Citations

Abstract Context The impact of active hypercortisolism on sleep is incompletely characterized. Studies report impaired sleep in patients with Cushing syndrome (CS). Patients with mild autonomous cortisol secretion (MACS) demonstrate mild nocturnal hypercortisolism that could impact sleep. Objectives To characterize sleep abnormalities in patients with CS and MACS using the Pittsburgh Sleep Quality Index (PSQI), identify factors associated with poor sleep, and compare sleep abnormalities in patients with MACS vs referent subjects. Methods We conducted a single-center cross-sectional study of adults with active CS and MACS. Clinical and biochemical severity scores for hypercortisolism were calculated. Parallelly, we enrolled referent subjects. Quality of life was assessed using (1) the Short Form-36 (SF-36) in all participants and (2) the CushingQoL in patients with active hypercortisolism. Sleep quality was assessed using PSQI. Results PSQI was assessed in 154 patients with CS (mean 12, SD ±4.5), 194 patients with MACS (mean 11, SD 4.6), and 89 referents (mean 5, SD ±3.4). Patients with MACS exhibited shorter sleep duration, longer sleep latency, more severe daytime dysfunction, lower sleep efficiency, and a higher sleep medication use compared to referent subjects (P = <.001 for all). Age-, sex, and body mass index-adjusted analysis demonstrated no differences in PSQI or its subcomponents between patients with CS and MACS (P > .05 for all). In a multivariable analysis of patients with MACS, younger age, female sex, and higher clinical hypercortisolism severity score were associated with impaired sleep. In patients with CS, only younger age was associated with poor sleep. Conclusion Patients with MACS demonstrate sleep impairment that is similar to patients with CS. Younger women with higher clinical severity of MACS are more likely to have impaired sleep.

Abstract Context Patients with endogenous hypercortisolism experience glucocorticoid withdrawal syndrome (GWS) after surgery. Meditation may be an effective intervention to alleviate the severity of GWS. Objective To determine the acceptability of a portable, wearable electroencephalography device for guided meditation (MUSE headband) and the impact of MUSE use on GWS and quality of life 12 weeks postsurgery. Methods We conducted a single-center prospective cohort study of adults with endogenous hypercortisolism undergoing curative surgery from 2019 to 2024. Patients had baseline and postsurgical assessments over 12 weeks. The study comprised patients using MUSE for ≥ 6 weeks (MUSE cohort) and patients matched by age, sex, BMI, hypercortisolism type, and glucocorticoid type at 1:4 ratio. Quality of life and GWS symptoms were assessed with AddiQoL, CushingQoL, and 36-item Short Form Health Survey mental and physical component (SF-36 MCS and PCS) questionnaires. Results MUSE was offered to 52 patients, and 22 (42%) used MUSE for ≥ 6 weeks within 12 weeks after surgery. At baseline, compared to 88 matched subjects, 22 MUSE participants demonstrated similar prevalence of comorbidities and clinical and biochemical hypercortisolism severity, but lower AddiQoL (mean 73 vs 66, P = .031) and SF-36 MCS (mean 39 vs 33, P = .022). At 12 weeks, these differences in quality of life were no longer present. After adjusting for age, sex, BMI, clinical severity score, and baseline quality of life, MUSE use was an independent predictor of improved SF-36 PCS at 12 weeks postsurgery (beta 4.2, 95% CI: 0.5-7.9, P = .026). Conclusion Postsurgical meditation intervention may improve physical symptoms and accelerate recovery.

Abstract Context Data on diagnostic accuracy of dehydroepiandrosterone sulfate (DHEA-S) for mild autonomous cortisol secretion (MACS) and adrenal insufficiency (AI) are discrepant. Objective We conducted a systematic review and meta-analysis of published studies assessing the accuracy of DHEA-S in diagnosing MACS or AI. Methods From inception to January 8, 2024, we searched databases for original studies of at least 20 participants with MACS or AI. MACS was defined as postdexamethasone cortisol greater than 1.8 mcg/dL or postsurgical hypocortisolism. AI was defined by abnormal dynamic testing. QUADAS-2 was used to assess the risk of bias. Bivariate random effects meta-analysis was used to generate pooled diagnostic accuracy estimates. Results Seven studies on DHEA-S accuracy in diagnosing MACS (574 patients with MACS, 830 referent individuals), and 2 studies on DHEA-S accuracy in diagnosing AI (52 patients with AI, 59 referent individuals) were included. A meta-analysis of studies using DHEA-S cutoff between 60 and 70 mcg/dL to diagnose MACS demonstrated a sensitivity of 82% (95% CI, 64%-93%) and a specificity of 82% (95% CI, 74%-88%). In the 2 studies evaluating DHEA-S in diagnosing AI, the reference standard was a 1-mcg cosyntropin stimulation test. The sensitivity of DHEA-S for diagnosing AI ranged from 70.3% to 86.7%, and the specificity was 87.1%. Most studies were at a moderate risk of bias. Conclusion Based on limited heterogeneous evidence, measurement of DHEA-S provides additional value in diagnosing MACS, as well as AI.

