Overexpression of wild-type HRAS drives non-alcoholic steatohepatitis to hepatocellular carcinoma in mice.

Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human HRAS overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum.

Value of Spinal Infection Treatment Evaluation Score, Pola Classification, and Brighton Spondylodiscitis Score from Decision to Surgery in Patients with Spondylodiscitis: A Receiver-Operating Characteristic Curve Analysis.

STUDY DESIGN: This was a retrospective study. PURPOSE: This study aimed to assess the value of the Spinal Infection Treatment Evaluation (SITE) score, Brighton Spondylodiscitis Score (BSDS), and Pola classification to predict the need for surgical intervention in patients with spondylodiscitis. OVERVIEW OF LITERATURE: Spondylodiscitis is a rare disease, and the prediction of its outcome is crucial in the decision-making process. METHODS: All case records were assessed to extract information on the American Spinal Injury Association (ASIA), Visual Analog Scale (VAS), and Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ) scores before and after surgery. The SITE score, Pola classification, and BSDS were recorded. The receiver-operating characteristic (ROC) curve analysis and the area under the curve (AUC) were applied to estimate the predictive ability of the scoring systems. Patients' satisfaction with surgery outcomes was evaluated using the VAS, ASIA, JOABPEQ, and Likert scale for quality-of-life evaluation. RESULTS: In all 148 patients, case records were reviewed. The mean±standard deviation age of the patients was 54.6±14.7 years. Of these, 112 patients underwent surgery. The AUC scores were 0.86, 0.81, and 0.73 for the SITE score, BSDS, and Pola classification, respectively. In the comparison of the AUC of ROC curves, SITE score vs. BSDS showed a significantly greater AUC, 0.13 (Z =2.1, p =0.037); SITE score vs. Pola classification, 0.05 (Z =0.82, p =0.412); and Pola classification vs. BSDS, 0.08 (Z =1.22, p =0.219). The optimal cutoff score was 8.5 (sensitivity, 80.6%; specificity, 81.2%) for the SITE score and 9.5 (sensitivity, 52.8%; specificity, 83.0%) for the BSDS in the decision to surgery. VAS back pain and JOABPEQ subscales showed a significant difference when compared with preoperative scores. According to ASIA grading, none of the patients experienced neurological deterioration. Overall, patients' satisfaction was observed. CONCLUSIONS: The findings suggest that the SITE score is a useful measure and helps clinicians make clinically sound decisions in patients with spondylodiscitis.

Efficacy and Acceptance of Cognitive Behavioral Therapy in Adults with Chronic Fatigue Syndrome: A Meta-analysis.

BACKGROUND: The systematic aggregation of research on cognitive behavioral therapy (CBT) in chronic fatigue syndrome (CFS) needs an update. Although meta-analyses evaluating interventions typically focus on symptom reduction, they should also consider indicators of treatment acceptability, e.g., drop-out rates. METHODS: Randomized controlled trials (RCTs) investigating CBT in adults with CFS compared to inactive and non-specific control groups were included. First, efficacy was examined, considering fatigue, depression, anxiety, and perceived health. Secondly, drop-out rates through different trial stages were analyzed: Non-completion of all mandatory sessions, drop-out (primary study definition), treatment refusal (non-starters), and average of sessions completed. RESULT: We included 15 RCTs with 2015 participants. CBT was more effective than controls in fatigue (g = -0.52, 95%CI -0.69 to -0.35), perceived health, depression, and anxiety at post-treatment. At long-term follow-up the effects were maintained for fatigue and anxiety. Rates of non-completion (22%, 95%CI 3-71), drop-out (15%, 95%CI 9-25), and treatment refusal (7%, 95%CI 3-15) were relatively low, with a high average proportion of sessions completed. Total time of therapy moderated the effect on fatigue, while the number of sessions moderated the effect on perceived health. Fatigue severity influenced adherence. CONCLUSION: The results indicate that CBT for CFS is effective in reducing fatigue, fatigue related impairment, and severity of depression and anxiety. Conclusions on efficacy at follow-ups are still limited. However, adherence is high in CBT. The results may help to inform clinical practice. Future research should focus on examining the maintenance of effects, while also emphasizing the importance of treatment acceptance.

