United States

Background: Trust in health insurance plays a crucial role in shaping individuals’ engagement with healthcare services, particularly as insurers assume more proactive roles in care delivery. However, limited research has examined which factors influence trust in health insurance plans and companies at the national level.

Methods: We used data from 7,702 adults in the 2021 Health Reform Monitoring Survey (HRMS) to assess factors associated with trust in health insurance. The primary outcome was a binary indicator of trust, derived from agreement with the statement: “I trust my health insurance plan and company.” Weighted bivariate analyses were employed to assess the relationships between trust and sociodemographic, health-related, and insurance-related characteristics. Variables significantly associated with trust in bivariate analyses were included in a multivariate logistic regression model to assess their independent effects. All analyses accounted for the survey’s probability weights.

Results: Among the 7,702 respondents, 69.1% reported trusting their health insurance provider. In bivariate analyses, trust varied significantly by age, race, education, income, self-rated health, usual source of care, type of insurance, perceived respect from the insurer, and perceived affordability of care (all p &lt; 0.01). In the multivariate logistic regression model, individuals with better health status, lower income, lower education, a usual source of care, or non-private insurance had higher odds of trusting their insurance. Notably, respondents who felt respected by their insurer had substantially higher odds of reporting trust (adjusted odds ratio (OR) = 67.41; 95% confidence interval (CI): 52.25–86.97). Perceived affordability of care was also positively associated with trust (adjusted OR = 1.21 per unit increase in score; 95% CI: 1.11–1.31). After adjustment, Hispanic respondents were 65% more likely to report trust (95% CI: 1.29–2.11) than White individuals.

Conclusion: Both access-related experiences and perceived interpersonal respect from insurers shape conclusions about trust in health insurance. These findings underscore the importance of fostering dignity and responsiveness in insurance interactions, as well as addressing affordability barriers to strengthen beneficiaries’ trust, particularly as insurers assume a greater role in population health and care coordination.

AMA Research Challenge 2025 

What Drives Trust in Health Insurance? Secondary Analysis of a Nationally Representative US Survey

The Inter-University Big Data Challenge (IUBDC) is a unique inquiry-driven, experiential learning program that invites students from any undergraduate or graduate program to apply their problem-solving while gaining familiarity with the fundamentals of data science. The IUBDC fosters scientific inquiry, pioneering thinking, and a solution-focused mindset to drive innovative ideas in health economics, public health, and health supply chain management.

The Sustainability Of Health Economics

National Inter-University Big Data Challenge 2022 -

Please find lead student research projects in Health Economics, such as, but not limited to:

1. Strengthening the healthcare industry against economic damage through destressing the healthcare supply chain shortages.

2. Affordable Healthcare for all, where students investigate the economics behind the delivery of quality healthcare for all.

3. The economics behind public vs private healthcare systems, which one is more sustainable, and/or how they can possibly be integrated.

4. How personal and public healthcare are affected by inflation, and how to find sustainable ways to mitigate its effects.

5. Preparing for strain on healthcare systems given the discovery of new COVID-19 variants.

Background: Trust in health insurance plays a crucial role in shaping individuals’ engagement with healthcare services, particularly as insurers assume more proactive roles in care delivery. However, limited research has examined which factors influence trust in health insurance plans and companies at the national level.

Methods: We used data from 7,702 adults in the 2021 Health Reform Monitoring Survey (HRMS) to assess factors associated with trust in health insurance. The primary outcome was a binary indicator of trust, derived from agreement with the statement: “I trust my health insurance plan and company.” Weighted bivariate analyses were employed to assess the relationships between trust and sociodemographic, health-related, and insurance-related characteristics. Variables significantly associated with trust in bivariate analyses were included in a multivariate logistic regression model to assess their independent effects. All analyses accounted for the survey’s probability weights.

