Clinical Need Research Articles

Development and Evaluation of an Automated Multimodal Mobile Detection of Oral Cancer (mDOC) Imaging System to Aid in Risk-based Management of Oral Mucosal Lesions

Abstract Oral cancer is a major global health problem. It is commonly diagnosed at an advanced stage although often preceded by clinically visible oral mucosal lesions, termed oral potentially malignant disorders associated with an increased risk for oral cancer development. There is an unmet clinical need for effective screening tools to assist front-line healthcare providers to determine which patients should be referred to an oral cancer specialist for evaluation. This study reports the development and evaluation of the mobile Detection of Oral Cancer (mDOC) imaging system and an automated algorithm that generates a referral recommendation from mDOC images. mDOC is a smartphone-based autofluorescence and white light imaging tool that captures images of the oral cavity. Data were collected with mDOC from a total of 332 oral sites in a study of 29 healthy volunteers and 120 patients seeking care for an oral mucosal lesion. A multimodal image classification algorithm was developed to generate a recommendation of “Refer” or “Do Not Refer” from mDOC images, using expert clinical referral decision as the ground truth label. A referral algorithm was developed using cross-validation methods on 80% of the dataset, then retrained and evaluated on a separate holdout test set. Referral decisions generated in the holdout test set had a sensitivity of 93.9% and a specificity of 79.3% with respect to expert clinical referral decisions. The mDOC system has the potential to be utilized in community physicians’ and dentists’ offices to help identify patients who need further evaluation by an oral cancer specialist.

Restorative Neurostimulation Therapy Compared to Optimal Medical Management: A Randomized Evaluation (RESTORE) for the Treatment of Chronic Mechanical Low Back Pain due to Multifidus Dysfunction.

Many interventional strategies are commonly used to treat chronic low back pain (CLBP), though few are specifically intended to target the distinct underlying pathomechanisms causing low back pain. Restorative neurostimulation has been suggested as a specific treatment for mechanical CLBP resulting from multifidus dysfunction. In this randomized controlled trial, we report outcomes from a cohort of patients with CLBP associated with multifidus dysfunction treated with restorative neurostimulation compared to those randomized to a control group receiving optimal medical management (OMM) over 1 year. RESTORE is a multicenter, open-label randomized controlled trial. Candidates were assessed for CLBP associated with multifidus dysfunction, with no indication for or history of lumbar spine surgery. Participants were randomized to either restorative neurostimulation with the ReActiv8 system or OMM. The primary endpoint was a comparison of the mean change in the Oswestry Disability Index (ODI) between the treatment and control arms at 1 year, and secondary endpoints included pain (numeric rating scale [NRS]) and health-related quality of life (EuroQol Five-Dimension [EQ-5D-5L]). A total of 203 patients, average age 47 years, and with an average 11-year history of low back pain, were included in the analysis. The primary endpoint was a statistically significant demonstration of a clinically relevant mean improvement in the Oswestry Disability Index (ODI) between restorative neurostimulation and OMM arms: ODI (-19.7 ± 1.4 vs. -2.9 ± 1.4; p < 0.001). Additionally, improvements in both the numeric rating scale (NRS) (-3.6 ± 0.2 vs. -0.6 ± 0.2; p < 0.001) and EuroQol Five-Dimension (EQ-5D-5L) (0.155 ± 0.012 vs. 0.008 ± 0.012; p < 0.001) were statistically and clinically significant in the restorative neurostimulation arm compared to the OMM arm. The RESTORE trial demonstrates that restorative neurostimulation is a safe, reversible, clinically effective, and highly durable option for patients suffering with nonoperative CLBP associated with multifidus dysfunction. This demonstration of treatment superiority over OMM through 1 year is a significant milestone in addressing a major health burden and unmet clinical need. ClinicalTrials.gov Identifier: NCT04803214.

Time-lapse HR-pQCT reliably assesses and monitors local bone turnover in patients with chronic kidney disease.

