Citations

AbstractObjectiveThis study aimed to evaluate the impact of endoscopic sinus surgery (ESS) on asthma severity up to 12 months after surgical intervention.Study DesignRetrospective cohort.SettingTertiary care center.MethodsPatients with a history of asthma and Chronic Rhinosinusitis (CRS) who underwent ESS between 2013 and 2023 were included. Asthma severity was assessed according to current Global Initiative for Asthma (GINA) guidelines, classifying patients into mild, moderate, and severe based on medication requirements. Asthma severity was evaluated up to 3 months prior to ESS and 1‐year post‐ESS. Patients with aspirin‐exacerbated respiratory disease (AERD) were excluded. Statistical analysis was performed using McNemar test and Wilcoxon signed‐rank test to assess differences in asthma severity, medication doses, and number of medications.ResultsSixty‐five patients were included, of which 44 (67.7%) had CRS with nasal polyps (CRSwNP) and 21 (32.3%) had CRS without nasal polyps (CRSsNP). No significant differences were found in asthma severity pre‐ and post‐ESS (P = .175). Similarly, no differences were found in ICS doses (P = .999), total number of prescribed medications (P = .157) or presence of exacerbations before and after ESS (P = .078). However, a significant increase in time from last rescue inhaler use was noted after ESS, increasing from a median of 6.71 to 23.1 weeks (P = .004).ConclusionThis study is the first to assess the impact of ESS on asthma severity in a real‐world setting. Our findings suggest that ESS does not impact asthma severity classification. However, it might provide relief of asthma symptoms in the early postoperative period.

Introduction: The Mindfulness-Based Stress Reduction (MBSR) Program for breast cancer survivors (BCS) is designed to enhance cognitive training through formal and informal meditational practices. This randomized clinical trial (RCT) aimed to evaluate if BCS assigned to either the MBSR(BC), Breast Cancer Education Support (BCES), or Usual Care (UC) regimens experienced greater improvements at 6, 12, and 26 weeks on objective and subjective cognitive performance. Methods: BCS ( n = 212) randomized to a three-group RCT: MBSR(BC) ( n = 91), BCES ( n = 90), or UC ( n = 31) were assessed on cognitive performance and symptoms at baseline, 6, 12, and 26 weeks. Linear mixed models were fit to evaluate the effects of the MBSR(BC) program, hypothesizing ordered effect improvements: (MBSR[BC] highest, BCES intermediate, UC lowest) along with baseline characteristics evaluated as moderators. Results: Of the BCS (mean age of 57), 73% were White, and non-Hispanic, and 77% received both chemotherapy (CT) and radiation. Cognitive performance improved in all groups. Although there were no statistically significant between-group differences in cognitive outcomes, significant symptom reductions occurred for the MBSR(BC) group ( p = 0.003). Within-group effect size analysis at 26 weeks showed substantial improvements in all three groups (effect sizes >0.50) in subjective impairments and quality of life (effect size >0.50) and objective measures of cognitive performance. MBSR(BC) showed the largest within-group effect size in the reduction of fatigue (effect size = 0.81). Effect sizes occurred in the hypothesized direction for 10 of the 18 outcomes. Discussion: Although the MBSR(BC) program did not show significant differences in cognitive performance compared with BCES and UC, all groups improved and reductions in fatigue were beneficial for MBSR(BC). Results suggest that cognitive performance may improve after CT over time considering one’s natural history. Furthermore, BCS enrolled in RCTs may be more motivated to improve their health status (NCT02786797).

Background and Aims: This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Methods: A case–control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease ( N = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) ( N = 22), acute pancreatitis ( N = 33), recurrent acute pancreatitis ( N = 57), and definite CP ( N = 63). Results: Circulating AEA concentrations were higher in women than in men ( p = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight ( p = 0.003). Asymptomatic controls with no pancreatic disease had significantly ( p = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly ( p = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower ( p = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. Conclusions: Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.

