Final Analysis of Post-Marketing Surveillance for Avelumab + Axitinib in Patients With Renal Cell Carcinoma in Japan.

Introduction: Avelumab, an anti-programmed death ligand 1 antibody, was approved in combination with axitinib for curatively unresectable or metastatic renal cell carcinoma (RCC) in Japan in December 2019. Because the pivotal JAVELIN Renal 101 study included a limited number of Japanese patients, post-marketing surveillance (PMS) was required to evaluate outcomes (safety and effectiveness) in patients with RCC who received avelumab + axitinib treatment in clinical practice in Japan.

Materials And Methods: We report data from prospective, noncomparative, multicenter, observational PMS in patients with RCC who received ≥ 1 dose of avelumab.

Mindfulness Training vs Recovery Support for Opioid Use, Craving, and Anxiety During Buprenorphine Treatment: A Randomized Clinical Trial.

Importance: During buprenorphine treatment for opioid use disorder (OUD), risk factors for opioid relapse or treatment dropout include comorbid substance use disorder, anxiety, or residual opioid craving. There is a need for a well-powered trial to evaluate virtually delivered groups, including both mindfulness and evidence-based approaches, to address these comorbidities during buprenorphine treatment.

Objective: To compare the effects of the Mindful Recovery Opioid Use Disorder Care Continuum (M-ROCC) vs active control among adults receiving buprenorphine for OUD.

Comparing quantitative imaging biomarker alliance volumetric CT classifications with RECIST response categories.

Purpose: To assess agreement between CT volumetry change classifications derived from Quantitative Imaging Biomarker Alliance Profile cut-points (ie, QIBA CTvol classifications) and the Response Evaluation Criteria in Solid Tumors (RECIST) categories.

Materials And Methods: Target lesions in lung, liver, and lymph nodes were randomly chosen from patients in 10 historical clinical trials for various cancers, ensuring a balanced representation of lesion types, diameter ranges described in the QIBA Profile, and variations in change magnitudes. Three radiologists independently segmented these lesions at baseline and follow-up scans using 2 software tools.

Effect of different doses of ciprofol on hemodynamics induced by general anesthesia in elderly diabetic patients undergoing spinal surgery: a double-blind, randomized, controlled study.

Background: To evaluate the safety and efficacy of different doses of ciprofol for the induction of general anesthesia in elderly patients with diabetes undergoing spinal surgery.

Methods: Ninety elderly diabetic patients scheduled for elective single-level posterior lumbar interbody fusion (PLIF) under general anesthesia were enrolled and randomly assigned to three groups according to the induction dose of ciprofol: group A (0.2 mg/kg), Group B (0.

Comparing apples and oranges in youth depression treatments? A quantitative critique of the evidence base and guidelines.

Objectives: Should a young person receive psychotherapy or medication for their depression and on what evidence do we base this decision? In this paper, we test the factors across modalities that may influence comparability between medication and psychotherapy trials.

Methods: We included 92 randomised controlled trials (RCTs) of psychotherapy and medication for child and adolescent depression (mean age 4-18 years). Using meta-analyses, we compared (a) participant characteristics and (b) trial characteristics in medication and psychotherapy trials.

Resting state EEG in young children with Tuberous Sclerosis Complex: associations with medications and seizures.

Background: Tuberous Sclerosis Complex (TSC) is a rare genetic condition caused by mutation to TSC1 or TSC2 genes, with a population prevalence of 1/7000 births. TSC manifests behaviorally with features of autism, epilepsy, and intellectual disability. Resting state electroencephalography (EEG) offers a window into neural oscillatory activity and may serve as an intermediate biomarker between gene expression and behavioral manifestations.

Long-term hemodynamic responses and reverse remodeling after pharmacotherapy in HFpEF versus HFrEF: a systematic review and meta-analysis.

The acute response to therapeutic afterload reduction differs between heart failure with preserved (HFpEF) versus reduced ejection fraction (HFrEF), with larger left ventricular (LV) stroke work augmentation in HFrEF compared to HFpEF. This may (partially) explain the neutral effect of HFrEF-medication in HFpEF. It is unclear whether such differences in hemodynamic response persist and/or differentially trigger reverse remodeling in case of long-term afterload reduction.

Discordance, accuracy and reproducibility study of pathologists' diagnosis of melanoma and melanocytic tumors.

Accurate melanoma diagnosis is crucial for patient outcomes and reliability of AI diagnostic tools. We assess interrater variability among eight expert pathologists reviewing histopathological images and clinical metadata of 792 melanoma-suspicious lesions prospectively collected at eight German hospitals. Moreover, we provide access to the largest panel-validated dataset featuring dermoscopic and histopathological images with metadata.

