Efficacy of acellular fish skin graft in the management of chronic ulcer: a systematic review and meta-analysis.

Chronic low back pain (cLBP) is the second leading cause of disability in the United States, with significant physical and financial implications. Development of a multifaceted treatment plan that is cost effective and optimizes patients' ability to function on a daily basis is critical. To date, there have been no published prospective studies comparing the cost of osteopathic manipulative treatment to that of standard care for patients with cLBP. To contrast the cost for standard of care treatment (SCT) for cLBP with standard of care plus osteopathic manipulative treatment (SCT+OMT). This prospective, observational study was conducted over the course of 4months with two groups of patients with a diagnosis of cLBP. Once consent was obtained, patients were assigned to the SCT or the SCT+OMT group based on the specialty practice of theirphysician. At enrollment and after 4 months of treatment, all patients in both groups completed two questionnaires: the 11 point pain intensity numerical scale (PI-NRS) and the Roland Morris Disability Questionnaire (RMDQ). Cost data was collected from the electronic medical record of each patient enrolled in the study. Chi-square (χ2Yates) tests for independence using Yates' correction for continuity were performed to compare the results for each group. There was a total of 146 patients: 71 (48.6%) in the SCT+OMT group and 75 (51.4%) in the SCT group. The results showed no significant differences between themean total costs for the SCT+OMT ($831.48±$553.59) and SCT ($997.90±$1,053.22) groups. However, the utilization of interventional therapies (2; 2.8%) and radiology (4;5.6%) services were significantly less for the SCT+OMT group than the utilization of interventional (31; 41.3%) and radiology (17; 22.7%) therapies were for the SCT group (p<0.001). Additionally, the patients in the SCT+OMT group were prescribed fewer opioid medications (15; 21.1) than the SCT (37; 49.3%) patients (p.001). Patients in the SCT group were approximately 14.7 times more likely to have received interventional therapies than patients in the SCT+OMT group. Likewise, the patients in the SCT group were approximately four times more likely to have received radiological services. Paired t tests comparing the mean pre- and 4 month self reported pain severity scores on the RMDQ for 68 SCT+OMT patients (9.91±5.88 vs. 6.40±5.24) and 66 SCT patients (11.44±6.10 vs. 8.52±6.14) found highly significant decreases in pain for both group (<0.001). The mean total costs for the SCT and SCT+OMT patients were statistically comparable across 4 months of treatment. SCT+OMT was comparable to SCT alone in reducing pain and improving function in patients with chronic low back pain; however, there was less utilization of opioid analgesics, physical therapy, interventional therapies, radiologic, and diagnostic services for patients in the SCT+OMT group.

Purpose: Inadequate response to wound management is defined as a reduction in the wound area of <40-50% following four weeks of standard of care (SOC) and should be managed with a skin substitute product. We set out to evaluate a novel outcome-based model focusing on the management of hard-to-heal venous leg ulcers (VLUs) and diabetic foot ulcers (DFUs) using SOC treatment or intact fish skin grafts (FSGs) in a regional hospital. Methods: We built an outcome-based model applying surrogate markers and endpoints of wound healing for VLU and DFU to determine the healing trajectory with SOC treatment. We could predict if VLU and DFU would heal by weeks 20 and 24, respectively, after four weeks of evaluating the initial wound area reduction. 51 patients were recruited (26 VLUs and 25 DFUs) and 42 wounds were randomized. 17 wounds deemed unlikely to heal by week 8 received management with FSG as per the Swiss Society for Dermatology and Venereology (SGDV) and the Swiss Association for Woundcare (SAfW) guidelines for the use of skin replacement products, and 26 wounds continued SOC for weeks 5-8. Results/Discussion: 12 wounds managed with FSG beat the modeled SOC healing predictions, with the majority healed >50% sooner and as early as <10% of the time than was predicted. Of these 17, five wounds failed to achieve the required size reduction in Week 4-8 (over 25% improvement in wound area vs. SOC). The FSG were assigned to treatment-resistant VLU and DFUs and were still able to heal these wounds most of the time and even changed the wound's healing trajectory that increased in size in the initial four weeks. Conclusion: This pilot study showed that management with FSG results in faster healing wounds than SOC predicted, while SOC-treated wounds mostly followed model predictions.

