Risk factors for neurocognitive impairment, emotional distress, and poor quality of life in survivors of pediatric rhabdomyosarcoma: A report from the Childhood Cancer Survivor Study.

BACKGROUND: Prevalence and risk of poor psychological outcomes following rhabdomyosarcoma (RMS) are not well-established. METHODS: Participants in this cross-sectional, case-control study (n = 713 survivors, 42.5% female; mean [SD] age, 30.5 [6.6] years; n = 706 siblings, 57.2% female; mean age, 32.8,[7.9] years) completed measures of neurocognition, emotional distress, and health-related quality of life (HRQOL). Multivariable logistic regression models identified treatments, health behaviors, and chronic conditions associated with impairment. RESULTS: Relative to siblings, more survivors reported neurocognitive impairment (task efficiency: 21.1% vs. 13.7%, emotional regulation: 16.7% vs. 11.0%, memory: 19.3% vs. 15.1%), elevated emotional distress (somatic distress: 12.9% vs. 4.7%, anxiety: 11.7% vs. 5.9%, depression: 22.8% vs. 16.9%) and poorer HRQOL (physical functioning: 11.1% vs. 2.8%, role functioning due to physical problems: 16.8% vs. 8.2%, pain: 17.5% vs. 10.0%, vitality: 22.3% vs. 13.8%, social functioning: 14.4% vs. 6.8%, emotional functioning: 17.1% vs. 10.6%). Cranial radiation increased risk for impaired task efficiency (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.14-4.63), whereas chest and pelvic radiation predicted increased risk of physical functioning (OR, 2.68; 95% CI, 1.16-6.21 and OR, 3.44; 95% CI, 1.70-6.95, respectively). Smoking was associated with impaired task efficiency (OR, 2.06; 95% CI, 1.14-3.70), memory (OR, 2.23; 95% CI, 1.26-3.95), anxiety (OR, 2.71; 95% CI, 1.36-5.41) and depression (OR, 1.77; 95% CI, 1.01-3.11). Neurologic conditions increased risk of anxiety (OR, 2.30; 95% CI, 1.04-5.10), and hearing conditions increased risk of depression (OR, 1.79; 95% CI, 1.05-3.03). Neurologic and hearing conditions, respectively, were associated with impaired memory (OR, 2.44; 95% CI, 1.20-4.95 and OR, 1.87; 95% CI, 1.05-3.35) and poor health perception (OR, 2.62; 95% CI, 1.62-1.28 and OR, 2.33; 95% CI, 1.34-4.06). CONCLUSIONS: RMS survivors are at significant risk for poor psychological outcomes. Advancing therapies for local control, smoking cessation, and managing chronic medical conditions may mitigate poor outcomes following RMS.

Digital PCR to Measure SARS-CoV-2 RNA, Variants, and Outcomes in Youth.

BACKGROUND: The role of SARS-CoV-2 viral load in predicting contagiousness, disease severity, transmissibility, and clinical decision-making continues to be an area of great interest. However, most studies have been in adults and have evaluated SARS-CoV-2 loads using cycle thresholds (Ct) values, which are not standardized preventing consistent interpretation critical to understanding clinical impact and utility. Here, a quantitative SARS-CoV-2 reverse-transcription digital PCR (RT-dPCR) assay normalized to WHO International Units was applied to children at risk of severe disease diagnosed with COVID-19 at St. Jude Children's Research Hospital between March 28, 2020, and January 31, 2022. METHODS: Demographic and clinical information from children, adolescents, and young adults treated at St. Jude Children's Research Hospital were abstracted from medical records. Respiratory samples underwent SARS-CoV-2 RNA quantitation by RT-dPCR targeting N1 and N2 genes, with sequencing to determine the genetic lineage of infecting virus. RESULTS: Four hundred and sixty-two patients aged 0-24 years (median 11 years old) were included during the study period. Most patients were infected by the omicron variant (43.72%), followed by ancestral strain (22.29%), delta (13.20%), and alpha (2.16%). Viral load at presentation ranged from 2.49 to 9.14 log10 IU/mL, and higher viral RNA loads were associated with symptoms (OR 1.32; CI 95% 1.16-1.49) and respiratory disease (OR 1.23; CI 95% 1.07-1.41). Viral load did not differ by SARS-CoV-2 variant, vaccination status, age, or baseline diagnosis. CONCLUSIONS: SARS-CoV-2 RNA loads predict the presence of symptomatic and respiratory diseases. The use of standardized, quantitative methods is feasible, allows for replication, and comparisons across institutions, and has the potential to facilitate consensus quantitative thresholds for risk stratification and treatment.

Aberrant nuclear ß-catenin distribution does not prognosticate recurrences of endometrioid endometrial cancers - A retrospective single-institutional study.

