Improve Treatment Outcomes Research Articles

Combining ultrasound technology with targeted fucoidan/arginine-gelatin nanoparticles loaded with doxorubicin to enhance therapeutic efficacy and modulate bioeffects in drug-resistant triple-negative breast cancer.

Triple-negative breast cancer (TNBC) presents formidable challenges due to its aggressive nature and high recurrence rates, compounded by the involvement of epithelial-mesenchymal transition (EMT) in its progression and metastasis. Standard chemotherapy, which typically employs doxorubicin (DOX), remains a primary treatment approach. However, multidrug resistance (MDR) mechanisms, which include ATP-binding cassette transporters and EMT, contribute to treatment failures. Ultrasound has emerged as a promising modality among the various strategies explored to address MDR in TNBC. It serves as a diagnostic tool and holds therapeutic potential by inducing various biological effects depending on the exposure level. Targeted nanoparticles offer a means to enhance drug delivery efficiency. Our study aims to advance ultrasound technology combined with biocompatible nanoparticles using simplified preparation methods to improve treatment outcomes for drug-resistant TNBC. In particular, employing DOX-loaded fucoidan/arginine-gelatin nanoparticles facilitated the targeted delivery of chemotherapy drugs to tumors by effectively interacting with P-selectin, resulting in tumor growth inhibition. Furthermore, these nanoparticles mitigated MDR and EMT, particularly when combined with ultrasound treatment. This integrated approach of nanoparticle delivery with ultrasonography opens up a promising and innovative avenue for clinical cancer research.

Effectiveness of a Novel Web-Based Intervention to Enhance Therapeutic Relationships and Treatment Outcomes in Adult Individual Psychotherapy: Randomized Controlled Trial and Analysis of Predictors of Dropouts.

Routine process and outcome monitoring interventions added to psychotherapy are known to improve treatment outcomes, although they vary in format and effectiveness. This study aimed to evaluate whether a therapist-independent, internet-based routine process monitoring and feedback system could significantly reduce psychological distress and enhance the quality of the therapeutic relationship compared with a treatment-as-usual control group among individuals already engaged in individual psychotherapy. We randomized 475 participants into either the intervention group, which received access to an internet-based routine process monitoring and feedback system in addition to psychotherapy, or the control group, which received only psychotherapy. The trial lasted for 10 weeks. Follow-up assessments at 5 weeks and 10 weeks used the Clinical Outcomes in Routine Evaluation-Outcome Measure as the primary outcome, with the Working Alliance Inventory-Short Revised and the Real Relationship Inventory-Client form as secondary outcomes. Per-protocol analyses (n=166) showed that psychological distress decreased in both groups, but there was no significant advantage for the intervention group. The intervention group experienced a decline in the genuineness dimension score of the real relationship, with an effect size of d=-0.27, compared with d=0.01 in the control group. In the intervention group (but not in the control group), dropouts showed significantly lower real relationship levels (P=.002), working alliance quality (P=.051), and emotional disclosure (P=.01) compared with those who completed the study. Additionally, logistic regression revealed distinct predictors of dropout within the control group and intervention group. The findings do not provide conclusive evidence for the efficacy of the new internet-based intervention in enhancing self-monitoring and prompting reflection on patients' emotional responses to their therapists. However, the intervention appears to influence patients' perceptions of the genuineness dimension in the therapeutic relationship, warranting further investigation. We hypothesize that this alteration in the genuineness dimension could be attributed to the intervention facilitating a more realistic and accurate perception of the therapeutic relationship among participants. ClinicalTrials.gov NCT06038747; https://clinicaltrials.gov/study/NCT06038747. RR2-10.2196/55369.

