Poor Treatment Research Articles

Naturalistic outcomes of patients discharged from a community treatment order: QA project.

To study outcomes for patients after they are discharged from Community treatment orders (CTO) including rate of relapse, median time to relapse and to identify the risk factors associated with relapse. The study population included patients discharged from CTO from July 2017 to December 2021, managed by a major metropolitan* case management team (CMT). The data were collected from electronic medical records (EMR). Descriptive analysis was conducted to study the sample characteristics. Logistic regression using univariate and multivariate analysis was performed to examine the associations between factors related to relapse. A total of 128 patients were studied. The relapse rate was 27.4% with median time to relapse of 72 days. Poor insight, poor treatment compliance, duration of CTO and number of CMT contacts were significantly associated with relapse while substance use, psychiatric comorbidities and psychosocial factors were not. The findings suggest that people who relapsed had poor insight and poor medication adherence, had CTO for a longer period and had frequent contact from CMT even after discharge from CTO.

Application effect of case management nursing based on patient safety in patients with prostate cancer.

Globally, prostate cancer has become a major threat to men's health, with an increasing incidence and causes serious effects on the quality and length of life of patients. Despite the rapid development of medical technology, which provides treatments, including surgery, radiotherapy, and endocrine therapy, the treatment of patients with prostate cancer, especially with endocrine therapy, has become a major challenge in clinical treatment owing to the lengthy course of treatment, side effects of drugs, and impact of the disease on the psychological and physiological functioning of the patient, producing poor treatment adherence and a decline in quality of life. To explore effects of nursing intervention prioritizing patient safety and case management in patients with prostate cancer undergoing endocrine therapy. Eighty patients with prostate cancer who received endocrine therapy at our hospital between January 2022 and January 2024 were divided into observation and control groups with 40 cases per group. The control group was treated using a routine nursing workflow while the observation group received case management nursing guidance prioritizing patient safety. Scores for anxiety and depression, prostate cancer symptoms, and quality of life and patient compliance and satisfaction were compared between the groups after three months of intervention. After the nursing intervention, the anxiety and depression scores of the observation group were significantly lower than those of the control group (P < 0.05). The quality of life score, sexual function, and hormone function were significantly higher than those in the control group (P < 0.05). Case management guidance based on patient safety effectively reduced anxiety and depression in patients undergoing endocrine therapy for prostate cancer and improved their quality of life, treatment compliance, and satisfaction.

Health service utilization, substance use treatment response, and death in patients with opioid use disorder and comorbid hepatitis C findings from prospective cohort study with administrative database linkage

BackgroundAmong patients with opioid use disorder (OUD), high rates of overdose and death have been reported in subgroups with Hepatitis C Virus (HCV). Evidence on the comorbid effect of HCV on clinical and substance use trajectories has been limited by small sample sizes, short follow-up, and heavy reliance on administrative data which lacks granularity on important prognostic factors. Additionally, few studies include populations on substance use treatment. AimTo establish the impact of HCV exposure (antibody positivity) on health care utilization patterns, substance use treatment response, and death in a cohort of patients with OUD on opioid agonist therapy (OAT). MethodsThis multi-center prospective cohort study recruited adult patients with OUD on OAT from 57 substance use treatment centers in Ontario, Canada. The study collected substance use outcomes, and classified patients with ≥50 % positive opioid urine screens over one year of follow-up as having poor treatment response. Additional data obtained via linkage with ICES administrative databases evaluated the relationship between HCV status, healthcare service utilization, and death over 3 years of follow-up. Multiple logistic regression models established the adjusted impact of HCV on various outcomes. ResultsAmong recruited participants (n = 3430), 44.10 % were female with a mean age of 38.64 years (Standard deviation: 10.96). HCV was prevalent in 10.6 % of the cohort (n = 365). Methadone was used most often (83.9 %, n = 2876), followed by sublingual buprenorphine (16.2 %, n = 554). Over the three-year follow-up, 5.3 % of patients died (n = 181). Unadjusted results reveal rates of hospitalization (all-cause, mental-health related, critical care) and emergency department visits (mental health-related), were significantly higher among HCV patients. Associations diminished in adjusted models. Active injection drug use exhibited the highest predictive risk for all outcomes. ConclusionA high degree of acute physical and mental illness and its resulting health service utilization burden is concentrated among patients with OUD and comorbid HCV. Future research should explore the role for targeted interventions and how best to implement integrated healthcare models to better address the complex health needs of HCV populations who inject drugs.