BackgroundDiabetic foot ulcers (DFUs) have become a global health concern, which can lead to diabetic foot infection (DFI), lower leg amputation, and even mortality. Though the standard of care (SOC) practices have been recognized as the “gold standard” for DFU care, SOC alone may not be adequate to heal all DFUs and prevent their recurrence. The use of dermal matrix has emerged as an adjuvant treatment to enhance DFU healing. The current study aimed to evaluate the effectiveness and safety of dermal matrix application as an adjuvant treatment to the SOC.MethodsThe databases of PubMed, Embase and CENTRAL were independently searched by two authors, with the following key terms: “diabetic foot ulcer”, “acellular dermal matrix”, “wound healing”, and so on. Randomized controlled trials (RCTs) evaluated the efficacy and safety of dermal matrix in the treatment of DFUs were eligible for inclusion. The primary outcomes analyzed included time to complete healing and complete healing rate at the final follow-up, while secondary outcomes included wound area, ulcer recurrence rate, amputation risk and complication risk. Meta-analyses were performed using random-effect or fixed-effect models, based on the heterogeneity test.ResultsThis study included a total of 15 RCTs with a total of 1524 subjects. Of these, 689 patients were treated with SOC alone, while 835 patients received SOC plus dermal matrix. Compared to the SOC group, significantly shorter time (MD = 2.84, 95%CI: 1.37 ~ 4.32, p < 0.001***) was required to achieve complete healing in dermal matrix group. Significantly higher complete healing rate (OR = 0.40, 95%CI: 0.33 ~ 0.49, p < 0.001***) and lower overall (RR = 1.83, 95%CI: 1.15 ~ 2.93, p = 0.011*) and major (RR = 2.64, 95%CI: 1.30 ~ 5.36, p = 0.007**) amputation risks were achieved in dermal matrix group compared to SOC group. No significant difference was found in the wound area, ulcer recurrence rate, and complication risk between the two groups.ConclusionsThe application of dermal matrix as an adjuvant therapy in conjunction with SOC effectively improved the healing process of DFUs and reduced the amputation risk when compared to SOC alone. Furthermore, dermal matrix application was well tolerated by the subjects with no added complication risk.

Background: Assessment of patient-reported outcomes (PRO) can inform how real-life standard of care (SOC) treatments affect health-related quality of life (HRQoL) for patients with relapsed/refractory multiple myeloma (RRMM). We present measures of symptoms, functioning, and overall HRQoL from LocoMMotion (NCT04035226), the first prospective, multinational study of real-life SOC in triple-class exposed patients with RRMM. Aims: To assess HRQoL in patients with RRMM receiving real-life current SOC in the LocoMMotion study. Methods: All patients provided informed consent. LocoMMotion is a noninterventional study across 76 sites (63 Europe, 13 United States) in patients who had received ≥3 prior lines of therapy (LOT) or were refractory to proteasome inhibitor (PI) and immunomodulatory drug (IMiD). Patients received PI, IMiD, and anti-CD38 monoclonal antibody and had disease progression during/after their last LOT. Real-life SOC treatments were defined as those used in local clinical practice. The following questionnaires were used: European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30), 4 single items from EORTC QLQ-myeloma-specific module (EORTC QLQ-MY20), and EuroQol 5-Dimension 5-Level (EQ 5D-5L). HRQoL data were collected at baseline (BL), day 1 of each treatment cycle, end of treatment visit, and during follow-up (every 4 weeks). Established thresholds were used to evaluate improvement compared with BL health status. Mixed models for repeated measures were used to assess within-group change. Results: The questionnaire completion rate was 75.6% during SOC treatment in the LocoMMotion study (N=248; male: 54.4%; median age: 68 years; median cycles of SOC: 4.0 [range: 1-20]). Most patients did not achieve meaningful improvement (defined by a literature-based minimally important difference of 10 points in mean score) in PRO scores. This was most pronounced in pain symptoms, with 62% of patients showing no meaningful improvement during the first 3 months of treatment and 55% showing no improvement during the full treatment duration. Least square (LS) mean changes from BL during SOC treatment and subsequent LOT for the overall population are described (Table). Patients with ≥very good partial response during SOC treatment showed greater improvement in PRO scores, including LS mean change for pain score (-14.9 [95% confidence interval: -22.9, -7.0]). Image:Summary/Conclusion: This first prospective study of real-life current SOC in triple-class exposed patients with RRMM reported limited gains in HRQoL, most notably in pain symptoms. There is an urgent and unmet need for therapies that lead to deep responses and delayed disease progression, as these are associated with improvements in HRQoL.

