United States

Abstract Title
Double Trouble: Lynch syndrome and KRAS Mutation in a Young Male With Stage IV Colon Adenocarcinoma

Background
Lynch syndrome is a hereditary cancer syndrome caused by germline mutations in mismatch repair (MMR) genes, resulting in microsatellite instability (MSI) and a significantly increased lifetime risk of early-onset colorectal cancer (50%–70%). KRAS mutations, frequently observed in sporadic colorectal cancers, are less commonly associated with Lynch syndrome. Their presence can influence both prognosis and response to targeted therapies, especially anti-epidermal growth factor receptor (EGFR) agents.

Case Presentation
A 35-year-old man with a history of lumbar radiculopathy and diverticulosis presented in August 2020 with diffuse abdominal pain and altered bowel habits. An abdominal CT scan revealed hepatic metastases, and colonoscopy identified a circumferential, partially obstructing mass in the distal descending colon. Biopsy confirmed a moderately differentiated adenocarcinoma, consistent with colorectal cancer (CRC) with distant metastasis (stage IV).
In October 2020, immunohistochemistry demonstrated loss of MLH1, MSH6, and PMS2 expression, consistent with deficient mismatch repair (dMMR) and suggestive of Lynch syndrome. Molecular profiling revealed a concurrent KRAS mutation. The patient was initiated on FOLFOX chemotherapy (5-fluorouracil, leucovorin, and oxaliplatin), administered biweekly, and completed five cycles by November 2020. His current status is unknown, as he was lost to follow-up.

Discussion
The co-occurrence of dMMR, consistent with Lynch syndrome, and a KRAS mutation presents diagnostic and therapeutic complexity in metastatic CRC. While dMMR or MSI-high (MSI-H) status predicts robust responses to immune checkpoint inhibitors, concurrent KRAS mutations can negate the benefit of anti-EGFR therapies and may influence overall prognosis.
In this case, early genomic profiling identified both Lynch syndrome and a somatic KRAS mutation. This guided the decision to initiate FOLFOX chemotherapy, in line with American Society of Clinical Oncology (ASCO) recommendations. However, recent evidence, including the KEYNOTE-177 trial (February 2016-2018) , supports the use of pembrolizumab as first-line therapy in MSI-H/dMMR metastatic CRC, demonstrating superior progression-free survival compared with standard chemotherapy (median, 16.5 vs 8.2 months).
Importantly, the presence of a KRAS mutation does not preclude benefit from immune checkpoint inhibitors. Studies demonstrate durable responses in dMMR/MSI-H tumors regardless of KRAS status. Given that KRAS mutations are found in 15% to 35% of Lynch-associated metastatic CRC cases, early and comprehensive molecular testing is essential to guide treatment, assess prognosis, and inform familial risk.
This case underscores the evolving role of precision oncology in tailoring individualized treatment by integrating germline and somatic genomic data.

AMA Research Challenge 2025 

Double Trouble: Lynch Syndrome and KRAS Mutation in a Young Male With Stage IV Colon Adenocarcinoma

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poster

MicroRNAs (miRNAs) are critical regulators of gene expression. The co-expressed miRNAs, miR-24 and miR-27, are known to restrain T helper 2 (Th2) cell differentiation and the production of cytokines like Interleukin-4 (IL-4), which are central to allergic diseases. However, a comprehensive map of their target network is incomplete. High-throughput sequencing of RNA isolated by crosslinking immunoprecipitation (HITS-CLIP) can identify miRNA targets transcriptome-wide, but analyzing these large datasets to find differential targets between conditions remains a major computational challenge. To address this, we developed DeepRNA-Reg, a novel deep learning algorithm designed for high-fidelity comparative analysis of HITS-CLIP experiments.

A Deep-Learning Based Approach Uncovers Novel Mediators of Micro-RNA Restraint of Type-2 Immunity

Background
Second generation antipsychotics (SGAs) are widely used for managing psychiatric conditions due to their favorable side effect profile in comparison to first-generation agents, particularly their lower risk of extrapyramidal (EPS) symptoms. Despite their favorable profile, SGAs still carry a risk of EPS. This case highlights the course and treatment of EPS symptoms following administration of a long-acting SGA: Invega (paliperidone ER).

Case Presentation
This is a 30-year-old male with a past medical history of bipolar disorder type I who presented to our facility with diffuse muscle rigidity following recent injections of Invega. He experienced a manic episode requiring an inpatient psychiatric hospital stay 9 days prior to his presentation. During that admission he received 2 injections of Invega over the course of his 4 day stay. Post-discharge, he developed progressive muscle rigidity, facial expression changes, and weakness. These symptoms worsened over the next 5 days, at which point he presented. 