Therapeutic drug monitoring for antimicrobial agents for people living with HIV (TAP)

Background Antimicrobial resistance (AMR) is a growing health concern, particularly in Africa, and is predicted to be the leading cause of death after cancer by 2050. Factors like overuse or inappropriate use of antibiotics, contribute to this crisis. People living with HIV (PLWH) are particularly vulnerable to AMR with potential drug-drug interactions between antiretroviral and antimicrobial agents against common organisms like Mycobacterium tuberculosis. There is limited data on the concentrations of commonly used antimicrobial agents in people living with HIV in resource-limited settings. Therapeutic Drug Monitoring (TDM) offers a promising approach to optimize antibiotic dosing and improve treatment outcomes for those with sub-optimal drug concentrations. TDM has been recommended for PLWH on anti-tuberculosis treatment due to sub-optimal drug concentrations found in a significant proportion of those with TB. Objectives The main objectives of this study are to determine the concentrations of selected antimicrobial agents in people living with HIV requiring antimicrobial therapy and to assess the utility of therapeutic drug monitoring in achieving therapeutic targets for PLWH receiving rifampicin and isoniazid for the treatment of tuberculosis Methods This prospective observational study will enroll adult PLWH receiving amoxicillin, azithromycin, ciprofloxacin, rifampicin, isoniazid, or ceftriaxone. Concentrations of these antibiotics will be measured locally using validated liquid chromatography mass spectrometry methods and high-performance liquid chromatography with ultraviolet detection. TDM with dose adjustment will be performed in a subset of participants on TB treatment. Pharmacokinetic parameters will be estimated using non-linear mixed effects models. Results This study was reviewed and approved by the research and ethics committee in February 2024. Enrolment is projected to begin by August 2024. Conclusions We anticipate that the findings from this research will characterize pharmacokinetic and pharmacodynamics relationships to predict treatment response for optimal antimicrobial therapeutic and anti-tuberculosis dosing among people living with HIV (PLWH). Clinical registration The study is registered with Pan African Clinical Trials Registry, registration number PACTR202409710100607, registration date 07 August 2024, pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=31764

Educational video assistance in shared decision-making for psoriasis: Effectiveness and outcomes.

Psoriasis is a chronic inflammatory skin condition associated with significant comorbidities that impact quality of life. Effective patient engagement through shared decision-making (SDM) is crucial for optimal management. This study aimed to evaluate the effectiveness of adding clinician-created educational videos in enhancing patient knowledge and engagement during SDM for psoriasis treatment. Forty-eight patients with moderate to severe psoriasis participated in this single-center study. After reading an educational pamphlet, patients took a knowledge assessment test. Subsequently, they watched an educational video and completed a second test using the same questions. Feedback questionnaires on the video and the SDM process were also administered. Paired t tests revealed that postpamphlet plus video test scores (mean ± SD: 86.25 ± 17.58) were significantly higher than postpamphlet scores (72.08 ± 26.33, p < 0.0001). Older patients, in particular, showed greater improvement in comprehension after watching the video. Descriptive analysis of the feedback questionnaire on the video indicated strong agreement (average score: 4.240 ± 0.816 on a five-point Likert scale) regarding its greater effectiveness compared with the pamphlet in aiding SDM. Patients also rated the video-assisted SDM process positively (average score: 4.521 ± 0.5443 on a five-point Likert scale), highlighting increased trust and improved communication with healthcare providers. These findings underscore the value of video-assisted SDM in patient education and decision-making processes, potentially improving treatment outcomes and patient satisfaction in dermatologic care.

Decision support systems in the diagnosis of urological diseases

The need to process large amounts of data has led to the creation of software that can improve and facilitate the work of medical staff. Decision support systems (DSS) are now used in many branches of medicine both at the outpatient and inpatient stages of medical care, helping clinicians to choose the tactics of treatment and management of each individual patient. These systems to a certain extent can improve treatment results and diagnostic process. The introduction of DSS in clinical practice has shown many advantages in reducing the frequency of misdiagnosis and, consequently, the risk of medical errors. At the same time, DSS can have a number of disadvantages. For example, physicians may view them as a threat to their “clinical autonomy”, and the implementation and subsequent maintenance of DSS can be quite costly. Artificial intelligence, which is increasingly being used not only for diagnosis, but also for treatment and prediction of outcomes in various diseases, should be considered as a prerequisite for the creation of DSS. Active development of artificial intelligence has been noted in almost all branches of medicine. A non-systematic review of the available literature published in the period between 2012 and 2022 has shown that the application of AI in prostate cancer diagnosis has great potential in clinical practice, as it helps both in the choice of treatment method and in planning the course of further surgery.