Mediational Analyses of the Effects of Social Behaviour and Network Therapy on Alcohol Use.

INTRODUCTION: Social behaviour and network therapy involves an active participation of the practitioner in recruiting a supportive network to change the client's alcohol use. Despite achieving beneficial effects on alcohol consumption, its possible mechanisms of change are a relatively under-studied topic compared to those of other alcohol treatment interventions. This study aimed to explore therapist skills through which social behaviour and network therapy may achieve effects on alcohol consumption in comparison with motivational enhancement therapy. METHODS: This study was secondary analysis of data from the UK Alcohol Treatment Trial, a multicentre, pragmatic, randomized controlled trial. The sample comprised 376 participants randomized to motivational enhancement therapy or social behaviour and network therapy. We used the UK Alcohol Treatment Trial Process Rating Scale to assess therapist skills. Outcomes drinks per drinking day and percentage of days abstinent were assessed 12 months after treatment initiation. Analyses were conducted in a simple mediation framework. RESULTS: Therapist skills score (combining frequency and quality) for involving others in behaviour change mediated social behaviour and network therapy effects on percentage of days abstinent (b = 0.06, 95% CI: 0.02; 0.10, p = 0.01). The frequency with which therapists acted as an active agent for change also mediated the effects of social behaviour and network therapy on percentage of days abstinent (b = 0.03, 95% CI: 0.003; 0.05, p = 0.03). The frequency with which the therapist stressed social support as a key factor in achieving change unexpectedly mediated an increase in drinks per drinking day (b = 0.10, 95% CI: 0.01; 0.18, p = 0.02). The two latter mediation effects were not sustained when quality was considered. All other indirect effects tested were non-significant. DISCUSSION/CONCLUSIONS: How social behaviour and network therapy exerts effects on alcohol outcomes is not yet well understood and in this study was not attributable to observed ratings of therapist treatment-specific skills. Therapist skill in planning the involvement of others during treatment, however, warrants further study. We suggest that the present findings should be regarded as hypothesis generating as it identifies specific targets for further investigation in alcohol treatment process studies.

Research progress on the diagnosis, treatment evaluation and prognostic prediction of hepatocellular carcinoma using ultrasound elastography / 中华肝胆外科杂志

Ultrasound elastography is a non-invasive imaging technique that can measure tissue hardness and provide valuable information for diagnosis and treatment of hepatocellular carcinoma. It offers numerous advantages, including non-invasiveness, rapidity, safety, excellent repeatability, cost-effectiveness, and high patient acceptance. This article reviews the current research progress of ultrasound elastography in diagnosis, treatment evaluation, and prognosis prediction of hepatocellular carcinoma, aiming to help clinicians to tailor treatment strategy, reduce complications, and improve prognosis.

Therapeutic Impacts of Hyperbaric Oxygen Therapy and Risperidone on Children with Autism: A Clinical Trial.

Introduction: In this research, we investigated any possible effect of receiving hyperbaric oxygen therapy (HBOT) or risperidone on the core symptoms of autism in children diagnosed with autism spectrum disorder (ASD). Methods: This study was a randomized, controlled clinical trial in Minia and Assiut University hospitals in Egypt with three parallel groups. One hundred and eighty children with autism, aged 5-8 years were divided into three equal groups (n=60). Group 1 (G1) received 40 sessions of HBOT within two months, group 2 (G2) received risperidone (dose: 0.25 mg per day in children weighing less than 20 kg and 0.5 mg per day in cases weighing more) for six months, and group 3 (G3) as the control group, received a placebo for six months. The assessment was done using childhood autism rating scale (CARS) and autism treatment evaluation checklist (ATEC) at the beginning of the study (baseline) and after one year. Results: The mean total CARS and ATEC scores significantly decreased (improved) by varying degrees in the three groups after a year of follow-up compared to the baseline scores, but the best results were found in G1, G2, and G3, respectively. Conclusion: Using HBOT or risperidone is effective in treating the core symptoms of autism in children diagnosed with autism spectrum disorder, but using HBOT gives better results than risperidone therapy. Highlights: Non-pharmacologic therapy can be used for the treatment of the core symptoms of autism.Both hyperbaric oxygen therapy and risperidone reduce the core symptoms of autism.Hyperbaric oxygen therapy gives better effects than risperidone in reducing the core symptoms of autism. Plain Language Summary: Since the long-term use of drug therapy in children with autism leads to the occurrence of side effects in addition to the difficulty in complying with the drugs for long-term use, efforts have begun to use non-traditional alternative treatments, such as hyperbaric oxygen therapy. The current study assessed the therapeutic effect of hyperbaric oxygen therapy and risperidone on the core symptoms of autism. The results revealed that both hyperbaric oxygen therapy and risperidone reduced the core symptoms of autism, but hyperbaric oxygen therapy gave better therapeutic results than risperidone.

