Clinical outcomes in patients infected with ertapenem-only-resistant Enterobacterales versus multi-carbapenem-resistant Enterobacterales.

BACKGROUND: Use of anti-carbapenem-resistant Enterobacterales (anti-CRE) agents such as ceftazidime/avibactam has been associated with improved clinical outcome in cohorts that primarily include patients infected with CRE that are resistant to meropenem (MCRE). OBJECTIVES: To clarify whether patients with CRE resistant to ertapenem but susceptible to meropenem (ertapenem-only-resistant Enterobacterales; EORE) benefit from therapy with anti-CRE agents. METHODS: Patients treated for CRE infection in hospitals in the USA between 2016 and 2019 and enrolled in the CRACKLE-2 study were included. The primary outcome was the desirability of outcome ranking (DOOR) assessed at 30 days after index cultures. RESULTS: The EORE group included 213 patients and the MCRE group included 643. The demographics were similar between the groups except for the patients' race and origin before admission. The MCRE group received anti-CRE agents for definitive therapy significantly more frequently compared with the EORE group (30% versus 5% for ceftazidime/avibactam). We did not observe a significant difference between the groups in the adjusted DOOR probability of a more desirable outcome for a randomly selected patient in the EORE group compared with the MCRE group (52.5%; 95% CI, 48.3%-56.7%). The MCRE group had a similar proportion of patients who died at 30 days (26% versus 21%) and who were discharged to home (29% versus 40%), compared with the EORE group. CONCLUSIONS: Patients with clinical EORE infection rarely received anti-CRE agents, but attained similar outcomes compared with patients with MCRE infection. The findings support current IDSA treatment guidance for meropenem- or imipenem-based therapy for treatment of EORE infections.

Probiotic and high-fat diet: effects on pain assessment, body composition, and cytokines in male and female adolescent and adult rats.

Obesity in adolescence is increasing in frequency and is associated with elevated proinflammatory cytokines and chronic pain in a sex-dependent manner. Dietary probiotics may mitigate these detrimental effects of obesity. Using a Long-Evans adolescent and adult rat model of overweight (high-fat diet (HFD) - 45% kcal from fat from weaning), we determined the effect of a single-strain dietary probiotic [Lactiplantibacillus plantarum 299v (Lp299v) from weaning] on the theoretically increased neuropathic injury-induced pain phenotype and inflammatory cytokines. We found that although HFD increased fat mass, it did not markedly affect pain phenotype, particularly in adolescence, but there were subtle differences in pain in adult male versus female rats. The combination of HFD and Lp299v augmented the increase in leptin in adolescent females. There were many noninteracting main effects of age, diet, and probiotic on an array of cytokines and adipokines with adults being higher than adolescents, HFD higher than the control diet, and a decrease with probiotic compared with placebo. Of particular interest were the probiotic-induced increases in IL12p70 in female adolescents on an HFD. We conclude that a more striking pain phenotype could require a higher and longer duration caloric diet or a different etiology of pain. A major strength of our study was that a single-strain probiotic had a wide range of inhibiting effects on most proinflammatory cytokines. The positive effect of the probiotic on leptin in female adolescent rats is intriguing and worthy of exploration.NEW & NOTEWORTHY A single-strain probiotic (Lp299v) had a wide range of inhibiting effects on most proinflammatory cytokines (especially IL12p70) measured in this high-fat diet rat model of mild obesity. The positive effect of probiotic on leptin in female adolescent rats is intriguing and worthy of exploration.

Venetoclax with decitabine or azacitidine in relapsed or refractory acute myeloid leukemia.

Relapsed or refractory acute myeloid leukemia (AML) is associated with poor outcomes and resistance to therapy. The addition of venetoclax, a BCL-2 antagonist, to lower-intensity therapies results in improved survival in the first-line setting compared to monotherapy with a hypomethylating agent or low-dose cytarabine. Despite this, much remains unknown about the performance of venetoclax with a hypomethylating agent following the first-line setting. Additionally, while the ELN 2022 guidelines appear to improve the prognostication of AML, clarification is needed to determine how the revision applies to lower-intensity strategies. To investigate this, we retrospectively analyzed the performance of venetoclax with decitabine or azacitidine in relapsed or refractory AML under the ELN 2022 guidelines. We demonstrated that the ELN 2022 revision is not optimized for lower-intensity venetoclax-based strategies. To refine the prognostication schema, we showed significantly improved response and survival benefits for patients with mutated NPM1 and IDH. Relatively, patients with mutated NRAS, KRAS, and FLT3-ITD were associated with inferior response and survival. Furthermore, there is an unmet clinical need for tools to improve the selection of lower-intensity therapy candidates with borderline functional status. Using an incremental survival computation method, we discovered that a CCI score threshold of 5 distinguishes patients at an elevated risk of death. Together, these novel findings highlight areas of refinement to improve survival in relapsed or refractory AML.

