United States

Background
Protocolizing pain management perioperatively can reduce opioid exposure in children. Our group designed a multi-modal, opioid free pain management protocol with intent to decrease opioids in children undergoing hernia repair. The purpose of this study is to evaluate protocol usage and outcomes after implementation.
Methods
The protocol utilizes non-opioid analgesics, nerve blocks, and child life perioperatively. Patient characteristics, pre plus intra-operative (PIO) and post-operative (PO) opioid use, and protocol adherence were compared pre- and post-implementation. Adherence was stratified by level of opioid use - high (no PIO or PO use), medium (no PIO but + PO use), and low (+PIO, +PO use).
Results
After seven months, 175 cases were analyzed with 103 pre- and 72 post-implementation. There were no significant differences in demographics or hernia type. The median age and weight were 4.00 years (IQR 1.60, 6.00) and 17.60 kg (IQR 11.97, 24.90). Post-implementation, there was a significant increase in nerve blocks (37 (51.4%) vs. 6 (5.8%), p&lt;.0001) and PIO non-opioid analgesics (64 (88.9%) vs. 24 (23.3%), p&lt;.0001). We also saw a significant decrease in PIO opioids (8 (11.1%) vs. 89 (86.4%), p&lt;.0001). Additionally, we noted a significant increase in PO non-opioid pain medications (38 (52.8%) vs. 34 (33%), p=.012). And again, there was a significant decrease in PO opioid usage in the post-implementation group (22 (30.6%) vs. 77 (74.8%), p &lt;.0001). Pain scores where not significantly affected. No significant differences were found in PO complications, including nausea, vomiting or respiratory events. 89% of cases had either high or medium protocol adherence.
Conclusion
Our protocol decreased the use of opioids in pediatric patients undergoing hernia repair. Adherence to the protocol was good and resulted in increased use of non-opioid analgesics for pain.

AMA Research Challenge 2024 

Implementation of an Opioid Free Pediatric Hernia Repair Protocol​

Background
Protocolizing pain management perioperatively can reduce opioid exposure in children. Our group designed a multi-modal, opioid free pain management protocol with intent to decrease opioids in children undergoing hernia repair. The purpose of this study is to evaluate protocol usage and outcomes after implementation.
Methods
The protocol utilizes non-opioid analgesics, nerve blocks, and child life perioperatively. Patient characteristics, pre plus intra-operative (PIO) and post-operative (PO) opioid use, and protocol adherence were compared pre- and post-implementation. Adherence was stratified by level of opioid use - high (no PIO or PO use), medium (no PIO but + PO use), and low (+PIO, +PO use).
Results
After seven months, 175 cases were analyzed with 103 pre- and 72 post-implementation. There were no significant differences in demographics or hernia type. The median age and weight were 4.00 years (IQR 1.60, 6.00) and 17.60 kg (IQR 11.97, 24.90). Post-implementation, there was a significant increase in nerve blocks (37 (51.4%) vs. 6 (5.8%), p<.0001) and PIO non-opioid analgesics (64 (88.9%) vs. 24 (23.3%), p<.0001). We also saw a significant decrease in PIO opioids (8 (11.1%) vs. 89 (86.4%), p<.0001). Additionally, we noted a significant increase in PO non-opioid pain medications (38 (52.8%) vs. 34 (33%), p=.012). And again, there was a significant decrease in PO opioid usage in the post-implementation group (22 (30.6%) vs. 77 (74.8%), p <.0001). Pain scores where not significantly affected. No significant differences were found in PO complications, including nausea, vomiting or respiratory events. 89% of cases had either high or medium protocol adherence.
Conclusion
Our protocol decreased the use of opioids in pediatric patients undergoing hernia repair. Adherence to the protocol was good and resulted in increased use of non-opioid analgesics for pain.

poster

Welcome to the **largest national, multi-specialty research** event featuring research from more than 750 medical students, residents, fellows, and international medical graduates.

Use the buttons below or navigation menu to access the event.
 