Results: Among the 7,702 respondents, 69.1% reported trusting their health insurance provider. In bivariate analyses, trust varied significantly by age, race, education, income, self-rated health, usual source of care, type of insurance, perceived respect from the insurer, and perceived affordability of care (all p < 0.01). In the multivariate logistic regression model, individuals with better health status, lower income, lower education, a usual source of care, or non-private insurance had higher odds of trusting their insurance. Notably, respondents who felt respected by their insurer had substantially higher odds of reporting trust (adjusted odds ratio (OR) = 67.41; 95% confidence interval (CI): 52.25–86.97). Perceived affordability of care was also positively associated with trust (adjusted OR = 1.21 per unit increase in score; 95% CI: 1.11–1.31). After adjustment, Hispanic respondents were 65% more likely to report trust (95% CI: 1.29–2.11) than White individuals.

Conclusion: Both access-related experiences and perceived interpersonal respect from insurers shape conclusions about trust in health insurance. These findings underscore the importance of fostering dignity and responsiveness in insurance interactions, as well as addressing affordability barriers to strengthen beneficiaries’ trust, particularly as insurers assume a greater role in population health and care coordination.

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Introduction:
Crohn's Disease (CD) is a chronic inflammatory bowel disease affecting any part of the gastrointestinal tract and leading to debilitating symptoms. It impacts a substantial number of people in the US, including an estimated 80,000 children (half with CD) and over 0.7% of adults. Current treatments focus on symptom management through immune suppression, inflammation reduction, and inducing remission using immunomodulators, biologics, nutritional therapy, or surgery. However, CD can still lead to severe long-term complications significantly impacting quality of life and daily activities. Further research is essential to understand the role of gut microbiota dysbiosis in CD pathogenesis and the potential benefits of microbiota transplant.

Method: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, a systematic review was conducted on the impact of gut microbiota on CD studies published between January 2024 to April 2025. Our inclusion criteria include systematic review, randomized control trials (RCTs) done on the pediatric and adult populations. Exclusion criteria were studies done on animals. DAta was collected from Pubmed. The following keywords were used: Crohn’s Disease, Microbiota, and Microbiota transplantation. All data were assessed independently for eligibility. 4 authors collected data using the above-mentioned keywords. All eligible publications were added to a spreadsheet. To minimize bias, 4 authors reviewed, analyzed, and approved the data that was collected according to our pre-set criteria. Any publication that was duplicated or didn’t meet our inclusion criteria, was marked as so and was not included in our literature review. Moreover, any disagreements concerning the eligibility of the publication were discussed among the researchers, and a consensus was met.

Results: 
Our study included 257 studies, of which 5 met the inclusion criteria. These studies with limited pediatric studies reported potential benefits with 56.3% clinical remission rates in small cohorts. Microbiota interventions consistently led to beneficial gut microbiome changes, including increases in beneficial bacteria (e.g., Faecalibacterium prausnitzii) and decreases in harmful bacteria (e.g., Escherichia coli). Responders to Fecal Microbiota Transplantation (FMT) showed microbiome shifts towards donor profiles, increased alpha diversity, and enrichment of short-chain fatty acid-producing bacteria. Safety profiles were generally favorable, with most adverse events being minor and no mortality reported.

Conclusion:
In summary, the studies highlighted positive potential in implementing microbiota transplantation in the management of CD. That being said, more studies are needed to better understand the Microbiota transplantation in treating CD and its consequences. Bringing awareness to the dire need to modulate effective treating strategies to prevent long term complications associated with CD.


Exploring The Effects of Gut Microbiota Transplantation on Crohn’s Disease: 
A Systematic Review  

