Results Of Trial Research Articles

Conversion surgery after gemcitabine and cisplatin plus durvalumab for advanced intrahepatic cholangiocarcinoma: A case report

BACKGROUND The combination of immune checkpoint inhibitors and chemotherapy has shown promising results for the treatment of advanced biliary tract cancer (BTC). Based on the results of the TOPAZ-1 trial, a gemcitabine and cisplatin plus durvalumab (GCD) regimen was recently approved as first-line therapy for patients with advanced BTC. However, post-GCD conversion surgery has not been previously studied. Herein, we describe a case of advanced intrahepatic cholangiocarcinoma (ICC) successfully treated with radical surgery after GCD. CASE SUMMARY A 65-year-old female diagnosed with advanced ICC with periductal infiltration into the hepatic hilum underwent eight cycles of GCD, followed by durvalumab maintenance treatment, with mild adverse events. Partial response was obtained. Subsequently, a conversion surgery with extended left hepatectomy and bile duct resection was performed. The resection margins were negative, and the pathological diagnosis was compatible with small duct type ICC. The patient remained disease-free for 8 months without adjuvant chemotherapy. CONCLUSION We describe the case of a patient who received successful conversion surgery after GCD treatment for advanced ICC.

Efficacy and safety of edoxaban in patients with cardioembolic stroke

Ischemic strokes due to cardiogenic embolism are associated with an increased risk of death or permanent disability, which emphasizes the importance of their prevention. Edoxaban is a Xa inhibitor that is widely used globally as a new oral anticoagulant to prevent thromboembolic complications in patients with atrial fibrillation and an increased risk of stroke. The purpose of this review is to summarize data on the efficacy and safety of edoxaban in the secondary stroke prevention. The literature review was conducted using PubMed and Medscape databases to search for publications on clinical trials and clinical guidelines on oral anticoagulant treatment for stroke prevention. The results of clinical trials show that in patients with atrial fibrillation, edoxaban is non-inferior to warfarin in efficacy for primary and secondary stroke prevention, but compared to warfarin, edoxaban treatment is much safer (significantly reduces the risk of serious bleedings, including intracranial ones). The safety profile of edoxaban makes it one of the best drugs for the treatment of elderly patients and those with chronic kidney disease. In general, the results of recent clinical trials indicate that in cardioembolic stroke due to atrial fibrillation, the early initiation of treatment with direct oral anticoagulants is safe and reduces the risk of recurrent embolic events. Timely determination of the etiological subtype of ischemic stroke, in particular the detection of paroxysmal atrial fibrillation, and consideration of individual patient characteristics are the key to an optimal secondary prevention strategy that minimizes the risk of recurrent brain damage and improves the quality of life after stroke.

Evaluation of electrolyzed water to control fungal trunk pathogens in grapevine nurseries.

Grapevine producers demand solutions to control fungal trunk pathogens (FTPs) in nurseries. Adopting integrated strategies combining several control methods has been indicated as the best approach to prevent or reduce infections on grapevine propagation material. In recent years, electrolyzed water (EW) has emerged as a sustainable alternative for disinfection. Thus, the objectives of our study were: (i) to determine the effect of EW on the conidial germination and mycelial growth of a wider selection of FTPs associated with different grapevine trunk diseases; and (ii) to evaluate the efficacy of EW to reduce infections caused by FTPs on grapevine planting material during the propagation process in a commercial nursery. In vitro experiments demonstrated the capacity of different EW products to reduce conidial germination and mycelium survival of selected FTPs belonging to different genera and species, even given that the results were variable depending on the type of product, pathogen evaluated and time of treatment. In two different nursery experiments, conducted in 2021 and 2023, EW-treated plants showed lower incidence of Petri and black-foot associated pathogens when compared with the untreated ones, although these differences were statistically significant only in 2023. Moreover, there were no negative effects of the EW treatments regarding the viability of the grafted plants. Our results about the effect of EW against conidia germination and mycelium survival of FTPs, and the results of the nursery trials, suggest that EW could have promising applications in the grapevine nursery process. This treatment could be integrated with other complementary management strategies and also be extended to nurseries of other fruit and nut crops, in which FTPs are currently becoming important emerging diseases. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Methodological insights from the EPISTOP trial to designing clinical trials in rare diseases-A secondary analysis of a randomized clinical trial.

