The incidence and characterization of weight gain associated with MEK inhibitors in pediatric patients.

BACKGROUND: Mitogen-activated protein kinase enzyme (MEK) inhibitors are used in the treatment of pediatric patients with neurofibromatosis, low grade glioma, and astrocytoma, and may demonstrate a unique side effect profile in this population. Inhibition of MEK has been shown to decrease interleukin (IL)-6 production, a proinflammatory cytokine. The inhibition of IL-6 and other proinflammatory cytokines is thought to decrease muscle wasting and may contribute to weight gain. However, there is limited information on the association of MEK inhibition and weight gain in children and adolescents. This study aimed to characterize and define the incidence of significant weight gain associated with MEK inhibitors in pediatric patients. METHODS: This was a retrospective chart review conducted at a tertiary pediatric hospital. Children 1-18.99 years old were included if they started a MEK inhibitor from July 1, 2013-October 31, 2021, and continued therapy for at least 6 months. Significant weight gain was defined as ≥5% increase in patient's weight-for-age percentile. RESULTS: Sixty-seven patients were included in the analysis. Sixty-two received trametinib and 5 received selumetinib. An increase in weight-for-age percentile ≥5% was seen in 60% of patients receiving selumetinib and 56% on trametinib. The Dunnett's multiple comparisons test revealed a difference in weight-for-age percentile from baseline to end of data collection (p = .0173). Patients who were obese at baseline were more likely to lose weight during treatment, while underweight patients increased in weight-for-age percentiles. CONCLUSIONS: Weight gain may be a notable side effect associated with the use of MEK inhibitors in pediatric patients.

Revisiting resilience: Examining the relationships between stress, social support, and drinking behavior among black college students with parental substance use disorder histories.

The study examined the role social support plays in the relationship between life stress and problem alcohol use behavior in a sample of Black emerging adults in college with histories of parental substance use disorders (SUD). Participants were 1,007 Black emerging adult college students, recruited as part of a larger multi-wave, multisite, study investigating coping behavior among emerging adults in college. Findings suggest that Black college students with parental SUDs engage in riskier and coping motivated drinking behaviors more than those without such histories, and their alcohol use behaviors are more strongly linked to experiencing life stress, despite similar levels of perceived social support. Social support from friends and sufficient global social support help to mediate this adverse relationship. Parental SUD may serve as a readily identifiable risk factor for risky drinking behavior among Black college students. Implications for future research and clinical practice are presented.

Synthesis of apo-13- and apo-15-lycopenoids, cleavage products of lycopene that are retinoic acid antagonists.

Consumption of the tomato carotenoid, lycopene, has been associated with favorable health benefits. Some of lycopene's biological activity may be due to metabolites resulting from cleavage of the lycopene molecule. Because of their structural similarity to the retinoic acid receptor (RAR) antagonist, ß-apo-13-carotenone, the "first half" putative oxidative cleavage products of the symmetrical lycopene have been synthesized. All transformations proceed in moderate to good yield and some with high stereochemical integrity allowing ready access to these otherwise difficult to obtain terpenoids. In particular, the methods described allow ready access to the trans isomers of citral (geranial) and pseudoionone, important flavor and fragrance compounds that are not readily available isomerically pure and are building blocks for many of the longer apolycopenoids. In addition, all of the apo-11, apo-13, and apo-15 lycopenals/lycopenones/lycopenoic acids have been prepared. These compounds have been evaluated for their effect on RAR-induced genes in cultured hepatoma cells and, much like ß-apo-13-carotenone, the comparable apo-13-lycopenone and the apo-15-lycopenal behave as RAR antagonists. Furthermore, molecular modeling studies demonstrate that the apo-13-lycopenone efficiently docked into the ligand binding site of RARα. Finally, isothermal titration calorimetry studies reveal that apo-13-lycopenone acts as an antagonist of RAR by inhibiting coactivator recruitment to the receptor.

Mobilization with Femoral Catheters in the Burn ICU: A retrospective review following change in practice guidelines.

Femoral catheters are a known barrier for Burn ICU mobility progression due to the anatomical location and potential risk of complications. The purpose of this study was to examine outcomes and complication rates following implementation of femoral catheter mobilization guidelines, as well as determine safety and feasibility of mobilization with femoral catheters in place within the burn population. Retrospective review was completed on 17 patients prior to and following implementation of new femoral catheter mobility guidelines, 34 patients total. Burn therapy notes were reviewed for burn admissions with at least one femoral catheter in place, including arterial, central, and dialysis catheters. Demographic data, admission statistics, line placement timelines, and active mobility achieved during therapy sessions were recorded for both the non-mobilization (NMG) and mobilization groups (MG). The 34 patients reviewed had 99 total lines placed (30 NMG, 69 MG). Change in mobility protocols for the MG resulted in more therapy sessions (n=516 vs 281) and a significant increase in active mobility sessions (n=83 vs 5, p < 0.001), including 146 total mobility activities such as transitions to chairs, tilt table, sitting edge of bed (EOB), standing, active chair transfers, ambulation, and cycle ergometry. No catheter associated adverse events occurred during active mobility sessions and no complications were associated with participation in mobility. This study supports that the presence of femoral catheters alone should not limit the progression of mobility interventions. Using clinical judgement and specialty training, burn therapists can safely mobilize burn ICU patients with femoral catheters in place.

