Improve Treatment Outcomes Research Articles

Survey of Access to and Use of Narrowband UVB Phototherapy in Pediatric Vitiligo.

This study sought to evaluate narrowband UVB phototherapy in pediatric vitiligo through an online patient and caregiver survey to better understand patient experiences and barriers to care in this population. In a survey of 111 respondents, 51.4% were offered nbUVB and 45.1% utilized nbUVB for treatment of vitiligo before age 18 years. The primary reasons for not pursuing nbUVB included it not being offered (36.1%), difficulty attending appointments (11.5%), and satisfaction with the current skin condition (11.5%). Our results suggest nbUVB may be underutilized in pediatric vitiligo; addressing obstacles to access is crucial for improving treatment outcomes and quality of life.

Hair follicle stem cell-derived secretome protects astrocytes in an in vitro ischemia/reperfusion model.

Ischemic stroke causes significant neuronal and glial cell damage. Recent studies suggest that stem cell-derived secretomes may offer therapeutic benefits for neural injuries. This study evaluates the protective effects of hair follicle stem cell (HFSC)-derived secretome on astrocytes subjected to oxygen-glucose deprivation (OGD), an in vitro model of ischemic stroke. In this regard, the primary astrocyte cultures were exposed to OGD conditions for 24 hours, followed by treatment with HFSC-derived secretome for 48 hours to create an environment rich in paracrine factors. The neuroprotective effect of HFSC-derived secretome on injured astrocytes was assessed using MTT assay, apoptosis flow cytometry, and qRT-PCR. The HFSC secretome mitigated cell death and apoptosis in OGD-induced astrocytes. Additionally, the secretome reduced the mRNA expression levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α compared to the injured cells. Furthermore, it upregulated the mRNA levels of neurotrophic factors BDNF, and VEGF after OGD in astrocytes. These findings suggest that the reparative effects of the secretome are associated with astrocyte neuroprotection, anti-inflammatory properties, and anti-apoptotic effects. The neuroprotective effect of HFSC secretome may be associated with the upregulation of neurotrophic and angiogenic factors. Restored astrocytes create a conducive environment for repair, thereby expediting the recovery of impaired brain function. This study provides preclinical evidence supporting the potential of HFSC secretome in stroke therapy to improve treatment outcomes of patients who suffered from ischemic stroke.

Clarification of the Clinical Characteristics of Autoimmune Disease-Related Ulcers to Improve Treatment Outcomes: A Retrospective Study.

AimTo clarify the clinical characteristics of autoimmune disease (AID)-related ulcers to improve treatment outcomes.Materials and MethodsThe medical records of 189 patients treated for AID-related ulcers at two tertiary hospitals in Nanjing, China, from January 1, 2018 to December 31, 2022 were retrospectively reviewed. The relevant clinical data included diagnosis, type and severity of wounds, and prescribed medications.ResultsOf the 189 patients with AID-related ulcers, 146 (77.25%) were female and 43 (22.75%) were male. The top four immunological diagnoses were rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome, and vasculitis. The four most common wound sites were the lower limb, foot, hand, and upper limb. Regarding the number of wounds, 81 (42.86%) patients had one ulcer, 43 (22.75%) had two, 30 (15.87%) had three, and 35 (18.52%) had four or more. More than half of the patients (54%, 102/189) were previously treated for AID-related ulcers. Of these 102 patients, 27 (26.47%) had one previous diagnosis, 49 (40.83%) had two, and 26 (25.49%) had three or more. Among all 189 patients, 142 (75%) had clinical symptoms of local infection. Of these 142 patients, bacteria cultures were conducted for 70 (49.30%), of which 63 (90.00%) were positive. The most commonly detected bacteria were Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. The median (interquartile range) duration of AID-related ulcers was 55 (39, 90) days. Most patients (87.3%, 165/189) received systemic therapy with immunosuppressants and hormones.ConclusionsThe most common clinical characteristics of AID-associated ulcers were spontaneous rupture, long duration, multiple wounds, bacterial infection, and recurrence. Clarification of the clinical characteristics of AID-associated ulcers can improve treatment outcomes.

