Outcomes from Partner2Lose: a randomized controlled trial to evaluate 24-month weight loss in a partner-assisted intervention.

BACKGROUND: Partner support is associated with better weight loss outcomes in observational studies, but randomized trials show mixed results for including partners. Unclear is whether teaching communication skills to couples will improve weight loss in a person attempting weight loss (index participant). PURPOSE: To compare the efficacy of a partner-assisted intervention versus participant-only weight management program on 24-month weight loss. METHODS: This community-based study took place in Madison, WI. Index participants were eligible if they met obesity guideline criteria to receive weight loss counseling, were aged 18-74 years, lived with a partner, and had no medical contraindications to weight loss; partners were aged 18-74 years and not underweight. Couples were randomized 1:1 to a partner-assisted or participant-only intervention. Index participants in both arms received an evidence-based weight management program. In the partner-assisted arm, partners attended half of the intervention sessions, and couples were trained in communication skills. The primary outcome was index participant weight at 24 months, assessed by masked personnel; secondary outcomes were 24-month self-reported caloric intake and average daily steps assessed by an activity tracker. General linear mixed models were used to compare group differences in these outcomes following intent-to-treat principles. RESULTS: Among couples assigned to partner-assisted (n = 115) or participant-only intervention (n = 116), most index participants identified as female (67%) and non-Hispanic White (87%). Average baseline age was 47.27 years (SD 11.51 years) and weight was 106.55 kg (SD 19.41 kg). The estimated mean 24-month weight loss was similar in the partner-assisted (2.66 kg) and participant-only arms (2.89 kg) (estimated mean difference, 0.23 kg [95% CI, -1.58, 2.04 kg], p=0.80). There were no differences in 24-month average daily caloric intake (estimated mean difference 50 cal [95% CI: -233, 132 cal], p=0.59) or steps (estimated mean difference 806 steps [95% CI: -1675, 64 steps], p=0.07). The percentage of participants reporting an adverse event with at least possible attribution to the intervention did not differ by arm (partner-assisted: 9%, participant-only, 3%, p = 0.11). CONCLUSIONS: Partner-assisted and individual weight management interventions led to similar outcomes in index participants. TRIAL REGISTRATION: Clinicaltrials.gov NCT03801174, January 11, 2019.

A non-randomized comparison of engagement and outcomes for in-person versus virtual delivery of the Partner2Lose weight management trial.

Objective: Existing behavioral weight management interventions produce clinically meaningful weight loss. The onset of the COVID-19 pandemic led to the quick transition of such interventions from in-person to virtual platforms. This provided a unique opportunity to compare engagement and outcomes for an in-person versus virtually delivered weight management intervention. Methods: A non-randomized comparison of engagement and weight outcomes was performed between two cohorts who participated in a weight management intervention in person (N = 97) versus three who participated virtually via videoconference (N = 134). Various metrics of engagement were examined, including group class and individual phone call attendance and duration, and retention for weight assessments. Behavioral targets of daily caloric intake and step-counts and the clinical weight outcome were explored. Results: Cohorts (mean [standard deviation] age 47.3 (11.5), 67.1% women: 86.8% White) that participated virtually attended more group sessions (p < 0.001) and had maintenance telephone calls that were of a longer duration (p < 0.001). No other engagement or weight outcomes significantly differed by delivery modality. Conclusions: Virtual weight management programs are promising and may generate similar outcomes to those delivered in-person. Future research should seek to understand how best to promote and sustain engagement in virtual interventions.

Defining estimand for the win ratio: Separate the true effect from censoring.

The win ratio has been increasingly used in trials with hierarchical composite endpoints. While the outcomes involved and the rule for their comparisons vary with the application, there is invariably little attention to the estimand of the resulting statistic, causing difficulties in interpretation and cross-trial comparison. We make the case for articulating the estimand as a first step to win ratio analysis and establish that the root cause for its elusiveness is its intrinsic dependency on the time frame of comparison, which, if left unspecified, is set haphazardly by trial-specific censoring. From the statistical literature, we summarize two general approaches to overcome this uncertainty-a nonparametric one that pre-specifies the time frame for all comparisons, and a semiparametric one that posits a constant win ratio across all times-each with publicly available software and real examples. Finally, we discuss unsolved challenges, such as estimand construction and inference in the presence of intercurrent events.