Predictors of willingness to participate in COVID-19 clinical trials among Black and Latino adults.

Introduction: Black and Latino individuals are underrepresented in COVID-19 treatment and vaccine clinical trials, calling for an examination of factors that may predict willingness to participate in trials.

Methods: We administered the Common Survey 2.0 developed by the Community Engagement Alliance (CEAL) Against COVID-19 Disparities to 600 Black and Latino adults in Baltimore City, Prince George's County, Maryland, Montgomery County, Maryland, and Washington, DC, between October and December 2021.

Design and validation of cell-based potency assays for frataxin supplementation treatments.

Friedreich's ataxia (FRDA) is a multisystem, autosomal recessive disorder caused by mutations in the frataxin () gene. As FRDA is considered an FXN deficiency disorder, numerous therapeutic approaches in development or clinical trials aim to supplement FXN or restore endogenous expression. These include gene therapy, protein supplementation, genome editing or upregulation of transcription.

Novel therapies in SLE treatment: A literature review.

Systemic lupus erythematosus (SLE) is a chronic, autoimmune inflammatory disease with a multisystem manifestation and a variety of clinical symptoms. Over the last decades, the prognosis and life expectancy of patients with SLE improved significantly due to the implementation of corticosteroids combined with immunosuppressive agents. Nevertheless, the use of these medications is often associated with the occurrence of serious side effects and additional deterioration of organ function.

Updates on neonatal cell and novel therapeutics: Proceedings of the Second Neonatal Cell Therapies Symposium (2024).

Cell therapies as treatments for neonatal conditions have attracted significant research and parent interest over the last two decades. Mesenchymal stromal cells, umbilical cord blood cells and neural stem cells translate from lab, to preclinical and into clinical trials, with contributions being made from all over the world. Effective and timely translation involves frequent reflection and consultation from research-adjacent fields (i.

Therapist-Guided Internet-Delivered Acceptance-Enhanced Behavior Therapy for Skin-Picking Disorder: A Randomized Controlled Trial.

Despite its high prevalence, individuals suffering from skin-picking disorder (SPD) face limited access to treatment due to several factors, including geographical and economic barriers, as well as a shortage of properly trained therapists. Offering Internet-delivered therapy could be a solution to these barriers. This study aimed to evaluate the efficacy of therapist-guided Internet-delivered acceptance-enhanced behavior therapy (iBT) for SPD compared to a wait-list control condition.

Content Validity of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a validated and highly utilized measure for evaluating patients with Friedreich Ataxia. While construct validity of FARS-ADL has been shown for spinocerebellar ataxia (SCA), content validity has not been established.

Methods: Individuals with SCA1 or SCA3 (n = 7) and healthcare professionals (HCPs) with SCA expertise (n = 8) participated in qualitative interviews evaluating the relevance, clarity, and clinical meaningfulness of FARS-ADL for assessment of individuals with SCA.

'Which treatment do you believe you received?' A randomised blinding feasibility trial of spinal manual therapy.

Background: Blinding is essential for mitigating biases in trials of low back pain (LBP). Our main objectives were to assess the feasibility of blinding: (1) participants randomly allocated to active or placebo spinal manual therapy (SMT), and (2) outcome assessors. We also explored blinding by levels of SMT lifetime experience and recent LBP, and factors contributing to beliefs about the assigned intervention.

Association of age and performance status with adverse events in older adults with diffuse large B-cell lymphoma receiving frontline R-CHOP therapy: Alliance 151930, a secondary analysis of the phase III trial CALGB 50303.

Introduction: Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP) therapy is the standard of care for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, detailed delineation of toxicity data is limited and has not been examined by age. We sought to examine adverse event data in patients receiving R-CHOP from the Cancer and Leukemia Group B (CALGB) 50303 trial to determine if there were differences in grade 3+ toxicities by age cohort or ECOG performance status (PS), and if outcome was impacted by age cohort or toxicity occurrence.

Estimating the ovarian cancer CA-125 preclinical detectable phase, in-vivo tumour doubling time, and window for detection in early stage: an exploratory analysis of UKCTOCS.

Background: The ovarian cancer (OC) preclinical detectable phase (PCDP), defined as the interval during which cancer is detectable prior to clinical diagnosis, remains poorly characterised. We report exploratory analyses from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

Methods: In UKCTOCS between Apr-2001 and Sep-2005, 101,314 postmenopausal women were randomised to no screening (NS) and 50,625 to annual multimodal screening (MMS) (until Dec-2011) using serum CA-125 interpreted by the Risk of Ovarian Cancer Algorithm (ROCA).

