NorthShore University HealthSystem

<h2>Abstract:</h2> Despite advances in endovascular repair of aortic arch pathologies, the gold standard remains open surgical repair. Two single-branched options for zone 0 exist in the United States for high-risk patients. Both systems require adjunctive multiple cervical debranching, which carries significant morbidity. We describe a practical endovascular solution that simplifies modification, implantation, and adjunctive cervical debranching, by performing a single left carotid transposition and creating an additional fenestration within the existing Gore TBE platform (FEN-TBE). We present our initial series of 6 patients.

Previous single-center studies conducted in the United States in women with suspected preeclampsia indicated that serum soluble fms-like tyrosine kinase 1-to-placental growth factor ratio values of >38 measured on a widely available Elecsys immunoassay platform during the third trimester of pregnancy predicted the development of preeclampsia with severe features and adverse outcomes within 2 weeks of testing. This study aimed to validate the Elecsys soluble fms-like tyrosine kinase 1-to-placental growth factor ratio test for the prediction of preeclampsia with severe features in a United States population using the prospective Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification cohort that recruited women with a hypertensive disorder of pregnancy (gestational hypertension, chronic hypertension, de novo and superimposed preeclampsia) across 18 tertiary and community hospitals throughout the United States. We measured soluble fms-like tyrosine kinase 1-to-placental growth factor ratios using the Elecsys platform in archived serum samples from the Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification study that recruited hospitalized women with a hypertensive disorder of pregnancy between 23 0/7 and 34 6/7 weeks of gestation. The primary study outcome was prediction of preeclampsia with severe features within 2 weeks after testing. The secondary outcomes included a composite of adverse maternal and fetal/neonatal outcomes and prediction of delivery within 2 weeks. In the validation cohort of the Preeclampsia Risk Assessment: Evaluation of Cut-offs to Improve Stratification study (556 enrollments), the serum soluble fms-like tyrosine kinase 1-to-placental growth factor ratio at a cutoff value of >38 demonstrated a 67% positive predictive value (95% confidence interval, 61-73) and a 95% negative predictive value (95% confidence interval, 92-97) for the progression to preeclampsia with severe features within 2 weeks. Among women at <30 weeks of gestation (n=188), serum soluble fms-like tyrosine kinase 1-to-placental growth factor ratio at a cutoff value of >38 demonstrated a 78% positive predictive value (95% confidence interval, 68-86) and a 100% negative predictive value (95% confidence interval, 96-100) for the progression to preeclampsia with severe features within 2 weeks. The Elecsys soluble fms-like tyrosine kinase 1-to-placental growth factor ratio test performed better than standard-of-care clinical measures, with an area under the receiver operating characteristic curve of 0.92 (95% confidence interval, 0.89-0.90) for soluble fms-like tyrosine kinase 1-to-placental growth factor ratio vs <0.70 for standard-of-care tests, such as liver enzymes, platelet count, and serum creatinine (P<.001). Compared with women with a ratio of ≤38, those with a ratio of >38 had a higher risk of developing adverse maternal (relative risk, 4.9 [95% confidence interval, 2.6-9.9]; P<.001) and fetal/neonatal (relative risk, 3.2 [95% confidence interval, 2.6-4.0]; P<.001) outcomes and were more likely to deliver within 2 weeks (adjusted hazard ratio, 3.3 [95% confidence interval, 2.7-4.0]; P<.001). The soluble fms-like tyrosine kinase 1-to-placental growth factor ratio of >38 measured on the Elecsys platform predicted the development of preeclampsia with severe features, delivery, and adverse maternal and fetal/neonatal outcomes within 2 weeks of testing among preterm pregnant women hospitalized with a hypertensive disorder of pregnancy.

