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Background: Alzheimer's disease (AD), the most common cause of dementia, is a neurodegenerative disease resulting from extracellular and intracellular deposits of amyloid-β (Aβ) and neurofibrillary tangles in the brain. Although many clinical studies evaluating pharmacological approaches have been conducted, most have shown disappointing results; thus, innovative strategies other than drugs have been actively attempted. Objective: This study aims to explore low-dose radiation therapy (LDRT) for the treatment of patients with AD based on preclinical evidence, case reports, and a small pilot trial in humans. Methods: This study is a phase II, multicenter, prospective, single-blinded, randomized controlled trial that will evaluate the efficacy and safety of LDRT to the whole brain using a linear accelerator in patients with mild AD. Sixty participants will be randomly assigned to three groups: experimental I (24 cGy/6 fractions), experimental II (300 cGy/6 fractions), or sham RT group (0 cGy/6 fractions). During LDRT and follow-up visits after LDRT, possible adverse events will be assessed by the physician's interview and neurological examinations. Furthermore, the effectiveness of LDRT will be measured using neurocognitive function tests and imaging tools at 6 and 12 months after LDRT. We will also monitor the alterations in cytokines, Aβ42/Aβ40 ratio, and tau levels in plasma. Our primary endpoint is the change in cognitive function test scores estimated by the Alzheimer's Disease Assessment Scale-Korea compared to baseline after 6 months of LDRT. Conclusions: This study is registered at ClinicalTrials.gov [NCT05635968] and is currently recruiting patients. This study will provide evidence that LDRT is a new treatment strategy for AD. [ABSTRACT FROM AUTHOR]

Background: LRRC6 is an assembly factor for dynein arms in the cytoplasm of motile ciliated cells, and when mutated, dynein arm components remained in the cytoplasm. Here, we demonstrate the role of LRRC6 in the active nuclear translocation of FOXJ1, a master regulator for cilia-associated gene transcription. Methods: We generated Lrrc6 knockout (KO) mice, and we investigated the role of LRRC6 on ciliopathy development by using proteomic, transcriptomic, and immunofluorescence analysis. Experiments on mouse basal cell organoids confirmed the biological relevance of our findings. Results: The absence of LRRC6 in multi-ciliated cells hinders the assembly of ODA and IDA components of cilia; in this study, we showed that the overall expression of proteins related to cilia decreased as well. Expression of cilia-related transcripts, specifically ODA and IDA components, dynein axonemal assembly factors, radial spokes, and central apparatus was lower in Lrrc6 KO mice than in wild-type mice. We demonstrated that FOXJ1 was present in the cytoplasm and translocated into the nucleus when LRRC6 was expressed and that this process was blocked by INI-43, an importin α inhibitor. Conclusions: Taken together, these results hinted at the LRRC6 transcriptional regulation of cilia-related genes via the nuclear translocation of FOXJ1. 9eDfA3zLzmCEQkVeGa2G9M Video Abstract [ABSTRACT FROM AUTHOR]

Purpose: We aimed to compare breast-related complications between hypofractionated adjuvant postmastectomy radiation therapy (PMRT) and conventional fractionated radiation therapy (RT) in patients with breast cancer undergoing reconstruction by reconstruction surgery type.Methods and Materials: Data from a total of 396 patients with breast cancer who underwent breast reconstruction after mastectomy between 2009 and 2018 were retrospectively reviewed. All patients received adjuvant PMRT according to either a conventional fractionation or hypofractionation schedule. We analyzed breast-related complications according to the timing of breast reconstruction (immediate or delayed). In cases of delayed reconstruction, only PMRT delivered before final delayed reconstruction was included. A major breast complication was defined as a breast-related toxicity that required reoperation or rehospitalization after the end of RT.Results: The median follow-up time was 35.3 months (range, 8.8-122.7 months). Of all patients, 267 received immediate breast reconstruction and 129 received delayed breast