Safety and efficacy of histotripsy delivery through overlying gas-filled small bowel in an ex vivo swine model.

PURPOSE: To evaluate the safety and efficacy of performing histotripsy through overlying gas-filled bowel in an ex vivo swine model. METHODS: An ex vivo model was created to simulate histotripsy treatment of solid organs through gas-filled bowel. Spherical 2.5 cm histotripsy treatments were performed in agar phantoms for each of five treatment groups: 1) control with no overlying bowel (n = 6), 2) bowel 0 cm above phantom (n = 6), 3) bowel 1 cm above phantom (n = 6), 4) bowel 2 cm above phantom (n = 6), and 5) bowel 0 cm above the phantom with increased treatment amplitude (n = 6). Bowel was inspected for gross and microscopic damage, and treatment zones were measured. A ray-tracing simulation estimated the percentage of therapeutic beam path blockage by bowel in each scenario. RESULTS: All histotripsy treatments through partial blockage were successful (24/24). No visible or microscopic damage was observed to intervening bowel. Partial blockage resulted in a small increase in treatment volume compared to controls (p = 0.002 and p = 0.036 for groups with bowel 0 cm above the phantom, p > 0.3 for bowel 1 cm and 2 cm above the phantom). Gas-filled bowel was estimated to have blocked 49.6%, 35.0%, and 27.3% of the therapeutic beam at 0, 1, and 2 cm, respectively. CONCLUSION: Histotripsy has the potential to be applied through partial gas blockage of the therapeutic beam path, as shown by this ex vivo small bowel model. Further work in an in vivo survival model appears indicated.

Correction: The role of the Basic Public Health Service program in the control of hypertension in China: Results from a cross-sectional health service interview survey.

[This corrects the article DOI: 10.1371/journal.pone.0217185.].

Repeat Surgery after Percutaneous Endoscopic Lumbar Discectomy for Adolescent Lumbar Disc Herniation: A Multicenter Observational Study.

OBJECTIVE: The reported date in the repeat surgical intervention for adolescent lumbar disc herniation (ALDH) after percutaneous endoscopic lumbar discectomy (PELD) was quite scarce. This study aims to introduce cases of repeat surgeries after PELD for ALDH and assess the incidence, chief causes, repeat surgery methods, and surgical outcomes of repeat surgeries after PELD for ALDH. METHODS: A retrospective multicenter observational study was conducted on patients undergoing repeat surgeries after PELD for ALDH at four tertiary referral hospitals from January 2014 through August 2022. The incidence of repeat surgeries, chief causes, strategies for repeat surgeries, and timing of repeat surgeries were recorded and analyzed. The clinical outcomes were evaluated by the Numeric Rating Scales (NRS) scores and the modified MacNab criteria. Statistical analyses were performed with the Wilcoxon signed-rank test. RESULTS: A total of 23 patients who underwent repeat surgeries after PELD for ALDH were included. The chief causes were re-herniation (homo-lateral re-herniation at the same level, new disc herniation of adjacent level). The repeat surgery methods were revision PELD, micro-endoscopic discectomy (MED), open discectomy and instrumented lumbar inter-body fusion. The NRS scores decreased significantly in follow-up evaluations and these scores demonstrated significant improvement at the last follow-up (p < 0.002). For the modified MacNab criteria, at the last follow-up, 18 patients (78.26%) had an excellent outcome, and the overall success rate was 86.95%. CONCLUSION: This study's data suggest that young patients who underwent repeat surgery improved significantly compared to baseline. The chief cause was re-herniation. Revision PELD was the main surgical procedure, which provides satisfactory clinical results in young patients who underwent repeat surgeries.

Virtual Visiting Professorship Program as an Opportunity for Academic and Clinical Advancement Beyond the COVID-19 Pandemic: A Survey of Participants.