Perioperative methadone for posterior spinal fusion in adolescents: Results from a double-blind randomized-controlled trial.

BACKGROUND: Posterior spinal fusion is the most common surgical procedure performed for correction of adolescent idiopathic scoliosis in the United States. Intraoperative methadone has been shown to improve pain control in adult patients undergoing complex spine surgery, and current pediatric studies show encouraging results; however, prospective randomized-controlled trials are lacking in the pediatric literature. AIMS: We conducted a single-center double-blind randomized-controlled trial to compare intraoperative use of methadone to morphine in pediatric patients undergoing posterior spinal fusion. METHODS: A total of 47 adolescents undergoing posterior spinal fusion were randomized (stratified by sex) to either a methadone (n = 25) or morphine (n = 22) group. The primary outcome was postoperative opioid consumption. Secondary outcomes included postoperative pain severity, opioid-related side effects, and ratio of patient-controlled analgesia injections: attempts as a behavioral index of uncontrolled pain. RESULTS: Patients in the methadone group consumed less total opioid postoperatively (median [interquartile range], 0.3 mg/kg [0.1, 0.5]) than patients in the morphine group (0.3 mg/kg [0.2, 0.6]), median difference [95% confidence interval] -0.07 [-0.2 to 0.02]; (p = .026). Despite the lower amount of opioid used postoperatively, pain scores for the methadone group (3.5 [3.0, 4.3]) were not significantly different from those in the morphine group (4.0 [3.2, 5.0]; p = .250). Groups did not differ on opioid-related side effects. CONCLUSIONS: A two-dose intraoperative methadone regimen resulted in decreased opioid consumption compared to morphine. Although the clinical significance of these results may be limited, the analgesic equipoise without increased opioid-related side effects and potential for a lower incidence of chronic pain may tip the balance in favor of routine methadone use for adolescents undergoing posterior spinal fusion.

The Rating of Perceived Exertion-Pediatric (RPE-P) Scale: Preliminary Validation.

Physical activity is critical to functional rehabilitation for youth with chronic pain, which may be especially true for those with co-occurring obesity. To facilitate the development of physical activity interventions for youth with chronic pain, the newly developed "Rating of Perceived Exertion-Pediatric" scale was modeled after the widely used pain numeric rating scale-11. This study is an initial evaluation of the scale in a sample of adolescents (n = 157, 13-17 years, 51% female) with four subgroups: (1) healthy controls (healthy weight/no pain); (2) chronic pain/healthy weight; (3) obese (no pain); (4) chronic pain/obese. Participants rated perceived exertion using the new scale and the Borg 6-20 Scale of Perceived Exertion while holding a three-minute yoga pose (Warrior II). In the whole sample, the Perceived Exertion-Pediatric scale showed good concurrent (p < 0.001), convergent (all ps < 0.05), discriminant (p = 0.431), and known-groups validity (all ps < 0.05). The chronic pain subgroup also showed good concurrent (p < 0.001), mixed convergent (ps < 0.001 to 0.315), and good discriminant validity (p = 0.607). Limitations include the restricted age range, lack of diversity, and lack of test-retest reliability. The RPE-P shows promise as an assessment tool for perceived exertion in adolescents with and without chronic pain.

Secondary-Type Mutations in Acute Myeloid Leukemia: Updates from ELN 2022.

The characterization of the molecular landscape and the advent of targeted therapies have defined a new era in the prognostication and treatment of acute myeloid leukemia. Recent revisions in the European LeukemiaNet 2022 guidelines have refined the molecular, cytogenetic, and treatment-related boundaries between myelodysplastic neoplasms (MDS) and AML. This review details the molecular mechanisms and cellular pathways of myeloid maturation aberrancies contributing to dysplasia and leukemogenesis, focusing on recent molecular categories introduced in ELN 2022. We provide insights into novel and rational therapeutic combination strategies that exploit mechanisms of leukemogenesis, highlighting the underpinnings of splicing factors, the cohesin complex, and chromatin remodeling. Areas of interest for future research are summarized, and we emphasize approaches designed to advance existing treatment strategies.

Venetoclax with decitabine or azacitidine in the first-line treatment of acute myeloid leukemia.