reconstruction. In patients with immediate breast reconstruction, 91 were treated with conventional RT and 176 received hypofractionated RT. The occurrence of major breast-related complications did not differ significantly between the 2 fractionation regimens. Hypofractionated RT did not increase major wound problems (infection and dehiscence) compared with conventional RT. Furthermore, major contracture occurred significantly less frequently in hypofractionated RT. Of the patients who had delayed breast reconstruction, 48 received conventional RT and 81 received hypofractionated RT. There was no difference in the incidence of major breast complications between these 2 RT groups, and no difference in major breast complications were reported for either 1- or 2-stage delayed reconstruction. A time interval of >10 months between PMRT and final definitive reconstruction had a significantly lower incidence of major breast complications.Conclusions: Hypofractionated RT appears to be comparable with conventional fractionated RT in terms of breast-related complications in patients with breast cancer undergoing reconstruction, regardless of breast reconstruction type. An ongoing prospective randomized trial should confirm our findings. [ABSTRACT FROM AUTHOR]

Background: Genome‐wide association studies (GWASs) of asthma have identified several risk alleles and loci, but most have been conducted in individuals with European‐ancestry. Studies in Asians, especially children, are still lacking. We aimed to identify susceptibility loci by performing the first GWAS of asthma in Korean children with persistent asthma. Methods: We used a discovery set of 741 children with persistent asthma as cases and 589 healthy children and 551 healthy adults as controls to perform a GWAS. We validated our GWAS findings using UK Biobank data. We then used the Genotype‐Tissue Expression database to identify expression quantitative trait loci of candidate variants. Finally, we quantified proteins of genes associated with asthma. Results: Variants at the 17q12‐21 locus and SNPs in CYBRD1 and TNFSF15 genes were associated with persistent childhood asthma at genome‐wide thresholds of significance. Four SNPs in the TNFSF15 gene were also associated with childhood‐onset asthma in British white participants in the UK Biobank data. The asthma‐associated rs7856856‐C allele, the lead SNP, was associated with decreased TNFSF15 expression in whole blood and in arteries. Korean children with asthma had lower serum TNFSF15 levels than controls, and those with the asthma risk rs7856856‐CC genotype exhibited the lowest serum TNFSF15 levels overall, especially asthmatic children. Conclusions: Our GWAS of persistent childhood asthma with allergic sensitization identified a new susceptibility gene, TNFSF15, and replicated associations at the 17q12‐21 childhood‐onset asthma locus. This novel association may be mediated by reduced expression of serum TNFSF15 and loss of suppression of angiogenesis. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to compare the treatment efficacy and safety of re-irradiation (re-RT) using stereotactic ablative radiotherapy (SABR) and initial SABR for primary, recurrent lung cancer or metastatic lung tumor.Methods: A retrospective review of the medical records of 336 patients who underwent lung SABR was performed. Re-RT was defined as the overlap of the 70% isodose line of second-course SABR with that of the initial radiotherapy, and 20 patients were classified as the re-RT group. The median dose of re-RT using SABR was 54 Gy (range 48-60 Gy), and the median fraction number was 4 (range 4-6). One-to-three case-matched analysis with propensity score matching was used, and 60 patients were included in the initial SABR group of the matched cohort.Results: The 1- and 2-year local control rates for the re-RT group were 73.9% and 63.3% and those for the initial SABR group in the matched cohort were 92.9% and 87.7%, respectively (P = 0.013). There was no difference in distant metastasis-free, progression-free, and overall survival rates. The crude grade ≥ 2 toxicity rates were 40.0% for the re-RT group and 25.0% for the initial SABR group (P = 0.318). Re-RT group had higher acute grade ≥ 2 toxicity rates (25.0% vs 5.0%, P = 0.031). One incident of grade 3 toxicity (pulmonary) was reported in the re-RT group; there was no grade 4‒5 toxicity.Conclusions: The local control rate of the in-field re-RT SABR was lower than that of the initial SABR without compromising the survival rates. The toxicity of re-RT using SABR was acceptable. [ABSTRACT FROM AUTHOR]