More rTMS pulses or more sessions? The impact on treatment outcome for treatment resistant depression.

Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment-resistant depression (TRD). Optimal rTMS parameters remain unclear, especially whether number of sessions or amount of pulses contribute more to treatment outcome. We hypothesize that treatment outcome depends on the number of sessions rather than on the amount of pulses. We searched databases for randomized clinical trials (RCTs) on high-frequent (HF) or low-frequent (LF)-rTMS targeting the left or right DLPFC for TRD. Treatment efficacy was measured using standardized mean difference (SMD), calculated from pre- and post-treatment depression scores. Meta-regressions were used to explore linear associations between SMD and rTMS pulses, pulses/session and sessions for HF and LF-rTMS, separately for active and sham-rTMS. If these variables showed no linear association with SMD, we divided the data into quartiles and explored subgroup SMDs. Eighty-seven RCTs were included: 67 studied HF-rTMS, eleven studied LF-rTMS, and nine studied both. No linear association was found between SMD and amount of pulses or pulses/session for HF and LF-rTMS. Subgroup analyses showed the largest SMDs for 1200-1500 HF-pulses/session and 360-450 LF-pulses/session. The number of sessions was significantly associated with SMD for active HF (β = 0.09, p < 0.05) and LF-rTMS (β = 0.06, p < 0.01). Thirty was the maximal number of sessions, in the included RCTs. More rTMS sessions, but not more pulses, were associated with improved treatment outcome, in both HF and LF-rTMS. Our findings suggest that 1200-1500 HF-pulses/session and 360-450 LF-pulses/session are already sufficient, and that a treatment course should consist of least 30 sessions for higher chance of response.

Surgical treatment of patients with varicose veins of the lower extremities from the origins to the present day

Varicose vein disease of the lower extremities is a common problem today. In various countries, approximately 25–30% of women and 10–15% of men sufferfrom this condition. Surgical methods hold a special place in the treatment of such patients. Currently, despite the development of effective minimally invasive endovenous techniques, doctors still face recurrences of the disease due to insufficiency of radical surgery, as well as the natural progression of varicose vein disease as genetically determined, which necessitates further exploration for solutions to improve treatment outcomes. The article describes the history of the development of surgical methods, including the first mentions of this disease, vessel ligation, phlebectomy, minimally invasive techniques, and others.

Large B Cell Lymphoma as A Rare Cause of Gastrointestinal Bleeding and Melena in An Elderly Patient: A Case Report

Large B-cell lymphoma is a rare form of non-Hodgkin lymphoma that can affect the gastrointestinal (GI) tract and poses diagnostic challenges owing to its non-specific symptoms. This study reports the case of a 70-year-old male with a history of cardiovascular disease who presented with melena and vague abdominal pain, initially regarded as emerging from common GI disorders. Endoscopic findings revealed large gastric ulcers with suspicious features, and biopsy confirmed the diagnosis of large B-cell lymphoma. Imaging showed metastasis, complicating the patient’s condition. Managing this case required careful balancing of antiplatelet therapy for his cardiovascular disease with the pressing need to control GI bleeding. The patient benefited from a multidisciplinary approach involving gastroenterology, cardiology, and oncology teams. This case shows the importance of early endoscopic evaluation and biopsy in elderly patients with persistent GI symptoms, as early diagnosis of rare conditions like gastric lymphoma can significantly improve treatment outcomes.

Exosomal ncRNAs in reproductive cancers.

Extracellular vesicles, particularly exosomes, play a pivotal role in the cellular mechanisms underlying cancer. This review explores the various functions of exosomes in the progression, growth, and metastasis of cancers affecting the male and female reproductive systems. Exosomes are identified as key mediators in intercellular communication, capable of transferring bioactive molecules such as miRNAs, proteins, and other nucleic acids that influence cancer cell behavior and tumor microenvironment interactions. It has been shown that nc-RNAs transported by exosomes play an important role in tumor growth processes. Significant molecules that may serve as biomarkers in the development and progression of male reproductive cancers include miR-125a-5p, miR-21, miR-375, the miR-371 ~ 373 cluster, and miR-145-5p. For female reproductive cancers, significant miRNAs include miR-26a-5p, miR-148b, miR-205, and miRNA-423-3p. This review highlights the potential of these ncRNAs as biomarkers and prognostics in tumor diagnostics. Understanding the diverse roles of exosomes may hold promise for developing new therapeutic strategies and improving treatment outcomes for cancer patients.