Prostate cancer diagnosis and management: current practices in Africa a consultant-based survey

IntroductionIn Africa, prostate cancer poses significant diagnostic and treatment challenges due to limited access to diagnostic tools and healthcare resources. This survey aimed to assess current prostate biopsy practices, patient classification methods, and available therapeutic means among African urologists to propose strategies for improved screening, diagnosis, and management.MethodsA web-based self-administered questionnaire was distributed to urologists in 58 African centres, focusing on biopsy practices, cancer diagnosis, management, and treatment protocols. After pretesting and validation, data collection spanned six weeks, followed by duplicate elimination and arithmetical analysis, with results expressed in absolute, mean, or percentage values.ResultsFeedback was received from 58 centres across diverse African regions, including Central, Southern, West, East Africa, and Madagascar, comprising general, private, and university hospitals. Prostate cancer emerged as the most frequent urological cancer in all regions studied. The assay for prostate-specific antigen (PSA) was available in nearly all centres. Biopsy techniques varied, with ultrasound-guided biopsies being the most common (30 centres), followed by digital-guided (20 centres) and MRI-guided biopsies (5 centres). One centre lacked the expertise to perform biopsies. Radiological workup availability was high, with CT available in 56 centres, MRI in 54, PET scans in 14, and scintigraphy in 29. Treatment capabilities varied, with 53.4% of centres able to perform radical prostatectomies, 86.2% offering radiotherapy, and 94.8% providing medical castration. Among the centres, 56 performed fewer than 5 radical prostatectomies per month, while only 2 centres performed between 5 and 10 per month.ConclusionIt is important to standardise prostate cancer diagnosis and treatment protocols across Africa while improving access to advanced diagnostic technologies and treatment facilities. Implementing these changes could enhance early detection, improve treatment outcomes, and reduce the burden of prostate cancer in Africa.

Mediators and Predictors of Treatment Response in a Brief Online Intervention for Rumination and Worry

Abstract Background Repetitive Negative Thinking (RNT) is a key transdiagnostic mechanism underlying anxiety and depressive disorders, and targeting RNT specifically leads to improved treatment outcomes. There is a lack of research however into mechanisms of change in RNT-focused interventions and factors that predict treatment response. The aim of this study was to examine the mediators and predictors of outcome (RNT, depression, anxiety, and distress) in a brief online intervention for RNT in adults. Methods This study used secondary data from a Randomised Controlled Trial of the Managing Rumination and Worry Program (Joubert et al. in Beh Res Therapy, 168:104378, 2023) in which N = 137 adults with elevated levels of RNT were randomly allocated to a 3-lesson clinician-guided or self-guided version of the program delivered over 6 weeks, or a treatment-as-usual (TAU) control condition. Self-report measures of depression, anxiety, distress, and RNT were administered at baseline, post-treatment, and 3-month follow-up; RNT and distress were also measured prior to each lesson. Results Intention-to-treat linear mixed models showed a gradual reduction in RNT and distress over treatment in both active conditions, with the largest reductions in RNT occurring after the lessons containing the active treatment strategies (2 and 3). Structural equation modelling mediation analyses showed that reductions in transdiagnostic RNT mediated reductions in distress between Lessons 2 and 3, and reductions in rumination specifically mediated reductions in distress and depression between post-treatment and follow-up, but there was no consistent pattern of mediation by RNT throughout treatment. Finally, higher baseline symptom severity (particularly rumination) significantly predicted poorer post-treatment outcomes, while higher treatment expectancy and clinician guidance significantly predicted better post-treatment outcomes. Conclusion This is one of the first studies to examine mediators and predictors of change in a brief, online RNT-focused intervention for adults with elevated RNT. Further research in larger samples is needed, examining additional possible mediating and predictor variables and across more time points, to better understand how and for whom this intervention reduces RNT, anxiety and depression. Australian and New Zealand Clinical Trials Registration number: ACTRN 12620000959976. Date of registration: 25/09/2020.