ATH434, a promising iron-targeting compound for treating iron regulation disorders.

Cytotoxic accumulation of loosely bound mitochondrial Fe2+ is a hallmark of Friedreich's Ataxia (FA), a rare and fatal neuromuscular disorder with limited therapeutic options. There are no clinically approved medications targeting excess Fe2+ associated with FA or the neurological disorders Parkinson's disease and Multiple System Atrophy. Traditional iron-chelating drugs clinically approved for systemic iron overload that target ferritin-stored Fe3+ for urinary excretion demonstrated limited efficacy in FA and exacerbated ataxia. Poor treatment outcomes reflect inadequate binding to excess toxic Fe2+ or exceptionally high affinities (i.e. ≤10-31) for non-pathologic Fe3+ that disrupts intrinsic iron homeostasis. To understand previous treatment failures and identify beneficial factors for Fe2+-targeted therapeutics, we compared traditional Fe3+ chelators deferiprone (DFP) and deferasirox (DFX) with additional iron-binding compounds including ATH434, DMOG, and IOX3. ATH434 and DFX had moderate Fe2+ binding affinities (Kd's of 1-4 µM), similar to endogenous iron chaperones, while the remaining had weaker divalent metal interactions. These compounds had low/moderate affinities for Fe3+(0.46-9.59µM) relative to DFX and DFP. While all compounds coordinated iron using molecular oxygen and/or nitrogen ligands, thermodynamic analyses suggest ATH434 completes Fe2+ coordination using H2O. ATH434 significantly stabilized bound Fe2+ from ligand-induced autooxidation, reducing reactive oxygen species (ROS) production, whereas DFP and DFX promoted production. The comparable affinity of ATH434 for Fe2+ and Fe3+ position it to sequester excess Fe2+ and facilitate drug-to-protein iron metal exchange, mimicking natural endogenous iron binding proteins, at a reduced risk of autooxidation-induced ROS generation or perturbation of cellular iron stores.

Evaluating the Effects of Decentralized District-Based Treatment of Drug-Resistant Tuberculosis in Pakistan: An Alternative Model of Care

Background: Pakistan faces a high burden of drug-resistant tuberculosis (DR-TB), with traditional centralized care resulting in delays and poor treatment outcomes. Decentralizing care to district-level hospitals offers a potentially more effective alternative.Objective: This study aimed to evaluate the impact of decentralized DR-TB care on treatment initiation time, patient follow-up, and treatment outcomes.Methods: A descriptive post-intervention study was conducted at a decentralized DR-TB clinic in Sheikhupura, Punjab, between June 2021 and December 2022. Data from 100 patients were retrospectively collected from hospital records and diagnostic labs, including demographic information, treatment compliance, smear and culture conversion rates, and adverse drug reactions. SPSS 25 was used for statistical analysis, including descriptive statistics.Results: The average time from diagnosis to treatment initiation was 14.9 days. Smear conversion by the sixth month was 99%, while culture conversion was 98%. The treatment success rate was 70%, with a 7% loss to follow-up, 2% treatment failure, and 15% mortality.Conclusion: Decentralized DR-TB care significantly reduced delays in treatment initiation and improved patient outcomes. This model is feasible for national implementation with potential to enhance DR-TB management in Pakistan.

Advancing Cholangiocarcinoma Care: Insights and Innovations in T Cell Therapy.

