School of Medicine

IMPORTANCE: Placement of intravenous access is challenging in pediatric patients. Complications and replacement of IV access is a common occurrence in pediatric patients. OBJECTIVE: This project evaluated a new training program for placement of pediatric USGIV lines. DESIGN: Quality improvement: pre-post cohort. SETTING: A tertiary pediatric hospital in the southwest United States. PARTICIPANTS: The pre-intervention cohort included 400 IV lines identified through retrospective chart review. A subset of 68 lines placed in the three months prior to the intervention were specific to the nurses undergoing training. The post-intervention cohort consisted of 359 lines obtained via convenience sampling. Lines were excluded if documentation lacked insertion/removal dates or reasons for removal. METHODS: The educational intervention was based on best practices, including appropriate catheter-to-vessel diameter ratios and optimal catheter length within the vessel. Training was delivered through asynchronous PowerPoint presentations, one-on-one clinical rounding, and badge card distribution. Mean dwell time and complication rates were assessed through chart review. A sample size of 353 lines was calculated to detect a 25% increase in dwell time; 359 lines were reviewed post-intervention. RESULTS: The average patient age was similar between groups (pre: 11.22 years; post: 11.28 years). A statistically significant increase in dwell time was observed post-intervention (mean 2.17 vs. 1.72 days, p = 0.0015). While overall complication rates remained stable, a significant reduction in early complications (within 0-1 day) was noted (p = 0.01778). CONCLUSIONS: These findings support integration of measurement-based decision-making in pediatric vascular access. Further multi-site studies are needed to confirm generalizability.

OBJECTIVES: To challenge the perception that endometriosis uniformly regresses after menopause by presenting the case of repeated, pathology-confirmed symptomatic recurrences spanning two decades after menopause, and to emphasize key considerations for hormone therapy use and surgical management in postmenopausal endometriosis. METHODS: We report the case of a 70-year-old postmenopausal patient with prior hysterectomy, bilateral salpingo-oophorectomy, appendectomy, and pathology-confirmed endometriosis who presented with pelvic pain while receiving subcutaneous estrogen pellet therapy. Preoperative imaging was suggestive of recurrent endometriosis. The patient underwent laparoscopic excision for diagnostic and therapeutic purposes, with final pathology confirming recurrent disease. Written informed consent was obtained for publication of this case report and use of de-identified clinical images. A focused narrative literature review was performed to contextualize this case within existing data on postmenopausal endometriosis. RESULTS: Laparoscopy revealed a cystic mass arising from the right round ligament with associated retroperitoneal fibrosis and multiple peritoneal implants consistent with endometriosis. Surgical management included resection of the round ligament mass, excision of peritoneal implants, lysis of adhesions, and right ureterolysis. Histopathologic examination confirmed a round ligament adenomyoma and peritoneal endometriosis. Postoperatively, the patient experienced symptomatic improvement and was transitioned to low-dose transdermal estradiol combined with progestogen therapy. CONCLUSIONS: Endometriosis can develop, persist, or recur after menopause, particularly in the setting of unopposed and potentially supraphysiologic exogenous estrogen. This case highlights the importance of appropriate menopausal hormone therapy selection, including consideration of progestogen use regardless of uterine status, and reinforces the role of surgical excision in postmenopausal patients with suspected disease.

Ovulation is triggered by a surge in luteinizing hormone (LH) secretion from the pituitary. The LH surge is itself driven by a surge in GnRH release induced by estrogen positive feedback action in the hypothalamus. While ERα-expressing kisspeptin (Kiss1) neurons in the preoptic area (in mice, the rostral periventricular region of the third ventricle [RP3V]) are proposed to mediate this estrogen positive feedback event, the functional necessity of RP3V-derived kisspeptin for the LH surge has not been directly tested. Here we leveraged Cre/lox technology and the known high co-expression of tyrosine hydroxylase (TH) with Kiss1 in only the RP3V region to generate novel transgenic mice with selective knockout (KO) of the Kiss1 gene in just RP3V neurons (Kiss1RP3V KO mice). In situ hybridization confirmed a significant 70% reduction in cells expressing Kiss1 in the RP3V region, but not in the arcuate nucleus, along with no change in RP3V Th expression. Kiss1RP3V KO females exhibited normal pubertal timing and estrous cycles. However, functional interrogation of the ability of Kiss1RP3V KO females to generate an estradiol-induced LH surge demonstrated markedly blunted LH surges and reduced occurrence of surges, in line with the partial Kiss1RP3V knockout in this group. Correspondingly, fertility assessment revealed significant subfertility, including fewer and smaller litters. This subfertility is consistent with the observed impaired LH surges, though the downstream ovarian mechanism(s) underlying the smaller litters still needs to be determined. These findings provide direct causal evidence that RP3V-derived kisspeptin is essential for normal LH surge magnitude and optimal fertility.

