Purpose: This review describes the historical motivations, development, and evolution of the Communication Bridge (CB) research program, which is designed to maximize quality of life and minimize burden for individuals living with dementia and their communication partners. The CB trials described comprise a series of dyadic, nonpharmacologic interventions supporting individuals with primary progressive aphasia (PPA) and their communication partners. Across trials, the CB intervention integrates speech-language, educational, and psychosocial approaches to maximize communication participation, confidence, and self-efficacy. Method: The CB trials are contextualized within the National Institutes of Health (NIH) Stage Model for Behavioral Intervention Development and the Readiness Assessment for Pragmatic Trials (RAPT) framework to illustrate a systematic pathway from feasibility to implementation readiness. Three sequential telehealth-delivered trials are described: CB1, a pilot feasibility study; CB2, an international randomized controlled trial (RCT); and CB3, an ongoing international RCT designed with clinical practice-aligned procedures to advance readiness for future implementation testing. Results: Application of the NIH Stage Model and the RAPT framework highlights how staged intervention development can support rigor, reproducibility, and implementation readiness in behavioral intervention research for neurodegenerative conditions. Across trials, person-centered outcomes demonstrated meaningful benefit and maintenance over time, while iterative design refinements addressed feasibility, fidelity, acceptability, and scalability. Conclusions: The CB research program illustrates how implementation science frameworks can be applied to advance meaningful, dyadic interventions for PPA toward real-world use. Lessons from early-phase trials underscore the importance of person-centered outcomes, staged rigor, and early attention to implementation considerations, with implications for future PPA intervention research and broader speech-language clinical trials.

INTRODUCTION:Primary progressive aphasia (PPA), a language-based neurodegenerative dementia, negatively impacts communication and quality of life. Previous non-pharmacologic interventions show promise but lack efficacy trials. Here, outcomes are provided from Communication Bridge-2 (CB2), a speech-language randomized controlled trial (RCT) for PPA. METHODS:CB2 is the first Phase 2, Stage II, parallel-group RCT delivered via video chat with global enrollment. Ninety-five dyads were randomized into one of two speech-language intervention arms. Primary outcomes included communication confidence and participation measures. Marginal linear models assessed efficacy across ≈12 months. RESULTS:Ninety-five dyads were randomized from four countries. Experimental arm superiority in communication-participation measurement of goal attainment was demonstrated (66.7% vs 49.1%, respectively, p = 0.006), and corroborated by post-study interviews. DISCUSSION:Outcomes demonstrate the feasibility and initial efficacy of a person-centered telemedicine intervention for maximizing communication participation for mild-to-moderate PPA, providing a pathway for developing and implementing clinically meaningful interventions for Alzheimer's disease and related dementias. HIGHLIGHTS:Primary progressive aphasia (PPA) negatively impacts communication participation. Communication Bridge-2 (CB2) is a telemedicine-delivered randomized controlled trial (RCT). Global recruitment of 95 PPA participant dyads into an RCT with low dropout. First international superiority trial for PPA using video chat shows efficacy. The study provides a model for rigorous non-pharmacologic trials for Alzheimer's disease/Alzheimer's disease and related dementias (AD/ADRD).

Abstract As the global population ages, dementia prevalence is increasing. Primary Progressive Aphasia (PPA) is a clinical dementia syndrome characterized by progressive language decline. Access to care for individuals living with PPA is limited by a shortage of qualified clinicians and evidence-based interventions. While technology-supported interventions have the potential to overcome this barrier, there has been no systematic exploration of factors affecting web application use in this population. This study aimed to evaluate feasibility and acceptability and identify clinical and demographic factors affecting app usage in individuals with PPA. Web application data were analyzed from participants (N=95) of Communication Bridge-2, an NIH stage 2 randomized controlled trial of speech-language therapy for PPA (NCT03371706). Participants were encouraged to complete app-based practice exercises five days per week over the 12-month intervention. Data-driven user-type clustering determined engagement groups based on number of logins. Multinomial logistic regression identified demographic and clinical factors that differed between groups. On average, participants completed 13.7 (SD = 5.95) home practice exercises 3.99 days per week (SD = 1.19) and logged into the app 5.88 times per week (SD = 1.29). Older age and increased education significantly predicted increased app engagement (p <.05), even when accounting for work status; other clinical and demographic factors were nonsignificant. All participants logged into and completed practices exercises on the app at least weekly, demonstrating high feasibility and acceptability. These findings suggest that technology-supported interventions may be a valuable tool to improve access to evidence-based care to individuals with PPA and related conditions.