Bone turnover assessment and monitoring are essential for chronic kidney disease (CKD)-associated bone care. Patients with CKD suffer from significantly elevated fracture risk due to abnormally high or low bone turnover, which requires diametrically opposite treatments informed by patient-specific bone turnover data. However, a reliable, accessible, non-invasive bone turnover assessment and monitoring tool remains an unmet clinical need. Combining time-lapse (TL) analysis with high-resolution peripheral quantitative computed tomography (HR-pQCT) scans obtained over time allows for in vivo temporospatial bone remodeling assessment. This study aimed to evaluate the feasibility of applying TL HR-pQCT to assess and monitor local bone formation and resorption in patients with CKD. A customized TL HR-pQCT pipeline was developed on a second-generation HR-pQCT platform and optimized using ex vivo cadaveric phantom and in vivo scan-rescan HR-pQCT images. The annualized least significant change in bone formation and resorption were evaluated using in vivo longitudinal reproducibility images. Finally, the feasibility of the TL HR-pQCT pipeline in assessing and monitoring bone turnover was evaluated in patients with end stage kidney disease (ESKD; n = 9). We found that a 2-month time-lapse period was sufficient for the TL HR-pQCT pipeline to reliably assess and monitor local bone turnover in a cohort of patients with ESKD. We also demonstrated the importance of characterizing TL HR-pQCT precision metrics using longitudinal baseline/follow-up rather than short-term scan-rescan datasets. The TL HR-pQCT pipeline assessed a range of bone formation metrics consistent with the gold standard histomorphometric bone formation reported in the literature for patients with CKD and ESKD. Our findings highlight that TL HR-pQCT holds promise as a "virtual bone biopsy" that reliably assesses and monitors local bone turnover for CKD bone care. Subsequent work will focus on validating this TL HR-pQCT pipeline against the gold standard bone biopsy with quantitative histomorphometry.

Modified Endothelial Activation and Stress Index: A New Predictor for Survival Outcomes in Classical Hodgkin Lymphoma Treated with Doxorubicin-Bleomycin-Vinblastine-Dacarbazine-Based Therapy

Background: Although the cure rates of classical Hodgkin Lymphoma (cHL) are as high as 90% using the current treatment protocols, the prognosis is poor for primary refractory patients. Thus, a biomarker that can predict patients with early progression at the time of diagnosis is an unmet clinical need. Endothelial activation and stress index (EASIX) and its variant modified EASIX (mEASIX) is a scoring system currently used for the prediction of prognosis in hematologic malignancies. This study aimed to investigate the prognostic value of the mEASIX score in newly diagnosed cHL patients. Methods: Data from 206 patients who underwent positron emission tomography (PET)-guided doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) therapy for cHL between January 2007 and November 2023 were retrospectively analyzed. The prognostic value of the mEASIX score was evaluated using the receiver operating characteristic (ROC) analysis, Cox regression analysis, and the Kaplan–Meier method, and then compared with standard risk assessment methods. Results: The median age at diagnosis was 33 years, and the rate of patients in the advanced stage was 67%. ROC analysis determined an optimal mEASIX score cut-off of 17.28, categorizing patients into mEASIXhigh (47%) and mEASIXlow (53%) groups. The 5-year progression-free survival (PFS) (60% vs. 84.3%) and overall survival (OS) (79.6% vs. 95.8%) were significantly lower in the mEASIXhigh group (p &lt; 0.001). Additionally, multivariate analysis showed that the independent variables affecting PFS included the nodular sclerosing subtype (HR: 0.4), bone marrow involvement (HR: 2.6), and elevated mEASIX (HR: 3.1). Independent variables, which had an effect on OS included elevated mEASIX (HR:3.8) and higher IPS-3 scores (HR:1.9). Furthermore, a higher mEASIX score (≥17.28) was identified as an independent variable indicating primary refractory disease (OR: 6.5). Conclusions: mEASIX is a powerful and easy-to-access marker for the detection of primary refractory disease and prognosis in newly diagnosed cHL cases.