OBJECTIVE: To identify structure, benefits, and shortcomings of a multi-institutional virtual visiting professorship (VVP) program from 2020 to 2022, 2 years after inception and after gradual resumption of an in-person, prepandemic academic environment. METHODS: An IRB-exempt, 70-question survey about structure, benefits, and shortcomings of the VVP program was distributed to its participants (14 breast imaging departments across the U.S.), using the snowball sampling technique. RESULTS: A total of 72 responses were received; 54.2% (32/59) radiologists >5 years of experience, 18.6% (11/59) radiologists <5 years of experience, 15.3% (9/59) residents, and 8.5% (5/59) fellows. Radiologists' attendance increased from 8% (5/59) to 53% (31/59) over 2 years, with 69% (41/59) of respondents supporting continued participation. The most important factors for attendance were expanding breast imaging knowledge (86.4% [51/59]) and the virtual format (76.2% [45/59]). The number of presented lectures increased from 1 to 3 lectures in 43.7% (7/16) of programs in year 1 and from 4 to 9 lectures in 50% (8/16) of programs in year 2. The greatest professional benefits were collaborations on publications for organizers (56.3% [9/16]) and building academic portfolios for presenters (50% [7/14]). For trainees, attending the program increased their knowledge (64.3% [9/14]) and enthusiasm for breast imaging (50% [7/14]). CONCLUSION: The VVP program facilitated scholarly collaboration among breast imaging radiologists, promoted academic portfolios for junior faculty, and increased enthusiasm for breast imaging for trainees. These accomplishments extended beyond the COVID-19 pandemic, as evidenced by the growth of the program after resumption of an in-person academic environment. Future expansion to other programs would benefit more practicing radiologists.

Circular RNA-GRIN2B Suppresses Neuropathic Pain by Targeting the NF-κB/SLICK Pathway.

The role of circular RNAs (circRNAs) in neuropathic pain is linked to the fundamental physiological mechanisms involved. However, the exact function of circRNAs in the context of neuropathic pain is still not fully understood. The functional impact of circGRIN2B on the excitability of dorsal root ganglion (DRG) neurons was investigated using siRNA or overexpression technology in conjunction with fluorescence in situ hybridization and whole-cell patch-clamp technology. The therapeutic efficacy of circGRIN2B in treating neuropathic pain was confirmed by assessing the pain threshold in a chronic constrictive injury (CCI) model. The interaction between circGRIN2B and NF-κB was examined through RNA pulldown, RIP, and mass spectrometry assays. CircGRIN2B knockdown significantly affected the action potential discharge frequency and the sodium-dependent potassium current flux (SLICK) in DRG neurons. Furthermore, knockdown of circGRIN2B dramatically reduced the SLICK channel protein and mRNA expression in vivo and in vitro. Our research confirmed the interaction between circGRIN2B and NF-κB. These findings demonstrated that circGRIN2B promotes the transcription of the SLICK gene by binding to NF-κB. In CCI rat models, the overexpression of circGRIN2B has been shown to hinder the progression of neuropathic pain, particularly by reducing mechanical and thermal hyperalgesia. Additionally, this upregulation significantly diminished the levels of the inflammatory cytokines IL-1ß, IL-6, and TNF-α in the DRG. Upon reviewing these findings, it was determined that circGRIN2B may mitigate the onset of neuropathic pain by modulating the NF-κB/SLICK pathway.

Primary outcomes from Partner2Lose: A randomized controlled trial to evaluate partner involvement on long-term weight loss.

Background: Partner support is associated with better weight loss outcomes in observational studies, but randomized trials show mixed results for including partners. Unclear is whether teaching communication skills to couples will improve weight loss in index participants. Purpose: To compare the efficacy of a partner-assisted intervention versus participant-only weight management program on long-term weight loss. Methods: This community-based study took place in Madison, WI. Index participants were eligible if they met obesity guideline criteria to receive weight loss counseling, were aged 74 years or younger, lived with a partner, and had no medical contraindications to weight loss; partners were aged 74 years or younger and not underweight. Couples were randomized 1:1 to a partner-assisted or participant-only intervention. Index participants in both arms received an evidence-based weight management program. In the partner-assisted arm, partners attended half of the intervention sessions, and couples were trained in communication skills. The primary outcome was index participant weight at 24 months, assessed by masked personnel; secondary outcomes were 24-month self-reported caloric intake and average daily steps assessed by an activity tracker. General linear mixed models were used to compare group differences in these outcomes following intent-to-treat principles. Results: Among couples assigned to partner-assisted (n=115) or participant-only intervention (n=116), most index participants identified as female (67%) and non-Hispanic White (87%). Average baseline age was 47.27 years (SD 11.51 years) and weight was 106.55 kg (SD 19.41 kg). The estimated mean 24-month weight loss was similar in the partner-assisted (2.66 kg) and participant-only arms (2.89 kg) (estimated mean difference, 0.23 kg [95% CI, -1.58, 2.04 kg]). There were no differences in 24-month average daily caloric intake (50 cal [95% CI: -233, 132 cal]) or steps (806 steps [95% CI: -1675, 64 steps]). The percentage of participants reporting an adverse event with at least possible attribution to the intervention did not differ by arm (partner-assisted: 9%, participant-only, 3%, p=0.11). Conclusions: Partner-assisted and individual weight management interventions led to similar outcomes in index participants. Trial registration: Clinicaltrials.gov NCT03801174.