In clinical research, the most appropriate way to assess the effect of an intervention is to conduct a randomized controlled trial (RCT). In the field of rare diseases, conducting an RCT is challenging, resulting in a low rate of clinical trials, with a high frequency of early termination and unpublished trials. The aim of the EPISTOP trial was to compare outcomes in infants with tuberous sclerosis (TSC) who received vigabatrin preventively before the seizures onset with those who received it conventionally after. The study was designed as a prospective, multicentre, randomized clinical trial. However, ethics committees at four centres did not approve this RCT design, resulting in an open-label trial (OLT) in these four centres and an RCT in the other six centres. In this paper, we re-analyse the data from the EPISTOP trial using methods to investigate the influence of allocation bias on the results of the EPISTOP trial. A bias-corrected analysis is used to support and strengthen the published results. We included a term representing the effect of selection bias as an influencing factor on the corresponding endpoint in the statistical model. Thus, the treatment effect estimates for the primary endpoint of time to first seizure and additional secondary endpoints are adjusted for the bias effect. The bias-corrected analyses for the primary endpoint show that the estimated hazard ratio and associated confidence intervals are in a very similar range (original analysis: HR 2.91, 95%-CI [1.11 to 7.67], p-value 0.0306; bias-corrected analysis: HR 2.89, 95%-CI [1.10 to 7.58], p-value 0.0316). This was also the case for the secondary endpoints. The statistical re-analysis of the raw trial data therefore supports the published results and confirms that there is no additional bias introduced by randomization, thereby increasing the value of the results. However, this highlights that this aspect needs to be considered in future trials, especially in rare diseases, to avoid additional biases in an already small sample size where it may be difficult to reach significance.

Robotic versus laparoscopic liver resection for difficult posterosuperior segments: a systematic review with a meta-analysis of propensity-score matched studies.

The outcomes of minimally invasive liver surgery for posterosuperior segments (PS) are still debated. Since the results of ongoing trials focusing on the results of laparoscopic liver resection (LLR) and robotic liver resection (RLR) in this setting are still awaited, the best evidence currently comes from retrospective propensity-score matched (PSM) studies. The aim of this meta-analysis was to assess the outcomes of RLR for difficult located lesions and to provide evidence for its use in clinical practice. A systematic review with meta-analysis was conducted to evaluate the safety and efficacy of LLR and RLR for PS segments. The Medline, Embase and Web of Science Library electronic databases were searched to identify available research published up to June 2024. Five studies with a total of 2907 patients (RLR: n = 1084; LLR: n = 1823) were included in the meta-analysis. The RLR group had less estimated blood loss (EBL) (MD: -88.3, 95% CI -144.2--32.3; p = 0.012), fewer blood transfusions (OR 0.70, 95% CI 0.39-0.80, p = 0.033), and a shorter operative time (MD -27.3, 95% CI -49.4--5.1; p = 0.027). No differences in postoperative morbidity, mortality and R1 resection rates were observed. RLR for lesions in the PS segments are safe and effective, and may have superior surgical outcomes than LLR.

Family Care Intervention Effect on the Family Support Needs of Residents in Nursing Homes: A Cluster Randomized Trial

Purpose To assess the impact of a home care intervention on the family support needs of nursing home residents through a group clinical trial and blinded outcome assessment. Method A cluster randomized trial was conducted at two nursing homes in Zhengzhou. Each nursing home was randomized to either the intervention or control group. Eighty-two residents were enrolled in the study. Intervention group participants ( n = 41) received a family support intervention, and those in the control group ( n = 41) received the institution's standard daily care routine. The Questionnaire of Family Support Needs; Perceived Social Support Scale; and Family Adaptation, Partnership, Growth, Affection, Resolve Index were used to assess post-intervention outcomes. Results There were no significant differences between groups regarding baseline data. There were statistically significant ( p < 0.05) within-subject, between-subject, and interaction effects for both groups regarding family support needs, perceived social support, and family functioning. Conclusion Findings contribute to strengthening the care of residents in nursing homes, indicating the importance of family support, which can positively influence perceived social support and family function. The long-term efficacy of the intervention should be further verified. [ Journal of Gerontological Nursing, xx (xx), xx–xx.]

