United States

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: &quot;osteosarcoma&quot;, &quot; CAR-T cell therapy&quot;, and &quot; 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.

AMA Research Challenge 2024 

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

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.

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/)

You need to log in with the email address you registered with. Access credentials have been sent to your email. 

Please be sure to check your spam and other email folders if you do not see an email confirmation right away.

Please log in to explore this event.

**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 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: 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

Mortality Risk Factors Associated with Enterococcus Infection in Hematopoietic Stem Cell Transplant (HSCT) Recipients.

Introduction 
Databases such as the National Cancer Database (NCDB) are important for analyzing care provisions and clinical outcomes. However, missing data limits the scope and skews the accuracy of analyses. It may be correlated with the quality of care at the institution. This study aims to assess the prevalence of and characteristics of missing data in the NCDB for gallbladder, biliary, and hepatic cancers.

Methods 
This retrospective cohort study reviewed 12 key variables within the NCDB for missing values for patients diagnosed with a hepatic, biliary, or gallbladder cancers from 2010 to 2019. Key variables included demographic (age, race, ethnicity, insurance, education, income, comorbidities), tumor (grade, TNM stages), and treatment characteristics (surgery, chemotherapy, radiation therapy). The percentage of patients with complete and missing number of key variables was analyzed. Characteristics of the missing data including the distribution of missing data by cancer stage, percentage of patients with missing data by year, and the percentage of patients missing per number of studied variables was calculated. 

Results 
A total of 308,354 patients (mean [SD] age, 66.3 [11.5] years; 197,876 [64.2%] male) in the NCDB were identified; 13.1% were missing at least 1 key variable. Missing data was similarly prevalent amongst the cancers (12.2% in gallbladder, 13.25% in liver, and 13.26% in biliary cancers). Demographic data was most likely to be missing in biliary cancers (13.2%) and tumor data was most likely to be missing in liver cancers (0.12%), though very little tumor data was missing. Of those missing data, most patients were missing seven key variables. Gallbladder and biliary cancers are most likely to be missing stage 4 data, while liver cancers are more likely to be missing stage 1 cancer. The percentage of patients with missing data has increased from 2010-2019.

Conclusion 
Missing data of select variables in the NCDB prevalent and the percentage of missing key variables is similar across hepatic, biliary, and gallbladder cancers. Understanding that the patients missing data are not random impacts the generalizability of NCDB analysis.

Prevalence and Characteristics of Missing Variables in the National Cancer Database for Hepato-Biliary-Gallbladder Cancers

Background
Viral infections, including SARS-CoV2/COVID-19, have been associated with high incidence of DVT. There is evidence that patients infected during the first wave of COVID-19, and especially those with pre-existing cardiovascular disease (CVD), have increased immediate risk of thrombosis and mortality. However, the short- and long- term incidence and risk of thrombosis, in patients with SARS-CoV2/COVID-19 with CVD in the era of vaccine availability is less clear. The purpose of this study is to evaluate the rate of venous and arterial thrombotic events and mortality at 1 month after COVID-19 diagnosis in patients with and without CVD.
Methods
This is a retrospective analysis from 9/12/2021 to 10/12/2022, during the Delta and Omicron variant eras, of patients over 18 years old with and without preexisting CVD and a positive COVID-19 diagnosis at our university hospital. Patient data including sex, age, BMI, comorbidities, lab tests, imaging, and procedures were reviewed at time of COVID diagnosis and at the 1-month timepoint following COVID-19 diagnosis. Pearson’s chi square tests were performed to calculate the statistical significance of the relation between pre-existing CVD and thrombotic outcomes of interest within 1 month of COVID-19 diagnosis.
Results
This interim analysis includes 16,228 patients who were diagnosed with COVID-19 over a 1- year time period with a mean age of 31 ± 23 years. Of these, 2,938 had pre-existing CVD with advanced age compared to patients without CVD (CVD 59 ± 18 years vs 25 ± 19 years). There is a significant relationship between pre-existing CVD and the development of venous thrombosis; venous thromboembolism (p < .00001), deep venous thrombosis (p = .0001), and pulmonary embolism (p = .0001). There was also a significant relationship between CVD and the development of arterial thrombosis; stroke (p = .00002) and myocardial infarction (p < .00001). Lastly there was a significant relationship with mortality (p < .00001).
Conclusion
Our preliminary data show that patients with CVD may have increased rates of thromboembolic events in the month following COVID-19 infections occurring after the availability of vaccines. Further multivariate analysis may be helpful to evaluate the combined effect of multiple factors including age, gender, and smoking on thrombotic risk. Additional studies investigating the persistence of the increased risk of thrombotic events after viral infections such as COVID-19 may help guide preventative or prophylactic strategies and duration for patients with CVD.

