Comparison of epidural infusion versus intrathecal morphine block as part of enhanced recovery after open pancreatoduodenectomy.

BACKGROUND AND OBJECTIVES: The accepted approach to pain management following open pancreatoduodenectomy (PD) remains controversial, with the most recent enhanced recovery after surgery (ERAS) protocols recommending epidural anesthesia (EA). Few studies have investigated intrathecal (IT) morphine, combined with transversus abdominis plane (TAP) blocks. We aim to compare the different approaches to pain management for open PD. METHODS: Patients who underwent open PD at our institution from 2020 to 2022 were included in the study. Patient characteristics, pain management, and postoperative outcomes between EA, IT morphine with TAP blocks, and TAP blocks only were compared using univariate analysis. RESULTS: Fifty patients were included in the study (58% male, median age 66 years [interquartile range, IQR: 58-73]). Most patients received IT morphine (N = 24, 48%) or EA (N = 18, 36%). The TAP block-only group required higher doses of postoperative narcotics while hospitalized (p = 0.004) and at discharge (p = 0.017). The IT morphine patients had a shorter median time to Foley removal (p = 0.007). Postoperative pain scores, non-opioid administration, postoperative bolus requirements, postoperative outcomes, and length of stay were similar between pain modalities. CONCLUSIONS: IT morphine and EA showed comparable efficacy with superior results compared to TAP blocks alone. Integration of IT morphine into PD ERAS protocols should be considered.

Plasma IL13Rα2 as a novel liquid biopsy biomarker for glioblastoma.

PURPOSE: Glioblastoma (GBM) is the most common and deadliest brain tumor with unrelenting and rapid disease progression. The standard of care for GBM is surgical excision followed by radiation with concurrent and adjuvant temozolomide-centered chemotherapy (TMZ). Treatment failure and resistance is the rule and despite advances in imaging technology, early detection of treatment failure or impending resistance remains a challenge. There is a dire, unmet, need in clinical practice for minimally-invasive diagnostic tools to enable timely understanding of disease progression and treatment response. Here, we aim to address this clinical need by leveraging a unique characteristic of GBM: the overexpression of the α2 variant of the IL-13 receptor in over 75% of GBM tumors. METHODS: In this study we examined patients with primary GBM from Penn State and Cleveland Clinic compared to healthy controls. RESULTS: IL13Rα2 was detectable in plasma of GBM patients using ELISA but detection could be optimized by PEG precipitation to enrich for extracellular vesicles (EVs). Patients with GBM had elevated levels of plasma IL13Rα2, which correlated to levels of this receptor in the tumor tissue. Elevated plasma levels of IL13Rα2 predicted longer overall survival (OS) (19.8 vs. 13.2 months). Similarly, detection of IL13Rα2 + cells in tumor tissue also predicted longer OS (22.1 vs. 12.2 months). CONCLUSION: These findings strongly suggest that expression of the IL13Rα2 receptor confer survival advantage in GBM patients, which can be determined through a minimally-invasive liquid biopsy. Detection of plasma IL13Rα2 can also be used to select GBM patients for targeted tumor therapy.

The temporal relationship between antibiotic and opioid prescription on the risk of developing an opioid use disorder: A national database study.

Background: Previously, we discovered that subjects co-prescribed both antibiotics and opioids on the same day in a hospital setting displayed an increased risk of developing an opioid use disorder (OUD) 12 months following hospital discharge. The goal of this study was to examine whether prescribing antibiotics in the inpatient or emergency department setting at various time points before or after an opioid prescription impacted the risk OUD.Methods: A propensity score matched cohort study was conducted to identify subjects (18-65 years old) with no previous history of OUD. Two cohorts were defined: subjects who were prescribed antibiotics 0-1, 2-4, 5-7, 8-10, 11-12 months before or after the date of an opioid prescription while in the emergency department or inpatient setting, from the years 2010-2019. The diagnosis of an Opioid Related Disorder (F11.10-F11.20) 12 months following discharge from the emergency department or inpatient unit was then observed.Results: Primary analysis showed that subjects prescribed an antibiotic 0-1 month or 8-10 months before an opioid prescription showed a modest risk of developing an OUD 12 months following an opioid prescription (0.04% and 0.20%, respectively). Similarly, subjects prescribed an antibiotic 0-1 month, 5-7 months, or 8-10 months after an opioid prescription displayed a modest risk of developing OUD 12 months after an opioid prescription (0.02% risk, 0.14% risk, and 0.16% risk, respectively).Conclusions: These findings suggest that there is little to no effect on the risk of developing OUD when antibiotics are prescribed at various time points before or after opioid prescription.

