Citations

AbstractBackgroundThis study examined the trajectory of health‐related quality of life (HRQoL) for patients with clinical stage N0 HNSCC enrolled in ACRIN 6685 who underwent elective neck dissection(s).MethodsHRQoL of 230 patients in the ACRIN 6685 trial was measured prospectively up to 2 years following surgery using the University of Washington Quality of Life instrument.ResultsGeneral Health Within the Last 7 Days did not differ significantly from baseline at any follow‐up. General Health Relative to Before Cancer fell significantly by 5.8 points following surgery (p = 0.048), and then returned to 3.0 points above baseline at 1 year (p = 0.65). For Overall Quality of Life, HRQoL fell significantly by 4.3 points following surgery (p = 0.031) and then returned to levels not significantly different from baseline.ConclusionsPatients with stage N0 HNSCC experience significant declines in HRQoL immediately following surgery, including neck dissection, which recovers to near or better than baseline within 1–2 years.

This study aimed to evaluate and compare the performance of three anti-S and one anti-N assays that were available to the project in detecting antibody levels after three commonly used SARS-CoV-2 vaccines (Pfizer, Moderna, and Johnson & Johnson). It also aimed to assess the association of age, sex, race, ethnicity, vaccine timing, and vaccine side effects on antibody levels in a cohort of 827 individuals. In September 2021, 698 vaccinated individuals donated blood samples as part of the Association for Diagnostics & Laboratory Medicine (ADLM) COVID-19 Immunity Study. These individuals also participated in a comprehensive survey covering demographic information, vaccination status, and associated side effects. Additionally, 305 age- and gender-matched samples were obtained from the ADLM 2015 sample bank as pre-COVID-19-negative samples. All these samples underwent antibody level analysis using three anti-S assays, namely Beckman Access SARS-CoV-2 IgG (Beckman assay), Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG (Ortho assay), Siemens ADVIA Centaur SARS-CoV-2 IgG (Siemens assay), and one anti-N antibody assay: Bio-Rad Platelia SARS-CoV-2 Total Ab assay (BioRad assay). A total of 827 samples (580 COVID-19 samples and 247 pre-COVID-19 samples) received results for all four assays and underwent further analysis. Beckman, Ortho, and Siemens anti-S assays showed an overall sensitivity of 99.5%, 97.6%, and 96.9%, and specificity of 90%, 100%, and 99.6%, respectively. All three assays indicated 100% sensitivity for individuals who received the Moderna vaccine and boosters, and over 99% sensitivity for the Pfizer vaccine. Sensitivities varied from 70.4% (Siemens), 81.5% (Ortho), and 96.3% (Beckman) for individuals who received the Johnson & Johnson vaccine. BioRad anti-N assays demonstrated 46.2% sensitivity and 99.25% specificity based on results from individuals with self-reported infection. The highest median anti-S antibody levels were measured in individuals who received the Moderna vaccine, followed by Pfizer and then Johnson & Johnson vaccines. Higher anti-S antibody levels were significantly associated with younger age and closer proximity to the last vaccine dose but were not associated with gender, race, or ethnicity. Participants with higher anti-S levels experienced significantly more side effects as well as more severe side effects (e.g., muscle pain, chills, fever, and moderate limitations) (p < 0.05). Anti-N antibody levels only indicated a significant correlation with headache. This study indicated performance variations among different anti-S assays, both among themselves and when analyzing individuals with different SARS-CoV-2 vaccines. Caution should be exercised when conducting large-scale studies to ensure that the same platform and/or assays are used for the most effective interpretation of the data.