[![](https://assets.underline.io/markdown_image/1/image/20e1e77aa954efeac7a15d84c85eb383.jpg)](https://underline.io/events/468/sessions?searchGroup=all)
 
[![](https://assets.underline.io/markdown_image/1/image/068522d81aca0b68a369787c7dfccd1b.jpg)](https://underline.io/events/468/posters?searchGroup=all)
 
[![](https://assets.underline.io/markdown_image/1/image/d3971ece79d5e5575b178bdc2c8bbfae.jpg)](https://underline.io/events/468/help-desk)
 

#### Event Details

The 2024 American Medical Association Research Challenge includes a poster symposium hall and a semifinals hall with the top scored research. **Log in at any time throughout the event to:**

* **View posters and presentations** on a variety of topics and specialties
* **Score posters in the semifinals** to help decide the top five finalists (AMA member exclusive opportunity)
* **Connect with participants** and provide feedback to help advance their research

At the conclusion of this event, the AMA will announce the top five finalists who will advance to the AMA Research Challenge finals, present their research to an elite panel of judges, and compete to win a $10,000 grand prize presented by Laurel Road. 

### Grand Prize Sponsor

AMA would like to thank Laurel Road for sponsoring a $10,000 grand prize for the winner of the AMA Research Challenge. Laurel Road is not involved in winner selection process. The winner will be announced on February 20, 2025 during the AMA Research Challenge finals. Payment of the grand prize will be directly from Laurel Road. See the AMA Research Challenge Official Rules for terms and conditions.

[![](https://assets.underline.io/uploads/markdown_image/1/image/611e331d4a0eba0920f240cfc04b4d77.png)](https://www.laurelroad.com/)

**There is no registration fee for this event! **

If you have used the AMA Research Challenge platform previously, please click the ‘Log-in’ button below. If you do not remember your password, please click “forgot password” and follow prompts to reset your password. After resetting your password, please refresh your webpage to access the platform.

Register to explore research in a variety of topics. AMA members get exclusive access to score posters in the semifinals. 

**Please use this link [here](https://www.ama-assn.org/member-benefits/events/ama-research-challenge) to register for free.**

Registration or Log-in Is Required

Join the AMA Research Challenge poster symposium and semifinals to explore top research posters and score posters in the semifinals (an AMA member exclusive opportunity).

Background. Unintentional injuries are a major cause of death in the US, with unintentional falls being the most significant cause of hospitalization for injury in adults. A known contributor to fall risk is frailty, an age-related state of physiological decline and vulnerability to life stressors. Frailty itself is a significant predictor of fall risk and poor outcomes among both midlife (50 to 64 years old) and older adults (65 years old and greater), yet CDC fall screening guidelines are restricted to older adults. Moreover, the incidence and impact of frailty on outcomes in midlife trauma patients remains understudied. Herein, we assessed the incidence of frailty among midlife trauma patients from 2012 to 2021 and evaluated the impact of frailty on patients’ outcomes.

Methods. The American College of Surgeons Trauma Quality Improvement Program (TQIP) database was used. Trauma patients aged 50 to 64 were included to assess the incidence of frailty over a 10-year period (2012-2021) and the impact of frailty on outcomes in midlife adults. Demographics, injury and hospital information, comorbidities, complications, mortality, and discharge disposition were extracted. Frailty was scored using the modified frailty index-5 (mFI-5). Descriptive statistics were obtained. Frailty incidence was assessed using Poisson regression analysis, and multivariate analyses were performed on 2021 data to assess the impact of frailty on patients’ outcomes. Our primary endpoints were hospital length of stay (LOS) and discharge disposition; secondary endpoints included ICU LOS, days on a ventilator, complications, and mortality. P < 0.001 was considered significant.

Results. The frailty rate of midlife trauma patients more than doubled over the 10-year period, rising from 2.40% in 2012 to 5.09% in 2021. Upon adjustment for demographics, the incidence of frailty in this population increased by 8% per year (incidence rate ratio (IRR)=1.08 [95% CI 1.08, 1.09]). On multivariate analysis adjusting for demographics, insurance status, injury severity score, vitals on arrival, and mode of transportation, frailty was associated with increased risk of death (OR=2.272 [2.006-2.574]), longer hospital and ICU stay (MR=1.458 [1.427-1.489] and MR=1.297[1.242-1.355]), and discharge requiring higher level of care (OR=2.270 [2.163-2.383]).