A Longer Duration of Intravenous Antibiotic Treatment for Patients with Early Periprosthetic Joint Infections Is Not Associated with a Lower Failure Rate

Background: In recent years, many studies have demonstrated the efficacy of an early switch to oral antibiotics after surgical treatment in orthopedic-related infections. However, large analyses on periprosthetic joint infections (PJIs) are lacking. Material and Methods: We conducted a retrospective observational multicenter study in patients diagnosed with an early post-operative PJI, defined as one occurring &lt;3 months after the index arthroplasty and treated with debridement, antibiotics, and implant retention (DAIR). Patients from Europe and the USA were included. We took advantage of the fact that an early oral antibiotic switch is routine practice in Europe as opposed to a long duration of intravenous (IV) antibiotic treatment in the USA. Failure was defined as the clinical need for (i) a second unintended DAIR procedure, (ii) implant removal, (iii) suppressive antibiotic treatment, or (iii) PJI-related death, all within one year after DAIR. Results: A total of 668 patients were included. A total of 277 received IV antibiotics for &lt;14 days, 232 between 14 and 27 days, and 159 for &gt;27 days. The overall 1-year failure rate within the 3 groups was 41.5%, 44.4%, and 42.1%, respectively (p = 0.80). This observation remained when excluding patients who failed during IV therapy. A longer duration of IV therapy seemed beneficial for those patients with a high pre-operative C-reactive protein level and lack of modular component exchange. Conclusion: In early post-operative PJIs, a longer duration of IV therapy is not associated with a lower failure rate but may be continued until a sufficient bacterial load reduction has been achieved.

Next-Generation Immunotherapy for Hepatocellular Carcinoma: Mechanisms of Resistance and Novel Treatment Approaches

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide, and, with only 15–20% of HCC patients being suitable for potentially curative treatments, the vast majority of patients with HCC ultimately require systemic therapy. For decades, the choice of effective systemic therapy for HCC remained sparse. In recent years, after the combination of atezolizumab and bevacizumab demonstrated superior overall survival over the first-line standard, sorafenib, there has been a major therapeutic paradigm shift to immunotherapy-based regimens for HCC. While representing a great leap forward for the treatment of this cancer, the reality is that less than one-third of patients achieve an objective response to immune checkpoint inhibitor-based therapy, so there remains a significant clinical need for further therapeutic optimization. In this review, we provide an overview of the current landscape of immunotherapy for unresectable HCC and delve into the tumor intrinsic and extrinsic mechanisms of resistance to established immunotherapies with a focus on novel therapeutic targets with strong translational potential. Following this, we spotlight emerging immunotherapy approaches and notable clinical trials aiming to optimize immunotherapy efficacy in HCC that include novel immune checkpoint inhibitors, tumor microenvironment modulators, targeted delivery systems, and locoregional interventions.

Effects of natural source polysaccharides on neurological diseases: A review.

With the aging of society and changes in lifestyle, the incidence of neurological diseases (NDs) has been increasing year by year, bringing a heavy burden to patients and society. Although the efficacy of chemical drugs in the treatment of NDs is remarkable, there are problems such as high side effects and high costs. Therefore, finding mild and efficient drugs for NDs treatment has become an urgent clinical need. Natural source polysaccharides (NSPs) are macromolecules with unique bioactivity and low toxicity characteristics, which have great potential to become novel therapeutic agents for NDs. In the present study, the pharmacological activities and potential molecular mechanisms of NSPs to alleviate NDs are systematically reviewed from the perspectives of inflammation, oxidative stress, apoptosis, neuronal cell autophagy, neurotoxicity, and sedation-hypnosis. In addition, the limitations of the existing studies were analyzed and discussed, and the future research direction was suggested. This study may provide scientific basis for the research and development of therapeutic agents for NDs based on NSPs.

1-year patency of a novel biorestorative polymeric coronary artery bypass conduit.