Enhanced Tear Film Concentrations of Cefazolin and Chloramphenicol Using Cross-Linked Hyaluronic Acid in Canine Eyes.

To evaluate the impact of two excipients, 1.4% polyvinyl alcohol (PVA) and 0.75% cross-linked hyaluronic acid (XHA), on tear film concentrations of cefazolin and chloramphenicol. Ten ophthalmologically healthy dogs. Cefazolin and chloramphenicol were compounded into 5.5% and 0.5% solutions, respectively, using either 1.4% PVA or 0.75% XHA. In the first trial, each dog received cefazolin-PVA in one randomly assigned eye and cefazolin-XHA in the contralateral eye. One month later, the experiment was repeated using chloramphenicol formulations. Tear fluid was sampled at 0, 1, 5, 10, 15, 30, 60, 120, 240, 360, and 480 min following eyedrop administration using 2 μL capillary tubes. Tear concentrations of cefazolin and chloramphenicol were measured using UV-Vis spectrophotometry. Tear film concentrations of cefazolin and chloramphenicol were significantly higher with XHA compared to PVA at all time points (p ≤ 0.020), except for baseline (both antibiotics), times 1 min, 60 min, and 120 min for cefazolin. The tear film kinetics exhibited a biphasic pattern, with drug levels decreasing from 0 to 120 min, then slightly increasing between 120 and 360 min before declining again until 480 min. The area under the time-concentration curve (AUC0-480) was significantly greater with XHA versus PVA formulations (p = 0.002), with a median 2.4 and 4.2 times higher for cefazolin and chloramphenicol, respectively. The cross-linked hyaluronic acid significantly enhanced the retention and overall exposure of both cefazolin and chloramphenicol in the canine tear film. These findings suggest that XHA could serve as a superior delivery vehicle for ocular antibiotics, potentially improving treatment outcomes for ophthalmic infections.

The Interplay between Anemia and Malaria Treatment Outcomes in East Africa: Implications for Clinical Recovery and Complication Risks

Anemia is a common and often severe complication of malaria, especially in East Africa, where the dual burden of these conditions significantly contributes to morbidity and mortality. The complex interplay between malaria and anemia impedes clinical recovery, increases the risk of complications, and challenges the effectiveness of malaria treatment regimens. This review explores the pathophysiology of malaria-induced anemia, highlighting mechanisms such as hemolysis, impaired erythropoiesis, and nutritional deficiencies. The impact of anemia on malaria treatment outcomes is discussed, including delayed recovery, increased risk of multi-organ dysfunction, and reduced efficacy of antimalarial therapies. Special populations, such as children under five, pregnant women, and individuals with hemoglobinopathies, face heightened risks. The review emphasizes the need for integrated management strategies, including early anemia detection, tailored antimalarial treatments, and targeted nutritional interventions, to improve treatment outcomes in anemic malaria patients. Additionally, the review identifies critical research gaps and outlines future directions for enhancing malaria and anemia management, with a focus on cost-effective interventions and the development of comprehensive treatment protocols. Addressing both malaria and anemia simultaneously offers a promising approach to reducing disease burden and improving recovery rates in East Africa. Keywords: Malaria, Anemia, East Africa, Treatment Outcomes, Plasmodium falciparum.

New pyrazole-based derivatives targeting MmpL3 transporter in Mycobacterium tuberculosis: design, synthesis, biological evaluation and molecular docking studies.