Repurposing Atypical Antipsychotics for Aggressive Prostate Cancer Treatment: Investigating Their Role in Cell Proliferation, Migration, and ER Stress
Grace Lee, OMS-III, Berony Geneste, OMS-III, Dalal Dawud, B Pharm, Zakaria Y Abd Elmageed, PhD
Department of Biomedical Science, Discipline of Pharmacology, Edward Via College of Osteopathic Medicine, Monroe, LA 71203, USA
Background & Aim: Repurposing atypical antipsychotics for untreated metastatic castration-resistant prostate cancer (mCRPC) therapy is an intriguing area of research. Several studies have shown that some antipsychotic drugs, originally developed to treat psychiatric disorders, exhibit anticancer properties. This study aimed to evaluate atypical antipsychotics anticancer properties for treatment of mCRPC by reducing cellular proliferation and migration while inducing endoplasmic reticulum (ER) stress, with fewer side effects compared to first-generation antipsychotics.
Methods: This study explored the anticancer potential of four atypical antipsychotics: cariprazine, xanomeline, pimavanserin, and iloperidone. Cytotoxic assay was performed to determine the half-maximal inhibitory concentration IC50 values of these drugs in mCRPC cells. Colony formation assay was also used to assess the ability of cells to inhibit clonogenic survival. Transwell migration assay was conducted to evaluate the impact of these agents on cell migration. To elucidate the underlying molecular mechanisms, immunoblotting analysis was conducted to evaluate pimavanserin’s role in inducing ER stress by quantifying protein markers such as CHOP, BiP, calnexin, PDI, and PERK.
Results
We found that MTT assay identified a wide range of IC50 values for the tested antipsychotics, with pimavanserin demonstrating the highest potency in reducing cell viability. Therefore, pimavanserin was selected for further investigation due to its superior efficacy and tolerability profile. Colony formation assay further confirmed pimavanserin’s superior ability to impair clonogenic survival. The transwell migration assay revealed significant inhibition of mCRPC cell migration by all four drugs, with pimavanserin exhibiting the strongest effect. These results highlight pimavanserin as a promising candidate for mCRPC therapy. Western blot analysis will validate whether pimavanserin induces ER stress by upregulating markers such as CHOP, BiP, calnexin, PDI, and PERK, which are critical components of the unfolded protein response.
Conclusion: Repurposing atypical antipsychotics offers a promising approach to cancer treatment. Among the tested agents, pimavanserin displayed the most potent effects in reducing mCRPC cell proliferation, clonogenic survival, migration, and positioning it as a leading candidate for further research. Ongoing studies will focus on elucidating the molecular mechanisms underlying its anticancer activity, particularly its capacity to induce ER stress. These results support the potential development of pimavanserin for preclinical and clinical trials.
Keywords: mCRPC, atypical antipsychotic agents, cel proliferation, colony formation, migration


Repurposing Atypical Antipsychotics for Aggressive Prostate Cancer Treatment: Investigating Their Role in Cell Proliferation, Migration, and ER Stress

Background
Acanthamoeba keratitis (AK) is an opportunistic infection caused by Acanthamoeba castellanii. In immunocompromised individuals, the organism can also lead to disseminated infections and granulomatous encephalopathy. Although there are limited resources for novel drug discovery, there remains a pressing need for new antiamoebal agents. One practical approach in such settings involves drug repurposing, which means testing compounds originally developed for other diseases. Since some proteases in Acanthamoeba are known to contribute to its pathogenicity, protease inhibitors were selected as candidates for evaluation.

Methods
Phenotypic assays compatible with high-throughput screening were developed for A. castellanii. A Resazurin-based fluorescence assay was optimized in a 96-well plate format using YPG medium supplemented for amoebae. Compounds were screened at 0.5% DMSO and incubated for 72 h. The growth or inhibition of A. castellanii was monitored fluorescence on a microplate reader. Microscopy was performed on oil immersion at 100x magnification. 

Results
The diverse protease inhibitor panel included aspartyl and cysteine protease inhibitors with previously reported activity in conditions like ischemia, AIDS, and COVID-19. Several compounds were identified as growth inhibitors of A. castellanii, representing a range of pharmacophores. One of the most active, TUN-00065 (a calpain inhibitor) demonstrated low micromolar potency. Morphological analysis suggested that TUN-00065-treated cells exhibited compromised cell walls. In contrast, cells treated with TUN-00064, a SARS-CoV-2 Mpro inhibitor, showed increased vacuolization. Additional screening revealed synergistic effects between certain protease inhibitors and existing antiparasitic agents. Sequence alignment of four putative Acanthamoeba protease homologs revealed 5 to 25 percent identity with human calpains and 15 to 25 percent identity among the amoebic sequences themselves. 

Conclusion
These findings support the potential of repurposing protease inhibitors as therapeutic or preventative agents against A. castellanii. The identification of active compounds, including TUN-00065, along with evidence of synergistic effects and conserved protease homologs, supports further investigation into targeted therapeutic strategies. Future work will focus on enzyme-based validation of these protease inhibitors in amoebal homologs.


