Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer

Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and mechanisms of 5-FU and Mito-FF, individually or in combination, were compared through both in vitro and in vivo models of gastric cancer. Our experiments consistently demonstrated that the 5-FU and Mito-FF combination therapy was superior to monotherapy with either, as manifested by both higher reduction of proliferation as well as an induction of apoptotic cell death. Interestingly, we found that combining 5-FU with Mito-FF leads to a significant increase of reactive oxygen species (ROS) and reduction of antioxidant enzymes in gastric cancer cells. Moreover, the inhibition of ROS abrogated the pro-apoptotic effects of combination therapy, suggesting that enhanced oxidative stress could be the principal mechanism of the action of combination therapy. We conclude that the combination of 5-FU and Mito-FF exerts potent antineoplastic activity against gastric cancer cells, primarily by promoting ROS generation and suppressing the activities of antioxidant enzymes

Evaluating a social risk screening and referral program in an urban safety‐net hospital emergency department

Abstract Objective The emergency department (ED) is an opportune venue to screen for unmet social needs and connect patients with social services. This quality improvement study incorporates both qualitative and quantitative data to examine unmet social needs among ED patients and program implementation. Methods From September 2020 to December 2021, an urban safety‐net hospital adult ED implemented a social needs screening and referral program. Trained emergency staff screened eligible patients for 5 social needs (housing, food, transportation, utilities, employment), giving resource guides to patients who screened positive (THRIVE+). We collected screening data from the electronic health record, conducted semi‐structured interviews with THRIVE+ patients and clinical staff, and directly observed discharge interactions. Results Emergency staff screened 58.5% of eligible patients for social risk. Of the screened patients, 27.0% reported at least 1 unmet social need. Of those, 74.8% requested assistance. Screened patients reported housing insecurity (16.3%) as the most prevalent unmet social need followed by food insecurity (13.3%) and unemployment (8.7%). Among interviewed patients, 57.1% recalled being screened, but only 24.5% recalled receiving resource guides. Patients who received guides reported little success connecting with resources and supported universal guide dissemination. Staff expressed preference for warm handoff to social services. Of 13 observed discharge interactions, clinical staff only discussed guides with 2 patients, with no positive endorsement of the guides in any observed interactions. Conclusions An ED social needs screening program can be moderately feasible and accepted. We identified housing as the most prevalent need. Significant gaps exist between screening and referral, with few patients receiving resources. Further training and workflow optimization are underway

Social Determinants of Health Screening at an Urban Emergency Department Urgent Care During COVID-19

Introduction: Social determinants of health (SDoH) impact patients’ health outcomes, yet screening methods in emergency departments (ED) are not consistent or standardized. The SDoH-related health disparities may have widened during the coronavirus 2019 (COVID-19) pandemic, especially among patients who primarily receive their medical care in EDs. We sought to identify SDoH among ED urgent care patients during the COVID-19 pandemic at an urban safety-net hospital, assess the impact of the pandemic on their SDoH, study the feasibility of SDoH screening and resource referrals, and identify preferred methods of resource referrals and barriers to accessing resources.Methods: Research assistants screened ED urgent care patients using a validated SDoH screener, inquiring about the impact of COVID-19 on their SDoH. A printed resource guide was provided. Two weeks later, a follow-up telephone survey assessed for barriers to resource connection and patients’ preferred methods for resource referrals. This study was deemed exempt by our institutionalreview board.Results: Of the 418 patients presented with a screener, 414 (99.0%) patients completed the screening. Of those screened, 296 (71.5%) reported at least one adverse SDoH, most commonly education (38.7%), food insecurity (35.3%), and employment (31.0%). Housing insecurity was reported by 21.0%. Over half of patients (57.0%) endorsed COVID-19 affecting their SDoH. During follow-up, 156 of 234 (67%) attempted calls were successful and 36/156 (23.1%) reported attempting to connect with a resource, with most attempts made for stable housing (11.0%) and food (7.7%). Reasons for not contacting the provided resources included lack of time (37.8%) and forgetting to do so (26.3%). Patients preferred resource guides to be printed (34.0%) and sent via text message to their mobile devices (25.6%).Conclusion: Many urgent care patients of this urban ED reported at least one adverse SDoH, the majority of which were exacerbated by the COVID-19 pandemic. This finding further emphasizes the need to allocate more resources to standardize and expand SDoH screening in EDs. Additionally, hospitals should increase availability of printed or electronic SDoH resource guides, resource navigators, and interpreters both during and after ED visits

