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Neutralizing Antibody Immune Correlates for a Recombinant Protein Vaccine in the COVAIL Trial
Fong, Youyi; Dang, Lauren; Zhang, Bo; Fintzi, Jonathan; Chen, Shiyu; Wang, Jing; Rouphael, Nadine G; Branche, Angela R; Diemert, David J; Falsey, Ann R; Losada, Cecilia; Baden, Lindsey R; Frey, Sharon E; Whitaker, Jennifer A; Little, Susan J; Kamidani, Satoshi; Walter, Emmanuel B; Novak, Richard M; Rupp, Richard; Jackson, Lisa A; Yu, Chenchen; Magaret, Craig A; Molitor, Cindy; Borate, Bhavesh; Babu, Tara M; Kottkamp, Angelica C; Luetkemeyer, Anne F; Immergluck, Lilly C; Presti, Rachel M; Bäcker, Martín; Winokur, Patricia L; Mahgoub, Siham M; Goepfert, Paul A; Fusco, Dahlene N; Atmar, Robert L; Posavad, Christine M; Mu, Jinjian; Makowski, Mat; Makhene, Mamodikoe K; Nayak, Seema U; Roberts, Paul C; Follmann, Dean; Gilbert, Peter B; ,
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.
PMCID:11797383
PMID: 39325506
ISSN: 1537-6591
CID: 5783432
Closed-loop neural interfaces for pain: Where do we stand?
Wang, Jing; Chen, Zhe Sage
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.
PMID: 39413730
ISSN: 2666-3791
CID: 5711692
Clinical pain management: Current practice and recent innovations in research
Wang, Jing; Doan, Lisa V
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.
PMID: 39383871
ISSN: 2666-3791
CID: 5706162
Prevention of Post-Mastectomy Pain Syndrome: A Review of Recent Literature on Perioperative Interventions
Wu, Rachel R; Katz, Simon; Wang, Jing; Doan, Lisa V
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.
PMID: 38814502
ISSN: 1534-6269
CID: 5663762
Neutrophil Elastase Remodels Mammary Tumors to Facilitate Lung Metastasis
Lulla, Amriti R; Akli, Said; Karakas, Cansu; Caruso, Joseph A; Warma, Lucas D; Fowlkes, Natalie W; Rao, Xiayu; Wang, Jing; Hunt, Kelly K; Watowich, Stephanie S; Keyomarsi, Khandan
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.
PMCID:10987287
PMID: 37796181
ISSN: 1538-8514
CID: 5735922
Neutrophil Elastase Remodels Mammary Tumors to Facilitate Lung Metastasis
Lulla, Amriti R; Akli, Said; Karakas, Cansu; Caruso, Joseph A; Warma, Lucas D; Fowlkes, Natalie W; Rao, Xiayu; Wang, Jing; Hunt, Kelly K; Watowich, Stephanie S; Keyomarsi, Khandan
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.
PMCID:10987287
PMID: 37796181
ISSN: 1538-8514
CID: 5735912
Optimizing the use of ketamine to reduce chronic postsurgical pain in women undergoing mastectomy for oncologic indication: study protocol for the KALPAS multicenter randomized controlled trial
Wang, Jing; Doan, Lisa V; Axelrod, Deborah; Rotrosen, John; Wang, Binhuan; Park, Hyung G; Edwards, Robert R; Curatolo, Michele; Jackman, Carina; Perez, Raven; ,
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.
PMCID:10797799
PMID: 38243266
ISSN: 1745-6215
CID: 5624462
Application of the Uniform Data Set version 3 tele-adapted test battery (T-cog) for remote cognitive assessment preoperatively in older adults
Rockholt, Mika M; Wu, Rachel R; Zhu, Elaine; Perez, Raven; Martinez, Hamleini; Hui, Jessica J; Commeh, Ekow B; Denoon, Romario B; Bruno, Gabrielle; Saba, Braden V; Waren, Daniel; O'Brien, Courtney; Aggarwal, Vinay K; Rozell, Joshua C; Furgiuele, David; Macaulay, William; Schwarzkopf, Ran; Schulze, Evan T; Osorio, Ricardo S; Doan, Lisa V; Wang, Jing
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.
PMCID:11782117
PMID: 39897457
ISSN: 1663-4365
CID: 5783672
AMPAkines have site-specific analgesic effects in the cortex
Zhu, Elaine; Mathew, Dave; Jee, Hyun Jung; Sun, Mengqi; Liu, Weizhuo; Zhang, Qiaosheng; Wang, Jing
Different brain areas have distinct roles in the processing and regulation of pain and thus may form specific pharmacological targets. Prior research has shown that AMPAkines, a class of drugs that increase glutamate signaling, can enhance descending inhibition from the prefrontal cortex (PFC) and nucleus accumbens. On the other hand, activation of neurons in the anterior cingulate cortex (ACC) is known to produce the aversive component of pain. The impact of AMPAkines on ACC, however, is not known. We found that direct delivery of CX516, a well-known AMPAkine, into the ACC had no effect on the aversive response to pain in rats. Furthermore, AMPAkines did not modulate the nociceptive response of ACC neurons. In contrast, AMPAkine delivery into the prelimbic region of the prefrontal cortex (PL) reduced pain aversion. These results indicate that the analgesic effects of AMPAkines in the cortex are likely mediated by the PFC but not the ACC.
PMCID:10860473
PMID: 37921508
ISSN: 1744-8069
CID: 5635122
What Matters to Chinese and Korean American Dementia Caregivers: Navigating Cultural Influences in Dementia Care from Caregivers' Perspectives
Wang, Jing; Leong, I Tek; Johnson, Min Kyoung; Pei, Yaolin; Lee, Kyung Hee; Mittelman, Mary S; Epstein, Cynthia; Cho, Soyeon; Wu, Bei
BACKGROUND/UNASSIGNED:Chinese and Korean Americans are among the fastest-growing minority groups in the US but face disparities in income and limited English proficiency, leading to health inequities in Alzheimer's disease and related dementias (ADRD) care. OBJECTIVE/UNASSIGNED:This study aims to understand cultural influences in ADRD care from the perspectives of Chinese and Korean American caregivers to inform culturally sensitive support for caregivers in Asian immigrant populations. METHODS/UNASSIGNED:We conducted a study that was part of a broader project aimed at informing the cultural adaptation of the NYU Caregiver Intervention-Enhanced Support (NYUCI-ES) program specifically for Chinese and Korean American caregivers managing multiple chronic conditions. In our interviews with 14 Chinese American and 11 Korean American caregivers, we focused on how their roles as primary caregivers were influenced by cultural and family expectations, the impact of caregiving on their personal and emotional well-being, and the specific barriers they face in accessing healthcare for themselves and their relatives with dementia. RESULTS/UNASSIGNED:Cultural beliefs and values significantly influenced the perceptions and utilization of support systems among Chinese and Korean American caregivers. Family stigma and adherence to cultural norms impacted their caregiving experiences. The study also highlighted the added burden during the pandemic and the potential benefits of telehealth and information technology in ADRD care. CONCLUSIONS/UNASSIGNED:Developing culturally tailored, person-centered programs is crucial to meeting the unique needs of Chinese and Korean American caregivers. This research contributes to understanding and supporting this vulnerable population, promoting healthcare equity for ADRD patients and caregivers.
PMID: 38427483
ISSN: 1875-8908
CID: 5644292