Citations

Background: Mu opioid receptors (MORs) in peripheral tissues mediate adverse effects of opioids that impair health-related quality of life (HRQoL) and may stimulate cancer progression via mitogenic signaling. Naloxegol, a peripherally acting MOR antagonist (PAMORA), is approved for opioid-induced constipation. Safety and efficacy of naloxegol have not been evaluated concurrently with systemic cancer therapy. Methods: We conducted a randomized, double-blind, placebo-controlled trial of naloxegol in patients with advanced lung adenocarcinoma starting first-line systemic therapy. Results: Only 50 patients were enrolled; the trial was terminated early due to slow accrual. Two of the three components of the feasibility primary endpoint were not met (accrual and PRO completion). At 6 months, FACT-L emotional well-being was better with naloxegol (p = 0.0113). There were trends towards better Trial Outcome Index (p = 0.0505) and physical well-being (p = 0.0628) with naloxegol. Bowel function favored naloxegol for constipation (p = 0.0223), rectal pain during defecation (p = 0.0075), and abdominal pain from constipation (p = 0.0113). Adverse event frequency and severity, PRO-CTCAE, urinary hesitancy, pain scores, and progression-free and overall survival were comparable between naloxegol and placebo. Conclusions: Naloxegol appears to be safe and tolerable, with a signal of improved HRQoL and previously unappreciated benefit for emotional well-being, without adverse clinical outcomes. Our findings should be confirmed in larger studies. ClinicalTrials.gov ID: NCT03087708.

Background: Sinonasal undifferentiated carcinoma (SNUC) is an extremely rare, high-grade, and aggressive tumor of the sinonasal tract. Due to the rarity of this malignancy, current treatment guidelines are based on small and often/mainly single-center retrospective datasets. In the absence of a universally accepted standard of care for SNUC, treatment approaches vary across countries and institutions, reflecting real-world clinical practice. The primary aim of this study was to describe real-world treatment and outcomes for patients with confirmed SNUC. Methods: This was an international, multi-center, retrospective, observational cohort study that pooled patients into the largest SNUC dataset to date. Fifteen centers were enrolled to contribute data, including seven from Europe, four from the United States, three from the United Kingdom, and one from Canada. In the absence of a universally accepted standard of care for SNUC, treatment approaches varied across countries and institutions, reflecting real-world clinical practice. Patients included were those with histologically confirmed SNUC who were treated between 1997 and 2021. Results: This study yielded 485 patients treated for SNUC. The median age at diagnosis was 55.6 years (IQR: 44.5–67.6), and 63.7% were male. Most cases presented at advanced stages, with 70.8% as T4a or T4b. Overall survival (OS) outcomes were available for 412 patients, with a median follow-up of 26.0 months. The 5- and 10-year OS were 47.2% (95% CI: 40.8–53.3%) and 39.6% (95% CI: 32.5–46.6%), respectively. Advanced age, dichotomized T-stage (T4a/b vs. T1–3), M-stage, and orbital involvement were significant poor prognostic factors on univariable analysis (p’s < 0.01). On multivariable analysis, orbital involvement (HR: 2.73, 95% CI: 1.42–5.27, p = 0.003) and distance metastasis stage (HR: 3.00, 95% CI: 1.25–7.21, p = 0.014) were both independently associated with worse OS. Conclusions: This observational study presents the largest multi-center cohort analysis of SNUC to date, providing new insights into prognostic factors for a rare cancer treated at global centers of excellence. Orbital involvement and the presence of metastases are candidate independent risk factors associated with poorer OS.