Social Determinants of Health Screening at an Urban Emergency Department Urgent Care During COVID-19

Introduction: Social determinants of health (SDoH) impact patients’ health outcomes, yet screening methods in emergency departments (ED) are not consistent or standardized. The SDoH-related health disparities may have widened during the coronavirus 2019 (COVID-19) pandemic, especially among patients who primarily receive their medical care in EDs. We sought to identify SDoH among ED urgent care patients during the COVID-19 pandemic at an urban safety-net hospital, assess the impact of the pandemic on their SDoH, study the feasibility of SDoH screening and resource referrals, and identify preferred methods of resource referrals and barriers to accessing resources. Methods: Research assistants screened ED urgent care patients using a validated SDoH screener, inquiring about the impact of COVID-19 on their SDoH. A printed resource guide was provided. Two weeks later, a follow-up telephone survey assessed for barriers to resource connection and patients’ preferred methods for resource referrals. This study was deemed exempt by our institutional review board. Results: Of the 418 patients presented with a screener, 414 (99.0%) patients completed the screening. Of those screened, 296 (71.5%) reported at least one adverse SDoH, most commonly education (38.7%), food insecurity (35.3%), and employment (31.0%). Housing insecurity was reported by 21.0%. Over half of patients (57.0%) endorsed COVID-19 affecting their SDoH. During follow-up, 156 of 234 (67%) attempted calls were successful and 36/156 (23.1%) reported attempting to connect with a resource, with most attempts made for stable housing (11.0%) and food (7.7%). Reasons for not contacting the provided resources included lack of time (37.8%) and forgetting to do so (26.3%). Patients preferred resource guides to be printed (34.0%) and sent via text message to their mobile devices (25.6%). Conclusion: Many urgent care patients of this urban ED reported at least one adverse SDoH, the majority of which were exacerbated by the COVID-19 pandemic. This finding further emphasizes the need to allocate more resources to standardize and expand SDoH screening in EDs. Additionally, hospitals should increase availability of printed or electronic SDoH resource guides, resource navigators, and interpreters both during and after ED visits

2021 SAEM Consensus Conference Proceedings: Research Priorities for Implementing Emergency Department Screening for Social Risks and Needs

Introduction: Despite literature on a variety of social risks and needs screening interventions in emergency department (ED) settings, there is no universally accepted or evidence-based process for conducting such interventions. Many factors hamper or promote implementation of social risks and needs screening in the ED, but the relative impact of these factors and how best to mitigate/leverage them is unknown.  Methods: Drawing on an extensive literature review, expert assessment, and feedback from participants in the 2021 Society for Academic Emergency Medicine Consensus Conference through moderated discussions and follow-up surveys, we identified research gaps and rated research priorities for implementing screening for social risks and needs in the ED. We identified three main knowledge gaps: 1) screening implementation mechanics; 2) outreach and engagement with communities; and 3) addressing barriers and leveraging facilitators to screening. Within these gaps, we identified 12 high-priority research questions as well as research methods for future studies.  Results: Consensus Conference participants broadly agreed that social risks and needs screening is generally acceptable to patients and clinicians and feasible in an ED setting. Our literature review and conference discussion identified several research gaps in the specific mechanics of screening implementation, including screening and referral team composition, workflow, and use of technology. Discussions also highlighted a need for more collaboration with stakeholders in screening design and implementation.  Additionally, discussions identified the need for studies using adaptive designs or hybrid effectiveness-implementation models to test multiple strategies for implementation and sustainability.  Conclusion: Through a robust consensus process we developed an actionable research agenda for implementing social risks and needs screening in EDs. Future work in this area should use implementation science frameworks and research best practices to further develop and refine ED screening for social risks and needs and to address barriers as well as leverage facilitators to such screening