Conclusion. Frailty has increased in midlife adult trauma patients over the 10-year period studied. Moreover, frailty is associated with several negative health outcomes for midlife adults. These results underscore the need for fall screening in midlife adult patients and further exploration into methods to delay the onset of frailty.

Incidence and impact of frailty in midlife trauma patients

Background
Compared to standard breast conserving surgery (BCS), oncoplastic breast conserving surgery (OBCS) has improved tumor exposure, resection of wider diameters and higher volumes, low rates of recurrence and re-resection, superior cosmetic outcomes, improved patient satisfaction, and decreased postoperative breast volume requiring lower doses of postoperative radiotherapy. OBCS has no difference in postoperative complications or overall survival compared to BCS. Racial disparities exist in both rates of reconstruction after mastectomy as well as complication rate after breast reconstruction, and though the use of OBCS has increased, there is little research investigating how race affects outcomes in OBCS. Our study compares outcomes between Hispanic and Non-Hispanic patients undergoing OBCS at a large community hospital.

Methods
A retrospective review was performed on patients who underwent oncoplastic surgery for breast cancer. Subjects were divided into Hispanic vs non-Hispanic groups. Primary outcomes included need for re-excision, hematoma formation, wound infection, areolar loss, skin necrosis, and delayed wound healing. 

Results
There were 30 patients (73%) in the Hispanic group and 11 patients (27%) in the non-Hispanic group. There was no significant difference in smoking status, hypertension, and diabetes mellitus (p=0.361, p=0.126, p=0.909) between the two groups. The average age in the Hispanic group was 55.8 +/- 9.1 whereas in the non-Hispanic group it was 58.4 +/-8.6 (p=0.416). The average BMI in the Hispanic group was 29.86 +/- 5.3 compared to 30.98 +/- 4.91 (p=0.549) in the non-Hispanic group. The average tumor size in the Hispanic group was 19.6mm +/- 11.1mm compared to 28.8mm +/- 26.4mm (p=0.148) in the non-Hispanic group. 

There were no significant differences in the need for margin re-excision (p=0.969) or post operative hematoma formation (p=0.478). There was no documented post operative wound infection, areolar loss, or skin necrosis in either group. The Hispanic group had significantly lower rates of delayed wound healing (3% in the Hispanic group vs 27% the non-Hispanic group, p=0.022). 

Conclusion
Oncoplastic breast conserving surgery is a valuable option when considering reconstruction for lumpectomy in the Hispanic population. There were no significant differences in demographics or outcomes amongst our two populations, except the Hispanic group had a lower rate of delayed wound healing. This study is limited by its small sample size and a future study with large samples is needed to corroborate these findings. Nonetheless, the benefits of oncoplastic breast conserving surgery cannot be understated and should always be considered for all patients who are appropriate candidates.


Oncoplastic Breast Conservation Surgery Outcomes are Similar Amongst Hispanic and Non-Hispanic Populations at a Large Community Hospital

Objectives: 
Vascular Ehlers-Danlos Syndrome (VEDS) is a rare connective tissue disorder impacting type III collagen production. We aim to delineate the impact of sex on variation in aortopathy, arteriopathy, and mortality among patients with VEDS. 
Methods: 
A cross-sectional analysis of 557 patients with VEDS and COL3A1 pathogenic variants was performed. Primary outcomes were distribution of aortopathy and arteriopathy, and all-cause mortality. Statistical analysis was performed utilizing Student’s t-tests (continuous data) and Pearson’s c2 tests (categorical data). 
Results:  
In the cohort, males were younger (35.8±16.6 vs. 39.2±16.0 years, P=0.017) and had more diagnoses of hypertension (16.1% vs. 8.1%, P=0.003), inguinal hernias (10.9% vs. 0.6%, P<0.001), and spontaneous pneumothoraces (10.5% vs 5.8%, P=0.043) compared to females. There was no difference in age of VEDS diagnosis, family history, or genotype frequency between males and females. Additionally, there were no statistical differences in stroke, myocardial infarction, intestinal perforation, musculoskeletal conditions. Aortopathy and arteriopathy differed between sexes. Aortopathy and arteriopathy was more common in males (74.2% vs. 57.9%, P<0.001), with more involvement of the visceral arteries (29% vs 18.4%, P=0.003), iliac arteries (23.8% vs 14.9%, P=0.008), and aorta (35.5% vs. 18.8%, P<0.001). Females had more frequent carotid cavernous fistulae (CCF, 6.2% vs 0.8%, P<0.001), carotid and great vessel involvement (23.6% vs. 15.7%, P = 0.21), and spontaneous coronary arterial dissection (SCAD, 3.2% vs 0.8%, P=0.05). Males had higher all-cause mortality (32.3% vs 20.4%, P=.001). 
Conclusions:  
Males with VEDS had more visceral artery, iliac artery, and aortic involvement, and females had greater frequency of SCAD, CCF, and carotid and great vessel involvement. These findings are similar to aortic and arterial disease in the general population. Unlike the general population, the age of onset appears to be similar between males and females with VEDS. These findings demonstrate sex-based differences in VEDS manifestation and highlight potential gaps in our understanding of patient risk factors.

