Publications by Year: 2026

OBJECTIVES: To comprehensively review the available literature on prehabilitation and rehabilitation exercise, nutrition, and psychological support interventions for patients with kidney cancer (KC), to summarise the clinically relevant efficacy and cost-effectiveness of interventions, to expose key knowledge gaps, and to inform future investigations and initiatives.

METHODS: This review was performed according to the per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews Guidelines. We included randomised controlled trials (RCTs) assessing programmes of prehabilitation or rehabilitation, exercise, psychological support, or nutrition components in patients with KC or KC caregivers from January 2004 to March 2022. Statistically significant positive (SS+) and negative (SS-) results were summarised.

RESULTS: The systematic search yielded 10 968 records including 18 RCTs, involving 2774 unique subjects, 706 of whom were KC patients/survivors. None included caregivers or assessed cost-effectiveness. Two interventions were implemented before surgery, one was implemented prior to initiation of systemic therapy, eight were implemented during systemic or radiation therapy, three were implemented after treatment, while implementation time was not specified for four interventions.

CONCLUSION: Most (14/18) RCTs involving exercise, nutrition, psychological support, or prehabilitative or rehabilitative programmes for KC performed to date demonstrated SS+ results. The evidence was most robust regarding previously evaluated psychological support, especially mindfulness-based interventions (9/10 studies demonstrating SS+ improvement in primary outcomes), followed by therapeutically valid exercise with/without psychological support (5/8 RCTs demonstrated efficacy), then nutrition or pharmacological interventions (2/5 demonstrated efficacy). Level 1 evidence supports counselling patients and referral to mindfulness-based psychological therapy along with physical therapy or physical medicine and rehabilitation, as well as consideration of preoperative carbohydrate drinks. No studies have examined impact on caregivers, or cost-effectiveness, which are both critical areas for future study.

BackgroundAvailable evidence for many prescription drugs comes from clinical trials that often exclude older patients. Real-world evidence (RWE) generated post-approval can provide new evidence on effectiveness and safety for these populations. We sought to understand physicians' perceptions of clinical trial and RWE for prescribing decisions. To frame the study, we used examples of drugs for heart failure and anticoagulation, which are more like to be prescribed to older adults.MethodsWe conducted an interview study of 15 US physicians specializing in geriatrics, cardiology, or primary care and affiliated with academic medical centers. Interviews were coded using a qualitative thematic analysis approach to construct themes and identify patterns in responses.ResultsAll participants described limitations in current believed real-world evidence could help inform patient care and their practice. However, they had concerns about the data. If clinical trial and RWE findings diverged, all would need more information to determine which findings to follow.ConclusionsPhysicians who routinely prescribe to older patients are optimistically cautious about RWE for drugs but would rely on trusted sources, like professional society guidelines, for incorporating it into practice. Therefore, RWE researchers should identify opportunities to work alongside guideline developers and database editors on the practice-relevant interpretation and dissemination of the evidence.

CONTEXT: This review synthesizes current literature regarding metabolic aspects of athlete bone health and incorporates evidence-based recommendations into a clinician-friendly algorithm.

EVIDENCE ACQUISITION: Published manuscripts listed in PubMed between 1993 and 2024 were reviewed. Relevant terms including keywords and section titles of manuscripts were searched, and relevant studies identified.

STUDY DESIGN: Clinical review.

LEVEL OF EVIDENCE: Level 1-3.

RESULTS: A metabolic workup is often appropriate in the context of an athlete with bone stress injury (BSI) but varies based on clinical scenario. Evidence supports that all athletes with BSI be considered for a minimum workup including 25-hydroxyvitamin D (SORT A), complete blood count (CBC) (SORT B), and an iron panel with ferritin (SORT B). Athletes with features of low energy availability, including ≥2 Triad risk factors (low body mass index, abnormal uterine bleeding), or with multiple features of relative energy deficiency in sport require an initial strategy to correct energy availability (increased energy intake and/or decreased training load) and should be considered for dual-energy x-ray absorptiometry (DXA) (SORT A) and additional laboratory testing. If there is persistent clinical concern, a comprehensive laboratory evaluation should be considered, and varies based on athlete sex and clinical context. People with recurrent or multiple BSI or requiring surgical fixation also warrant detailed, stepwise testing for underlying causes (SORT C). A reasonable strategy starts with a focused workup for more common conditions (eg, CBC, complete metabolic panel, iron panel, 25-OH vitamin D, DXA) and may expand based on initial findings and clinical suspicion.