This study addresses the urgent need for new drugs to combat multi-drug-resistant tuberculosis (MDR-TB). Focusing on MmpL3, a protein essential for mycobacterial cell wall synthesis, we designed and synthesised 50 new pyrazole-based amide derivatives. These compounds were then tested for their ability to inhibit the growth of various Mycobacterium tuberculosis (Mtb) strains, including both drug-susceptible and drug-resistant strains (resistant to isoniazid, rifampicin, or both). Two compounds, 15 and 35, emerged as potent inhibitors. They showed strong activity against both drug-susceptible and drug-resistant Mtb strains, with low minimum inhibitory concentration (MIC) values of 2µg/mL and 2-4µg/mL, respectively. Importantly, these compounds also demonstrated a high selectivity index, meaning they were significantly more toxic to Mtb cells than to human liver cells (HepG2). Compound 15 further proved to be bactericidal, effectively killing Mtb within six days. Interestingly, compounds 15 and 35 were inactive against lab-generated Mtb strains resistant to SQ109, a known MmpL3 inhibitor. This finding, supported by molecular docking, molecular dynamics simulations, and genetic analysis of the mmpl3 gene in the SQ109-resistant strains, strongly suggests that these novel compounds also target MmpL3. This research highlights the potential of pyrazole-based amides as a promising new class of anti-TB drugs. By targeting MmpL3, these compounds offer a novel mechanism of action to combat drug-resistant TB, potentially leading to improved treatment outcomes.

Enhancer transcription profiling reveals an enhancer RNA-driven ferroptosis and new therapeutic opportunities in prostate cancer

Enhancer RNAs (eRNAs), a subclass of non-coding RNAs transcribed from enhancer regions, have emerged as critical regulators of gene expression; however, their functional roles in prostate cancer remain largely unexplored. In this study, we performed integrated chromatin accessibility and transcriptomic analyses using ATAC-seq and RNA-seq on twenty pairs of prostate cancer and matched benign tissues. By incorporating chromatin immunoprecipitation sequencing data, we identified a subset of differentially expressed eRNAs significantly associated with genes involved in prostate development and oncogenic signaling pathways. Among these, lactotransferrin-eRNA (LTFe) was markedly downregulated in prostate cancer tissues, with functional analyses revealing its tumor-suppressive role. Mechanistically, LTFe promotes the transcription of its target gene, lactotransferrin (LTF), by interacting with heterogeneous nuclear ribonucleoprotein F (HNRNPF) and facilitating enhancer-promoter chromatin interactions. Furthermore, we demonstrate that the LTFe-LTF axis facilitates ferroptosis by modulating iron transport. Notably, androgen receptor (AR) signaling disrupts LTFe-associated chromatin looping, leading to ferroptosis resistance. Therapeutically, co- administration of the AR inhibitor enzalutamide and the ferroptosis inducer RSL3 significantly suppressed tumor growth, offering a promising strategy for castration-resistant prostate cancer. Collectively, this study provides novel insights into the mechanistic role of eRNAs in prostate cancer, highlighting the LTFe-LTF axis as a critical epigenetic regulator and potential therapeutic target for improved treatment outcomes.

The Ready for Safe Cancer Treatment (RESET) tool: enhancing quality and optimizing timely and safe discharge with transitional care adjustments for Head and Neck Cancer patients.

