UC Irvine Department of Medicine

Introduction: Children and adolescents are not impervious to the unprecedented epidemic of opioid misuse in the United States. In 2016 more than 88,000 adolescents between the ages of 12–17 reported misusing opioid medication, and evidence suggests that there has been a rise in opioid-related mortality for pediatric patients. A major source of prescribed opioids for the treatment of pain is the emergency department (ED). The current study sought to assess the complex relationship between opioid administration, pain severity, and parent satisfaction with children’s care in a pediatric ED.

Methods: We examined data from a tertiary pediatric care facility. A health survey questionnaire was administered after ED discharge to capture the outcome of parental likelihood of providing a positive facility rating. We abstracted patient demographic, clinical, and top diagnostic information using electronic health records. Data were merged and multivariable models were constructed. 

Results: We collected data from 15,895 pediatric patients between the ages of 0–17 years (mean = 6.69; standard deviation = 5.19) and their parents. Approximately 786 (4.94%) patients were administered an opioid; 8212 (51.70%) were administered a non-opioid analgesic; and 3966 (24.95%) expressed clinically significant pain (pain score >/= 4). Results of a multivariable regression analysis from these pediatric patients revealed a three-way interaction of age, pain severity, and opioid administration (odds ratio 1.022, 95% confidence interval, 1.006, 1.038, P = 0.007). Our findings suggest that opioid administration negatively impacted parent satisfaction of older adolescent patients in milder pain who were administered an opioid analgesic, but positively influenced the satisfaction scores of parents of younger children who were administered opioids. When pain levels were severe, the relationship between age and patient experience was not statistically significant.

Conclusion: This investigation highlights the complexity of the relationship between opioid administration, pain severity, and satisfaction, and suggests that the impact of opioid administration on parent satisfaction is a function of the age of the child.

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Oncogenic gene fusions occur across a broad range of cancers and are a defining feature of some cancer types. Cancers driven by gene fusion products tend to respond well to targeted therapies, where available; thus, detection of potentially targetable oncogenic fusions is necessary to select optimal treatment. Detection methods include non-sequencing methods, such as fluorescence in situ hybridization and immunohistochemistry, and sequencing methods, such as DNA- and RNA-based next-generation sequencing (NGS). While NGS is an efficient way to analyze multiple genes of interest at once, economic and technical factors may preclude its use in routine care globally, despite several guideline recommendations. The aim of this review is to present a summary of oncogenic gene fusions, with a focus on fusions that affect tyrosine kinase signaling, and to highlight the importance of testing for oncogenic fusions. We present an overview of the identification of oncogenic gene fusions and therapies approved for the treatment of cancers harboring gene fusions, and summarize data regarding treating fusion-positive cancers with no current targeted therapies and clinical studies of fusion-positive cancers. Although treatment options may be limited for patients with rare alterations, healthcare professionals should identify patients most likely to benefit from oncogenic gene fusion testing and initiate the appropriate targeted therapy to achieve optimal treatment outcomes.

SARS-CoV-2, first identified in December 2019, caused a global pandemic, resulting in over 6.8 million deaths by March 2023. The elderly, or individuals over 65, accounted for the majority of COVID-19 deaths, with 81% of fatalities in the US in 2020 occurring in this group. Beyond mortality, aging populations are also at higher risk of long-term cardiovascular complications and acute respiratory distress syndrome (ARDS). Although these outcomes may be influenced by comorbidities common in the elderly, age has been found to be a standalone risk factor for severe COVID-19 infection. Therefore, investigating age-related factors in COVID-19 outcomes is crucial in protecting this vulnerable group. Of particular interest is the cytokine storm phenomenon, an excessive inflammatory response that contributes to severe COVID-19 symptoms, including ARDS and cardiovascular damage. Elevated levels of multiple cytokines are common in severe cases of COVID-19. We propose that changes that occur to cytokine profiles as we age may contribute to these aberrant inflammatory responses. This review specifically explored the interleukin class cytokines IL-1, IL-6, IL-17, and IL-23 and considered the potential of biologics targeting these cytokines to alleviate severe outcomes in both COVID-19 and aging individuals.

Neuroinflammation is a key contributor to the onset and progression of neurodegenerative diseases, driven by factors such as viral infections, autoimmune disorders, and peripheral inflammation. However, the mechanisms linking peripheral inflammation or viral infections to neuroinflammation remain poorly understood, limiting the development of effective therapies. Proinflammatory cytokines are implicated in these processes but their effects on brain cells, including microglia, remain insufficiently characterized. Here, we demonstrate that IL-21, a proinflammatory cytokine elevated in autoimmune disorders, chronic viral infections, and Alzheimer's disease, activates microglia and promotes lipid accumulation within these cells. Young, healthy mice injected with IL-21 to mimic chronic exposure exhibited increased proinflammatory cytokine levels and microglial activation in the brain. Notably, microglia in these mice displayed enhanced lipid accumulation, accompanied by upregulation of lipid uptake receptors such as CD36 and TREM-2. These findings were corroborated using the human microglial cell line HMC-3, where IL-21 exposure similarly induced lipid accumulation and increased expression of CD36 and ApoE. Mechanistic investigations revealed that IL-21 upregulates HIF-1α, a transcription factor critical for lipid metabolism and lipid droplet formation. Additionally, we observed elevated IL-21 levels in the circulation of elderly individuals compared to younger counterparts, with IL-21 increases associated with CMV seropositivity. Aged mouse brains mirrored the microglial lipid accumulation and activation patterns seen in IL-21-injected mice. In summary, we identify a novel IL-21-driven mechanism involving lipid accumulation in microglia that contributes to neuroinflammation.