Renal remodeling by CXCL10-CXCR3 axis-recruited mesenchymal stem cells and subsequent IL4I1 secretion in lupus nephritis

Human umbilical cord mesenchymal stem cells (hUC-MSCs) have shown potential as a therapeutic option for lupus nephritis (LN), particularly in patients refractory to conventional treatments. Despite extensive translational research on MSCs, the precise mechanisms by which MSCs migrate to the kidney and restore renal function remain incompletely understood. Here, we aim to clarify the spatiotemporal characteristics of hUC-MSC migration into LN kidneys and their interactions with host cells in microenvironment. This study elucidates that the migration of hUC-MSCs to the LN kidney is driven by elevated levels of CXCL10, predominantly produced by glomerular vascular endothelial cells through the IFN-γ/IRF1-KPNA4 pathway. Interestingly, the blockade of CXCL10-CXCR3 axis impedes the migration of hUC-MSCs to LN kidney and negatively impacts therapeutic outcomes. Single cell-RNA sequencing analysis underscores the importance of this axis in mediating the regulatory effects of hUC-MSCs on the renal immune environment. Furthermore, hUC-MSCs have been observed to induce and secrete interleukin 4 inducible gene 1 (IL4I1) in response to the microenvironment of LN kidney, thereby suppressing Th1 cells. Genetically ablating IL4I1 in hUC-MSCs abolishes their therapeutic effects and prevents the inhibition of CXCR3+ Th1 cell infiltration into LN kidneys. This study provides valuable insights into the significant involvement of CXCL10-CXCR3 axis in hUC-MSC migration to the LN kidneys and the subsequent remodeling of renal immune microenvironment. Regulating the CXCL10-CXCR3 axis and IL4I1 secretion may be developed as a novel therapeutic strategy to improve treatment outcomes of LN.

One Acne™: a holistic management approach to improve overall skin quality and treatment outcomes in acne with or without sensitive skin

AbstractAcne and sensitive skin can take a profound toll on patients' well‐being, which can be exacerbated if the conditions are experienced together. This narrative review aims to identify appropriate treatments to facilitate a holistic management approach to acne (One Acne™), sensitive skin, and acne‐induced sequelae and describe the role of treatments in improving skin quality. Topical retinoids are considered the preferred first‐line option for acne treatment by dermatologists, either as monotherapy or in combination with other treatments, because of their ability to target various aspects of the disease. Tretinoin, trifarotene, adapalene, and tazarotene have all been assessed in clinical studies for managing acne‐associated scarring, with varying success, with the latter three reported to improve skin quality. Moreover, some corrective procedures, e.g., injectable non‐animal stabilized hyaluronic acid (NASHA) fillers, have proven effective for treating acne scarring. Both treatment types may complement each other to provide optimal treatment outcomes and patient satisfaction, as observed in several patients receiving concomitant treatment with NASHA fillers/topical trifarotene. Adjunctive use of cleansers, moisturizers, and photoprotection‐containing ingredients such as vitamin B3, glycerin, or pro‐vitamin B3 may also complement drug/corrective treatments to reduce skin irritation and risk of scarring, as well as improve skin hydration, tone, and overall appearance. This narrative review highlights that comprehensive skincare regimens should be used throughout acne patients' journeys to reduce treatment‐related irritation, improve treatment outcomes, adherence, and satisfaction, and enhance overall skin quality. Patients with sensitive skin should choose tailored skincare products to maintain skin barrier integrity and restore skin function.

