University of Massachusetts Chan Medical School

‘As our understanding of the biology of clonal hematopoiesis expands, a pressing need in the field becomes the design and implementation of clinical trials to help mitigate the risk for progression to overt myeloid neoplasm. Effective clinical trial design will be informed by use of personalized genetic risk to determine eligibility, strategic endpoint selection, and identification of suitable interventions with a goldilocks balance of toxicity and reduced risk of progression. We will only reach this milestone through collaboration’. Commentary on: Haque et al. A blueprint for pursuing therapeutic interventions and early phase clinical trials in clonal haematopoiesis. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19925.

Organ and tool detection and segmentation in real time during surgery have been significant challenges in the development of robotic surgery. Most existing detection methods are unsuitable for the surgical environment, where the lighting conditions, occlusions, and anatomical structures can vary significantly. This study presents an organ and surgical tool segmentation and detection algorithm using a manually annotated dataset based on YOLOv8 (You Only Look Once), a state-of-the-art object detection framework. The YOLOv8 deep learning neural network is trained to detect and segment organs and tools during laparoscopic cholecystectomy using a manually annotated dataset of frames taken from actual surgeries. After four experiments using combinations of small and extra-large model sizes and the original and a modified dataset, the resulting algorithm is evaluated and tested in real time on a new surgical video. The method shows it can provide real-time feedback to the surgeon by accurately locating and segmenting the target organs displayed in the surgical video. The method outperforms the baseline methods, with a “bounding box” mean average precision (mAP50) and precession (P) of (50.2%, 51.6%), (52.8%, 76.9%), (83.2%, 81.1%), and (86.3%, 85.7%) for the first, second, third, and fourth experiments, respectively, and a “masking segment” of mAP50 and precession of (50.5%, 51.8%), (54.3%, 76.1%), (82.6%, 80.4%), (86.0%, 85.4%) for the first, second, third, and fourth experiments, respectively. The best-performing model has a speed of around 13.1 ms per frame. This novel application could be a stepping stone in future work, such as developing an algorithm to display the results to the surgeon in a heads-up-display (HUD) to help navigate the scenes or even be implemented in robotic surgeries.

The lack of physician training in serving patients with intellectual and developmental disabilities (IDDs) has been highlighted as a key modifiable root cause of health disparities experienced by this high-priority public health population. To address gaps in medical education regarding the lack of IDD curriculum, lack of evaluation/assessment, and lack of coordination across institutions, the American Academy of Developmental Medicine and Dentistry created the National Inclusive Curriculum for Health Education–Medical (NICHE-MED) Initiative in 2016. The aims of NICHE-MED are to: (1) impact medical students’ attitudes and/or knowledge to address underlying ableism and address how future physicians think about disability; (2) apply a lens of health equity and intersectionality, centering people with IDD, but fostering conversation and learning about issues faced by other disability and minoritized populations; and (3) support community-engaged scholarship within medical education. As of 2024, the NICHE-MED initiative consists of close to 40 Medical School Partners, each with their own community-engaged disability curriculum intervention paired with a rigorous evaluation that ties centrally to coordinated program evaluation. The NICHE-MED initiative demonstrates implementation success at scale and is a successful community-engaged curriculum change model that may be replicated regarding disability more broadly and regarding necessary medical education efforts that center other marginalized populations.

PURPOSE Very little is known about primary care involvement in the care of cancer survivors beyond the initial 5 years post-treatment when transitioning to primary care is guideline-recommended for many survivors. METHODS The ICanCare study is a longitudinal survey of women diagnosed with breast cancer in 2014-2015 identified in the Georgia and Los Angeles SEER registries. Women were surveyed during initial treatment and again approximately 6 years later in survivorship (2021-2022; n = 1,412, 60% response rate). Respondents were asked which provider led their survivorship care (oncology, shared care, primary care provider [PCP]) and PCP management of eight common survivorship issues (range, 0-32). Multivariable-adjusted associations of participant characteristics with survivorship care delivery and PCP management of survivorship issues were evaluated using logistic and linear regression models, respectively. RESULTS Over half of the women (57.2%) reported oncologist-led survivorship care delivery, 20.5% shared care, and 22.4% PCP-led. PCP management of survivorship issues was moderate (mean, 11.4, 95% CI, 11.0 to 11.8) and was highest (often/always discussed) for medication management (50.1%), improving physical activity (49.1%), and chronic disease management (43.6%). Greater confidence in PCP's ability to manage survivorship care ( v no or little confidence) was associated with PCP-led delivery ( P = .01) and more PCP management of survivorship issues ( P < .0001). CONCLUSION In this diverse cohort of breast cancer survivors, primary care involvement in survivorship care delivery and management of common survivorship issues remains low even more than 5 years after completing treatment and little variation was seen across survivor sociodemographic or clinical characteristics. Confidence in PCP ability to manage survivorship care was found to be important and may represent an opportunity to foster transition to primary care-led survivorship care delivery.