INTRODUCTION:Non-pharmacological interventions may offer significant benefits to the quality of life for persons with primary progressive aphasia (PPA) and their care partners but have lacked efficacy trials. To help fill the efficacy gap, we provide the feasibility of recruitment, enrollment, randomization, and baseline data for the Communication Bridge-2 (CB2) randomized controlled trial (RCT). METHODS:CB2 is the first international, single enrollment site, Phase 2, Stage 2, parallel-group, active control, RCT delivered via video chat to individuals with PPA and their care partners. Participants were recruited, screened, and randomized into one of two speech-language intervention arms. RESULTS:Ninety-five participant dyads (PPA mean baseline age: 67.1; 48% female) from four countries were enrolled and randomized. DISCUSSION:Global recruitment, enrollment, and randomization of individuals with PPA into a video chat-delivered non-pharmacologic RCT is feasible. This trial provides a potential model for conducting rigorous non-pharmacologic efficacy trials for Alzheimer's disease and related dementias. HIGHLIGHTS:Primary progressive aphasia (PPA) negatively impacts communication participation. Communication Bridge-2 (CB2) is a telemedicine-delivered randomized controlled trial. CB2 included global recruitment and randomization of 95 PPA participant dyads. CB2, the first international superiority trial for PPA using video chat shows feasibility. The study provides a model for rigorous non-pharmacologic trials for Alzheimer's disease and related dementias.

Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and tolerability of bevacizumab as salvage therapy in this population. Eligible patients received bevacizumab 10 mg/kg intravenously every 2 weeks until progression. The primary endpoint was radiologic response using Response Assessment in Neuro-Oncology (RANO) criteria. The secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety. Quality of life (QOL) was studied using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) scale. Twenty-seven patients were enrolled, with twenty-four having evaluable data for response. The majority of histologies (n = 21, 78%) were breast cancer. The remaining histologies were non-small-cell lung cancer (n = 4, 15%), neuroendocrine cancer (n = 1, 3%), and papillary fallopian serous adenocarcinoma (n = 1, 3%). Eighteen patients had radiologic response, with two patients demonstrating partial response (8.33%) and sixteen patients demonstrating stable disease (66.7%). The median duration of response was 203 days. PFS at 6 months was 46%, median PFS was 5.3 m, and median OS was 9.5 m. Treatment was well tolerated, with six patients experiencing grade 3 lymphopenia and hypertension. There was one grade 3 thromboembolism. QOL was not negatively impacted. Bevacizumab is a safe and feasible salvage treatment with durable response and favorable overall survival for patients with progressive brain metastases after whole-brain radiation.

Distribution of the patients according to the change of treatment based on ctDNA findings.