Cardiac and mortality outcome differences between methadone, buprenorphine and naltrexone prescriptions in patients with an opioid use disorder.

IMPORTANCE: More than 109,000 Americans died of drug overdose in 2022, with 81,231 overdose deaths involving opioids. Methadone, buprenorphine and naltrexone are the most widely used medications for opioid use disorders (MOUD) and the most effective intervention for preventing overdose deaths. However, there is a concern that methadone results in long QT syndrome, which increases the risk for fatal cardiac arrythmias. Currently few studies have systematically evaluated both the short-term and long-term differences in cardiac and mortality outcomes between MOUD. OBJECTIVES: To compare the risks of cardiac arrythmias, long QT syndrome and overall mortality between patients with opioid use disorders (OUD) who were prescribed methadone, buprenorphine or naltrexone. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study based on a multicenter and nationwide database of electronic health records (EHRs) in the United States. The study population was comprised of 144,141 patients who had medical encounters for OUD in 2016-2022, were prescribed MOUD within 1 month following a medical encounter for OUD diagnosis and had no diagnosis of cardiac arrythmias or long QT syndrome before any MOUD prescription. The study population was divided into three cohorts: (1) Methadone cohort (n = 40,938)-who were only prescribed methadone. (2) Buprenorphine cohort (n = 80,055)-who were only prescribed buprenorphine. (3) Naltrexone cohort (n = 5,738)-who were only prescribed naltrexone. EXPOSURES: methadone, buprenorphine, or naltrexone. MAIN OUTCOMES AND MEASURES: Cardiac arrythmias, long QT syndrome, and death. Hazard ratio (HR) and 95% confidence interval (CI) of outcomes at six different follow-up time frames (1-month, 3-month, 6-month, 1-year, 3-year, and 5-year) by comparing propensity-score matched cohorts using Kaplan-Meier survival analysis. RESULTS: Patients with OUD who were prescribed methadone had significantly higher risks of cardiac arrhythmias, long QT syndrome and death compared with propensity-score matched patients with OUD who were prescribed buprenorphine or naltrexone. For the 1-month follow-up, the overall risk for cardiac arrythmias was 1.03% in the Methadone cohort, higher than the 0.87% in the matched Buprenorphine cohort (HR: 1.20, 95% CI: 1.04-1.39); The overall risk for long QT syndrome was 0.35% in the Methadone cohort, higher than the 0.15% in the matched Buprenorphine cohort (HR: 2.40, 95% CI: 1.75-3.28); The overall mortality was 0.59% in the Methadone cohort, higher than the 0.41% in the matched Buprenorphine cohort (HR: 1.48, 95% CI: 1.21-1.81). The increased risk persisted for 5 years: cardiac arrhythmias (HR: 1.31, 95% CI: 1.23-1.38), long QT syndrome (HR: 3.14, 95% CI: 2.76-3.58), death (HR: 1.50, 95% CI: 1.41-1.59). CONCLUSIONS AND RELEVANCE: Methadone was associated with a significantly higher risk for cardiac and mortality outcomes than buprenorphine and naltrexone. These findings are relevant to the development of guidelines for medication selection when initiating MOUD treatment and inform future medication development for OUD that minimizes risks while maximizing benefits.

Efficacy of mindfulness- and acceptance-based cognitive-behavioral therapies for bodily distress in adults: a meta-analysis.