OBJECTIVE: Aberrant ß-catenin distribution has been theorized as a predictive biomarker for recurrence in early stage, low grade endometrioid endometrial cancer. METHODS: This retrospective single-institution cohort study reviewed 410 patients with endometrial cancer from May 2018 to May 2022. Only endometrioid histology was included. Demographic and clinicopathological data were collected from the medical records. Univariate and multivariate logistic regressions, and sensitivity analyses for early stage, low grade and no specific molecular profile (NSMP) tumors were performed. RESULTS: 297 patients were included for analysis. Most patients were over 60 years old, White, and with a BMI >30 and early stage low grade disease. Aberrant ß-catenin distribution was found in 135 patients (45.5%) and wild type membranous ß-catenin distribution in 162 (54.5%). While TP53 mutation correlated with endometrial cancer recurrence in this cohort (OR = 4.78), aberrant ß-catenin distribution did not correlate in the overall population (OR = 0.75), the early stage low grade cancers (OR = 0.84), or the NSMP group (OR = 1.41) on univariate or multivariate analysis. No correlation between ß-catenin distribution and local (OR = 0.61) or distant recurrences (OR = 0.90) was detected. CONCLUSIONS: Aberrant ß-catenin distribution did not significantly correlate with recurrence in endometrioid endometrial cancer, nor in the early stage, low grade and NSMP sub-cohorts.

Gene therapy in sickle cell disease: Attitudes and informational needs of patients and caregivers.

BACKGROUND: Sickle cell disease (SCD) is an inherited blood disorder that results in serious morbidity and early mortality. Novel therapies for SCD, most notably genetic therapies (GTs) and HLA-mismatched donor hematopoietic cell transplantation, are in clinical trials. While potentially curative, these interventions are some of the most intensive treatments for SCD and are associated with serious and life-altering side effects, which may manifest several years after treatment. Little is known about knowledge, beliefs, and attitudes of individuals with SCD, or their caregivers, toward existing and these emerging therapies. METHODS: Patients with SCD at least 13 years of age (n = 66) and caregivers (n = 38) were surveyed about knowledge, attitudes, and beliefs surrounding treatments for SCD. RESULTS: Only 4.8% felt "extremely knowledgeable" about GT for SCD while the majority (63.4%) reported little knowledge. Overall, health literacy was low among respondents. Most respondents had a neutral attitude regarding the safety of GT for SCD, and whether it was a good treatment for the disorder (56.7% and 58.6%, respectively). Only a few respondents endorsed the idea that GT was "unsafe" or "not a good treatment" (5.8% and 4.8%, respectively). There was an association between increasing knowledge about GT and agreement that it is safe (p = .012) and a good treatment for SCD (p = .031). CONCLUSIONS: Given that very few patients with SCD feel knowledgeable about GT and a majority have neutral feelings about the safety and utility of this new approach, culturally appropriate patient-centered education is urgently needed as these treatments get regulatory approval and proceed to the clinic.

MRSA screening: incidence and maternal postpartum outcomes in an obstetric population at a tertiary care center.

PURPOSE: To assess the incidence of MRSA positive patients in pregnancy, as well as the postpartum outcomes in MRSA positive patients. METHODS: This is a retrospective cohort study of women who underwent universal MRSA universal at a tertiary medical center. A MRSA swab was routinely collected as part of the patient's prenatal care at 35-37 weeks gestation or on admission to labor and delivery. Demographic information and decolonization antibiotics were collected by electronic medical record review, using ICD-9 codes. Outcome data were collected, including mode of delivery, hospital length of stay, endometritis, wound cellulitis, and wound infection. p < 0.05 was considered significant. A univariate logistic regression and a multivariable binary logistic regression model were used to analyze the strength of association between outcomes and MRSA status. Statistical analysis was performed with SAS, version 9.4. RESULTS: The incidence of MRSA during the 4 year study period was 1.9% (82 MRSA positive out of 4369 total patients). 90.2% (74/82) of MRSA positive patients received decolonization antibiotics. No difference was noted in mode of delivery. Logistic regression failed to identify any significant differences in other relevant outcomes for MRSA positive women including endometritis 1.1 (0.1-17.5) [positive 0, versus negative 0.6% (n = 24)], wound cellulitis 5.9 (0.4-82.1) positive 0, versus negative 0.1% (Gorwitz et al. in J Infect Dis 197:1226-1234, 2008) and wound infection 3.3 (0.6-16.9) [positive 1.2%, versus negative 0.5% ( in Am J Infect Control 32:470-85, 2004)] when compared to MRSA negative women. CONCLUSION: When universal MRSA screening was performed at an academic tertiary care center, the overall incidence of MRSA was low. MRSA positive and subsequently decolinzed patients did not have any identified increase in postpartum infectious morbidity, as compared to MRSA negative patients.

A retrospective investigation of the relationship between neuroblastoma response to anti-GD2 monoclonal antibodies and exposure to opioids for pain management.