Cholangiocarcinoma (CCA) is a rare and aggressive malignancy originating from the bile ducts, with poor prognosis and limited treatment options. Traditional therapies, such as surgery, chemotherapy, and radiation, have shown limited efficacy, especially in advanced cases. Recent advancements in immunotherapy, particularly T cell-based therapies like chimeric antigen receptor T (CAR T) cells, tumor-infiltrating lymphocytes (TILs), and T cell receptor (TCR)-based therapies, have opened new avenues for improving outcomes in CCA. This review provides a comprehensive overview of the current state of T cell therapies for CCA, focusing on CAR T cell therapy. It highlights key challenges, including the complex tumor microenvironment and immune evasion mechanisms, and the progress made in preclinical and clinical trials. The review also discusses ongoing clinical trials targeting specific CCA antigens, such as MUC1, EGFR, and CD133, and the evolving role of precision immunotherapy in enhancing treatment outcomes. Despite significant progress, further research is needed to optimize these therapies for solid tumors like CCA. By summarizing the most recent clinical results and future directions, this review underscores the promising potential of T cell therapies in revolutionizing CCA treatment.

Abstract C050: Breast cancer in Ghana: assessment of multidrug-resistant genes among breast cancer patients

Abstract Breast cancer (BC) is the most frequently diagnosed cancer among women globally and chemotherapy plays a crucial role in its management in sub-Saharan Africa. The long-term BC survival rate remains poor due to chemoresistance. Over 80% of currently used chemotherapy drugs are substrates of ABC transporter genes, ABCB1, ABCC1 and ABCG2. Possessing the wild-type genotype and alleles of these genes reduces intracellular drug accumulation and leads to poorer treatment outcomes due to the upregulation of efflux function. This study therefore determined the allelic and genotype frequencies of three variant alleles, rs1045642, rs28706727 and rs2231142 in these transporter genes, and assessed the association between the variant statuses and BC recurrence or metastasis in the Ghanaian BC population. A quantitative, observational, case-control study was conducted using a purposive and convenience sampling method. Sociodemographic and clinical data were collected from study participants using questionnaires and a review of medical records. Extracted blood DNA from participants was used to determine the gene variants in ABCB1, ABCC1 and ABCG2 genes using the TaqMan Allelic Discrimination assays. A significantly high frequency (p ≤ 0.001) of the homozygous wild-type genotypes and alleles (ABCB1 had 77.3%/88% for CC/C, ABCC1 had 95.3%/97.7% for GG/G and ABCG2 had 100%/100% for CC/C) was found in both case and control groups. The wild-type genotypes and alleles of ABCB1, ABCC1 and ABCG2 may contribute to poor BC treatment outcomes among Ghanaian BC patients receiving chemotherapy. Citation Format: Gloria Agyekum Boaitey, Rachel Martini, Nourddine Dean Djeddar, Brian Stonaker, Stevens M. Patino, Jason White, Ernest Osei Bonsu, Yaw Agyekum Boaitey, Christian Obirikorang, Melissa B. Davis, Linda Ahenkorah Fondjo. Breast cancer in Ghana: assessment of multidrug-resistant genes among breast cancer patients [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C050.

Abstract B092: ‘We’ve got to go to the doctor and we’re scared to death’: Community members perspectives on sexual orientation and gender identity data collection in healthcare settings