Background Adults with intellectual disabilities (IDs) are at greater risk for psychiatric disorders than the general population. Yet, they have limited access to mental health services. Objectives To examine the prevalence of psychiatric disorders in adults with ID. To describe evidence-based interventions for this population, their access to mental health care, and outline opportunities for improved access. Design This manuscript summarizes literature regarding psychiatric disorders in adults with ID and their access to behavioral health care. We considered articles referencing mental health care for adults with ID. PubMed and a variety of search terms were used. Studies published in English from 2010 to the date of the searches were included. Quantitative and qualitative study designs, review articles, program descriptions, and opinion papers were considered for inclusion. Additional references from the selected articles were also considered. Results We identified 2864 records. One hundred two records were included, consisting of work commenting on mental health and ID and access to care in the United States. The articles describe increased psychiatric comorbidities in adults with ID. They highlight the few evidence-based interventions for psychiatric comorbidities and the limited access to care. Conclusions Our mental health care providers generally have minimal training and experience with people with ID, limiting access to appropriate care for these individuals. Improved access could be created by increasing education and experiences with these populations for mental health providers. Aligning policies, financing, and adequate insurance reimbursement to develop a continuum of care will be critical for these individuals.

Dermatosparaxis Ehlers Danlos syndrome (dEDS) is a very rare monogenic EDS that occurs due to biallelic pathogenic variants in ADAMTS2 . Fifteen individuals with dEDS have been reported in the literature, with the oldest being 19 years at follow‐up. Given the lack of information regarding adults with dEDS, our aim was to describe adults with dEDS to inform management recommendations in adulthood. We report five individuals (2:3 male:female) with an age range of 22–42 years. Complications include extreme skin fragility resulting in iatrogenic injury, redundant skin folds often requiring surgical resection, severe complications following a gastric volvulus secondary to a diaphragmatic hernia, and multiple fractures. Discussion of management considerations includes thorough investigations of acute pain, careful consideration of skin closure techniques and manual handling, as well as monitoring for reduced bone mineral density after low‐impact fracture and/or post‐menopause.

Background Over the past several years, there have been several changes affecting the available options for oral HIV preexposure prophylaxis, including approvals for tenofovir alafenamide with emtricitabine in 2019 and a generic formulation of tenofovir disoproxil fumarate with emtricitabine in 2020. Methods In order to better understand providers’ decision-making processes when deciding between these two drugs for pre-exposure prophylaxis, we conducted semi-structured in-depth interviews with resident, fellow and attending physicians in internal medicine and infectious diseases between May 2020 and March 2021. These interviews were analyzed to identify emergent codes, which were utilized in an inductive thematic analysis to identify major themes pertinent to pre-exposure prophylaxis decision-making. Results Of 21 participants, 18 expressed a general preference for prescribing tenofovir disoproxil fumarate with emtricitabine, 2 preferred tenofovir alafenamide with emtricitabine and 1 had no specific preference. Providers perceived similar efficacy of the two formulations, and their clinical decisions were influenced primarily by whether HIV pre-exposure prophylaxis users belonged to a population with an indication for each of the two drugs (e.g. gender-related restrictions for tenofovir alafenamide), the medications’ differing side effect profiles, cost and insurance considerations, prior personal and collective experience with each of these medications, and personal preferences. Respondents also noted that both providers and HIV pre-exposure prophylaxis users were influenced by external factors, including institutional prescribing guidance, advertising, and social influences, including from peers and colleagues. Conclusions Our findings suggest that unbiased educational campaigns for both prescribers and users of HIV pre-exposure prophylaxis will be important to support evidence-based prescribing practices and cost-effective decisions among oral pre-exposure prophylaxis options.