California Stress, Trauma, and Resilience Study (CalSTARS) protocol: A multiomics-based cross-sectional investigation and randomized controlled trial to elucidate the biology of ACEs and test a precision intervention for reducing stress and enhancing resilience

Adverse Childhood Experiences (ACEs) are very common and presently implicated in 9 out of 10 leading causes of death in the United States. Despite this fact, our mechanistic understanding of how ACEs impact health is limited. Moreover, interventions for reducing stress presently use a one-size-fits-all approach that involves no treatment tailoring or precision. To address these issues, we developed a combined cross-sectional study and randomized controlled trial, called the California Stress, Trauma, and Resilience Study (CalSTARS), to (a) characterize how ACEs influence multisystem biological functioning in adults with all levels of ACE burden and current perceived stress, using multiomics and other complementary approaches, and (b) test the efficacy of our new California Precision Intervention for Stress and Resilience (PRECISE) in adults with elevated perceived stress levels who have experienced the full range of ACEs. The primary trial outcome is perceived stress, and the secondary outcomes span a variety of psychological, emotional, biological, and behavioral variables, as assessed using self-report measures, wearable technologies, and extensive biospecimens (i.e. DNA, saliva, blood, urine, & stool) that will be subjected to genomic, transcriptomic, proteomic, metabolomic, lipidomic, immunomic, and metagenomic/microbiome analysis. In this protocol paper, we describe the scientific gaps motivating this study as well as the sample, study design, procedures, measures, and planned analyses. Ultimately, our goal is to leverage the power of cutting-edge tools from psychology, multiomics, precision medicine, and translational bioinformatics to identify social, molecular, and immunological processes that can be targeted to reduce stress-related disease risk and enhance biopsychosocial resilience in individuals and communities worldwide.

Scientific Validity and Fair Subject Selection: An Empirical Analysis of Recruitment Practices in Clinical Trials

This study investigates the relationship between scientific validity and fair subject selection in clinical trials, focusing on recruitment practices. By analyzing 200 clinical trials across oncology, cardiology, and neurology, this research identifies key barriers to diversity and assesses the effectiveness of institutional policies in promoting equitable recruitment. The findings reveal that despite efforts to improve inclusivity, demographic disparities persist, particularly in terms of racial and ethnic representation. Recruitment barriers, including logistical challenges, mistrust among minority groups, and insufficient outreach resources, are prevalent, with oncology trials exhibiting the most significant issues related to minority participation. Additionally, the study highlights that stronger Institutional Review Board (IRB) policies with enforced diversity guidelines lead to higher minority representation in trials. Through a mixed-methods approach, combining systematic trial reviews, surveys of recruitment personnel, and institutional policy assessments, the study emphasizes the importance of community engagement and culturally competent recruitment strategies. The research suggests that while progress has been made, greater transparency, targeted outreach, and mandatory diversity tracking are necessary to achieve equitable and scientifically valid clinical trial outcomes. The study concludes with recommendations for future research to explore technological innovations and broader therapeutic areas, offering potential solutions for overcoming the barriers to diversity in clinical trials.

Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Final Results of the ORATOR Randomized Trial.

Radiotherapy (RT) and transoral robotic surgery (TORS) are both curative-intent treatment options for oropharyngeal squamous cell carcinoma (OPSCC). Herein, we report the final outcomes of the ORATOR trial comparing these modalities, 5 years after enrollment completion. We randomly assigned 68 patients with T1-2N0-2 OPSCC to RT (with chemotherapy if node-positive) versus TORS plus neck dissection (± adjuvant RT/chemoradiation). The primary end point was swallowing quality of life (QOL) assessed with the MD Anderson Dysphagia Inventory (MDADI). Secondary end points included overall and progression-free survival (OS, PFS), adverse events (AEs), and other QOL metrics. The primary end point has been previously reported (Nichols 2019). In this report, the median follow-up was 5.1 years (IQR, 5.0-5.3 years). MDADI total scores converged by 5 years and were not significantly different across the follow-up period (P = .11). EORTC QLQ-C30 and H&N35 scores demonstrated differing profiles, including worse dry mouth in the RT arm (P = .032) and worse pain in the TORS arm (P = .002). Grade 2-5 AE rates did not differ between arms (91% [n = 31] v 97% [n = 33] respectively, P = .61), with more neutropenia and hearing loss in the RT arm, and more dysphagia and other pain in the TORS arm based on grades 2-5 (all P < .05). There were no differences in OS or PFS. In conclusion, toxicity and QOL profiles differ in some domains between RT and TORS, but oncologic outcomes were excellent in both arms. Choice of treatment should remain a shared decision between the patient and their providers.