Introduction: The optimal salvage treatment strategies for lymph node-positive (LNP) patients after radical surgery have not been clearly defined in prostate cancer with biochemical recurrence or persistence of elevated prostate-specific antigen (PSA). In this study, we compared the clinical outcomes of two different salvage treatments, androgen deprivation therapy (ADT) alone versus ADT with radiotherapy (RT). We also investigated prognostic factors that could support the use of ADT with RT in LNP prostate cancer. Materials and methods: We retrospectively reviewed 94 LNP prostate cancer patients who underwent radical prostatectomy (RP) followed by salvage treatment between 2004 and 2018. Salvage treatments involved either ADT alone or ADT with RT according to the clinical judgment of the physician. We analyzed clinicopathological and treatment factors related to 2nd biochemical failure (2nd BCF), clinical progression (CP), and progression-free survival (PFS). The cumulative failure after salvage treatment was defined as including both 2nd BCF and CP. Results: The median duration of follow-up was 55 months (interquartile range, 35–97 months). Thirty-seven (39.4%) patients were treated with ADT alone, and 57 patients (60.6%) were treated with a combination of ADT with RT. During follow-up period, the incidence of failure after salvage treatment in the ADT alone group and the combined treatment group was 89.2% and 45.6%, respectively (HR, 22.4; 95% CI 5.43–92.1; P < 0.001). The combination of ADT with RT was associated with better 2nd BCF and PFS than ADT alone (P = 0.007 and P = 0.015, respectively). In multivariate analyses, number of positive LN ≥ 2 and PSA nadir ≥ 0.005 ng/ml after RP were associated with poor 2nd BCF, CP, and PFS after salvage treatment. Salvage by combined ADT plus RT showed better 2nd BCF and PFS than ADT alone. Specifically, patients with number of positive LN ≥ 2 or PSA nadir ≥ 0.005 ng/ml after RP showed better 2nd BCF (P = 0.004) or PFS (P = 0.011) when treated with ADT plus RT rather than ADT alone. Conclusions: In patients with LNP prostate cancer, salvage ADT plus RT improved 2nd BCF and PFS compared to ADT alone. In particular, when the patients had more than two positive lymph nodes or PSA nadir ≥ 0.005 ng/ml after RP, ADT with RT seems to be a more beneficial salvage treatment resulting in better 2nd BCF and PFS. [ABSTRACT FROM AUTHOR]

Preclinical studies have shown that radiation therapy modulates antitumor immune responses. However, circulating T-cell responses after radiation therapy in patients with cancer have been poorly characterized. This study aims to explore the changes in circulating T cells after stereotactic body radiation therapy (SBRT). Peripheral blood samples of 30 patients with breast cancer who underwent SBRT for bone metastasis were analyzed using multicolor flow cytometry. Phenotypes of PD-1+ CD8+ T cells and regulatory T (T REG) cells were examined. Additionally, plasma protein levels were analyzed using a bead-based immunoassay. Circulating PD-1+ CD8+ T cells, which are enriched for tumor-specific clonotypes, were activated at 1 week after SBRT. However, circulating T REG cells were also activated after SBRT; this pattern was also evident among effector Foxp3hiCD45RA− T REG cells. We observed no difference in T-cell responses according to the fraction size and number. Notably, activation of T REG cells was more prominent in patients who experienced greater activation of PD-1+ CD8+ T cells. Plasma level changes in TGF-β1, soluble CTLA-4, and soluble 4-1BB at 1 week after SBRT were associated with PD-1+ CD8+ T-cell responses. Activation of T REG cells at 1 week after SBRT was associated with worse progression-free survival. Clinical factors including molecular subtype were not associated with the T-cell responses. SBRT induced activation of both potentially tumor-specific CD8+ T cells and T REG cells, which were tightly associated with each other. These results may support the use of T REG cell-modulating strategies with SBRT to improve the antitumor immune response. [ABSTRACT FROM AUTHOR]