Amyloid-proteinopathy is observed in type 2 diabetes, where Islet amyloid polypeptide is secreted atypically and impedes cellular homeostasis. The thiazolidinediones family is reported to influence amyloid-beta aggregations. However, research on drug-based stimulation of insulin signaling to alleviate Islet amyloid aggregations is lacking. To understand the impact of pioglitazone on islet amyloid aggregation, we conducted an in vivo and in silico analysis. For in vivo analysis, we generated a transgenic Drosophila harboring the preproform of human Islet amyloid polypeptide (IAPP) that can be ectopically expressed in a spatio-temporal manner. We show that the unprocessed form of IAPP also has the propensity to form aggregates and cause degeneration. Pioglitazone feeding effectively reduces the burden of Islet amyloid aggregations in the larval brain. In silico analysis shows that there is a higher protein–ligand binding energy for IAPP with pioglitazone than amyloid-beta. These results suggests that pioglitazone might be repurposed as a drug to cure islet amyloidogenesis.

The human pulvinar is considered a prototypical associative thalamic nucleus as it represents a key node in several cortico‐subcortical networks. Through this extensive connectivity to widespread brain areas, it has been suggested that the pulvinar may play a central role in modulating cortical oscillatory dynamics of complex cognitive and executive functions. Additionally, derangements of pulvinar activity are involved in different neuropsychiatric conditions including Lewy‐body disease, Alzheimer's disease, and schizophrenia. Anatomical investigations in nonhuman primates have demonstrated a topographical organization of cortico‐pulvinar connectivity along its dorsoventral and rostrocaudal axes; this specific organization shows only partial overlap with the traditional subdivision into subnuclei (anterior, lateral, medial, and inferior) and is thought to coordinate information processing within specific brain networks. However, despite its relevance in mediating higher‐order cognitive functions, such a structural and functional organization of the pulvinar in the human brain remains poorly understood. Track‐weighted dynamic functional connectivity (tw‐dFC) is a recently developed technique that combines structural and dynamic functional connectivity, allowing the identification of white matter pathways underlying the fluctuations observed in functional connectivity between brain regions over time. Herein, we applied a data‐driven parcellation approach to reveal topographically organized connectivity clusters within the human pulvinar complex, in two large cohorts of healthy human subjects. Unsupervised clustering of tw‐dFC time series within the pulvinar complex revealed dorsomedial, dorsolateral, ventral anterior, and ventral posterior connectivity clusters. Each of these clusters shows functional coupling to specific, widespread cortico‐subcortical white matter brain networks. Altogether, our findings represent a relevant step towards a better understanding of pulvinar anatomy and function, and a detailed characterization of his role in healthy and pathological conditions.

Objective We determined if metabolic syndrome, its components, and adipokines (adiponectin, leptin, and fibroblast growth factor‐21) were associated with response to advanced therapies among patients with rheumatoid arthritis (RA). Methods This study included participants with RA initiating either tumor necrosis factor inhibitor (TNFi) or non‐TNFi biologic therapies from the Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) cohort within the CorEvitas registry. Metabolic syndrome was defined according to the National Cholesterol Education Program Adult Treatment Panel III definition. Adipokines were assessed on stored samples from a subsample of responders and nonresponders (n = 200). The primary outcome was the achievement of a change as large as the minimal clinically important difference (MCID) for the Clinical Disease Activity Index (CDAI) at 6 months. Results Among 2,368 participants, 687 (29%) had metabolic syndrome. Metabolic syndrome was associated with lower odds of achieving CDAI MCID (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.56–0.86, P = 0.001) with a dose‐dependent decrease in response rate according to the number of components present. Model fit was superior for metabolic syndrome compared with body mass index. Associations between metabolic syndrome and MCID achievement were similar between patients receiving TNFi (OR 0.65, 95% CI 0.49–0.87, P = 0.003) versus non‐TNF therapies (OR 0.76, 95% CI 0.55–1.04, P = 0.08 [P for interaction = 0.49]). Adipokines were not associated with MCID achievement. Conclusion Metabolic syndrome is associated with lower response rates with the initiation of an advanced therapy in RA, with similar effects for both TNFi and non‐TNFi agents. Adipokines were strongly associated with metabolic syndrome but were not associated with clinical response.

Alcohol use is one of the leading contributors to global burden of disease (https://www.who.int/news/item/21-09-2018-harmful-use-of-alcohol-kills-more-than-3-million-people-each-year%2D%2Dmost-of-them-men), yet only a small percentage of the population has access to psychoeducation and treatment for alcohol use disorder (https://www.niaaa.nih.gov/alcohols-effects-health/alcohol-topics/alcohol-facts-and-statistics/alcohol-treatment-united-states-age-groups-and-demographic-characteristics). Alcohol use-related policies and health advocacy efforts have played an important role in bridging this gap, but there remains a great need for effective prevention, detection, and treatment of alcohol use disorders. This chapter outlines a history of alcohol use in the United States, governmental policies regulating its distribution and consumption, advocacy work aimed at helping those with alcoholism, and healthcare systems in place to treat alcohol use disorder. Finally, it explores future directions to further address the rising rates of disordered alcohol use and its detrimental outcomes.