Cefepime-Induced Nonconvulsive Status Epilepticus in a Pediatric Patient with Normal Renal Function.

Introduction: Cefepime, a fourth-generation cephalosporin, is known to risk the induction of neurotoxic impairment from confusion to nonconvulsive status epilepticus (NCSE). Neurotoxic effects of cefepime are most commonly evident in the setting of impaired renal function in adults; however, are rarely present in those with normal renal excretion function or in the pediatric population. Case: We present a case of a 16-year-old female with a complicated past medical history but no accounts of impaired renal function yet, after starting cefepime, presented with encephalopathy, intermittent stimulus-induced posturing, and was found to have NCSE. Discontinuation of cefepime and administration of additional antiepileptics provided significant improvement in EEG and allowed the patient to return to baseline within two days. Conclusion: Cefepime-induced nonconvulsive status epilepticus should be considered in any patient with or without impaired renal function that shows acute changes in mental status, and/or reduced consciousness, after initiating cefepime treatment.

Cardiovascular Outcomes Among Older Individuals With Depression Prescribed Amphetamines: A Retrospective Cohort Study.

BACKGROUND: Prescription amphetamines are utilized for treatment of depression in older adults, yet cardiovascular risks in this population are not well described. The purpose of this study is to evaluate risk of cardiovascular events among adults aged 65 and older with depression who were prescribed amphetamines. METHODS: We conducted a retrospective matched cohort study utilizing the TriNetx database and statistical software. The 1:1 propensity score matching technique was performed using logistic regression to balance the baseline characteristics of the population. Inclusion criteria were a diagnosis of depression and age 65 years and older. We excluded individuals with an adverse cardiovascular event or diagnosis of attention deficit and hyperactivity disorder prior to enrollment. Individuals were followed from January 1, 2018 to December 31, 2020. Those prescribed an amphetamine were considered exposed and others served as controls. We used descriptive statistics and calculated risk ratios to assess the relationship between amphetamine prescriptions and cardiovascular events in these cohorts. RESULTS: There were 4 434 included in the exposed cohort and 4 434 matched controls in the unexposed group. The cohort exposed to amphetamines had higher high-density lipoprotein along with lower low-density lipoprotein, total cholesterol, hemoglobin A1C, systolic blood pressure, and body mass index than the control group, but increased risk of cardiovascular events (risk ratio: 8.9; 95% confidence interval: 6.39, 12.48). CONCLUSIONS: Amphetamines offer potential benefits to people with depression; however, these data suggest increased risk of cardiovascular events among older individuals. Additional research is warranted to fully characterize risk among subpopulations of older adults and inform patient-provider decision making.

Are Amphetamines Associated with Adverse Cardiovascular Events Among Elderly Individuals?

BACKGROUND: Prescription amphetamines are the most common pharmacological treatment for attention deficit hyperactivity disorder (ADHD) and use among older age groups is increasing. The purpose of this study is to assess the risk of adverse cardiovascular events among individuals older than 65 years. METHODS: We conducted a retrospective matched cohort study using TriNetX database with propensity score matching (PSM) to assess the odds of a cardiovascular event among individuals with ADHD exposed to amphetamine compared with individuals with ADHD who were not exposed to this medication. During the index period of January 1, 2018, through December 31, 2020, 13,233 individuals older than 65 years (mean age = 69 years) met the study criteria. RESULTS: The cohort exposed to amphetamine had increased blood pressure and increased odds of cardiovascular events (odds ratio [OR], 6.16; absolute risk difference = 3.31%) compared with the control group. CONCLUSIONS: Amphetamines have clear safety data in younger age cohorts; however, this safety data may not generalize to older populations. Additional research is warranted to clarify further exposure and subpopulation-level risk factors associated with adverse cardiovascular events among older patients.