Coronary artery bypass graft surgery (CABG) remains the gold standard in the treatment of complex coronary artery disease (CAD). Saphenous vein grafts (SVG) are commonly used for the non-left anterior descending artery (LAD). However, SVG failure rates in CABG surgery have been reported to be as high as 30% at 1 year and ∼50% at 10 years. Despite suboptimal performance, ∼80% of all CABG surgery includes SVG graft use. Therefore, an off-the-shelf, small-diameter vascular conduit with good patency rates remains a large unmet clinical need. XABG (Xeltis BV, Eindhoven, The Netherlands), a novel supramolecular electrospun biorestorative polymeric conduit with an embedded nitinol microskeleton, is under clinical development to fulfill this unmet need. This case report aims to demonstrate the safety and feasibility of this conduit in a routine CABG operation with implantation in a 70-year-old male patient with 3 vessel disease. The XABG conduitremained patent with TIMI 3 flow at 6 months and patency was confirmed by cardiac computed tomography (CT) at 12 months.

Efgartigimod efficacy and safety in refractory myasthenia gravis: UK’s first real-world experience

BackgroundWe report our experience of patients with generalised myasthenia gravis (gMG) treated with efgartigimod, an neonatal Fc receptor antagonist, under the Early Access to Medicine Scheme (EAMS) in the UK.MethodsData...

Advancement of the Dragon Heart 7-Series for Pediatric Patients With Heart Failure.

Safe and effective pediatric blood pumps continue to lag far behind those developed for adults. To address this growing unmet clinical need, we are developing a hybrid, continuous-flow, magnetically levitated, pediatric total artificial heart (TAH). Our hybrid TAH design, the Dragon Heart (DH), integrates both an axial flow and centrifugal flow blood pump within a single, compact housing. The axial pump is embedded in the central hub region of the centrifugal pump, and both pumps rotate around a common central axis, while maintaining separate fluid domains. In this work, we concentrated our design and development effort on the centrifugal blood pump by performing computational modeling. An iterative process was employed to improve the DH design. The pressure generation, scalar stress levels, and fluid forces exerted on the magnetically levitated impellers were computationally estimated. A shaft driven centrifugal prototype was also manufactured and tested using a hydraulic flow loop circulating a water-glycerol blood analog. Pressure and flow performance of the pump prototype was measured for a given rotational speed for comparison to computational predictions. Our design achieved the target pump pressures of 60-140 mm Hg for flow rates of 1-5 L/min, and strong agreement in pressure rise was demonstrated between the experimental data and simulation results (less than 10% deviation on average). Fluid stress levels were, however, found to exceed thresholds in the outflow region of the pump, and fluid residence times were less than 600 ms. The findings of this work demonstrate that the more compact, next-gen DH's centrifugal pump design is able to achieve pressure-capacity requirements. Next steps will require a focused strategy to reduce hemolytic potential and to integrate magnetic suspension components for full rotor levitation.

Brain MRI Screening for Bilateral Retinoblastoma Patients

ABSTRACT Purpose Trilateral retinoblastoma (TRB), intracranial neoplasm in heritable retinoblastoma patients, is a very rare fatal disease. Many ocular oncology centers conduct routine screening of retinoblastoma patients by brain imaging. Nevertheless, there is a debate regarding its ability to prolong TRB patients’ survival and the number-needed-to-treat. We recommend baseline screening brain imaging in bilateral retinoblastoma patients, followed by imaging according to clinical need. We aim to see if this screening schedule has an impact on patients’ survival. Methods In a retrospective observational study, we reviewed the medical records of patients diagnosed with bilateral retinoblastoma at a tertiary medical center ocular oncology unit between 1.7.1986 and 1.2.2020, who had at least 36 months follow-up or retinoblastoma-related death. We collected data on patients’ demographics, clinical features, systemic evaluation, treatment, follow-up, and outcome. Results The analysis included 109 patients, 60 males and 49 females, diagnosed with bilateral retinoblastoma at a median age of 7.0 months (range 0.43–70.5 months). Germline mutation was found in 43 patients (39.4%) and somatic mutation in 15 patients (13.8%). Genetic status was not recorded in 51 patients (46.8%). Fifty-eight patients (53.0%) underwent baseline brain imaging (MRI in 42 patients and CT scan in 16 patients), in all of whom it was within normal limits. During a median follow-up of 138 months (range 19–787 months), 35 children had follow-up brain imaging (MRI in 25 patients and CT in 10 patients). One patient developed symptomatic TRB during follow-up, and is alive and disease-free (0.9%, Cl:0.02%-5.6%). Looking at survival, six patients (5.5%) developed metastatic disease, and eight patients (7.3%) expired, in all of whom death was retinoblastoma-related. Conclusions Due to TRB rarity, routine screening by baseline brain MRI may be sufficient, avoiding anesthesia, expenses, distress, and unnecessary interventions, without a significant impact on patients’ survival. Nevertheless, due to TRB fatality and treatment morbidity, periodic brain MRI until age 3 is a legitimate option.