Abstract C005: Tumor vaccines and oncolytic virotherapy: systemic immunity vs. tumor microenvironment

Abstract Tumor vaccines, particularly the innovative mRNA variants, hold immense promise in cancer immunotherapy. Despite their potential, these vaccines encounter formidable challenges in surmounting immune tolerance, the immune-suppressive tumor microenvironment (TME) and more importantly, the resistance developed in cancer cells that are antigen negative. Concurrently, oncolytic virotherapy (OV), a distinct facet of tumor vaccination, significantly alters the TME and releases tumor antigens via lysis to generate a broader spectrum of tumor antigens. This unique property positions OV to induce anti-tumor immunity, as evidenced by prolonged overall survival and abscopal tumor suppression. Recognizing the complementary strengths of mRNA tumor vaccines and OV, we propose a combined approach to address the limitations inherent in each modality. Our study tested this hypothesis by combining a mRNA vaccine targeting HER2 with oncolytic viruses, utilizing a prime-boost strategy on a HER2-expressing CT26 mouse tumor model. Notably, while the mRNA vaccine alone induced specific anti-HER2 systemic immunity, the combination demonstrated a potent immune response against both anti-HER2 and anti-CT26, leading to durable tumor eradication. Our findings highlight that peripheral vaccination has the potential to elicit an immune response in non-immune suppressive environments. However, combining it with virotherapy not only amplifies specific immunity but also induces a broader immune response against a spectrum of tumor antigens. This synergistic combination represents a promising avenue for advancing cancer immunotherapy, offering the potential for improved treatment outcomes and broader applicability of tumor vaccines across diverse cancer types. Citation Format: William Jia. Tumor vaccines and oncolytic virotherapy: systemic immunity vs. tumor microenvironment [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C005.

A review of retinoblastoma on its discovery, genetic aspects, and treatments

Abstract. Retinoblastoma, a critical early-childhood retinal cancer, poses significant challenges and opportunities for oncological research. This paper provides a comprehensive examination of Retinoblastoma, from its historical context and genetic underpinnings to contemporary diagnostic and therapeutic strategies. It delves into the pivotal role of the RB1 gene in the diseases hereditary and sporadic forms, underscoring the importance of genetic mutations and the potential of molecular genetics in advancing patient care. Through an analysis of current findings and treatment approaches, this study highlights the ongoing evolution in managing Retinoblastoma, emphasizing early detection, the exploration of genetic landscapes, and the development of targeted therapies. Future research directions are proposed, aiming at refining diagnostic accuracy and improving treatment outcomes, thereby offering hope for affected children and their families.

Conservative therapy for lumbar disc herniation

Herniated discs are acommon cause of neurological symptoms that often lead to reduced quality of life. They affect around 20% of 45-56-year olds and, therefore, represent acorrespondingly major challenge for healthcare. Conservative therapy methods are usually used as the first treatment option; surgical interventions should only be considered in special symptom constellations. This study aims to evaluate the effectiveness of conservative therapy methods in the treatment of lumbar disc herniation and to demonstrate their influence on pain reduction and functional improvement. The current valid AWMF guideline was analyzed, and asystematic literature search was conducted to identify relevant information on the conservative treatment of herniated discs. The therapeutic approaches analyzed included physiotherapy, drug treatment, manual therapy and injection therapies. Inclusion criteria covered reviews and meta-analyses from 2019 to 2024. The analysis showed that conservative treatment methods led to asignificant reduction in pain and improvement in functional abilities in the majority of patients. Not all frequently clinical used forms of therapy have been well proven. The results of this study underline the importance of conservative treatment methods as an effective treatment option for herniated discs. In particular, the combination of different treatment approaches can improve treatment outcomes. However, further long-term studies are needed to determine the long-term effects and optimal treatment protocols.

Improved DeTraC Binary Coyote Net-Based Multiple Instance Learning for Predicting Lymph Node Metastasis of Breast Cancer From Whole-Slide Pathological Images.

Early detection of lymph node metastasis in breast cancer is vital for improving treatment outcomes and prognosis. This study introduces an Improved Decompose, Transfer, and Compose Binary Coyote Net-based Multiple Instance Learning (ImDeTraC-BCNet-MIL) method for predicting lymph node metastasis from Whole Slide Images (WSIs) using multiple instance learning. The method involves segmenting WSIs into patches using Otsu and double-dimensional clustering techniques. The developed multiple instance learning approach introduces a paradigm into computational pathology by shaping pathological data and constructing features. ImDeTraC-BCNet-MIL was utilised for feature generation during both training and testing to differentiate lymph node metastasis in WSIs. The proposed model achieves the highest accuracy of 95.3% and 99.8%, precision values of 98% and 99.8%, and recall rates of 92.9% and 99.8% on the Camelyon16 and Camelyon17 datasets. These findings underscore the effectiveness of ImDeTraC-BCNet-MIL in enhancing the early detection of lymph node metastasis in breast cancer.

