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Translational randomized phase II trial of cabozantinib in combination with nivolumab in advanced, recurrent, or metastatic endometrial cancer
(BMJ, 2022-03) Lheureux, Stephanie; Matei, Daniela E.; Konstantinopoulos, Panagiotis A.; Wang, Ben X.; Gadalla, Ramy; Block, Matthew S.; Jewell, Andrea; Gaillard, Stephanie L.; McHale, Michael; McCourt, Carolyn; Temkin, Sarah; Girda, Eugenia; Backes, Floor J.; Werner, Theresa L.; Duska, Linda; Kehoe, Siobhan; Colombo, Ilaria; Wang, Lisa; Li, Xuan; Wildman, Rachel; Soleimani, Shirin; Lien, Scott; Wright, John; Pugh, Trevor; Ohashi, Pamela S.; Brooks, David G.; Fleming, Gini F.; Obstetrics and Gynecology, School of Medicine
Background
Combining immunotherapy and antiangiogenic agents is a promising treatment strategy in endometrial cancer. To date, no biomarkers for response have been identified and data on post-immunotherapy progression are lacking. We explored the combination of a checkpoint inhibitor (nivolumab) and an antiangiogenic agent (cabozantinib) in immunotherapy-naïve endometrial cancer and in patients whose disease progressed on previous immunotherapy with baseline biopsy for immune profiling.
Patients and methods
In this phase II trial (ClinicalTrials.gov NCT03367741, registered December 11, 2017), women with recurrent endometrial cancer were randomized 2:1 to nivolumab with cabozantinib (Arm A) or nivolumab alone (Arm B). The primary endpoint was Response Evaluation Criteria in Solid Tumors-defined progression-free survival (PFS). Patients with carcinosarcoma or prior immune checkpoint inhibitor received combination treatment (Arm C). Baseline biopsy and serial peripheral blood mononuclear cell (PBMC) samples were analyzed and associations between patient outcome and immune data from cytometry by time of flight (CyTOF) and PBMCs were explored.
Results
Median PFS was 5.3 (90% CI 3.5 to 9.2) months in Arm A (n=36) and 1.9 (90% CI 1.6 to 3.4) months in Arm B (n=18) (HR=0.59, 90% CI 0.35 to 0.98; log-rank p=0.09, meeting the prespecified statistical significance criteria). The most common treatment-related adverse events in Arm A were diarrhea (50%) and elevated liver enzymes (aspartate aminotransferase 47%, alanine aminotransferase 42%). In-depth baseline CyTOF analysis across treatment arms (n=40) identified 35 immune-cell subsets. Among immunotherapy-pretreated patients in Arm C, non-progressors had significantly higher proportions of activated tissue-resident (CD103+CD69+) ɣδ T cells than progressors (adjusted p=0.009).
Conclusions
Adding cabozantinib to nivolumab significantly improved outcomes in heavily pretreated endometrial cancer. A subgroup of immunotherapy-pretreated patients identified by baseline immune profile and potentially benefiting from combination with antiangiogenics requires further investigation.
“I’m supposed to be a helper”: Spiritual distress of abortion providers after Dobbs v. Jackson
(2024-04) Bode, Leah; Kumar, Komal; McQuillan, Josie; Scott, Nicole; Bernard, Caitlin
INTRO
On June 24, 2022, the Supreme Court of the United States voted to overturn Roe v. Wade, the 1970 landmark case protecting abortion rights in America, in Dobbs v. Jackson Women’s Health Organization. The decision has the potential to affect the way that abortion providers practice their specialty by interacting with patients and making meaning from their work. Meaning making in one’s work has been shown to be integral in fostering spiritual well-being and preventing burnout in medicine. We sought to demonstrate the spectrum of spirituality of abortion providers and their subsequent spiritual distress in the aftermath of Dobbs.
METHODS
We conducted thirty-minute interviews on Zoom with 26 abortion providers from 17 states from November 2022 to February 2023. Demographics collected included age, racial identity, location of practice (by state), years in practice, fellowship training, and practice setting (community, academic, hybrid). States were then classified according to the Guttmacher Institute classifications of Most restrictive, Restrictive, Some restrictions/protections, Protective, and Very protective as of December 2022. Interviews consisted of questions such as "What are the major tenants of your spiritual beliefs (if none, how you make meaning)?” and “Tell me about any spiritual distress or alienation from your religious or spiritual community as a result of the Dobbs decision.” Interviews were transcribed using the closed caption feature on Zoom and coded by LB, KK, and JM. After achieving consensus, interviews were analyzed using NVivo 14.