Sex Differences in Vascular Ehlers-Danlos Syndrome

Background
Despite advances in revascularization strategies, lower extremity amputations remain a mainstay of treatment for chronic limb threatening ischemia (CLTI). Peripheral arterial occlusive disease results in approximately 185,000 major amputations in the United States per year. The Society for Vascular Surgery guidelines on the management of CLTI emphasize the importance of engaging patients in physical rehabilitation and obtaining prosthetics to optimize functional status after major amputation. Amputees who ambulate with a prosthetic are more well equipped to perform activities of daily living and have a survival advantage versus non-ambulatory amputees. We hypothesize that sociodemographic variables, particularly disadvantaged financial environments, have the potential to impact both rate of prosthetic utilization and the achievement of ambulation post major amputation. 

Methods
All cases in the Vascular Quality Initiative amputation module were queried. Inclusion was limited to below-, through-, and above-knee amputations. Two outcomes were investigated: Non-ambulatory status after amputation (min 120 days F/U) and not having obtained a prosthetic (min 90 days F/U). The ambulation status and prosthetic status analyses had 6984 and 6793 patients meet inclusion. Multivariable binary logistic regression was performed for the outcomes using significant (P<0.05) factors on univariable analysis.

Results
Factors with significant multivariable association for the outcome of no prosthetic utilization in follow up included: advancing age (aOR 1.011/year (1.006-1.016), P<.001); female sex (aOR 1.43 (1.28-1.61), P<.001); top 20% area of deprivation index representing most deprived areas (aOR 1.24 (1.09-1.41) P=.001); race (P=.002) with incidence of no prosthetic use at 61% for Native American, 46% for Asians; 52% for Black, 62% for Hawaiian/Pacific Islanders, 43% for White, 53% for multiracial, and 50% for unidentified race; Insurance status (P=.028) with protective status for commercial insurance (39% rate of no prosthetic) and non US insurance (33%) versus Medicare (51%), Medicaid (48%), VA insurance (49%), Self Pay (42%) and Medicare Advantage (51%). 

Conclusions
Living within the most financially disadvantaged areas and race both have a significant independent association with lack of prosthetic use following major amputation. Black, Native American and Pacific Islander demographic patients experience lack of prosthetic use at a higher rate than White and Asian patients independent of co-morbidities and socioeconomic co-variables. Female patients utilize a prosthetic and ambulate less frequently than males after major amputation, largely due to a higher rate of above knee amputation. Co-morbidities, and not socioeconomic variables are the leading drivers of non-ambulation.

The Impact of Sociodemographic Variables on Functional Recovery Following Lower Extremity Amputation

Introduction
In preparation for bariatric surgery, patients undergo nutritional counseling and are recommended to follow strict dietary instructions for weight loss. Significant weight loss reduces liver volume, reduces perioperative complications, and sets the foundation for long-term surgical success. Research suggests that educating patients about various food choices and integrating exercise routines into their daily lives can further enhance surgical outcomes and promote healthier long-term decision making. 