When he initially presented his major concerns were stiffness and slowness of movements. He was accompanied by his sister who corroborated his primary concerns and also noted diminished facial expressions. His examination displayed lead-pipe rigidity of the extremities with mild cog-wheeling, masked-facies, bradykinesia, and a shuffling gait. He was tachycardic and afebrile. Labs were significant for a mildly elevated CK at 235 IU/L, lactic acidosis, and serum lithium level within normal limits. He was admitted for further management and workup of EPS and was started on benztropine. NMS was considered as a diagnosis given recent antipsychotic exposure, rigidity, and tachycardia. However, the absence of fever and significant CK elevation ruled it out.

Following two days of benztropine therapy the patient’s rigidity, bradykinesia and facial animations improved and were markedly better by discharge. The patient reported feeling closer to his baseline. He was discharged with a 1 month supply of benztropine and instructions to follow up with psychiatry as an outpatient.


Discussion
This case underscores the need for vigilance when prescribing long-acting SGAs, as EPS can emerge and persist due to their prolonged pharmacokinetics. While SGAs are less likely to cause EPS, they still are capable of creating the discomforting constellation EPS symptoms. This patient’s clinical features aligned well with drug-induced parkinsonism, a subtype of EPS. The gradual onset of this patient’s symptoms and temporal relation to Invega administration were key in making this diagnosis. Clinicians should be aware of the prolonged action of Invega necessitating further follow-up as an outpatient.


A Case of Extrapyramidal Symptoms with a Long-Acting Second-Generation Antipsychotic

Background
Neurofibromatosis type 1 (NF1)—von Recklinghausen’s disease—results from mutations in the NF1 gene, leading to the absence of neurofibromin, a tumor suppressor protein. This loss promotes uncontrolled cell growth and tumor formation. NF1 presents variable clinical features, including: Cafe-au-lait macules, neurofibromas, freckling, Lisch nodules, scoliosis, pseudarthrosis, and neurological abnormalities including cognitive dysfunction and developmental delay. The genitourinary tract is rarely involved. When affected, symptoms may include recurrent urinary tract infections (UTIs), hematuria, and irritative urinary symptoms. Obstructive symptoms and urinary retention are less common and are typically associated with plexiform neurofibromas that affect multiple nerve fascicles. We present a case of an adult male with neurofibromatosis type 1 (NF1) who developed extensive systemic neurofibromas leading to recurrent urinary tract infections (UTIs) and septic shock. 

Case Presentation
We present a 31 year old male with a history of NF1, psychiatric disorders, functional quadriplegia, and numerous inoperable tumors. He developed sacral decubitus ulcers and extensive systemic neurofibromas leading to neurogenic bladder that required an indwelling Foley catheter for 1 to 2 years. This resulted in recurrent UTIs with multidrug-resistant bacteria, sepsis, and septic shock. A suprapubic catheter was placed to reduce the risk of recurrent UTIs. Despite this, he continued to experience recurrent UTIs and was readmitted with significant urine leakage around the suprapubic catheter site, severe sepsis, and acute kidney injury (AKI). Imaging revealed moderate to severe bilateral hydronephrosis and hydroureter, along with a new nodular focus along the posterior bladder wall, suspected to be a bladder neurofibroma. He also had multiple neurofibromas in the retroperitoneum, contributing to obstructive symptoms. Bilateral nephrostomy tubes were placed with frank pus noted in both tubes upon placement. Following this procedure, patient continued to experience episodes of fever, malaise, fatigue, and chills. The patient was admitted again with sepsis secondary to UTI, AKI and/or bacteremia. He responded well to a sepsis bundle and early antibiotic therapy and also underwent nephrostomy tube exchange. 

Discussion
The diagnosis of NF1 is primarily clinical. Genitourinary involvement in NF1 is uncommon. Symptoms may arise from mass effect, leading to recurrent UTIs, hematuria, dysuria, irritative symptoms, and, less commonly, obstructive symptoms. Malignant transformation of neurofibromas into malignant peripheral nerve sheath tumors can occur but is rare. Management of genitourinary involvement in NF1 is challenging and requires a multidisciplinary approach. Early diagnosis and intervention are crucial to prevent complications such as sepsis and kidney damage. 


