Impact of CD19 CAR T-cell product type on outcomes in relapsed or refractory aggressive B-NHL.

CD19-targeted chimeric antigen receptor-engineered (CD19 CAR) T cells are novel therapies showing great promise for patients with relapsed or refractory (R/R) aggressive B-cell non-Hodgkin lymphoma (B-NHL). Single-arm studies showed significant variations in outcomes across distinct CD19 CAR T-cell products. To estimate the independent impact of the CAR T-cell product type on outcomes, we retrospectively analyzed data from 129 patients with R/R aggressive B-NHL treated with cyclophosphamide and fludarabine lymphodepletion followed by either a commercially available CD19 CAR T-cell therapy (axicabtagene ciloleucel [axicel] or tisagenlecleucel [tisacel]), or the investigational product JCAR014 on a phase 1/2 clinical trial (NCT01865617). After adjustment for age, hematopoietic cell transplantation-specific comorbidity index, lactate dehydrogenase (LDH), largest lesion diameter, and absolute lymphocyte count (ALC), CAR T-cell product type remained associated with outcomes in multivariable models. JCAR014 was independently associated with lower cytokine release syndrome (CRS) severity compared with axicel (adjusted odds ratio [aOR], 0.19; 95% confidence interval [CI]; 0.08-0.46), with a trend toward lower CRS severity with tisacel compared with axicel (aOR, 0.47; 95% CI, 0.21-1.06; P = .07). Tisacel (aOR, 0.17; 95% CI, 0.06-0.48) and JCAR014 (aOR, 0.17; 95% CI, 0.06-0.47) were both associated with lower immune effector cell-associated neurotoxicity syndrome severity compared with axicel. Lower odds of complete response (CR) were predicted with tisacel and JCAR014 compared with axicel. Although sensitivity analyses using either positron emission tomography- or computed tomography-based response criteria also suggested higher efficacy of axicel over JCAR014, the impact of tisacel vs axicel became undetermined. Higher preleukapheresis LDH, largest lesion diameter, and lower ALC were independently associated with lower odds of CR. We conclude that CD19 CAR T-cell product type independently impacts toxicity and efficacy in R/R aggressive B-NHL patients.

The Use and Impact of Diaries in PICUs and Neonatal ICUs: A Scoping Review.

OBJECTIVE: Several studies have investigated the impact of diaries in adult ICUs, which have been used as a tool to support recall and reduce post-traumatic stress disorder in patients and their families. We conducted a scoping review to determine the definition of ICU diaries, and the extent, range, and nature of research conducted on NICU and PICU diaries, describe their use and impact, as well as identify gaps in knowledge and areas for future research. DATA SOURCES: The following databases were searched from inception to March 2022: Cumulated Index to Nursing and Allied Health Literature, Cochrane Library, Embase, PubMed, and American Psychological Association PsycINFO. Searches were also conducted in the following gray literature databases: Google Scholar, University of South Australia, and WorldCat. STUDY SELECTION: All studies that discussed the use and impact of diaries or journals involving patients (<18 yr old) in PICUs and NICUs and/or their family members were included. DATA SYNTHESIS: Sixteen studies were identified. Most studies defined diaries as daily entries written by nurses and/or family members regarding the patient's condition during their ICU admission. The majority reported that diaries were beneficial to children and their families as they helped to fill in memory gaps, provided a means to express their feelings, and served as effective health communication tools. Several gaps were identified: extent of the use of diaries as a means of communication, the significance of diaries as a coping mechanism for bereaved parents, and the impact of PICU diaries on the children, their families, and healthcare professionals. CONCLUSIONS: There is a paucity of data on the use of NICU and PICU diaries. Nonetheless, the limited data revealed that NICU and PICU diaries were beneficial to children and their families. Our review demonstrated a heterogeneity in the terminology, content, use of photos, and the author/s of the NICU and PICU diaries. Further research is needed to investigate the impact of the use of NICU and PICU diaries on patient-reported outcomes.

The Impact of Ethnic and Cultural Differences on Parental Satisfaction in the PICU.

OBJECTIVES: This study examined satisfaction of parents whose children were admitted to the PICU to identify priority areas for improvement. We hypothesized that differences exist in satisfaction of parents of different ethnicities. DESIGN: Prospective observational study. SETTING: PICU in a tertiary care pediatric hospital. PATIENTS: All English-literate parents whose child was admitted to our PICU between February 2014 and February 2015 were eligible after informed consent was obtained. Parents included in this study in previous admission(s) were excluded. INTERVENTION: Nil. MEASUREMENTS AND MAIN RESULTS: We adapted Empowerment of Parent in the Intensive Care Questionnaire, a validated questionnaire survey specific for measuring parental satisfaction in PICUs. This adapted survey consisted of 31 questions (based on a scale of 1-6) examining five domains as follows: information giving, care and cure, parental participation, organization, and professional attitude. Reliability of Empowerment of Parent in the Intensive Care Questionnaire in our population was analyzed using Cronbach's alpha. We used ordinal logistic regression, controlling for socioeconomic status and educational level, to examine differences in parental perceptions of various ethnicities. We obtained a total of 206 responses (36.5%) from 543 admissions. There were 116 (56%) emergency and 90 (44%) elective admissions. The proportion of respondents were Chinese (126 [61%]), Malay (32 [16%]), Indian (23 [11%]), and "Others" (25 [12%]). Cronbach's alpha for domains of information giving (α = 0.80), care and cure (α = 0.93), parental participation (α = 0.84), organization (α = 0.79), and professional attitude (α = 0.88) were good. In all five domains, our median PICU scores were 6 (interquartile range, 5-6). Compared to other ethnic groups, Malay parents did perceive that domains of "care and cure," "parental participation," and "professional attitude" were less satisfactory. CONCLUSIONS: Significant differences were found in satisfaction ratings between parents of different ethnicities. Further studies are needed to explore and determine reasons for these differences.

