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PURPOSE The primary objective of this randomized, double-blind, placebo-controlled, multicenter phase II study (Alliance A221805) was to screen two doses of duloxetine for preventing sensory oxaliplatin-induced peripheral neuropathy (OIPN). METHODS Participants were randomly assigned 1:1:1 to receive once daily 30 mg duloxetine, 60 mg duloxetine, or placebo. Eligible participants had stage II to III colorectal cancer and no baseline neuropathy, had Eastern Cooperative Oncology Group performance status 0-2, were age 25 years and older, and received oxaliplatin via one of the following doses and schedules: 85 mg/m 2 every 2 weeks (6 or 12 doses) or 130 mg/m 2 every 3 weeks (4 doses). Duloxetine/placebo was taken once daily beginning day 1 of cycle 1 and continued for 17 weeks. The primary end point, a composite response reflecting sensory OIPN symptom severity and onset, was measured in weeks 19-21 using a validated participant-reported outcome survey assessing extremity numbness, tingling, and pain. Response was defined as a participant-reported highest score of ≤2 (ie, 1 = not at all; 2 = a little) on survey items. To be evaluable for the response end point, eligible participants must have initiated oxaliplatin and submitted ≥1 postbaseline OIPN survey. RESULTS Of the 199 participants (n = 66, 30 mg duloxetine; n = 66, 60 mg duloxetine; n = 67, placebo), 46, 47, and 50 (N = 143, 71.8%), respectively, were evaluable for primary end point analysis based on modified intention-to-treat criteria. Participant mean age was 55.1 years (standard deviation = 10.4). Most were White (n = 113, 80.7%) and male (n = 82, 58.6%). The proportion of responders among those receiving placebo (68.0%) was similar to those receiving duloxetine 30 mg (65.2%) or 60 mg (66.0%). Duloxetine adherence rates, measured via pill counts—30 mg (54%), 60 mg (57%), and placebo (59%) groups—were low (<75%). CONCLUSION Duloxetine is not more promising than placebo for preventing sensory OIPN.

Obesity is a persistent public health issue, often resulting in metabolic complications such as insulin resistance (IR). The secretion of pro-inflammatory cytokines from adipose tissue (AT) is increased during obesity, contributing to the impairment of systemic insulin sensitivity. While interventions in animal models have shown that reducing inflammation restores insulin sensitivity, human studies reducing systemic inflammation have produced inconsistent results. We recently demonstrated that three months of high-dose (4 g/daily) ω-3PUFA (fish oil, FO) supplementation improved insulin sensitivity, and decreased systemic and AT inflammation in individuals with obesity (BMI ≥ 30 kg/m2). Given recent studies highlighting the involvement of microRNA (miRNA) in inflammatory cytokine production, we investigated the effect of ω-3PUFA supplementation on AT miRNA expression in this cohort. AT biopsies were collected before and after ω-3PUFA supplementation. miRNA was processed on the Affymetrix miRNA 4.0 GeneChip and analyzed using existing inflammatory gene sets sourced from MSigDB. Unbiased, differentially expressed miRNA analysis identified miR-4498 and miR-5689 as significantly increased after three months of ω-3PUFA supplementation. Real-time PCR confirmed bioinformatic analysis findings. Our study reports the modulation of miRNA in AT, reductions in systemic and AT markers of inflammation, and the improvement of IR post ω-3PUFA supplementation. Further research is needed to elucidate the link between miR-4498, miR-5689, and whole-body insulin sensitivity.

Abstract Background Patients with inflammatory bowel disease (IBD) receiving immunosuppressive therapies are at increased risk of vaccine-preventable diseases, including influenza. Despite recommendations for annual influenza vaccination, uptake remains suboptimal. The COVID-19 pandemic prompted a surge in telemedicine (Tele-M) use, raising concerns about its impact on vaccination rates due to reduced in-person interactions. This study aimed to assess the impact of IBD-specific Tele-M on influenza vaccine uptake and identify predictors of vaccination in patients with IBD. Methods This single-center retrospective study evaluated influenza vaccine uptake among adult patients with IBD seen between September 2021 and April 2022. Patients were categorized into two groups: Tele-M only and ≥1 in-person visit. Vaccination status was confirmed using the Wisconsin Immunization Registry. Primary outcome was influenza vaccination frequency by visit type, while secondary outcomes evaluated the impact of Tele-M on other vaccinations and predictors of influenza vaccine uptake. Results Among 547 patients, 53.2% received Tele-M only and 46.8% had ≥1 in-person visit. Influenza vaccine uptake was similar between the Tele-M only and ≥1 in-person visit groups (69.0% vs. 75.1%, respectively, p = 0.11). The uptake of pneumococcal, hepatitis B, and zoster vaccines was also comparable. Predictors of higher influenza vaccine uptake included age ≥65, female sex, receipt of ≥ 3 COVID-19 vaccines, and previous influenza vaccination. Conclusions IBD-specific Tele-M did not adversely affect influenza vaccine uptake among patients with IBD. These findings highlight the importance of ensuring vaccination compliance irrespective of healthcare delivery modes. Collaboration among healthcare providers is crucial to improve vaccination rates in patients with IBD.