A machine learning approach to unravel client and program-specific effects in opioid treatment retention

This study examines the impact of workforce diversity, particularly the presence of Black/African American staff, on client retention in opioid use disorder (OUD) treatment, recognizing the historically low retention rates among Black and Hispanic populations in such programs. Using a novel machine learning technique called &amp;ldquo;causal forest,&amp;rdquo; we explored the heterogeneous treatment effects of staff diversity on client retention, aiming to identify strategies that enhance client retention and improve treatment outcomes. Analyzing data from four waves of the National Drug Abuse Treatment System Survey spanning the years 2000, 2005, 2014, and 2017 (n = 627), we focus on the relationship between workforce diversity and retention. The findings revealed diversity-related variations in retention across 61 out of 627 OUD treatment programs (&lt;10%), with potential beneficial effects attenuated by other program characteristics. These characteristics include programs that are more likely to be private-for-profit, have lower percentages of Black and Latino clients, lower staff-to-client ratios, higher proportions of staff with graduate degrees, and lower percentages of unemployed clients. Our results suggest that workforce diversity alone is insufficient for improving retention. Programs with characteristics linked to greater retention are better positioned to leverage a diverse workforce to enhance retention, offering important implications for policy and program design to better support Black clients with OUDs.

A decision support system to increase the compliance of diagnostic imaging examinations with imaging guidelines: focused on cerebrovascular diseases.

Diagnostic imaging decision support (DI-DS) system has emerged as an innovative evidence-based solution to decrease inappropriate diagnostic imaging. The aim of the present study was to design and evaluate a DI-DS system for cerebrovascular diseases. The present study was an applied piece of research. First, the conceptual model of the DI-DS system was designed based on its functional and non-functional requirements. Afterwards, to create the system's knowledge base, cerebrovascular diseases diagnostic imaging algorithms were extracted from the American College of Radiology Appropriateness Criteria (ACR-AC). Subsequently, the system was developed based on the obtained conceptual model and the extracted algorithms. The software was programmed by means of the C#. After debugging the system, it was evaluated regarding its performance and also the users' satisfaction with it. Assessing the users' satisfaction with the system demonstrated that all the evaluation criteria met the acceptable threshold (85 %). The retrospective evaluation of the system's performance indicated that from among 76 imaging examinations, which had previously been performed for 30 patients, 12 (15.78 %) were deemed inappropriate. And, the system accurately identified all the inappropriate physicians' decisions. The concurrent evaluation of the system's performance indicated that the system's recommendations helped the physicians remove 100 % (4 out of 4) of the inappropriate and 40 % (2 out of 5) of the inconclusive imaging examinations from their initial choices. A DI-DS system could increase the compliance of the physicians' decisions with diagnostic imaging guidelines, and also improve treatment outcomes through correct diagnosis and providing timely care.

A novel mouse model recapitulating the MMR-defective SCLC subtype uncovers an actionable sensitivity to immune checkpoint blockade