The Relationship of Diuretics and Dietary Sodium in Patients with Heart Failure: An Analysis of the SODIUM-HF Trial

BackgroundSODIUM-HF was a large clinical trial testing dietary sodium restriction compared to usual care in patients with heart failure that showed no reduction in clinical events. It has been suggested that diuretic doses in response to dietary sodium modification may have influenced the trial results. ObjectiveWe assessed the effects of baseline diuretic dose and diuretic dose changes on clinical outcomes in the SODIUM-HF trial. MethodsDiuretics were converted to furosemide-equivalent diuretic total daily doses. Furosemide dose was treated as a continuous variable and also stratified into 0 mg, 1–39 mg, 40 mg, 41–80 mg, and >80 mg daily. The baseline diuretic dose and change in diuretic dose were assessed and correlated with dietary sodium restriction and changes in dietary sodium intake. We then examined the relationship between diuretic dosing and the primary outcomes of SODIUM-HF (cardiovascular-related emergency department visit, cardiovascular-related hospitalization, and all-cause mortality). ResultsOf the 806 patients enrolled in the SODIUM-HF trial, 784 had known diuretic status at baseline: 209 patients (26.7%) with 0 mg, 134 patients (17%) with 1-39 mg, 205 patients (26.1%) with 40 mg, 118 patients (15.1%) with 41-80 mg, and 118 patients (15.1%) with >80 mg. No correlation was found between dietary sodium intake and diuretic dose, either at baseline or change throughout the study (P>0.05). For the primary outcomes, the 2-year risk of primary outcomes was strongly correlated with diuretic dose at baseline across the overall SODIUM-HF population (P<0.001). No significant association was found between the treatment arm and the risk of primary outcomes, within each baseline diuretic dose range or with change in diuretic dose (both P>0.05). ConclusionsAlthough a higher baseline diuretic dose was associated with worse clinical outcomes, no association was found between dietary sodium restriction, baseline or change in diuretic dose and the primary outcomes.

Joint Models Inform the Longitudinal Assessment of Patient-Reported Outcomes in Clinical Trials: A Simulation Study and Secondary Analysis of the Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery (RELIEF) Randomized Controlled Trial

Evaluate the utility of a joint model when analysing a patient-reported endpoint as part of a randomized controlled trial in which censoring occurs when patients die during follow-up. The present study comprises two parts: first we re-analyzed data from a previously published randomized controlled trial comparing two fluid regimens in the first 24 hours of major abdomino-pelvic surgery ('RELIEF' trial). In this trial, patient-reported disability was measured at multiple timepoints before and after surgery. Next, we conducted a simulation study to jointly emulate patient-reported disability and survival, similar to the RELIEF trial, under nine treatment-outcome scenarios. In both parts, we compared a joint model analysis to a linear mixed effect model combined with one of several traditional methods of handling longitudinal missingness: available data analysis, complete case analysis, last observation carried forward, and worst-case assumption. In part one, the joint model revealed no between-group differences in patient-reported disability at one, three, six, and 12 months after surgery. The worst-case approach consistently resulted in the largest deviation from the joint model estimates, although in this particular setting none of the approaches materially changed the study's conclusions. In part two, the simulations revealed that across all treatment-outcome scenarios, the joint model expectedly produced unbiased estimates of patient-reported disability. Similarly, employing an approach based on all available data (i.e., relying on the maximum likelihood estimator for handling missingness) yielded disability estimates close to the simulated values, albeit with slight bias across some scenarios. The last observation carried forward approach mirrored the joint model's estimates except when the treatment had a non-null effect on patient-reported disability. The worst case analysis resulted in high bias, which was particularly evident when the treatment had a large effect on survival. The complete case analysis resulted in high bias across all scenarios. In randomized trials that employ a patient-reported outcome as one of their endpoints, a joint model can address bias arising from informative missingness related to death. Methods for handling missingness based on all available data appear to be a reasonable alternative to joint models, with only slight bias across some simulated scenarios.