<b>Introduction:</b> The Ready for Safe Cancer Treatment (RESET) tool is a structured, multimodal program designed to optimize hospitalization and enhance the quality of perioperative care for oncological patients. While RESET has been developed as a general framework for surgical oncology, its adaptation to Head and Neck Cancer (HNC) patients remains unexplored despite their unique physiological and psychological needs. HNC patients frequently face severe functional impairments affecting speech, swallowing, and respiration, as well as heightened nutritional deficiencies, sarcopenia, and psychological distress. This study explores the feasibility of tailoring the RESET tool to meet the specialized requirements of HNC patients. <br><br><b>Aim:</b> The aim of this study is to assess the feasibility of adapting the RESET to the specific needs of HNC patients. The research focuses on identifying key areas requiring modification to optimize perioperative care, including prehabilitation, nutritional support, functional rehabilitation, and psychological care. Epidemiological analysis, patient needs assessment, and a review of the core RESET modules will help determine effective strategies for improving treatment quality and recovery outcomes in this patient group. The ultimate goal is to develop a more personalized, evidence-based approach that could be implemented in oncology centers to enhance treatment outcomes for HNC patients. <br><br><b>Methods:</b> RESET is structured into four modules: pre-admission prehabilitation, advanced communication and need assessment upon admission, intra-hospital recovery optimization, and transitional care planning at discharge. This study includes a cross-sectional epidemiological assessment of HNC patient representation at two oncological centers in Poland, an analysis of prehabilitation requirements, a comparative evaluation of core RESET modules, and a gap analysis identifying necessary protocol enhancements. The proposed methodological approach integrates both quantitative and qualitative assessments to ensure a comprehensive evaluation of RESET's adaptation to HNC patients. <br><br><b>Results:</b> Data from 2023-2024 indicate that HNC patients constitute 11-25% of the total oncological population at the studied centers, demonstrating distinct demographic characteristics such as younger age distribution and extended hospitalization periods. Prehabilitation needs analysis underscores the importance of structured nutritional support, targeted muscle preservation strategies, and psychological interventions, including cognitive behavioral therapy. Additionally, core RESET module evaluations highlight the necessity of enhanced post-discharge transitional care, particularly for patients requiring tracheostomy or prolonged enteral nutrition support. The gap analysis identifies critical areas requiring reinforcement, such as comprehensive sarcopenia screening, specialized dysphagia management protocols, and a multidisciplinary approach to psychosocial rehabilitation. <br><br><b>Discussion:</b> HNC patients present unique challenges that demand tailored modifications to the RESET framework. Unlike other oncological cohorts, HNC patients are predisposed to functional impairments, high nutritional deficits, and significant psychosocial burdens. The inclusion of dedicated nutritional strategies, prehabilitation exercises, and psychological support within the RESET protocol may significantly improve treatment outcomes, reduce postoperative complications, and enhance the quality of life. Despite its structured approach, the main limitation of the RESET adaptation for HNC remains the need for dedicated funding and further validation through prospective clinical trials. <br><br><b>Conclusions:</b> Adapting the RESET tool to the needs of HNC patients has the potential to optimize perioperative care, ensuring a more individualized, evidence-based approach. The proposed modifications emphasize enhanced nutritional, physical, and psychological support, aligning RESET with the specific challenges faced by HNC patients. Further research and implementation studies are required to validate the effectiveness of this adapted framework in improving patient outcomes within oncological network hospitals.

Terminologies and definitions used to classify patients with osteoarthritis: a scoping review

ObjectivesOsteoarthritis (OA), a prevalent and disabling condition, significantly burdens individuals and healthcare systems worldwide. It is characterized by joint pain, stiffness, and structural changes in cartilage, bone, and synovium. The clinical manifestations of OA vary widely, reflecting complex interactions among genetic, metabolic, biomechanical, and environmental factors. Despite progress in identifying OA clinical phenotypes, inconsistent terminology, including “phenotypes,” “subtypes,” and “subgroups,” hinders effective communication and research translation. This review aims to synthesize existing literature on clinical OA phenotypes, terminology, and definitions and propose a research agenda.MethodThis scoping review followed PRISMA-ScR guidelines, focusing on publications from 2010 to 2023 investigating clinical phenotypes in adult OA patients. Searches were conducted in MEDLINE, SCOPUS, and EBSCOhost using combinations of terms related to clinical phenotypes in OA. Studies were screened, duplicates removed, and relevant data were charted and analyzed by two independent reviewers.ResultsFrom 196 identified studies, 50 were included in the final analysis. Eight clinical phenotypes were categorized, including inflammatory, biomechanical, metabolic, and pain-sensitization. minimal joint disease, psychologically driven, menopause, severe radiographic. Most studies focused on knee OA, with limited exploration of hand, midfoot, and hip OA. Phenotype-based management strategies demonstrated potential for improving treatment outcomes and guiding research.ConclusionStandardizing terminology and leveraging phenotype-based frameworks hold promise for advancing personalized OA care and research. Future efforts should focus on validating criteria, developing accessible diagnostic tools, and addressing understudied OA phenotypes. This work highlights the value of tailoring interventions to specific OA phenotypes for improved patient outcomes.Clinical trial numberNot applicable

Mapping the patient journey: Understanding oral anticancer medication use among patients diagnosed with breast cancer.