Abstract INTRODUCTION The infectious hypothesis suggests that microbes like herpesviruses may play a role in the pathogenesis of Alzheimer's disease (AD) and other related dementias through methods that may include viral genome integration. The occurrence of herpesvirus genome integration in dementia patients has not been thoroughly characterized. METHODS Over 7500 total whole‐genome sequences from control, frontotemporal dementia/amyotrophic lateral sclerosis spectrum, Lewy body dementia (LBD), multiple system atrophy (MSA), and AD cohorts were screened for the integration of pathogen genomes using the PathSeq computational tool. RESULTS Low PathSeq scores for human herpesvirus 6 (HHV‐6) were consistent with the suspected integration of viral genome segments. The LBD and MSA cohorts had a significantly higher prevalence of this partial HHV‐6 genome integration. DISCUSSION This higher prevalence in both synucleinopathies was not noted in other herpesviruses, suggesting that the integration of HHV‐6 may play a role in a subset of these patients. Highlights Over 7500 whole‐genome sequences from controls and dementia patients were analyzed. Sequences consistent with integrated herpesviruses were identified using PathSeq. Prevalence of partial HHV‐6 integration was higher in synucleinopathies. Herpesviruses genome integration may play a role in subsets of dementia patients.

ABSTRACT Background Decision‐making (DM) dynamics between adolescents and young adults (AYAs) with cancer, parents, and oncologists remain underexplored in diverse populations. We examined cancer treatment DM preferences among an ethnically and socioeconomically diverse group of AYAs and their parents. Procedure We surveyed AYAs with cancer ( n = 75) and their parents ( n = 52) participating in the Texas KidsCanSeq study. Among AYA‐parent pairs, we compared preferred and actual treatment DM roles. We explored associations among DM roles, having pediatric‐to‐adult care transition discussions, and clinical and sociodemographic characteristics. We report AYAs’ and parents’ preferences for involvement in shared decision‐making (SDM) with oncologists about cancer treatment. Results AYAs’ DM role preferences varied: 44% preferred to equally share DM with parents, 31% preferred AYA‐led DM, and 25% preferred parent‐led DM. Parents who preferred parent‐led DM had younger AYAs than parents who preferred equally shared DM ( p = 0.011). For actual DM, 48% of AYAs reported DM was equally shared, 24% reported DM was AYA‐led, and 28% reported DM was parent‐led. Most AYAs had their preferred role (73%). AYAs’ actual role did not significantly differ from their own or their parents’ preferences (both p > 0.05). Approximately half of AYAs reported recent pediatric‐to‐adult care transition discussions. AYAs’ DM preferences and participation in transition discussions did not significantly differ along clinical or sociodemographic characteristics (all p > 0.05). AYAs and parents perceived high importance across all aspects of SDM with oncologists. Conclusion In this diverse study population, AYAs desired engagement in treatment DM and SDM. Although specific role preferences varied, opportunities existed to increase discussion around pediatric‐to‐adult care transition.