Gene editing of Angiotensin for blood pressure management

Arterial hypertension has remained the world's leading cause of morbidity and mortality for more than 20 years. While early Genome-Wide Association Studies raised the hypothesis that a precision medicine approach could be implemented in the treatment of hypertension, the large number of single nucleotide polymorphisms that were found to be associated with blood pressure and their limited impact on the blood pressure values have initially hampered these expectations. With the development and refinement of gene-editing and RNA-based approaches allowing selective and organ-specific modulation of critical systems involved in blood pressure regulation, a renewed interest in genetic treatments for hypertension has emerged. The CRISPR-Cas9 system, antisense oligonucleotides (ASO) and small interfering RNA (siRNA) have been used to specifically target the hepatic angiotensinogen (AGT) production, with the scope of safely but effectively reducing the activation of the renin-angiotensin system, ultimately leading to an effective reduction of the blood pressure with extremely simplified treatment regimens that involve weekly, monthly or even once-in-life injection of the drugs. Among the various approaches, siRNA and ASO that reduce hepatic AGT production are in advanced development, with phase I and II clinical trials showing their safety and effectiveness. In the current manuscript, we review the mode of action of these new approaches to hypertension treatment, discussing the results of the clinical trials and their potential to revolutionize the management of hypertension.

Self-criticism predicts antidepressant effects of intermittent theta-burst stimulation in Major Depressive Disorder

BackgroundSelf-criticism is a risk factor for depression, however higher degrees of self-criticism have been associated with greater antidepressant benefits from repetitive transcranial magnetic stimulation (rTMS), suggesting that self-criticism may act as a proxy for function of the targeted circuit.We test this hypothesis using secondary data from an rTMS treatment trial where an NMDA receptor agonist (D-Cycloserine) was used to enhance TMS synaptic plasticity to improve efficacy. We hypothesized that self-criticism would be more strongly associated with treatment outcome when stimulation was paired with D-Cycloserine than with a placebo. MethodsIn a 4-week single-site double-blind randomized placebo-controlled trial, fifty adults with Major Depressive Disorder (MDD) (NCT03937596) were randomized to receive placebo or D-Cycloserine (100 mg) with daily intermittent theta-burst stimulation (iTBS) to the left dorsolateral prefrontal cortex (DLPFC). At baseline and after treatment, self-criticism was assessed using the Depressive Experiences Questionnaire as a secondary trial outcome and depressive symptoms were assessed using the clinician rated Montgomery Asberg Depression Rating scale (MADRS). Clinical response was defined as a ≥50 % decrease on the MADRS. ResultsSelf-criticism differentially predicted antidepressant effects when operationalized as both percent decrease on the MADRS and clinical response (≥50 % decrease), with a statistically significantly stronger association in the iTBS+D-Cycloserine group than the iTBS+Placebo condition. Self-criticism did not significantly change in either condition over the course of treatment. ConclusionsOur data suggests that iTBS to the left DLPFC engages a circuit related to self-criticism. Higher levels of self-criticism predicted better response to iTBS with an adjuvant that enhances synaptic plasticity. This suggests that personality traits may be used to tailor non-invasive neurostimulation treatments.

The Influence of Body Language in Legal Settings

This paper examines the significant role of body language in legal environments and its implications for various courtroom participants, including jurors, judges, attorneys, and witnesses. While verbal communication remains the primary focus in courtrooms, non-verbal cues play a pivotal role in shaping perceptions of credibility, truth, and persuasion. The study reviews common body language signals and their interpretations, considering how these affect judgments, credibility assessments, and decision-making processes. By examining these dynamics, this research aims to highlight the importance of non-verbal communication in the legal field and propose strategies for legal professionals to utilize body language effectively to strengthen courtroom interactions and outcomes. Case studies provide real-world applications, demonstrating how an awareness of body language can impact trial outcomes and suggesting that training in non-verbal communication could be beneficial for legal professionals. Keywords: Body Language, Legal Communication, Non-verbal Cues, Credibility, Persuasion.