Background Phosphoinositide 3-kinase alpha (PI3Kα) H1047R mutations are activating oncogenic events that occur in ~15% of breast cancers (BC). Early generation PI3Kα inhibitors target both wild-type (WT) and mutant PI3Kα and, as a result, their efficacy may be limited by on-target WT PI3Kα-mediated toxicities, including hyperglycemia, skin rash, and diarrhea. LOXO-783 is an oral, potent and highly mutant-selective, brain-penetrant allosteric PI3Kα H1047R inhibitor that is currently in phase 1 testing. Preclinically, LOXO-783 as a single agent is highly selective for PI3Kα H1047R over WT PI3Kα and other PI3K isoforms, and induces single-agent tumor regressions in ER+, HER2- PI3Kα H1047R-mutant breast cancer models without causing hyperglycemia or increases in plasma insulin/C-peptide. LOXO-783 also demonstrates brain penetration in vivo with dose-dependent tumor growth inhibition in brain metastasis models. Here we report the efficacy of LOXO-783 with SOC treatments in preclinical breast cancer models. Methods Cell proliferation assays and in vivo studies to evaluate combination effects were performed in various PI3Ka H1047R mutant HR+, HER2- and triple negative breast cancer models. For each combination in vitro, a combination index (CI) based on the Loewe Additivity Method was calculated (CI&amp;gt;2 antagonism, 0.5&amp;gt;CI&amp;lt; 2 additivity, CI&amp;lt; 0.5 synergy). For the in vivo studies, the Bliss Independence Method was used to evaluate the statistical significance of the combination effects. Results Combining LOXO-783 with either fulvestrant (FUL; CI at 50% inhibition = 0.28) or imlunestrant (CI at 50% inhibition = 0.43) showed increased efficacy in cell proliferation assays using the HR+, HER2-, PI3Kα H1047R-mutant T47D model. LOXO-783 also demonstrated an additive effect in combination with these endocrine therapies in vivo. Similar results were observed in a T47D model engineered to express ESR1 D538G, as well as in an HR+, HER2- PI3Kα double in-cis mutant model (H1047R/D350G) also harboring ESR1 D538G and derived from a patient who had progressed on prior letrozole plus taselisib. Moreover, LOXO-783 plus abemaciclib demonstrated an additive effect in vitro (CI at 50% inhibition = 0.61), and in T47D xenograft and PDX models in vivo. Combinations of LOXO-783 with abemaciclib plus imlunestrant resulted in a mean tumor regression of –48.1%; LOXO-783 with abemaciclib plus FUL showed mean tumor regression of –43.9% in T47D xenografts. Similar efficacy was not observed in the absence of LOXO-783 (mean tumor regression was –7.3% with abemaciclib plus imlunestrant, and 3.2% with abemaciclib plus FUL). We observed comparable results in PDX models. These data collectively demonstrate the additive effect of LOXO-783 with SOC treatments. Extending these studies to additional treatment settings, LOXO-783 was similarly efficacious as a single agent in abemaciclib-resistant and abemaciclib/FUL double-resistant models, and was additive in combination with paclitaxel in a triple negative breast cancer model in vitro and in vivo. Conclusions LOXO-783 shows additive effects when combined with SOC in breast cancers harboring the PI3Kα H1047R-mutation (as single or double in-cis mutations) in both HR+ and triple negative settings. LOXO-783 is also efficacious in ESR1 mutant as well as in abemaciclib and abemaciclib/FUL double-resistant models. A phase 1 trial of LOXO-783 alone or in combination with anticancer therapies is ongoing (PIKASSO-01; NCT05307705). Citation Format: Loredana Puca, Michele S. Dowless, Carmen M. Perez-Ferreiro, Maria Jesus Ortiz-Ruiz, Gregory P. Donoho, Andrew Capen, Lysiane Huber, Sarah M. Bogner, Dongling Fei, Jason R. Manro, Chun Ping Yu, Wei Guo Xu, Rui Wang, Shuang Chen, Mark A. Hicks, Parisa Zolfaghari, Andrew Faber, Raymond Gilmour, Monica D. Ramstetter, Matthew T. Chang, Maria Jose Lallena, Xuequian Gong, David M. Hyman, Lillian M. Smyth, Barbara J. Brandhuber, Barry S. Taylor, Anke Klippel. LOXO-783: A potent, highly mutant selective and brain-penetrant allosteric PI3Kα H1047R inhibitor in combination with standard of care (SOC) treatments in preclinical PI3Kα H1047R-mutant breast cancer models [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-08-02.