Treatment paradigms for acute myeloid leukemia (AML) have evolved at a rapid pace in recent years. The combination of venetoclax with a hypomethylating agent prolonged survival in clinical trials when compared to hypomethylating agent monotherapy. However, little is known about the performance of venetoclax-based regimens outside of clinical trials, given conflicting safety and efficacy data. Even less is known about the impact of the hypomethylating agent backbone. In this study, we demonstrate that decitabine-venetoclax is associated with a significantly higher rate of grade three or higher thrombocytopenia, but lower rates of lymphocytopenia compared to azacitidine-venetoclax. There was no difference in response or survival across ELN 2017 cytogenetic risk categories in the overall cohort. Significantly more patients succumb to relapsed or refractory disease than death from any other cause. We demonstrated that a Charlson comorbidity index score threshold of seven identifies exceptionally high-risk patients, providing evidence for clinical use to reduce the risk of early treatment-related mortality. Lastly, we provide evidence that measurable residual disease negativity and an IDH mutation predict a significant survival benefit outside clinical trials. Taken together, these data illuminate the real-world performance of venetoclax and decitabine or azacitidine in the treatment of AML.

Stress Numerical Rating Scale-11: Validation in Pediatric Inpatient and Outpatient Pain Settings.

Stress is a commonly reported issue in pediatric populations of chronic and acute pain. Both outpatient and inpatient settings impose time constraints, which decreases opportunities to measure and address patient stress. The aim of these studies was to evaluate the validity of the Stress Numeric Rating Scale-11 (SNRS-11) in both inpatient and outpatient settings. The SNRS-11 is a single item stress measure ranging from 0 to 10 with endpoint anchors: 0 = "No stress" and 10 = "Highest stress possible". Results showed discriminative validity in the inpatient sample and convergent and discriminant validity in both outpatient and inpatient samples. Additionally, approximately 40% to 50% of the sample reported moderate-severe stress on all post-operative days. The SNRS-11 shows promise as a quick, easy, and free stress measure to be used in both inpatient and outpatient settings.

Family Caregiver Acceptability of Assessing Caregiver Adverse Childhood Experiences (ACEs) and Distress in Pediatric Specialty Care.

INTRODUCTION: Providing quality healthcare for children includes assessing and responding to needs of their family caregivers. Three salient domains to consider are caregivers' early adverse childhood experiences (ACEs), their current levels of distress, and their resilience in coping with both prior and current stressors. OBJECTIVE: Determine acceptability of assessing caregiver ACEs, current distress, and resilience in pediatric subspecialty care settings. METHODS: Caregivers of patients in two pediatric specialty care clinics completed questionnaires about their ACEs, recent emotional distress, and resilience. Importantly, caregivers also rated the acceptability of being asked these questions. Participants included 100 caregivers of youth ages 3-17 across Sickle Cell Disease and Pain clinic settings. The majority of participants were mothers (91.0%) who identified as non-Hispanic (86.0%). Caregiver race was primarily African American/Black (53.0%) and White (41.0%). The Area Deprivation Index (ADI) was used to assess socioeconomic disadvantage. RESULTS: High levels of caregiver acceptability or neutrality with assessing ACEs and distress, as well as high ACEs, distress, and resilience. Associations were found between caregiver ratings of acceptability with caregiver resilience and socioeconomic disadvantage. Caregivers reported openness to being asked about their experiences during childhood and recent emotional distress, although ratings of acceptability varied according to other contextual variables, such as level of socioeconomic disadvantage and caregiver resilience. In general, caregivers perceived themselves to be resilient in the face of adversity. CONCLUSIONS: Assessing caregiver ACEs and distress in a trauma-informed way may provide opportunities for better understanding the needs of caregivers and families in order to support them more effectively in the pediatric setting.

Mechanisms of myeloid leukemogenesis: Current perspectives and therapeutic objectives.

Acute myeloid leukemia (AML) is a heterogeneous hematopoietic neoplasm which results in clonal proliferation of abnormally differentiated hematopoietic cells. In this review, mechanisms contributing to myeloid leukemogenesis are summarized, highlighting aberrations of epigenetics, transcription factors, signal transduction, cell cycling, and the bone marrow microenvironment. The mechanisms contributing to AML are detailed to spotlight recent findings that convey clinical impact. The applications of current and prospective therapeutic targets are accentuated in addition to reviews of treatment paradigms stratified for each characteristic molecular lesion - with a focus on exploring novel treatment approaches and combinations to improve outcomes in AML.

Interaction of chronic pain, obesity and time of day on cortisol in female human adolescents.

