Atrium Health Wake Forest Baptist

Sacrospinous hysteropexy (SSH) is increasingly being performed, yet limited evidence exists on whether an anterior versus posterior compartment surgical approach may affect postoperative prolapse symptoms or differences in adverse events. The objectives of this study were to evaluate whether an anterior versus posterior approach to SSH affects short-term postoperative bulge symptoms; secondarily, assess differences in intraoperative and 30-day postoperative complication rates. A retrospective cohort analysis of women who underwent anterior or posterior compartment approach native tissue transvaginal SSH between 2016 and 2024 at 2 academic institutions was performed. The primary outcome was the presence of bulge symptoms. Secondary outcomes were retreatment with pessary or surgery, operative data, and 30-day postoperative adverse events categorized by the Clavien-Dindo system. Study inclusion criteria were met by 316 women. Women in the anterior approach group were older (mean ± SD shown), (70 ± 7 vs 64 ± 15) years, P < 0.0001, had a higher Charlson Comorbidity Index (CCI), median (IQR) (3 [2-4] vs 0 [0-0], P <0.0001), proportion of stage 3 and 4 prolapse (95/162 [58.6%] vs 65/154 [42.2%], P = 0.004), and greater point Ba on Pelvic Organ Prolapse Quantification (POP-Q) examination (2 [1, 3] vs 0 [-1, 2], P < 0.0001), respectively. Controlling for age, preoperative POP-Q stage, preoperative dominant prolapse compartment, and concomitant midvaginal repairs, proportional hazards modeling showed bulge symptoms earlier in the posterior approach group ( P = 0.002). There was a higher proportion of Clavien-Dindo I and II 30-day complications in the anterior approach group (21.6% vs 7.1%, P = 0.0002). Undergoing an anterior approach to native tissue SSH may be protective to both bulge symptom recurrence and retreatment but was associated with higher short-term complications. Prospective longer-term outcomes are needed.

Introduction: Withdrawal of life-sustaining treatment (WLST) is the most common mode of death in pediatric intensive care units (PICUs), yet data on how WLST is operationalized remain limited. Prior studies have not adequately examined variability in WLST medical management practices for children across institutions or over time. We hypothesized that substantial institutional and temporal variation exists in WLST practices related to analgesic and sedative use, vasoactive medication discontinuation, neuromuscular blockade, and post-extubation respiratory support. Methods: We performed a secondary analysis of the multicenter DONATE study (2009-2021), which included 905 pediatric patients who died following WLST defined as terminal extubation. Data were abstracted from 9 U.S. tertiary-care PICUs and included medications and interventions administered before and after extubation. Site-level differences were assessed using chi-square or Fisher’s exact tests. Logistic regression was used to assess temporal trends. Results: Of 905 patients, 75.1% died within 1 hour of WLST. Opioids were administered in 79.7% (site range 68-89%, p< 0.001; no significant temporal trend); benzodiazepines in 56.0% (site range 41-66%, p< 0.001; decrease over time OR 0.95 per year, 95% CI 0.90-0.99, p=0.04); dexmedetomidine in 15.5% (site range 4-21%, p=0.002; increase over time OR 1.16 per year, 95% CI 1.05-1.27, p=0.004). Vasoactive infusions were discontinued in 88.1% of cases (site range 59-100%, p< 0.001; increase over time OR 1.15 per year, 95% CI 1.04-1.26, p=0.007). Neuromuscular blockade was used in 5.1% of patients (site range 0-13%, p< 0.001; increase over time OR 1.23 per year, 95% CI 1.08-1.40, p=0.002). Use of any post-extubation respiratory support was rare (5.5%) with no significant site or temporal variation. Conclusions: There is substantial institutional and temporal variability in WLST practices across US PICUs. These findings highlight a need for clearer guidance to reduce variability and support consistent, high-quality end-of-life care for critically ill children.