Abstract Purpose: Much research is needed to advance our knowledge of LGBTQ cancer disparities, but research is hindered by inconsistency in collection of data on sexual orientation and gender identity (SOGI) across clinical and research settings. Nationally, there have been increased efforts to standardize SOGI data collection. The purpose of this study was to identify potential patient-level barriers and facilitators to SOGI data collection within the catchment area of a midwestern cancer center. Methods: Investigators conducted 4 focus groups in partnership with community-based organizations and stakeholder groups that reflected the catchment area’s diverse populations. Using a semi-structured approach, participants were asked about their experiences with SOGI data collection, barriers and facilitators to this collection, and how they viewed the practice of collecting SOGI data. Focus groups were audio recorded and transcribed. Data was coded and interpreted using applied thematic analysis. Results: Four focus groups were conducted with 32 participants in total. There were 2 LGBTQ groups (one mixed race/ethnicity, one African American), and 2 predominantly non-LGBTQ groups (one African American and one Middle Eastern/North African or MENA). Across all participants, 53% were African American (n=17), 25% identified as MENA (n=8), 28% were White (n=9), 44% of the participants identified as women (n=19), one individual identified as a transgender woman &amp; 2 individuals as non-binary, and 53% reported their sexual orientation as gay/lesbian/same-loving. In all groups, participants emphasized a need to educate both patients and providers about the importance of SOGI data collection, why it is collected, and its relevance to improving medical care. Participants further discussed the quality and depth of the patient-provider relationship as a critical factor in a patient’s comfort and willingness to share SOGI data. Participants also underscored the importance of privacy ownership (i.e., the ownership of one’s own private information) and control in relation to SOGI status, and the desire to minimize potential privacy turbulence of an unexpected and unwelcome disclosure breach. All groups discussed how the potential for harm resulting from SOGI disclosure could deter patients from sharing SOGI information. Those who identified as LGBTQ, recounted both personal experiences and the experiences of others in which disclosure of SOGI information directly led to poor treatment by a healthcare professional. It is this potential for harm and discrimination that led many participants to stress the need for privacy control until a safe environment is established. Conclusions: Findings highlight a number of potential patient barriers to SOGI data collection from community members’ perspectives, including the need for widespread education on this topic and clinical environments in which patients are safe disclosing SOGI status. Future research and practice should consider specific methods to normalize the practice of SOGI data collection in the cancer care context. Citation Format: Ariel Washington, Ali Fakih, Lindsey Toman, Riham Ayoub, Emma Noble, Susan Musto, Brittany Dowe, Scott Ellis, Andrea Sakleh, Hayley S. Thompson, Latonya Riddle-Jones. ‘We’ve got to go to the doctor and we’re scared to death’: Community members perspectives on sexual orientation and gender identity data collection in healthcare settings [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B092.

Executive Function and Adherence in Children and Adolescents Living with HIV: Evidence from the HIV-associated Neurocognitive Disorders in Zambia (HANDZ) Study.

Executive function (EF) may be impaired in people with human immunodeficiency virus (HIV) infection, and poor EF may affect medication adherence. However, there is little data on EF in children with HIV in sub-Saharan Africa. 208 children/adolescents with perinatally acquired HIV and 208 HIV-exposed uninfected controls were recruited in Zambia for this prospective cohort study. EF was measured using performance-based, self-report, and parental report measures. Adherence over one year of follow-up was assessed through questionnaires and viral load measurement. Children with HIV performed significantly worse on all three measures of EF. Lower parental rating of EF was associated with poorer antiretroviral therapy adherence (OR: 1.5, 95% CI = 1.02 - 2.2, p = 0.04). Children with HIV have EF impairments which may lead to consequences like poor medication adherence and treatment failure. Interventions to improve EF or compensate for impaired EF may be necessary in this population.