Background/Objectives: Proton therapy delivers highly conformal doses to the target area without producing an exit dose, minimizing cumulative doses to healthy liver tissue. This study aims to evaluate current practices, challenges, and variations in the implementation of proton stereotactic body radiation therapy (SBRT) and hypofractionated therapy for liver malignancies, with the goal of providing a technical assessment to promote broader adoption and support future clinical trials. Methods and Materials: An extensive survey was conducted by NRG Oncology across North American proton treatment centers to assess the current practices of proton liver SBRT and hypofractionated therapy. The survey focused on key aspects, including patient selection, prescription and normal tissue constraints, simulation and motion management, treatment planning, quality assurance (QA), treatment delivery, and the use of image-guided radiation therapy (IGRT). Results: This survey captures the current practice patterns and status of proton SBRT and hypofractionated therapy in liver cancer treatment. Proton therapy is increasingly preferred for treating inoperable liver malignancies due to its ability to minimize healthy tissue exposure. However, the precision required for proton therapy presents challenges, particularly in managing uncertainties and target motion during high-dose fractions and short treatment courses. Survey findings revealed significant variability in clinical practices across centers, highlighting differences in motion management, dose fractionation schedules, and QA protocols. Conclusion: Proton SBRT and hypofractionated therapy offer significant potential for treating liver malignancies. A comprehensive approach involving precise patient selection, treatment planning, and QA is essential for ensuring safety and effectiveness. This survey provides valuable insights into current practices and challenges, offering a foundation for technical recommendations to optimize the use of proton therapy and guide future clinical trials.

BACKGROUND: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection. METHODS: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks. RESULTS: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P =0.02; I 2 =0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P =0.03, I 2 =0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants. CONCLUSIONS: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection.

Abstract Objective Glucocorticoid withdrawal syndrome (GWS) may develop in patients following successful surgery for endogenous hypercortisolism. Effective strategies to minimize GWS and improve quality of life (QoL) are currently lacking. We aimed to determine the impact of hydrocortisone vs prednisone therapy on GWS and QoL during the first 12 weeks postsurgery. Methods Single-center prospective cohort study (2019-2024) of adults with endogenous hypercortisolism who developed postoperative adrenal insufficiency and treated with either prednisone or hydrocortisone. Quality of life was assessed with Short Form-36 (SF-36) and Cushing QoL questionnaires at baseline and at 12 weeks postsurgery. GWS was assessed using weekly AddiQoL questionnaires for the first 12 weeks postsurgery. Results Of 165 patients, 101 (61%) were treated with hydrocortisone and 64 (39%) with prednisone. At baseline, no group differences were found in the hypercortisolism subtype, comorbidities, or QoL assessments. At follow-up, no group differences in final total daily hydrocortisone equivalent dose were seen. When adjusting for the baseline QoL assessment, patients treated with prednisone demonstrated a higher degree of improvement in their QoL, particularly in the SF-36 mental component score (estimate 0.33, 95% CI, 0.04-0.63), SF-36 role-emotional limitation (estimate 0.52, 95% CI, 0.2-0.84), and SF-36 body pain (estimate 0.31, 95% CI, 0.07-0.56) subcomponents. In the multivariable analysis of age, sex, body mass index, glucocorticoid type, baseline clinical severity score, and baseline QoL assessment, prednisone therapy was an independent predictor of better SF-36 mental component at 12 weeks postsurgery. Conclusions Prednisone therapy was associated with better mental health QoL than hydrocortisone at 12 weeks postsurgery in patients with hypercortisolism.

Abstract Oncogenic translocations involving the MET gene have been reported in several cancer types, but detailed clinicogenomic characterization of these cancers is not well defined. In addition, prospective clinical trials evaluating the antitumor activity of MET inhibitors in MET rearrangement–positive cancers are limited. In this study, in a pan-cancer analysis of >46,000 solid tumors with comprehensive genomic profiling, we identified oncogenic MET rearrangements in ∼0.04% of cancers. Preliminary analysis from a phase II clinical trial of the type I MET tyrosine kinase inhibitor (TKI) vebreltinib in MET fusion–positive solid tumors demonstrated an objective response rate of 50% and disease control rate of 79%, with antitumor activity seen in diverse cancer types, including lung adenocarcinoma and intrahepatic cholangiocarcinoma, among others. Similar to MET exon 14–altered lung cancer, secondary mutations in the kinase domain can confer resistance to MET TKIs in MET fusion–positive cancers. Overall, these data categorize MET rearrangements as actionable targets in solid tumors. Significance: MET rearrangement–positive cancers are not well-characterized, and optimal treatment strategies are yet to be defined. Through comprehensive genomic analysis, preclinical modeling, and preliminary results of a phase II clinical trial, we demonstrate that MET fusions are a unique molecular subtype of cancers targetable with vebreltinib, a TKI in development.