Background: Simultaneous carpal tunnel release (sCTR) with emergent forearm fasciotomy in the setting of acute compartment syndrome (ACS) has been reported, but the national incidence and cost of delayed carpal tunnel release (CTR) remain unknown. This large database study aims to evaluate how often sCTR is performed, the frequency of delayed CTR when not performed simultaneously, and the associated costs. Methods: The PearlDiver Mariner database was queried for patients who underwent forearm fasciotomies between January 1, 2015, and October 31, 2022. Patients were grouped based on CTR timing: simultaneous, within 2 weeks, 2 weeks to 1 year, 1 to 5 years, or no CTR. Reimbursement data were collected, and patient numbers and costs were analyzed across cohorts. Results: More than half of patients undergoing emergent forearm fasciotomy received sCTR. Among those who did not, 31% required CTR within 1 year and 35% within 5 years. The total cost was highest when CTR was performed within 1 year but not on the same day as fasciotomy. After 1 year, the additional cost of CTR was similar to that of patients who never underwent fasciotomy. Conclusions: This large database study shows that over one-third of patients who did not undergo sCTR at the time of emergent forearm fasciotomy required it within 1 year, incurring significantly higher costs. Including sCTR during initial fasciotomy may reduce delayed care and associated expenses. While these findings suggest that including sCTR during initial fasciotomy may reduce delayed care and expenses, the retrospective design precludes definitive recommendations, and clinical judgment remains essential Level of Evidence: 4

Purpose: To quantify the prevalence of neural axial abnormalities in congenital early-onset scoliosis (C-EOS) patients stratified by age group, correlate prevalence of treatment, and determine if a delay in MRIs affects outcomes. Methods: A multicenter registry with data on 751 C-EOS patients was retrospectively reviewed, of which 659 patients were included. Data included demographics, pre-index major coronal curve, age at first MRI, intraspinal MRI findings, neurosurgical interventions and scoliosis fixation performed, intraoperative and postoperative complications, and unplanned return to the operating room (UPROR) for orthopaedic complications. Patients were divided into 2 cohorts utilizing age 3 as a cutoff. This age cutoff was selected based on an FDA warning of the potential neurocognitive effects of anesthesia used for MRIs in patients younger than 3 years. Spearman Rho correlations, independent t tests, and χ 2 tests were used for statistical analysis. Results: Patients were divided into 2 groups: first MRI younger than or equal to 3 years of age (n=277) and older than 3 years of age (n=382). One hundred thirty-three abnormal MRIs were identified (20%). There was no significant correlation between age at MRI and abnormal intraspinal findings (rs= −0.018, P =0.64). Among patients with abnormal MRIs, no correlation existed between age at MRI and UPROR. In this cohort, 23 neurosurgical procedures were performed and no significant difference was found in UPROR between groups ( P =0.54). There were 3 neurologic complications in the younger than or equal to 3-year group and 0 in the older than 3-year group ( P =0.07). No significant difference was found in mean pre-index major coronal curve ( P =0.25). Conclusions: The prevalence of neural axis abnormalities in C-EOS was 20%. There was no significant correlation between age at first MRI and the chance of an abnormal MRI. There were no significant differences in neurological complications and UPROR between the younger than or equal to 3-year and older than 3-year groups. Thus, in C-EOS, MRI may be cautiously deferred until after the age of 3 in patients with normal neurological examinations and radiological findings.

Enhancing stability is a crucial factor in selecting bioactive compounds in most applications, while encapsulation techniques have proven to be a promising solution.

Abstract Medial meniscus extrusion, particularly in the setting of medial meniscus posterior root tears (MMPRTs), has become an area of interest in recent years due to the correlation between meniscus extrusion with inferior clinical outcomes, progression to osteoarthritis, and increased rate of conversion to total knee arthroplasty after MMPRT repair. This correlation led to the development of meniscus centralisations procedures that can be performed in addition to MMPRT repair and/or high tibial osteotomy. Although it was originally thought that medial meniscus extrusion was a consequence of MMPRTs, it has been reported that meniscus extrusion often precedes the development of MMPRTs, which suggests that there may be underlying meniscus pathology that predisposes to the development of both meniscus extrusion and MMPRTs. The purpose of this narrative review is to provide an overview of the anatomy, pathology, and surgical management of meniscus extrusion and MMPRTs, while identifying areas of future research to further elucidate the relationship meniscus extrusion and MMPRTs that may be necessary to improve outcomes after MMPRT repair. Level of Evidence Level V.