RESULTS
Providers’ practices were equally distributed amongst community (34.6%), academic (34.6%), and hybrid (30.8%) settings. Location of practice (state) was well-distributed across the restrictive-protective spectrum: 7.7% Most restrictive, 30.8% Restrictive, 15.4% Some restrictions/protections, 30.8% Protective, and 15.4% Very protective. The majority of participants identified a personal spirituality, while less than half were tied to an organized religion. Sixteen participants (61.5%) cited ethical principles of justice, non-maleficence, respect for human life, or autonomy as major tenets of their spirituality. Ten subjects (38.5%) felt spiritually called to provide abortion care, 11 others (42.3%) perceived abortion care as a spiritual obligation, and 12 participants (46.2%) noted the act of providing an abortion as a spiritual act, for provider and/or patient. Most participants experienced spiritual distress relating to the Dobbs decision. Those who did not experience spiritual distress (26%) noted location and the alignment of their work with spiritual values as protective factors. Of note, 92% of participants described their spirituality as helpful in coping with the fall of Roe v. Wade. Sources of strength included advocacy, agency (e.g., “I feel strength knowing that I’m still able to do this job”), legislative work, and community; 57.7% specifically cited the abortion provider community.
CONCLUSION
The decision to be an abortion provider is often motivated by one’s spiritual identity. Regarding the fall of Roe v. Wade, many abortion providers endorsed feelings of spiritual distress related to not being able to comply with their moral and/or spiritual obligation of providing abortions secondary to new restrictions. Location played a large role in whether providers were experiencing this distress, suggesting that state restrictions on abortions have directly impacted the spiritual well-being of abortion providers. As many laws pertaining to abortion are influenced by religious beliefs, it is important to recognize that abortion providers themselves are overwhelming spiritual.
Caught in a Loop with Advance Care Planning and Advance Directives: How to Move Forward?
(Mary Ann Liebert, Inc., 2022-03) Periyakoil, Vyjeyanthi S.; von Gunten, Charles F.; Arnold, Robert; Hickman, Susan; Morrison, Sean; Sudore, Rebecca; Medicine, School of Medicine
Completion of an advance care planning (ACP) process and/or an advance directive should result in patients receiving the care they desire at the end of life. However, three decades of research have shown that is just not the case. ACP has been a front runner in developing the science within palliative care. Some positive outcomes such as lowering levels of surrogate grief may be associated with ACP. Yet, it does not appear that further ACP research will ensure that seriously ill patients will get goal-concordant care. An unfortunate consequence of palliative care research and advocacy so far is the misguided notion of many hospital systems trying to solve their palliative care problems by only implementing an ACP initiative. At best, ACP is but one tool in the collective palliative care toolbox. New tools are needed. Given that we have finite resources, future research should focus more on tools to improve symptom management, better models of care, and systems that will ensure goal-concordant care that meet the needs of the population that the health care system is designed to meet.
Pediatric Traumatic Brain Injury: An Update on Preclinical Models, Clinical Biomarkers, and the Implications of Cerebrovascular Dysfunction
(Sage, 2022-05-22) Nwafor, Divine C.; Brichacek, Allison L.; Foster, Chase H.; Lucke-Wold, Brandon P.; Ali, Ahsan; Colantonio, Mark A.; Brown, Candice M.; Qaiser, Rabia; Neurological Surgery, School of Medicine
Traumatic brain injury (TBI) is a leading cause of pediatric morbidity and mortality. Recent studies suggest that children and adolescents have worse post-TBI outcomes and take longer to recover than adults. However, the pathophysiology and progression of TBI in the pediatric population are studied to a far lesser extent compared to the adult population. Common causes of TBI in children are falls, sports/recreation-related injuries, non-accidental trauma, and motor vehicle-related injuries. A fundamental understanding of TBI pathophysiology is crucial in preventing long-term brain injury sequelae. Animal models of TBI have played an essential role in addressing the knowledge gaps relating to pTBI pathophysiology. Moreover, a better understanding of clinical biomarkers is crucial to diagnose pTBI and accurately predict long-term outcomes. This review examines the current preclinical models of pTBI, the implications of pTBI on the brain’s vasculature, and clinical pTBI biomarkers. Finally, we conclude the review by speculating on the emerging role of the gut-brain axis in pTBI pathophysiology.
Evaluation of Interprofessional Practice Education for Master of Social Work Students
(IU School of Social Work, 2022-06-14) Walsh, Matthew A.; Jaggers, Jeremiah W.; Satre, Carol; Hall, James; School of Social Work
As interprofessional education (IPE) continues to grow as part of social work programs, it is important to evaluate how best to engage students in understanding this material and explore possible barriers. With this in mind, researchers conducted qualitative interviews and focus groups to explore perceptions of three cohorts of social work students (n=29) participating in short-term interprofessional practicum experiences. Perceived benefits included improvements in communication and client care. The study also uncovered various barriers with implementing IPE-focused practicums such as time, scheduling and role uncertainty. Students shared the impact their experience had on knowledge and perceptions of the social work role in interprofessional collaboration. Even so, students were able to observe important elements of interprofessional practice from these relatively short practicums, indicating they may be a viable option for programs looking to expose students to real world interprofessional experience.