United States

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&lt;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&lt;.001); female sex (aOR 1.43 (1.28-1.61), P&lt;.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.


AMA Research Challenge 2024 

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

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AMA Research Challenge 2023

Join the AMA Research Challenge poster symposium and semifinals to explore top research posters, score posters in the semifinals (an AMA member exclusive opportunity) and attend education sessions with experienced physicians to learn tips to advance your research and career. 

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.

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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

Background
Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening thrombotic disorder. Therapeutic plasma exchange (TPE) remains the mainstay treatment, with thawed plasma (TP) being the primary product used. Liquid plasma (LP), derived from whole blood donations and stored at 4°C, shares the same expiration as the corresponding unit of whole blood and primarily serves as a bridge to TP for emergency transfusions. While the efficacy of coagulation profiles in TP and LP is well-documented, there is limited information on the stability
of ADAMTS13 activity during the shelf life of these products and the experience of LP utilization in iTTP management.
Methods
Ten units of LP from distinct whole blood donations were collected on day 27. Ten units of TP from products frozen within 24 hours (PF24) were collected on day 6. Two units of LP within 5 days of collection underwent longitudinal sampling until day 30, with the initial collection designated as day 0. ADAMTS13 activity was assessed using fluorescence resonance energy transfer (FRETS) and ELISA-based assays. A retrospective study was performed to identify the use of LP in TPE for iTTP patients in our institute from June 15, 2019, to January 1, 2023.
Results
The average level of ADAMTS13 activity in 10 LP units was 0.97±0.14 IU/mL by FRETS assay, with a median of 0.967 IU/mL (range: 0.79-1.22 IU/mL). For 10 TP units, the average level of ADAMTS13 activity was 0.89±0.13 IU/mL with a median of 0.91 IU/mL (range: 0.63-1.05 IU/mL). No statistically significant difference was observed between the two products regarding ADAMTS13 activity on day 1 post-expiration (P=0.1717). ADAMTS13 activity in LP consistently remained stable over the 30-day observation period. ELISA results were consistent with FRETS assay findings. The retrospective analysis showed that seven iTTP patients with nine acute
episodes received a total of 93 TPE sessions, of which, 25 (26.9%) included LP. The amount of LP was 23.7±19.7% of total plasma units. The median number of TPE sessions per episode was 10, which was comparable to that in the literature. All patients achieved complete remission, and no adverse events associated with the use of LP were observed.
Conclusion
Both liquid plasma and thawed plasma exhibit comparable and sustained ADAMTS13 activity throughout their shelf-life. A successful utilization of LP during TPE in a small cohort of iTTP patients suggests that LP may be a potential alternative to TP in the management of iTTP.

Liquid Plasma: A Potential Product in Managing Immune Thrombotic Thrombocytopenic Purpura

Background
The obesity paradox has been shown in many cancers, with improved overall survival in higher BMI groups. Lower incidence, better prognosis, and improved treatment response of lung cancer have been associated with increased BMI. However, these differences have varied based on age, gender, and race. This variability can be explained by the heterogeneity of fat deposition across gender and race, which is poorly captured by BMI. Other measures of central adiposity better portray the effects of obesity on lung cancer risk and prognosis. We report the results of another measure of central adiposity, liver fat, on survival and treatment tolerance in NSCLC.
Methods:
This retrospective cohort study enrolled 106 patients with stage IIIA-IIIC NSCLC treated to 60 Gy at Fox Chase Cancer Center. Liver fat percentage was assessed via CT in Hounsfield units (HU). Patients were separated into two groups, high HU and low HU, correlating to low and high liver fat percentages, respectively. The primary objective assessed mortality while secondary objectives assessed treatment response, disease progression, and acute/chronic treatment toxicities.
Results
Initial staging was the only categorical variable with significant difference in HU groups. BMI and primary tumor size varied significantly between groups. Overall survival (OS) and progression-free survival (PFS) appeared to be better in the higher HU group, but not statistically significant. No significant difference in acute or chronic treatment-related adverse events between HU groups.
Conclusion
Liver fat percentage has the potential to be used as a proxy for central adiposity to risk stratify NSCLC patients. Excess adiposity may provide an energy reserve to endure biological stress from disease progression and treatment, leading to a survival advantage. This study showed no statistical significance in OS or PFS between HU groups. One limitation is the small sample size leading to reduced statistical power and difficulty in detecting subgroup effects. Future studies should focus on involving large and diverse cohorts, considering confounding factors like BMI, smoking history, and tumor characteristics. If statistical significance can be measured, liver fat may have the potential to be used as a prognostic marker for outcomes to stratify patients into different risk categories, guiding treatment decisions and improving personalized medicine approaches.

Liver Adiposity as a Predictor of Mortality in NSCLC Patients

Background: Osteosarcoma, a highly aggressive pediatric cancer originating from aberrant bone cells, presents with symptoms like local pain and swelling, often leading to delayed diagnosis with imaging and biopsy. Chemotherapy and resection boosts prognosis, but metastatic cases, often lung-affected, have a poor 20% survival rate. Despite advancements, osteosarcoma remains prevalent, with 4.4 million cases annually and a 60% survival rate; early detection is paramount. CAR-T cell therapy is a cutting-edge personalized immunotherapy where genetically engineered patient T-cells, expanded ex vivo, recognize and target tumor cells. They show promise in treating malignancies by targeting the tumor microenvironment. However, their effectiveness against solid tumors is uncertain due to challenges in marker specificity and expression. High specificity against tumor-expressed markers is essential for solid tumor treatment to avoid off-target effects and maximize efficacy.