Inhibiting Pathogenic Amoeba Growth Like a Pro(tease Inhibitor)

Abstract Title
Heart transplantation for amyloid cardiomyopathy has comparable outcomes with other etiologies: The UNOS perspective

Background
Previous evidence suggests that heart transplantation in patients with amyloid cardiomyopathy (ACM) may be suboptimal given the risk of amyloid recurrence. This study aimed to provide updated nationwide data on outcomes in heart transplantation in ACM compared with other cardiomyopathy etiologies.

Methods
United Network for Organ Sharing data for patients over eighteen who underwent heart transplant for ACM and other cardiomyopathies including idiopathic dilated cardiomyopathy (DCM), ischemic cardiomyopathy (ICM), idiopathic restrictive cardiomyopathy (RCM) and cardiomyopathy associated with congenital heart disease (CHD) were reviewed from January, 2001 through December, 2022. The data were analyzed with a propensity score-matched analysis comparing ACM patients with transplant for the cardiomyopathies to measure primary outcomes including five-year, ten-year, and all-cause mortality accounting for differences at baseline.

Results
Of 21,457 heart transplant recipients that met eligibility criteria, there was a 100% increase of heart transplants for ACM from 2010 to 2020 (p<0.001). The unadjusted mortality did not differ significantly among ACM, DCM, ICM, RCM, and CHD groups, and five-year mortality was comparable between ACM and DCM patients. ACM patients had significantly lower incidence of postoperative stroke (p=0.044), and risk factors for ACM transplant mortality were identified as mechanical ventilation at the time of transplant (HR: 3.8, p = 0.023) and older donor age (HR: 1.1, p = 0.015). Our analysis further revealed a trend towards an increasing rate of transplants for patients with ACM compared to the DCM, RCM, ICM, and CHD from 2001 to 2022.

Conclusion
The number of heart transplants for ACM has increased in recent years, and medical data on these ACM transplants has shown similar survival outcomes to transplant for other cardiomyopathies. Despite historical concerns regarding poor prognosis and amyloid recurrence, our findings suggest that carefully screened ACM patients can benefit from heart transplantation as the outcomes of heart transplantation for ACM patients are not inferior to those for patients with other cardiomyopathies. However, our results have limitations including the inherent limitations of a retrospective study design, our data set was limited to the US organ system, and we did not assess waitlist mortality. Therefore, further research is warranted along with investigating optimization of ACM patient eligibility criteria and patient selection alongside investigation of concurrent adjunct therapies such as chemotherapy and stem cell transplantation and management strategies, to offer a promising treatment of ACM with heart transplantation.


Nationwide Outcomes of Heart Transplantation for Amyloid Cardiomyopathy are Comparable with other Etiologies: The UNOS Perspective


Background:
Patients undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction are at elevated risk for venous thromboembolism (VTE) due to prolonged operative times, cancer-associated hypercoagulability, and postoperative immobility. Despite the prevalence of VTE risk, there is limited consensus on standardized prophylaxis regimens in this high-risk population.
Methods:
A retrospective chart review was conducted of all patients who underwent DIEP flap breast reconstruction performed by the senior author between October 2021 and July 2024. A standardized VTE prophylaxis protocol was applied to all patients, including preoperative education, subcutaneous heparin, intraoperative efficiency techniques, and a postoperative regimen consisting of early ambulation (physical therapy initiated at 8:00 AM on postoperative day one), sequential compression devices, compressive garments, and two weeks of enoxaparin. Patient demographics, operative details, and VTE outcomes were recorded.
Results:
A total of 187 DIEP flaps were performed on 110 patients. The average age was 49.3 years, and the mean BMI was 29.7 kg/m². All flaps were performed by a single surgeon. There was one reported VTE event—an upper extremity deep vein thrombosis (DVT) 119 days after surgery, associated with intravenous access during a revision procedure. No lower extremity DVTs or pulmonary embolisms were reported. Therefore, the VTE rate attributable directly to DIEP flap reconstruction was 0.0%.
Conclusions:
A standardized, multimodal VTE prophylaxis protocol integrating pre-, intra-, and postoperative measures—including structured early ambulation—can result in a remarkably low VTE rate in DIEP flap patients. Our findings support that such a regimen is safe, effective, and may obviate the need for risk-based pharmacologic stratification using tools such as the Caprini Risk Assessment Model in this population.

