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Inhibition of acyl-CoA synthetase long-chain isozymes decreases multiple myeloma cell proliferation and causes mitochondrial dysfunction
No full textMultiple myeloma (MM) is an incurable cancer of plasma cells with a 5-year survival rate of 59%. Dysregulation of fatty acid (FA) metabolism is associated with MM development and progression; however, the underlying mechanisms remain unclear. Herein, we explore the roles of long-chain fatty acid coenzyme A ligase (ACSL) family members in MM. ACSLs convert free long-chain fatty acids into fatty acyl-CoA esters and play key roles in catabolic and anabolic fatty acid metabolism. Analysis of the Multiple Myeloma Research Foundation (MMRF) CoMMpass study showed that high ACSL1 and ACSL4 expression in myeloma cells are both associated with worse clinical outcomes for MM patients. Cancer Dependency Map (DepMap) data showed that all five ACSLs have negative Chronos scores, and ACSL3 and ACSL4 were among the top 25% Hallmark Fatty Acid Metabolism genes that support myeloma cell line fitness. Inhibition of ACSLs in myeloma cell lines in vitro, using the pharmacological inhibitor Triacsin C (TriC), increased apoptosis, decreased proliferation, and decreased cell viability, in a dose- and time-dependent manner. RNA-sequencing analysis of MM.1S cells treated with TriC showed a significant enrichment in apoptosis, ferroptosis, and endoplasmic reticulum (ER) stress, and proteomic analysis of these cells revealed enriched pathways for mitochondrial dysfunction and oxidative phosphorylation. TriC also rewired mitochondrial metabolism by decreasing mitochondrial membrane potential, increasing mitochondrial superoxide levels, decreasing mitochondrial ATP production rates, and impairing cellular respiration. Overall, our data support the hypothesis that suppression of ACSLs in myeloma cells is a novel metabolic target in MM that inhibits their viability, implicating this family as a promising therapeutic target in treating myeloma
The Osmolal Gap: A Valuable Test for Identifying Toxic Alcohol-Induced Anion Gap Metabolic Acidosis
No full textC-Reactive Protein Changes in Adult and Pediatric People With Cystic Fibrosis During Treatment of Pulmonary Exacerbations
No full textOBJECTIVE: Although studies have examined changes in C-reactive protein (CRP) during pulmonary exacerbations (PEX) in people with cystic fibrosis (PwCF), few have evaluated CRP profiles across age groups. Here, we characterize age-related CRP responses to PEX treatment. METHODS: We measured CRP concentrations at the beginning and end of intravenous (IV) antibiotic therapy for PEX in 100 pediatric and 147 adult PwCF at 10 US CF Centers. We examined relationships between CRP and age, lung function, severity of PEX symptoms, and time to next PEX. RESULTS: CRP measured at initiation of IV antibiotic treatment for PEX was higher in adults than children, median 8 mg/L (IQR 4, 32) versus 5 mg/L (IQR 2, 10), respectively (p \u3c 0.001). There was a significant correlation between the initial CRP and drop in lung from baseline to the beginning of IV antibiotics in adults and children. Adjusted CRP dropped in response to PEX treatment more commonly in adults than in children (70% vs. 48%, respectively). The range of treatment responses was greater in adults, in those with higher symptom scores, and in those with more advanced lung disease. In adults elevated CRP at the end of treatment was also associated with incomplete recovery of lung function. CRP at the start of IV antibiotics was inversely related to time until the next PEX. CONCLUSION: In children and adults with CF, CRP is increased at the initiation of IV antibiotic therapy for PEX and declines with treatment. The response is more pronounced in highly symptomatic adults with advanced lung disease
Treatment of Pediatric Obesity in Rural Settings: Identifying and Overcoming Barriers to Care
No full textThe purpose of this study is to review the current data regarding implementing pediatric obesity treatment recommendations in rural areas. Data considering barriers to care, challenges as well as opportunities, including leveraging telemedicine, provider training, e-consults to improve pediatric obesity care are provided. Given the pediatric obesity prevalence, particularly in rural settings, a multipronged approach is needed to provide equitable access to vital care. This requires continued advocacy to address barriers, including coverage of treatments, improving broadband in rural areas, and educating patients and providers to decrease bias and stigma
A Case Report of Calcium-Alkali Syndrome
Get PDFIntroduction: Calcium-alkali syndrome has recently grown in prevalence and now represents an important cause of hypercalcemia-associated morbidity.
Clinical findings: A patient between 50 and 59 years old was admitted to the hospital with severe hypercalcemia, encephalopathy, and acute kidney injury that was secondary to milk-alkali syndrome.
Clinical course: The patient initially received 2 L of intravenous fluids and then was treated with 4 doses of calcitonin, a single dose of zoledronic acid, and continuous intravenous fluids. His hypercalcemia resolved with treatment and after an initial increase in his serum creatinine, his renal function eventually returned to near baseline.
