Citations

Objectives: Esophageal cancer (EC) often presents with dysphagia due to tumor obstruction. Esophageal stenting has the potential of palliating dysphagia, improving nutrition, preventing aspiration, and improving quality of life (QoL) but may be associated with risks. The present systematic review and guidelines are intended to assist treatment decision-making when considering stent placement in patients with EC based on the available evidence. Methods: Using the population, intervention, comparator, outcome, timing and study design framework, the evidence was assessed using Cochrane and PRISMA 2020 methodology. Eligible studies included prospective phase II-III trials and retrospective analyses published between January 1, 2010 and December 3, 2024 in the Ovid Medline database. These references were assessed by American Radium Society (ARS) Appropriate Use Criteria (AUC) methodology. RAND-UCLA consensus methodology was used to rate the appropriateness of the use of stents. Results: ARS AUC recommendations include (1) esophageal stenting is usually not appropriate in patients with early-stage EC in whom upfront surgery is planned; (2) esophageal stenting is usually not appropriate in patients with locally-advanced EC in whom neoadjuvant/perioperative therapy and esophagectomy or definitive chemoradiation is planned; (3) esophageal stenting may be appropriate in the setting of metastatic EC, especially in patients with short life expectancy with limited treatment options; (4) esophageal stenting is usually not appropriate for benign stricture following curative-intent therapy; (5) esophageal stenting is usually not appropriate for locally recurrent tumor in the setting of prior radiation; and (6) esophageal stenting is usually appropriate for management of tracheoesophageal fistula before curative-intent treatment. Conclusions: This ARS AUC summary provides guidelines for the use of esophageal stents in patients with EC provides based on available evidence.

Abstract Severe aplastic anemia (SAA) is a rare and life-threatening bone marrow failure disorder. Immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporine has long been a frontline treatment option in SAA; however, its limited durability and risk of long-term complications such as secondary malignancies remain a drawback in this treatment modality. Allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option with significantly improved outcomes over the long term, particularly with HLA-matched related donors. However, the use of alternative donors, such as haploidentical, mismatched, or matched unrelated donors, has previously been limited due to increased transplant-related morbidity, particularly graft-versus-host disease (GVHD). HCTs have therefore been limited to young recipients and those with HLA-matched related donors, creating significant disparity for older adults and those who lack matched donor options. Nevertheless, more recent advances in HCT, such as posttransplant cyclophosphamide for GVHD prophylaxis, have led to improved outcomes of HCT with alternative donors; however, alternative donor HCT remains underused as up-front therapy, in part because of limited multicenter trial data. This review discusses current SAA treatment approaches, including both IST and HCT, and highlights remaining gaps. It also discusses how ongoing clinical trials such as CureAA and TransIT could help address these gaps. Furthermore, we discuss the importance of stakeholder engagement and implementation science in the integration of research-based evidence into clinical practice. Bridging these gaps is necessary for achieving equitable access for patients historically excluded from frontline HCT, including older adults and racially or ethnically diverse populations.

OBJECTIVE In many individuals, type 2 diabetes (T2D) remains poorly controlled despite taking multiple glucose-lowering therapies. Several studies have demonstrated that endogenous hypercortisolism is prevalent among these individuals. We tested whether cortisol-directed therapy improves their glycemic control. RESEARCH DESIGN AND METHODS In this prospective, multicenter, double-blind study, 136 individuals with T2D (hemoglobin A1c [HbA1c] 7.5%–11.5% [58–102 mmol/mol] on multiple medications) and hypercortisolism (by dexamethasone suppression test) were randomized 2:1 to the glucocorticoid receptor antagonist mifepristone (300–900 mg once daily; n = 91) or placebo (n = 45) for 24 weeks, with stratification by presence/absence of an adrenal imaging abnormality. The primary end point was the change in HbA1c. Secondary end points included changes in glucose-lowering medications, weight, and waist circumference and safety. RESULTS Mean baseline HbA1c in the study cohort was 8.55% (69.9 mmol/mol). At 24 weeks, the least squares mean (LSM) difference from placebo in HbA1c was −1.32% (95% CI −1.81 to −0.83; P < 0.001). Participants receiving mifepristone experienced reductions in body weight and waist circumference (placebo-adjusted LSM differences of −5.12 kg [95% CI −8.20 to −2.03] and −5.1 cm [−8.23 to −1.99], respectively). Of participants on mifepristone, 46% discontinued therapy, compared with 18% on placebo. Adverse events with mifepristone (>10% of participants) included hypokalemia, fatigue, nausea, vomiting, headache, peripheral edema, diarrhea, and dizziness, consistent with mifepristone’s known tolerability profile. Increases in blood pressure also occurred. CONCLUSIONS In individuals with inadequately controlled T2D and hypercortisolism, cortisol-directed medical therapy with mifepristone reduced HbA1c, with a manageable tolerability profile.