Optimizing Venous Thromboembolism (VTE) Prophylaxis Following Deep Inferior Epigastric Perforator (DIEP) Flap Breast Reconstruction

Strong therapeutic alliances in healthcare provider-patient relationships contribute to positive patient outcomes. Non-verbal behaviors from providers, such as tone of voice, facial expression, eye contact/gaze, non-verbal encouragement, and physical positioning, help build strong therapeutic relationships. Historically, acquisition of such non-verbal behaviors, and feedback on effectiveness have been limited, but, with technological advances present, opportunities for automated feedback without requiring highly trained instructors are more accessible, improving therapeutic alliance and medical care overall. This scoping review aims to summarize technology-assisted methods to assess the non-verbal behaviors of current and future healthcare providers in clinical, research, and educational settings that are known to contribute to the therapeutic alliance quality.

Technology-assisted methods to assess quality of the therapeutic alliance between healthcare providers and patients: a scoping review

Abstract Title
Approximating SIR-type structured-population models using data-driven homogeneous-population analogs.

Background
Infectious disease models are crucial tools for policymakers and public health experts when proposing mitigation strategies and allocating scarce healthcare system resources. One of the most common model frameworks used in these applications is the SIR-type family of state transition models. At their core, these models assume a homogeneous population of individuals who are partitioned into several states based on their interaction with the disease, e.g. susceptible (S), infectious (I), and recovered (R). This is the homogeneous-population model. However, this assumption of homogeneity in the population is not always justified. Taking COVID-19 as an example, the rates of hospitalization and death can differ by multiple orders of magnitude across age groups. This heterogeneity indicates that partitioning the population into sub-populations may provide more accurate modeling. This is the heterogeneous-population model. But this strategy comes with its own drawbacks of increased data needs, model overparameterization, and increased computational complexity. This work introduces a modeling approach that strikes a practical balance between simplistic homogeneous population models and their structured-population model counterparts. This new model will be known as the averaged-rates model.

Methods
Three different models: homogeneous-population, heterogeneous-population, and averaged-rates, were described. Fixed parameters (transmissibility, infectious period, death rate, etc.) were assumed for the homogeneous- and heterogeneous-population models, as is common in literature. Population-weighted time-varying averages of parameters from the heterogeneous-population model were used to generate forcing functions. These forcing functions were used in place of fixed parameters in the averaged-rates model. These models were then fitted to artificially-generated and real-world data from Washoe County, Nevada COVID-19 spikes and used to create forecasts.

Results
The averaged-rates model outperformed the homogeneous-population model with respect to goodness of fit, estimation of susceptible, exposed, infected, and recovered populations, and accuracy of forecasts. It outperformed the heterogeneous-population model with respect to computation time and degrees of freedom.

Conclusion
The averaged-rates model successfully incorporates information about population heterogeneity in disease outcomes while avoiding computational and statistical costs incurred by including an explicit sub-population structure.

Approximating SIR-type structured-population models
using data-driven homogeneous-population analogs

Single-use micropipette tips and disposable gloves contribute substantially to non-biodegradable laboratory waste and associated greenhouse gas (GHG) emissions. This study assessed the effectiveness of micropipette tip washers (MTWs) and energy-from-glove-waste programs (EGWs) in reducing annual single-use plastic and nitrile waste in laboratory environments. Four research laboratories at Arizona State University’s Biodesign Institute (BDI) were sampled, with results extrapolated to institutional and national scales. Implementation of MTWs resulted in a statistically significant reduction in micropipette tip waste (x̄ = 10 kg, σ = 4.8 kg before; x̄ = 0.84 kg, σ = 0.40 kg after; p = 0.012). While glove waste was completely eliminated in sampled labs (x̄ = 37 kg, σ = 40 kg before; x̄ = 0 kg, σ = 0 kg after), the difference was not statistically significant (p = 0.082). Combined waste reduction across both interventions approached significance (x̄ = 47 kg, σ = 43 kg before; x̄ = 0.07 kg, σ = 0.03 kg after; p = 0.059). At the institutional level, MTWs reduced micropipette tip waste by 92% (0.9 ± 0.3 metric tons) and associated carbon emissions by ~84% (31 ± 9 metric tons). EGWs reduced glove waste by 100% (36 ± 19 metric tons) and glove-related emissions by ~5.0% (1.2 ± 0.7 metric tons). Nationally, projected annual reductions were 8,100 ± 2,300 tons of plastic and 33,000 ± 18,000 tons of nitrile waste. These findings support the scalable environmental benefits of targeted waste reduction technologies in research settings.