Rates of thrombotic events in patients with cardiovascular disease following COVID-19 delta variant in the era of vaccine availability

The Impact of Cancer on one year mortality in multimorbid geriatric patients with palliative consultation

Authors: Ellie Soheili, Hussain Dalal, Nadeem Hussain, Michael J. Mader, Hanh Trinh, Aneela Hussain, Sandra Sanchez-Reilly, Marcos I. Restrepo

Affiliation: University of Texas Health San Antonio and South Texas Veterans Health care system

Background 
In older adults, malignancy and other comorbidities can pose substantial challenges to treatment and complicate clinical outcomes. Palliative care is one solution to address the challenges of treating multimorbid older adults. Currently, there are limited studies comparing mortality rates among multimorbid patients receiving palliative care that focus on the independent impact of malignancy on mortality. We aimed to assess the effect of cancer on one-year mortality among multimorbid older adults. 
Methodology 
We conducted a cohort study with outpatient geriatric veterans at the South Texas Veterans Health System. The inclusion criteria encompassed older adults > 65 with complex medical comorbidities (Charleson comorbidity index (CCI) > 1) irrespective of cancer for a period of 5 years prior to the initial palliative consultation. The primary objective as to compare the one-year mortality among the two groups. We adjusted for comorbidities including congestive heart failure, chronic obstructive pulmonary disease, diabetes mellitus, dementia, renal and hepatic diseases.
Results 
We selected 1,449 outpatient geriatric veterans with comorbidities. Among these, 425 veterans (29.3%) had concurrent cancer and complex medical conditions (CCI > 1) while 1,024 geriatric patients (70.7%) had only complex medical conditions. The median CCI among the veteran with comorbidities and cancer was 6 as compare to CCI of 3 among veterans without cancer. Patients with cancer had a higher 1-year mortality 55.3% (n=235) as compared to 44% (n=450) patients without cancer (aOR 1.97, 95% CI). 
Conclusion   
Our analysis showed that cancer, combined with high comorbidity, led to a higher one-year mortality rate in older adults receiving palliative care, while those receiving palliative care with high comorbidity alone had a lower one-year mortality rate. After adjusting for comorbidities, cancer independently doubled the odds ratio of 1 year mortality, emphasizing the need for earlier interventions and palliative care in this population.



The Impact of Cancer on one year mortality in multimorbid geriatric patients with palliative consultation