Objective: Bodily distress, i.e., somatoform disorders and associated functional somatic syndromes, is highly prevalent, often persistent and highly disabling. It has been proposed that "third wave" therapies may be beneficial variants of cognitive behavioral treatments. However, evidence on their efficacy is scarce. This meta-analysis examines the efficacy of "third wave" psychotherapies (mindfulness-based cognitive therapy [MBCT], mindfulness-based stress reduction [MBSR], and acceptance and commitment therapy [ACT]) in adults with bodily distress. Method: We included randomized controlled trials (RCTs) treating adults with bodily distress using MBCT, MBSR, and ACT compared to inactive and non-specific control groups. A random effects model was used. The primary outcome was somatic symptom severity. Secondary outcomes were degrees of depression and of anxiety, health anxiety, perceived health status, mindfulness, psychological inflexibility, and pain acceptance. Results: Sixteen RCTs with 1,288 participants were included in the analysis (k = 4 MBCT, k = 7 MBSR, k = 5 ACT; k = 7 fibromyalgia, k = 5 irritable bowel syndrome, k = 1 chronic fatigue syndrome, k = 2 bodily distress, k = 1 medically unexplained symptoms). However, not all studies provided data for each of the relevant outcomes. The analyses revealed that "third wave" therapies were more effective than control conditions in reducing somatic symptom severity (k = 15, n = 1,100, g = -0.51, 95%CI -0.69; -0.32). Heterogeneity was moderate (I 2 = 52.8%, 95%CI 15.1 to 73.8). Effects for secondary outcomes were small to moderate with varying degrees of heterogeneity. We did not find differences between the different therapy approaches (mindfulness- vs. acceptance-based therapies); neither therapy dosis (i.e., total duration of therapy sessions) nor number of sessions were significant moderators of efficacy. Conclusions: The therapies addressing mindfulness and acceptance proved to be more effective than control conditions. Hence, they are promising treatment approaches for bodily distress. However, there is still need for research on which patient groups may benefit from these psychological approaches. Systematic review registration: https://osf.io/g7hby, identifier: 10.17605/OSF.IO/4RZGC.

Examining the performance of engineering treatment evaluation methodologies using the hypothetical treatment and actual treatment settings.

The selection of treatment evaluation methodology is paramount in determining reliable crash modification factors (CMFs) for engineering treatments. A lack of ground truth makes it cumbersome to examine the performance of treatment evaluation methodologies. In addition, a sound methodological framework is critical for evaluating the performances of treatment evaluation methodologies. In addressing these challenges, this study proposed a framework for assessing treatment evaluation methodologies by hypothetical treatments with known ground truth and actual real-world treatments. In particular, this study examined three before-after treatment evaluation approaches: 1) Empirical Bayes, 2) Simulation-based Empirical Bayes, and 3) Full Bayes methods. In addition, this study examined the Cross-Sectional treatment evaluation methodology. The methodological framework utilized five datasets of hypothetical treatment with known ground truth based on the hotspot identification method and a real-world dataset of wide centerline treatment on two-lane, two-way rural highways in Queensland, Australia. Results showed that all the methods could identify the ground truth of hypothetical treatments, but the Full Bayes approach better predicts the known ground truth compared to Empirical Bayes, Simulation-based Empirical Bayes, and Cross-Sectional methods. The Full Bayes approach was also found to provide the most precise estimate for real-world wide centerline treatment along rural highways compared to other methods. Moreover, the current study highlighted that the Cross-Sectional method offers a viable estimate of treatment effectiveness in case the before-period data is limited.

IONPs-Based Medical Imaging in Cancer Care: Moving Beyond Traditional Diagnosis and Therapeutic Assessment.

Cancer-related burden of morbidity and mortality is rapidly rising worldwide. Medical imaging plays an important role in every phase of cancer management, including diagnosis, staging, treatment planning and evaluation. Iron oxide nanoparticles (IONPs) could serve as contrast agents or labeling agents to enhance the identification and visualization of pathological tissues as well as target cells. Multimodal or multifunctional imaging can be easily acquired by modifying IONPs with other imaging agents or functional groups, allowing the accessibility of combined imaging techniques and providing more comprehensive information for cancer care. To date, IONPs-enhanced medical imaging has gained intensive application in early diagnosis, monitoring treatment as well as guiding radio-frequency ablation, sentinel lymph node dissection, radiotherapy and hyperthermia therapy. Besides, IONPs mediated imaging is also capable of promoting the development of anti-cancer nanomedicines through identifying patients potentially sensitive to nanotherapeutics. Based on versatile imaging modes and application fields, this review highlights and summarizes recent research advances of IONPs-based medical imaging in cancer management. Besides, currently existing challenges are also discussed to provide perspectives and advices for the future development of IONPs-based imaging in cancer management.