Gentiopicroside ameliorates psoriasis-like skin lesions in mice via regulating the Keap1-Nrf2 pathway and inhibiting keratinocyte activation.

Psoriasis is a chronic, systemic immune-mediated skin disease. Although many new strategies for psoriasis treatment have been developed, there is great need in clinic for treating psoriasis. Gentiopicroside (GPS), derived from Gentiana manshurica Kitagawa, has multiple pharmacological activities including anti-inflammatory, anti-oxidative and antiviral activities. In this study, we investigated the potential effects of GPS in imiquimod (IMQ)-induced psoriasis mouse model and the underlying mechanisms. The mice were sensitized on their shaved back with IMQ cream for 7 days with or without topical application of 1% or 2% GPS cream. We showed that the application of GPS cream significantly ameliorated psoriasis-like skin lesions; GPS effect was better than that of calcipotriol. GPS rectified the immune cells infiltration and keratinocytes activation in the skin lesions, and significantly inhibited TNF-α/IFN-γ stimulated human keratinocyte (HaCaT) activation in vitro. Proteomic analysis from keratinocytes with and without GPS treatment prompted that GPS regulated the Keap1-Nrf2 pathway, which was the most important pathway in regulating oxidative stress and inflammation. We demonstrated that GPS regulated the protein expression of p62 and Keap1, induced Nrf2 nuclear translocation followed by transcription of Nrf2 downstream antioxidant genes in HaCaT cells. Furthermore, the antioxidant effects of GPS were abolished in Nrf2-/- keratinocytes. Simultaneously, Nrf2-/- mice showed increased psoriasiform symptoms with a diminished protective effect in response to GPS treatment. Collectively, the study discloses that GPS inhibits keratinocyte activation and ameliorates psoriasis-like skin lesions in an Nrf2-dependent manner.

Cellular interactions in self-directed immune mediated liver diseases.

