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Esophageal Disorders in the Older Adult

Babbar, Shaili; Sachar, Moniyka; Faye, Adam; Knotts, Rita M
PURPOSE OF REVIEW/UNASSIGNED:Dysphagia is a common medical condition among the geriatric population that can significantly impact a patient's quality of life. The manifestations, diagnosis, and treatment of esophageal dysphagia differ greatly based on the underlying etiology, especially in older individuals who may have accompanying complex medical comorbidities. This review explores the intricacies of esophageal dysphagia in the older population and how they are managed. RECENT FINDINGS/UNASSIGNED:Novel modalities, like the functional luminal imaging probe (FLIP) and timed barium esophagram (TBE), are now woven into our diagnostic schemas for esophageal dysphagia. Studies have also looked at the safety profile of available therapeutic interventions for older individuals. There are newer, less invasive treatment options, including radiofrequency application (RFA) and transoral incisionless fundoplication (TIF) for GERD management, that may benefit the geriatric population. SUMMARY/UNASSIGNED:In this review, we discuss the most likely etiologies of esophageal dysphagia in the elderly population. We then explore a diagnostic schema and highlight treatment choices based on diagnosis. Our review specifically explores the risks and benefits of management options in more medically complex geriatric patients.
PMCID:11887613
PMID: 40061442
ISSN: 1092-8472
CID: 5808142

Appropriate use and complications of corticosteroids in inflammatory bowel disease: A comprehensive review

Feuerstein, Joseph D; Rubin, David T; Aberra, Faten N; Yarur, Andreas; Malter, Lisa
Corticosteroids are one of the most frequently prescribed medications for the management of inflammatory bowel disease. While corticosteroids have a critical role for select cases for induction of remission, there is a notable risk of over-use and miss-use of corticosteroids. This narrative review updates the evolving use of corticosteroids in the management of inflammatory bowel disease. The review focuses on the appropriate use, route of administration and duration for the use of corticosteroids. Additionally, this review summarizes the side effects, use of steroids in special populations (e.g. geriatrics, pregnancy, underrepresented minorities), and their use in the peri-operative setting.
PMID: 40588110
ISSN: 1542-7714
CID: 5887642

Addendum: Unravelling cysteine-deficiency-associated rapid weight loss

Varghese, Alan; Gusarov, Ivan; Gamallo-Lana, Begoña; Dolgonos, Daria; Mankan, Yatin; Shamovsky, Ilya; Phan, Mydia; Jones, Rebecca; Gomez-Jenkins, Maria; White, Eileen; Wang, Rui; Jones, Drew R; Papagiannakopoulos, Thales; Pacold, Michael E; Mar, Adam C; Littman, Dan R; Nudler, Evgeny
PMID: 40579778
ISSN: 1476-4687
CID: 5887242

Proximity between LAG-3 and the T cell receptor guides suppression of T cell activation and autoimmunity

Du, Jasper; Chen, Hui; You, Jia; Hu, Wei; Liu, Jia; Lu, Qiao; Zhang, Yong; Gao, Jie; Lin, Meng-Ju; Foster, Connor James Ryan; Rao, Eric; Cammer, Michael; Yin, Weiwei; Koide, Shohei; Lu, Catherine Pei-Ju; Chen, Wei; Lou, Jizhong; Wang, Jun
Therapeutically targeting pathogenic T cells in autoimmune diseases has been challenging. Although LAG-3, an inhibitory checkpoint receptor specifically expressed on activated T cells, is known to bind to major histocompatibility complex class II (MHC class II), we demonstrate that MHC class II interaction alone is insufficient for optimal LAG-3 function. Instead, LAG-3's spatial proximity to T cell receptor (TCR) but not CD4 co-receptor, facilitated by cognate peptide-MHC class II, is crucial in mediating CD4+ T cell suppression. Mechanistically, LAG-3 forms condensate with TCR signaling component CD3ε through its intracellular FSAL motif, disrupting CD3ε/lymphocyte-specific protein kinase (Lck) association. To exploit LAG-3's proximity to TCR and maximize LAG-3-dependent T cell suppression, we develop an Fc-attenuated LAG-3/TCR inhibitory bispecific antibody to bypass the requirement of cognate peptide-MHC class II. This approach allows for potent suppression of both CD4+ and CD8+ T cells and effectively alleviates autoimmune symptoms in mouse models. Our findings reveal an intricate and conditional checkpoint modulatory mechanism and highlight targeting of LAG-3/TCR cis-proximity for T cell-driven autoimmune diseases lacking effective and well-tolerated immunotherapies.
PMID: 40592325
ISSN: 1097-4172
CID: 5887772