ECG Changes during Adult Life in Fabry Disease: Results from a Large Longitudinal Cohort Study.

Background: Fabry disease (FD) is an X-linked, lysosomal storage disorder leading to severe cardiomyopathy in a significant proportion of patients. To identify ECG markers that reflect early cardiac involvement and disease progression, we conducted a long term retrospective study in a large cohort of FD patients. Methods: A total of 1995 ECGs from 133 patients with classical FD (64% females, 80% treated with enzyme replacement therapy), spanning 20 years of follow-up, were compared to ECGs from 3893 apparently healthy individuals. Generalized linear mixed models were used to evaluate the effect of age, FD and sex on: P-wave duration, PR-interval, QRS-duration, QTc, Cornell index, spatial QRS-T angle and frontal QRS-axis. Regression slopes and absolute values for each parameter were compared between FD patients and control subjects. Results: At a younger age (<40 years), the Cornell index was higher and frontal QRS-axis more negative in FD patients compared to controls (p < 0.05). For the other ECG parameters, the rate of change, more than the absolute value, was greater in FD patients compared to controls (p < 0.05). From the fifth decade (men) or sixth (women) onwards, absolute values for P-wave duration, QRS-duration, QTc and spatial QRS-T angle were longer and higher in FD patients compared to control subjects. Conclusions: ECG abnormalities indicative of FD are age and sex dependent. Tracking the rate of change in ECG parameters could be a good way to detect disease progression, guiding treatment initiation. Moreover, monitoring ECG changes in FD can be used to evaluate the effectiveness of treatment.

Comparison of palatal volume and surface changes between bone-borne and tooth-tissue-borne maxillary expansion on cone beam computed tomography digital cast models.

OBJECTIVES: To compare the changes of palatal volume and area in patients treated with tooth-tissue-borne palatal expanders (conventional Haas) and miniscrew-supported palatal expanders (modified Haas). MATERIALS AND METHODS: The sample included casts of 22 patients treated as part of a clinical study at the Department of Orthodontics, Al-Azhar University, to correct their crossbite malocclusion. Patients were divided equally into two groups upon arrival. The first group, with a mean age of 12 years and 6 months, received the miniscrew-supported palatal expander. The second group, with a mean age of 12 years and 2 months, received the Haas design-palatal expansion appliance. Pre- and post-expansion dental casts were cone beam computed tomography scanned and the slices were constructed into 3D volumes. Fully automated superimposition was done for pre- and post-expansion 3D models. Palatal volume and area were determined, and all measurements were carried out blindly. Paired t-test was used to assess the mean differences within each group and Welch's t-test was applied to assess the mean changes between the two groups. Shapiro-Wilk test was used to test for the normality of the data. RESULTS: There were no statistical differences in volume changes either within each group or between the groups. Although area changes were statistically significant within each group, the difference between the groups was not significant. CONCLUSIONS: Changes that result from the use of either method to expand the upper arch occur primarily in the shape of the palate, but not in its size.

Extended treatment of multimodal cognitive behavioral therapy in children and adolescents with obsessive-compulsive disorder improves symptom reduction: a within-subject design.