Introduction: Bronchiolitis is one of the most common reasons for pediatric intensive care unit (PICU) admission in the U.S., yet it has significant disparities in treatment based on social determinants of health. The purpose of this study was to assess for associations between the Child Opportunity Index (COI) and PICU outcomes in children with bronchiolitis. Methods: Secondary analysis of a multicenter retrospective cohort study including data from 15 PICUs from 1/1/2019-12/31/2020. The dataset was queried for patients 0-2 years of age with bronchiolitis as the primary diagnosis for PICU admission. Patient addresses were mapped to COI 2.0 and assigned to a quintile (very low, low, moderate, high, very high). Demographics and clinical features were compared by COI quintile. Primary outcomes were severity of illness on presentation via PRISM III score and use of invasive mechanical ventilation (IMV) and noninvasive ventilation (NIV). Secondary outcomes were PICU length of stay (LOS) and mortality. Results: Of 3,671 total admissions, the very low COI group had the highest proportion of admissions (28.1%) and history of prematurity (33%). There was no difference in PRISM III scores across all groups. Paired comparisons of COI groups revealed significantly higher use of NIV in the very high COI group compared to the lowest 3 COI groups (p ≤ 0.008). Both the very high and very low groups had lower rates of intubation compared to low and moderate groups (p ≤ 0.04). Neither PICU LOS nor mortality differed significantly across all groups. Multivariate analysis showed PRISM III score (aOR 2.77, 95% CI 2.34-3.27) and prematurity (aOR 1.32, 95% CI 1.05-1.66) as independent risk factors for any positive pressure ventilation (PPV [both IMV and NIV]), but no difference for COI group. Conclusions: In this study, children admitted to the PICU with bronchiolitis are more often from very low COI neighborhoods. Patients from very high COI neighborhoods are more likely to receive NIV support and less likely to require intubation. Interestingly, patients from the very low COI group are also less likely to need intubation compared to the low and moderate COI groups. Higher PRISM III scores and prematurity were risk factors for PPV use, but COI group was not.

The prognosis and optimal management of bladder cancer are closely dependent on accurate clinical staging. Traditional staging has relied on transurethral resection for T-staging in combination with cross-sectional imaging for N and M-staging. Computed tomography (CT) is the most accessible and common cross-sectional imaging modality to assess for local and distant spread of disease. However, CT alone lacks the contrast resolution to distinguish between non-muscle-invasive and muscle-invasive disease and has known difficulty distinguishing metastatic from normal lymph nodes (LNs). Magnetic resonance imaging (MRI) and positron emission tomography (PET) have been increasingly used in the workup of bladder cancer to address the shortcomings of CT imaging. MRI using the multiparametric combination of T2-weighted, dynamic contrast-enhanced, and diffusion-weighted imaging can more clearly delineate the extent of tumor involvement in the bladder. PET can use a variety of metabolically active radiotracers to visualize cancerous tissue, allowing the identification of metastases that may not be readily visible on CT. PET scans can also detect disease in normally sized LNs that do not meet conventional CT size thresholds. The combination of MRI and PET scans has not been explored in detail with respect to bladder cancer workup but may theoretically combine the strengths of both approaches to provide the most comprehensive, noninvasive tool for preoperative staging, with improved sensitivity and accuracy compared to other modalities. This narrative review uses a systematic search of the PubMed database from 2000 to 2025 to analyze MRI and PET, both separately and in synergy, for the local and distant staging of bladder cancer, as well as key technical advancements in these imaging technologies. Synergy of the imaging modalities potentially increases efficacy in bladder cancer staging.

Glioblastoma (GBM) is an extremely aggressive and incurable primary tumor of the brain. GBM is characterized by interpatient and intratumoral heterogeneity, making this cancer particularly resistant to therapy and likely to recur. Mapping the complex dynamics that underpin the development and evolution of gliomas with human-based in vitro models is difficult. This study aimed to generate 3D glioma patient-derived tumor constructs (PTCs) using a clinically relevant, Matrigel-free, hyaluronic acid system, evaluate their suitability in drug screening assays, and determine the stability of their genetic profiles compared to originating tumors. In this study, we utilized a synthetically modified hyaluronic acid and gelatin hydrogel system to generate tumor constructs containing cells from clinical glioma biospecimens. PTCs were characterized phenotypically, after which they were deployed in chemotherapy drug screens using temozolomide (TMZ) and a P53 activator compound. Drug responses of these 3D cultures were compared with 2D cultures, as well as PTCs that were generated after passaging in 2D. RNA sequencing was used to evaluate genetic parity between PTCs or 2D cultures with originating tumor tissues, using The Cancer Genome Atlas (TCGA) GBM subpopulations for subcategorizing. PTCs were created successfully from five World Health Organization (WHO) grade 4, two grade 3, and two grade 2 gliomas. PTCs were maintained with high viability. Chemotherapy drug screens demonstrated that expected TMZ responses were observed for Isocitrate dehydrogenase (IDH) mutant diffuse gliomas while drug response was variable for IDH wildtype GBM PTCs. PTCs demonstrated stable drug response over time, while 2D passaging resulted in significant shifts in drug sensitivity. RNA sequencing revealed maintenance of subpopulation signatures for PTCs which clustered with their originating patient tumor tissue. In contrast, 2D cultures largely clustered together regardless of the patient. Our PTC approach utilizes a defined hydrogel biomaterial system that maintains the genotypic and drug response characteristics of patient tumors making this an ideal ex vivo model for translational applications.