The lymphocyte population must traverse a complex path throughout their journey to the liver. The signals which these cells must detect, including cytokines, chemokines and other soluble factors, steer their course towards further crosstalk with other hepatic immune cells, hepatocytes and biliary epithelial cells. A series of specific chemokine receptors and adhesion molecules drive not only the recruitment, migration, and retention of these cells within the liver, but also their localisation. Perturbation of these interactions and failure of self-recognition drives the development of several autoimmune liver diseases. Understanding the nature of these interactions develops our understanding of immune mediated liver disease pathogenesis, providing new opportunities for intervention to resolve uncontrolled inflammation. In this review, we provide an overview of the complex recruitment pathways and cellular interactions which position lymphocyte populations in the liver. We discuss how these are disrupted in autoimmune diseases and highlight the mechanism of immune cells inside hepatocytes (emperipolesis) in autoimmune hepatitis and immune cells inside biliary epithelial cells (intra-epithelial lymphocyte) in primary biliary cholangitis as well as avenues to manipulate these pathways for therapy. We also cover the immune mediated tissue injury mechanisms impacted by checkpoint inhibitors, leading to checkpoint inhibitor-induced liver injury (CHILI). Finally, we describe emerging immune-based therapies, including regulatory T cell, anti-cytokine and anti-chemokine therapies, cytokine supplementation such as interleukin-2 as well as numerous modalities of co-inhibitory molecule manipulation, including bispecific T cell engagers (BiTEs) and checkpoint inhibitor bispecific T cell engagers (CiTEs) and discuss their potential application in the treatment of autoimmune liver diseases. Immune-mediated liver disease encompasses two broad categories: autoimmune and inflammatory liver injury, the former resulting from a breakdown in immunological self-tolerance. These share common features, namely histologically dense immune infiltrates, autoantibody positivity and immunoglobulin elevation. Whilst well defined in their epidemiology, presentation and diagnostic evaluation, their treatment remains an unmet clinical need. Our incomplete understanding of the mechanisms leading to breakdown in immunological self-tolerance and our inability to restore immune homeostasis hampers present progress in treatment. This review summarises recent advances in our understanding of the loss of hepatic tolerance and the cellular interactions leading to this, including immune cell invasion towards hepatocytes and biliary epithelial cells, checkpoint-induced immune-mediated liver injury (CHILI) and concludes with current progress in treatment strategies.

Thromboelastography may assess the effect of anticoagulation reversal in intracranial hemorrhage.

Intracranial hemorrhage (ICH) is a complication of oral anticoagulation and is associated with significant morbidity and mortality. Clinical need exists for biomarkers to measure anticoagulation in patients with factor Xa inhibitor-associated ICH to assess the hemostatic effect of reversal agents. This study explored the utility of thromboelastography (TEG) to assess anticoagulation in emergency department (ED) patients who received activated prothrombin complex concentrate (aPCC) reversal for factor Xa-inhibitor-associated ICH. This was a prospective, single-center, cohort study in a convenient sample of adult patients presenting to the ED with acute factor Xa-associated ICH. Exclusion criteria included pregnancy, incarceration, polytrauma, hepatic failure, or other known coagulopathic conditions. TEG samples were collected prior to anticoagulation reversal, as well as at 30-minutes, 12-hours, and 24-hours post-reversal. Only patients who received aPCC reversal were included in the final analysis. Pre-reversal TEG was collected on 10 participants prior to aPCC administration. A significant decrease in TEG R-time was observed at 30 minutes post-aPCC reversal (Beta = -0.91, p = 0.035). R-time increased at 12- and 24-hours post-aPCC reversal to baseline levels. Significant changes were not observed in K-time, clot strength, maximum amplitude, or coagulation index. TEG R-time decreases acutely after anticoagulation reversal with aPCC and rebounds at 12- and 24-hours post-reversal. TEG R-time may serve as a potential sensitive biomarker of the residual anticoagulation activity of factor Xa inhibitors in patients with ICH that undergo anticoagulation reversal with aPCCs.

Investigating the Impacts of Perianal Skin Cancer on Patient Quality of Life

Perianal skin cancer, while rare, can have severe consequences on patient quality of life. This study sought to address this question by examining patient lived experience, social impact, psychological symptoms, and perceived informational needs following a diagnosis of perianal skin cancer. Mixed methods enabled contextualization, exploration, and illumination of pertinent patient issues. Results indicated that stigma, communication, psychological and physical effects, and concern for survival may impact patient care. Psychometric data support these findings. Patient informational needs suggest a reduction in the perceived frequency of all needs and a strong preference for digital over face-to-face information provision. As a truly patient-centered study, this paper provides an important starting point for the consideration of psychosocial support for perianal skin cancer patients. The outcomes are disseminated across clinical policy, offering highlighted points of consideration. Perianal skin cancers are rare. They are rare enough that, in general, the evidence base lacks the larger studies and data that could enable more consistent practice worldwide. This is the first patient-centered investigation of the impacts of perianal skin cancer on quality of life and patient well-being, and it is the first patient study to cascade into policy amendment within the United Kingdom, notably within the clinical unit. This study provides concrete, specific outcomes related to patient experience and clinical need, and suggests both the generic nature of the support available to assist these patients and the lack of productive practice that could be molded and strengthened from it.