Ecological momentary assessment models trajectories of expectancy following exposure: A proof-of-concept pilot study

Background and objectivesThe Inhibitory Retrieval Approach to exposure therapy for fears and anxiety emphasizes prediction error as one of several strategies for improving outcomes. Prediction error depends on disconfirmation of expectancies for the feared outcome, and thus exposure strategies that derive from inhibitory retrieval approaches emphasize expectancy violation during exposure. However, research studies examining expectancy violation in exposure therapy have treated expectancy as a stable characteristic, assuming that expectancy following an exposure exercise remains constant over time. This brief report outlines two different uses of a methodology for using ecological momentary assessment (EMA) to assess between-session expectancy following exposure during treatment for anxiety, and reports on pilot trial results. MethodsAdults with social anxiety disorder (N = 12) and spider phobia (N = 31) taking part in larger trials investigating exposure therapy completed EMA questionnaires assessing expectancy for their feared outcome for 2–4 days following each of two exposure sessions. ResultsExpectancy ratings decreased from pre-to post-exposure and remained stable for 2–4 days following exposure. LimitationsThis pilot study used a very limited sample size and should be replicated in a larger sample. ConclusionsExpectancy for feared outcome may be assessed using EMA following exposure sessions. Pilot results suggest that expectancy decreases immediately following exposures and remains stable afterwards.

Высокомасличный сорт рапса ярового Юбилейный 23

In 2023, to the State commission of the Russian Federation on testing and protection of breeding achievements, approved for cultivation, the new variety of spring rapeseed Yubileyny 23 was submitted. It was developed in the Siberian Experimental Station – a branch of V.S. Pustovoit All-Russian Research Institute of Oil Crops by a method of individual selection from the variety Yubileyny, which has been included into the State register of breeding achievements since 1998. The breeding work was aimed on improvement of main economically valuable traits: very early maturation, yield, oil content, resistance to lodging, shattering, and main pathogens. In 2016, an elite plant No. 34863 was selected. The main feature of this variety is high fat content in seeds (up to 53.0%) that allows increasing oil yield per unit area. Due to competitive trial results (2021–2023), the variety if spring rapeseed Yubileyny 23 exceeded the standard variety Granit by seed yield by 0.25 t/ha and by oil yield by 168 kg/ha, and the variety Yubileyny – by 0.46 t/ha and 298 kg/ha, respectively. The new variety is supposed to be produced in Volga-Vyatka (4), Middle Volga (7), Urals (9), Western Siberian (10), and Eastern Siberian (11) regions of cultiva-tion. An originator of the variety Yubileyny 23 is V.S. Pustovoit All-Russian Research Institute of Oil Crops.

The Emerging Treatment of BCG (Bacillus Calmette-Guérin)-Unresponsive Non–Muscle-Invasive Bladder Cancer

Bacillus Calmette-Guérin (BCG) remains the cornerstone in the treatment of high-risk non-muscle-invasive bladder cancer (NMIBC), effectively preventing recurrence and progression. Unfortunately, a significant proportion of patients are classified as BCG-unresponsive, and there have been no definite alternative treatments for these disease group except for radical cystectomy, which is still challenging and sometimes not applicable. Therefore, there has been a need for alternative bladder-preserving treatments for patients who desire a bladder-sparing approach or are too frail for major surgery. Intravesical therapies, such as gemcitabine, mitomycin C and docetaxel, are mostly studied approaches, showing some promising results. However, no definitive conclusion has be drawn because of the heterogeneity of the studies and protocols and the limited number of patients enrolled in most of these studies. Immunotherapy and anti-inflammatory agents, though promising, require further validation through ongoing clinical trials to ensure their safety and efficacy. Gene therapy is also being explored, though it is in its early stages, with challenges in gene delivery and immune regulation still to be addressed. Photodynamic therapy and hyperthermia, particularly in combination with other treatments like intravesical chemotherapy, have shown potential in improving outcomes for BCG-unresponsive patients, though they are not yet considered first-line treatments. While these novel approaches hold promise, more robust data and clinical trial results are necessary to guide treatment protocols. In conclusion, ongoing research and clinical trials will continue to shape the future of NMIBC management, with the aim of providing more effective and bladder-preserving options for patients.

The role of living donor liver transplantation in colorectal cancer liver metastases.

Despite technical and therapeutic advances, only 20-40% of patients with colorectal liver metastases (CRLM) have resectable disease. Historically, the remaining patients with unresectable, liver-only CRLM would receive palliative chemotherapy, with a median survival of 8 months. Liver transplantation has emerged as a viable option for selected patients with CRLM. This advancement stems from improved understanding of tumour genomics and biology and better patient selection criteria. The results of recent prospective clinical trials have further ignited enthusiasm for liver transplantation as a viable therapeutic option. Living donor liver transplantation (LDLT) offers several advantages over deceased donor liver transplantation (DDLT) for this disease, including reduced wait-time and optimized timing and coordination of oncologic therapy. On-going LDLT clinical trials have demonstrated favourable outcomes as compared with other liver transplantation indications. However, there is no established consensus or standardization in the implementation of LDLT for CRLM, beyond trials and centre-specific protocols. LDLT is an excellent therapeutic option in highly selected patients with CRLM. Refining prognostic factors and selection criteria will help to further optimize the utility and broaden the acceptance and implementation of LDLT for patients with CRLM.

