Faculty Bibliography

BACKGROUND:Preterm infants encounter DEHP through medical devices and equipment. While hyperoxia is known to promote cardiac remodeling and dysfunction, the impact of early phthalate exposure is understudied. We hypothesized that independent and combined DEHP and hyperoxia exposure would impair neonatal cardiovascular development. METHODS:Newborn rats were exposed from birth to day 14 to one of four conditions: control (21% oxygen), hyperoxia (60% oxygen), DEHP (25 mg/m3), and DEHP + hyperoxia (25 mg/m3 DEHP and 60% oxygen). Cardiac tissue and serum were analyzed by histology, RT-qPCR and ELISA for markers of contractility, angiogenesis, and inflammation: myosin heavy chain 6 (Myh6), vascular endothelial growth factor (VEGF), interleukin-4 (IL-4), interleukin-10 (IL-10), and fractalkine (CX3CL1). RESULTS:Histology found increased cell size, cytoplasm per nucleus, and nuclear area in all exposures. DEHP exposure and hyperoxia exposure reduced Myh6 and VEGF gene expression. Serum VEGF was higher in the DEHP + hyperoxia group compared to hyperoxia alone. IL-10 was decreased in all exposed groups. IL-4 was reduced in the DEHP + hyperoxia group. CXC3L1 was increased in the DEHP + hyperoxia group compared to hyperoxia alone. CONCLUSION(S)/CONCLUSIONS:Independent and concurrent DEHP and hyperoxia exposure during early neonatal development significantly disrupted markers of cardiac morphology, contractility, angiogenesis, and inflammation. IMPACT/CONCLUSIONS:Key Message: Postnatal exposure to DEHP adversely impacts neonatal rat cardiovascular development. Adds to Existing Literature: This is the first study to examine concurrent long-term hyperoxia and DEHP exposure on cardiovascular development in an animal model relevant to preterm infants. Identifies a modifiable contributor, DEHP, to adverse cardiovascular development. Identifies various cardiovascular components affected by DEHP and hyperoxia, including structural, angiogenic, contractile, and inflammatory aspects. Leads to a new approach to investigate the impact of environmental toxins and the origin of cardiovascular disease in the newborn period.

BACKGROUND:Improvements in cardiovascular health (CVH), an integral component of diabetes self-management, significantly reduce the risk of cardiovascular disease. OBJECTIVE:In this study, we aimed to compare CVH scores and explore barriers and facilitators to optimal CVH among 2 populations with type 1 diabetes (T1D) and type 2 diabetes (T2D). METHODS:This is a secondary analysis from 2 parent-sequential explanatory mixed-methods studies: the first examined a subsample of emerging adults living with T1D; the second included emerging to middle-aged adults living with T2D. Participants' CVH was assessed using the American Heart Association's definition of CVH (Life's Simple 7). Semistructured interviews explored participants' achievement of CVH behaviors. An inductive content analysis method guided data analysis. RESULTS:The T1D sample (n1 = 50) consisted of 90% self-identifed White adults with a mean age of22 ± 2.4 years and 70% females. The T2D sample (n2 = 60) included adults who self-identifed as Black (63%) and Hispanic (47%), with a mean age of 34.4 ± 5.0 years and 75% females. The mean CVH scores for the T1D and T2D groups were 9.4 ± 2.1 and 8.6 ± 2.2, respectively. For the T1D group, barriers included knowledge deficits, whereas self-efficacy and diabetes technology facilitated self-management. For the T2D group, barriers consisted of unhealthy food convenience and limited space for physical activity, whereas access to healthcare services facilitated CVH behaviors. Shared barriers included time constraints/competing demands and financial burdens; facilitators were social support and individualized care. CONCLUSIONS:Our analysis highlights distinct and shared barriers and facilitators to CVH in 2 emerging adult populations with diabetes, emphasizing the need to assess age-specific factors and tailor clinical interventions accordingly.

BackgroundPostoperative care following endoscopic sinus surgery (ESS) aims to optimize mucosal healing, reduce inflammation, and minimize infectious complications. Although saline irrigation is considered standard of care, the potential benefit of adding topical antibiotics, such as mupirocin, during the early postoperative period remains uncertain.ObjectiveTo evaluate whether short-term postoperative mupirocin nasal irrigation improves clinical, endoscopic, and microbiological outcomes compared with saline irrigation alone following ESS.MethodsThis prospective, randomized, double-blinded, placebo-controlled trial included adults with chronic rhinosinusitis undergoing ESS. Patients were randomized to receive either mupirocin (0.05%) nasal irrigation or placebo saline irrigation twice daily for 21 days postoperatively. Outcomes assessed within the first 3 months included patient-reported symptoms using the sinonasal outcomes test (SNOT-22) and visual analog scale (VAS), endoscopic findings (mucosal edema, polyp formation, crusting, granulation tissue, and purulence), postoperative sinus culture results, and need for systemic antibiotics.ResultsSixty-eight patients were enrolled, and 56 completed follow-up. Both groups demonstrated significant postoperative improvement in SNOT-22 and VAS scores compared with preoperative baseline, without significant between-group differences. However, the mupirocin group showed significantly lower rates of endoscopic mucosal edema and polyp formation at 1 month postoperatively. Negative postoperative cultures were also more frequent in the mupirocin group, with reduced need for systemic oral antibiotics. No significant differences were observed in crusting, granulation tissue, purulence, steroid use, or pain medication requirements.ConclusionShort-term prophylactic postoperative mupirocin nasal irrigation after ESS does not confer additional improvement in patient-reported quality-of-life outcomes compared with saline alone but appears to reduce early inflammatory endoscopic changes, bacterial culture positivity, and need for systemic antibiotics. Larger studies with longer follow-up are needed to confirm these findings.