Peritoneal and Pleural Drains in Pediatric Hematopoietic Cell Transplant Recipients with Veno-Occlusive Disease are Safe and Do Not Adversely Impact Clinical Outcomes.

There is a lack of data on the safety and efficacy of peritoneal drain (PD) and chest tube (CT) in the management of effusions in stem cell transplant recipients with veno-occlusive disease (VOD). In this retrospective pediatric study, clinical outcomes and health resource utilization (HRU) were compared in 32 patients with VOD who had a PD (PD+) post-HCT versus 27 patients who did not (PD-). Nine patients also had a CT (7 PD+ and 2 PD-). PD + patients were more likely than PD-patients to have received myeloablative conditioning (100% vs. 85.2%; p = 0.04) and have severe or very severe VOD (100% vs. 56% p < 0.01). Mechanical obstruction (38%) and hypotension (38%) were common complications, and 13% developed peritonitis. While the frequencies of cardiac dysfunction and acute kidney injury were comparable between both groups, respiratory support and its median duration were higher in PD + patients. The hospital and intensive care unit length of stay, albumin use, and the duration of defibrotide and albumin therapy was significantly longer in PD + patients. At a median follow-up of 1.04 years (range:0.03-14.6), the 2-year overall survival was similar in both groups (53.8% vs. 51.5%; p = 0.73). Although PD use was similar between 1995 and 2007 vs. 2008-2021; (47% vs. 58%; p = 0.65), day+100 mortality was improved in recent years (53.3% vs. 17.8%; p = 0.01), coinciding with the use of defibrotide (0% vs. 84%; p < 0.01). PD in pediatric patients with VOD post-HCT, although associated with increased HRU, was safe when clinically indicated and did not adversely impact clinical outcomes.

Five-Year Retrospective Analysis of a Vented Mobility Algorithm in the Burn ICU.

Early mobilization with mechanically ventilated patients has received significant attention within recent literature; however, limited research has focused specifically on the burn population. The purpose of this single-center, retrospective analysis was to review the use of a burn critical care mobility algorithm, to determine the safety and feasibility of a burn vented mobility program, share limitations preventing mobility progression at our facility, and discuss unique challenges to vented mobility with intubated burn patients. A retrospective review was completed for all intubated burn center admissions between January 2015 and December 2019. Burn therapy notes were then reviewed for data collection, during the intubation period, using stages of the mobility algorithm. In the 5-year period following initial implementation, the vented mobility algorithm was utilized on 127 patients with an average TBSA of 22.8%. No adverse events occurred. Stage 1 (range of motion) was completed with 100% of patients (n = 127). Chair mode of bed, stage 2a, was utilized in 39.4% (n = 50) of patients, while 15.8% (n = 20) of patients were dependently transferred to the cardiac chair in stage 2b. Stage 3 (sitting on the edge of the bed) was completed with 25% (n = 32) of patients, with 11% (n = 14) progressing to stage 5 (standing), and 3.9% (n = 5) actively transferring to a chair. In the 5 years, only 4.7% (n = 6) reached stage 6 (ambulation). The most common treatment limitations were medical complications (33%) and line placement (21%). Early mobilization during mechanical ventilation is safe and feasible within the burn population, despite challenges, including airway stability, sedation, and line limitations.

Double jeopardy: Intimate partner violence vulnerability among emerging adult women through lenses of race and sexual orientation.

Objective: Intimate partner violence (IPV) remains a public health concern for women age 18-25. While much is known about the IPV risk and experiences of heterosexual women, little is known about the IPV risk and experiences of their LGBTQ + counterparts and any contributions of multiple marginalization in such risk. This study examines the emotional, physical, and sexual intimate partner violence (IPV) vulnerability of emerging adult college women with and without multiple minority statuses (e.g., women with both racial/ethnic and sexual minority identities). Participants: Participants were 9,435 women ages 18-25 from the National College Health Assessment (NCHA). Results: Findings demonstrate that being a sexual minority increases risk vulnerability for all forms of IPV, regardless of race. Conclusions: The risk for college women with multiple marginalized identities is exponentially greater than either their White or heterosexual counterparts. Implications for colleges/universities, university counseling centers and professionals, and future research directions are discussed.

Psychological Distress as a Primer for Sexual Risk Taking Among Emerging Adults.

Emerging adults experience increased morbidity as a result of psychological distress and risky sexual behavior. This study examines how sexual behaviors (e.g., condom use inconsistency and past year STI history) differ among emerging adults with low, moderate, and high psychological distress. Participants are 251,254 emerging adults attending colleges and universities in the United States who participated in the National College Health Assessment (NCHA). Findings suggest a dose-response relationship between psychological distress, condom use inconsistency, and past STI history, such that an association between greater psychological distress and condom use inconsistency and/or past year history of sexually transmitted infections (STIs).