GFRs in Chinese CKD: A systematic review.

This was an evidence-based study to assess which creatinine-based equation was most useful for estimated glomerular filtration rate (eGFR) in Chinese adults with chronic kidney disease (CKD). Multiple databases were searched to collect relevant studies on creatinine-based eGFR equations for Chinese adults with CKD in Chinese and English from January 2009 to January 2023, using "glomerular filtration rate", "GFR equations", "Chinese CKD", "chronic kidney disease", "equation development" and "equation validation". The quality of each study was assessed using the diagnostic test accuracy review by RevMan 5.4 software. The equation name, study publication year, first author, reference method for eGFR, CKD numbers, age (age ranges) of individuals, mGFR value, bias, precision, and 30% accuracy (P30) of each included equation were recorded accordingly by 2 independent investigators. Of the 838 studies identified, 23 studies based on 6 creatinine-based GFR equations were included in the present review, ie, the CKD-EPI, Asian modified CKD-EPI, FAS, EKFC, Xiangya, and BSI1 equations. A total of 2979 CKD patients were included for FAS equation external assessment, and the total P30 was 72.6%; 970 CKD patients for the EKFC equation, and the total P30 was 73.1%. 1778 CKD patients (≥60years of age) with a mean eGFR from 39.7 to 47.6mL/min/1.73m2 were pooled to assess the prediction accuracy of the BSI1 equation and demonstrated that the bias was small (-3.8-3.5mL/min/1.73m2), the precision was excellent (10.2-16.8mL/min/1.73m2), and the total P30 was 69.6%. Currently, the FAS and EKFC equations have higher P30 for eGFR among Chinese adult CKD patients. The bias and precision of BSI1 formulas was acceptable for eGFR in elderly≥60years of age, while the P30 was relatively low. Therefore, there is a clinical need to develop more accurate equations for eGFR in older CKD adults. While promising, these findings require further validation in large well controlled clinical studies.

Disparities in Alcohol Treatment Use at the Intersection of Race, Ethnicity, Gender, and Insurance.

Treatment for alcohol use disorder (AUD) has the potential to improve health and quality of life. Little is known about disparities in AUD treatment utilization at the intersection of race and gender. We examined disparities in AUD treatment utilization among those diagnosed with AUD in a community sample, by race, ethnicity, and gender, and whether disparities varied by insurance. We also examined whether criminal legal history and socioeconomic status moderated disparities in treatment. We used data from the nationally representative 2017 to 2019 National Survey on Drug Use and Health, the most recent 3-year period available. The analytic sample included noninstitutionalized adults aged 18 to 64 who met criteria for past year AUD and identified as White, Black, or Latinx (n = 7782). We examined disparities in AUD treatment utilization by race, ethnicity, and gender subgroup and by insurance status, estimating weighted logistic regressions, and adjusting for indicators of clinical need in concordance with the Institute of Medicine definition of healthcare disparity. Only 5.4% of adults with AUD in the United States utilized AUD treatment in the past year. AUD treatment utilization did not significantly differ between White males and other racial, ethnic, and gender groups; however, we did identify disparities among Medicaid enrollees and those who were uninsured. Among Medicaid enrollees, Latinx females (3.2%) had lower treatment utilization than White males (9.3%, P < .05). Among uninsured individuals, Latinx males (1.8%) had lower treatment utilization than White males (6.2%, P < .05). AUD treatment utilization was extremely low among adults in the United States aged 18 to 64 who met criteria for AUD. Ethnic and gender disparities in treatment utilization were revealed when examining differences in AUD treatment utilization by insurance status. Strategies for improving access to AUD treatment that address structural barriers to care are needed and should consider targeted approaches for Medicaid enrollees and those uninsured.

First-generation high-affinity ST14 radiopharmaceutical: Design, synthesis, and preclinical PET imaging evaluation for pancreatic cancer detection.