Introduction: Identifying responsive outcome measures for assessing functional change related to cognition, communication, and quality of life for individuals with neurodegenerative disease is important for intervention design and clinical care. Goal Attainment Scaling (GAS) has been used as an outcome measure to formally develop and systematically measure incremental progress toward functional, patient-centered goals in clinical settings. Evidence suggests that GAS is reliable and feasible for use in older adult populations and in adult populations with cognitive impairment, but no review has assessed the suitability of GAS in older adults with neurodegenerative disease experiencing dementia or cognitive impairment, based on responsiveness. This study conducted a systematic review to evaluate the suitability of GAS as an outcome measure for older adult populations with neurodegenerative disease experiencing dementia or cognitive impairment, based on responsiveness. Methods: The review was registered with PROSPERO and performed by searching ten electronic scientific databases (PubMed, Medline OVID, CINAHL, Cochrane, Embase, Web of Science, PsycINFO, Scopus, OTSeeker, REHABDATA) and four registries (Clinicaltrials.gov, Grey Literature Report, Mednar, OpenGrey). A summary measure of responsiveness (post-intervention minus pre-intervention mean GAS T-score) was compared across eligible studies using a random-effects meta-analysis. Risk of bias in included studies was assessed using the NIH Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group. Results: 882 eligible articles were identified and screened by two independent reviewers. Ten studies met inclusion criteria for the final analysis. Of the ten included reports, 3 focus on all-cause dementia, 3 on multiple sclerosis, 1 on Parkinson’s disease, 1 on mild cognitive impairment, 1 on Alzheimer’s disease, and 1 on primary progressive aphasia. Responsiveness analyses showed pre- and post-intervention GAS goals were significantly different from zero (Z = 7.48, p < 0.001), with post-intervention GAS scores being higher than pre-intervention GAS scores. Three included studies showed a high risk of bias, 3 showed a moderate risk of bias, and 4 showed a low risk of bias. Overall risk of bias of included studies was rated as moderate. Conclusion: GAS showed an improvement in goal attainment across different dementia patient populations and intervention types. The overall moderate risk of bias suggests that while bias is present across included studies (e.g., small sample size, unblinded assessors), the observed effect likely represents the true effect. This suggests that GAS is responsive to functional change and may be suitable for use in older adult populations with neurodegenerative disease experiencing dementia or cognitive impairment.

Guardant360TM: 70-Gene Panel.

Purpose: Primary progressive aphasia (PPA) is a clinical neurodegenerative dementia syndrome characterized by early, selective, and progressive language impairment. PPA onset is gradual, providing time to potentially identify additional or alternative expressive communication modes; however, reports of communication mode use and effectiveness by persons with PPA have not been described. This study characterized the use, frequency, and perceived effectiveness of communication modes reported by individuals with PPA. Method: Forty-one participants with mild-to-moderate PPA completed a structured interview detailing the type, frequency, and perceived effectiveness of 12 potential communication modes, categorized by technology required (no-tech, low-tech, and high-tech). The ratio of modes used was compared across technology categories with a repeated-measures generalized linear model assuming a binomial distribution with an overall Wald chi-square statistic, followed by pairwise post hoc t -test comparisons. Results: Of the 12 communication modes assessed, participants reported using a median of eight (range: 5–10). All participants affirmed using speech, facial expressions, and talking on the phone. Frequency and perceived effectiveness ratings for these three modes were endorsed at the “some/most of the time” level for more than 80% of the participants. No-tech mode use was significantly higher than reported high-tech and low-tech modes ( p = .004 and p < .0001, respectively). Even so, while some high-tech modes (apps) and some low-tech modes (nonelectronic augmentative and alternative communication) had fewer users, effectiveness ratings were moderate to high for all but one user. Conclusions: Persons with mild-to-moderate language impairment due to PPA report using a range of communication modes with moderate-to-high frequency and perceived effectiveness. These outcomes provide practical information when considering mode refinement or expansion during intervention to maximize communication participation. Barriers to modality use may include low awareness or access, which could be queried by future studies and supported by speech and language interventions. Supplemental Material: https://doi.org/10.23641/asha.21614262

Distribution of the previous treatments (before the ESR1 mutation detection) in the subgroup of patients with ER+ ESR1+ disease versus the patients with ER+ ESR1- disease.