Traditionally, nutritional counseling for bariatric surgery patients was given through one-on-one in-person sessions. However, during the COVID-19 pandemic, most of these sessions were conducted virtually. Despite the growing prevalence of virtual sessions, there has been limited research on their effectiveness in comparison to in-person sessions. This study analyzes the efficacy of preoperative nutritional counseling by comparing in-person sessions to virtual sessions. 

Methods
A retrospective chart review of 365 patients who underwent bariatric weight loss surgery at Carle Foundation Hospital from 2018-2023 was conducted. Based on the method of pre-operative diet counseling, two groups were identified: patients who received virtual counseling and those who received in-person counseling. Data was collected on weight and BMI changes between the initial nutrition consultation date and the surgery date. Significance was calculated using the independent t-test and Spearman's correlation coefficient.

Results
Of the cohort of 365 patients, 80.8% (295) of patients received in-person counseling while 19.2% (70) of patients received virtual counseling. 81.4% (297) of patients were female. The in-person group demonstrated greater average weight losses compared to the virtual group (7.46 kg vs. 0.51 kg, p = 0.011). Similarly, the in-person group had a greater mean BMI change (-2.60 kg/m² vs. -0.39 kg/m², p = 0.019). The average minutes spent in the first nutrition consultation for the in-person and virtual groups was 48.0 minutes and 41.1 minutes respectively. While there was no correlation between time spent during consultation and weight loss for the in-person group (r = 0.064, p > 0.05), there is a positive correlation for the virtual group (r = 0.415, p < 0.001). 

Conclusion
Our results suggest that in-person education is more effective for weight loss and BMI reduction. There is a positive correlation between time spent in the first pre-operative nutrition consult and weight loss for virtual patients.

The Impact of Virtual Nutrition Counseling on Preoperative Weight Loss Prior to Bariatric Surgery

Background: 
Patients with peripheral artery disease (PAD) are at high risk of thrombosis leading to critical limb ischemia, amputation, and death. Many PAD patients also develop anemia, which affects the composition of blood, but its effect on the coagulation profile is not fully understood. We used thromboelastography with platelet mapping (TEG-PM) to measure viscoelastic properties of blood clotting in addition to the traditional clotting labs to examine the effect of anemia on coagulation parameters in PAD patients. 


Methods: 
PAD patients were prospectively evaluated from 2021 to 2024 at a large single center. TEG-PM was performed on whole blood samples that were collected prior to the patient’s revascularization. Past medical history, medication regimen, coagulation and complete blood count labs were taken from the patient’s medical record. Patients were stratified as anemic or non-anemic per WHO hemoglobin guidelines, and non-parametric T-tests were used to compare numerical variables, while Fisher’s exact test was used for categorical variables.  

Results: 
Of 397 patients, data from 211 anemic and 124 non-anemic patients were analyzed. Anemic patients displayed significantly higher values for clot strength (MA) in CK (65.5(±6.7) vs 61.3(±6.3), p<0.0001), CFF (29.1(±10.7) vs 21.4(±7.7), p<0.0001), Actf (16.1(±7.5) vs 10.3(±5.4), p<0.0001), ADP (52.8(±15.0) vs 44.6(±15.4), p<0.0001), and AA (41.4(±19.7) vs 35.3(±17.0), p=0.0072). This shows that anemic patients had greater fibrin activation (MA-ActF), fibrin contribution to clot strength (MA-CFF), and greater activation from platelets (MA-AA and MA-ADP). Anemics had significantly lower TEG-PM values of CKk (1.32(±0.70) vs 1.61(±0.63), p<0.0001), CKa (71.0(±10.5) vs 68.6(±8.9), p<0.0001), and CFFflev (515(±201) vs 400 (±145), p<0.0001), indicating faster clot propagation. In traditional coagulation labs, anemic patients had significantly longer times for INR (1.28(±0.42) vs 1.19(±0.49), p<0.0001), PT (16.0(±7.7) vs 15.3(±5.7), p=0.0023), and APTT (49.5(±26.6) vs 35.4(±14.1), p<0.0001), showing longer clotting times.  

Conclusion: 
PAD patients with anemia showed hypercoagulability through TEG-PM parameters of clot strength and fibrin activation, and hypocoagulability through traditional clotting labs. These results underscore the complexity of the effect of anemia along the coagulation cascade. Understanding this interaction can inform therapies to optimally prevent thrombosis in the anemic PAD patient population.