ABSTRACT Background Previous studies have shown an increased prevalence of eosinophilic gastrointestinal disease (EGID) in pediatric liver and heart transplant recipients. However, EGID after other solid organ and bone marrow transplantations has not been extensively evaluated. Aims The purpose of this study is to determine relationships between subsets of EGID with different solid organ and bone marrow transplants in pediatric patients. Methods We performed a single‐center retrospective chart review of pediatric patients with transplant and EGID between 2007 and 2023. For comparison between transplant groups, ANOVA was used for statistical analysis of continuous variables, and Fisher's exact test was used for categorical variables. Results There were 30 patients with EGID (eosinophilic esophagitis [EoE] = 21; eosinophilic gastritis [EoG] = 4; EoE + EoG = 3; EoE + eosinophilic colitis [EoC] = 1; eosinophilic duodenitis [EoD] = 1) and history of transplant (liver = 15; heart = 9; bone marrow = 3; multivisceral liver + small bowel + pancreas = 2; kidney = 1). When comparing the transplant groups, there was a significant difference in EoE + EoG incidence ( p = 0.011), specifically, EoE + EoG was present in 2 (100%) multivisceral and in 1/15 (7%) liver transplant patients. A statistically significant difference in the presence of gastroesophageal reflux (GER) and oral allergy syndrome between groups was noted ( p = 0.036, p = 0.033). There was no significant difference in the symptoms leading to EGID work‐up: incidence; morphologic features; achievement of histologic remission; medications; or family history of atopy between groups. Conclusion This retrospective biopsy‐confirmed cohort demonstrates that EGID subtype varies by transplant type, with higher rates of EoE + EoG in multivisceral recipients. Findings are exploratory and hypothesis‐generating; larger multicenter studies including more non‐liver and non‐heart transplant patients are needed.

Coronary microvascular dysfunction (CMD) is increasingly recognized as a central mechanism underlying myocardial ischemia, heart failure with preserved ejection fraction, and adverse cardiovascular outcomes in patients with and without obstructive coronary artery disease. The coronary microcirculation plays a critical role in regulating myocardial perfusion through tightly coordinated myogenic, metabolic, and endothelial pathways. Disruption of these mechanisms results in impaired vasodilatory capacity, abnormal coronary flow reserve, and microvascular ischemia. This review summarizes the anatomy and physiology of coronary microcirculation and examines the pathophysiologic mechanisms driving CMD, including endothelial dysfunction, structural remodeling, inflammation, and neurohormonal dysregulation. Contemporary diagnostic strategies are reviewed, with emphasis on invasive coronary function testing and advanced noninvasive imaging modalities such as positron emission tomography and cardiac magnetic resonance imaging. The clinical implications of CMD across diverse disease states, including ischemia with nonobstructive coronary arteries, heart failure, and cardiomyopathies, are discussed. Finally, current therapeutic approaches, prognostic considerations, and emerging research directions aimed at improving diagnosis and targeted treatment of CMD are highlighted.

Abstract Studies on the association between pineal gland calcification (PGC) and non-breathing sleep-related symptoms are inconclusive. The present study aims to evaluate this association in middle-aged and older adults living in rural villages located in coastal Ecuador. Community-dwellers aged ≥ 40 years enrolled in the Three Villages Study cohort were interviewed with the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality and received head computed tomography for automated measurement of PGC volumes. Generalized linear and logistic regression models were used to assess the association between PGC volumes (exposure) and the PSQI score and sleep quality (as separate dependent variables), after adjusting for age and sex. The study included 1,009 participants (mean age: 56.5 ± 12.6 years; 57% women). The mean volume of PGC was 51 ± 53.5 µL. The mean score of the PSQI was 5.3 ± 2.8 points, with 399 (40%) participants having poor sleep quality. Locally-Weighted Scatterplot Smoothing showed a linear relationship between continuous PGC volumes and PSQI scores. An unadjusted generalized linear regression model showed a significant association between PGC volumes stratified in tertiles and the continuous PSQI score. However, this association lost statistical significance after adjustment for age and sex. The association between tertiles of PGC and poor sleep quality was non-significant in both unadjusted and multivariate logistic regression models. Study results did not find an association between increased PGC and sleep quality after adjusting for demographics, suggesting that PGC may not necessarily indicate pineal dysfunction but could reflect adaptive physiological mechanisms.