Spinal Teratoma with Recurrent Epileptic Episodes in Adults: A Case Report

Introduction: Spinal teratomas are rare, accounting for nearly 0.2–0.5% of all spinal tumors and 2% of all teratomas. Teratomas at the conus medullaris location do not inherently lead to epilepsy. However, potential epileptic seizures are caused when teratoma ruptures and the chemical stimulation of teratoma components enter the dural sac. Case Presentation: A 31-year-old Asian male patient suffering from epileptic onset and poor antiepileptic treatment was demonstrated. The spinal imaging examination was performed, and the patient suffered a space-occupying lesion within the conus medullaris related to spinal deformity, spinal embolism, etc. The autoimmune encephalitis spectrum revealed mGluR5 antibody IgG (+) 1:10 response. The patient stabilized after treatment with hormones and human immunoglobulin. Some hair and lipid droplets could be observed in the dural sac intraoperatively, and more hair and lipid-like material were present in the spinal cord. Postoperative pathology established the diagnosis as a conus medullaris teratoma in adults. Epileptic seizures stopped after surgery, and no additional seizures were reported during the 33-month follow-up period. Conclusions: Conus medullaris teratoma rupture in adults rarely causes epileptic seizures. For spinal deformity patients with unexplained epileptic symptoms, spinal MRI can be helpful in early diagnosis, and more appropriate treatment improves disease prognosis.

A novel murine syngeneic CD8 peripheral T-cell lymphoma model with preclinical applications

Peripheral T-cell Lymphoma (PTCL) represents a heterogenous group of aggressive non-Hodgkin Lymphomas with poor prognostic outcomes and limited treatment options. The development and refinement of therapeutic strategies for PTCL are impeded by a paucity of reliable preclinical models that accurately mimic the disease’s pathophysiology. There is a dire need for more physiologically relevant models for PTCL. Here we describe a spontaneousCD8+ peripheral T-cell lymphoma cell line (LM-23) derived from a 12-week-old female Balb/cJ mouse. Both intravenous and subcutaneous administration of this cell line to syngeneic Balb/cJ mice resulted in rapid establishment of tumor growth. CHOP and anti-PD1 treatment both displayed no benefit to mice in regulating tumor growth. Such results along with its phenotypic characteristics, rapid growth, and metastatic behavior in syngeneic mice highlight its value in studying the elusive disease and discovery of novel therapeutics.

Trunk-to-leg volume and appendicular lean mass from a commercial 3-dimensional optical body scanner for disease risk identification

Body shape expressed as the trunk-to-leg volume ratio is associated with diabetes and mortality due to the associations between higher adiposity and lower lean mass with Metabolic Syndrome (MetS) risk. Reduced appendicular muscle mass is associated with malnutrition risk and age-related frailty, and is a risk factor for poor treatment outcomes related to MetS and other clinical conditions (e.g.; cancer). These measures are traditionally assessed by dual-energy X-ray absorptiometry (DXA), which can be difficult to access in clinical settings. The Shape Up! Adults trial (SUA) demonstrated the accuracy and precision of 3-dimensional optical imaging (3DO) for body composition as compared to DXA and other criterion measures. Here we assessed whether trunk-to-leg volume estimates derived from 3DO are associated with MetS risk in a similar way as when measured by DXA. We further explored if estimations of appendicular lean mass (ALM) could be made using 3DO to further improve the accessibility of measuring this important frailty and disease risk factor. SUA recruited participants across sex, age (18-40, 40-60, >60 years), BMI (under, normal, overweight, obese), and race/ethnicity (non-Hispanic [NH] Black, NH White, Hispanic, Asian, Native Hawaiian/Pacific Islander) categories. Each participant had whole-body DXA and 3DO scans, and measures of cardiovascular health. The 3DO measures of trunk and leg volumes were calibrated to DXA to express equivalent trunk-to-leg volume ratios. We expressed each blood measure and overall MetS risk in quartile gradations of trunk-to-leg volume previously defined by National Health and Nutrition Examination Survey (NHANES). Finally, we utilized 3DO measures to estimate DXA ALM using ten-fold cross-validation of the entire dataset. Participants were 502 (273 female) adults, mean age=46.0±16.5y, BMI=27.6±7.1kg/m2 and a mean DXA trunk-to-leg volume ratio of 1.47±0.22 (females: 1.43±0.23; males: 1.52±0.20). After adjustments for age and sex, each standard deviation increase in trunk-to-leg volume by 3DO was associated with a 3.3 (95% odds ratio [OR]=2.4-4.2) times greater risk of MetS, with individuals in the highest quartile of trunk-to-leg at 27.4 (95% CI: 9.0-53.1) times greater risk of MetS compared to the lowest quartile. Risks of elevated blood biomarkers as related to high 3DO trunk-to-leg volume ratios were similar to previously published comparisons using DXA trunk-to-leg volume ratios. Estimated ALM by 3DO was correlated to DXA (r2=0.96, root mean square error=1.5kg) using ten-fold cross-validation. Using thresholds of trunk-to-leg associated with MetS developed on a sample of US-representative adults, trunk-to-leg ratio by 3DO after adjustments for offsets showed significant associations to blood parameters and MetS risk. 3DO scans provide a precise and accurate estimation of ALM across the range of body sizes included in the study sample. The development of these additional measures improves the clinical utility of 3DO for the assessment of MetS risk as well as the identification of low muscle mass associated with poor cardiometabolic and functional health.