Background: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myeloid leukemia (CML), significantly improving patient outcomes, particularly in the chronic phase (CML-CP). First-generation TKI imatinib and second-generation TKIs such as dasatinib and nilotinib have proven highly effective, achieving deep molecular responses like major molecular response (MMR). However, resistance or intolerance to TKIs results in treatment failure in 20%–25% of cases, despite an initial good response.
Methods: This clinical study involved ten CML patients, aged between 38 and 83 years, including 6 males and 4 females, receiving TKI therapy at our clinic. Patients were treated with imatinib, dasatinib, or nilotinib, depending on insurance approval. BCR-ABL levels were monitored through regular PCR tests, with relapse defined as a 10-log increase from a previous level. Potential causes of relapse, including non-compliance, side effects, and resistance development, were identified through medical records, patient interviews, and consultations.
Results: The study analyzed the causes of relapse in ten CML patients treated with TKIs:
Patient 1: Noncompliance and developed resistance to dasatinib, so was switched to imatinib, eventually achieving remission.
Patient 2: Switched from dasatinib to nilotinib for pleural effusion, achieving undetectable BCR-ABL levels.
Patient 3: Stable on imatinib with steady BCR-ABL levels.
Patient 4: Switched from dasatinib to nilotinib due to heavy vaginal bleeding.
Patient 5: Reached negative BCR-ABL on nilotinib, then switched to dasatinib due to GI side effects.
Patient 6: Responded well, BCR-ABL undetectable on Scemblix.
Patient 7: Non-compliance due to side effects of vomiting and nausea led to erratic BCR-ABL levels, switched from nilotinib to dasatinib, eventually achieving remission.
Patient 8: Non-compliance on imatinib due to insurance problems. Stable after switching from imatinib to nilotinib due to progression.
Patient 9: Non-compliant, fluctuating BCR-ABL levels.
Patient 10: Positive response to nilotinib, with significant reduction in BCR-ABL levels.
Conclusion: CML is a highly treatable hematological cancer with the use of TKIs. We employ highly sensitive PCR tests to detect even the slightest molecular relapse. Our study revealed that 7 out of 10 patients experienced a molecular relapse at some point during their treatment. The primary cause of relapse was non-compliance, followed by side effects, and, although rare, resistance to TKIs. Therefore, patient education and effective communication during consultations are crucial components of treatment.


Why Effective Treatments for CML Fail: Investigating Loss of Response

Introduction
Colon cancer is the third most common cancer worldwide, with signet ring cell carcinoma (SRCC) being a rare subtype accounting for 1-2% of cases. SRCC incidence is increasing among younger patients, and is associated with worse survival rates and poor treatment response compared to other colorectal cancers. This study aims to analyze SRCC’s epidemiology, metastatic patterns, and survival rates, focusing on early-onset cases using the SEER database to provide robust statistical insights.

Methods
The study is a retrospective analysis that utilizes a cohort from the Surveillance, Epidemiology, and End Results database from 2000-2020. This study uses several demographic and clinical factors that include age, race, median income, housing, tumor stage, tumor size, lymph node status, metastasis, and treatment modalities (surgery, radiation, chemotherapy). 

Results
The median age of onset is increasingly earlier, now at 41 years, with most cases occurring between 36-50 years. Common metastasis sites are other locations (38.3%), liver (8.9%), bone (4.2%), and lung (3.8%), with the rectum being the most frequent primary tumor site (29.1%). Predominantly affecting males (62.3%), the cohort includes white (50.6%), Hispanic (21.9%), and African American (12.3%) patients. Surgery with adjuvant chemotherapy is the most common treatment, while chemotherapy-only has the lowest 5-year survival rate (2.6%) and surgery-only the highest (40.2%). Multivariate analysis identifies tumor stage (H.R. 2.15, p <0.001), nodal status (H.R. 3.28, p <0.001), and tumor size (H.R. 2.08, p =0.013) as prognostic factors.

Conclusion

The study indicates a declining median age for young-onset SRCC, which often presents with distant metastasis and advanced-stage due to delayed symptom onset. Worse outcomes are linked to tumor location, nodal status, and size. These findings can guide clinicians in creating personalized treatment plans and risk stratification for SRCC patients.

Young-onset Colorectal with Signet Ring Cell Morphology; Clinicopathological Analysis and Patterns of Metastases in US Population