Influenza Vaccine Immune Response in Patients With High-Risk Cardiovascular Disease: A Secondary Analysis of the INVESTED Randomized Clinical Trial.

Importance: High-dose trivalent compared with standard-dose quadrivalent influenza vaccine did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations in patients with high-risk cardiovascular disease in the INVESTED trial. Whether humoral immune response to influenza vaccine is associated with clinical outcomes is unknown. Objective: To examine the antibody response to high-dose trivalent compared with standard-dose quadrivalent inactivated influenza vaccine and its associations with clinical outcomes. Design, Setting, and Participants: This secondary analysis is a prespecified analysis of the immune response substudy of the randomized, double-blind, active-controlled INVESTED trial, which was conducted at 157 sites in the United States and Canada over 3 influenza seasons between September 2016 and January 2019. Antibody titers were determined by hemagglutination inhibition assays at randomization and 4 weeks during the 2017-2018 and 2018-2019 seasons. Eligibility criteria included recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor. Data were analyzed from February 2023 to June 2023. Main Outcomes and Measures: Mean antibody titer change, seroprotection (antibody titer level ≥1:40) and seroconversion (≥4-fold increase in titer) at 4 weeks, and the association between seroconversion status and the risk for adverse clinical outcomes. Interventions: High-dose trivalent or standard-dose quadrivalent inactivated influenza vaccine, with revaccination up to 3 seasons. Results: Antibody data were available for 658 of 5260 randomized participants (12.5%; mean [SD] age, 66.2 [11.4] years; 507 male [77.1%], 151 female [22.9%]; 348 with heart failure [52.9%]). High-dose vaccine was associated with an increased magnitude in antibody titers for A/H1N1, A/H3N2, and B-type antigens compared with standard dose. More than 92% of all participants achieved seroprotection for each of the contained antigens, while seroconversion rates were higher in participants who received high-dose vaccine. Seroconversion for any antigen was not associated with the risk for cardiopulmonary hospitalizations or all-cause mortality (hazard ratio, 1.09; 95% CI, 0.79-1.53; P = .59), irrespective of randomized treatment (P = .38 for interaction). Conclusions and Relevance: High-dose vaccine elicited a more robust humoral response in patients with heart failure or prior myocardial infarction enrolled in the INVESTED trial, with no association between seroconversion status and the risk for cardiopulmonary hospitalizations or all-cause mortality. Vaccination to prevent influenza remains critical in high-risk populations. Trial Registration: ClinicalTrials.gov Identifier: NCT02787044.

Percutaneous Microwave Ablation for Treatment of Retroperitoneal Tumors.