Effect of Anemia on Coagulation Parameters in Patients with Peripheral Arterial Disease 

Background: CDK4/6 inhibitors (CDKi) + endocrine therapy (ET) comprise the standard 1st line treatment for ER+ HER2- metastatic breast cancer (MBC). However, there is a gap in understanding how timing of MBC recurrence affects clinical outcomes on CDKi. We conducted a study to compare clinical outcomes of MBC patients on CDKi based on timing of MBC recurrence.
Methods: This retrospective study enrolled ER+ HER2- MBC patients diagnosed from Jan 2015 to Jan 2023, who received CDKi + ET as 1st line treatment for MBC. Patients were categorized as de novo MBC (dMBC), if they had 1. Stage 4 disease at initial diagnosis or 2. MBC diagnosed < 6 months of the primary breast cancer (PBC) diagnosis and before starting any systemic treatment for PBC. Patients with distant recurrence occurring < 5 years, 5-10 years, and >10 years from PBC were categorized as early, intermediate, and late MBCs (eMBC, iMBC, laMBC). Endpoints were Progression-Free Survival (PFS) and Overall Survival (OS) from MBC diagnosis. Baseline variables were compared using t-tests (continuous) and Chi-square tests (categorical). Endpoint analyses were conducted using Kaplan-Meier method and compared using Log rank test. Multivariate analyses were performed using Cox models.
Results: Out of 280 patients enrolled, 67 were dMBC, 75 eMBC, 56 iMBC, and 82 laMBC. The laMBC group had a higher mean age (years) compared to other groups (71 vs. 62 in dMBC+ eMBC + iMBC, p<0.001). 64.5% of laMBC had visceral disease compared to 50.5% of dMBC + eMBC + iMBC (p=0.031). 65.7% of dMBC patients were treated with palbociclib compared to 80.8% of eMBC + iMBC + laMBC (p=0.010). Higher % of eMBC were PR- vs other cohorts (41.3 vs 23.9 dMBC + iMBC + laMBC, p<0.001). Among the 3 non dMBC groups, prior ET sensitivity (no recurrence for 2 years on adjuvant ET) was lower in eMBC (45.3%) compared to iMBC + laMBC (81.9%, p<0.001). 61.3% of eMBC patients were on adjuvant ET at recurrence compared to 17.4% of iMBC + laMBC (p<0.001). Other variables were similar. Table shows unadjusted endpoint analyses. In multivariate analyses, the risk of PFS events were not significantly different among cohorts (age<=65, ECOG performance status (PS) >=2 and PR- were independently associated with shorter PFS); risk of death was higher in eMBC vs laMBC (HR 1.73, p=0.047).
Conclusions: In this retrospective study of ER+ HER2- MBC patients treated with 1st line CDKi + ET, timing of MBC recurrence was not associated with PFS differences after adjusting for other variables. However, patients with MBC recurring < 5 years of PBC had the higher likelihood of death compared to those recurring >10 years of PBC.

Cohort PFS events Median PFS, years [95% Confidence Interval (CI)] p value
dMBC 35/66 2.7 [1.8-Not Evaluable (NE)] 0.024
eMBC 57/74 1.6 (1.3-1.9) 
iMBC 35/56 2.1 (1.4-5.0) 
laMBC 44/82 3.2 (2.2-5.2) 

OS events Median OS, years (95% CI) p value
23/67 4.1 (3.9-8.1) 0.179
40/75 3.8 (2.6-4.9) 
22/56 4.6 (2.8-7.7) 
28/82 5.2 (4.1-NE)

Effect of timing of recurrence on outcomes in patients with metastatic breast cancer treated with CDK4/6 inhibitors

Title: FOLR1 Upregulation- A Mechanism Behind Minimal Residual Disease in Tepotinib-Treated MET Amplified NSCLC

[1]Soumya Malhotra, [2] Simon Baldacci, [2 ] Francesco Facchinetti, [2] William Feng, [2] Pasi A. Janne
[1]Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Fort Lauderdale, Florida
[2]Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts

Background: MET proto-oncogene encodes a receptor tyrosine kinase involved in cell proliferation and survival. Therefore, MET dysregulation can lead to unchecked tumor growth, invasion, and metastases. MET tyrosine kinase inhibitors (TKIs), such as tepotinib, have changed the landscape of MET Amplified Non-Small Cell Lung Cancer (NSCLC); however, patients relapse frequently due to the incomplete removal of tumor cells, resulting in the establishment of minimal residual disease (MRD). MRD, described as persister cancer cells remaining in the body after treatment, forms the basis for increased resistance development in MET Amplified NSCLC. In recent years, through systematic evaluation, Folate Receptor Alpha (FOLR1), a cell surface folate binding protein, has been implicated in cell growth regulation, DNA biosynthesis, repair, and methylation, contributing to cancer growth and metastases in solid tumors. This study investigates FOLR1 upregulation as a resistance mechanism in tepotinib-treated MET Amplified NSCLC.

Methods: Cell populations were divided into control and treated. The control population was subdivided into two to account for growth time and plate crowding. Drug toxicity assays were conducted using the Pierce BCA Protein Assay protocol to determine optimal treatment dosage. The control population was treated with low concentrations of dimethyl sulfoxide (DMSO), while the treated population received 5nM tepotinib. Both populations were treated the day following cell plating, with drug renewal performed on day five. All live cells and their culture media were harvested separately on day ten. FOLR1 expression was assessed in the harvested cells utilizing Reverse Transcription- Quantitative Polymerase Chain Reaction (RT-qPCR), Flow Cytometry, Western Blot, and in the culture media using enzyme-linked immunosorbent assay (ELISA) assays. 

Results: The results were analyzed using the GraphPad Prism program. Both populations were confirmed to express FOLR1. Control populations showed a baseline FOLR1 expression, thus confirming its presence in MET Amplified cancer cells. Moreover, the persister cells in the treated population showed a significant upregulation consistent across qPCR, ELISA, Western Blot, and Flow Cytometry assays. These results indicate that FOLR1 changes start at the transcriptional level, as shown by the increased mRNA expression through RT-qPCR. mRNA changes lead to increased cell surface and total FOLR1 protein, evidenced by the Flow Cytometry and Western Blot. Furthermore, increased FOLR1 concentrations in the culture media, measured through ELISA, affirms high FOLR1 cleavage in persister cells. These results are consistent with previous studies confirming increased FOLR1 serum concentrations in NSCLC patients.

Conclusion: Our findings provide a rationale for targeting FOLR1 in MET Amplified NSCLC. Ongoing studies to elucidate tepotinib response on FOLR1 knockout cells would strengthen our results. Furthermore, simultaneous in-vivo testing is helping progress our understanding of adverse effects related to targeting FOLR1. Antibody-drug conjugates and Chimeric Antigen Receptor T-cells are at the forefront of cancer research as targeted agents that link a cytotoxic drug to a monoclonal antibody or re-engineer T cells to specifically recognize a cellular surface antigen, improving the efficacy of chemotherapy and reducing systemic exposure and toxicity. Using this technology for FOLR1 targeted treatments could provide a new advent for managing MET Amplified NSCLC with decreased resistance-related failures.

FOLR1 Upregulation- A Mechanism Behind Minimal Residual Disease in Tepotinib-Treated MET Amplified NSCLC

Background: Pre-treatment characteristics of women with early breast cancer that are associated with persistent fatigue or suboptimal health-related quality of life (HRQOL) post-chemotherapy need to be identified as potential targets for pre-habilitation. 

Patients and Methods: Ancillary analysis of previously collected data from patients with newly diagnosed Stage I-III breast cancer scheduled to receive chemotherapy. The objective was to identify baseline (pre-chemotherapy) variables associated with meaningful deteriorations in fatigue and other measures of HRQOL from pre-treatment to 6 months after chemotherapy completion. Percentages are reported along with unadjusted and adjusted relative risks.

