had a urine culture taken immediately prior to UDS (94%, 993/1057). Patients on clean intermittent catheterization (CIC) were more likely to be on pre-UDS antibiotics, 22.8% (106/464) vs. 17.9% of those not on CIC (106/593) (p = 0.04). Of patients who had a urine culture, it was positive in 40% (402/993) with more positive cultures in patients on CIC vs. not (72.0%, 316/439 vs. 15.5%, 86/554, p < 0.0001). Factors significantly associated with clinical/possible post-UDS UTI included clinical UTI within 30 days before UDS, immunosuppression, overnight Foley catheter use, febrile UTI as indication, and symptoms on day of procedure (Table). Fifteen patients (1.4%, 95% confidence interval 0.7-2.1%) developed a clinical/possible post-UDS UTI, of which 40% (6/15) were febrile, with one requiring hospitalization. Of patients with post-UDS UTIs, 33% (5/15) had negative cultures at the time of UDS. DISCUSSION: If urine cultures were obtained selectively based on our study findings, 78% of pre-UDS urine cultures could be eliminated, while "missing" clinically relevant cultures in only 0.4% (4/1057). Study limitations include the retrospective design. However, prospective data collection will now be possible by using standardized, templated UDS and post-UDS follow-up notes with extractable data elements that automatically populate a database. CONCLUSION: Post-UDS UTI is uncommon (1.4%), even in the setting of bacteriuria. This finding calls into question the utility of routine pre-UDS urine culture. Data from this study and a future prospective study will be used to refine a new working protocol, with the goal of targeting future urine cultures to a high-risk subset of patients.

Agreement between electronic medical records and self-reported urologic domains in the National Spina Bifida Patient Registry (NSBPR): Implications for future research.

BACKGROUND: Self-report (SR) is an efficient data collection method. However, SR data have been shown to be discrepant with medical record (MR) documentation, which raises questions about using SR to supplement retrospective chart review in research. In this study, pediatric spina bifida (SB) patients who completed SR interviews about continence status and personal bladder/bowel management were identified. We examined agreement between SR data and Urology provider notes in MRs. OBJECTIVE: This study aimed to (1) identify demographic, medical, or methodological factors that might contribute to SR/MR disagreement; (2) postulate how these findings might be significant clinically; and (3) recommend improvements to SR data collection and MR documentation. STUDY DESIGN: Our institution participates in the National Spina Bifida Patient Registry (NSBPR). NSBPR-enrolled subjects typically complete annual interviews about their urologic outcomes; we consider this to be a form of SR. After identifying patients who interviewed within 1 month of an encounter with a urology provider, we systematically reviewed and compared their SR responses to the MR. Overall SR/MR agreement (no. of agreeing data pairs/no. of complete data pairs) and strength of agreement (kappa, κ) were assessed. Agreement about daytime continence status was assessed for children ≥5 years or in younger children who were toilet trained. Analyses were also stratified by diagnosis, type of bladder management, and ethnicity. RESULTS: Eleven urologic domains were analyzed for 176 patients. Overall SR/MR agreement was ≥90% for nine out of 11 domains (figure). Daytime urinary and stool incontinence (DUSI) domains demonstrated the lowest overall agreement, at 69% and 74% respectively. Patients with myelomeningocele (MM) and those on clean intermittent catheterization demonstrated twice as much SR/MR disagreement about DUSI than patients without MM and those who void. There was no significant difference in rates of SR/MR agreement about DUSI when analyzed by ethnicity, race, and ambulatory function status. Among cases of SR/MR disagreement about DUSI, the SR and MR had a roughly equal percentage of better outcomes reported for both UI and SI. DISCUSSION: There was strong SR/MR agreement for the majority of urologic data we analyzed. Medically complex patients faced lower SR/MR agreement, which is consistent with findings in other patient populations. Biased reporting by patients/families or providers was not found. CONCLUSION: Minimizing SR/MR disagreement through standardized data collection methods and tools, improved definitions of patient outcomes, and documentation of respondent identity will improve large, multisite studies that utilize SR and MR concurrently.

Ultrasound Shear Wave Elastography: A Novel Method to Evaluate Bladder Pressure.

PURPOSE: Children with bladder dysfunction resulting in increased storage pressure are at risk for renal deterioration. The current gold standard for evaluation of bladder pressure is urodynamics, an invasive test requiring catheterization. We evaluated ultrasound shear wave elastography as a novel means of assessing bladder biomechanical properties associated with increased bladder pressure. MATERIALS AND METHODS: Concurrent shear wave elastography and urodynamics were performed. Ultrasound shear wave elastography images were obtained of the anterior and posterior wall when empty and at 25%, 50%, 75% and 100% expected bladder capacity, and end fill volume. Regions of interest were confirmed by a pediatric radiologist. Bladder cohorts were defined as compliant (capacity detrusor pressure less than 25 cm H2O) and noncompliant (25 cm H2O or greater). Pearson correlation coefficients and a mixed effects model evaluated the relationship between shear wave speed and detrusor pressure, compliance and normalized compliance. An unpaired t-test was used for between cohort analyses. RESULTS: In all 23 subjects mean shear wave speed of the anterior and posterior bladder walls significantly correlated with detrusor pressure throughout filling. When comparing compliant and noncompliant bladders, mean shear wave speed and detrusor shear wave speed of the anterior wall significantly increased with filling of noncompliant bladders. Shear wave speed remained at baseline levels in compliant bladders. Mean shear wave speed of the anterior wall was significantly correlated with compliance and normalized compliance. CONCLUSIONS: Ultrasound shear wave elastography bladder measurements correlate well with bladder storage pressure, and shear wave speed measurements differ between compliant and noncompliant bladders. This is the first known study to demonstrate that shear wave elastography is promising as a bedside modality for the assessment of bladder dysfunction in children.