Purpose To determine if microwave ablation (MWA) of retroperitoneal tumors can safely provide high rates of local tumor control. Materials and Methods This retrospective study included 19 patients (median age, 65 years [range = 46-78 years]; 13 [68.4%] men and six [31.6%] women) with 29 retroperitoneal tumors treated over 22 MWA procedures. Hydrodissection (0.9% saline with 2% iohexol) was injected in 17 of 22 (77.3%) procedures to protect nontarget anatomy. The primary outcomes evaluated were local tumor progression (LTP) and complication rates. Oncologic outcomes, including overall survival (OS), progression-free survival (PFS), and treatment-free interval (TFI), were examined as secondary outcome measures. Results Median follow-up was 18 months (range = 0.5-113). Hydrodissection was successful in displacing nontarget anatomy in 16 of 17 (94.1%) procedures. The LTP rate was 3.4% (one of 29; 95% CI: 0.1, 17.8) per tumor and 5.3% (one of 19; 95% CI: 0.1, 26.0) per patient. The overall complication rate per patient was 15.8% (three of 19), including two minor complications and one major complication. The OS rate at 1, 2, and 3 years was 81.8%, 81.8%, and 72.7%, respectively, with a median OS estimated at greater than 7 years. There was no evidence of a difference in OS (P = .34) and PFS (P = .56) between patients with renal cell carcinoma (six of 19 [31.6%]) versus other tumors (13 of 19 [68.4%]) and patients treated with no evidence of disease (15 of 22 [68.2%]) versus patients with residual tumors (seven of 22 [31.8%]). Median TFI was 18 months (range = 0.5-108). Conclusion Treatment of retroperitoneal tumors with MWA combined with hydrodissection provided high rates of local control, prolonged systemic therapy-free intervals, and few serious complications. Keywords: Ablation Techniques (ie, Radiofrequency, Thermal, Chemical), Retroperitoneum, Microwave Ablation, Hydrodissection © RSNA, 2024.

COL6A3 enhances the osteogenic differentiation potential of BMSCs by promoting mitophagy in the osteoporotic microenvironment.

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) have been widely recognized as a highly promising option for cell-based tissue engineering therapy targeting osteoporosis. However, the osteogenic differentiation of BMSCs is impeded by the limited viability and diminished capacity for bone formation within the osteoporotic microenvironment. METHODS: In this study, the COL6A3 gene was confirmed through an extensive analysis of the preceding single-cell sequencing database. The generation of an inflammatory microenvironment resembling osteoporotic cell transplantation was achieved by employing lipopolysaccharide (LPS). A lentivirus targeting the COL6A3 gene was constructed, and a Western blotting assay was used to measure the marker proteins of osteogenesis, adipogenesis, and mitophagy. Immunofluorescence was utilized to observe the colocalization of mitochondria and lysosomes. The apoptosis rate of each group was evaluated using the TUNEL assay, and the mitochondrial membrane potential was assessed using JC-1 staining. RESULTS: This investigation discovered that the impaired differentiation capacity and decreased viability of BMSCs within the inflammatory microenvironment were markedly ameliorated upon overexpression of the specific COL6A3 gene. Moreover, the administration of COL6A3 gene overexpression successfully mitigated the inhibitory impacts of LPS on mitophagy and the expression of inflammatory mediators, specifically inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), in BMSCs. To clarify the underlying mechanism, the role of mitophagy during the differentiation of COL6A3 gene-modified BMSCs in the inflammatory microenvironment was evaluated using the mitophagy inhibitor Mdivi-1. CONCLUSIONS: In the context of lipopolysaccharide (LPS) stimulation, COL6A3 enhances the differentiation of BMSCs into osteogenic and adipogenic lineages through the promotion of mitophagy and the maintenance of mitochondrial health. Our findings may provide a novel therapeutic approach utilizing stem cells in the treatment of osteoporosis.

Comparison of MRI and arthroscopy findings for transitional zone cartilage damage in the acetabulum of the hip joint.

OBJECTIVE: To assess the performance of morphologic and hypointense signal changes on MRI to predict grades and types of acetabular cartilage damage in the chondrolabral transitional zone (TZ) of the hip identified at arthroscopy. MATERIALS AND METHODS: This retrospective single-center study reviewed conventional 3T MRI hip studies from individuals with symptomatic femoroacetabular impingement (FAI) and subsequent hip arthroscopy surgery within 6 months. Independent review was made by three radiologists for the presence of morphologic damage or a hypointense signal lesion in the TZ on MRI. Fleiss' kappa statistic was used to assess inter-reader agreement. The degree of TZ surfacing damage (modified Outerbridge grades 1-4) and presence of non-surfacing wave sign at arthroscopic surgery were collected. Relationship between sensitivity and lesion grade was examined. RESULTS: One hundred thirty-six MRI hip studies from 40 males and 74 females were included (mean age 28.5 years, age range 13-54 years). MRI morphologic lesions had a sensitivity of 64.9-71.6% and specificity of 48.4-67.7% for arthroscopic surfacing lesions, with greater sensitivity seen for higher grade lesions. Low sensitivity was seen for wave sign lesions (34.5-51.7%). MRI hypointense signal lesions had a sensitivity of 26.3-62% and specificity of 43.8-78.0% for any lesion. Inter-reader agreement was moderate for morphologic lesions (k = 0.601) and poor for hypointense signal lesions (k = 0.097). CONCLUSION: Morphologic cartilage damage in the TZ on MRI had moderate sensitivity for any cartilage lesion, better sensitivity for higher grade lesions, and poor sensitivity for wave sign lesions. The diagnostic value of hypointense signal lesions was uncertain.