IntroductionA growing number of patients with breast cancer use oral anticancer medications (OAMs) but may face barriers in managing their therapy at home, potentially impacting their treatment outcomes. Understanding these barriers is essential to designing effective interventions. This study aimed to identify unmet medication management needs of patients with breast cancer receiving OAMs.MethodsQualitative semi-structured interviews were conducted to create patient-specific journey maps describing OAM use. Participants were recruited from a federally qualified health center's breast cancer clinic in central Indiana. Eligible patients were 18 years of age or older, diagnosed with breast cancer, and currently receiving OAMs. Participants completed a sociodemographic survey, and researchers and participants collaborated to create visual storyboards of medication use experiences, highlighting timelines, key markers, and barriers. Journey maps were consolidated, and personas were created to represent patients with similar characteristics. Participants were categorized by medication type: specialty (requiring specialty pharmacies) or traditional (available at community pharmacies).ResultsTwelve participants (11 females, 1 male; median age 65.5 years, range 37-75) were interviewed. Four were receiving specialty medications (palbociclib, ribociclib), and eight were receiving traditional medications (tamoxifen, anastrozole, exemestane). Two personas were created. The specialty medication group reported difficulties navigating the insurance system, whereas the traditional group did not. All participants experienced side effects, and sub-optimal adherence (n = 2) was reported only in the traditional group.ConclusionThis study provides insights into the patient experience with OAMs. Personas and journey maps can guide the development of tailored interventions to improve treatment outcomes.

Clinically available predictors of obstructive sleep apnoea requiring treatment in type 2 diabetes patients in primary care

Obstructive sleep apnoea is a common yet frequently underdiagnosed condition in patients with type 2 diabetes, particularly in primary care. Early detection is important, as untreated sleep apnoea may contribute to worsened metabolic control and increased cardiovascular risk. This study evaluated 164 patients with type 2 diabetes and found that 75% had obstructive sleep apnoea, with 31% requiring treatment for moderate to severe cases. Predicting obstructive sleep apnoea for which medical treatment is indicated (i.e., moderate to severe OSA) proved challenging, as typical clinical symptoms and most other readily available clinical parameters proved to be unreliable indicators. However, central fat distribution, indicated by a higher waist-to-hip ratio (odds ratio 3.31, 95% confidence interval 1.91–6.25, p = 0.0032), and the presence of albuminuria (odds ratio 7.46, 95% confidence interval 1.99–27.89, p = 0.0244), emerged as significant predictors, with albuminuria representing a novel finding. Screening tools such as the STOP-Bang questionnaire had limited predictive accuracy. These findings highlight the importance of targeted screening in patients with type 2 diabetes, particularly those with central fat distribution or albuminuria, to reduce underdiagnosis and potentially improve treatment outcomes.

Association between HIV-1 Nef-mediated MHC-I downregulation and the maintenance of the replication-competent latent viral reservoir in individuals with virally suppressed HIV-1 in Uganda: an exploratory cohort study.

Association between HIV-1 Nef-mediated MHC-I downregulation and the maintenance of the replication-competent latent viral reservoir in individuals with virally suppressed HIV-1 in Uganda: an exploratory cohort study.

Self-Perception as a Predictor of Eating Disorder Severity in a Residential Sample of Women and Girls With Eating Disorders.

Eating disorders are serious mental health conditions with significant negative health outcomes, high mortality rates, and comorbid mental health conditions. Despite many available interventions for eating disorders, treatment remains challenging due to the difficulty in maintaining treatment gains. Understanding effective treatment processes is crucial. This study aimed to examine the role of self-perception components in predicting eating disorder severity in a residential sample of women and girls. Participants (N = 175) completed measures assessing eating disorder severity, self-kindness, self-judgment, and self-esteem at admission. Correlational analyses and structural equation modeling were used to explore these relationships. Results indicated that self-judgment and self-esteem were significant predictors of eating disorder severity, while self-kindness was not. These findings highlight the importance of targeting self-judgment and self-esteem in treating eating disorders, suggesting potential areas for therapeutic focus to improve treatment outcomes. Further research is needed to refine transdiagnostic interventions for eating disorders and explore their efficacy across clinical settings.