Methods: An online search in the PubMed database was conducted from 2019 to 2024 using the following keywords: "osteosarcoma", " CAR-T cell therapy", and " Chimeric Antigen Receptor T-cell”.

Results: Orthotopic implantation models demonstrated superior representation of osteosarcoma biology and metastasis compared to traditional models. Utilizing this model, targeting markers like ALP, B7-H3, CD166, and GD2, showed significant tumor suppression and improved survival rates.

Targeting ALP, two CAR-T constructs targeting OSCAR-1 and OSCAR-3 efficiently controlled peritoneal and lung metastases, significantly prolonging animal survival. Further, targeting the B7-H3 surface marker with CAR-T cells resulted in significantly smaller tumors, indicating its potential therapeutic benefit. Flow cytometric analysis revealed preferentially higher expression of B7-H3 in osteosarcoma cells, validating its suitability as a CAR-T target. CD166 CAR-T therapy efficiently targeted osteosarcoma cells, correlating with tumor CD166 expression. In mice, it effectively regressed tumors without acute toxicity. Additionally, a clinical trial evaluating GD2-CAR-T cell therapy highlighted the correlation between monocytes expressing CXCR3 and poor tumor eradication, suggesting the importance of immune cell dynamics in CAR-T therapy outcomes. In addressing CAR-T therapy drawbacks, an alternative approach employing IL12-modified mononuclear cells demonstrated efficacy against osteosarcoma with reduced toxicity and constrained tumor growth, serving as a promising alternate.

Conclusion: CAR-T cell therapy has shown limited success in treating blood cancers, but its effectiveness in solid tumors has been less promising, possibly due to lower surface expression levels of antigens on cancer cells. Skepticism exists about its superiority over alternative treatments like mononuclear cell therapy. However, CAR-T cell therapy has made strides in personalized treatment for osteosarcoma and holds potential as adjunct therapy for metastases, although its long-term efficacy remains uncertain.

Modern Treatments for Bone Cancer: The role of CAR-T cell Therapy in Aggressive Osteosarcoma

Background: Hematopoietic stem cell transplantation (HSCT) can significantly disrupt gut 
microbiota, increasing susceptibility to Enterococcus infections. These infections pose a high 
mortality risk, with rates between 18% on day 7 and 31% by day 30 post-transplant. This study 
investigates the mortality in HSCT recipients admitted for Enterococcus bloodstream infections 
(EBSI).
Methods: We conducted a cross-sectional study utilizing the 2018-2021 National Inpatient 
Sample database, focusing on adult HSCT recipients (≥18 years) primarily hospitalized for EBSI 
(n=471). Our analysis included descriptive statistics, propensity score matching (based on age, 
gender, race, and comorbidities), and multivariate regression to adjust for confounding 
variables. The results were expressed as adjusted Odds Ratios (aOR) with significance at 
p≤0.05.
Results: Among 198,045 transplant patients, 20.4% (n=40,462) had undergone HSCT, with 
1.3% (n=531) being admitted due to EBSI. Among HSCT recipients, EBSI was seen in 1.4% of 
HSCT-Leukemia cohort and 2.4% of HSCT-AML cohort. In all HSCT recipients, the 
Enterococcus cohort had 38.98% of patients with urinary tract infection and 0.56% had 
peritoneal abscesses. In HSCT recipients with EBSI, patients with pancytopenia revealed higher 
mortality than survival (63.64% vs 44.33%, p<0.01). Crude analysis suggested higher all-cause 
mortality in the Enterococcus cohort compared to non-Enterococcus cohort (10.4% vs 4.6%, 
p<0.001). However, after adjusting for confounders, the mortality risk in the Enterococcus cohort 
was found to be lower (aOR 0.09, 95% CI 0.03-0.3, p<0.001). Key factors associated with 
increased mortality (p≤0.05) included the need for invasive ventilation (aOR=9.7), acute 
respiratory failure (aOR=4.3), fungal infections (aOR=4.2), severe sepsis (aOR=3.0), and 
acidosis (aOR=2.9). Additionally, palliative care was needed more in the Enterococcus cohort 
compared to the non-Enterococcus cohort (11.1% vs. 6.9%, p<0.001).
Conclusion: Enterococcus infections in HSCT recipients have a high mortality rate, but their 
mortality risk is low. This indicates that Enterococcus infection is a sign of clinical deterioration 
but is not a direct cause of mortality. When encountering patients with signs of bone marrow 
failure and severe sepsis, along with symptoms of respiratory failure and urinary tract infection, 
aggressive treatment and multidisciplinary care are required, as Enterococcus infection is a 
marker of poor prognosis.
Keywords: Hematopoietic stem cell transplant, Enterococcus infection, Mortality, Sepsis, HSCT, Transplant

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