The non-specificity of 18F-FDG, coupled with high false-positive rates in pancreatitis, underscores an unmet clinical need for using specific positron emission tomography (PET) radiopharmaceuticals in noninvasive pancreatic cancer detection. ST14, a trypsin-like protease and a member of the type II transmembrane serine protease family, is overexpressed in various solid malignancies, including pancreatic cancer. This study aimed to develop a 68Ga-labeled PET radiopharmaceutical targeting ST14 for pancreatic cancer detection. A precursor ST14-06 was designed, and molecular docking was employed to preliminarily predict the binding mode. ST14-06 emerged as the preferred precursor with experimental inhibition assays confirming its high affinity for ST14 (IC50=1.06±0.08nM). 68Ga-ST14-06 was successfully synthesized with high radiochemical purity (RCP, >95%) and molar activity (25-30GBq/μmol) and was stable in saline and serum. In vitro studies demonstrated specific binding of the tracer to ST14-positive AsPC-1 cells compared to the blocking group (11.45±0.12% vs. 2.48±0.34%, P<0.01). PET/CT imaging in AsPC-1 tumor-bearing mice confirmed ST14-specific uptake, which was reduced by co-administration of an excess blocking agent. Biodistribution studies revealed higher distribution in AsPC-1 tumors (0.99±0.08%ID/g) than in PANC-1 tumors (0.32±0.02%ID/g) and the blocking group (0.32±0.04%ID/g) at 1h post-injection. Immunohistochemistry results showed that ST14 was highly positive in AsPC-1 tumors, but was negative in PANC-1 tumors. These preliminary findings suggest that 68Ga-ST14-06 has potential as a first-generation PET radiopharmaceutical for ST14-specific imaging, offering a promising tool for pancreatic cancer detection.

Mental Health Consequences of Opioid Pain Medication Use Behaviors and Motives Among Adolescents and Young Adults With Cancer: Results From a National Survey.

Adolescents and young adults (AYA) with cancer experience long-term consequences into survivorship that impact quality of life, including mental health symptoms, substance use, and persistent pain. Given the elevated rates of pain, AYA cancer survivors are at increased risk for opioid pain medication (OPM) exposure, increasing risk for opioid-related negative consequences, particularly for those with mental health symptoms. Minimal research has documented that a considerable proportion of AYAs with cancer receive OPM that continues into survivorship, yet the lack of consensus on the definition of problematic opioid use coupled with the high clinical need for OPM makes it particularly challenging to understand the impact of OPM use in this population. Therefore, the current study examined differences in opioid pain medication use, use behaviors, and motives between AYA cancer survivors and non-cancer controls. Using the National Survey on Drug Use and Health, we tested the impact of OPM use behaviors and motives on depressive symptoms and mental healthcare utilization variables. Results show that, compared to non-cancer controls, AYA cancer survivors evince higher rates of opioid use, behaviors, and pain relief motives. Within the cancer survivor group only, there were differential patterns of associations between OPM behaviors, motives, depressive symptoms, and mental healthcare utilization, with using opioid pain medication for emotion coping/to get high showed the largest effect sizes with outcome variables. The results highlight the importance of moving beyond use itself and examining how and why AYAs with cancer are using opioids to understand potential negative consequences.

Image-Based Estimation of Left Ventricular Myocardial Stiffness.

Elevation in left ventricular (LV) myocardial stiffness is a key remodeling-mediated change that underlies the development and progression of heart failure (HF). Despite the potential diagnostic value of quantifying this deterministic change, there is a lack of enabling techniques that can be readily incorporated into current clinical practice. To address this unmet clinical need, we propose a simple protocol for processing routine echocardiographic imaging data to provide an index of left ventricular myocardial stiffness, with protocol specification for patients at risk for heart failure with preserved ejection fraction. We demonstrate our protocol in both a preclinical and clinical setting, with representative findings that suggest sensitivity and translational feasibility of obtained estimates.