Conclusions: Calcium-alkali syndrome represents 9% to 12% of cases involving hypercalcemia and is an increasingly common cause of hospitalization with severe hypercalcemia
Part 1-Non-Pharmacologic Management of the Substance Exposed Newborn Part 2-Safe Sleep Efforts at the Barbara Bush Children\u27s Hospital
No full textCME available for 1 year after presentation
CME Text Code: 97004
In order to claim CME credit, please complete an evaluation in CloudCME for each presentation.https://knowledgeconnection.mainehealth.org/pediatrics_gr/1062/thumbnail.jp
Working with Community Health Workers for Improved Clinical Care: Overview of Development and Outcomes of a Unique Project ECHO Series
Get PDFProblem: Maine has seen an influx of immigrants in recent years. Many of these people face numerous barriers to accessing health care. Community health workers (CHWs) are trusted liaisons who help bridge the gaps in care. However, they are newly embedded in the MaineHealth system, so education for care teams is needed.
Approach: Using coproduction, our team developed a unique Project ECHO (Extension for Community Healthcare Outcomes) series that centered community members and CHWs as subject matter experts. A community advisory board guided session development. Participants, interprofessional care team members across MaineHealth, completed questionnaires after each session to rate pre-session and post-session knowledge and confidence in working with CHWs on a Likert scale. Primary outcomes were changes in self-reported knowledge and confidence after the sessions.
Outcomes: A total of 19 sessions were held. The sessions were attended by a wide range of care team members in clinical and non-clinical roles. Applicability of information to participants was high at 4.3/5. The averages of self-reported knowledge and confidence both increased significantly (P \u3c .0001) between the pre-session and post-session.
Next Steps: The Project ECHO format supported coproduction and was an effective way to increase knowledge and confidence about immigrant health and working with immigrant communities. Our unique Project ECHO focused on meeting the needs of recent immigrants in Maine, provided a successful educational model for care teams, and ensured that our team amplified the voices and actual needs of the community. The next steps include creating a collaborative community health ECHO with academic and clinical partners across the state with a similar evaluation
Training and Assessment of Nontechnical Skills in Cardiothoracic Surgery: Current Literature Review
No full textBACKGROUND: This review explores the surgical and psychological literature on cardiothoracic (CT) surgeons\u27 intraoperative nontechnical skills (NTS). Successful task performance depends on the seamless integration of technical skills (TS) and NTS. This paper aims to identify the training and assessment modalities for NTS in cardiothoracic surgery (CTS). METHODS: PubMed, Cochrane Library, BioMed Central, Medline, EDINA BIOSIS, Web-of-Knowledge, PsychINFO, and ScienceDirect were searched through to December 2023. Additionally, a manual search of the referenced work of each included article and relevant reviews in PubMed were performed to avoid missing any important data. Original research articles were included if they described NTS training modalities and their assessment in cardiac or thoracic surgeries. Exclusion criteria included any study without full-text availability, non-peer-reviewed publications, studies without extractable data, and duplicates. Retrieved articles were screened, and data extracted in duplicate by 2 independent reviewers. RESULTS: The literature search found 371 relevant references related to cardiothoracic surgery, 17 articles were included in this literature review, and 12 training tools were identified. CONCLUSIONS: This review demonstrates the need for additional work to create reliable training and assessment methods for NTS in CTS
Adapting and implementing a pre-hospital trauma program for community health responders: A pilot study from rural Nepal
No full textINTRODUCTION: Effective pre-hospital care is critical for improving trauma outcomes, yet pre-hospital systems are underdeveloped in low-and middle-income countries (LMICs) like Nepal, where trauma-related deaths are rising. Community health responders (CHRs) have the potential to reduce time to post-injury care in rural settings, where other health infrastructure may be unavailable. This pilot study assessing the feasibility and preliminary impact of CHR based program in rural Nepal. METHODS: This quasi-experimental study adapted and implemented a trauma training intervention for CHRs in Achham, Nepal. The program adapting the trauma portion of the World Health Organization\u27s (WHO) Basic Emergency Care (BEC) course for the Achham context through a modified Delphi process. The final implemented program included three items: initial two-day skills-based training, a pictorial guide handbook for CHR\u27s quick reference, and a one-day refresher training at three months. Two rural municipalities of Achham district were assigned into intervention or control. All CHRs from the intervention municipality underwent the training program. Assessment includes the program\u27s impact on CHRs\u27 knowledge and confidence, and impact on pre-hospital trauma care metrics, which was assessed through pre-, immediately, and six-months post-course evaluations, and pre-hospital service metrics data, respectively. A repeated measures ANOVA was used to assess change in knowledge over time by study groups. Bivariate analysis was performed to explore differences in pre-hospital patient metrics of trauma care by study group. RESULTS: The intervention group showed a significant increase in knowledge and confidence immediately post-course and sustained over six months. There was no significant difference in mean patient age (26.5 years versus. 22.1) and trauma mechanism (p = 0.14) across two groups. The most common mechanism was falls (n = 165, 77.5 %). Intervention municipalities had higher rates of pre-hospital care provision, including fracture immobilization (51.4 % versus. 17.1 %, p \u3c .001) and cervical collar use, compared to controls. CONCLUSION: This study adapted and implemented a contextual trauma training program for CHRs in rural Nepal. Results shows early feasibility and appropriateness in this context. The program leverages existing community networks and offers a potential approach in LMICs to bridge the existing critical gaps in rural pre-hospital trauma care that requires further investigation