Combinatorial Gli activity directs immune infiltration and tumor growth in pancreatic cancer.

Proper Hedgehog (HH) signaling is essential for embryonic development, while aberrant HH signaling drives pediatric and adult cancers. HH signaling is frequently dysregulated in pancreatic cancer, yet its role remains controversial, with both tumor-promoting and tumor-restraining functions reported. Notably, the GLI family of HH transcription factors (GLI1, GLI2, GLI3), remain largely unexplored in pancreatic cancer. We therefore investigated the individual and combined contributions of GLI1-3 to pancreatic cancer progression. At pre-cancerous stages, fibroblast-specific Gli2/Gli3 deletion decreases immunosuppressive macrophage infiltration and promotes T cell infiltration. Strikingly, combined loss of Gli1/Gli2/Gli3 promotes macrophage infiltration, indicating that subtle changes in Gli expression differentially regulate immune infiltration. In invasive tumors, Gli2/Gli3 KO fibroblasts exclude immunosuppressive myeloid cells and suppress tumor growth by recruiting natural killer cells. Finally, we demonstrate that fibroblasts directly regulate macrophage and T cell migration through the expression of Gli-dependent cytokines. Thus, the coordinated activity of GLI1-3 directs the fibroinflammatory response throughout pancreatic cancer progression.

"Once you get one maternal death, it's like the whole world is dropping on you": experiences of managing maternal mortality amongst obstetric care providers in Ghana.

BACKGROUND: Maternal mortality has a significant global impact, especially in low-resource settings. Little prior research has been conducted on the potential effects of poor maternal outcomes on the personal and professional well-being of healthcare providers. This study explores the in-depth experiences and perspectives of obstetric providers in Ghana who work in a setting with frequent maternal mortalities. METHODS: This is a qualitative study of semi-structured interviews conducted at the Komfo Anokye Teaching Hospital in Ghana. Participants were obstetric healthcare providers, defined as midwives, house officers currently rotating on the obstetrics/gynecology service, and obstetrician/gynecologists at any training or practice level (residents, fellows, and specialists). Interviews were audio-recorded, transcribed verbatim, and uploaded into NVivo for qualitative analysis. Using the Attride-Stirling qualitative model, an incremental and iterative process was used to code interviews with keyword phrases and develop a framework of organizing and global themes. RESULTS: Interviews were conducted with 27 participants-15 midwives and 12 physicians (three obstetrician/gynecologist residents, six obstetrician/gynecologist specialists, and three house officers), with sample size determined by data saturation. Obstetric providers' experiences in a setting with frequent maternal mortalities were dependent on their level of preparedness to manage maternal mortalities and the workplace environment. Providers' level of preparedness was dependent on both the training they had received on the medical management of obstetric emergencies, as well as a lack of training on the mental health aspects of coping with maternal mortality. The impact of the workplace environment was dependent on systems failures and limited resources, blame from colleagues and supervisors, and a lack of support in the workplace. In turn, obstetric providers' experiences managing frequent maternal mortalities impacted their clinical care performance and mental health. CONCLUSIONS: Maternal deaths have profound personal and professional impacts on the healthcare providers who manage them. A large need exists for additional institutional training and support for obstetric providers who manage maternal mortality, especially in low-resource settings like Ghana.

Predictors of burnout: the role of agency among obstetric providers in Kumasi, Ghana.

Burnout rates among sub-Saharan African healthcare providers are high. In particular, obstetric providers experience unique stressors surrounding poor neonatal and maternal outcomes. This study explores predictors of burnout among obstetric providers at the Komfo Anokye Teaching Hospital (KATH) in Kumasi, Ghana. A survey was electronically distributed to midwives, house officers, and Obstetrician Gynecologists (OBGYNs) at KATH in Ghana. Demographic and clinical practice information was collected. Burnout was assessed using a 4-point Likert scale. To evaluate perceived agency caring for critically ill obstetric patients, participants responded to three statements and responses were summed to create an Agency Scale. Logistic regression was used to evaluate predictors of burnout. Marginal effects were calculated for factors significantly associated with burnout. Participants were 48 physicians and 222 midwives. Mean age was 32.4 years, mean years in practice was 6.5 years, and 83% had completed their medical training. Nearly half (49.6%) have personal experience with maternal mortality and 28.3% manage more than 5 maternal mortalities annually. The majority of participants (n = 152, 62%) reported feeling burned out from their work. After adjusting for role, number of annual maternal mortalities managed, and personal experience with maternal mortality, participants with more years in practice were 15.8% more likely to report being burned out (marginal effect = 0.158). Even after adjusting for years in practice, participants who scored higher on the Agency Scale had a significantly lower likelihood of reporting burnout (OR 0.76, 95% CI 0.66-0.88, p < 0.001). For each step up the Agency Scale, participants were 6.4% less likely to report they felt burned out. Rates of burnout are high among obstetric providers, particularly among providers who have practiced longer. Supporting provider agency to manage critically ill patients may reduce burnout rates.

Preparedness to deal with maternal mortality among obstetric providers at an urban tertiary hospital in Ghana.

OBJECTIVE: This study explores the impacts of managing frequent maternal mortalities on obstetric healthcare providers in Ghana. METHODS: Two hundred and seventy obstetric providers at the Komfo Anokye Teaching Hospital in Ghana completed an electronic survey. Questions included coping strategies, sources and adequacy of support, training, and emotional impact. Logistic regression assessed predictors of perceived preparedness to manage maternal mortalities. RESULTS: Over half of participants (55.1%) did not report adequate support to deal with maternal death and only 35.9% received training. The vast majority (96.4%) agreed that managing maternal deaths takes a large emotional toll-27.6% considered giving up their obstetric practice, half experienced guilt or shame, and half worried about legal or disciplinary action. After adjusting for age, gender, years in practice, and annual maternal mortalities managed, perceived adequacy of support (odds ratio [OR] 6.6, 95% confidence interval [CI] 3.0-14.7, P < 0.001) and receiving training (OR 9.5, 95% CI 3.5-25.8, P < 0.001) were significantly associated with preparedness to deal with maternal mortality. CONCLUSION: Managing maternal mortalities has significant emotional impact on obstetric healthcare providers. Preparedness to deal with maternal death is significantly improved when providers receive adequate support and training.