Citations

Abstract Modern radiation therapy (RT) technologies allow for improved sparing of normal tissues, decreasing the risk of both acute and long-term toxicities. Existing RT dose constraints for prospective trials within the National Clinical Trials Network (NCTN) were formulated in the context of solid malignancies. As patients with hematologic malignancies are often treated with lower RT doses and are usually younger with more favorable prognoses, customized dose constraints are needed. The NRG Oncology Hematologic Malignancies Working Group (NRG HEME) commissioned a review of existing organ-at-risk (OAR) constraints from published primary literature, the NRG Center for Innovation in Radiation Oncology (CIRO), and national guidelines. Customized constraints were developed by iterative review by NRG HEME. Final recommendations were approved by radiation oncology representatives from all the lymphoma NCTN groups (NRG Oncology, Children’s Oncology Group, Alliance, ECOG-ACRIN, SWOG, Canadian Cancer Trials Group). For 49 OARs, a strict recommended constraint was determined, of which 20 were not present in CIRO. Of the remaining 29 constraints, 20 were lower, 2 were the same, and 5 used different metrics; 2 were higher than at least 1 CIRO trial constraint. Acceptable variations were determined and unacceptable variations were added for select critical OARs for plan scoring. While doses to OARs without explicit unacceptable variations should not exceed acceptable variations, violations should not be considered for plan quality assessment on trials. This consensus list of standard OAR constraints should be incorporated for all future NCTN trials in hematologic malignancies. Strict dose constraints will minimize long-term toxicities in this patient population.

Abstract Purpose: This multicenter, multi-surgeon retrospective study aimed to identify risk factors for postoperative cerebrospinal fluid (CSF) leak following endonasal resection of craniopharyngioma, while evaluating the "perception gap" through a surgeon survey. Methods: A retrospective review was conducted on 416 patients who underwent endoscopic transsphenoidal surgery (ETS) for craniopharyngioma from 20 institutions. Factors were compared between patients with and without postoperative CSF leak, and between Early (2007-2015) and Late (2016-2025) Epochs. Complementing the clinical data, a survey of 19 neurosurgeons captured expert perspectives on risk stratification and management strategies. Results: Overall postoperative CSF leak rate was 13.5% (56/416 patients). Univariate analysis identified predominantly cystic tumors (34% vs. 21%, p = 0.034)and intraoperative lumbar drain (LD) use ( p < 0.028) as associated with postoperative CSF leak. BMI ( p = 0.587), prior surgery ( p = 0.576), and tumor size ( p = 0.363) were not significant. In the multivariable analysis, LD use was associated with a higher postoperative CSF leak rate (OR 1.91, 95% CI 1.06–3.46; p = 0.030). Between Epochs, nasoseptal flap (NSF) utilization increased from 70.7% to 87.6% ( p <0.001). NSF was protective (OR 0.28, 95% CI 0.07–0.92; p = 0.037) in the Early Epoch; no factors were significant in the Late Epoch. The surgeons’ survey identified prior surgery and intraoperative high flow leaks as primary risks; however, their LD protocols diverged from clinical data. Conclusion: Despite increased use of NSF, CSF leak persists. The study highlights a significant divergence between expert perception and clinical data regarding lumbar drains.

Measuring intraperitoneal pressure (IPP) has been proposed as a means to help maintain optimal ultrafiltration and prevent complications such as hernias, peritoneal leaks, and gastroesophageal reflux, which are linked with high IPP levels. The Durand method is a commonly accepted method for measuring IPP; however, it is cumbersome and not routinely used in clinics due to its complexity. Here we report the outcome of a pilot study that evaluated the agreement between IPP measured using an in-line pressure transducer and IPP measured using the Durand method during in-clinic automated peritoneal dialysis (APD) therapy. This was an exploratory, descriptive, early feasibility study conducted among patients with a diagnosis of kidney failure who were on APD therapy. IPP was continuously measured using an investigational device (x-MIP transducer) and at fixed timepoints using the Durand method. The study included 10 patients with a median age of 47.0 years and a median body mass index of 28.1 kg/m 2 . The study population was predominantly female, comprising 70% of the participants. The transducer IPP showed a moderate agreement with manual IPP, as most differences in measurements were within ±3 cmH 2 O. Overall, IPP did not correlate with fill-volume. However, when examined on a per-patient level, six patients showed stronger correlations ( ρ > 0.7) between IPP and fill-volume, while the remaining four patients had weaker correlations ( ρ < 0.5). No safety concerns were identified in the study. In summary, this study indicates that a transducer-based IPP measurement device could serve as an alternative to the Durand method.