Critical care nutrition: a Bayesian re-analysis of trial data.

Nutritional support and optimal glucose control are key components of care during critical illness, yet evidence surrounding their use remains conflicting, making translation into clinical practice challenging. This review explores Bayesian methods to enhance the interpretation of frequentist critical care trials, particularly for interventions with inconclusive outcomes. Bayesian re-analysis frameworks may clarify conflicting evidence in critical care, thus enhancing interpretability and supporting clinical decision-making. This review focuses on the Bayesian re-analysis of three recent trials with indeterminate results for mortality - NUTRIREA-3, EFFORT Protein, and TGC-Fast - that examined the effects of enteral nutrition and glucose control strategies. We re-analyzed the mortality outcomes of these trials within a Bayesian framework, contrasting our findings with the original trial results to illustrate how Bayesian methods can enhance the clinical applicability of trial outcomes. Although Bayesian and frequentist analyses generally agree on the direction and magnitude of effect, Bayesian methods offer the advantage of providing posterior probabilities of benefit and harm, thus identifying promising and potentially harmful interventions. This review underscores the value of Bayesian analysis in re-evaluating clinical trial data and guiding clinical practice.

Sleep Treatment Education Program for Cancer Survivors: Protocol for an Efficacy Trial.

Cancer survivors are at increased risk for chronic insomnia, even years after treatment completion. As insomnia is associated with a variety of long-term health consequences, access to insomnia treatment is critically important for the survivor population. Cognitive behavioral therapy for insomnia (CBTI) is the recommended first-line treatment for insomnia but remains largely unavailable to survivors. Treatment barriers include geographic limitations, a shortage of trained providers, and demanding treatment regimens. Designed with these limitations in mind, the Sleep Treatment Education Program (STEP-1) delivers components of CBTI in a low-intensity educational intervention delivered online. This is a phase II pilot randomized controlled trial. The primary aims are to test the efficacy of STEP-1 to improve (1) insomnia symptoms and (2) mood in cancer survivors compared to a control condition. The secondary aims will (1) explore participant factors associated with clinically significant response, (2) evaluate acceptability of the control intervention, (3) explore feasibility of delivering individualized coaching sessions for participants who do not have a significant response to STEP-1, and (4) describe participants' satisfaction with STEP-1 and suggestions for improvement. This 2-arm randomized controlled trial enrolled 70 off-treatment cancer survivors aged 40-89 years with clinically significant insomnia. Participants are randomized to receive either the STEP-1 intervention or control condition (relaxation education); interventions are delivered in one-on-one, synchronous, virtual videoconference sessions by trained interventionists. The STEP-1 intervention presents educational information on the development of insomnia after cancer and offers suggestions for improving insomnia symptoms based on the CBTI elements of sleep hygiene, stimulus control, and cognitive restructuring. With the interventionist, participants review the suggestions and develop a personalized sleep action plan for implementation. The relaxation education session provides information on the potential benefits of relaxation and how to independently access online relaxation exercises. The Insomnia Severity Index is used to measure insomnia symptoms, and the Profile of Mood States Short Form is used to measure mood at baseline and 4 and 8 weeks after intervention. The primary end point is change in the Insomnia Severity Index score at 8 weeks, and the secondary end point is change in mood symptoms (Profile of Mood States Short Form) at 8 weeks. This trial was funded in July 2022. Enrollment and data collection began in February 2023 and concluded in October 2024, with 70 participants enrolled. The analysis will begin in fall 2024, and the results are expected in winter 2025. Trial results will determine if STEP-1 effects go beyond those that could be attributed to placebo and other nonspecific treatment factors. Should results support the efficacy of STEP-1 to improve mood and insomnia symptoms, we anticipate developing efficacy and implementation trials of STEP-1 in larger and more diverse samples. ClinicalTrials.gov NCT05519982; https://clinicaltrials.gov/study/NCT05519982. DERR1-10.2196/60762.