Abstract Title:
“Why Did They Die?” The Hidden Surge of Pulmonary Thromboembolism in Post-COVID
Saint Vincent and the Grenadines – A JoinPoint Regression Analysis (2013-2023)
Background:
Pulmonary thromboembolism (PTE) is a critical cardiovascular condition with significant
mortality risk. The COVID-19 pandemic has been associated with increased thromboembolic
events, likely due to virus-related hypercoagulability. This study investigates the trends and
demographic shifts in PTE-related mortality in Saint Vincent and the Grenadines over an 11-year
period, exploring both pre- and post-COVID eras.
Methods:
Data on PTE-related deaths from Kingstown, Saint Vincent and the Grenadines, were obtained
from the population-based death registration system. Crude mortality rates were calculated for
the period 2013-2023. Joinpoint regression analysis was employed to identify significant changes
in mortality trends. The analysis also explored demographic shifts across different age groups
and genders.
Results:
A total of 209 PTE-related deaths were recorded during the study period, with notable peak
significant stratifications seen as 56.5% of the cases being men and 24.9% occurring in
individuals aged 51-60 years. The crude mortality rate for PTE increased by 66.5% from the pre-
COVID era (2013-2019) to the COVID/post-COVID era (2020-2023). Joinpoint regression
analysis revealed a significant increase in the annual percent change (APC) of PTE mortality:
11.5% (95% CI −1.2 to 25.89, P = 0.99) for males and 13.85% (95% CI −2.58 to 33.07, P = 0.83)
for females. A peak in PTE mortality was observed in 2020, with a subsequent decline from
2021-2023.
Conclusion:
The mortality trend for PTE showed a marked increase during the COVID-19 era compared to
the pre-COVID period, particularly among males and those aged 51-60 years. Despite the
significant surge in 2020, a decline in crude mortality rates was noted from 2021-2023,
potentially attributable to various factors such as improved clinical management and increased
vaccine uptake. More research is needed to fully understand the impact these factors could have
played. This study underscores the need for targeted interventions to mitigate PTE risk and
improve outcomes in vulnerable populations during and after pandemics.
Keywords: Pulmonary embolism, Mortality trends, Crude mortality rate, Joinpoint regression,
COVID-19 impact, Saint Vincent and the Grenadines, Vaccine uptake.
Anderson E. Ikeokwu (M.D MPH)
Promise Okereke (M.D)
Hilary Daniel (MD)

“Why Did They Die?” The Hidden Surge of Pulmonary Thromboembolism in Post-COVID

Insulin Resistance Spawns Hypertriglyceridemia-induced Acute Pancreatitis and Diabetic Ketoacidosis: Unboxing a New Metabolic Crisis

Background
Insulin resistance (IR) in adipose tissue (Adipo-IR) is linked to uncontrolled lipolysis with free fatty acids (FFAs) dissipation, ectopic fat deposition and hypertriglyceridemia (HTG). As a valuable component in the metabolic syndrome, HTG increases the likelihood of atherosclerotic cardiovascular disease (ASCVD). By analyzing two cases with severe HTG in poorly controlled T2DM which provoked hypertriglyceridemic acute pancreatitis (HTGAP) and diabetic ketoacidosis (DKA), we suggest an Adipo-IR-induced new metabolic crisis of lipid and glucose metabolism underlying HTGAP and DKA.
Case Presentation
In this case series, case 1 involves a 48-year-old female with triglyceride of 3841 mg/dL and HbA1c 10.1%, while case 2 describes a 32-year-old male with triglyceride of 650 mg/dL initially which was up to 5359 mg/dL 9 months later with HbA1c 12%. Both had increased anion gap, positive ketones and elevated c-peptide with significant IR. Both developed significantly increased lipase with abdomen CT scan showing edematous pancreatitis. Both patients were admitted to the intensive care unit receiving continuous insulin and Lactated Ringer’s solution infusion. The DKAs were resolved in 24 hours and triglycerides gradually decreased to < 1000 mg/dL on days 5 to 6. Both were discharged with Fenofibrate, Atorvastatin and insulin therapy. 3-month follow-up showed well controlled triglyceride and HbA1c levels. Insulin injection was switched to oral hypoglycemic medications. 
Discussion
This scenario represents an acute crisis of lipid and glucose metabolism induced by Adipo-IR and its consequent over-activated lipolysis. Adipo-IR and over-activated lipolysis create a two-way feedback between white adipose tissue and liver (Hep-IR), which further damages pancreases with pancreatic self-hydrolysis leading to HTGAP. HTGAP further triggers counter-regulatory hormone worsening hyperglycemia and lipolysis and ultimately causing downward spiral of HTGAP-DKA. Acute management involves fluid resuscitation, insulin infusion, and nutrition management and complications prevention. Chronic management includes non-pharmacological measures and medications including Fibrates, Statin, Omega-3 fatty acids, Metformin and Sodium-glucose cotransporter-2 inhibitors. Further investigation is needed for clinically applicable assessment and stratification of Adipo-IR/Hep-IR axis.

