Faculty Bibliography

BACKGROUND:Despite evidence supporting the efficacy of culturally tailored interventions in reducing stigma, such approaches are lacking for women living with HIV/AIDS (WLWHAs) in China. We conducted this study to determine the efficacy of the culturally tailored Helping Overcome Perceived Stigma (HOPES) intervention in reducing perceived stigma among WLWHAs in China. METHODS:A single-blinded, two-arm parallel-group randomized clinical trial was conducted from 2023 to 2024 in South and Southwest China. WLWHAs from four hospitals were assigned using a WeChat-embedded randomization application to the control group (usual care) or the HOPES intervention. Data analysts remained blinded. Interventions were conducted virtually using Leave No One Behind (LNOB) platform for 3 months. The primary outcome, perceived stigma score, was assessed at baseline, immediately after the intervention and at 3 months post-intervention using 7 items from the HIV/AIDS Stigma Experience Questionnaire (HASEQ), with data analyzed through repeated measures analysis. RESULTS:Of 136 WLWHAs screened, we randomized 101 WLWHAs (50 HOPES; 51 controls). The HOPES group demonstrated a statistically significant reduction in perceived stigma scores immediately after the intervention (-3.86 points, 95 % CI: 5.34 to -2.38, P < .001) and at three months post-intervention (-5.83 points, 95 % CI: 7.20 to -4.47, P < .001) compared to the control group. CONCLUSION/CONCLUSIONS:The findings demonstrate HOPES' efficacy in reducing perceived stigma in WLWHA. However, the clinical significance of these changes needs further investigation. Future research should focus on defining meaningful patient-reported thresholds, assessing long-term impact, and optimizing delivery methods.

To characterise the effectiveness of Bruton tyrosine kinase inhibitors with venetoclax in patients with refractory or relapsed mantle cell lymphoma, with or without the addition of an anti-CD20 antibody. Progression-free and overall survival were estimated for forty-nine patients treated with Bruton tyrosine kinase inhibitors and venetoclax (200 mg, daily) or in combination with an anti-CD20 monoclonal antibody between June 2018 and February 2022 in China. The median number of treatment lines before combination therapy was three (range, 2-7). The median patient age was 62 years, with a male-to-female ratio of 3.08:1. Patients exhibited high-risk features including Ki-67 ≥ 30% (89.8%), blastoid/pleomorphic histology (36.7%), high-risk mantle cell lymphoma International Prognostic Index group (42.9%), complex karyotype (27.7%), TP53 mutations (71.4%), TP53 mutations combined with other high-risk gene mutations including KMT2D, NSD2, CCND1, NOTCH1, CDKN2A, NOTCH2 and SMARCA4 (57.1%), and progression of disease within 24 months (65.3%), with similar efficacy and prognosis to low-risk cases. Basic clinical and cytogenetic characteristics, as well as efficacy and survival, were similar between the dual and triple combination therapy groups (all p > 0.05). The optimal overall response and complete remission rates were 67.4% and 53.1%, respectively. The 3-year progression-free and overall survival rates were 37.5% and 50.8%, respectively. Eastern Cooperative Oncology Group≥2was an independent predictor of progression-free survival. Eastern Cooperative Oncology Group performance status ≥ 2, TP53 mutations combined with other high-risk gene mutationswere independent factors for poor overall survival. The most common adverse reactions were haematological and pulmonary infections. The leading cause of death was disease progression (19/22). The combination of Bruton tyrosine kinase inhibitors and venetoclax, demonstrated good efficacy in patients with refractory or relapsed mantle cell lymphoma, particularly in the early treatment. There was no efficacy or survival advantages of adding CD20 antibodies. Patients in the ultrahigh-risk group required more aggressive treatments.

For COVAIL recipients of a coronavirus disease 2019 (COVID-19) Sanofi booster vaccine, neutralizing antibody titers were assessed as a correlate of risk (CoR) of COVID-19. Peak and exposure-proximal titers were inverse CoRs with covariate-adjusted hazard ratios (95% confidence intervals) 0.30 (0.11, 0.78) and 0.25 (0.07, 0.85) per 10-fold increase in weighted average titer.

BACKGROUND/UNASSIGNED:The informed consent process has traditionally taken place in person. The introduction of electronic consent (eConsent) has made remote consenting processes possible. Use of eConsent has increased since the COVID-19 pandemic. It has streamlined the process of consenting patients and has been shown to benefit the research study team and participants. ECONSENT IN THE KETAMINE ANALGESIA FOR LONG-LASTING PAIN RELIEF AFTER SURGERY KALPAS STUDY/UNASSIGNED:The KALPAS study is a multicenter, double-blind, randomized controlled study investigating the effectiveness of ketamine in reducing chronic post-mastectomy pain in women undergoing mastectomy for oncologic indication. The study uses a two-part consent form consisting of a master consent with information applicable to all sites and site-specific information. All potential participants receive the full two-part consent form for review. When signing the eConsent, however, all potential participants are provided with a concise summary of the informed consent document, an approach not widely used by multicenter studies. eConsent has been noted to be beneficial to research staff when trying to gather informed consent from participants who live far away from the hospital, want to include their family and friends, and for researchers who can approach patients outside of their clinical appointments. CONCLUSION/UNASSIGNED:The ability to consent patients remotely has allowed for a flexible workflow within sites and a more patient-centric process that focuses on including loved ones in the discussion and scheduling time to speak to a principal investigator. Demand for eConsent will likely continue in the post-COVID era, and use of a concise summary can allow for a more efficient consenting process.