Diabetic foot ulcers are a common complication of diabetes and require specialized treatment. Cold atmospheric plasma (CAP) has been associated with benefits in wound infection and healing in previous smaller series of case reports. Yet the effect of CAP compared with standard care therapy in wound healing in diabetic foot ulcers remains to be studied. To determine whether the application of CAP accelerates wound healing in diabetic foot ulcers compared with standard care therapy. A prospective, randomized, placebo-controlled, patient-blinded clinical trial was conducted at 2 clinics with recruitment from August 17, 2016, to April 20, 2019. Patients were scheduled to remain in follow-up until April 30, 2024. Patients with diabetes and diabetic foot ulcers described using the combined Wagner-Armstrong classification of 1B or 2B (superficial or infected diabetic foot ulcers extending to tendon) were eligible. A patient could participate with 1 or more wounds in both groups in both intervention and control groups. Wounds were randomized separately, allowing a participant to be treated several times within the study following a 2 × 2 × 2 randomization strata considering sex, smoking status, and age (≤68 years and >68 years). Standard care treatment with 8 applications of either CAP generated from argon gas in an atmospheric pressure plasma jet or 8 applications of placebo treatment in a patient-blinded manner. Primary end points were reduction in wound size, clinical infection, and microbial load compared with treatment start. Secondary end points were time to relevant wound reduction (>10%), reduction of infection, parameters of patient's well-being, and treatment-associated adverse events. Of 65 diabetic foot ulcer wounds from 45 patients assessed for study, 33 wounds from 29 patients were randomized to CAP and 32 wounds from 28 to placebo, with 62 wounds from 43 patients (31 wounds per group) included for final evaluation (mean [SD] age, 68.5 [9.1] years for full sample). Four patients with 5 wounds of 31 (16.1%) wounds in the CAP group and 3 patients with 4 wounds of 31 (13%) wounds in the placebo group were active smokers. CAP therapy yielded a significant increase in wound healing, both in total mean (SD) area reduction (CAP vs placebo relative units, -26.31 [11.72]; P = .03) and mean (SD) time to relevant wound area reduction (CAP vs placebo relative units, 10% from baseline, 1.60 [0.58]; P = .009). Reduction of infection and microbial load was not significantly different between CAP and placebo. No therapy-related adverse events occurred during therapy; patient's perceptions during therapy were comparable. In this randomized clinical trial, CAP therapy resulted in beneficial effects in chronic wound treatment in terms of wound surface reduction and time to wound closure independent from background infection. ClinicalTrials.gov Identifier: NCT04205942.