ABSTRACT Myelofibrosis is characterized by perturbation of the JAK/STAT pathway and upregulation of anti‐apoptotic factors leading to myeloproliferation, bone marrow fibrosis (BMF), extramedullary hematopoiesis, splenomegaly, and cytopenias. Navitoclax, a potent oral B‐cell lymphoma (BCL)‐X L /BCL‐2 inhibitor, promotes apoptosis of malignant myelofibrosis cells. Herein, we present results of Cohort 3 of the Phase 2 REFINE study (NCT03222609), which evaluated efficacy and safety of navitoclax plus ruxolitinib in JAKi‐naïve patients with myelofibrosis. JAKi‐naïve patients with primary or secondary myelofibrosis (≥ 18 years with splenomegaly, DIPSS intermediate‐2 and high‐risk myelofibrosis, and ECOG 0–2) and platelet count > 100 × 10 9 /L were enrolled and treated with navitoclax 100 mg once daily (QD) or 200 mg QD according to platelet count (≤ 150 × 10 9 /L or > 150 × 10 9 /L, respectively). Ruxolitinib was given twice daily (dose per label). Primary endpoint: spleen volume reduction of ≥ 35% (SVR 35 ) at week 24. Secondary endpoints: ≥ 50% reduction in total symptom score (TSS 50 ) at week 24, change in grade of BMF, anemia response, and safety. Thirty‐two patients received ≥ 1 dose of navitoclax plus ruxolitinib. Median (range) duration of follow‐up was 44 months (5–58). 63% (20/32) of patients achieved SVR 35 at week 24; median (range) time to first SVR 35 was 12 weeks (11─48). Of 24 evaluable patients, 21% achieved ≥ 50% reduction in driver gene variant allele frequency (VAF). Of 27 evaluable patients, 11 (41%) achieved TSS 50 at week 24; median (range) time to first TSS 50 of 3 weeks (0─16). BMF improved from baseline by ≥ 1 grade in 13/27 patients (48%) at any time on study. Anemia response rates were 38% (5/13) for transfusion‐independent and 100% (2/2) for transfusion‐dependent patients. No bleeding events or deaths were attributed to navitoclax. These findings suggest navitoclax plus ruxolitinib has a tolerable safety profile and provides clinically meaningful improvements for JAKi‐naïve patients with myelofibrosis. Trial Registration NCT03222609.

Failed pediatric endotracheal intubation, prompting surgical airway management via emergency front of neck access (eFONA), is an intrinsically challenging topic. While rare, all emergency airway providers must be equipped to handle these complex clinical scenarios, both through initial training and maintenance of competency. Needle cricothyrotomy is a commonly taught method in cannot intubate cannot oxygenate (CICO) scenarios for children under age eight. However, needle cricothyrotomy is technically difficult, profoundly rare, and maintaining competency is a challenge. From a multidisciplinary perspective, we examine the utility of continuing to teach needle cricothyrotomy and explore alternatives. This project group suggests that pediatric eFONA training across disciplines should focus on surgical tracheotomy rather than needle cricothyrotomy, with consideration given to specialty-specific human performance factors.

Triple-negative breast cancer (TNBC) remains highly aggressive and refractory to conventional treatments, underscoring the need for novel combination strategies. Here, we employed 2D and 3D in vitro models, transcriptomic profiling, and in vivo xenograft studies to evaluate the anticancer efficacy of cannabinoids combined with the terpene β-caryophyllene (BC) in resistant TNBC models. Among the tested cannabinoids, cannabichromene (CBC) exhibited the greatest potency, and its combination with BC at sub-toxic concentrations significantly reduced IC50 values, enhanced cytotoxicity in spheroids, and suppressed colony formation and migration. The combination treatment induced pronounced G1 cell cycle arrest and increased apoptotic cell death. Western blot analyses revealed downregulation of PARP, Survivin, mTOR, Vimentin, Glypican-5, and PD-L1, while RNA sequencing demonstrated suppression of proliferative and migratory signaling pathways alongside activation of apoptosis, autophagy, and ferroptosis-related pathways. In vivo, CBC + BC significantly inhibited tumor growth in MDA-MB-231 xenografts, outperforming single-agent treatments. Collectively, these findings demonstrate that BC synergistically enhances cannabinoid activity, yielding superior antiproliferative and anti-migratory effects, and highlight this combination as a promising therapeutic strategy for resistant TNBC.

Most palliative care (PC) physicians will change jobs over the course of their career, yet few supports exist to guide them through this often unfamiliar process. Job transitions frequently elicit stress and uncertainty, as individuals balance personal and professional priorities, navigate complex negotiations, and assume the inherent risks of pursuing new opportunities. Yet, when approached intentionally, a job transition can also be a transformative process that allows for self-discovery, cultivation of new skills and connections, and reshaping of one’s professional identity. This article, written by a team of PC physicians who have made job transitions themselves, offers 10 tips for navigating this professional step successfully. With emphases on authentic communication, skilled mentorship, relationship building, and exploration of local culture—the article offers practical advice to help PC physicians navigate a job transition confidently, while staying grounded in their personal values and the work they find most meaningful.