Complications of Plexiform Neurofibromatosis of the Bladder leading to Neurogenic Bladder and Recurrent Sepsis

Abstract Title 
Primary Pancreatic Liposarcoma: A Rare Case and Presentation 

Background 
Primary pancreatic liposarcoma is an extremely rare malignancy, with fewer than ten documented cases between 1979 and 2016. Unlike more common epithelial pancreatic neoplasms, these tumors arise from mesenchymal tissue and often present diagnostic and management challenges. This is due to their rarity, variable imaging characteristics, and absence of standardized treatment protocols. This case offers insight into hospital-based diagnostic workup, imaging studies, and complex surgical management of a rare and aggressive tumor, highlighting several dilemmas frequently encountered in clinical practice. 

Case Presentation 
A 64-year-old woman with a history of breast cancer and a benign thyroid nodule presented with upper abdominal and back pain. Laboratory studies showed elevated alkaline phosphatase, with otherwise unremarkable tumor markers. CT imaging revealed a 10.0 cm heterogeneously enhancing pancreatic tail mass with coarse calcifications causing mass effect on the left kidney. Endoscopic ultrasound-guided fine-needle aspiration confirmed a hyperechoic mass with calcifications; pathology demonstrated malignant cells and osteoblast-like giant cells, consistent with dedifferentiated liposarcoma. 

The patient underwent extensive surgical resection, including distal pancreatectomy, nephrectomy, adrenalectomy, and resection of adjacent bowel segments. Follow-up imaging two months post-operatively revealed multiple hypoenhancing hepatic lesions and metastatic lymphadenopathy, confirmed on biopsy to be consistent with metastatic dedifferentiated liposarcoma. Despite initial surgical success, the disease rapidly recurred locally and metastatically. Radiotherapy and chemotherapy were deferred due to the patient’s clinical decline. She passed away shortly thereafter. 

Discussion 
This case illustrates multiple clinical dilemmas relevant to patient care. Radiologically, the absence of typical liposarcoma features, such as intralesional fat, and the presence of coarse calcifications underscore the diagnostic uncertainty associated with rare tumors such as pancreatic liposarcoma. Therapeutically, it highlights the challenges of managing aggressive malignancies for which no consensus guidelines exist. Despite complete resection, the patient experienced rapid recurrence, emphasizing the limited curative potential of surgery alone in dedifferentiated pancreatic tumor subtypes. From an educational perspective, this case reinforces the importance of maintaining a broad differential diagnosis for atypical pancreatic masses and highlights the need for interdisciplinary coordination in tumor board review, surgical planning, and palliative decision-making. This case underscores the value of recognizing rare tumor variants in hospital practice, managing rapid postoperative recurrence, and balancing aggressive intervention with patient-centered care in the absence of evidence-based treatment algorithms.

Primary Pancreatic Liposarcoma: A Rare Case and Presentation

Abstract Title
Interventions to Improve Post-Acute Care Linkage to Outpatient Treatment for Alcohol Use Disorder: A Systematic Review 

Ariyani Challapalli, BA1; Lisa Bero, PhD2; Kelsey Hills-Dunlap, MD3; Susan L. Calcaterra, MD, MPH, MS4,5; E. Jennifer Edelman, MD, MHS6,7; Gina R. Kruse, MD, MS, MPH5, Ben Harnke MLIS8; Eden Y. Bernstein, MD, MPH4

1 University of Colorado School of Medicine, Aurora, CO, USA
2 Center for Bioethics and Humanities, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
3 Division of Pulmonary Sciences & Critical Care, Department of Medicine, University of Colorado, Aurora, CO, USA
4 Division of Hospital Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
5 Division of General Internal Medicine, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA
6 Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
7 Program in Addiction Medicine, Yale School of Medicine, New Haven, CT, USA.
8 Health Sciences Library, University of Colorado Anschutz Medical Campus, Aurora, CO, USA



Background
In the United States, alcohol use contributes to nearly 180,000 annual deaths, and over 2 million adults with alcohol use disorder (AUD) are hospitalized annually. While hospitalizations provide opportunities for AUD treatment engagement, fewer than half of patients with AUD attend outpatient follow-up after discharge. We are conducting a systematic review to synthesize evidence regarding interventions that facilitate linkage to outpatient AUD treatment following acute care admissions. 