Effects of behavioral interventions on stress reactivity in adults with substance use disorders.

Heightened reactivity to stress is associated with poor treatment outcome in people with substance use disorders (SUDs). Behavioral strategies can reduce stress reactivity; however, these strategies are understudied in people with SUDs. The objective of this study was to test the effect of two behavioral strategies (cognitive reappraisal and affect labeling) on stress reactivity in people with SUDs. Treatment-seeking adults with SUDs (N = 119) were randomized to receive brief training in cognitive reappraisal, affect labeling, or a psychoeducational control, followed by a standardized stress induction. Markers of stress reactivity were collected before and following stress induction and included self-reported negative affect and substance craving, as well as salivary cortisol, and skin conductance response. Analyses of covariance did not indicate a significant effect of treatment condition on negative affect, cortisol, or skin conductance response. Participants in the affect labeling condition had greater increase in craving than those in the cognitive reappraisal condition; neither condition differed from control. Results indicated that, although participants were able to implement behavioral skills following a brief training, training condition did not modify stress reactivity, on average, relative to control. Future directions include consideration of individual differences in response to training and determination of whether higher "dosing" of skills via multiple sessions or extended practice is needed to influence stress reactivity in people with SUDs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Stimuli-Responsive Polymeric Nanocarriers Accelerate On-Demand Drug Release to Combat Glioblastoma.

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with a poor prognosis and limited treatment options. Drug delivery by stimuli-responsive nanocarriers holds great promise for improving the treatment modalities of GBM. At the beginning of the review, we highlighted the stimuli-active polymeric nanocarriers carrying therapies that potentially boost anti-GBM responses by employing endogenous (pH, redox, hypoxia, enzyme) or exogenous stimuli (light, ultrasonic, magnetic, temperature, radiation) as triggers for controlled drug release mainly via hydrophobic/hydrophilic transition, degradability, ionizability, etc. Modifying these nanocarriers with target ligands further enhanced their capacity to traverse the blood-brain barrier (BBB) and preferentially accumulate in glioma cells. These unique features potentially lead to more effective brain cancer treatment with minimal adverse reactions and superior therapeutic outcomes. Finally, the review summarizes the existing difficulties and future prospects in stimuli-responsive nanocarriers for treating GBM. Overall, this review offers theoretical guidelines for developing intelligent and versatile stimuli-responsive nanocarriers to facilitate precise drug delivery and treatment of GBM in clinical settings.

Ferroptosis in Renal Cancer Therapy: A Narrative Review of Drug Candidates.