BACKGROUND: Based on the current state of research regarding the treatment in pediatric obsessive-compulsive disorder (OCD), cognitive behavioral therapy (CBT) (in severe cases with additional pharmacotherapy) is considered as the first-line treatment according to internationally recognized guidelines. Research is mostly based on randomized controlled trials (RCTs; efficacy research). Thus, examined treatment conditions, especially the treatment duration, and patients' characteristics do not necessarily correspond to those found within routine care. Studies showed CBT packages as a whole to be efficacious, but less is known about the effects of individual CBT components. Furthermore, effects on comorbid symptoms or psychosocial impairment have been often neglected and different rater perspectives have been hardly considered in previous research. METHODS: This effectiveness study aimed to examine the effects of multimodal CBT in children, adolescents, and young adults (age 6-20 years) with OCD (n = 38) within routine care. Effects on obsessive-compulsive and co-existing symptoms were evaluated in a within-subject design by comparing changes during the assessment phase with 12-week standard treatment and with individually tailored extended treatment. Additionally, within the standard treatment, non-exposure treatment was compared to exposure treatment. Multi-informant assessment was applied, and the analyses included multilevel modeling and t-tests for pre-post comparisons. RESULTS: During the standard treatment and extended treatment, obsessive-compulsive symptoms, strain, and functional impairment significantly decreased. Moreover, a significant reduction of overall comorbid symptoms emerged, particularly regarding internalizing symptoms, including anxiety and depression. Comparisons of treatment components indicated that adding exposure with response prevention (ERP) has an additional positive effect. Clinical improvement and remission rates increased considerably when more treatment sessions were provided. CONCLUSIONS: These results suggest that improvement after an initial 12-week course of treatment may not allow for the prediction of non-responders/non-remitters and for the termination of treatment. Overall, the findings show that results from randomized controlled trials are transferrable to routine care. Trial registration number This study was registered retrospectively at the German Clinical Trials Register ( https://drks.de/search/de/trial/DRKS00030050 ).

Potential clinical utility of liquid biopsy in early-stage non-small cell lung cancer.

BACKGROUND: Liquid biopsy has been widely researched for early diagnosis, prognostication and disease monitoring in lung cancer, but there is a need to investigate its clinical utility for early-stage non-small cell lung cancer (NSCLC). METHODS: We performed a meta-analysis and systematic review to evaluate diagnostic and prognostic values of liquid biopsy for early-stage NSCLC, regarding the common biomarkers, circulating tumor cells, circulating tumor DNA (ctDNA), methylation signatures, and microRNAs. Cochrane Library, PubMed, EMBASE databases, ClinicalTrials.gov, and reference lists were searched for eligible studies since inception to 17 May 2022. Sensitivity, specificity and area under the curve (AUC) were assessed for diagnostic values. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted from the recurrence-free survival (RFS) and overall survival (OS) plots for prognostic analysis. Also, potential predictive values and treatment response evaluation were further investigated. RESULTS: In this meta-analysis, there were 34 studies eligible for diagnostic assessment and 21 for prognostic analysis. The estimated diagnostic values of biomarkers for early-stage NSCLC with AUCs ranged from 0.84 to 0.87. The factors TNM stage I, T1 stage, N0 stage, adenocarcinoma, young age, and nonsmoking contributed to a lower tumor burden, with a median cell-free DNA concentration of 8.64 ng/ml. For prognostic analysis, the presence of molecular residual disease (MRD) detection was a strong predictor of disease relapse (RFS, HR, 4.95; 95% CI, 3.06-8.02; p < 0.001) and inferior OS (HR, 3.93; 95% CI, 1.97-7.83; p < 0.001), with average lead time of 179 ± 74 days between molecular recurrence and radiographic progression. Predictive values analysis showed adjuvant therapy significantly benefited the RFS of MRD + patients (HR, 0.27; p < 0.001), while an opposite tendency was detected for MRD - patients (HR, 1.51; p = 0.19). For treatment response evaluation, a strong correlation between pathological response and ctDNA clearance was detected, and both were associated with longer survival after neoadjuvant therapy. CONCLUSIONS: In conclusion, our study indicated liquid biopsy could reliably facilitate more precision and effective management of early-stage NSCLC. Improvement of liquid biopsy techniques and detection approaches and platforms is still needed, and higher-quality trials are required to provide more rigorous evidence prior to their routine clinical application.

Assessment of Adherence to Clinical Guidelines in Patients with Chronic Hepatitis B.