Even though many oral glucose-lowering or lipid-lowering agents have already been reported to improve hepatic steatosis to some degree, which drug had a more beneficial effect on hepatic steatosis among those drugs has not been precisely explored. We analysed the effect of empagliflozi, a selective sodium-glucose cotransporter 2 inhibitor, and ezetimibe on developing hepatic steatosis. Using 4005,779 patients with type 2 diabetes mellitus (T2DM) or dyslipidemia provided by the Korean National Health Insurance Service (NHIS) between January 2015 and December 2015, we analyzed the odds ratio (OR) of fatty liver development (fatty liver index [FLI] >60). Additionally, we examined the metabolic effects of ezetimibe and empagliflozin in mice fed with a choline-deficient high-fat diet, mimicking the features of human NAFLD. The experiment for agents was performed for the non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) mouse models independently. In the NHIS data, ORs for the development of fatty liver were significantly lower in all treatment groups than in the reference group, which did not receive ezetimibe or empagliflozin. (Ezetimibe therapy; OR=0.962, empagliflozin therapy; OR=0.527, ezetimibe plus empagliflozin; OR=0.509 compared to reference therapy). Unlike non-alcoholic steatohepatitis mouse model, ezetimibe, empagliflozin, and combination therapy also reduced liver steatosis in the non-alcoholic fatty liver mouse model. Compared with other agents, empagliflozin and/or ezetimibe treatment reduced the risk of developing hepatic steatosis. Our data suggest that empagliflozin or ezetimibe can be primarily considered in type 2 DM or dyslipidemia patients to prevent hepatic steatosis. • There are no ideal treatments for people with T2DM or dyslipidemia who also have NAFLD. • Patients with T2DM or dyslipidemia (< 5 years) and the NAFL mouse model appeared to benefit from combination therapy the most. • Combination therapy might be beneficial for the first treatment of T2DM and/or dyslipidemia patients to stop the progression of the NAFLD. [ABSTRACT FROM AUTHOR]

UV-curable coatings have numerous advantages, including environmental sustainability due to 100% solid content, economic feasibility attributable to relatively fast curing time, decent appearance, mechanical properties, chemical resistance, and abrasion resistance. However, UV-curable polyurethane acrylate coatings on metals apparently restrict their engineering applications owing to low mechanical properties and poor thermal stability, giving UV-curable coatings less flexibility and formability. In this study, we evaluated the property change of films according to the type of reactive diluents that lowers the viscosity of UV-curing coatings for pre-coated metal and has a substantial effect on the curing rate, viscoelastic properties, adhesive properties, and flexibility of the film. Moreover, there are many changes in the properties of coatings according to varied curing conditions in order to evaluate the oxygen inhibition phenomenon during the curing process in the atmosphere. In particular, to evaluate the effect of reactive diluents on forming formability, which is the most crucial property for the pre-coated metal, this study used conventional formability tests, such as t-bending or the Erichsen test. Moreover, a cross-die cup drawing mold with a similar form as failure and Safety Zone was utilized in order to obtain clearer information on its actual formability. The analysis on the effect of failure and safety zone on the material used in press forming was conducted by assessing limit punch height and forming a limit diagram of the manufactured film according to varied reactive diluents. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Methods and results Conclusions The TRANSFORM‐HF trial demonstrated no significant outcome differences between torsemide and furosemide following hospitalization for heart failure (HF), but may have been impacted by non‐adherence to the randomized diuretic. The current study sought to determine the treatment effect of torsemide versus furosemide using an on‐treatment analysis inclusive of all randomized patients except those confirmed non‐adherent to study diuretic.TRANSFORM‐HF was an open‐label, pragmatic randomized trial of 2859 patients hospitalized for HF from June 2018 through March 2022. Patients were randomized to a loop diuretic strategy of torsemide versus furosemide with investigator‐selected dosage. This post‐hoc on‐treatment analysis included all patients alive with either known or unknown diuretic status, and excluded patients confirmed to be non‐adherent to study diuretic. This modified on‐treatment definition was applied separately at time of hospital discharge and 30‐day follow‐up. All‐cause mortality and hospitalization outcomes were assessed over 12 months. Overall, 2570 (89.9%) and 2374 (83.0%) patients were included in on‐treatment analyses at discharge and 30‐day follow‐up, respectively. There was no significant difference in all‐cause mortality between torsemide and furosemide in patients on‐treatment at discharge (17.5% vs. 17.8%; hazard ratio [HR] 1.01 [95% confidence interval [CI] 0.83–1.22], p = 0.96) and at 30‐day follow‐up (14.5% vs. 15.0%; HR 1.02 [95% CI 0.81–1.27], p = 0.90). All‐cause mortality or all‐cause hospitalization was similar between torsemide and furosemide in patients who were on‐treatment at discharge (58.3% vs. 61.3%; HR 0.92 [95% CI 0.82–1.03]) and 30‐day follow‐up (60.9% vs. 64.4%; HR 0.93 [95% CI 0.82–1.05]). In patients who were on‐treatment at 30‐day follow‐up, there were 677 total hospitalizations in the torsemide group and 686 total hospitalizations in the furosemide group (rate ratio 0.99 [95% CI 0.86–1.14], p = 0.87).In TRANSFORM‐HF, a post‐hoc on‐treatment analysis did not meaningfully differ from the original trial results. Among those deemed compliant with the assigned diuretic, there remained no significant difference in mortality or hospitalization after HF hospitalization with a strategy of torsemide versus furosemide.Clinical Trail Registration: ClinicalTrials.gov Identifier: NCT03296813. [ABSTRACT FROM AUTHOR]

Consider the choice of outcome for overall treatment benefit in a clinical trial which measures the first time to each of several clinical events. We describe several new variants of the win ratio that incorporate the time spent in each clinical state over the common follow‐up, where clinical state means the worst clinical event that has occurred by that time. One version allows restriction so that death during follow‐up is most important, while time spent in other clinical states is still accounted for. Three other variants are described; one is based on the average pairwise win time, one creates a continuous outcome for each participant based on expected win times against a reference distribution and another that uses the estimated distributions of clinical state to compare the treatment arms. Finally, a combination testing approach is described to give robust power for detecting treatment benefit across a broad range of alternatives. These new methods are designed to be closer to the overall treatment benefit/harm from a patient's perspective, compared to the ordinary win ratio. The new methods are compared to the composite event approach and the ordinary win ratio. Simulations show that when overall treatment benefit on death is substantial, the variants based on either the participants' expected win times (EWTs) against a reference distribution or estimated clinical state distributions have substantially higher power than either the pairwise comparison or composite event methods. The methods are illustrated by re‐analysis of the trial heart failure: a controlled trial investigating outcomes of exercise training. [ABSTRACT FROM AUTHOR]

Aim: Among patients discharged after hospitalization for heart failure (HF), a strategy of torsemide versus furosemide showed no difference in all‐cause mortality or hospitalization. Clinicians have traditionally favoured torsemide in the setting of kidney dysfunction due to better oral bioavailability and longer half‐life, but direct supportive evidence is lacking. Methods and results: The TRANSFORM‐HF trial randomized patients hospitalized for HF to a long‐term strategy of torsemide versus furosemide, and enrolled patients across the spectrum of renal function (without dialysis). In this post‐hoc analysis, baseline renal function during the index hospitalization was assessed as categories of estimated glomerular filtration rate (eGFR; <30, 30–<60, ≥60 ml/min/1.73 