Unreimbursed Costs of Multidisciplinary Conferences to a Radiology Department: A Prospective Analysis at an Academic Medical Center.

PURPOSE: Multidisciplinary conferences (MDCs) are important for clinical care but are unreimbursed and can be time-consuming for radiologists to prepare for and present. The purpose of this single-center, prospective, survey-based study is to measure the per-conference time and total time radiologists devote to MDCs at a single academic medical center. Secondary objectives are to determine the source of radiologist preparation time, and calculate the per conference and overall radiology departmental costs of MDC participation. METHODS: A prospective survey was performed to capture all radiology preparation and presentation time for MDCs in a 3-month period, which was then annualized. Total cost was calculated on the basis of Association of Administrators in Academic Radiology survey data for nonchair academic radiologist compensation plus a 30% fringe-benefit rate. RESULTS: The survey response rate was 86.9%. A total of 3,358 hours were devoted annually to MDCs, which represents time equivalent to 1.9 full-time equivalents or $1,155,152 in unreimbursed radiology departmental costs. Per-MDC total preparation and presentation time was 2.7 hours, at an annual cost of $46,440 for each weekly MDC. Radiologists used a combination of personal time (49.7%), academic time (42%), and/or clinical time (35.4%) to prepare for MDCs. Radiologists devoted a mean of 47.9 hours (1.2 weeks) of time per annum to MDCs. CONCLUSIONS: Radiologist time devoted to MDCs at the survey institution was substantial, and preparation time was drawn disproportionately from personal and academic time, which may have negative implications for burnout, recruitment and retention, and academic productivity unless it is effectively mitigated.

Statistical inference for time-to-event data in non-randomized cohorts with selective attrition.

In multi-season clinical trials with a randomize-once strategy, patients enrolled from previous seasons who stay alive and remain in the study will be treated according to the initial randomization in subsequent seasons. To address the potentially selective attrition from earlier seasons for the non-randomized cohorts, we develop an inverse probability of treatment weighting method using season-specific propensity scores to produce unbiased estimates of survival functions or hazard ratios. Bootstrap variance estimators are used to account for the randomness in the estimated weights and the potential correlations in repeated events within each patient from season to season. Simulation studies show that the weighting procedure and bootstrap variance estimator provide unbiased estimates and valid inferences in Kaplan-Meier estimates and Cox proportional hazard models. Finally, data from the INVESTED trial are analyzed to illustrate the proposed method.

Apparent Variation in Measurement Size of Colorectal Cancer Metastases to the Liver on Dual Contrast MRI.

PURPOSE: The aim of this study was to formally investigate the apparent variation in lesion size of hepatic metastatic lesions from colorectal cancer on hepatobiliary phase (HBP) and dual contrast images of magnetic resonance imaging performed with both hepatobiliary and extracellular contrast agents. METHODS: Patients with known colorectal carcinoma who had undergone dual contrast liver magnetic resonance imaging were identified in our institutional database. Metastatic lesions were measured semiautomatically on both HBP and dual contrast images with a custom software tool that automatically identifies the lesion edge and thereby the lesion diameter. Lesion measurements from both sets of images were compared with a Student t test and Bland-Altman analysis. Lesions were also measured on both HBP and dual contrast images by 2 fellowship-trained abdominal radiologists. Measurements from the software and radiologists were compared with a Student t test and Bland-Altman analysis; interreader agreement was evaluated with the intraclass correlation coefficient. RESULTS: A total of 70 liver lesions in 39 patients was identified. Software-based measurements were significantly larger on HBP than dual contrast images ( P < 0.001), with a mean lesion size of 10.9 ± 4.2 mm for HBP and 10.5 ± 4.2 mm for dual contrast measurements. Radiologist-based measurements showed a similar trend, with HBP measurements being significantly larger than dual contrast measurements ( P < 0.001). Bland-Altman analysis indicated a mean bias ± 2 SD of +0.4 ± 1.6 mm for software-based measurements and +0.9 ± 2.9 mm and +0.7 ± 2.1 mm for readers 1 and 2, respectively. The intraclass correlation coefficient for interreader agreement was 0.9. CONCLUSIONS: Both software-based and radiologist-based measurements of colorectal cancer liver metastases are significantly larger on HBP than dual contrast images. Based on these findings, we recommend that longitudinal assessment be performed consistently on either HBP or dual contrast phases to avoid introduction of avoidable variability.