Figure S1: Alisertib treatment did not result in a consistent cytokine response. Figure S2: Alisertib did not have a consistent effect on TGF-b levels. Figure S3: Alisertib induced GATA1 expression in the SET2 megakaryocytic cell line. Figure S4: AURKA inhibition induces megakaryocytic gene expression. Figure S5: Alisertib increases GATA1 expression in the bone marrow of patients on therapy. Table S1: Correlation of Genotype and prior JAK inhibitor therapy with response and adverse events Table S2: Summary of Treatment Related Adverse Events Table S3: Association between GATA1 staining, degree of fibrosis and clinical response

Background Primary progressive aphasia (PPA) is a clinical dementia syndrome. Impairments in language (speaking, reading, writing, and understanding) are the primary and persistent symptoms. These impairments progress insidiously and devastate communication confidence, participation, and quality of life for persons living with PPA. Currently, there are no effective disease modifying treatments for PPA. Speech-language interventions hold promise for mitigating communication challenges and language symptoms. However, evidence regarding their efficacy in PPA is of low quality and there are currently no rigorous randomized trials. Method Communication Bridge™-2 (CB2) is a Stage 2, superiority, single-blind, randomized, parallel group, active-control, behavioral clinical trial delivered virtually within a telehealth service delivery model to individuals with PPA. Ninety carefully characterized participants with clinically confirmed PPA will be randomized to one of two speech-language intervention arms: (1) Communication Bridge™ a dyadic intervention based in communication participation therapy models that incorporates salient training stimuli or (2) the control intervention a non-dyadic intervention based in impairment therapy models addressing word retrieval and language production that incorporates fixed stimuli. The superiority of Communication Bridge™ over the Control arm will be evaluated using primary outcomes of communication confidence and participation. Other outcomes include accuracy for trained words and scripts. Participants complete two therapy blocks over a 12-month period. Outcomes will be measured at baseline, at each therapy block, and at 12 months post enrollment. Discussion The CB2 trial will supply Level 2 evidence regarding the efficacy of the Communication Bridge™ intervention delivered in a telehealth service delivery model for individuals with mild to moderate PPA. An important by-product of the CB2 trial is that these data can be used to evaluate the efficacy of speech-language interventions delivered in both trial arms for persons with PPA. The impact of these data should not be overlooked as they will yield important insights examining why interventions work and for whom, which will advance effectiveness trials for speech-language interventions in PPA. Trial Registration ClinicalTrials.gov NCT03371706 . Registered prospectively on December 13, 2017.

Navarro Motta, Jessica Z.; Sanchez, Alejandro; Ba aqeel, Sheeba H.; Ye, Minghao; Rehman, Mohammed Z.; Wysocki, Jan; Rademaker, Alfred; Molitch, Mark E.; Batlle, Daniel Author Information

Objectives Previous reports established the feasibility of a telehealth model for delivering speech-language therapy via Internet videoconferencing, which connects individuals with primary progressive aphasia (PPA) to an expert speech and language pathologist for treatment. This study reports feasibility of the same telehealth intervention in a larger set of progressive aphasia participants and explores factors potentially influencing functional intervention outcomes. Methods Participants with PPA or progressive aphasia in the context of a neurodegenerative dementia syndrome and their communication partners were enrolled into an 8-session intervention, with 3 evaluations (baseline, 2 months, and 6 months postenrollment). Half of the participants were randomized into a "check-in" group and received 3-monthly half-hour sessions postintervention. Mixed linear models with post hoc testing and percent change in area under the curve were used to examine communication confidence over time, as well as the influence of check-in sessions and the role of communication partner engagement on communication confidence. Results Communication confidence improved at the 2-month evaluation and showed no significant decline at the 6-month evaluation. Item-level analysis revealed gains in communication confidence across multiple communication contexts. Gains and maintenance of communication confidence were only present for the engaged communication partner group and were not bolstered by randomization to the check-in group. Discussion Internet-based, person-centered interventions demonstrate promise as a model for delivering speech-language therapy to individuals living with PPA. Maintenance is possible for at least 6 months postenrollment and is better for those with engaged communication partners, which supports the use of dyadic interventions.