PurposeSmall cell lung cancer (SCLC) has an extremely poor prognosis. Despite high initial response rates to chemotherapy and modest survival improvements with the addition of immune checkpoint inhibitors (ICI), almost all patients experience relapse and fatal outcomes. Recent genomic insights uncovered extensive molecular heterogeneity in addition to the almost uniform loss of RB1 and TRP53. Additionally, defective DNA mismatch repair (MMR) has recently been described in some SCLC cases. Here, we generated a novel SCLC mouse model capturing MMR deficiency and assessed immunotherapy responses.MethodsWe developed an MMR-deficient genetically engineered mouse model (GEMM) of SCLC by introducing a conditional Msh2 gene, crucial for maintaining MMR integrity, into the standard Rb1fl/fl;Trp53fl/fl (RP) model. Genomic characteristics and preclinical therapy responses were evaluated by focusing on overall survival and whole exome sequencing (WES) analyses.ResultsMMR-defective SCLC tumors (Rb1fl/fl;Trp53fl/fl;Msh2fl/fl (RPM)) developed later than tumors in MMR-proficient mice. However, the time from tumor manifestation to death of the affected animals was substantially shortened (median survival 55 days in RP vs. 46.5 days in RPM), indicating increased aggressiveness of MMR-defective tumors. RPM tumors exhibited MMR deficiency, high tumor mutational burden (TMB), and an elevated load of candidate neoantigens, compared to RP lesions (p = 0.0106), suggesting increased immunogenicity. Importantly, the overall survival of RPM animals was significantly improved when exposed to ICI.ConclusionWe propose a novel RPM mouse model as a suitable system to mimic MMR-defective SCLC and tumors with high TMB. We provide in vivo evidence that Msh2 deficiency enhances ICI sensitivity. These findings could contribute to stratifying SCLC patients to immunotherapy, thereby improving treatment outcomes.

The California collaborative network to promote data driven care and improve outcomes in early psychosis (EPI-CAL) project: rationale, background, design and methodology

BackgroundA prolonged first episode of psychosis (FEP) without adequate treatment is a predictor of poor clinical, functional, and health outcomes and significant economic burden. Team-based “coordinated specialty care” (CSC) for early psychosis (EP) has established effectiveness in promoting clinical and functional recovery. However, California’s CSC program implementation has been unsystematic and could benefit from standardizing its processes and data collection infrastructure. To address this, we established a consortium of EP clinics across the state via a Learning Health Care Network (LHCN) framework to develop the Early Psychosis Intervention Network of California (EPI-CAL). EPI-CAL’s LHCN developed a core battery of evidence-based measures for service users and family members and linked them together using a unique data collection and visualization application, Beehive.Methods and objectivesEPI-CAL’s LHCN collects, visualizes, and aggregates data at the individual and clinic level for EP programs across California via Beehive. Beehive was designed to: (1) collect outcomes data from service users receiving care at EP programs and their support persons, (2) provide the data to providers on a secure web-based dashboard to support measurement-based care, and (3) allow data to be used for program or research analysis. We will (1) determine the feasibility of implementing an LHCN across a diverse, decentralized network of early psychosis programs, (2) determine if the implementation of an LHCN increases the delivery of measurement-based care, and (3) determine if the implementation of measurement-based care is associated with significant improvements in key service user outcomes. EPI-CAL’s network will contribute data to the Early Psychosis Intervention Network (EPINET) program.DiscussionThe current study aims to establish an LHCN of EP clinics in California that implements harmonized data collection using Beehive and assesses the feasibility of establishing such a network. Our goal is for this harmonized data collection approach to be used to inform decisions and develop learning opportunities for service users, staff, and administrators, and to improve outcomes for service users and their supporters in CSC care. Further, the data will enable programs and research teams to examine what elements of care lead to program success and improved treatment outcomes for service users.Clinical trials registrationwww.ClinicalTrials.gov, identifier NCT04007510; registered 07/05/2019.

Unveiling A Rare Case of Labial Sarcomatoid Carcinoma

Sarcomatoid carcinoma is a rare and highly malignant tumor characterized by a dual histological differentiation with both epithelial and mesenchymal components, constituting less than 1% of all head and neck carcinomas and predominantly affecting males in their fifth to seventh decades of life. We present the case of a 60-year-old man with a six-year history of poorly managed left hemiplegia, who developed a large, aggressive, and bleeding mass in the left upper lip that extended to the maxilla and palate, accompanied by bone destruction and confirmed lymph node metastasis through biopsy. Due to the advanced stage of the disease and delayed consultation, surgical excision was not feasible, leading to a reliance on palliative treatment. This case highlights the diagnostic challenges of sarcomatoid carcinoma, often associated with delayed recognition, poor prognosis, and high mortality rates due to local and distant recurrences. Increased awareness and early diagnosis are critical for improving treatment outcomes. Further research is needed to establish standardized management protocols for this aggressive tumor.