CLNS1A regulates genome stability and cell cycle progression to control CD4 T cell function and autoimmunity

Wang, Liwei; Noyer, Lucile; Jishage, Miki; Wang, Yin-Hu; Tao, Anthony Y; McDermott, Maxwell; Gando, Ivan; Sidhu, Ikjot; Hu, Ke; Zhong, Li; Sun, Katherine; Drmic, Dominik; Kaufmann, Ulrike; Feske, Stefan
Pathogenic CD4 T cells drive autoimmunity in diseases such as multiple sclerosis (MS) and inflammatory bowel disease (IBD). Through a forward genetic screen, we identified chloride nucleotide-sensitive channel 1A (CLNS1A) as a key regulator of inflammation in the experimental autoimmune encephalomyelitis (EAE) model of MS. CLNS1A is expressed in several subsets of CD4 T cells, including pathogenic T helper 17 (pTH17) cells. Deletion of Clns1a in T cells resulted in DNA damage, cell cycle arrest, impaired T cell proliferation, and effector function, thereby protecting mice from both EAE and IBD. We found that CLNS1A interacts with protein arginine methyl transferase 5 (PRMT5). Moreover, CLNS1A regulates symmetric histone dimethylation and the expression of genes involved in DNA repair, replication, and cell cycle progression. Thus, CLNS1A plays an important role in CD4 T cells by promoting genome stability and cell cycle progression.
PMID: 40540585
ISSN: 2470-9468
CID: 5871302

Defining On-Treatment Remission in Plaque Psoriasis: A Consensus Statement From the National Psoriasis Foundation