Introduction: Smoking-related diseases affect 16 million Americans, causing approximately 480,000 deaths annually. The prevalence of cigarette smoking varies regionally across the United States, and previous research indicates that regional rates of smoking-related diseases demonstrate a negative association with altitude. The purpose of this study was to determine the relationship between altitude and the prevalence of cigarette smoking by county (N = 3106) in the United States. We hypothesized that smoking prevalence among adults would be negatively associated with mean county altitude. Methods: A multivariate linear regression was performed to examine the relationship between county-level mean altitude and county smoking rate. Covariates were individually correlated with 2020 smoking data, and significant associations were included in the final model. Results: The multivariate linear regression indicated that the county-level smoking rates are significantly reduced at high altitudes (p < 0.001). The model accounted for 89.5% of the variance in smoking prevalence, and for each 1000-foot increase in altitude above sea level, smoking rates decreased by 0.143%. Based on multivariate linear regression, the following variables remained independently and significantly associated: race, sex, educational attainment, socioeconomic status, unemployment, physical inactivity, drinking behavior, mental distress, and tobacco taxation. Conclusions: Our results indicate that smoking rates are negatively associated with altitude, which may suggest that altitude affects the pharmacokinetics, pharmacodynamics, and mechanistic pathways involved in cigarette use. Further research is needed to explore the relationship between altitude and smoking and how altitude may serve as a protective factor in the acquisition and maintenance of tobacco use disorders.

AbstractBackground and AimHealing rates of severe erosive esophagitis (EE; Los Angeles [LA] Grade C/D) in patients treated with a proton pump inhibitor (PPI) is suboptimal (~60–70%). Vonoprazan, a potassium‐competitive acid blocker, is suggested to have better healing rates in patients with severe EE. This meta‐analysis compares the efficacy and safety of vonoprazan 20 mg versus lansoprazole 30 mg daily in healing EE, specifically in those with LA Grade C/D.MethodsWe searched MEDLINE, Embase, and CENTRAL on May 24, 2023. Studies that randomized EE patients to vonoprazan 20 mg daily or lansoprazole 30 mg daily and compared healing rates were included. The risk of bias was assessed using Cochrane's Risk of Bias 2 tool. The fixed‐effect model was used to obtain the pooled efficacy and safety outcomes. Subgroup analysis was done to compare healing rates in mild (LA Grade A/B) versus severe EE and based on study location.ResultsFour randomized controlled trials (RCTs) with low risks of bias comprising 2208 participants were included. Vonoprazan 20 mg was superior to lansoprazole 30 mg daily in healing severe EE at all weeks (Week 2 RR 1.294 [95% CI 1.169–1.433], Week 4 1.160 [1.059–1.270], and Week 8 1.175 [95% CI 1.107–1.247]), but was similar for mild EE at all weeks (P‐interaction < 0.01). Vonoprazan 20 mg was more efficacious than lansoprazole 30 mg at Week 8 in Western versus Asian studies (P‐interaction < 0.01). Any, serious, and drug‐related treatment‐emergent adverse events were comparable between groups.ConclusionVonoprazan 20 mg is superior to lansoprazole 30 mg for healing severe EE but not mild EE. Vonoprazan 20 mg daily has a similar safety profile to lansoprazole 30 mg daily.

AbstractBackgroundComputed tomography (CT) is routinely used to guide cryoablation procedures. Notably, CT‐guidance provides 3D localization of cryoprobes and can be used to delineate frozen tissue during ablation. However, metal‐induced artifacts from ablation probes can make accurate probe placement challenging and degrade the ice ball conspicuity, which in combination could lead to undertreatment of potentially curable lesions.PurposeIn this work, we propose an image‐based neural network (CNN) model for metal artifact reduction for CT‐guided interventional procedures.MethodsAn image domain metal artifact simulation framework was developed and validated for deep‐learning‐based metal artifact reduction for interventional oncology (MARIO). CT scans were acquired for 19 different cryoablation probe configurations. The probe configurations varied in the number of probes and the relative orientations. A combination of intensity thresholding and masking based on maximum intensity projections (MIPs) was used to segment both the probes only and probes + artifact in each phantom image. Each of the probe and probe + artifact images were then inserted into 19 unique patient exams, in the image domain, to simulate metal artifact appearance for CT‐guided interventional oncology procedures. The resulting 361 pairs of simulated image volumes were partitioned into disjoint training and test datasets of 304 and 57 volumes, respectively. From the training partition, 116 600 image patches with a shape of 128 × 128 × 5 pixels were randomly extracted to be used for training data. The input images consisted of a superposition of the patient and probe + artifact images. The target images consisted of a superposition of the patient and probe only images. This dataset was used to optimize a U‐Net type model. The trained model was then applied to 50 independent, previously unseen CT images obtained during renal cryoablations. Three board‐certified radiologists with experience in CT‐guided ablations performed a blinded review of the MARIO images. A total of 100 images (50 original, 50 MARIO processed) were assessed across different aspects of image quality on a 4‐point likert‐type item. Statistical analyses were performed using Wilcoxon signed‐rank test for paired samples.ResultsReader scores were significantly higher for MARIO processed images compared to the original images across all metrics (all p < 0.001). The average scores of the overall image quality, iceball conspicuity, overall metal artifact, needle tip visualization, target region confidence, and worst metal artifact, needle tip visualization, iceball conspicuity, and target region confidence improved by 34.91%, 36.29%, 39.94%, 34.17%, 35.13%, and 45.70%, respectively.ConclusionsThe proposed method of image‐based metal artifact simulation can be used to train a MARIO algorithm to effectively reduce probe‐related metal artifacts in CT‐guided cryoablation procedures.