Renal cancer is a common and serious malignant tumor of the urinary system. While surgery effectively treats early-stage renal cancer, advanced cases pose a significant challenge due to poor treatment outcomes and chemotherapy resistance. Therefore, there is an urgent need to develop alternative therapeutic strategies. Ferroptosis is a newly defined form of programmed cell death characterized by the accumulation of iron-dependent lipid peroxides, which plays a critical role in tumor progression and drug resistance. Recent studies have shown that ferroptosis is involved in the occurrence and development of renal cancer, and ferroptosis-related genes can induce cell apoptosis and can be used as potential biomarkers for early diagnosis of renal cancer and participate in drug resistance of renal cancer chemotherapy. With the continuous improvement of the mechanism of ferroptosis, drugs targeting ferroptosis for the treatment of renal cancer are emerging in an endless stream. Based on the theoretical basis of the occurrence of ferroptosis, this paper reviewed drug-induced ferroptosis in renal cancer cells from the aspects of herbal medicine, natural compounds, drug resistance mechanisms, and nanomaterials, and delves into the clinical application potential of ferroptosis-related drugs in the treatment of renal cancer.

Hypoalbuminemia and hypercalcemia are independently associated with poor treatment outcomes of anti-PD-1 immune checkpoint inhibitors in patients with recurrent or metastatic head and neck squamous cell carcinoma

BackgroundRecent randomized phase III trials have demonstrated the efficacy of anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICIs) in treating patients with recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC). However, a large proportion of such patients still have poor response. This study aimed to identify biomarkers for predicting anti-PD-1 ICI treatment outcomes .MethodsWe retrospectively analyzed 144 patients with RMHNSCC who received anti-PD-1 ICIs after progression to platinum-based chemotherapy between January 2017 and December 2022 at Kaohsiung Chang Gung Memorial Hospital. Data on clinicopathological parameters, albumin levels, calcium levels, and other pretreatment peripheral blood biomarkers, including total lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and prognostic nutritional index (PNI) were collected and correlated with the treatment outcome of anti-PD-1 ICIs.ResultsLow tumor proportion score (TPS), low combined positive score (CPS), NLR ≥ 5, PLR ≥ 300, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly correlated with poor response of ICIs. The overall response rates were 25% and 3% in patients with calcium < 10 mg/dL and calcium ≥ 10 mg/dL, respectively (P = 0.007). The overall response rates were 6% and 33% in patients with albumin < 4 g/dL and albumin ≥ 4 g/dL, respectively (P < 0.001). Univariate survival analysis showed that low TPS, low CPS, NLR ≥ 5,, hypercalcemia, hypoalbuminemia, and PNI < 45 were significantly associated with worse progression-free survival (PFS) and inferior overall survival (OS). Multivariate analysis revealed that calcium ≥ 10 mg/dL and albumin < 4 g/dL were independent poor prognosticators for worse PFS and inferior OS. The two-year OS rates were 26% and 9% in patients with calcium < 10 mg/dL and ≥ 10 mg/dL, respectively (P < 0.001). The two-year OS rates were 10% and 33% in patients with albumin < 4 g/dL and ≥ 4 g/dL, respectively (P < 0.001).ConclusionsHypercalcemia and hypoalbuminemia can potentially predict poor treatment outcomes of anti-PD-1 ICIs in patients with RMHNSCC. Blood calcium and albumin levels may be helpful in individualizing treatment strategies for patients with RMHNSCC.

ADHD: prevalence and effect on opioid use disorder treatment outcome in a French sample of patients receiving medication for opioid use disorder—the influence of impulsivity as a mediating factor

BackgroundOpioid use disorder (OUD) poses a global health challenge, and despite medications for opioid use disorder (MOUD) and psychosocial interventions, relapse remains a significant concern. Comorbid psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), are one of the major factors associated with poor OUD treatment outcome. We aimed to estimate the frequency of probable ADHD (in childhood and in adulthood) in patients with OUD; to assess the factors associated with this comorbidity; and to explore the factors that mediate the relationship between ADHD and OUD treatment outcome.MethodsWe conducted an observational study using a sample of 229 patients aged 18 years and older who were diagnosed with OUD and had received MOUD for at least six months. Participants were assessed through a structured interview and self-report questionnaires. Multivariate logistic regressions and a mediation analysis were performed.ResultsAlmost half of the participants reported probable ADHD in childhood, and ADHD persisted into adulthood among two-thirds of the patients. The factors associated with poor OUD treatment outcome included earlier onset of OUD, lower education, and greater impulsivity. There was no direct effect of probable ADHD in childhood on OUD treatment outcome, but there was an indirect effect through negative urgency, the tendency to respond impulsively to negatively connoted emotional experiences.ConclusionsThe findings suggest that ADHD symptoms, particularly impulsivity, may contribute to vulnerability in opioid use and play a crucial role in treatment outcomes for this population.Trial registration: ClinicalTrials identifier NCT01847729.