Armstrong, April W; Gondo, George C; Merola, Joseph F; Roberts, Alyssa M; Pérez-Chada, Lourdes M; Balak, Deepak M W; Eakin, Guy S; Read, Charlotte; Le, Stephanie T; Gutierrez, Yasmin; Bhutani, Tina; Blauvelt, Andrew; Duffin, Kristina Callis; Fakharzadeh, Steven; Feldman, Steven R; Gelfand, Joel M; Gladman, Dafna D; Glick, Brad; Green, Lawrence J; Han, George; Hawkes, Jason E; Hwang, Samuel T; Johnsen, Nicole; Kalb, Robert E; Kircik, Leon; Langley, Richard G; Lebwohl, Mark G; Lewitt, G Michael; Maverakis, Emanual; Prussick, Ronald; Reddy, Soumya M; Rosen, Cheryl F; Scher, Jose U; Siegel, Evan L; Wallace, Elizabeth B; Weinberg, Jeffrey M; Yamauchi, Paul S; Yosipovitch, Gil; Liao, Wilson; ,
IMPORTANCE/UNASSIGNED:Defining on-treatment remission in plaque psoriasis is important for benchmarking patient responses to therapies. This also helps to facilitate shared understanding, align treatment expectations, and enable more effective psoriasis management. OBJECTIVE/UNASSIGNED:To establish a consensus-based definition of on-treatment remission for plaque psoriasis through a multistage Delphi initiative. EVIDENCE REVIEW/UNASSIGNED:The Remission Workgroup from the medical board and scientific advisory board of the National Psoriasis Foundation engaged various stakeholders, both US based and international, to participate in the consensus process. Following a working group meeting to determine the overall consensus approach, a systematic review of remission definitions in the current literature was performed. This review helped to inform the content of consensus materials. The consensus effort involved 2 stages: pre-Delphi interviews and surveys to inform the Delphi questions, followed by a Delphi exercise with physicians to define on-treatment remission for plaque psoriasis. Outcome measures considered included body surface area (BSA), Investigator Global Assessment (IGA), the product of the Physician Global Assessment and body surface area (PGA × BSA), and Psoriasis Area and Severity Index (PASI) score at various cutoff levels and time points. FINDINGS/UNASSIGNED:The consensus process involved 92 stakeholders, including dermatologists, rheumatologists, researchers, patients, payers, and life sciences professionals. In the pre-Delphi interviews and surveys, patients emphasized that on-treatment remission meant the absence of psoriasis signs and symptoms while recieving therapy. Payers expressed that defining remission is important for long-term treatment coverage. Following the Delphi exercise and discussion with participating physicians specializing in psoriatic disease management, on-treatment remission in plaque psoriasis was defined as patients maintaining a BSA of 0% or IGA of 0 for at least 6 months while on treatment. CONCLUSIONS AND RELEVANCE/UNASSIGNED:Through a Delphi consensus process, on-treatment remission for plaque psoriasis was defined as patients maintaining a BSA involvement of 0% or IGA of 0 for at least 6 months while on treatment. This clear and standardized benchmark is applicable to both research and practice settings.
PMID: 40531503
ISSN: 2168-6084
CID: 5871042

NF1 Loss Promotes EGFR Activation and Confers Sensitivity to EGFR Inhibition in NF1 Mutant Melanoma

Ibrahim, Milad; Illa-Bochaca, Irineu; Jour, George; Vega-Saenz de Miera, Eleazar; Fracasso, Joseph; Ruggles, Kelly; Osman, Iman; Schober, Markus
Targeted therapies and immunotherapy have improved treatment outcomes for many melanoma patients. However, patients whose melanomas harbor driver mutations in the neurofibromin 1 (NF1) tumor suppressor gene often lack effective targeted treatment options when their tumors do not respond to immunotherapy. In this study, we utilized patient-derived short-term cultures (STCs) and multiomics approaches to identify molecular features that could inform the development of therapies for patients with NF1 mutant melanoma. Differential gene expression analysis revealed that the epidermal growth factor receptor (EGFR) is highly expressed and active in NF1 mutant melanoma cells, where it hyper-activates ERK and AKT, leading to increased tumor cell proliferation, survival, and growth. In contrast, genetic or pharmacological inhibition of EGFR hindered cell proliferation and survival and suppressed tumor growth in patient-derived NF1 mutant melanoma models but not in NF1 wild-type models. These results reveal a connection between NF1 loss and increased EGFR expression that is critical for the survival and growth of NF1 mutant melanoma cells in patient-derived culture and xenograft models, irrespective of their BRAF and NRAS mutation status.
PMID: 40494652
ISSN: 1538-7445
CID: 5869162

Current Perspectives on Colorectal Cancer Screening and Surveillance in the Geriatric Population

Udaikumar, Jahnavi; Nimmagadda, Rithish; Ingawale, Sushrut; Lella, Vindhya Vasini; Vijayakumar, Keerthika; Faye, Adam S; Shaukat, Aasma
PURPOSE OF REVIEW/OBJECTIVE:Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with 44% of deaths occurring in individuals aged 75 years and older. With 78 million adults over 65 years projected by 2035, optimizing CRC screening and surveillance is crucial. This review examines guidelines, risks, and personalized approaches. RECENT FINDINGS/RESULTS:CRC screening reduces incidence by 17-33% and mortality by 11-53%. Colonoscopy lowers mortality by 61% but has a 6.8% complication rate in those aged 75 years and older. The risk of gastrointestinal bleeding is 8.7 per 1,000 for polypectomy, and perforation occurs in 0.6 per 1,000. Frailty indices assess suitability, but surveillance guidelines lack clear discontinuation criteria. Screening should balance risk, complications, and health status. It may be cost-effective up to age 86 years in healthy individuals, but more research is needed to refine surveillance strategies and reduce overtreatment in older adults.
PMID: 40455318
ISSN: 1534-312x
CID: 5862092