Changes in standard of care (SOC) medication during long-term mavacamten treatment for obstructive hypertrophic cardiomyopathy (HCM): results from the EXPLORER cohort of MAVA-Long-Term Extension (LTE)

IntroductionPatients with diabetes frequently develop diabetic foot ulcers, a significant clinical pathology that results in increased morbidity and mortality. Standard of care (SOC) treatment has been insufficient to prevent the poor outcomes associated with these wounds. This analysis aims to evaluate the supplementation of SOC with a human tissue allograft.MethodsThis evaluation is of two prospective, multicenter, randomized clinical studies (ELITE - ongoing and CAMPLIFE - terminated) comparing a dehydrated human amnion-intermediate layer-chorion membrane (dHAICM) tissue allograft (AmchoPlast®, Cellution Biologics, Inc., Roswell, GA, US) as a supplement to SOC (dHAICM + SOC) versus SOC alone. Eligible target ulcers must have been present for a minimum of four weeks with SOC treatment and not have reduced in size by more than 20% during the screening period. Participants were treated weekly for up to 10 weeks in the ELITE study and 12 weeks in the CAMPLIFE study.ResultsAcross the ELITE and CAMPLIFE studies, 90 participants were screened, with 64 total participants remaining eligible at the randomization visit who subsequently were enrolled. Of those, a total of 53 participants were eligible for inclusion in this analysis, 29 of whom had completed the study per protocol as of the data cutoff time for this analysis. A total of 18 participants (34%) achieved complete wound closure of their ulcers. In the SOC alone group, four participants healed (17%) compared to 14 (50%) in the dHAICM + SOC group, a statistically significant difference in healing between the two groups (P = 0.019). Utilizing a non-pooled sample from the ELITE study was also statistically significant; 12 participants (71%) in the dHAICM + SOC group healed, compared to three participants (23%) in the SOC alone group (P = 0.0253). A reduction in wound area of 71% ± 18.2% was observed for the dHAICM + SOC group and 46% ± 16.9% for the SOC alone group; however, this reduction did not reach statistical significance (P = 0.0517). In the interim analysis of the data from the ELITE study, a wound area reduction of 78% ± 23.3% was achieved by the dHAICM + SOC vs. a 38% ± 20.1% reduction for SOC alone, a statistically significant difference between the two groups (P = 0.018). No statistically significant improvements in pain scores, Wound Quality of Life assessments, or Forgotten Wound Score assessments were observed in either the pooled sample or the ELITE only analysis.DiscussionBoth analyzed study populations showed better outcomes for wound closure and wound area reduction when SOC was supplemented with dHAICM, although wound area reduction only reached statistical significance for the ELITE interim analysis.ConclusionsSupplementing SOC treatment for diabetic foot ulcers increases the likelihood of the ulcer healing completely and improves the reduction in wound area.

A multicentre, randomized, naturalistic, open-label study between aripiprazole and standard of care in the management of community-treated schizophrenic patients Schizophrenia Trial of Aripiprazole: (STAR) study