ABSTRACT Aims Common genetic variants have been linked to an increased risk of non-ischaemic cardiomyopathy (NICM). The primary objective of this study was to evaluate the significance of these variants in a general population. Methods and results Thirteen NICM risk alleles, previously validated by meta-analyses of case-control genetic association studies, were used to determine genetic risk (GR) in a large, unselected cohort (n = 1897) of Olmsted County residents aged >45 years. Clinical and echocardiographic data, with biomarkers, were correlated with this NICM-GR over a median of 16 years of follow-up (interquartile range [IQR] 15–17). There were no significant differences between the study population quartiles, based on NICM-GR, in terms of age (median 61.6 [IQR 53.6–70.4]), sex (48% male), and cardiovascular risk factors. A significant correlation was detected by specific linear-regression models between NICM-GR and left ventricular (LV) ejection-fraction (beta [standard error]: −2.68 [0.68], p < 0.001), LV end-systolic-diameter (0.22 [0.06], p < 0.001), and LV end-diastolic-diameter (0.14 [0.06], p = 0.01). During follow-up, 46 subjects developed NICM. Using a 3:1 matched-cohort of non-NICM versus NICM patients, linear-regression analysis found a significant correlation between NICM-GR and NICM development (odds ratio 2.27, 95% confidence interval 1.06–4.85, p = 0.03). There was no significant association between these variants and heart failure biomarkers (aldosterone, natriuretic peptides, ST2, galectin-3). Conclusions The NICM-GR correlates with LV function and dimension, and subsequent development of NICM in the general population. The lack of correlation of these variants with cardiovascular risk factors and the renin–angiotensin–aldosterone axis or natriuretic peptides suggest different biological mechanisms involved. These findings support the need to explore newer pathophysiologic pathways in the development of NICM.

Abstract Atrial fibrillation (AF) is increasingly diagnosed early, close to its first occurrence due to: (i) increased public awareness with self-screening; (ii) health care initiatives including population screening and opportunistic case finding; and (iii) increased use and surveillance of implantable cardiac devices. At its onset, AF is often low burden, and cardiovascular co-morbidities may be absent or at an early stage. Thus, the management of recent-onset AF has become an issue of growing importance. Professional guidelines have traditionally focused on anticoagulant thromboprophylaxis, generally recommending a cautious approach to rhythm control, and priority has been given to rate control to alleviate symptoms. In recent guidelines, the importance of managing lifestyle and co-morbidities has increased. The AF-SCREEN collaboration proposes that a vigorous approach to active management of recent-onset AF may be warranted. This includes addressing co-morbidities and promoting healthy lifestyles to prevent the emergence or progression of AF and associated cardiovascular disease, as well as the initiation of active rhythm control ± anticoagulation to prevent AF-related morbidity and mortality, including stroke and heart failure (HF). Intuitively, intervention early after AF onset would be beneficial since lifestyle and co-morbidity management, plus rhythm control and anticoagulation, are important contributors to improved outcomes in patients with established AF, but robust evidence is lacking for recent-onset AF. There is a delicate balance between achieving favourable outcomes such as preventing strokes, HF and AF progression vs the complications and potential adverse effects of interventions. Given the serious long-term consequences, innovative approaches are necessary to determine the value and risks of initiating active therapy very early in the course of AF. More data are needed to guide the best management of recent-onset AF, bearing AF burden in mind. Long-term studies using large national databases linked to electronic medical records and rhythm monitoring devices offer excellent opportunities. Shorter-term studies focusing on reducing AF burden to slow AF progression and studies focusing on outcomes such as HF could be used in both randomized clinical trials and observational cohort studies.