Abstract Recurrent respiratory papillomatosis (RRP) is a debilitating chronic disease of the airway caused by Human Papillomavirus (HPV). Here we describe the efficacy, safety, and immunogenicity from a Phase 1/2 trial of INO-3107, a DNA immunotherapy designed to elicit T-cell responses against HPV-6 and HPV-11, in adults with RRP (NCT04398433). Thirty-two eligible patients with HPV-6 and/or HPV-11 RRP, who required ≥2 surgical interventions in the year preceding dosing, were administered 4 doses of INO-3107 by intramuscular (IM) injection followed by electroporation (EP). The primary endpoint was safety and tolerability. Efficacy and immunology endpoints included the frequency of surgical interventions in the year following the first dose of INO-3107 and assessment of immune responses. The majority (26/32; 81%) of patients experienced a reduction in the number of surgeries in the year following initiation of treatment with INO-3107, when compared with the year prior. Peripheral blood assessments revealed HPV-6 and HPV-11 antigen-specific T-cell induction, inclusive of cytolytic CD8+ T-cells. RNA sequencing identified the presence of an inflammatory response in patient papillomas after treatment with INO-3107, inclusive of cytolytic CD8+ T-cell signatures. T-cell receptor sequencing revealed emergent T-cell clones in the blood and assessment of airway tissue confirmed trafficking of these clones to papillomas, which was associated with clinical benefit. Treatment was well tolerated, with 13/32 (41%) patients reporting a treatment-related adverse event (AE), all of which were low-grade. INO-3107 provides clinical benefit to adults with HPV-6 and/or HPV-11 associated RRP, is well tolerated, and generates an antigen-specific immune response against HPV. Importantly, treatment-induced peripheral T-cell responses traffick to airway tissue and are associated with clinical response, consistent with the proposed mechanism of action.

Background/Objectives: Multi-gene, multi-cancer, hereditary cancer risk screenings may be useful in cancer prevention and treatment, not only for cancer patients but also for patients’ family members. If genetic cancer screening is to have the widest possible benefit, it must be extended into diverse cancer care settings that serve diverse patient communities, providing cancer patients and their relatives with individualized cancer risk evaluations. Little research, to date, has examined the impact of extending multigenic cancer screening into diverse settings. Without empirical data characterizing the support needs of cancer patients and their family members, we may not adequately satisfy the needs of all patients and risk exacerbating existing disparities in cancer care and outcomes. Methods: We examined patient perspectives on the sharing of genetic results with at-risk family members by surveying a racially diverse sample of cancer patients receiving a multi-gene, multi-cancer risk screen in a community hospital setting. Results: In a survey of 230 cancer patients, we found that intent to share results with family members was high but varied across family member types. More respondents planned to disclose results to at least one sister (82.5%) compared to at least one brother (73.1%). Over one-fourth of participants (27.4%) were either uncertain about sharing or intended to withhold their genomic screening results from at least one at-risk family member eligible for cascade testing. Participants were more likely to withhold their results from a sibling than from a child. Furthermore, intent to share across all family member types was lower if probands failed to identify at least one benefit to sharing. Conclusions: Understanding factors associated with decisions to share results with at-risk relatives in diverse patient populations can help clinicians support cascade genetic cancer screenings in diverse communities and settings.