Elotuzumab is an approved monoclonal antibody targeting SLAMF7 on plasma and NK cells that enhances the activity of lenalidomide, pomalidomide, and bortezomib in multiple myeloma (MM). The OPTIMISMM study showed improved outcomes with the combination of pomalidomide, bortezomib, and dexamethasone (PVd) in relapsed/refractory MM. We therefore studied adding elotuzumab to PVd (elo-PVd) in relapsed/refractory MM in a multicenter phase 2 trial. The primary objective was to determine the overall response rate (ORR). Patients with relapsed/refractory disease and ≥1 prior line of treatment (including lenalidomide and a proteasome inhibitor) were eligible. For each 28 day cycle, elotuzumab was weekly for the first 2 cycles and then every other week; pomalidomide was on days 1-21; bortezomib was on days 1, 8, 15; and dexamethasone was weekly. The trial completed accrual in September 2018 with 48 patients receiving treatment. The median age was 64 (range 40-80) and the median number of prior lines was 3 (range 1-9); 25% had high risk FISH. Prior therapies included: pomalidomide (33%), daratumumab (25%), and isatuximab (4%). Best ORR was 56.3% and median PFS was 10 months. In patients with 1 prior line of therapy, ORR was 73.7% and median PFS was 23.4 months. Common grade ≥3 adverse events were neutropenia (33%); infections, any (33%); lung infection (27%); hypophosphatemia (19%); and thrombocytopenia (15%). Elo-PVd is one of the first trials of a quadruplet regimen in relapsed/refractory MM incorporating a monoclonal antibody to show efficacy across diverse prior treatments, including triple class exposed with prior anti-CD38 monoclonal antibody.

To gain insight into how researchers of aging perceive the process they study, we conducted a survey among experts in the field. While highlighting some common features of aging, the survey exposed broad disagreement on the foundational issues. What is aging? What causes it? When does it begin? What constitutes rejuvenation? Not only was there no consensus on these and other core questions, but none of the questions received a majority opinion—even regarding the need for consensus itself. Despite many researchers believing they understand aging, their understanding diverges considerably. Importantly, as different processes are labeled as “aging” by researchers, different experimental approaches are prioritized. The survey shed light on the need to better define which aging processes this field should target and what its goals are. It also allowed us to categorize contemporary views on aging and rejuvenation, revealing critical, yet largely unanswered, questions that appear disconnected from the current research focus. Finally, we discuss ways to address the disagreement, which we hope will ultimately aid progress in the field.

Body dysmorphic disorder (BDD) has many distinct features; however, it shares clinical characteristics with and has high rates of comorbidity with particular mental health conditions, including obsessive-compulsive disorder (OCD), social anxiety disorder (SAD), major depressive disorder (MDD), substance use disorders (SUD), and eating disorders (ED). In this chapter, we will review the similarities and differences between BDD and these mental health disorders. We will also discuss the differences between BDD and gender dysphoria.

Purpose This study, conducted as part of the Keep It Up! (KIU!) 3.0 trial, compares the implementation costs of two strategies – centralized direct-to-consumer (DTC) marketing and decentralized distribution via community-based organizations (CBO) – in delivering an evidence-based online HIV prevention program. Methods We conducted interviews and collected data to identify and quantify all costs for both delivery strategies. Costs were then categorized into start-up and ongoing (time-dependent and variable) costs and assigned dollar values based on established micro-costing protocols. Results In the DTC arm (1,468 enrollees), the program was implemented from October 2019 through August 2022. Total ongoing costs including overhead and excluding start-up costs were $735,953, averaging$501 per participant. Start-up costs were $398,384 ($376,393 for content design and development and $21,991 for other costs), time-dependent costs were$219,177 ($149 per participant), and variable costs were$491,658 ($335 per participant). In the CBO arm (656 enrollees across 22 sites), KIU! was implemented for a two-year period between October 2019 and December 2022. Total ongoing costs including overhead and excluding start-up costs were$2,780,682 ($4,239 per participant). Start-up costs were$511,528 ($401,141 for content design and development and$110,386 for other costs), time-dependent costs were $1,926,958 ($2,937 per participant), and variable costs were $256,543 ($391 per participant). Conclusion The DTC arm demonstrated a lower overall cost and a lower cost per participant compared to distribution via the CBO arm. Understanding these cost dynamics is pivotal for guiding decisions on program sustainability and determining funding requirements for future large-scale implementation.