Results: In a sample of 249 women post-chemotherapy, 32% reported worsening fatigue (FACIT-F), 35% worsening Physical Well-Being (PWB), 16% worsening Functional Well-Being (FWB), 8% worsening Emotional Well-Being (EWB), and 30% worsening Social Well-Being (SWB). In multivariable (MV) analysis, variables that were significant in univariate analysis – Black race, high BMI, and baseline poorer EWB – remained significant for worsening post-chemotherapy fatigue (FACIT-F). In MV analysis that included race, education, falls and baseline EWB, Black race and a positive falls history remained significant for worsening PWB. In MV analysis inclusive of race, Short Physical Performance Battery (SPPB) and FWB, lower SPPB and FWB remained significant predictors of worsening FWB. In MV analysis that included baseline Mental Health Index-Anxiety, EWB and SWB, a higher SWB and lower EWB remained significant for worsening SWB. 

Conclusion: Pre-chemotherapy characteristics in women with early-stage breast cancer that are associated with increased fatigue and reduced HRQOL post-treatment could be used to identify patients who may benefit from pre-habilitation interventions. 

Keywords: breast cancer, pre-habilitation, cancer-related fatigue, chemotherapy, long-term toxicity

Identifying pre-habilitation targets for the mitigation of long-term side effects of chemotherapy in patients with early breast cancer

Background: Leiomyomatosis Peritonealis Disseminata (LPD) is characterized by multiple smooth muscle intra-abdominal and pelvic nodules that may recur after complete resection. Predominantly described in females of childbearing age, LPD has only isolated case reports indicating its malignant potential, and a comprehensive collation of cases is lacking. This manuscript presents the first comprehensive collation of published data on LPD to provide insights into its management. Additionally, we present a case of a single patient's progression from benign to malignancy over two decades, highlighting the need for long-term follow up.
Methods: We present a case of LPD's malignant transformation over two decades. Initially diagnosed with a uterine atypical smooth muscle tumor, the patient later developed frank malignancy, resulting in liver and lung metastases almost 23 years later, as confirmed by our included imaging. Additionally, we compiled an Excel database of all 213 available cases in English literature, documenting hormone receptor status, age, tumor size, follow-up time, and surgical interventions. Patients were categorized into G1 (reportedly benign), G2 (malignant at presentation), and G3 (malignant transformation).
Results: Compared to G1, patients in G2 were more likely to be symptomatic (73% vs. 88%), larger in size (4.1 cm vs. 8.4 cm), and older in age (38 vs. 44 years). The average age in G1, G2, and G3 was 38.5, 44.3, and 37.5 years, respectively, while disease-specific survival was 100%, 71%, and 40%. The mean number of surgeries performed in G1, G2, and G3 was 1.6, 1.8, and 3.8, respectively. Hormone receptors were found in 24.4% of cases. The mean reported follow-up time in G1, G2, and G3 was 44.9, 13.1, and 70.5 months, respectively. This suggests that with longer follow up, even apparently benign tumors may develop malignancy. The transformation time to malignancy in G3 was 77.8 months, which is more than the average reported follow-up in G1 (32.9 months).
Conclusion: Although LPD has been considered benign, this case shows a significant lag between initial diagnosis and malignancy development. LPD is potentially malignant with a long latency period before transformation. Lifelong surveillance should be considered even for cases presumed benign. Our results suggest that loss of hormone receptor expression may indicate malignant transformation. Circulating tumor DNA (ctDNA) levels could be associated with hematogenous metastases and serve as a novel biomarker.

Leiomyomatosis Peritonealis Disseminata (LPD): A Potentially Malignant Disease Requiring Long Term Follow-Up, Comprehensive Literature Review and Case Report of Transformation Into Malignancy

Premium content

Implementation of an Opioid Free Pediatric Hernia Repair Protocol

Next from AMA Research Challenge 2024

Incidence and impact of frailty in midlife trauma patients

Stay up to date with the latest Underline news!

PRESENTATIONS

CONFERENCES

COMPANY

RESOURCES

Premium content

Implementation of an Opioid Free Pediatric Hernia Repair Protocol​

Next from AMA Research Challenge 2024

Incidence and impact of frailty in midlife trauma patients

Stay up to date with the latest Underline news!

PRESENTATIONS

CONFERENCES

COMPANY

RESOURCES

Implementation of an Opioid Free Pediatric Hernia Repair Protocol