Adaptive radiotherapy (ART) workflows are increasingly adopted to achieve dose escalation and tissue sparing under dynamic anatomical conditions. However, recontouring and time constraints hinder the implementation of real-time ART workflows. Various auto-segmentation methods, including deformable image registration, atlas-based segmentation, and deep learning-based segmentation (DLS), have been developed to address these challenges. Despite the potential of DLS methods, clinical implementation remains difficult due to the need for large, high-quality datasets to ensure model generalizability. This study introduces an InterVision framework for segmentation. The InterVision framework can interpolate or create intermediate visuals between existing images to generate specific patient characteristics. The InterVision model is trained in two steps: (1) generating a general model using the dataset, and (2) tuning the general model using the dataset generated from the InterVision framework. The InterVision framework generates intermediate images between existing patient image slides using deformable vectors, effectively capturing unique patient characteristics. By creating a more comprehensive dataset that reflects these individual characteristics, the InterVision model demonstrates the ability to produce more accurate contours compared to general models. Models are evaluated using the volumetric dice similarity coefficient (VDSC) and the Hausdorff distance 95% (HD95%) for 18 structures in 20 test patients. As a result, the Dice score was 0.81 ± 0.05 for the general model, 0.82 ± 0.04 for the general fine-tuning model, and 0.85 ± 0.03 for the InterVision model. The Hausdorff distance was 3.06 ± 1.13 for the general model, 2.81 ± 0.77 for the general fine-tuning model, and 2.52 ± 0.50 for the InterVision model. The InterVision model showed the best performance compared to the general model. The InterVision framework presents a versatile approach adaptable to various tasks where prior information is accessible, such as in ART settings. This capability is particularly valuable for accurately predicting complex organs and targets that pose challenges for traditional deep learning algorithms.

Summary Introduction Obesity is characterized by chronic low‐grade inflammation. This study presents an updated systematic review and meta‐analysis on the effect of caloric restriction (CR) and intermittent fasting (IF) on plasma inflammatory biomarkers (C‐reactive protein [CRP], tumor necrosis factor [TNF]‐alpha, and interleukin [IL]‐6) in individuals with obesity/overweight compared with unrestricted or ad libitum feeding. Methods PubMed, Web of Science, and SCOPUS databases were searched for randomized controlled trials (RCTs) reporting inflammatory biomarkers after at least 8 weeks of intervention. Standardized mean differences (SMDs) were calculated using a fixed effect model. Heterogeneity was determined using I 2 statistics. Sensitivity analysis was conducted using the “leave‐one‐out” approach. Results Relatively few RCTs have investigated the effect of IF on inflammatory biomarkers than with CR (6 vs. 15). Analysis of pooled data showed that CR was associated with a significant reduction in CRP with low heterogeneity (SMD −0.15 mg/L [95% CI −0.30 to −0.00], p = 0.04; I 2 = 0%, p = 0.69) and IL‐6 with high heterogeneity (SMD −0.31 pg/mL [95% CI −0.51 to −0.10], p = 0.004; I 2 = 73%, p = 0.001). IF was associated with a significant decrease in TNF‐alpha with moderate heterogeneity (SMD −0.32 pg/mL [95% CI −0.63 to −0.02], p = 0.04; I 2 = 44%, p = 0.13). No associations were detected between IF and CRP or IL‐6 and CR and TNF‐alpha. Conclusion CR may be more effective in reducing chronic low‐grade inflammation than IF. However, there were some concerns regarding the included studies' randomization and allocation sequence concealment process.

Abstract Objectives The red blood cell (RBC) D antigen is highly immunogenic, and anti-D alloimmunization can cause hemolytic transfusion reactions and hemolytic disease of the fetus and newborn. This study examined how RhD-negative patients who required packed RBCs (pRBCs) were handled during the COVID-19 pandemic and whether policies and practices on RhD-positive pRBC allocation to RhD-negative patients changed. Methods The Association for the Advancement of Blood & Biotherapies (AABB) Clinical Hemotherapy Subsection distributed a 17-question survey to physician AABB members to elucidate the impact of the COVID-19 pandemic on the policies and practices governing the provision of RhD-positive pRBCs to RhD-negative patients. Results There were 215 respondents who started the survey, but only 104 answered all the questions. Most institutional policies (130/155 [83.87%]) and personal practices (100/126 [79.37%]) on pRBC selection did not change during the COVID-19 pandemic. The practice of switching back to RhD-negative pRBCs after administration of RhD-positive pRBCs is variable. More than half of respondents (56/104 [53.85%]) reported offering Rh immunoglobulin to any Rh-negative patients who received RhD-positive pRBCs. Conclusions Despite RhD-negative pRBC supply challenges, most institutional policies and personal practices on when to provide RhD-positive pRBCs to RhD-negative patients did not change during the pandemic.