Adolescent obesity augments and impedes the treatment of chronic pain. This is associated with increased systemic inflammation and is more prominent in females. In addition, pain and obesity each independently affect the hypothalamic-pituitary-adrenal (HPA) axis. However, the interaction of pain and obesity on the HPA axis and the potential for sexual dimorphism in this phenomenon is not established. We hypothesized that dysregulation of the HPA axis occurs in female human adolescents with chronic pain, obesity, or the combination of the two and is associated with gonadal steroids. We measured serum cortisol, estradiol, and testosterone in 13-17-year-old adolescent females (N = 79) from venous blood drawn during the daytime (0830-1730 h) and analyzed the data in toto and partitioned by morning vs. afternoon sampling time. Subjects were categorized as healthy weight/no pain (controls; BMI = 56th percentile [37-71]), healthy weight with chronic pain, obese without pain (BMI = 97th percentile [95-99]), or the combination of obesity and chronic pain. Serum cortisol was lower with chronic pain and/or obesity compared to healthy controls and was lower with chronic pain and obesity compared to chronic pain alone (healthy weight). The lower serum cortisol in the pain alone group was more prominent in the morning compared to the afternoon. There was no relationship between serum estradiol and testosterone and study group. The decrease in the anti-inflammatory and other pain-ameliorating effects of cortisol may contribute to chronic pain and its resistance to treatment with concurrent obesity in female adolescents.

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study.

Background: Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common. Methods: This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding. Results: Notable differences between patients infected with CRO-R and CRO-S E coli BSI included the proportion with Pitt bacteremia score ≥4 (23% vs 15%, P = .079) and the median time to active antibiotic therapy (12 hours [interquartile range {IQR}, 1-35 hours] vs 1 hour [IQR, 0-6 hours]; P < .001). Unadjusted DOOR analyses indicated a 58% probability (95% confidence interval [CI], 52%-63%) for a worse clinical outcome in CRO-R versus CRO-S BSI. In the IPW-adjusted cohort, no difference was observed (54% [95% CI, 47%-61%]). Secondary outcomes included unadjusted and adjusted differences in the proportion of 30-day mortality between CRO-R and CRO-S BSIs (-5.3% [95% CI, -10.3% to -.4%] and -1.8 [95% CI, -6.7% to 3.2%], respectively), postculture median length of stay (8 days [IQR, 5-13 days] vs 6 days [IQR, 4-9 days]; P < .001), and incident admission to a long-term care facility (22% vs 12%, P = .045). Conclusions: Patients with CRO-R E coli BSI generally have poorer outcomes compared to patients infected with CRO-S E coli BSI, even after adjusting for important confounders.

Wisconsin's COVID-19 Safer-at-Home Order: Perspectives on Pain, Stress, and Functioning From Pediatric Patients With Chronic Pain.

BACKGROUND: Given that enforced quarantine is associated with psychological distress, our objective was to understand factors that either helped or harmed pediatric chronic pain patients during Wisconsin's 2020 safer-at-home quarantine. METHODS: We reviewed the electronic medical records of 145 pediatric chronic pain patients seen at the Jane B. Pettit Pain and Headache Center, Children's Wisconsin, between April 1 and July 30, 2020. RESULTS: Stress and poor/disturbed lifestyle factors were primary contributors to increased pain. Over half of the sample (58.7%) reported COVID-related stressors as contributing to increased stress levels. Coping, engagement, and socialization were primary contributors to patient functioning. CONCLUSIONS: Continued access to clinicians who can help with coping and stress management techniques is necessary for the well-being of pediatric chronic pain patients during a quarantine.

Use of Aromatherapy for Pediatric Surgical Patients.

BACKGROUND: Children having surgery experience distress from a myriad of sources. Aromatherapy may present an opportunity to promote a healing environment and decrease distress for children following surgery. AIM: Evidence regarding the use of aromatherapy with children is growing. The purpose of this project was to describe our implementation process, subsequent use of and response to aromatherapy for children undergoing surgery. METHODS: This quality improvement project and subsequent retrospective chart review included all patients with documentation of aromatherapy use over an 8-month period. Data collection included demographic data, patient diagnosis, location, information about which oils were used, for which indications, and any outcome the nurse was able to observe (e.g., improved, no change, worsening of symptoms). A nurse-led workgroup developed and implemented a process for aromatherapy in a limited scope when discomfort, nausea/vomiting, nervousness, and sleep disturbances were reported . Charts of all patients with documented aromatherapy use were reviewed for indication/reason for use, oil, and patient response. RESULTS: Results suggest a successful implementation process. Aromatherapy was used by 191 patients (aged 3-22 years). Upset stomach, discomfort, and nervousness were most frequently reported as leading to aromatherapy use. Lavender and peppermint were the most frequently used oils. Of those patients with documented responses, the majority reported improvement. CONCLUSIONS: We were able to successfully implement a new aromatherapy program as an adjunct to care in children undergoing surgery. No adverse events were reported. Documentation is crucial to evaluating any new service.