m2). The interaction between baseline renal function and treatment effect of torsemide versus furosemide was assessed with respect to mortality and hospitalization outcomes, and the change in Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ‐CSS). Of 2859 patients randomized, 336 (11.8%) had eGFR <30 ml/min/1.73 m2, 1138 (39.8%) had eGFR 30–<60 ml/min/1.73 m2, and 1385 (48.4%) had eGFR ≥60 ml/min/1.73 m2. Baseline eGFR did not modify treatment effects of torsemide versus furosemide on all adverse clinical outcomes including individual components or composites of all‐cause mortality and all‐cause (re)‐hospitalizations, both when assessing eGFR categorically or continuously (p‐value for interaction all >0.108). Similarly, no treatment effect modification by eGFR was found for the change in KCCQ‐CSS (p‐value for interaction all >0.052) when assessing eGFR categorically or continuously. Conclusion: Among patients discharged after hospitalization for HF, there was no significant difference in clinical and patient‐reported outcomes between torsemide and furosemide, irrespective of renal function. [ABSTRACT FROM AUTHOR]

Background: Loop diuretics are a primary therapy for the symptomatic treatment of heart failure (HF), but whether torsemide improves patient symptoms and quality of life better than furosemide remains unknown. As prespecified secondary end points, the TRANSFORM-HF trial (Torsemide Comparison With Furosemide for Management of Heart Failure) compared the effect of torsemide versus furosemide on patient-reported outcomes among patients with HF. Methods: TRANSFORM-HF was an open-label, pragmatic, randomized trial of 2859 patients hospitalized for HF (regardless of ejection fraction) across 60 hospitals in the United States. Patients were randomly assigned in a 1:1 ratio to a loop diuretic strategy of torsemide or furosemide with investigator-selected dosage. This report examined effects on prespecified secondary end points, which included Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS; assessed as adjusted mean difference in change from baseline; range, 0–100 with 100 indicating best health status; clinically important difference, ≥5 points) and Patient Health Questionnaire-2 (range, 0–6; score ≥3 supporting evaluation for depression) over 12 months. Results: Baseline data were available for 2787 (97.5%) patients for KCCQ-CSS and 2624 (91.8%) patients for Patient Health Questionnaire-2. Median (interquartile range) baseline KCCQ-CSS was 42 (27–60) in the torsemide group and 40 (24–59) in the furosemide group. At 12 months, there was no significant difference between torsemide and furosemide in change from baseline in KCCQ-CSS (adjusted mean difference, 0.06 [95% CI, –2.26 to 2.37]; P =0.96) or the proportion of patients with Patient Health Questionnaire-2 score ≥3 (15.1% versus 13.2%: P =0.34). Results for KCCQ-CSS were similar at 1 month (adjusted mean difference, 1.36 [95% CI, –0.64 to 3.36]; P =0.18) and 6-month follow-up (adjusted mean difference, –0.37 [95% CI, –2.52 to 1.78]; P =0.73), and across subgroups by ejection fraction phenotype, New York Heart Association class at randomization, and loop diuretic agent before hospitalization. Irrespective of baseline KCCQ-CSS tertile, there was no significant difference between torsemide and furosemide on change in KCCQ-CSS, all-cause mortality, or all-cause hospitalization. Conclusions: Among patients discharged after hospitalization for HF, a strategy of torsemide compared with furosemide did not improve symptoms or quality of life over 12 months. The effects of torsemide and furosemide on patient-reported outcomes were similar regardless of ejection fraction, previous loop diuretic use, and baseline health status. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296813. [ABSTRACT FROM AUTHOR]