Advances in closed-loop neural interfaces and neuromodulation have offered a potentially effective and non-addictive treatment for chronic pain. These interfaces link neural sensors with device outputs to provide temporally precise stimulation. We discuss challenges and trends of state-of-the-art neural interfaces for treating pain in animal models and human pilot trials.

Chronic pain affects one in five adults. It is not only a major cause of disability for individual patients but also a driver of costs for entire healthcare systems. Treatment of pain remains a challenge, and the use of opioids has further led to a concurrent opioid epidemic. In this review, we discuss current standard treatment options for chronic pain, including pharmacological, behavioral, and interventional treatments. In addition, we review ongoing research in different areas that will potentially unlock new therapies.

PURPOSE OF REVIEW/OBJECTIVE:Up to 60% of breast cancer patients continue to experience pain three months or more after surgery, with 15 to 25% reporting moderate to severe pain. Post-mastectomy pain syndrome (PMPS) places a high burden on patients. We reviewed recent studies on perioperative interventions to prevent PMPS incidence and severity. RECENT FINDINGS/RESULTS:Recent studies on pharmacologic and regional anesthetic interventions were reviewed. Only nine of the twenty-three studies included reported a significant improvement in PMPS incidence and/or severity, sometimes with mixed results for similar interventions. Evidence for prevention of PMPS is mixed. Further investigation of impact of variations in dosing is warranted. In addition, promising newer interventions for prevention of PMPS such as cryoneurolysis of intercostal nerves and stellate ganglion block need confirmatory studies.

Metastatic disease remains the leading cause of death due to cancer, yet the mechanism(s) of metastasis and its timely detection remain to be elucidated. Neutrophil elastase (NE), a serine protease secreted by neutrophils, is a crucial mediator of chronic inflammation and tumor progression. In this study, we used the PyMT model (NE+/+ and NE-/-) of breast cancer to interrogate the tumor-intrinsic and -extrinsic mechanisms by which NE can promote metastasis. Our results showed that genetic ablation of NE significantly reduced lung metastasis and improved metastasis-free survival. RNA-sequencing analysis of primary tumors indicated differential regulation of tumor-intrinsic actin cytoskeleton signaling pathways by NE. These NE-regulated pathways are critical for cell-to-cell contact and motility and consistent with the delay in metastasis in NE-/- mice. To evaluate whether pharmacologic inhibition of NE inhibited pulmonary metastasis and phenotypically mimicked PyMT NE-/- mice, we utilized AZD9668, a clinically available and specific NE inhibitor. We found AZD9668 treated PyMT-NE+/+ mice showed significantly reduced lung metastases, improved recurrence-free, metastasis-free and overall survival, and their tumors showed similar molecular alterations as those observed in PyMT-NE-/- tumors. Finally, we identified a NE-specific signature that predicts recurrence and metastasis in patients with breast cancer. Collectively, our studies suggest that genetic ablation and pharmacologic inhibition of NE reduces metastasis and extends survival of mouse models of breast cancer, providing rationale to examine NE inhibitors as a treatment strategy for the clinical management of patients with metastatic breast cancer.

BACKGROUND:Mastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25-60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP. METHODS:Ketamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale. DISCUSSION/CONCLUSIONS:This project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

INTRODUCTION/UNASSIGNED:Older adults undergoing surgery are at risk of postoperative neurocognitive disorders, prompting the need for preoperative cognitive screening in this population. Traditionally, cognitive screening has been conducted in-person using brief assessment tools such as the Montreal Cognitive Assessment (MoCA) or the Mini-Mental State Examination (MMSE). More comprehensive test batteries, such as the Uniform Data Set (UDS) Neuropsychological Battery, and its remote testing version, the Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 T-cog), have been developed to assess cognitive decline in normal aging and disease conditions, but have not been applied in the perioperative setting. METHODS/UNASSIGNED:We assessed the feasibility of using this remote UDS v3.0 T-cog battery for preoperative cognitive assessment in 81 older adults 65+ scheduled for lower extremity joint replacement surgery. RESULTS/UNASSIGNED:Our results indicate that the UDS v3.0 T-cog achieves 99% completion rates and demonstrates high patient satisfaction. Further, we found 28% of subjects were cognitively impaired in this patient cohort. DISCUSSION/UNASSIGNED:These findings suggest that the UDS v3.0 T-cog is a feasible tool for assessing cognitive function in the older adult perioperative population. To our knowledge, this is the first study to apply this comprehensive remote test battery in the preoperative setting.