Anesthetic Implications in Alternating Hemiplegia of Childhood: A Case Report.

The following case report describes a 13-year-old child with alternating hemiplegia of childhood (AHC) who underwent magnetic resonance imaging MRI with general anesthesia and experienced a hemiplegic spell, seizure, apnea, and sudden cardiac arrest with successful resuscitation. AHC is a rare neurodevelopmental disorder characterized by repeated episodes of weakness or paralysis affecting one or both sides of the body and multiple other neurologic problems. The challenges associated with this disorder include management of developmental delay, dystonia, hemiplegia, cerebrovascular dysfunction, apnea, and autonomic dysfunction. The current literature is extremely limited in describing the effects of general anesthesia for a patient with AHC. While the neurologic manifestations of AHC are well described, autonomic dysfunction and the potential for sudden cardiac arrest have not been widely reported. To our knowledge, this is the first case report to emphasize anesthetic considerations in a pediatric patient with AHC, specifically the unrecognized potential for cardiac arrhythmia and sudden cardiac arrest.

Effects of Weight and Pain on Physical Activity: Insights from the Lived Experiences of Youth with Co-Occurring Chronic Pain and Obesity.

Objective: Pediatric obesity and chronic pain are each associated with an increased risk for numerous poor physical and mental health outcomes. Co-occurring chronic pain and obesity (CPO) result in greater functional disability compared with either condition alone. The aim of the present study was to use qualitative methods to better understand the challenges experienced by adolescents with CPO, with a specific focus on physical activity. Methods: Semistructured interviews were conducted with 13 youth with CPO. Participants were questioned about pain, physical activity, coping strategies, and the perceived relationship between weight and pain. Interviews were audiorecorded, transcribed, and analyzed according to Interpretative Phenomenological Analysis. Results: Superordinate themes expressed by youth included: Impact of Chronic Pain on Relationships, Impact of Pain on Self-Perception, Using Food to Cope with Pain, Perceived Relationship between Pain and Weight after Onset of Pain, Attitudes toward Physical Activity, Barriers to Physical Activity, and Supports to Physical Activity. Conclusions: Participants identified challenges associated with CPO. Notably, participants identified pain as a greater barrier to exercise than weight, implicating the salience of chronic pain in the lives of youth with CPO. Furthermore, participants identified a desire to be more physically active, yet discussed struggles and concerns about attempts to increase their physical activity and indicated a desire for guidance about being more active. This study highlights the complexities of the relationship between CPO and underscores the importance of providers collaboratively working with patients to develop a practical plan to resume movement and physical activity.

An evaluation of short anxiety measures for use in the emergency department.

BACKGROUND: The emergency department (ED) is a stressful environment for children. Few studies assess pediatric anxiety in the ED. "Gold standard" for measuring state-anxiety, Spielberger's State-Trait Anxiety Inventory for Children (STAI-C state), is lengthy and of limited use in this setting. OBJECTIVE: The objective was to evaluate agreement between STAI-C, Likert, and modified Yale Preoperative Anxiety Scale (m-YPAS) and determine if shorter measures may be adequate replacements for STAI-C in the ED. METHODS: This is a secondary analysis of data from a previous observational cohort study of a convenience sample of children 5-17 years old presenting to the ED. Anxiety was measured using STAI-C, Likert, and m-YPAS. Spearman correlations were used to evaluate agreement between STAI-C and the brief scales. A sub-analysis evaluated agreement between scales for children ≥9 years old to assess the impact of age. RESULTS: Eighty children were included. Median (IQR) STAI-C state score was 32.5 (30.0, 37.8). This represents moderate state anxiety with 30% of children exhibiting elevated state anxiety. Median (IQR) Likert score was 2.0 (1.0, 2.0). Correlation between the Likert and STAI-C was moderate (rs = 0.51; p < 0.0001). Median (IQR) m-YPAS was 28.3 (24.2, 33.3). The m-YPAS and STAI-C were unrelated (rs = 0.12; p > 0.05). For children ≥9 years old, correlation between Likert and STAI-C remained moderate (rs = 0.52; p < 0.0001); STAI-C and m-YPAS were unrelated (rs = 0.10; p > 0.05). CONCLUSIONS: Children in the ED experienced moderate-elevated state anxiety. Likert scale may be an acceptable substitute for STAI-C state. Further studies of this scale will aid in identifying patients with anxiety to facilitate timely management.