The meta-analysis was performed to evaluate the efficacy and safety associated with the application of human amniotic membrane (HAM) in individuals with chronic nonhealing wounds. The research conducted a comprehensive search of nine electronic databases from their inception to August 1, 2024, aiming to identify randomized controlled trials (RCTs) that evaluated the efficacy of HAM compared with conventional management alone in individuals suffering from chronic wounds. The risk of bias of included studies and the certainty of the evidence in the meta-analysis were evaluated by two investigators and confirmed by a third. The meta-analysis was performed using RevMan 5.4 software. We identified 14 RCTs encompassing a total of 1,056 participants. The potential risk of bias was determined to be moderate. HAM therapy demonstrated significantly greater efficacy than conventional treatment alone in achieving complete wound healing among patients with chronic ulcers (relative risk [RR] = 1.82; 95% confidence interval [CI]: 1.48-2.24; moderate-quality evidence). In patients with diabetic foot ulcers, HAM reduced the mean time to complete healing by 22 days compared with standard care alone (mean difference = -22.09 days; 95% CI: -39.13 to -5.05; low-quality evidence) and increased the rate of complete healing at 6 weeks (RR = 3.02; 95% CI: 2.04-4.47; moderate-quality evidence) and at 12 weeks (RR = 1.74; 95% CI: 1.37-2.21; low-quality evidence). Similarly, in patients with venous leg ulcers, HAM was associated with more than twice the likelihood of complete healing (RR = 2.03; 95% CI: 1.45-2.86; moderate-quality evidence). No statistically significant differences were noted in the incidence of adverse events among patients with chronic ulcers (moderate-quality evidence). Our study suggests that HAM represents a promising and viable therapeutic strategy for the management of chronic wounds, including lower-extremity diabetic ulcers and venous ulcers. The application of HAM provides a safer and more effective therapeutic approach compared with conventional management alone for patients suffering from chronic refractory ulcers.

Non-contact low-frequency ultrasound (NCLF-US) devices have been increasingly used for the treatment of chronic non-healing wounds. The appropriate dose for NCLF-US is still in debate. The aims of this pilot study were to evaluate the relationship between dose and duration of treatment for subjects with non-healing diabetic foot ulcers (DFUs) and to explore the correlation between wound healing and change of cytokine/proteinase/growth factor profile. This was a prospective randomised clinical study designed to evaluate subjects with non-healing DFUs for 5 weeks receiving standard of care and/or NCLF-US treatment. Subjects were randomly assigned to one of the three groups: application of NCLF-US thrice per week (Group 1), NCLF-US once per week (Group 2) and the control (Group 3) that received no NCLF-US. All subjects received standard wound care plus offloading for a total of 4 weeks. Percent area reduction (PAR) of each wound compared with baseline was evaluated weekly. Profiles of cytokines/proteinase/growth factors in wound fluid and biopsied tissue were quantified to explore the correlation between wound healing and cytokines/growth factor expression. Twelve DFU patients, 2 (16·7%) type 1 and 10 (83·3%) type 2 diabetics, with an average age of 58 ± 10 years and a total of 12 foot ulcers were enrolled. Average ulcer duration was 36·44 ± 24·78 weeks and the average ABI was 0·91 ± 0·06. Group 1 showed significant wound area reduction at weeks 3, 4 and 5 compared with baseline, with the greatest PAR, 86% (P < 0·05); Groups 2 and 3 showed 25% PAR and 39% PAR, respectively, but there were no statistically significant differences between Groups 2 and 3 over time. Biochemical and histological analyses indicated a trend towards reduction of pro-inflammatory cytokines (IL-6, IL-8, IL-1β, TNF-α and GM-CSF), matrix metalloproteinase-9 (MMP-9), vascular endothelial growth factor (VEGF) and macrophages in response to NCLF-US consistent with wound reduction, when compared with control group subjects. This proof-of-concept pilot study demonstrates that NCLF-US is effective in treating neuropathic diabetic foot ulcers through, at least in part, inhibiting pro-inflammatory cytokines in chronic wound and improving tissue regeneration. Therapeutic application of NFLU, thrice (3) per week, renders the best wound area reduction.

P.2.139 Effectiveness of quetiapine up to 1600 mg/day: Short-term results with 14-month follow-up