Introduction: Angiotensinogen (AOG) is the precursor of peptides of the renin angiotensin system (RAS). Because insulin up-regulates transcriptional factors that normally repress kidney AOG synthesis, we evaluated urinary AOG (uAOG) in patients with type 1 diabetes (T1D) and microalbuminuria who are receiving either intensive or conventional insulin therapy.Methods: Urine samples from participants of the Diabetes Control and Complications Trial (DCCT) were used for the following: (i) uAOG/creatinine measurements in 103 patients with microalbuminuria and 103 patients with normoalbuminuria, matched for age, gender, disease duration, and allocation to insulin therapy; and (ii) uAOG/creatinine measurements from patients with microalbuminuria allocated to intensive insulin therapy (n = 58) or conventional insulin therapy (n = 41) after 3 years on each modality.Results: uAOG was higher in patients who started with microalbuminuria than in those with normoal-buminuria (6.65 vs. 4.0 ng/mg creatinine, P < 0.01). uAOG was higher in females than in males with microalbuminuria (11.7 vs. 5.4 ng/mg creatinine, P = 0.015). uAOG was lower in patients with micro-albuminuria allocated to intensive insulin therapy than in conventional insulin therapy (3.98 vs. 7.42 ng/mg creatinine, P < 0.01). These differences in uAOG were observed though albumin excretion rate (AER) was not significantly different.Conclusion: In patients with T1D and microalbuminuria, uAOG is increased and varies with gender and the type of insulin therapy independently of AER. This suggests that AOG production is increased in females and it is decreased by intensive insulin therapy. The reduction in uAOG with intensive insulin therapy, by kidney RAS downregulation, may contribute to the known renoprotective action associated with intensive insulin and improved glycemic control.

Engaging in multiple health risk behaviors simultaneously may increase the risk for cardiometabolic diseases. This study examined the prevalence and clustering of three health behaviors (physical activity, fruit and vegetable consumption, and smoking) among Latino men. The participants were 99 Mexican and 104 Puerto Rican men who participated in a study addressing culture- and obesity-related factors. The health behaviors were obtained from self-reported and anthropometric assessments through objective measurements. Among all participants, 5% had no health risk behaviors, 30% had one, 47% had two, and 18% had all three; their most common health risk behavior cluster was low physical activity and low fruit and vegetable consumption (28%). Among Puerto Rican men, 7% had no health risk behaviors, 24% had one, 51% had two, and 18% had all three; their most common health risk behavior cluster was current smoker and low fruit and vegetable consumption (28%). Among Mexican men, 3% had no health risk behaviors, 36% had one, 43% had two and 19% had all three; their most common health risk behavior cluster was low physical activity and low fruit and vegetable consumption (33%). The findings highlight the need for lifestyle interventions that target multiple health risk behaviors related to cardiometabolic diseases in Latinos.

This study examined the logistical, practical, and cultural preferences of Latinos regarding the design of a healthy eating, physical activity, and body image intervention. Puerto Rican and Mexican men (n = 203) completed an interview as part of an NIH-funded study. Overall, 66.5% preferred the intervention to be in Spanish only or both Spanish and English; 88.67% said it was moderately, very or extremely important for the intervention leader to be bilingual; and 66.01% considered it moderately to extremely important for the leader to be Hispanic or Latino. Most participants (83.74%) reported they would be willing to attend an intervention that met twice per week and 74.38% said they would be willing to attend an intervention that met for 1.5 to 2 h, twice weekly. Overall, the majority said they would be moderately to extremely interested in attending an exercise program if it consisted of aerobics with Latin or salsa movements (74.88%) and if it consisted of aerobics with Latin or salsa music (70.44%). Some participants were moderately to extremely interested in attending an intervention if it included dichos (Latino sayings) (65.02%) and cuentos (folktales or stories) (69.46%). The findings have implications for lifestyle and body image interventions aimed at preventing cardiometabolic diseases.