Key Points: Question: Does torsemide reduce all-cause mortality compared with furosemide in patients with heart failure following hospitalization? Findings: In this randomized clinical trial of 2859 patients, 26.1% of patients randomized to torsemide and 26.2% randomized to furosemide died over a median follow-up of 17.4 months without a significant difference between groups. Meaning: Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months; however, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. Importance: Although furosemide is the most commonly used loop diuretic in patients with heart failure, some studies suggest a potential benefit for torsemide. Objective: To determine whether torsemide results in decreased mortality compared with furosemide among patients hospitalized for heart failure. Design, Setting, and Participants: TRANSFORM-HF was an open-label, pragmatic randomized trial that recruited 2859 participants hospitalized with heart failure (regardless of ejection fraction) at 60 hospitals in the United States. Recruitment occurred from June 2018 through March 2022, with follow-up through 30 months for death and 12 months for hospitalizations. The final date for follow-up data collection was July 2022. Interventions: Loop diuretic strategy of torsemide (n = 1431) or furosemide (n = 1428) with investigator-selected dosage. Main Outcomes and Measures: The primary outcome was all-cause mortality in a time-to-event analysis. There were 5 secondary outcomes with all-cause mortality or all-cause hospitalization and total hospitalizations assessed over 12 months being highest in the hierarchy. The prespecified primary hypothesis was that torsemide would reduce all-cause mortality by 20% compared with furosemide. Results: TRANSFORM-HF randomized 2859 participants with a median age of 65 years (IQR, 56-75), 36.9% were women, and 33.9% were Black. Over a median follow-up of 17.4 months, a total of 113 patients (53 [3.7%] in the torsemide group and 60 [4.2%] in the furosemide group) withdrew consent from the trial prior to completion. Death occurred in 373 of 1431 patients (26.1%) in the torsemide group and 374 of 1428 patients (26.2%) in the furosemide group (hazard ratio, 1.02 [95% CI, 0.89-1.18]). Over 12 months following randomization, all-cause mortality or all-cause hospitalization occurred in 677 patients (47.3%) in the torsemide group and 704 patients (49.3%) in the furosemide group (hazard ratio, 0.92 [95% CI, 0.83-1.02]). There were 940 total hospitalizations among 536 participants in the torsemide group and 987 total hospitalizations among 577 participants in the furosemide group (rate ratio, 0.94 [95% CI, 0.84-1.07]). Results were similar across prespecified subgroups, including among patients with reduced, mildly reduced, or preserved ejection fraction. Conclusions and Relevance: Among patients discharged after hospitalization for heart failure, torsemide compared with furosemide did not result in a significant difference in all-cause mortality over 12 months. However, interpretation of these findings is limited by loss to follow-up and participant crossover and nonadherence. Trial Registration: ClinicalTrials.gov Identifier: NCT03296813 This clinical trial compares the efficacy of torsemide vs furosemide in decreasing the risk of death from any cause among patients hospitalized for heart failure (regardless of ejection fraction). [ABSTRACT FROM AUTHOR]

Positron emission tomography (PET) is becoming an important tool for the investigation of emerging infectious diseases in animal models. Usually, PET imaging is performed after intravenous (IV) radiotracer administration. However, IV injections are difficult to perform in some small animals, such as golden hamsters. This challenge is particularly evident in longitudinal imaging studies, and even more so in maximum containment settings used to study high-consequence pathogens. We propose the use of intramuscular (IM) administration of 2-deoxy-2[18F]fluoro-D-glucose ([18F]F-FDG) for PET imaging of hamsters in a biosafety level 4 (BSL-4) laboratory setting. After [18F]F-FDG administration via IM or IV (through surgically implanted vascular access ports), eight hamsters underwent static or dynamic PET scans. Time–activity curves (TACs) and standardized uptake values (SUVs) in major regions of interest (ROIs) were used to compare the two injection routes. Immediately after injection, TACs differed between the two routes. At 60 min post-injection, [18F]F-FDG activity for both routes reached a plateau in most ROIs except the brain, with higher accumulation in the liver, lungs, brain, and nasal cavities observed in the IM group. IM delivery of [18F]F-FDG is an easy, safe, and reliable alternative for longitudinal PET imaging of hamsters in a BSL-4 laboratory setting. [ABSTRACT FROM AUTHOR]