Dissecting the restricted mean time in favor of treatment.

The restricted mean time in favor (RMT-IF) summarizes the treatment effect on a hierarchical composite endpoint with mortality at the top. Its crude decomposition into "stage-wise effects," i.e., the net average time gained by the treatment prior to each component event, does not reveal the patient state in which the extra time is spent. To obtain this information, we break each stage-wise effect into subcomponents according to the specific state to which the reference condition is improved. After re-expressing the subcomponents as functionals of the marginal survival functions of outcome events, we estimate them conveniently by plugging in the Kaplan -- Meier estimators. Their robust variance matrices allow us to construct joint tests on the decomposed units, which are particularly powerful against component-wise differential treatment effects. By reanalyzing a cancer trial and a cardiovascular trial, we acquire new insights into the quality and composition of the extra survival times, as well as the extra time with fewer hospitalizations, gained by the treatment in question. The proposed methods are implemented in the rmt package freely available on the Comprehensive R Archive Network (CRAN).

Design, synthesis, and anti-respiratory syncytial virus potential of novel 3-(1,2,3-triazol-1-yl)furoxazine-fused benzimidazole derivatives.

Respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections in infants, children, and older persons. Currently, the only approved anti-viral chemotherapeutic drug for RSV treatment is ribavirin aerosol; however, its significant toxicity has led to restricted clinical use. In a previous study, we developed various benzimidazole derivatives against RSV. In this study, we synthesised 3-azide substituted furoxazine-fused benzimidazole derivatives by sulfonylation and azide substitution of the 3-hydroxyl group of the furoxazine-fused benzimidazole derivatives. Subsequently, a series of 3-(1,2,3-triazol-1-yl)-substituted furoxazine-fused benzimidazole derivatives were synthesised using the classical click reaction. Biological evaluations of the target compounds indicated that compound 4a-2 had higher activity against RSV (EC50 = 12.17 µM) and lower cytotoxicity (CC50 = 390.64 µM). Compound 4a-2 exerted anti-viral effects against the RSV Long strain by inhibiting apoptosis and the elevation of reactive oxygen species (ROS) and inflammatory factors caused by viral infection in vitro. Additionally, the clinical symptoms of the virus-infected mice were markedly relieved, and the viral load in the lung tissues was dramatically decreased. The biosafety profile of compound 4a-2 was also favourable, showing no detectable adverse effects on any of the major organs in vivo. These findings underscore the potential of compound 4a-2 as a valuable therapeutic option for combating RSV infections while also laying the foundation for further research and development in the field.

Power and Sample Size Calculations for the Restricted Mean Time Analysis of Prioritized Composite Endpoints.

As a new way of reporting treatment effect, the restricted mean time in favor (RMT-IF) of treatment measures the net average time the treated have had a less serious outcome than the untreated over a specified time window. With multiple outcomes of differing severity, this offers a more interpretable and data-efficient alternative to the prototypical restricted mean (event-free) survival time. To facilitate its adoption in actual trials, we develop simple approaches to power and sample size calculations and implement them in user-friendly R programs. In doing so we model the bivariate outcomes of death and a nonfatal event using a Gumbel-Hougaard copula with component-wise proportional hazards structures, under which the RMT-IF estimand is derived in closed form. In a standard set-up for censoring, the variance of the nonparametric effect-size estimator is simplified and computed via a hybrid of numerical and Monte Carlo integrations, allowing us to compute the power and sample size as functions of component-wise hazard ratios. Simulation studies show that these formulas provide accurate approximations in realistic settings. To illustrate our methods, we consider designing a new trial to evaluate treatment effect on the composite outcomes of death and cancer relapse in lymph node-positive breast cancer patients, with baseline parameters calculated from a previous study.