CONCLUSION: Existing evidence supports optimizing nutrition and further evaluation for factors influencing bone health for all athletes with BSI. More extensive workup is required in athletes with multiple features of low energy availability, multiple/recurrent BSI, BSI requiring surgical fixation, and signs/symptoms of an underlying medical disorder.Strength-of-Recommendation Taxonomy (SORT):A, B, C.

INTRODUCTION: It is unknown if neurodegeneration trajectories differ between Down syndrome (DS) and autosomal dominant Alzheimer's disease (ADAD), both of which are genetic forms of Alzheimer's disease (AD).

METHODS: We compared brain volumes in DS, ADAD, and unaffected family members serving as controls. Participants underwent magnetic resonance imaging (MRI) and amyloid positron emission tomography (PET), deriving volumetric and amyloid burden, respectively. Nonlinear associations between regional volumes and estimated years to clinical symptom onset (EYO) were evaluated using generalized additive mixed-models.

RESULTS: Longitudinal data from 267 controls, 341 participants with DS, and 358 participants with ADAD were included, totaling 1908 scans. DS volumes were lower than ADAD and controls initially and dropped linearly. ADAD had similar volumes to controls until diverging, beginning at EYO -7. Amyloid was negatively associated with volume, with similar slopes in DS and ADAD.

DISCUSSION: ADAD and DS demonstrate distinct patterns of brain volume decline prior to symptom onset despite being similarly affected by amyloid.

INTRODUCTION: Research examining Alzheimer's disease (AD) neuroimaging markers of brain pathology and cognition in older Latino adults remains limited. We compared neuroimaging and cognitive profiles between cognitively unimpaired older Latino and non-Latino adults from the greater Boston area.

METHODS: Twenty Latino and 230 non-Latino cognitively unimpaired older adults from the Harvard Aging Brain Study were included. Participants underwent neuroimaging to assess amyloid beta (Aβ), inferior temporal tau and hippocampal volume, as well as cognitive testing with the Preclinical Alzheimer Cognitive Composite-5. Associations between ethnicity and these outcomes were examined using linear regressions adjusted for age, education attainment, and sex.

RESULTS: Latino participants had higher levels of inferior temporal tau (p = 0.02) and lower cognitive performance (p < 0.001) compared to non-Latinos, but comparable Aβ deposition and hippocampal volume (all ps > 0.05).

DISCUSSION: These results highlight potential differences in vulnerability to cognitive decline between Latinos and non-Latinos, underscoring the need for further investigation.

Individual tissues perform highly specialized metabolic functions to maintain whole-body metabolic homeostasis. Although Drosophila serves as a powerful model for studying human metabolic diseases, modeling tissue-specific metabolism has been limited in this organism. To address this gap, we reconstruct 32 tissue-specific genome-scale metabolic models (GEMs) by integrating a curated Drosophila metabolic network with pseudo-bulk single-nuclei transcriptomics data, revealing distinct metabolic network structures and subsystem coverage across tissues. We validate enriched pathways identified through tissue-specific GEMs, particularly in muscle and fat body, using metabolomics and pathway analysis. Moreover, to demonstrate the utility in disease modeling, we apply muscle-GEM to investigate high sugar diet (HSD)-induced metabolic dysregulation. Constraint-based semi-quantitative flux and sensitivity analyses identify altered NAD(H)-dependent reactions and distributed control of glycolytic flux, including GAPDH. This prediction is further validated through in vivo 13C-glucose isotope tracing study. Notably, decreased glycolytic flux, including GAPDH, is linked to increased redox modifications. Finally, our pathway-level flux analyses identify dysregulation in fructose metabolism. Together, this work establishes a quantitative framework for tissue-specific metabolic modeling in Drosophila, demonstrating its utility for identifying dysregulated reactions and pathways in muscle in response to HSD.

BACKGROUND: Genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) associated with perception to sweet taste. The influence of genetic predisposition to sweet taste on diet quality remains poorly understood.

OBJECTIVES: This study aimed to compare cross-sectional associations between a genetically driven sweet taste polygenic score (PGS) and alignment with diet quality indices in a cohort of Puerto Rican older adults residing in the Boston area.

METHODS: We used baseline data from Boston Puerto Rican Health Study participants with complete genetic and dietary data (n = 583). A weighted sweet taste PGS was constructed using 38 SNPs from published GWAS with perceived intensity sweet taste outcomes (aspartame, fructose, glucose, neohespedirin dihydrochalcone, sucrose, and sweet substances). We derived 3 diet quality indices using data from a food frequency questionnaire validated for this population: Alternate Healthy Eating Index-2010 (AHEI-2010), Dietary Approaches to Stop Hypertension (DASH), and Mediterranean diet (MeD). Multiple linear regression models between sweet taste PGS and diet quality indices were used to estimate associations and 95% confidence intervals (CIs).