Background and aims: Adherence to guidelines is associated with improved long-term outcomes in patients with chronic hepatitis B (CHB). We aimed to study the degree of adherence and determinants of non-adherence to management guidelines in a low endemic country. Methods: We reviewed the medical records of all CHB patients who visited our outpatient clinic in 2020. Adherence to guidelines was assessed based on predefined criteria based on the EASL guidance, and included the initiation of antiviral therapy when indicated, the optimal choice of antiviral therapy based on comorbidities, an assessment of HAV/HCV/HDV/HIV serostatus, renal function monitoring and enrolment in a HCC surveillance program if indicated. The adherence rates were compared across types of outpatient clinic (dedicated viral hepatitis clinic versus general hepatology clinic). Results: We enrolled 482 patients. Among the 276 patients with an indication for antiviral therapy, 268 (97.1%) received treatment. Among the patients with renal and/or bone disease, 26/29 (89.7%) received the optimal choice of antiviral agent. The assessment of HAV/HCV/HDV/HIV serostatus was performed in 86.1/91.7/94.4/78.4%. Among the 91 patients treated with tenofovir disoproxil, 57 (62.6%) underwent monitoring of renal function. Of the 241 patients with an indication for HCC surveillance, 212 (88.3%) were enrolled in a surveillance program. Clinics dedicated to viral hepatitis had superior adherence rates compared to general hepatology clinics (complete adherence rates 63.6% versus 37.2%, p < 0.001). Conclusions: Follow-up at a dedicated viral hepatitis clinic was associated with superior adherence to management guidelines.

Detection of Electroencephalographic Abnormalities and Its Associated Factors among Children with Autism Spectrum Disorder in Thailand.

Epilepsy often causes more severe behavioral problems in children with autism spectrum disorder (ASD) and is strongly associated with poor cognitive functioning. Interestingly, individuals with ASD without a history of epilepsy can have abnormal electroencephalographic (EEG) activity. The aim of this study was to examine associations between EEG abnormalities and the ASD severity in children. The children with ASD who enrolled at the Rajanagarindra Institute of Child Development, Thailand were included in this study. The severity of ASD was measured by interviewing their parents with the Thai autism treatment evaluation checklist. The short sensory profile checklist was used for screening the abnormality of children in each domain. Ordinal logistic regression analysis was used to examine associations between factors potentially linked to EEG abnormalities. Most of the study participants were boys (87.5%) and the median age was 5 years. Among the 128 children, 69.5% showed EEG abnormalities (41.4% slow-wave and 28.1% epileptiform-discharge). The results show that a larger number of symptoms and increased severity of ASD were independently associated with a higher risk of EEG abnormalities. Our results emphasize the need for guidelines on the presence of EEG abnormalities in children with ASD for the early detection of epilepsy and improving treatment outcomes.

Social prescribing from the patient's perspective: A literature review.

Social prescribing (SP) has aroused widespread interest across countries. SP is a way of linking patients in primary care with sources of support within the community by empowering patients to coproduce solutions to improve their health and well-being. While previous research has demonstrated that SP contributes to reducing the total cost of the National Health Service, the analysis of its effects on patients is still inadequate. This literature review critically evaluated SP from the patient's perspective through the lens of medical anthropology. The review was made with respect to the three key concepts: treatment evaluation, coproduction, and empowerment. The study revealed that SP services in the UK enabled patients to feel comfort in many cases, but general practitioners, link workers, and patients should be collaborative with each other, and their interrelationships should not be hierarchical. Nevertheless, certain modifications may be needed to introduce SP in other healthcare systems.

A nationwide registry for recurrent urolithiasis in the upper urinary tract - The RECUR study protocol.