Insulin Resistance Spawns Hypertriglyceridemia-induced Acute Pancreatitis and Diabetic Ketoacidosis: Unboxing a New Metabolic Crisis

Background: Vitamin B12 deficiency (B12D) is associated with multiple risk factors and comorbidities; however, there are no firm guidelines regarding screening for B12D in the population at risk. We aimed to identify the risk factors and comorbidities associated with B12D in an adult population.
Methods: Retrospective review of adult patients who received medical care in our large urban tertiary healthcare system between 1/1/2011 to 12/31/2020. Variables were compared between the group who had B12D and those who did not (NoB12D).
Results: Patients with B12D (n=2,666) were younger than the NoB12D group (n=2,334) (62.2±18.5 vs 76.5±7.6 years; P<0.001). There were significantly higher associations in B12D group compared to NoB12D group of female sex, recreational drug use, CHF, CVA, COPD, asthma, peripheral neuropathy (PN), subacute combined degeneration of spinal cord (SCD), dementia), mild cognitive impairment (MCI), GERD, gastritis, inflammatory bowel disease (IBD), small bowel resection (SBR), colorectal surgery (CRS), bariatric surgery (BS), depression, bipolar disorder, anxiety disorder, schizophrenia, anemia, use of NSAIDs, proton pump inhibitor (PPI), histamin-2 receptor antagonist (H2RA), and lithium. Compared to White race, Black and Hispanic races had higher odds of B12D (OR 1.43, 95% CI 1.02–2.01; P=0.040, and OR 3.15, 95% CI 2.23–4.45; P<0.001, respectively). Comorbidities with greater odds of B12D included COPD and asthma (OR 1.41, 95% CI 1.12–1.78; P=0.003), anemia (OR 253.72, 95% CI 164.66–390.93; P<0.001), PN and SCD (OR 2.78, 95% CI 2.16–3.58; P<0.001), dementia and MCI (OR 3.37, 95% CI 2.40–4.74; P<0.001), gastrointestinal disorders (GERD, gastritis, IBD, SBR, CRS and BS) (OR 2.38, 95% CI 1.95–2.90; P<0.001), PPI use (OR 2.81, 95% CI 1.88–4.20; P<0.001), and NSAID use (OR 1.40, 95% CI 1.08–1.81; P=0.011).
Conclusion: Younger age, female sex, Black and Hispanic races, recreational drug use, CHF, CVA, COPD, asthma, PN, SCD, dementia, MCI, GERD, IBD, SBR, colorectal surgery, bariatric surgery, depression, bipolar disorder, anxiety disorder, schizophrenia, anemia, use of PPI, H2RA, NSAIDs and lithium are associated with B12D.

Risk Factors and Comorbidities associated with Vitamin B12 Deficiency in an Adult Population

This systematic review examines the interplay between the MTHFR gene C677T genotype polymorphism, hyperhomocysteinemia (HHCY), and spontaneous cervical/vertebral artery dissection, a significant cause of ischemic stroke (IS) in young adults. Analyzing 11 studies involving 4,840 patients aged 18-45, the review highlights that HHCY contributes to vascular damage and tissue ischemia, often presenting with nonspecific symptoms such as neck pain or headache. The MTHFR C677T genotype is closely linked to elevated homocysteine levels, increasing stroke risk, yet remains underdiagnosed. Early detection and management through supplementation with vitamin B12, folates, and in severe cases, betaine, can mitigate these risks, underscoring the need for heightened clinical awareness to prevent severe outcomes.

Next from AMA Research Challenge 2024

Mortality Risk Factors Associated with Enterococcus Infection in Hematopoietic Stem Cell Transplant (HSCT) Recipients.

Stay up to date with the latest Underline news!

PRESENTATIONS

CONFERENCES

COMPANY

RESOURCES