While the function of many leukocytes in transplant biology has been well defined, the role of eosinophils is controversial and remains poorly explored. Conflicting data exist regarding eosinophils’ role in alloimmunity. Due to their prevalence in the lung, and their defined role in other pulmonary pathologies such as asthma, we set out to explore the role of eosinophils in the long-term maintenance of the lung allograft. We noted that depletion of eosinophils results in the generation of donor-specific antibodies. Eosinophil depletion increased memory B cell, plasma cell, and antibody-secreting cell differentiation and resulted in de novo generation of follicular germinal centers. Germinal center formation depended on the expansion of CD4 + Foxp3 – Bcl6 + CXCR5 + PD-1 + T follicular helper (Tfh) cells, which increase in number after eosinophil depletion. Mechanistically, we demonstrate that eosinophils prevent Tfh cell generation by acting as the dominant source of IFN-γ in an established lung allograft, thus facilitating Th1 rather than Tfh polarization of naive CD4 + T cells. Our data thus describe what we believe is a unique and previously unknown role for eosinophils in maintaining allograft tolerance and suggest that indiscriminate administration of eosinophil-lytic corticosteroids for treatment of acute cellular rejection may inadvertently promote humoral alloimmunity.

AbstractBackgroundImmune checkpoint inhibitor (ICI) therapy has led to significant improvement in outcomes for patients with nononcogene‐driven advanced non–small cell lung cancer (NSCLC). The rate of crossover and receipt of postprotocol ICI in frontline trials for advanced NSCLC has not been systematically evaluated.MethodsClinicalTrials.gov was used to identify phase 3 studies evaluating the use of immunotherapy or combination chemoimmunotherapy against chemotherapy alone in the frontline management of advanced NSCLC. Data on outcomes, rate of crossover and/or subsequent post‐protocol receipt of immunotherapy, and the start dates of these clinical trials were then extracted.ResultsTwenty‐three frontline trials in nononcogene‐driven advanced NSCLC were identified. Six trials with ICI monotherapy/dual ICI therapy and 17 trials evaluating chemotherapy/ICI in first‐line advanced NSCLC were included in the analysis. The crossover rate ranged 0% to 54% in ICI monotherapy/dual ICI trials and 0% to 52% in chemotherapy/ICI trials. Nineteen of 23 trials provided information on subsequent postprotocol therapies. Among the trials not allowing crossover, postprotocol ICI was administered to 17% to 45.8% of patients. Information regarding the eventual receipt of ICI therapy was available for 22 of 23 trials. Of 6631 patients, 2507 (37.8%) randomized to the control arm eventually received ICI therapy.ConclusionThe rate of crossover and postprotocol ICI use was low in frontline trials for first‐line NSCLC incorporating ICI. Given the proven improved overall survival of ICI in a broad population, there is a need to ensure availability of this life‐prolonging therapy in future trials, either by crossover treatment or postprotocol administration.