Right-Sided Dysplasia in Inflammatory Bowel Disease Is Not Associated with Conventional Risk Factors for Neoplasia

Bhattacharya, Sumona; Beaty, William; Faye, Adam S; Axelrad, Jordan E
INTRODUCTION/UNASSIGNED:In the general population, right I-sided dysplasia presents a higher risk for colorectal cancer (CRC) and metachronous dysplasia compared to left (L)-sided dysplasia. Given that patients with inflammatory bowel disease (IBD) are at higher risk for dysplasia than the general population, we sought to assess the risk factors as well as the differences in outcomes between patients with R-sided, L-sided, and both R- and L-sided dysplasia. METHODS/UNASSIGNED:A retrospective chart review was performed on patients at NYU Langone Health who had evidence of dysplasia on a colonoscopy between 2011 and 2021. Demographics and pertinent medical history were compiled. Cohorts were based on the dysplasia location (R-sided, L-sided, or R- and L-sided) and the IBD-related outcomes were analyzed. RESULTS/UNASSIGNED:= 0.03). CONCLUSIONS/UNASSIGNED:Patients with UC had a higher risk for L-sided colonic dysplasia compared to patients with CD; however, there were no differences in the progression of dysplasia between those who had R-sided and those who had L-sided dysplasia. Larger studies are needed to assess the risk factors and outcomes related to the laterality of dysplasia and further validate these findings among patients with IBD.
PMCID:11999668
PMID: 40242653
ISSN: 2036-7414
CID: 5828542

Evaluating Methods for Imputing Race and Ethnicity in Electronic Health Record Data

Conderino, Sarah; Divers, Jasmin; Dodson, John A; Thorpe, Lorna E; Weiner, Mark G; Adhikari, Samrachana
OBJECTIVE:To compare anonymized and non-anonymized approaches for imputing race and ethnicity in descriptive studies of chronic disease burden using electronic health record (EHR)-based datasets. STUDY SETTING AND DESIGN/METHODS:In this New York City-based study, we first conducted simulation analyses under different missing data mechanisms to assess the performance of Bayesian Improved Surname Geocoding (BISG), single imputation using neighborhood majority information, random forest imputation, and multiple imputation with chained equations (MICE). Imputation performance was measured using sensitivity, precision, and overall accuracy; agreement with self-reported race and ethnicity was measured with Cohen's kappa (κ). We then applied these methods to impute race and ethnicity in two EHR-based data sources and compared chronic disease burden (95% CIs) by race and ethnicity across imputation approaches. DATA SOURCES AND ANALYTIC SAMPLE/UNASSIGNED:Our data sources included EHR data from NYU Langone Health and the INSIGHT Clinical Research Network from 3/6/2016 to 3/7/2020 extracted for a parent study on older adults in NYC with multiple chronic conditions. PRINCIPAL FINDINGS/RESULTS: = 0.33). When these methods were applied to the NYU and INSIGHT cohorts, however, racial and ethnic distributions and chronic disease burden were consistent across all imputation methods. Slight improvements in the precision of estimates were observed under all imputation approaches compared to a complete case analysis. CONCLUSIONS:BISG imputation may provide a more accurate racial and ethnic classification than single or multiple imputation using anonymized covariates, particularly if the missing data mechanism is MNAR. Descriptive studies of disease burden may not be sensitive to methods for imputing missing data.
PMID: 40421571
ISSN: 1475-6773
CID: 5855152