A Case Study on Reducing Single-Use Plastic and Nitrile Waste in U.S. Research Institutions

Background:
Formalin-Fixed Paraffin-Embedded (FFPE) tissue is the most commonly archived specimen in clinical practice due to its ease of storage, long-term preservation, and compatibility with histopathological evaluation. However, the use of FFPE samples in molecular studies has been limited by the degraded and fragmented nature of RNA, often compromising the quality and reliability of downstream transcriptomic analyses. Recent advances in RNA extraction protocols and quantification methods have begun to overcome the molecular limitations associated with FFPE tissue, enabling more accurate and reproducible gene expression profiling from archival samples. Our goal was to compare gene expression profiles between FFPE and fresh liver biopsy samples from patients with physiologically normal livers (controls) and hepatitis C virus (HCV) infected livers, pre and post Direct-Acting antivirals (DAA) treatment, using an AI-based bioinformatics pipeline.

Methods:
We compared gene expression profiles derived from RNA isolated from FFPE vs fresh liver biopsies obtained from controls, HCV Pre-DAA, and HCV Post-DAA. Whole-transcriptome sequencing was performed using Smart-3SEQ. We developed an AI-bioinformatics pipeline through prompting with Claude Sonnet 4 within QualifiedHealth. FastQ pseudo-alignment and count generation were performed using Salmon within Galaxy (web toolkit. Filtering was performed with traditional CPM thresholds, TMM within edgeR, and non-coding gene removal. Normalization and Differential Expression (DE) analysis was performed with Limma-Voom.

Results:
No significant gene expression differences were found between FFPE and fresh samples in the control or post-DAA groups. However, in the pre-DAA group, 40 genes were initially found as significantly different. Subdividing the Pre-DAA condition according to immune-gene expression (PreCold for down-regulation and PreHot for up-regulation) resulted in no significant DEGs within each group. Furthermore, investigation of 17 housekeeping genes across all samples revealed no significant differences in expression between FFPE and fresh samples.

Conclusion: 
Gene expression profiles from FFPE samples showed high correlation with fresh tissue across three distinct liver conditions. Previous significant DEGs in the Pre-condition were attributed to immune gene expression rather than storage methodology. Commercially available LLMs enable rapid development of robust bioinformatics workflows for complex transcriptomic analyses, while the minimal differences between sample types validate FFPE tissue as a reliable source for retrospective molecular studies.


Comparison of FFPE to Fresh Liver Biopsies Using Whole Transcriptome Analysis from Patients with HCV using an AI-based Bioinformatics Pipeline