Abstract High-grade serous ovarian cancer (HGSOC) is the most lethal gynecologic malignancy in the U.S. and is marked by resistance to chemo- and immunotherapy. Although focal adhesion kinases (FAK and PYK2) are known to induce tumor microenvironment immunosuppression, their role in altering tumor-cell major histocompatibility complex class-II (MHC-II) presentation requires further investigation. HGSOC tumors have few mutations but frequently show FAK amplification (∼75%). Notably, elevated MHC-II expression correlates with longer progression-free survival in recurrent HGSOC, likely through enhanced CD4+ T-cell activation and improved anti-tumor immunity. Flow cytometry analysis revealed that ATP competitive small molecule inhibition of FAK kinase activity (FAKi) increases MHC-II antigen presentation in vitro and in vivo. Targeted FAK protein degradation following treatment with a FAK proteolysis targeting chimera (FAK-PROTAC) produced a similar effect. In a syngeneic orthotopic mouse model, FAK depletion induced MHC-II to levels comparable to kinase-dead FAK, consistent with the loss of FAK activity in promoting tumor MHC-II expression. As ovarian tumor cells also express the FAK-related homolog PYK2, CRISPR was employed to selectively inactivate FAK and or PYK2 expression in human OVCAR3, murine KMF, and murine HGS2 ovarian tumor models. Notably, loss of FAK, but not PYK2, resulted in enhanced MHC-II presentation in these cells. As tumor cell treatment with a dual FAK-PYK2 inhibitor or PROTAC that targets FAK and PYK2 does not induce MHC-II expression as does selective loss of FAK, our results support a distinct immunogenic role for PYK2 in ovarian tumor cells. Ongoing studies are evaluating PYK2 mechanism of action upon FAK inhibition and the regulation of CIITA (class II, major histocompatibility complex, transactivator) transcription. Collectively, our findings suggest roles for FAK-specific inhibitors that may potentiate MHC-II-related adaptive immune responses as a therapeutic strategy for advanced ovarian cancer. Citation Format: Terrance James Haanen, Xiao Lei Chen, David D. Schlaepfer., . Opposing control of MHC-II antigen presentation by FAK and PYK2: Implications for therapeutic intervention [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1603.

Background Some studies suggest that induction of labor at term is associated with lower rates of breastfeeding than spontaneous labor. Objective Our objective was to evaluate whether late preterm medically indicated induction of labor is associated with decreased rates of breastfeeding and/or increased rates of breastfeeding complications at the time of discharge from the delivery hospitalization. Study Design This secondary analysis of a randomized trial of individuals at high risk for late preterm delivery, defined as delivery between 34+0 and 36+6 weeks, included non-anomalous, singleton pregnancies and excluded those with unlabored cesareans or preterm prelabor rupture of membranes. The parent study collected detailed data on breastfeeding and the presence of breastfeeding difficulties, defined as issues in milk production or infant feeding. Subjects with incomplete breastfeeding data were additionally excluded. Participants undergoing late preterm indicted inductions were compared to those who presented with spontaneous preterm labor. The primary outcome, the rate of breastfeeding, was compared between groups. Breastfeeding difficulties were also compared. Baseline demographics were compared using bivariable analyses. We fit logistic regression models to adjust for confounders related to breastfeeding. Results 2,130 participants were included. Spontaneous and induction groups were similar in age, tobacco use, gestational diabetes, and insurance type but the induced group had higher body mass index, rates of chronic hypertension and hypertensive disorders of pregnancy (HDP). The rate of breastfeeding did not differ in induced versus spontaneous participants (69.0% vs 68.7%, P = 0.90). However, breastfeeding difficulties were more common in the induced group in unadjusted analyses (38.8% vs 32.3%, P= 0.01). After adjusting for confounders, neither breastfeeding rates nor breastfeeding difficulties were different between groups. Of note, government insurance was an independent risk factor for low breastfeeding rates and induction was associated with a decreased rate of cesarean delivery Conclusion Medically indicated late preterm labor induction was not associated with decreased rates of breastfeeding or increased breastfeeding problems at time of discharge from the delivery hospitalization. Those with government funded insurance may need additional breastfeeding support.