RESULTS: There were 428 females and 155 males, with mean age 52.2 ± 7.5 y. The PGS ranged from 30.0 to 50.1, mean (SD): 39.9 (3.4). There was an inverse association between PGS and DASH: β (95% CI) -0.03 [-0.05, -0.004, false discovery rate (FDR) = 0.06], but no association was observed with AHEI-2010: -0.02 (-0.04, 0.008), FDR = 0.19; or MeD: -0.02 (-0.04, 0.01), FDR = 0.19. Across all diet quality indices, higher sweet taste PGS was associated with lower alignment to recommendations for whole grain and vegetables. It also tended to be associated with lower intake of nuts/legumes in the AHEI-2010.

CONCLUSIONS: In Puerto Rican adults, higher sweet taste PGS was associated with lower DASH diet quality, but not the AHEI-2010, or MeD, and with lower intake of whole grains, vegetables, and possibly, nuts/legumes. More research is needed on taste perception and dietary intake across populations to inform future intervention.

OBJECTIVE: To evaluate the association between Child Opportunity Index (COI) and race and ethnicity and pediatric out-of-hospital cardiac arrest (OHCA) outcomes and the role of bystander response (bystander cardiopulmonary resuscitation and/or defibrillator use) as a mediator.

METHODS: This is a retrospective cohort study using the Cardiac Arrest Registry to Enhance Survival (CARES) of children ≤18 years with OHCA. The exposures are COI quintiles (very low indicates the most disadvantaged neighborhoods) and race and ethnicity. The primary outcome is survival to hospital discharge with favorable neurological outcome (Pediatric Cerebral Performance Category ≤2). Associations of exposures with outcome are determined using logistic regression and mediation analysis is used to evaluate the indirect effect of bystander response.

RESULTS: Overall, 1654/17,903 (9.2%) had a favorable outcome. Arrests in lower COI neighborhoods and in Black/African American children occurred more frequently in infants and were less likely to be witnessed and to receive bystander response. Arrests in very low COI areas (vs very high COI, adjusted odds ratio aOR 0.68 [95% CI 0.54-0.84], P < 0.001) and Black/African American race (vs White, aOR 0.81 [95% CI 0.69-0.96], P = 0.02) were independently associated with lower odds of a favorable outcome. Lower bystander response partially mediated worse outcomes associated with lower COI quintiles (adjusted percent mediated: 11.7% [95% CI 5.5-17.9], P < 0.001) and Black/African American race (15.6% [95% CI 7.5-23.6], P < 0.001).

CONCLUSIONS: Arrests occurring in lower COI areas and among Black/African American children are associated with lower odds of a favorable outcome. Lower bystander response partially explains these associations.

PURPOSE: Locally advanced endometrial cancers are heterogeneous and challenging to treat. Immunotherapy has transformed the treatment landscape. Given the complexity of tailoring adjuvant treatment recommendations, the multidisciplinary American Radium Society Gynecologic Cancer Panel created evidence-based guidelines for the management of locally advanced endometrial adenocarcinoma.

METHODS AND MATERIALS: Search terms, key questions, and associated clinical case variants were formed by panel consensus. A review of the literature was conducted from January 1, 1996, to March 5, 2024, using the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines to systematically search the PubMed, Embase, and Web of Science databases to retrieve a comprehensive set of relevant articles. A well-established methodology (modified Delphi) was used by the expert panel to rate the appropriate use of procedures.

RESULTS: Evidence for key questions in advanced-stage endometrial cancer was examined. Two rounds of voting were completed pertaining to the appropriateness of key management decisions for 4 clinical variants. Optimal adjuvant treatment is based on pathologic and molecular risk factors, and typically consists of combined modality therapy, with both chemotherapy and radiation, to minimize the risk of local and distant recurrence; there are no prospective data on optimal sequencing. Molecular data from PORTEC-3 highlights that adding chemotherapy to radiation is especially crucial for p53 abnormal tumors. Inclusion criteria for the NRG-GY018/RUBY trials can guide appropriateness of incorporating immunotherapy, which should be considered especially in mismatch repair-deficient (dMMR) patients. Radiation fields should be extended to include para-aortic lymph nodes in IIIC2 disease. Within pelvic radiation, intensity modulated radiation therapy is the preferred technique to mitigate toxicity as supported by prospective data.

CONCLUSION: Selecting appropriate adjuvant therapies for advanced-stage endometrial cancer is nuanced. Further prospective studies harnessing molecular markers as therapeutic targets will help advance and optimize therapies for more personalized treatment of this complex disease.