BACKGROUND: Urinary stone disease is a widespread disease with tremendous impact on those affected and on societies around the globe. Nevertheless, clinical and health care research in this area seem to lag far behind cardiovascular diseases or cancer. This may be due to the lack of an immediate deadly threat from the disease and therefore less public and professional interest. However, the patients suffer from recurring, sometimes intense pain and often must be treated in hospital. Long-term morbidity includes doubled rates of chronic kidney disease and arterial hypertension after at least one stone-related event. Observational studies, more specifically, registries and other electronic data sets have been proposed as a means of filling critical gaps in evidence. We propose a nationwide digital and fully automated registry as part of the German Ministry for Education and Research (BMBF) call for the "establishment of model registries". METHODS: RECUR builds on the technical infrastructure of Germany's Medical Informatics Initiative. Local data integration centres (DIC) of participating medical universities will collect pseudonymized and harmonized data from respective hospital information systems. In addition to their clinical data, participants will provide patient reported outcomes using a mobile patient app. Scientific data exploration includes queries and analysis of federated data from DICs of eleven participating sites. All primary patient data will remain at the participating sites at all times. With comprehensive data from this longitudinal registry, we will be able to describe the disease burden, to determine and validate risk factors, and to evaluate treatments. Implementation and operation of the RECUR registry will be funded by the BMBF for five years. Subsequently, the registry is to be continued by the German Society of Urology without significant costs for study personnel. DISCUSSION: The proposed registry will substantially improve the structural and procedural framework for patients with recurrent urolithiasis. This includes advanced diagnostic algorithms and treatment pathways. The registry will help us identify those patients who will most benefit from specific interventions to prevent recurrences. The RECUR study protocol and the registry's technical architecture including full digitalization and automation of almost all registry-associated proceedings can be transferred to future registries. TRIAL REGISTRATION: This study is registered at the German Clinical Trial Register (Deutsches Register Klinischer Studien), DRKS-ID DRKS00026923 , date of registration January, 11th 2022.

Establishment and evaluation of retroperitoneal liposarcoma patient-derived xenograft models: an ideal model for preclinical study.

Retroperitoneal liposarcoma (RLPS) is one of the most common subtypes of retroperitoneal soft tissue sarcomas. It is characterized by poor sensitivity to radiotherapy and chemotherapy and a low success rate of complete surgical resection. However, there are few reliable preclinical RLPS models for target discovery and therapy research. In this study, we aimed to establish RLPS patient-derived xenograft (PDX) models that are useful for biological research and preclinical drug trials. A total of 56 freshly resected RLPS tissues were subcutaneously transplanted into non-obese diabetic-severe combined immune deficient (NOD-SCID) mice, with subsequent xenotransplantation into second-generation mice. The tumor engraftment rate of first generation PDXs was 44.64%, and higher success rates were obtained from implantations of dedifferentiated, myxous, pleomorphic, high-grade liposarcomas and those with retroperitoneal organ infiltration. The first- and second- generation PDX models preserved the histopathological morphology, gene mutation profiles and MDM2 amplification of the primary tissues. PDX models can also provide the benefit of retaining original tumor biology and microenvironment characteristics, such as abnormal adipose differentiation, elevated Ki67 levels, high microvessel density, cancer-associated fibroblast presence, and tumor-associated macrophage infiltration. Overall survival (OS) and disease-free survival (DFS) of patients with successful first-generation PDX engraftment were significantly poorer than those with failed engraftment. Treatment with MDM2 inhibitor RG7112 significantly suppressed tumor growth of DDLPS PDX in mice. In conclusion, we successfully established RLPS PDX models that were histologically, genetically, and molecularly consistent with the original tissues. These models might provide opportunities for advancing RLPS tumor biology research, facilitating the development of novel drugs, particularly those targeting MDM2 amplification, adipose differentiation process, angiogenesis, cancer-associated fibroblasts, and so on.

Psychometric properties of the Parma Scale for the treatment evaluation of offenders with mental disorder: A new instrument for routine outcome monitoring in forensic psychiatric settings.

PURPOSE: Routine Outcome Monitoring (ROM) is still poorly implemented in the routine forensic psychiatric practice. As reliable ROM instruments are lacking, the aims of this research was to assess the psychometric properties of the Parma Scale (Pr-Scale) and its sensitivity to measure scores' longitudinal changes. METHODS: Interrater and test-retest reliability, internal consistency and concurrent validity were investigated in offenders with mental disorder. Scores' longitudinal changeability was examined after a 3-month period using the Wilcoxon test for repeated measure. RESULTS: Sixty male adult patients were recruited in this study. Our findings showed good to excellent interrater and test-retest reliability, concurrent validity and internal consistency for the Pr-Scale. Pr-Scale scores also display a moderate to large changeability over time. CONCLUSIONS: Our results support the clinical use of the Pr-Scale in forensic psychiatric settings as reliable ROM instrument.