749 Background: There is mounting data for neoadjuvant chemotherapy use in HG UTUC, but the role of neoadjuvant chemoimmunotherapy remains less clear, including in cisplatin-ineligible pts, representing an unmet need in this population. Our multicenter trial evaluated the efficacy and safety of neoadjuvant gemcitabine/durvalumab (GD) in pts with HG UTUC. Methods: Cisplatin-ineligible pts with localized cN0 HG UTUC planned for radical nephroureterectomy (NU) were assigned to 4 GD cycles. Primary endpoint was pCR (ypT0N0/x); accrual goal was 29 pts; 18% pCR was considered worthy of further study, while 4% pCR would not justify further pursuit. Simon’s two stage design was used and if ≥1 out of the first 14 pts (13 evaluable) had pCR in stage I, another 15 pts (14 evaluable) would be accrued. With 27 evaluable (eligible and treated) pts, success was defined as ≥3 pCRs. Secondary endpoints included safety/tolerability, event-free survival (EFS) and overall survival (OS) both measured from registration and disease-free survival (DFS) measured from NU. Results: From 2022–2025, 31 pts enrolled (19 men) with median age 79 (44-88), including 15 renal pelvis, 15 ureteral, and 1 multifocal tumor; 5 with sessile appearance. Thirty pts were eligible and received ≥ 1 therapy dose and 23 completed all 4 planned cycles. Three patients achieved pCR (10%; 90%CI: 3.0 - 25.2%), 10 achieved pathologic stage &lt; ypT2N0/x (33%, 90%CI: 19.3 – 49.9%). All 30 pts experienced treatment-related adverse events (TRAEs), 13 experienced G3-4 TRAEs (most common were anemia and neutropenia: 4 pts each), with no G5 TRAE. Among pts who underwent NU, median time from last neoadjuvant dose to NU was 10 weeks (range 5-22 weeks); 6 pts did not have lymph node dissection; 5 treated pts did not undergo NU: 1 due to progression before NU, 1 due to unresectable tumor, 1 due to cancer-related death, 1 due to refusal of further intervention, 1 due to deconditioning. With median follow-up of 11 months, the estimated 1-year EFS was 77.4% (60.9 – 98.3%). Conclusions: Neoadjuvant GD was feasible and relatively well tolerated in pts with HG UTUC; associated with 10% pCR, 33% &lt; ypT2N0/x and promising 1-year EFS. Follow-up continues to further assess EFS, DFS, OS, while biomarker analysis is planned. Lymph node dissection for pts with HG UTUC is standard of care. The addition of durvalumab to accelerated MVAC chemotherapy is being evaluated in the randomized phase 3 part of this trial for cisplatin eligible patients (cohort A vs B; NCT04628767). Clinical trial information: NCT04628767 .

Preterm infants are at risk for white matter brain injury characterized by periventricular leukomalacia (PVL) with exposure to in-utero inflammation. Our aim was to correlate placental pathology with PVL in a cohort of preterm infants. All infants born <1500 g between Jan 1, 2017 and July 31, 2022 with placental pathology reports and neonatal outcome data on PVL were included in this study. Placental pathology findings were divided into 4 major categories (acute inflammation (AI), chronic inflammation (CI), fetal vascular malperfusion (FVM), and maternal vascular malperfusion (MVM)); each category was graded as absent, low-grade, or high-grade. We identified 263 infants with data for PVL and placental pathology. Gestational age (GA) averaged 28 completed weeks and mean birthweight was 1050 g. 11/263 (4.2%) infants had PVL. Acute inflammation was seen in 9/11 (82%) infants with PVL and only 101/252 (40%) of those without PVL (P = .01). Eight of the nine infants with PVL and AI (89%) had high-stage AI. In analyses adjusted for gestational age, the prevalences of CI, FVM and MVM were not significantly different between infants with or without PVL. In a large cohort of preterm infants, we demonstrate a strong association between AI in the placenta (histologic chorioamnionitis) and PVL in infants born <1500 g.

Patellofemoral instability (PFI) is common in adolescents and may require surgical treatment. Patient-reported outcome scores (PROs) are frequently used to evaluate outcomes after treatment. Commonly used PROs for PFI include disease-specific Banff Patellofemoral Instability Instrument 2.0 (BPII 2.0) and region-specific measures such as the Kujala Anterior Knee Pain Scale (Kujala), Pediatric International Knee Documentation Committee Subjective Knee Form (Pedi-IKDC), and Knee injury and Osteoarthritis Outcome Score (KOOS). The study aimed to compare the performance of disease-specific and region-specific PROs in adolescents after PFI surgery, and to evaluate their sensitivity to change. It was hypothesized that disease-specific PROs would perform better than region-specific PROs. Case series; Level of evidence, 4. The JUPITER (Justifying Patellar Instability Treatment by Early Results) study database was used to evaluate PROs in 256 adolescents (263 knees) aged ≤18 years who underwent surgical treatment for PFI. Four commonly used PRO scores were analyzed at baseline and at least 1 year postoperatively. Statistical analysis included comparisons between pre- and postoperative scores, calculation of minimal clinically important difference (MCID), correlations among the 4 scores, and evaluation of their sensitivity to change, floor effects, and ceiling effects. The median age was 15 years. Isolated medial patellofemoral ligament reconstruction was the most common procedure. The mean BPII 2.0 scores were lower at baseline and postoperatively, and showed the most substantial change at 1-year follow-up. There was a moderate correlation between the BPII 2.0 and the Kujala, Pedi-IKDC, and KOOS scores, and a strong correlation among the latter 3 scores. All scores were more sensitive to change among those at the lower 50th percentile of baseline scores. The BPII 2.0 was the only PRO that did not exhibit ceiling effects at follow-up. When comparing the performance of disease-specific (BPII 2.0) and region-specific (Kujala, Pedi-IKDC, and KOOS) PROs, the BPII 2.0 was found to be the most sensitive to change after PFI surgery in adolescents, and the only scale that did not have a ceiling effect at baseline and 1-year follow-up. There was a moderate correlation-and thus limited interchangeability-between the BPII 2.0 and the Kujala, Pedi-IKDC, and KOOS scores, both at baseline and at 1-year follow-up, and a strong correlation among the latter 3 knee-specific PROs. The BPII 2.0 should be considered the PRO of choice when evaluating adolescent patients with PFI.