OBJECTIVE: Recent increased awareness and research studies reflect possible associations between opioid exposure and cancer outcomes. Children with neuroblastoma (NB) often require opioid treatment for pain. However, associations between tumor response to chemotherapy and opioid exposure have not been investigated in clinical settings. METHODS: This is a single-institution retrospective review of patients with NB treated between 2013 and 2016. We evaluated opioid consumption quantified in morphine equivalent doses (mg/kg) based on nurse- or patient-controlled analgesia during antibody infusions. We also analyzed their associations with change in primary tumor volume and total tumor burden. RESULTS: Of 42 patients given opioids for pain related to anti-disialoganglioside monoclonal antibodies (anti-GD2 mAb), data completion was achieved for 36, and details of statistical analyses were entered. Median total weight-based morphine equivalent (over 8 days) was 4.71 mg/kg (interquartile range 3.49-7.96). We found a statistically insignificant weak negative relationship between total weight-based morphine equivalents and tumor volume ratio (correlation coefficient -.0103, p-value .9525) and a statistically insignificant weak positive relationship between total weight-based morphine equivalent and Curie score ratio (correlation coefficient .1096, p-value .5247). CONCLUSION: Our study found no statistically significant correlation between opioid consumption and natural killer (NK) cell-mediated killing of NB cells as measured by effects on tumor volume/tumor load.

Prediction of Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection by Quantitative Digital Polymerase Chain Reaction Normalized to International Units.

Although numerous studies have evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using cycle threshold (Ct) values as a surrogate of viral ribonucleic acid (RNA) load, few studies have used standardized, quantitative methods. We validated a quantitative SARS-CoV-2 digital polymerase chain reaction assay normalized to World Health Organization International Units and correlated viral RNA load with symptoms and disease severity.

Retrospective descriptive analysis of a managed care population with obesity.

OBJECTIVES: To reveal the extent of obesity in a single healthcare system and provide a blueprint for other health systems to perform similar analyses, this study describes characteristics and weight change patterns of patients classified with overweight and obesity at a large integrated delivery network (IDN) in the South-Central United States. METHODS: A descriptive, observational, retrospective study was conducted using electronic medical records and claims data. Patients were ≥18 years old, body mass index (BMI) ≥27 kg/m2, and continuously enrolled in the IDN plan for ≥6 months before and ≥12 months after the index date. Demographics, comorbidities, BMI, and weight were collected. Weight changes were assessed annually, and anti-obesity medications (AOM) use was also captured. RESULTS: A total of 36,430 eligible patients were identified. A subset of 22,712 patients was continuously enrolled for the entire study period (mean age: 57.2) and were primarily white (83.3%) and commercially insured (54.3%). Most patients were categorized as overweight (40.1%) or obesity class I (32.5%) at baseline. At years 1 and 4 post-index, patients who maintained index weight (±3%) was 56.2% and 37.0%, respectively, whereas weight gain (≥3% increase) was 23.7% and 33.3%, respectively. AOM use (1.1%) primarily consisted of phentermine-hydrochloride (n = 114, 0.5%) and orlistat (n = 115, 0.5%). CONCLUSIONS: An increasing proportion of patients gained weight over time, combined with low AOM use, emphasizing the need for weight-loss interventions in this population. Findings from this study provide a foundation for health systems to perform similar analyses.

Association of Living in a Food Desert With Pregnancy Morbidity.

OBJECTIVE: To evaluate whether women living in areas deemed food deserts had higher rates of pregnancy morbidity, specifically preeclampsia, gestational hypertension, gestational diabetes, prelabor rupture of membranes, preterm labor, than women who did not live in food deserts at the time of their pregnancy and delivery. METHODS: This was a retrospective observational study in which we reviewed electronic medical records of all patients who delivered at Loyola University Medical Center in Maywood, Illinois in 2014. The Economic Research Service of the U.S. Department of Agriculture publishes the Food Access Research Atlas, which presents a spatial overview of food access indicators for low-income and other Census tracts using different measures of supermarket accessibility. A spatial join between the Food Access Research Atlas and patient coordinates was performed to identify patient point locations and determine whether each patient was located within or outside of a food desert. RESULTS: Data for 1,003 deliveries at Loyola University Medical Center in 2014 were provided by the Loyola University Chicago Clinical Research Database. Two deliveries were excluded owing to inability to map address coordinates; thus 1,001 deliveries were analyzed. Of the 1,001 patients, 195 (19.5%) women were designated to food deserts. Multivariable analysis was done by adjusting for age, race, and medical insurance class. Having at least one morbid condition was the only variable that demonstrated a significant association with the food desert in multivariable analyses (47.2% vs 35.6%) (odds ratio [OR] 1.62, 95% CI 1.18-2.22) (adjusted OR 1.64, 95% CI 1.18-2.29). CONCLUSION: The odds of having at least one of the studied morbid conditions in pregnancy were greater for patients living in a food desert. As there is an association of morbidity in pregnancy with living in a food desert, intervention trials to improve the built food environment or mitigate the effect otherwise are needed.