PARP-1 selectively impairs KRAS-driven phenotypic and molecular features in intrahepatic cholangiocarcinoma

ObjectiveIntrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with limited therapeutic options. KRAS mutations are among the most abundant genetic alterations in iCCA associated with poor clinical...

Microgel Encapsulated Mesoporous Silica Nanoparticles for Releasing Wnt16 to Synergistically Treat Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a commonly encountered degenerative joint disease in oral and maxillofacial surgery. Recent studies have shown that the excessive unbalanced activation of Wnt/β-catenin signaling is connected with the pathogenesis of TMJOA and due to the inability to inhibit the over-activated Wnt pathway, while Wnt16-deficient mice has a more severe Knee OA. However, the efficacy of direct intra-TMJ injection of Wnt16 for the relief of TMJOA is still not directly confirmed. Moreover, small-molecule drugs such as Wnt16 usually exhibit short-lived efficacy and poor treatment adherence. Therefore, in order to obtain a stable release of Wnt16 both in the short and long term, this study fabricates a double-layer slow-release Wnt16 carrier based on mesoporous silica nanospheres (MSNs) encased within hyaluronic acid (HA) hydrogels. The biofunctional hydrogel HA/Wnt16@MSN is analyzed both in vitro and in vivo to evaluate the treatment of TMJOA. As a result, it shows superior pro-cartilage matrix restoration and inhibition of osteoclastogenesis ability, and effectively inhibits the over-activation of the Wnt/β-catenin pathway. Taken together, biofunctional hydrogel HA/Wnt16@MSN is a promising candidate for the treatment of TMJOA.

High Schistosoma mansoni Co-Infection in Tuberculosis Patients with or without Human Immunodeficiency Virus: A Prospective Cohort Study.

Background People with Latent tuberculosis infection (LTBI) remain the reservoir of tuberculosis. One-third to 1/4 of the world's population is infected. Its reactivation is due to factors that disrupt the host's immune response. Recent findings showed that Schistosoma mansoni coinfection leads to a Th2/Th1 profile which results in an immune modulation that favors the escape of the Mycobacteria. Schistosoma mansoni may contribute to TB incidence in endemic regions. We aimed to investigate the coinfection rate and patient outcomes. Methods A prospective cohort study was conducted between 2020-2022 at University Clinical Research Center (UCRC), including culture-confirmed active pulmonary TB patients and tested for Schistosoma mansoni in stools using Kato-Katz Technique. After descriptive analysis a logistic regression was performed to determine risk factors associated with TB and Schistosoma mansoni co-infection. Results Data of 174 tuberculosis-confirmed patients, Kato-Katz tested were analyzed. Males represented 62.6%, mean age was 34.9 ± 13.8 years, 29.9% were smokers, alcohol consumption 13.8%, TB contact history 26.4%, HIV coinfection 11.5%, diabetes 6.3%, undernourished 55.7%. Schistosoma mansoni prevalence was 28.7%. The co-infection was associated with less lung cavitation [aOR = 0.24 [95% CI (0.06-0.85), p = 0.028], unfavorable treatment result [aOR = 2.95 (1.23-7.08), p = 0.015] and death [aOR = 3.43 (1.12-10.58), p = 0.032]. Conclusions Despite Kato-Katz's low sensitivity, Schistosoma mansoni coinfection was found in one-third of the TB patients; 2.5-fold higher than that of HIV. The coinfection was associated with poor treatment results and death.