A Comparative Study of Melittins from Apis florea and Apis mellifera as Cytotoxic Agents Against Non-Small Cell Lung Cancer (NSCLC) Cells and Their Combination with Gefitinib

Lung cancer remains one of the most lethal malignancies, often diagnosed at advanced stages, leading to limited treatment options. Thus, identifying natural products with potent anti-cancer activity is crucial for improving treatment outcomes. While the melittin from Apis mellifera (Mel-AM) has been extensively studied, the melittin from Apis florea (Mel-AF), a bee species native to Southeast Asia, remains relatively underexplored. These peptides were comparatively investigated against non-small cell lung cancer (NSCLC) cell lines, A549, NCI-H460, and NCI-H1975. Mel-AF demonstrated a superior cytotoxicity (cytotoxic concentration 50% (CC50) = 2.55–5.06 µg/mL) compared to Mel-AM (CC50 = 4.32–8.48 µg/mL). While both peptides induced apoptosis via the intrinsic mitochondrial pathway, Mel-AF exhibited a more pronounced effect, significantly enhancing apoptosis induction compared to Mel-AM. Both peptides inhibited cell migration and invasion; however, when combined with gefitinib, Mel-AF more effectively enhanced the drug’s inhibitory effects on the A549 and NCI-H460 cell lines compared to Mel-AM, underscoring its superior potential as a therapeutic agent. Altogether, we demonstrated that these peptides induced apoptosis in NSCLC cell lines, with Mel-AF having more pronounced effects, and the combination use of peptides with a chemotherapeutic drug showed synergistic effects against lung cancer cells, enhancing their practical use in lung cancer treatments.

Abstract B023: Patient-specific, organotypic head and neck cancer model for personalized medicine

Abstract Background: Head and neck cancer (HNC) treatment outcomes are highly variable among patients, and lack of actionable data on individual treatment responses limits effective clinical decision-making. Microphysiological systems (MPS) are advanced in vitro models that replicate the biological, physical, and functional properties of human tissues, offering a promising approach to testing treatment responses in vitro. Despite their potential, MPS adoption for evaluating standard clinical treatments—such as radiation and chemotherapy—has been hindered by the challenge of recreating the complexity of the tumor microenvironment. To address this, we developed an HNC MPS that mimics patient-specific tumor microenvironments using primary cells from patient tumors embedded in a 3D matrix with vascular components. This model was used to evaluate individualized responses to radiation and chemotherapy through cell-scale readouts, including DNA damage, proliferation, and migration. Methods: The HNC MPS comprises a microscale chamber containing two removable rods. A collagen-fibronectin matrix incorporating patient-derived tumor spheroids, fibroblasts, and immune cells was cast in the chamber. The matrix polymerized around the removable rods, which were subsequently extracted to create molded luminal structures. These lumens were lined with vascular and lymphatic endothelial cells to recreate a vascularized tumor microenvironment. An optimized media formulation supported the growth of all cell types within the MPS. The model was treated with radiation, cisplatin, or both to simulate the current standard of care. Cellular responses, including viability, proliferation, migration, and DNA damage, were assessed using immunofluorescence and cytokine secretion. A custom image processing pipeline analyzed multiple orthogonal readouts to reveal treatment responses at the cellular level with metrics to compare to actual patient outcomes under development. The model was further validated by comparing it with tumor tissue using single-cell RNA sequencing (scRNA-seq). Experiments were conducted with samples from multiple patients. Results: We successfully developed a patient-specific model of the HNC microenvironment using primary cells isolated from patient tumor tissue. This model captured key patient-specific features, such as angiogenesis and cell migration, and provided insights into treatment responses across different modalities. Cellular responses, such as proliferation and migration, were quantified, and scRNA-seq demonstrated close concordance between the MPS and patient tumor tissue. Our model presents a valuable functional assay for predicting patient-specific responses to therapy and validating biomarkers for treatment stratification. Conclusion: The HNC MPS is a robust in vitro platform that recapitulates patient-specific tumor microenvironments and treatment responses. It offers a promising approach for personalized cancer therapy, enabling functional assays to guide clinical decision-making and improve treatment outcomes for patients with HNC. Citation Format: Adeel Ahmed, Nathan W Hendrikse, Marcos A Lares, Fauzan Ahmed, Adam R Burr, Paul M Harari, David J Beebe, Sheena C Kerr. Patient-specific, organotypic head and neck cancer model for personalized medicine [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Functional and Genomic Precision Medicine in Cancer: Different Perspectives, Common Goals; 2025 Mar 11-13; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(5 Suppl):Abstract nr B023.