ABSTRACT The characteristics at diagnosis and clinical course of primary extranodal follicular lymphoma (EFL) have not been extensively described. The International Extranodal Lymphoma Study Group (IELSG) conducted an international retrospective survey aimed to describe the clinical features at diagnosis and the outcomes of FL cases with a clinically dominant extranodal component. The dataset included 605 pathologically reviewed cases from 19 different countries, and their outcomes were compared to those of nodal follicular lymphomas. The two most common presentation sites for EFL were the skin ( n = 334) and the gastrointestinal tract ( n = 72), with 22 cases having primary duodenal localization. These subsets exhibited unique features at diagnosis and significantly different overall survival (OS) patterns. After a median follow‐up of 5.5 years, primary cutaneous lymphomas showed a superior outcome [10‐year OS: 89% (95% CI, 83%–93%)], while primary gastrointestinal lymphomas had an intermediate outcome [10‐year OS: 79% (95% CI, 59%–90%)]. Among the gastrointestinal lymphomas, primary duodenal lymphomas tended toward the best outcome [10‐year OS: 95% (95% CI, 69%–99%)]. Other primary extranodal sites had inferior outcomes [10‐year OS: 59% (95% CI, 48%–68%)], similar to primary nodal lymphomas [10‐year OS: 57% (95% CI, 49%–64%)]. These findings support the identification of specific primary FL localizations as distinct entities with particular clinical and biological characteristics.

Objective: Diabetes is a defining disease of the 21st century because of its rising prevalence, association with obesity, and enormous health impact. Abundant evidence shows that lifestyle interventions can delay or prevent type 2 diabetes (T2D) in adults, offer relief, and sometimes achieve complete remission. Despite this empowering message, there are no clinical practice guidelines that focus primarily on lifestyle interventions as first-line management of prediabetes and T2D. Our objective, therefore, is to offer pragmatic, trustworthy, and evidence-based guidance for clinicians in using the 6 pillars of lifestyle medicine—nutrition, physical activity, stress management, sleep, social connectedness, avoidance of risky substances—for managing adults with T2D and in preventing T2D in adults with prediabetes or a history of gestational diabetes mellitus. Methods: We used well-established, peer-reviewed guideline methodology to develop evidence-based key action statements (recommendations) that facilitate quality improvement in clinical practice. The guideline development group included 20 members representing consumers, advanced practice nursing, cardiology, clinical pharmacology, behavioral medicine, endocrinology, family medicine, lifestyle medicine, nutrition and dietetics, health education, health and wellness coaching, sleep medicine, sports medicine, and obesity medicine. Recommendation strength was based on the aggregate evidence supporting a key action statement plus a comparison of associated benefits vs harms/costs. Multiple literature searches, conducted by an information specialist, identified 8 relevant guidelines, 118 relevant systematic reviews, and 112 randomized clinical trials. The guideline underwent extensive internal, external, and public review and comment prior to publication. Results: We developed 14 key action statements and associated evidence profiles, each with a distinct quality improvement goal in the context of lifestyle interventions for T2D. Strong recommendations were made regarding advocacy for lifestyle interventions; assessing baseline lifestyle habits; establishing priorities for lifestyle change; prescribing aerobic and muscle strength physical activity; reducing sedentary time; identifying sleep disorders; prescribing nutrition plans for prevention and treatment; promoting peer/familial support and social connections; counseling regarding tobacco, alcohol, and recreational drugs, and establishing a plan for continuity of care. Recommendations were made regarding identifying the need for psychological interventions and for adjusting (deprescribing) pharmacologic therapy. We include numerous tables and figures to facilitate implementation, a plain-language summary for consumers, and an executive summary for clinicians as separate publications. Conclusions: There is robust research evidence supporting the efficacy of lifestyle interventions in preventing, treating, and achieving remission of T2D in adults. Our multidisciplinary guideline development group successfully synthesized this evidence into 14 key action statements that can be used by clinicians and other healthcare professionals to improve quality of care for adults with, or at-risk for, T2D. Despite the research gaps and implementation challenges we highlight in the guideline we believe strongly that our recommendations have immediate relevance and can help raise awareness and shift the paradigm of T2D management towards optimal use of lifestyle interventions.

