Personalized Cell Therapy for Patients with Peripheral Arterial Diseases in the Context of Genetic Alterations: Artificial Intelligence-Based Responder and Non-Responder Prediction

Stem/progenitor cell transplantation is a potential novel therapeutic strategy to induce angiogenesis in ischemic tissue, which can prevent major amputation in patients with advanced peripheral artery disease (PAD). Thus, clinicians can use cell therapies worldwide to treat PAD. However, some cell therapy studies did not report beneficial outcomes. Clinical researchers have suggested that classical risk factors and comorbidities may adversely affect the efficacy of cell therapy. Some studies have indicated that the response to stem cell therapy varies among patients, even in those harboring limited risk factors. This suggests the role of undetermined risk factors, including genetic alterations, somatic mutations, and clonal hematopoiesis. Personalized stem cell-based therapy can be developed by analyzing individual risk factors. These approaches must consider several clinical biomarkers and perform studies (such as genome-wide association studies (GWAS)) on disease-related genetic traits and integrate the findings with those of transcriptome-wide association studies (TWAS) and whole-genome sequencing in PAD. Additional unbiased analyses with state-of-the-art computational methods, such as machine learning-based patient stratification, are suited for predictions in clinical investigations. The integration of these complex approaches into a unified analysis procedure for the identification of responders and non-responders before stem cell therapy, which can decrease treatment expenditure, is a major challenge for increasing the efficacy of therapies.

Personalized Cell Therapy for Patients With Peripheral Arterial Diseases in the Context of Genetic Alterations: Artificial Intelligence-based Responder and Non-responder Prediction

Stem/progenitor cell transplantation is a potential novel therapeutic strategy to induce angiogenesis in ischemic tissue, which can prevent major amputation in patients with advanced peripheral artery disease (PAD). Thus, clinicians can use cell therapies worldwide to treat PAD. However, some cell therapy studies did not report beneficial outcomes. Clinical researchers suggested that classical risk factors and comorbidities may adversely affect the efficacy of cell therapy. Some studies have indicated that the response to stem cell therapy varies among patients even in those harboring limited risk factors. This suggested the role of undetermined risk factors, including genetic alterations, somatic mutations, and clonal hematopoiesis. Personalized stem cell-based therapy can be developed by analyzing individual risk factors. These approaches must consider several clinical biomarkers and perform studies (such as genome-wide association studies (GWAS)) on disease-related genetic traits and integrate the findings with those of transcriptome-wide association studies (TWAS) and whole-genome sequencing in PAD. Additional unbiased analyses with state-of-the-art computational methods, such as machine learning-based patient stratification, are suited for predictions in clinical investigations. The integration of these complex approaches into a unified analysis procedure for the identification of responders and non-responders before stem cell therapy, which can decrease treatment expenditure, is a major challenge to increase the efficacy of therapies.

Hospital Mortality and Length of Stay for Patients with Myelodysplastic Syndrome Presenting with Acute ST-Elevation Myocardial Infarction (STEMI)

Introduction Ischemic heart disease remains the single largest cause of death worldwide. In the USA, 365,744 deaths were associated to coronary heart disease, and the mortality is highest in population older than 65 years old. Myelodysplastic syndromes (MDS) also mainly affect this group age and studies suggest an incidence as high as 75 cases per 100,000 aged >65 years. In the following abstract we analyze the mortality rate in patients with MDS and STEMI. Methods We conducted a retrospective analysis of 3 years of National inpatient sample (HCUP-NIS) data base from 2016 to 2018. Patients older than 60 years old and with or without MDS were selected using ICD-10 diagnosis code. Principal diagnosis of STEMI was included with the code. ICD-10 procedure code was used for left heart catheterization. Discharge-level weight analysis was used to produce a national estimate. Continuous variables were compared by t-test, while chi-square and Fisher's exact test were used for categorical variables. Finally, multivariate logistic regression was used to calculate odds ratio for inpatient mortality and multivariate linear regression for length of stay using STATA 17 statistical software. Results A total of 45,724,104 admissions met inclusion criteria, of those, 210,780 patients (0.46 %) have MDS. Patients with MDS are more likely to be of older age (78.7 v 74.8, p <0.00001), male (56.4% v 46.7%, p < 0.0001) and white (81.0% v 76.0%, p < 0.0001). They are also associated with lower prevalence of diabetes (16.2% v 20.1%, p < 0.003) and smoking (0.4% v 0.8%, p <0.0001) but higher prevalence of peripheral arterial diseases (12.7% v 11.6%, p <0.0001). During the study period, a total of 1,293,994 patients were admitted primarily due to STEMI, 3,270 of these patients (2.5%) had underlying MDS. Out of the 3,270, only 1,105 (33.8 %) underwent left heart catheterization. On the other hand, 735,610 patients without MDS (57.0%) underwent percutaneous coronary intervention. After adjusting for age, sex, race, diabetes, and Charlson comorbidity index, there was a statistical significant in mortality (OR 1.46, CI 1.08 - 1.98, p < 0.013) and longer length of stay by 0.59 day (p < 0.0001). Discussion In our study, MDS is associated with higher mortality and loner length of stay. Peripheral arterial diseases are found to be more prevalent in MDS even though other cardiovascular risk factors such as diabetes mellitus and smoking are less prevalent. It is consistent with prior study, by Jaiswal S et al, hypothesizing that MDS is an independence risk of atherosclerotic cardiovascular diseases. Interestingly, patients with MDS are less likely to undergo left heart catheterization which is the definitive intervention for diagnosis and treatment of ischemic heart diseases. We recommend our hematology society to identify and treat the cardiovascular risk factors in these patients. Further studies will be required to develop a standardized evaluation and management plans for MDS population. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The Association between Chronic Myeloid Leukemia and Heart Failure