BACKGROUND: Complex regional pain syndrome (CRPS) is a debilitating and painful condition accompanied by sensory, autonomic, trophic, and/or motor abnormalities. Although CRPS is rare in the general population, the prevalence among individuals at higher risk, particularly posttraumatic and postsurgical patients, remains unknown. This study aims to provide a benchmark that quantifies CRPS prevalence in high-risk groups, and offers insights on potential predictors of developing CRPS. METHODS: We conducted a systematic review and meta-analysis to identify studies reporting prevalence of CRPS after an inciting event (eg, fracture, surgery), specifically 12-month and 24-month prevalence (primary outcomes), as well as 3-month and 6-month prevalence (secondary outcomes). Estimates from individual studies were transformed using double-arcsine transformation, and the resulting estimates with 95% confidence interval (CI) were pooled in a meta-analysis using a random-effects model. RESULTS: We included 214 articles with data from 2491,378 participants worldwide (35 countries), of which 16,873 had CRPS. The pooled 12-month and 24-month global prevalence was 3.04% (95% CI, 2.64–3.48) and 6.46% (95% CI, 5.46–7.53), respectively. Subgroup analysis and meta-regression were performed to understand the impact of population-dependent (mechanism of injury, type of CRPS), contextual-dependent (socioeconomic status), and methodological-dependent (study design, publication year) factors. The 12-month prevalence was higher in countries with a high human development index (HDI) compared to those with a medium or very high HDI, was higher in participants with a traumatic inciting injury only versus those with surgical injury only or traumatic/surgical injury, and was higher in prospective versus retrospective studies. Meta-regression analysis showed that publication year was a significant moderator, with more recent articles reporting lower 12-month prevalence. CONCLUSIONS: This study provides a benchmark of the global prevalence of CRPS, which anesthesiologists and pain specialists can use to prioritize early diagnosis and identify those at the highest risk for CRPS.

Introduction Although the prevalence of chemotherapy-induced peripheral neuropathy (CIPN) has been reported, the proportion of patients with CIPN who report chronic moderate-to-severe neuropathy or chronic painful neuropathy remains poorly understood, despite its significant impact on patients’ quality of life and treatment outcomes. Methods A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was the pooled prevalence of chronic (≥3 months) moderate-to-severe CIPN or painful CIPN among patients diagnosed with CIPN. Estimates from each study were transformed using a double-arcsine transformation and pooled in a meta-analysis using an inverse variance heterogeneity model. Subgroup analysis was conducted based on geographical region, sex, chemotherapy regimen, primary cancer type, and funding source; metaregression analysis was conducted based on study design, human development index (HDI), and publication year. Results 76 studies from 29 countries, encompassing 13 635 patients with CIPN, were included. Among patients diagnosed with CIPN, the pooled prevalence of those reporting chronic moderate-to-severe CIPN or painful CIPN was estimated at 47.76% (95% CI 37.50 to 58.08; 95% prediction interval 24.68–71.84). Substantial heterogeneity was observed across studies ( I² =97.45%; 95% CI for I 2 97.15 to 97.72). Subgroup analysis revealed that patients treated with platinum-based agents and taxanes had the highest prevalence of chronic moderate-to-severe CIPN or painful CIPN (44.47% and 55.68%, respectively), and among primary cancers, those with breast cancer, multiple myeloma, and lung cancer reported the highest prevalence of chronic moderate-to-severe CIPN or painful CIPN (61.31%, 53.55%, and 50.85%, respectively). Study design, HDI, and publication year were non-significant moderators of prevalence estimates. Based on our Grading of Recommendations, Assessment, Development, and Evaluation assessment, the certainty of evidence was considered “very low.” Sensitivity analysis restricted to studies explicitly measuring painful CIPN (40.78%; 95% CI 29.08 to 52.74) or moderate-to-severe CIPN (49.04%; 95% CI 37.16 to 60.95) yielded similar prevalence estimates. Conclusion This study provides the first comprehensive global estimate of the prevalence of chronic moderate-to-severe CIPN or painful CIPN, highlighting its significant burden on patients worldwide. The variation in prevalence across geographical regions, chemotherapy regimens, and primary cancers underscores the need for tailored management strategies and further research to address potential disparities.