Acceptance, Safety, and Effect Sizes in Online Dialectical Behavior Therapy for Borderline Personality Disorder: Interventional Pilot Study.

Background: The potential of telehealth psychotherapy (ie, the online delivery of treatment via a video web-based platform) is gaining increased attention. However, there is skepticism about its acceptance, safety, and efficacy for patients with high emotional and behavioral dysregulation.

Objective: This study aims to provide initial effect size estimates of symptom change from pre- to post treatment, and the acceptance and safety of telehealth dialectical behavior therapy (DBT) for individuals diagnosed with borderline personality disorder (BPD).

Randomized Comparison of Magnetic Resonance Imaging Versus Transurethral Resection for Staging New Bladder Cancers: Results From the Prospective BladderPath Trial.

Purpose: Transurethral resection of bladder tumor (TURBT) is the initial staging procedure for new bladder cancers (BCs). For muscle-invasive bladder cancers (MIBCs), TURBT may delay definitive treatment. We investigated whether definitive treatment can be expedited for MIBC using flexible cystoscopic biopsy and multiparametric magnetic resonance imaging (mpMRI) for initial staging.

Protocol for a multisite randomised controlled trial assessing the effect of the Telehealth for Early Developmental Intervention in babies born very preterm (TEDI-Prem) programme on neurodevelopmental outcomes and parent well-being.

Introduction: Infants born very preterm (VPT, <32 weeks' gestation) are at increased risk for neurodevelopmental impairments including motor, cognitive and behavioural delay. Parents of infants born VPT also have poorer mental health outcomes compared with parents of infants born at term.We have developed an intervention programme called TEDI-Prem (Telehealth for Early Developmental Intervention in babies born very preterm) based on previous research.

Therapeutic alliance during trauma focused treatment in adolescent and young adult patients with PTSD.

Background: Greater therapeutic alliance has been associated with an improved treatment outcome in various clinical populations. However, there is a lack of evidence for this association in posttraumatic stress disorder (PTSD) in young patients. We therefore investigated the development of the therapeutic alliance during Developmentally adapted cognitive processing therapy (D-CPT) in adolescents and young adults with PTSD following abuse to answer the question whether there was a connection between the therapeutic alliance and symptom reduction.

Measurement Properties of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a valid, highly utilized measure for assessing ADL impacts in patients with Friedreich ataxia. We provide evidence of the psychometric validity of the FARS-ADL in two cohorts of patients with spinocerebellar ataxia (SCA).

Methods: Using data from a cohort of real-world subjects with SCA (recruited at Massachusetts General Hospital [MGH]; n = 33) and a phase 3 trial of troriluzole in adults with SCA (NCT03701399 [Study 206]; n = 217), comprising a subset of patients with the SCA3 genotype (n = 89), the psychometric measurement properties and minimal change thresholds of the FARS-ADL were examined.

Ramadan intermittent fasting for patients with gastrointestinal and hepatobiliary diseases: practical guidance for health-care professionals.

Ramadan intermittent fasting can pose challenges and risks for some groups of patients. Based on a narrative literature review and our clinical expertise, we provide practical guidance for clinicians managing patients with gastrointestinal and hepatobiliary conditions who wish to fast during Ramadan. Following the established International Diabetes Federation and Diabetes and Ramadan International Alliance risk stratification framework, we categorised patients' risk as low or moderate, high, or very high.

Cancer Neuroscience of Brain Tumors: From Multicellular Networks to Neuroscience-Instructed Cancer Therapies.

Deepening our understanding of neuro-cancer interactions can innovate brain tumor treatment. This mini review unfolds the most relevant and recent insights into the neural mechanisms contributing to brain tumor initiation, progression, and resistance, including synaptic connections between neurons and cancer cells, paracrine neuro-cancer signaling, and cancer cells' intrinsic neural properties. We explain the basic and clinical-translational relevance of these findings, identify unresolved questions and particularly interesting future research avenues, such as central nervous system neuro-immunooncology, and discuss the potential transferability to extracranial cancers.

Novel Inhibitors for MDM2-MDM4 E3 Ligase Potently Induce p53-Indepedent Apoptosis in Drug-Resistant Leukemic Cells.

MDM2 and MDM4 are major negative regulators of tumor suppressor p53. Beyond regulating p53, MDM2 possesses p53-independent activity in promoting cell cycle progression and tumorigenesis via its RING domain ubiquitin E3 ligase activity. MDM2 and MDM4 form heterodimer polyubiquitin E3 ligases via their RING domain interaction.