Methods
We conducted a search for English language observational studies and randomized trials published from January 2000 to February 2025 that included MeSH and text (title/abstract) terms for AUD, outpatient treatment, and acute care admissions. Two reviewers evaluated studies for inclusion in a two-phase process (title/abstract followed by full text) based on pre-defined criteria related to outcomes, study design, population, setting, and publication eligibility. Ongoing studies from ClinicalTrials.gov from January 2019 to January 2025 were included. Other database sources were Ovid MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane CENTRAL. Outcome criteria involved presence of a reported linkage to outpatient care defined as attendance to a setting where AUD treatment can be delivered, including primary care or specialty addiction treatment. Population included studies with adults age ≥18 years and >50% diagnosed with AUD or alcohol dependence. Setting included acute care admissions to hospitals and detoxification facilities but excluded residential treatment and emergency department visits. 

Results
The database search identified 4,827 unique citations, of which 4,720 were excluded during title and abstract review. Of the remaining 107 articles, 80 were excluded during full-text review: 33 (41%) were excluded due to lack of linkage to care outcome, 22 (28%) for study design, 15 (19%) for population, 8 (10%) for publication ineligibility, and 2 (3%) for setting. Of the 27 studies that met inclusion criteria, 16 (59%) were randomized controlled trials, 5 (19%) were non-randomized trials, 4 (15%) were ongoing studies, and 2 (7%) were observational studies. Of the interventions, 11 (41%) included brief interventions or motivational interviewing, 5 (19%) included medication initiation, 5 (19%) included peer or family member intervention, 4 (15%) included digital interventions, and 3 (7%) included referral strategies for outpatient treatment. Data extraction is ongoing. 


Conclusion
In this comprehensive systematic review, we identified 27 studies, including 16 randomized controlled trials, that describe interventions to link patients hospitalized with AUD to outpatient treatment. Ongoing data extraction will inform system-level design and implementation of interventions to improve outcomes in this population. 


Interventions to Improve Post-Acute Care Linkage to Outpatient Treatment for Alcohol Use Disorder: A Systematic Review

The Physician Payments Sunshine Act (2010) increased transparency in physician–industry financial relationships. This study examined industry payments to orthopaedic residency program directors (RPDs) and department chairs (RPCs) using Open Payments data from 2017–2023. Among 209 programs (209 PDs, 169 DCs), 95% received 41,465 payments totaling $126.3M. Most payments were under $1,000 and for Food & Beverage (PDs 60.7%, DCs 47.5%). Trauma RPDs and Arthroplasty RPCs had the highest average payments, while Trauma specialists received the greatest total. Funding was predominantly from Smith & Nephew (26%) and Stryker (21.6%), and disproportionately directed to males (91.1%) and MDs (88.9%). Industry funding to orthopaedic leaders is nearly universal, concentrated in certain subspecialties, and largely provided by a small number of companies.

Industry Payments to Orthopaedic Surgery RPDs and RPCs

Abstract Title
Non-Surgical Management of a Partial ACL Tear with Platelet-Rich Plasma: A Case Report

Background
Anterior cruciate ligament (ACL) injuries are common in pivoting sports and often result in long-term functional limitations. While complete ACL tears typically require surgical intervention, partial tears in active individuals may benefit from biologic therapies. We present a case of a recreational athlete with a partial ACL tear managed successfully with platelet-rich plasma (PRP) therapy.

Methods
A 29-year-old male recreational basketball player presented with acute right knee pain after landing awkwardly from a jump. He reported a mild "pop" sensation, immediate swelling, and difficulty bearing weight. He had no prior history of major knee injury. Initial conservative management included RICE and NSAIDs. Due to persistent pain and instability after 3 weeks, he was referred for further evaluation.

Results
Physical examination revealed mild effusion, tenderness along the medial joint line, and mild limitations in flexion and extension. Lachman test was mildly positive; anterior drawer test showed minimal translation. MRI demonstrated a partial tear of the ACL involving approximately 50% of the ligament fibers, with intact menisci and collateral ligaments. No chondral defects were noted. Given the partial nature of the injury and the patient's desire to avoid surgery, PRP therapy was recommended. The patient received two ultrasound-guided intra-ligamentous PRP injections over a four-week interval.

Conclusion
At the 3-month follow-up, the patient reported significant improvement in knee stability and function, with minimal pain. MRI demonstrated improved fiber continuity and decreased signal intensity in the ACL region. By 4 months post-injection, the patient had resumed non-contact basketball activity and continued with progressive strengthening and proprioception training. This case highlights the potential role of PRP therapy as a non-surgical treatment option in partial ACL tears, particularly in motivated patients seeking to return to activity. Further research is needed to better define indications and long-term outcomes of biologic therapies in ligamentous injuries.