Introduction The first and second leading causes of death in the United States are heart disease and cancer respectively. Chronic myeloid leukemia (CML) is a hematopoietic stem cell malignancy diagnosed at the mean age of 66. The rate of cardiovascular diseases in CML have been increased with the advent of therapies such as tyrosine kinase inhibitors (TKIs) as well as the improved survival rate with the treatments. Heart failure is one the most commonly identified cancer-therapy related cardiovascular adverse events. In this study, we are using national population cohort to study the association between CML and heart failure. Methods We conducted a retrospective analysis of 3 years of National inpatient sample (HCUP-NIS) from 2016 to 2018 data base. Patient older than 60 years old and with or without CML was selected using ICD-10 diagnosis code. Principal diagnosis of congestive heart failure and cardiogenic shock were included with the code. Discharge-level weight analysis was used to produce national estimate. Continuous variables were compared by t-test, while chi-square and Fisher's exact test for categorical variables. Finally, multivariate logistic regression was used to calculate odds ratio for inpatient mortality and multivariate linear regression for length of stay using STATA 17 statistical software. Results A total of 45,724,104 admissions met for inclusion criteria and 43,505 patients (0.095 %) have CML. Patients with CML are more likely to be of older age (75.2 v 74.9, p <0.002), male (55.2% v 46.8%, p < 0.0001) and white (79.7% v 76.0%, p < 0.0001). They are also associated with lower prevalence of diabetes (16.5% v 20.1%, p < 0.0001) and smoking (0.6% v 0.8%, p <0.0001) but higher prevalence of peripheral arterial diseases (13.7% v 11.6%, p <0.0001). During the study period, a total of 9,339,737 patients were admitted primarily due to CHF and 12,835 of patients (0.14%) have underlying CML. There was no statistical difference in deteriorating to cariogenic shock in CHF patients with and without CML (2.06% v 2.10%, p <0.805). After adjusting for age, sex, race, diabetes, Charlson comorbidity index, there was statistical significance in mortality (OR 1.18, CI 1.09 - 1.27, p < 0.0001) and longer length of stay by 0.28 day (p < 0.0001) Discussions This study describes patient's demographic, in-patient mortality rate and length of stay in patients with CML and heart failure. A comorbid heart failure is associated with higher mortality rate and longer length of stay in hospital. Even though multiple societies have published several guidelines for baseline assessment of the cardiovascular risk factors, there is no standardized assessment tool for risk stratification and management of heart failure in CML patients. Moreover, presence of heart failure can be a limitation on treatments of CML and carry a poor prognosis. Our study emphasizes the importance of assessing cardiovascular diseases and optimizing the care before, during and after the treatment of CML. Disclosures No relevant conflicts of interest to declare.

Acute Aorto-Illiac Occlusion with Bilateral Limb Ischemia Underwent Direct Catheter Thrombolysis in Older Patient: A Case Report

Background: Peripheral arterial diseases could be a major burden for the health system with a wide clinical spectrum from asymptomatic to limb-threatening. Sudden onset of limb deteriorations represent a vascular emergency and need proper treatment for limb preservation and life-saving. It is still challenging to choose proper management to reduce morbidity and mortality, despite the various advance in diagnostic and therapeutic tools were available. Objective: This case report aimed to elaborate on the management of acute aorto-illiac occlusion with bilateral limb ischemia underwent direct catheter thrombolysis in an older patient. Case Presentation: A 70-years-old man came to our hospital with a chief complaint of leg pain in both of his legs, suddenly since 18 hours before admission. He had paresthesia and paralysis in both of his legs. And the Doppler ultrasonography result was occlusion proximal to the right and left common iliac artery. Then we performed percutaneous intra-arterial thrombolysis using streptokinase with a successful outcome of peripheral revascular- ization but with gastrointestinal bleeding as an adverse event. Conclusion: Despite the various advancement of diagnostic and therapeutic tools available today, Acute Limb Ischemia (ALI) still proceed to be related to increasing major amputation and mortality rates in 20% of patients, more often due to the existing comorbidities such as other atherosclerotic diseases.

SCORING SYSTEM FOR ASSESSING RISK OF AMPUTATION IN PATIENT'S WITH DIABETIC FOOT

Diabetic foot problems are common throughout the world, resulting in major economic consequences for the patients, their families, and society. Our aim is “To formulate a risk scoring system that can predict the risk of amputation in a patient with an infected diabetic foot”. Previously published studies aimed at identifying independent risk factors for lower-extremity amputation in patients with a DFI have noted an association with older age, the presence of fever, elevated acute-phase reactants, higher HbA1c levels, and renal insufciency. In the current study, we have identied that Age, Duration of diabetes, History of amputations, Ulcer depth, Ankle-brachial index, Severity of infection, and Peripheral neuropathy, Peripheral arterial diseases are signicantly associated with Lower Extremity amputation. Peripheral vascular disease and infection were the most powerful predictors, as 65% of patients who underwent amputations in our study belonged to Rutherford grade 3 and grade 4. We developed a New Risk score for predicting amputation in diabetic patients with an infected foot ulcer, which can be readily used in daily clinical practice without the necessity of extensive lab investigations. Patients with a score of >16.5 are at increased risk of lower extremity amputation. 66.6% of our follow up cases who underwent reamputations belonged to the group with a score of >16.5. Risk of amputation increases as the score increases