High-grade serous ovarian cancer (HGSOC) is a lethal malignancy characterized by therapy resistance. Focal adhesion kinase (FAK) is highly expressed in HGSOC, yet its impact on tumor-immune communication remains incompletely defined. Using three syngeneic ovarian cancer models, we show that FAK inhibition (FAKi) increased macrophage CXCL13 expression and promoted peritoneal B cell infiltration. Combining FAKi with low-dose pegylated doxorubicin and anti-T cell immunoreceptor with Ig and ITIM domains (TIGIT) checkpoint blockade suppressed orthotopic ovarian tumor growth, extended survival, and induced tertiary lymphoid structures. Macrophage lineage factor GATA6 inactivation reduced CXCL13 expression, enhanced FAK-knockout tumor growth, and limited ascites B cell accumulation. Mechanistically, FAKi-treated or FAK-deficient tumor cells release exosomes enriched in omega-3 fatty acids that stimulated macrophage CXCL13 production. Exposure of macrophages to tumor-derived omega-3 lipids or eicosapentaenoic acid induced anti-tumor reprogramming and CXCL13 expression. Together, these findings reveal a tumor lipid-macrophage signaling axis activated by FAKi that supports B cell recruitment and anti-TIGIT immunotherapy.

Purpose Polycystic ovary syndrome and metabolic dysfunction–associated steatotic liver disease (MASLD) both emerge during adolescence; however, it remains unknown whether menstrual abnormalities and hyperandrogenism signals increased hepatic risk. Methods We analyzed 2011–2020 National Health and Nutrition Examination Survey data for 1,651 females aged 12–19 years in the United States who were at least 2 years postmenarche. Amenorrhea was defined as self-reported absence of menses in the past 12 months. Biochemical hyperandrogenism was defined as free androgen index ≥5. Elevated alanine aminotransferase (ALT; >22 U/L) was the primary hepatic outcome; suspected MASLD was defined as elevated ALT plus ≥1 cardiometabolic risk factor. Survey-weighted logistic regression models adjusted for age, race and ethnicity, and body mass index (BMI) percentile. Results Amenorrhea was reported by 2.8% of participants and was associated with higher odds of elevated ALT (adjusted odds ratio 2.5, 95% confidence interval 1.1–5.7). Biochemical hyperandrogenism was also associated with elevated ALT (adjusted odds ratio 2.6, 95% confidence interval 1.4–4.8). The positive association between insulin resistance and ALT was stronger among adolescents with amenorrhea (β = 2.7 vs. 1.1). Although ALT levels rose with increasing BMI, adolescents with amenorrhea had consistently higher ALT prevalence, including those with a normal BMI. Discussion Amenorrhea and hyperandrogenism, hallmark features of polycystic ovary syndrome, are independently associated with elevated ALT and suspected MASLD in adolescent females. These findings support ALT screening for youth with menstrual dysfunction, even in the absence of obesity, to enable earlier detection and more integrated endocrine-hepatic care.

Mutations in the SOX2 gene have been previously linked to a syndromic form of isolated hypogonadotropic hypogonadism, with additional ocular and neurodevelopmental phenotypes. Recently, we reported a functional role for SOX2 in hypothalamic kisspeptin-expressing neurons and established a mechanistic relationship between SOX2 heterozygous variants and isolated hypogonadotropic hypogonadism. To further test the role of Sox2 in the hypothalamic-pituitary-gonadal axis, we generated mice with a whole-body heterozygous knockout of Sox2 (Sox2WT/KO). We found that heterozygous loss of Sox2 significantly delayed pubertal onset in both male and female Sox2WT/KO mice compared to wild-ype (WT) controls. In females, fertility was also compromised, with fewer estrous cycles and a significant delay in time to first litter of Sox2WT/KO dams compared to WT controls. Circulating levels of gonadotropins were normal in both male and female Sox2WT/KO mice, suggesting a functional pituitary. Finally, we assessed the number of kisspeptin and GnRH neurons and found that Sox2WT/KO mice do not differ from controls in the number of kisspeptin neurons but have significantly fewer GnRH neurons. This deficit occurs before birth, as by embryonic day 15.5, there are already fewer GnRH neurons in the Sox2WT/KO mice. Using luciferase assays, we determined that Sox2 increases expression of GnRH in vitro; thus, the decrease in GnRH-expressing neurons in vivo is likely the result of Sox2 haploinsufficiency. Together, these data further substantiate a critical role for SOX2 in the hypothalamic-pituitary-gonadal axis via effects on GnRH neuron development and, therefore, pubertal timing and reproductive function.

The ability to record the real-time activity of specialized neurons in the brains of female mice is providing new insights into the hormonal control of ovulation.