64 Background: The standard of care (SOC) for stage II/III rectal cancer is neoadjuvant chemoradiation plus surgical resection. We aim to compare the treatment practices for patients with stage II and III rectal cancer in major insurance types. Methods: Using data from the National Cancer Database (NCDB), we analyzed the treatment patterns of 91,782 patients diagnosed with stage II/III rectal cancer from 2000 to 2009. The NCDB includes data from 70% of all U.S. cancer patients. This is the largest study of this kind to date. Results: In stage II/III rectal cancer, patients with private insurance received more SOC treatment (70.3%) than patients with VA Insurance (56.6%), Medicare (46.9%), Medicaid (66.5%), or no insurance (61.7%) (p&lt;.0001). VA patients received less SOC treatment than Medicaid or noninsured patients (p&lt;.0001). Medicare patients (26.9%) were treated with surgery alone more often than patients with private insurance (9.8%), Medicaid (10.4%), VAH (12.2%), or no insurance (9.4%) (p&lt;.0001). VA (4.8%) and Medicare (4.3%) patients more often did not receive any “First Course Treatment” than patients with private insurance (1.3%) (p&lt;.0001). Patients over 70 years old received less SOC treatment (42.2%) than patients under 70 years old (68.9%) (p&lt;.0001) and received more surgery without chemotherapy or radiation (29.3%) than patients less than 70 years old (9.2%) (p&lt;.0001). Conclusions: Stage II/III rectal cancer patients with private insurance received more SOC treatment than VA, Medicare, Medicaid or uninsured patients. VA patients received less SOC treatment than Medicaid or uninsured patients. [Table: see text]

P.3.d.044 - Effects of aripiprazole once-monthly and paliperidone palmitate in patients with schizophrenia stratified by disease severity: a post-hoc analysis of QUALIFY

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, since most PDAC tumors develop resistance to the standard of care (SoC) treatments like chemotherapy, radiation, and targeted therapies. All tumors consist of multiple, genetically related subpopulations of cancer cells that evolve in parallel and display heterogeneity at genomic, epigenetic, or phenotypic levels. As cancer develops, some subpopulations of cancer cells may show faster growth, increased metastatic potential, and resistance toward SoC treatment. A key challenge in PDAC management is understanding chemoresistance driven by cancer subpopulation dynamics. This would broaden our understanding of tumor adaptation to treatments and guide targeting resistant subpopulations to improve therapeutic outcomes. In this study, we identified PDAC cell subpopulations resistant to chemotherapy using our DNA barcoding system B-GLI (barcode-guide lineage isolation). The B-GLI system leverages a highly complex DNA barcode library and CRISPR activation (CRISPRa) to trace and isolate sub-lineages within heterogeneous cell populations by their DNA barcodes. PDAC cell lines PANC-1 and Mia-PaCa-2 were barcoded with the B-GLI barcode library, which consist of two optimized guide RNA binding sites in each barcode. After DNA barcoding, we performed treatments with two SoC chemotherapeutics, gemcitabine + paclitaxel and FOLFIRINOX, to induce a selection pressure in the PDAC cell lines, and then identified the resistant subpopulations through differentially represented barcodes and sequencing. Furthermore, we designed barcode-specific single guide RNAs (sgRNAs) targeting the resistant subpopulations and activated the expression of the puromycin resistance gene by CRISPRa. This allowed us to enrich and isolate chemoresistant subpopulations by puromycin treatment. After having isolated the resistant PDAC subpopulations, we performed ATAC-seq and RNA-seq for molecular characterization of the resistant and parental cell populations, along with phenotypic drug screening with 384 compounds to identify novel treatment vulnerabilities. The compound testing confirmed that the resistant cells were less sensitive to the two SoC treatments, as well as identified selective sensitivity to specific compounds. ATAC-seq and RNA-seq data will allow us to decode whether and how chromatin structure and transcriptomic changes are associated with the treatment resistance, and the confirmation screen of the drug sensitivities will identify potential compounds for future pre-clinical and clinical testing in PDAC models and patients with resistant disease. In summary, this study will identify targeted treatment alternatives, accompanied by molecular biomarkers for chemotherapy resistant PDAC. Citation Format: Subhendu Roy Choudhury, Shixiong Wang, Yevhen Akimov, Katarina Willoch, Biswajyoti Sahu, Alfonso Urbanucci, Thomas Fleischer, Tero Aittokallio. Identification, isolation and molecular characterization of drug-resistant sub-populations of pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5544.