BACKGROUND:Patients with femoroacetabular impingement syndrome (FAIS) experiencing >2 years of pain before hip arthroscopy have been linked with worse short-term and midterm outcomes. PURPOSE/OBJECTIVE:To examine the effect of preoperative pain duration on patient-reported outcomes (PROs), clinically significant outcomes, and reoperation rates in patients undergoing primary hip arthroscopy for FAIS. STUDY DESIGN/METHODS:Cohort study; Level of evidence, 3. METHODS:A prospectively maintained surgical repository was reviewed to select patients who underwent primary hip arthroscopy for FAIS between January 2012 and October 2014 with 10-year follow-up. Patients who reported pain ≥2 years before surgery were propensity score matched 1:1 to patients reporting preoperative pain <2 years by age, sex, and body mass index (BMI). PRO scores collected included those for the Hip Outcome Score-Activities of Daily Living (HOS-ADL), Hip Outcome Score-Sports Subscale (HOS-SS), modified Harris Hip Score (mHHS), and visual analog scale (VAS) for pain and satisfaction. Achievement rates of the minimal clinically important difference and patient acceptable symptom state were compared. Reoperation-free survivorship was compared with Kaplan-Meier analysis. RESULTS:= .11). CONCLUSION/CONCLUSIONS:Patients with pain ≥2 years before undergoing primary hip arthroscopy for FAIS significantly improved at 10 years but experienced worse function, pain, satisfaction, and achievement of clinically significant outcomes, with similar survivorship, compared to a matched group of patients with preoperative pain <2 years.

Patients with paroxysmal nocturnal hemoglobinuria (PNH) on anti-C5 often experience extravascular hemolysis with anemia. Iptacopan, the first oral proximal complement inhibitor targeting factor B, has shown efficacy and safety in PNH patients. APPULSE-PNH (NCT05630001), a phase 3b, single‑arm, open-label trial, enrolled adult patients with PNH and hemoglobin ≥10 g/dL on stable anti-C5 for ≥6 months. Patients switched to iptacopan monotherapy (200 mg twice daily; 24 weeks). Primary endpoint: mean hemoglobin change from baseline across four visits (Days 126-168). At baseline, 57.7% of patients had elevated absolute reticulocyte counts (ARCs; above ULN = 123 × 10⁹/L) and 50% had C3 deposition on red blood cells (RBCs) >10%, indicative of extravascular hemolysis. There was a statistically significant increase in hemoglobin during the trial; adjusted mean change from baseline (95% CI) was +2.0 g/dL (1.7-2.3) overall, and in patients with baseline hemoglobin <12 g/dL and ≥12 g/dL, +2.4 (2.0-2.7) and +1.4 (1.0-1.8), respectively. Patients maintained transfusion independence, 92.7% with hemoglobin ≥12 g/dL. Adjusted mean change from baseline (95% CI) in lactate dehydrogenase and ARC were -1.3% (-6.6 to 4.3) and -89.2 × 10⁹/L (-95.5 to -82.9), respectively. Mean (SD) proportion of C3d+ PNH RBCs, assessed by flow cytometry, decreased from 11.0% (8.6) to 0.2% (0.7) at Day 168. No patients had breakthrough hemolysis or major adverse vascular events. FACIT-Fatigue and treatment satisfaction scores improved by Days 84 and 168. Safety showed consistency with previous iptacopan PNH trials. Iptacopan improved hematologic outcomes in PNH patients with hemoglobin ≥10 g/dL on anti-C5, maintaining control of intravascular hemolysis and resolving extravascular hemolysis.