Non-Surgical Management of a Partial ACL Tear with Platelet-Rich Plasma: A Case Report

The COVID-19 pandemic accelerated telemedicine use, offering critical healthcare access for individuals with chronic illnesses while alos exposing disparities among marginalized communities. In Flint, Michigan, a city with high poverty rates and ongoing recovery from the Water Crisis, our study sought to understand community perceptions of telemedicine. The first phase focused on English-speaking participants, revealing barriers such as lack of equipment, internet access, and awareness, alongside benefits of convenience and safety. This second phase centers on spanish-speaking residents to explore their unique, culturally specific challenges and ensure their voices shape equitable healthcare solutions.

COVID-19 and Telemedicine: Perspective from the Spanish-speaking Community in Flint, MI: A qualitative approach

In the U.S., firearms are a leading cause of traumatic injury and mortality. Firearm reinjury significantly increases morbidity, healthcare utilization, and economic burden. Hospital-based violence intervention programs (HVIPs) meet firearm injury victims in a teachable moment after injury and connect patients with peer support and community services to prevent reinjury. Identifying factors that increase risk for reinjury can guide HVIP risk stratification and harm reduction strategies. Low socioeconomic status (SES) increases firearm injury risk and may confound other risk factors. Deprivation index (DI) estimates material deprivation in a census tract, correlating with SES. We describe a cohort of patients enrolled in a HVIP, including those with a history of firearm injury, to identify factors associated with reinjury.

Patients aged 0-44 presenting at our region’s level 1 adult and pediatric trauma centers for a firearm injury from October 2024 to August 2025 were eligible for enrollment. Patients completed surveys on demographics, current and prior injury, and social determinants of health. An item-level analysis of participant responses was conducted via multivariable logistic regression at 95% confidence, using prior firearm injury as predictor, adjusted for age and gender, and then compared to separate analysis also adjusting for DI. Base OR and DI – adjusted OR was compared to detect significant change, defined a priori as > 10% difference in log-OR.

A total of 122 patients enrolled, 32 with prior firearm injury. The mean age was 26.7 years and 79.5% were male. These, along with low DI, were significantly associated with having prior firearm injury. History of firearm injury was associated with not having a high school degree, knowing the perpetrator, having a family member who was previously a victim of gun violence, incident occurrence near home, and self-reported depressive symptoms. Patients who were employed were less likely to have a history of firearm injury. DI-adjusted analysis weakened an initial association with educational attainment.

These findings are supported by prior prospective investigations which identified low SES and related factors as risk factors for reinjury. Knowing the perpetrator and having a family member injured by firearms may be novel risk factors. Educational attainment was confounded by DI on this analysis. The protective effect of employment supports the goal of HVIPs to connect patients with wraparound services, including job training and employment assistance. Future investigations should evaluate novel risk factors and risk stratification tools prospectively to overcome limitations of cross-sectional design.

Identifying factors associated with firearm reinjury in a novel hospital-based violence intervention program

Background: Since 2020, first-year students at Geisinger Commonwealth School of Medicine students were required to attend the Northeastern Pennsylvania (NEPA) Trans Health Conference, an education forum where students learn directly from community members about their health experiences, fostering cultural and narrative humility to reduce the psychological harm and medical neglect gender-diverse people face. (1, 2) In 2025, attendance became optional, with the choice to either attend the conference or complete alternative coursework. Students subsequently submitted written reflections about what they learned and how it will impact their patient advocacy. 
Methods: We conducted a qualitative cross-sectional analysis of reflections submitted by medical students who attended the NEPA Trans Health conference or completed alternative coursework in 2024 and 2025. Researchers employed a constructivist grounded theory methodology to independently code de-identified reflections and applied the Delphi method to achieve consensus. (3, 4) 
Results: Reflections from 2024 demonstrated increased knowledge about the lived experience of transgender people in support of narrative humility. (5) They also demonstrated an understanding of gender-diverse patients’ needs and the ability to apply health equity frameworks to patient advocacy. Preliminary data from 2025 reveals lower conference attendance compared to 2024. We hypothesize that students completing the alternative assignment will have more cursory responses. (6) 
Discussion: The opportunity for students to learn directly from gender-diverse communities helps learners appreciate their lived experiences. This perspective is necessary to provide sufficient care across all patient populations. Early exposure to gender-diverse populations facilitates students’ self-directed life-long learning, as required for LCME accreditation. (7)

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A Deep-Learning Based Approach Uncovers Novel Mediators of Micro-RNA Restraint of Type-2 Immunity

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