A Novel Way of Preventing Postoperative Pancreatic Fistula by Directly Injecting Profibrogenic Materials into the Pancreatic Parenchyma

This paper aims to validate if intrapancreatic injection of penicillin G can enhance hardness and suture holding capacity (SHC) of the pancreas through prompting the fibrosis process. Soft pancreatic texture is constantly mentioned as one of the most contributory predictors of postoperative pancreatic fistula (POPF). Soft pancreas has poor SHC and higher incidence of parenchymal tearing, frequently leading to POPF. From a library of 114 antibiotic compounds, we identified that penicillin G substantially enhanced pancreatic hardness and SHC in experimental mice. Specifically, we injected penicillin G directly into the pancreas. On determined dates, we measured the pancreatic hardness and SHC, respectively, and performed molecular and histological examinations for estimation of the degree of fibrosis. The intrapancreatic injection of penicillin G activated human pancreatic stellate cells (HPSCs) to produce various fibrotic materials such as transforming growth factor-β1 (TGF-β1) and metalloproteinases-2. The pancreatic hardness and SHC were increased to the maximum at the second day after injection and then it gradually subsided demonstrating its reversibility. Pretreatment of mice with SB431542, an inhibitor of the TGF-β1 receptor, before injecting penicillin G intrapancreatically, significantly abrogated the increase of both pancreatic hardness and SHC caused by penicillin G. This suggested that penicillin G promotes pancreatic fibrosis through the TGF-β1 signaling pathway. Intrapancreatic injection of penicillin G promotes pancreatic hardness and SHC by enhancing pancreatic fibrosis. We thus think that penicillin G could be utilized to prevent and minimize POPF, after validating its actual effectiveness and safety by further studies

A Novel Hepatic Anti-Fibrotic Strategy Utilizing the Secretome Released from Etanercept-Synthesizing Adipose-Derived Stem Cells

Tumor necrosis factor-α (TNF-α)-driven inflammatory reaction plays a crucial role in the initiation of liver fibrosis. We herein attempted to design genetically engineered adipose-derived stem cells (ASCs) producing etanercept (a potent TNF-α inhibitor), and to determine the anti-fibrotic potential of the secretome released from the etanercept-synthesizing ASCs (etanercept-secretome). First, we generated the etanercept-synthesizing ASCs by transfecting the ASCs with mini-circle plasmids containing the gene insert encoding for etanercept. We subsequently collected the secretory material released from the etanercept-synthesizing ASCs and determined its anti-fibrotic effects both in vitro (in thioacetamide [TAA]-treated AML12 and LX2 cells) and in vivo (in TAA-treated mice) models of liver fibrosis. We observed that while etanercept-secretome increased the viability of the TAA-treated AML12 hepatocytes (p = 0.021), it significantly decreased the viability of the TAA-treated LX2 HSCs (p = 0.021). In the liver of mice with liver fibrosis, intravenous administration of the etanercept-secretome induced significant reduction in the expression of both fibrosis-related and inflammation-related markers compared to the control group (all Ps < 0.05). The etanercept-secretome group also showed significantly lower serum levels of liver enzymes as well as pro-inflammatory cytokines, such as TNF-α (p = 0.020) and IL-6 (p = 0.021). Histological examination of the liver showed the highest reduction in the degree of fibrosis in the entanercept-secretome group (p = 0.006). Our results suggest that the administration of etanercept-secretome improves liver fibrosis by inhibiting TNF-α-driven inflammation in the mice with liver fibrosis. Thus, blocking TNF-α-driven inflammation at the appropriate stage of liver fibrosis could be an efficient strategy to prevent fibrosis