BACKGROUND:Population-based studies have linked progestin exposure to increased meningioma risk. However, the molecular basis of meningiomas associated with depot medroxyprogesterone acetate (DMPA) - a common injectable contraceptive-remains undefined. METHODS:We performed an integrated clinicopathologic and genomic analysis of meningiomas from 10 women with long-term DMPA exposure. Tumors underwent histopathological analysis, targeted sequencing, and DNA methylation profiling. Data were integrated with reference cohorts (Baylor and Heidelberg) and analyzed through classifier assignment, consensus clustering, copy number analysis, differential methylation testing, and dimensionality reduction. RESULTS:DMPA-associated meningiomas were all newly diagnosed, WHO grade 1 tumors with a predilection for the anterior and central skull base (n = 6). Nine patients harbored multiple meningiomas. Four experienced regression of untreated meningiomas following DMPA cessation, while five demonstrated stabilization. Histopathology demonstrated relative overrepresentation of metaplastic morphology, an uncommon meningioma subtype. All DMPA-associated meningiomas mapped to benign molecular groups, and most exhibited low copy number alteration burden. Targeted sequencing revealed enrichment for TRAF7 mutations (n = 5), with no NF2 mutations detected. Eight tumors shared consensus cluster identity, with cohesive grouping on principal component analysis and t-distributed stochastic neighbor embedding. No differential methylation was identified at the progesterone receptor locus. CONCLUSIONS:DMPA-associated meningiomas represent a recognizable phenotype within the broader NF2-wildtype/TRAF7-enriched spectrum of benign meningiomas, characterized by chromosomal stability, a shared methylation profile, tumor multiplicity, and regression or stabilization following DMPA cessation. While derived from a small single-institution cohort, these findings provide a molecular framework for understanding progestin-associated meningioma biology, re-interpreting epidemiologic literature, and informing population-level risk stratification.

PURPOSE/OBJECTIVE:Central nervous system (CNS) involvement in multidrug-resistant tuberculosis (MDR-TB) is associated with high morbidity, and evidence guiding the use of standardized all-oral regimens in intracranial disease is limited. We describe radiographic evolution of a presumed cerebellar tuberculoma during BPaLM-based therapy for MDR-TB. METHODS:We report the clinical course, microbiologic data, treatment regimen, and serial neuroimaging of a man in his 30s with pulmonary MDR-TB, pleural involvement, and a small peripherally enhancing cerebellar lesion compatible with a tuberculoma. RESULTS:The patient presented with respiratory symptoms and mild headache, and was diagnosed with cavitary pulmonary tuberculosis, pleural involvement, and a small left cerebellar lesion. Further evaluation showed no ataxia, dizziness, or focal neurologic deficits. Sputum acid-fast culture was positive for Mycobacterium tuberculosis, and rapid molecular testing demonstrated rifampin resistance. Whole-genome sequencing confirmed resistance to rifampin, isoniazid, and ethambutol, and did not identify mutations associated with resistance to pyrazinamide, fluoroquinolones, linezolid, clofazimine, or bedaquiline. Treatment was transitioned to BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin) with adjunctive corticosteroids early in the course. Sputum cultures converted to negative approximately 6 weeks after treatment initiation. Serial brain MRI demonstrated progressive reduction in lesion size at 9 weeks, residual punctate enhancement at 21 weeks, near-complete resolution by 44 weeks, and complete radiographic resolution on subsequent imaging. The patient completed 52 weeks of therapy and remained clinically stable, without neurologic deficits or relapse more than 2 years after treatment completion. CONCLUSION/CONCLUSIONS:This case describes radiographic resolution of a small presumed cerebellar tuberculoma during extended BPaLM/BPaL-based therapy for disseminated MDR-TB, highlighting the evidence gap for standardized all-oral regimens in CNS drug-resistant tuberculosis.

The Cattell-Imanaga reconstruction (CIR) is considered a more physiologic reconstruction after pancreaticoduodenectomy, as it promotes a more physiological mixing of alimentary and biliopancreatic secretions and facilitates endoscopic access to the anastomoses compared with traditional techniques. However, its application after total pancreatectomy (TP) has not previously been reported. This study describes the surgical technique and institutional experience with CIR, named modified CIR (mCIR), in patients undergoing open TP at a high-volume pancreatic surgery center. The mCIR positions the gastro-/duodeno-jejunostomy (G/DJ) proximally and the hepatico-jejunostomy (HJ) distally on a single transmesocolic limb. 89 patients underwent open TP with mCIR. Both en bloc and stepwise TP were performed; stepwise was mainly used for positive frozen margins (51.7%), high POPF risk (34.8%), or need for vascular resection to reduce POPF-related vascular complications (12.4%). Grade B-C biliary fistula occurred in 6.7% of patients, cholangitis secondary to hepatico-jejunostomy (HJ) stricture in 2.2%, delayed gastric emptying (DGE) in 11%, and duodeno-jejunostomy (DJ) leakage in 1.1%. An endoscopic interventional approach was generally preferred for the management of HJ complications. Major morbidity and 90-day mortality were 23.6% and 3.4%, respectively. The readmission rate was 9.7%, mainly due to infected or symptomatic collections. This is the first study to describe mCIR following TP and to report postoperative outcomes in line with previously reported results for traditional reconstruction techniques.