Objective: To compare outcomes data of obese and non-obese pediatric patients with acute promyelocytic leukemia from the Cancer and Leukemia Group B trial C9710 and the Children’s Oncology Group trial AAML0631. Methods: Data including demographics, adverse events, overall survival and event free survival was analyzed, with a focus on mortality in obese patients. Results: The incidence of obesity was 34% on C9710 and 35% on AAML0631. There was significantly lower overall survival in the obese population on AAML0631. Thirteen patients died during therapy or in follow up; seven of these occurred during induction. Conclusion: The incidence of obesity is higher in patients with APL compared to the general population. The presence and degree of obesity can influence OS on the most current treatment regimen. This implies the need for close management of obese patients at diagnosis as well as reinforces the need for further research on obesity driven APL

Purpose: The use of telepractice in the field of communication disorders offers an opportunity to provide care for those with primary progressive aphasia (PPA). The Western Aphasia Battery-Revised (WAB-R) is used for differential diagnosis, to assess severity of aphasia, and to identify a language profile of strengths and challenges. Telehealth administration of the WAB-R is supported for those with chronic aphasia due to stroke but has not yet been systematically explored in neurodegenerative dementia syndromes. To fill this gap, in-person and telehealth performance on the WAB-R from participants with mild to moderate PPA was compared. Method: Nineteen participants with mild to moderate PPA were administered the WAB-R in person and over videoconferencing. Videoconferencing administration included modifications to the testing protocol to ensure smooth completion of the assessment. Subtest and Aphasia Quotient (WAB-AQ) summary scores were compared using concordance coefficients to measure the relationship between the administration modes. Results: In-person and telehealth scores showed strong concordance for the WAB-AQ, Auditory Verbal Comprehension subtest, and Naming & Word Finding subtest. The Spontaneous Speech test summary score had slightly lower concordance, indicating the need for caution when comparing these scores across administration modes. Conclusion: These findings support extending the use of telehealth administration of the WAB-R via videoconferencing to those with mild to moderate PPA given appropriate modifications to testing protocol.

Purpose: To evaluate the effect of the anatomic size on 3D radiomic imaging features of the breast cancer hepatic metastases. Materials and Methods: CT scans of 81 liver metastases from 54 patients with breast cancer were evaluated. Ten most common 3D radiomic features from the histogram and gray level co-occurrence matrix (GLCM) categories were calculated for the hepatic metastases (HM) and compared to normal liver (NL). The effect of size was evaluated by using linear mixed-effects regression models. The effect of size on different radiomic features was analyzed for both liver lesions and background liver. Results: Three-dimensional radiomic features from GLCM demonstrate an important size dependence. The texture-feature size dependence was found to be different among feature categories and between the HM and NL, thus demonstrating a discriminatory power for the tissue type. Significant difference in the slope was found for GLCM homogeneity (NL slope = 0.004, slope difference 95% confidence interval [CI] 0.06-0.1, p <0.001), contrast (NL slope = 45, slope difference 95% CI 205-305, p <0.001), correlation (NL slope = 0.04, slope difference 95% CI 0.11-0.21, p <0.001), and dissimilarity (NL slope = 0.7, slope difference 95% CI 3.6-5.4, p <0.001). The GLCM energy (NL slope = 0.002, slope difference 95% CI -0.0005 to -0.0003, p <0.007), and entropy (NL slope =1.49, slope difference 95% CI 0.07-0.52, p <0.009) exhibited size-dependence for both NL and HM, although demonstrating a difference in the slope between themselves. Conclusion: Radiomic features of breast cancer hepatic metastasis exhibited significant correlation with tumor size. This finding demonstrates the complex behavior of imaging features and the need to include feature-specific properties into radiomic models.