Mutations in protein tyrosine phosphatase non-receptor type 11 (PTPN11) have been considered late acquired mutations in acute myeloid leukemia (AML) development. Using single-cell DNA sequencing, we found that PTPN11 mutations can occur as initiating events in some patients with AML when accompanied by strong oncogenic drivers, commonly NPM1 mutations. The resulting AML has a diverse set of variably differentiated myeloid cells with few myeloid cells that lack leukemic mutations. The role of Ptpn11 as a codriver was confirmed in a murine model that exhibits an AML phenotype with a comparable immune diversity that is serially engraftable and reconstituted from early precursor cells. Furthermore, lineage-negative bone marrow cells from these mice reconstitute the full diversity of mature myeloid cells, and these cells exhibit an altered cytokine response after physiologic stimulation. Our work highlights how PTPN11-mutated AML is derived from a multitude of codominant and late acquired aberrations that have a previously unrecognized differentiated myeloid clonal expansion potentially contributing to pathogenesis of the disease.

The opportunity for new biomarker-based tests to predict treatment response and the appropriate use of emerging rheumatoid arthritis (RA) therapies may depend on patients' prior treatment history. We examined rheumatoid arthritis (RA) treatment sequences and biologic/JAKi initiation overall and by line of therapy (LoT) to estimate the size of the eligible RA patient population in the U.S. for a new predictive treatment response test using a population-based RA inception cohort. We utilized an augmented health plan claims database to create an inception cohort of RA patients and estimated the rate of advanced treatment (biologic or JAKi) addition or switch. Results were stratified by advanced treatment naïve vs. treatment-experienced status and also described specific RA treatment sequences and combinations over time. Among 37,656 RA patients, 59,557 new RA treatment initiations were identified. Most patients (85.2%) initiated biologics; the remainder initiated JAKi. Of these, 40.2% used biologics/JAKi as monotherapy. The overall biologic/JAKi addition/switch rate was 25.7 per 100 patient-years (22.7/100py in biologic-naïve patients, and >30/100py in treatment-experienced patients). Rates varied substantially between prescribers, with an observed add/switch rate in the practices of prescribers in the highest decile (53.8/100py) more than 4-fold greater than rates in the practice of prescribers in the lowest decile (12.1/100py). These findings highlight the size and characteristics of the eligible RA population in the U.S. initiating a new RA biologic or JAKi treatment each year, thus providing valuable insights for stakeholders developing or marketing new RA therapies or biomarker-based diagnostic tests to predict future treatment response.

This national survey of academic anesthesiology researchers offers an important and timely window into the evolving landscape of scholarly activity within our specialty. Over the past decade, anesthesiology has experienced a convergence of stressors--declining federal and foundation funding, inconsistent institutional investment in research infrastructure, shifting scientific priorities, and escalating clinical demands--that collectively threaten the stability and future growth of the academic workforce. Over 50% of the anesthesiology workforce is over 55 years of age. Many of these physicians are approaching retirement, and the anesthesiology workforce is shrinking relative to clinical need and demand. This places enormous pressure on Academic Medical Centers (AMCs) to retain and recruit faculty to not only engage in research but also teach the next generation of anesthesiologists. The preliminary survey findings reflect a community that is deeply committed to advancing scientific inquiry but increasingly strained by structural and systemic challenges that impede productivity, innovation, and career development.