This executive summary highlights evidence-based recommendations for using lifestyle interventions in the treatment and remission of type 2 diabetes (T2D) and prediabetes in adults. The summary and guideline are intended for any clinician or healthcare professional in a community or non-inpatient healthcare setting involved in managing non-pregnant adults with T2D, prediabetes or a history of gestational diabetes mellitus (GDM). The purpose of this executive summary is to provide a succinct overview of the key action statements (recommendations) from Lifestyle Interventions for Treatment and Remission of Type 2 Diabetes and Prediabetes in Adults: A Clinical Practice Guideline from the American College of Lifestyle Medicine. This is the first diabetes guideline to emphasize lifestyle interventions as the foundation of management and is also the first to focus on all six pillars of lifestyle medicine (plant-predomination nutrition, regular physical activity, restorative sleep, stress reduction, social connectedness, and avoiding risky substances), including behavior change strategies. This summary is not intended to substitute for the full guideline, which should be read before taking the recommended actions. The guideline on which this summary is based was developed with a priori methodology that has been previously published, refined, and used in over 20 multidisciplinary, trustworthy, and evidence-based national guidelines. The guideline development group included 20 members representing consumers, advanced practice nursing, cardiology, clinical pharmacology, behavioral medicine, endocrinology, family medicine, lifestyle medicine, nutrition and dietetics, health education, health and wellness coaching, sleep medicine, sports medicine, and obesity medicine. We developed 14 key action statements and associated evidence profiles, each with a distinct quality improvement goal in the context of lifestyle interventions for T2D. Strong recommendations were made regarding advocacy for lifestyle interventions; assessing baseline lifestyle habits; establishing priorities for lifestyle change; prescribing aerobic and muscle strength physical activity; reducing sedentary time; identifying sleep disorders; prescribing nutrition plans for prevention and treatment; promoting peer/familial support and social connections; counseling regarding tobacco, alcohol, and recreational drugs, and establishing a plan for continuity of care. Recommendations were made regarding identifying the need for psychological interventions and for adjusting (deprescribing) pharmacologic therapy. We include numerous tables and figures to facilitate implementation, a plain-language summary for consumers, and an executive summary for clinicians as separate publications. Although not a substitute for the full clinical practice guideline, this executive summary can provide insight into the key guideline recommendations, to whom they apply, and to how they might alter care. These recommendations offer detailed, explicit, and evidence-based strategies for successful lifestyle behavior change, making them relevant not only to our guideline but to other guidelines and standards that advocate for lifestyle change in managing adults with T2D.

AbstractPurposeWhile standard MR elastography (MRE) uses harmonic mechanical waves, there are some applications in which imaging and analysis of transient mechanical motion are of interest. Wavelet MRE has been developed for detecting broadband motion from transient excitation. The goal of this study was to evaluate the accuracy and efficiency of wavelet MRE for transient displacement detection in brain MRE applications.MethodsTransient motion was induced in a gel phantom, while MRE images were acquired using bipolar motion‐encoding gradient (MEG) at multiple frequencies (20–200 Hz). Displacements were estimated using (1) combinations of multiple MEGs forming the wavelet MRE and (2) deconvolution from a single MEG. These estimated displacements were used to calculate the MRE phase for each MEG. Correlation (r2) between the calculated and acquired phases was evaluated.Three healthy volunteers were scanned twice in a clinical scanner using wavelet MRE with an occipital impact. Time‐resolved brain translation, rotation, and maximal principal strain were calculated. Repeatability was assessed both qualitatively and through Pearson correlation.ResultsWavelet MRE outperformed standard MRE in displacement estimation, showing higher correlations between calculated and acquired phase, even with fewer phase offsets. In the volunteer study, consistent temporal motion dynamics and spatial maximal principal strain distributions across repeated scans demonstrated the repeatability of wavelet MRE.ConclusionThis study validated the accuracy and efficiency of wavelet MRE for broadband motion detection and demonstrated its feasibility and repeatability in vivo. This technique shows promise for advancing our understanding of the injury risks and mechanisms associated with sports‐related head trauma.