Intravacuolar persistence in neutrophils facilitates Listeria monocytogenes spread to co-cultured cells.

Listeria monocytogenes (Lm) is a significant foodborne pathogen responsible for high hospitalization rates in humans, especially vulnerable groups such as the elderly, pregnant women, and immunocompromised individuals. In animals like ruminants, Lm infection leads to severe disease manifestations, notably brainstem encephalitis. This study uncovers a novel mechanism by which bovine neutrophils (PMNs) harbor Lm in a viable but non-culturable (VBNC) state, enabling the bacteria to hide in the host. PMNs, traditionally viewed as bacteria killers, may serve as Trojan horses, allowing Lm to persist and spread within the host. This discovery has broad implications for understanding Lm's persistence, its role in recurrent infections, and the development of new therapeutic strategies targeting VBNC forms of Lm to improve treatment outcomes and disease control.

Effects of a strength physical exercise program in chronic lymphocytic leukemia patients on quality of life, mental health, and frailty: a randomized controlled trial study protocol

BackgroundChronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow, and it is the most prevalent form of leukemia in adults. Many patients experience symptoms that can significantly impact their quality of life, particularly in terms of physical ability, emotional health, and fatigue. Therapeutic exercise has shown to be an effective intervention for alleviating both physical and psychological symptoms in these patients. Specifically, strength training may help address some common treatment side effects.ObjectiveThis study aims to evaluate the effects of a therapeutic exercise program, focused on frailty in patients with CLL, along with secondary objectives including impacts on functional capacity, quality of life, psychological status, sleep quality, body composition, anthropometric variables, lipid profile and on proteins related to the immune system and inflammation.MethodsAn open label, randomized controlled trial will be carried out with 36 participants, divided into an intervention group (supervised resistance training twice a week and home exercises) and a control group (home exercise only). The primary outcome measure is fraility, assessed using Short Physical Performance Battery (SPPB). Secondary outcomes include assessments using HADS, FACT-F, EORTC QLQ-C30, EORT QLQ-CLL17.Results and conclusionsThis study will explore how physical exercise can improve quality of life and various health metrics in patients with CLL. By creating customized exercise protocols, the research seeks to boost patient well-being, improve treatment outcomes, and lessen debilitating side effects, ultimately promoting the integration of physical activity into routine care.Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT06654206).

Peptic Ulcer Disease

Although the incidence and complications of peptic ulcer disease have declined, <i>Helicobacter pylori</i> infection and nonsteroidal anti-inflammatory drug use remain key risk factors. Advances in proton pump inhibitors and potassium-competitive acid blockers have improved treatment outcomes. However, increasing antibiotic resistance has reduced the efficacy of the standard therapies for <i>H. pylori</i> eradication, necessitating the development of new approaches such as novel antibiotic combinations and bismuth-based regimens. Future studies should emphasize tailored strategies to address resistance and the development of innovative anti-ulcer therapies to enhance eradication and prevention efforts.