Abstract INTRODUCTION We examined when Alzheimer's disease biomarkers become informative by identifying age‐related breakpoints with slope‐changing trajectories. METHODS In 2082 Mayo Clinic Study of Aging participants, we modeled plasma amyloid beta (Aβ)42/40, phosphorylated tau (p‐tau)181, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid/tau positron emission tomography (PET), hippocampal volume (HVa), and global cognition. Generalized additive models described age trends; Davies' test and piecewise linear regression estimated breakpoints. A C2N subsample ( n = 462) provided mass‐spectrometry plasma markers (p‐tau181, p‐tau217, their ratios, Aβ42/40). RESULTS In the full cohort, Aβ42/40, HVa, and cognition declined with age; p‐tau181, NfL, GFAP, and amyloid/tau PET increased. We observed single breakpoints (years, 95% CI): GFAP 68.1 (63.5–71.8), NfL 70.7 (65.9–75.6), p‐tau181 67.2 (60.3–70.3), amyloid PET 62.3 (56.2–69.3), HVa 68.1 (63.1–71.9), cognition 59.8 (55.4–66.0); tau PET showed none. In the mass‐spectrometry subset, p‐tau217 and p‐tau181 broke at 72.6; their ratios and Aβ42/40 showed no breakpoints. DISCUSSION Breakpoints cluster near late midlife, suggesting windows for screening and monitoring.

Introduction Preoperative testosterone exposure has been associated with various health outcomes, but its impact on postoperative complications in patients undergoing total shoulder arthroplasty (TSA) has not been fully explored. This study aims to evaluate the association between preoperative testosterone exposure and postoperative medical and surgical complications in patients undergoing TSA. Methods A retrospective cohort study was conducted using the PearlDiver database. Patients who underwent TSA and used preoperative testosterone within 3 months of the index procedure were identified and matched 1:4 to controls without testosterone use using propensity score matching. Matching was performed based on age, gender, comorbidities, Charlson comorbidity index, obesity, tobacco use, and hypogonadism to balance the groups. Postoperative complications were assessed at 90 days and five years. Statistical comparisons were made using odds ratios (ORs) with 95% confidence intervals (CIs), and a p -value of <0.05 was considered statistically significant. Results The matched cohort included 677 testosterone users and 2554 controls. There were no statistically significant differences between the testosterone and control groups in 90-day complications such as myocardial infarction (OR 2.52, P = 0.31), pneumonia (OR 0.86, P = 0.70), and deep vein thrombosis (no cases in the testosterone group). Over five years, the testosterone group had a significantly higher risk of periprosthetic joint infection (4.1% vs. 2.4%, OR 1.76, 95% CI 1.10–2.75, P = 0.015), but no differences in revision rates, dislocation, aseptic loosening, or stiffness were observed. Conclusion Preoperative testosterone exposure was associated with a higher risk of periprosthetic joint infection following TSA, but no significant differences were found in major medical complications or revision rates.

Background Reductions in blood pressure (BP) control among patients with hypertension were observed early in the COVID‐19 pandemic. The degree to which BP control may have returned to prepandemic levels is unknown. Methods Individuals aged 18 to 85 years with hypertension from 17 health systems participating in the National Patient‐Centered Clinical Research Network were identified using electronic health record data collected as part of routine care. BP control (percentage of patients whose most recent BP measurement was <140/<90 mm Hg) was estimated in a series of 12‐month rolling measurement periods from 2017 through 2022 (January 1, 2017 through December 31, 2017; April 1, 2017 through March 31, 2018; … January 1, 2022 through December 31, 2022). Differences in average BP control between 2022 (January 1, 2022 through December 31, 2022) and 2019 (January 1, 2019 through December 31, 2019) were estimated overall (adjusted for age, sex, and race and ethnicity) and by race and ethnicity (adjusted for age and sex). Results Our sample included 1 193 314 persons with hypertension in 2019 (48.9% aged 65–85 years, 52.9% men, 66.2% non‐Hispanic White) and 1 499 418 individuals in 2022 (50.6% aged 65–85 years, 47.1% men, 62.7% non‐Hispanic White). The weighted average BP control dropped from 65.3% in 2019 to 61.8% in 2020 and then partially recovered to 62.6% in 2022 (adjusted mean difference, −2.6 percentage points [95% CI, −5.0 to −0.2]). Non‐Hispanic Asian individuals experienced the largest temporal drop in BP control, declining from 68.4% in 2019 to 63.9% in 2022. Conclusions BP control was disrupted during the COVID‐19 pandemic and had not fully rebounded to prepandemic levels by the end of 2022. Continued surveillance is needed to determine whether the decline in BP control will persist and will result in future adverse cardiovascular events.