BACKGROUND: Treatment-related side effects are common among women treated for early breast cancer and their effective management is essential to maintain quality of life, ensure treatment adherence, and optimise survival outcomes. This study aimed to investigate patient-reported experiences and preferences about information regarding side effects received during breast cancer care. METHODS: An international multi-stakeholder expert group conducted an online patient survey assessing comprehensiveness, timing, and delivery modality of information regarding treatment-related side effects among patients undergoing primary therapy (surgery, radiation, and [neo]adjuvant chemotherapy) and endocrine therapy for early breast cancer. Descriptive analyses were performed. RESULTS: From June-August 2023, 608 respondents from Brazil, France, Germany, Italy, Japan, and Spain completed the survey: 57.5 % were <50 years old, and all were or had been on endocrine therapy. Fatigue was the most reported side effect (47.0 % for primary and 42.3 % for endocrine therapy). A variable proportion of patients (14.4%-46.8 % across side effects) reported receiving information only after having experienced the side effect. Up to 43.6 % of respondents reported receiving insufficient or no information on side effects from their healthcare providers. Most patients reported preference for proactive communication from healthcare providers about side effects and prevention strategies. Respondents valued direct interactions with physicians and nurses and capitalised on a relevant role for peer-support, however utility of smartphone and web-based platforms to record and manage symptoms was acknowledged. CONCLUSION: The survey underscores critical needs and offers insight informing the provision of comprehensive and timely information on treatment-related side effects across the cancer survivorship continuum.

Rationale & Objective: While sleep disorders are common in patients treated with hemodialysis, the impact of sleep patterns on survival is not well defined. We thus examined the association of specific sleep patterns with mortality in this population. Study Design: An observational cohort study. Setting & Population: In-center hemodialysis patients from the multicenter prospective NIH Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease (MADRAD) cohort. Exposure: Sleep patterns ascertained using protocolized sleep surveys from March 2014 to June 2019. Outcomes: Mortality. Analytical Approach: Cox proportional hazards models. Results: Among 452 participants, the mean age was 55±14 years, among whom 46% were women and the median follow-up was 3.5 years. In expanded case-mix models, shorter sleep duration (≤ median of observed values) was associated with higher mortality on dialysis and nondialysis days (ref: > median): HRs (95% CIs) 1.59 (1.09-2.31) and 1.51 (1.04-2.19), respectively. Patients who reported high frequencies (often/almost always) of difficulty falling asleep, feeling unrested, fatigue/exhaustion post-dialysis, or fatigue/exhaustion on nondialysis days had higher mortality (ref: never/rarely having these symptoms): HRs (95% CIs) 1.74 (1.17-2.58), 1.69 (1.1-2.5), 2.42 (1.41-4.16), and 1.73 (1.11-2.69), respectively. Moderate to high frequency of sleeping pill use was associated with higher mortality (ref: never/rare use): HRs (95% CIs) 2.07 (1.08, 3.97) and 2.00 (1.22, 3.28) for sometimes and often/almost always using sleeping pills, respectively. Sleeping outside of the primary sleep period (intra-dialytic sleeping and napping) was not associated with worse survival. However, patients reporting frequent apnea or restless legs syndrome had higher mortality. Limitations: Potential recall bias, residual confounding, absence of time-varying observations, and limitations in generalizability. Conclusions: In a well-characterized prospective multicenter hemodialysis cohort, patients who reported shorter sleep duration, sleeping difficulty or feeling unrested, moderate to frequent sleeping pill consumption, and sleep disorders (apnea and restless legs) had a higher mortality risk. Plain Language Summary: Patients with kidney failure have a high burden of sleep disorders. However, the relationship between sleeping problems and the health of patients treated with dialysis is not well understood. To address this knowledge gap, we examined the relationship between various types of sleep disturbances and associated symptoms with survival among a diverse cohort of patients treated with hemodialysis from the multicenter prospective NIH Malnutrition, Diet, and Racial Disparities in Chronic Kidney Disease (MADRAD) study. We found that patients who reported shorter sleep duration, sleeping difficulty or feeling unrested, moderate to frequent sleeping pill consumption, and sleep disorders such as apnea or restless legs syndrome had a higher death risk.

We report results from a survey of members of the Society of Critical Care Medicine to assess ICU clinicians perceptions of artificial airway safety practices and unplanned extubation (UE) prevention. The survey was distributed between January and February 2024 and received 518 responses (68.5% response rate), with 87.5% from adult ICUs and 12.5% from Pediatric ICUs. Only 48% of adult ICU respondents tracked UE, compared with 73% tracking pressure injuries. Most respondents did not consider UE a never event, with over half viewing it as unavoidable. In adult ICUs, delirium was ranked as the highest UE risk factor, and commercial securement devices were the primary endotracheal tube securement method (75.2%). Significant variations were observed in artificial airway management practices and responsibility assignments across ICU settings. The results highlight substantial disparities in airway safety management beliefs and practices, underscoring the need for standardized, evidence-based guidelines.