Background
Lysosomal storage diseases (LSDs) are a heterogeneous group of over 70 inherited metabolic disorders caused by deficiency of lysosomal enzymes, leading to accumulation of undegraded substrates in multiple organs. Their collective incidence is approximately 1 in 7,700 live births, affecting an estimated 1.5 million individuals globally. Clinical presentations are diverse, often involving the multiple organ systems, and in particular, the skin and gastrointestinal (GI) tract. Dermatologic signs may be visible before visceral symptoms, yet their association with GI complications is explored. Given the diagnostic delays inherent to these rare conditions and their debilitating nature, early recognition of cutaneous manifestations could prompt timely evaluation for systemic involvement.
Methods
In this retrospective cohort study, we analyzed de-identified data from TriNetX - a comprehensive electronic health records network encompassing 143 healthcare systems across 18 countries and over 163 million patient records. Patients with a diagnosis of LSD - including Fabry disease, Gaucher disease, Niemann-Pick disease, and related LSDs - were divided into two cohorts: those with cutaneous manifestations (Cohort A) and those without (Cohort B). Presence of GI outcomes including hepatosplenomegaly, diarrhea, noninfectious gastroenteritis, malabsorption, and generalized abdominal pain were measured up to 1 year after diagnosis for both cohorts. Risk ratios and survival analyses were calculated.
Results
For Cohort A (N=2,983), GI outcomes occurred in 11.1% while in Cohort B (N=14,648), GI outcomes occurred in 7.2%. The risk difference was 3.9% (95% CI: 2.7–5.1%, p < 0.001). The risk ratio was 1.54 (95% CI: 1.37–1.73). Kaplan-Meier analysis showed lower 1-year survival free of GI outcomes in the skin manifestation group (86.0% vs 92.1%, log-rank test p < 0.0001).
Ó 2025 American Medical Association. All rights reserved.
Conclusion
Cutaneous manifestations in patients with LSD were significantly associated with 54% increased risk of GI complications within one year of diagnosis. Cutaneous manifestations may reflect systemic substrate accumulation, highlighting shared pathophysiology that causes both skin and GI involvement. Early recognition of dermatologic findings - such as angiokeratomas, xanthomas, or pruritus - in patients with LSD could prompt vigilant monitoring for GI symptoms, including hepatosplenomegaly, malabsorption, and abdominal pain. For example, clinicians may consider initiating interventions like enzyme replacement therapy, substrate reduction therapy, pharmacologic therapies, or supportive measures. Ultimately, these findings suggest that dermatologic evaluation could serve as a simple, noninvasive marker for risk stratification and facilitate a proactive approach to management of multisystem disease in LSD.
Background
Lysosomal storage diseases (LSDs) are a heterogeneous group of over 70 inherited metabolic disorders caused by deficiency of lysosomal enzymes, leading to accumulation of undegraded substrates in multiple organs. Their collective incidence is approximately 1 in 7,700 live births, affecting an estimated 1.5 million individuals globally. Clinical presentations are diverse, often involving the multiple organ systems, and in particular, the skin and gastrointestinal (GI) tract. Dermatologic signs may be visible before visceral symptoms, yet their association with GI complications is explored. Given the diagnostic delays inherent to these rare conditions and their debilitating nature, early recognition of cutaneous manifestations could prompt timely evaluation for systemic involvement.
Methods
In this retrospective cohort study, we analyzed de-identified data from TriNetX - a comprehensive electronic health records network encompassing 143 healthcare systems across 18 countries and over 163 million patient records. Patients with a diagnosis of LSD - including Fabry disease, Gaucher disease, Niemann-Pick disease, and related LSDs - were divided into two cohorts: those with cutaneous manifestations (Cohort A) and those without (Cohort B). Presence of GI outcomes including hepatosplenomegaly, diarrhea, noninfectious gastroenteritis, malabsorption, and generalized abdominal pain were measured up to 1 year after diagnosis for both cohorts. Risk ratios and survival analyses were calculated.
Results
For Cohort A (N=2,983), GI outcomes occurred in 11.1% while in Cohort B (N=14,648), GI outcomes occurred in 7.2%. The risk difference was 3.9% (95% CI: 2.7–5.1%, p < 0.001). The risk ratio was 1.54 (95% CI: 1.37–1.73). Kaplan-Meier analysis showed lower 1-year survival free of GI outcomes in the skin manifestation group (86.0% vs 92.1%, log-rank test p < 0.0001).
Ó 2025 American Medical Association. All rights reserved.
Conclusion
Cutaneous manifestations in patients with LSD were significantly associated with 54% increased risk of GI complications within one year of diagnosis. Cutaneous manifestations may reflect systemic substrate accumulation, highlighting shared pathophysiology that causes both skin and GI involvement. Early recognition of dermatologic findings - such as angiokeratomas, xanthomas, or pruritus - in patients with LSD could prompt vigilant monitoring for GI symptoms, including hepatosplenomegaly, malabsorption, and abdominal pain. For example, clinicians may consider initiating interventions like enzyme replacement therapy, substrate reduction therapy, pharmacologic therapies, or supportive measures. Ultimately, these findings suggest that dermatologic evaluation could serve as a simple, noninvasive marker for risk stratification and facilitate a proactive approach to management of multisystem disease in LSD.

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Exploring The Effects of Gut Microbiota Transplantation on Crohn’s Disease: A Systematic Review

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