Nutritional Intake in Children with Septic Shock: A Retrospective Single-Center Study.

Nutritional practice in children with severe sepsis or septic shock remains poorly described. We aimed to describe nutrition received by children with severe sepsis or septic shock and explore the association of nutritional intake with clinical outcomes. This study was a retrospective study of children who required pediatric intensive care unit (PICU) admission from 2009 to 2016. Outcomes were mortality, ventilator-free days (VFDs), and PICU-free days (IFDs). A total of 74 patients with septic shock or severe sepsis were identified. Forty-one (55.4%) patients received enteral nutrition (EN) only, 6 (8.1%) patients received parental nutrition (PN) only, 15 (20.3%) patients received both EN and PN, and 12 (16.2%) patients received intravenous fluids alone. Eight of 74 (10.8%) and 4 of 74 (5.4%) had adequate energy and protein intake, respectively. Patients who received early EN had lower odds of 28-day mortality (adjusted hazard ratio [HR] = 0.09, 95% confidence interval [CI]: 0.02, 0.45, p = 0.03) more 28-day VFDs (adjusted ß-coefficient = 18.21 [95% CI: 11.11, 25.32], p < 0.001), and IFDs (adjusted ß-coefficient = 16.71 [95% CI: 9.86, 23.56], p < 0.001) than patients who did not receive EN. Late EN was also associated with lower odds of mortality, more VFDs, and IFDs compared with no EN (HR = 0.06, 95% CI: 0.02, 0.23; p < 0.001; adjusted ß coefficient = 15.66, 95% CI: 9.31, 22.02; p < 0.001; and 12.34 [95% CI: 6.22, 18.46], p < 0.001; respectively). Inadequate calories and protein were not associated with mortality. EN in children with septic shock or severe sepsis was associated with improved clinical outcomes. Future prospective studies are required to explore the impact of EN timing and optimal nutritional intake in these children.

Respiratory Therapist-Driven Extubation Readiness Testing in a Single Pediatric ICU.

BACKGROUND: There is currently no standardized way to determine suitability for extubation of pediatric ICU (PICU) patients, potentially resulting in prolonged duration of mechanical ventilation. We aimed to design and implement a protocol for screening all intubated PICU patients for extubation readiness. METHODS: We adopted the quality improvement (QI) Model for Improvement with Plan-Do-Study-Act (PDSA) cycles to achieve this aim. This QI project was conducted over 11 months in a multidisciplinary PICU. Outcome measures included the (1) development of a standardized extubation readiness test (ERT) that was acceptable and safe; (2) performance of ERT on > 80% of all mechanically ventilated subjects; and (3) maintenance or reduction in mechanical ventilation duration, extubation failure (non-elective re-intubation within 48 h of extubation), and need for rescue noninvasive ventilation (NIV). Balancing measures were to ensure (1) no compromise of the subject's clinical status; and (2) acceptability of the ERT workflow by medical, nursing, and respiratory therapist (RT) teams. RESULTS: Four PDSA cycles were necessary to achieve the aims of this study. During the QI period, 438 subjects were admitted to the PICU. The ERT was championed by the RTs who conducted the test during office hours. ERT performance increased from 0% (baseline) to 90% (fourth PDSA cycle). Extubation failure rate after implementing ERT was reduced compared to baseline (4/31 [12.9%] vs 3/127 [2.4%], P = .01), whereas need for rescue NIV (3/31 [9.7%] vs 10/127 [7.9%], P = .74) and duration of mechanical ventilation (2 [1-7] d vs 1 [1-3] d, P = .09) were unchanged. PICU length of stay was reduced after implementing ERT (5 [3-10] d vs 3 [1-6] d, P = .01). No subject was destabilized as a result of ERT, and PICU staff found the workflow acceptable. CONCLUSIONS: An acceptable and safe ERT protocol was implemented and found to improve outcomes in PICU subjects on mechanical ventilation.

Association between admission body mass index and outcomes in critically ill children: A systematic review and meta-analysis.

BACKGROUND & AIMS: The association between nutritional status at pediatric intensive care unit (PICU) admission with clinical outcomes remains unclear. We conducted this systematic review to summarize the overall impact of PICU admission body mass index (BMI) on clinical outcomes. METHODS: We searched the following medical databases from inception through May 2020: PubMed, Excerpta Medica database (Embase), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Cochrane Library, and Web of Science. We included studies on patients ≤18 years old admitted to a PICU that investigated the effect of BMI on mortality, PICU or hospital length of stay (LOS), or duration of mechanical ventilation (MV). Classification of underweight, overweight, and obese were based on each study's criteria. RESULTS: There was a total of 21,558 patients from 20 included studies. 12,936 (60.0%), 2965 (13.8%), 2182 (10.1%), 3348 (15.5%) were normal weight, underweight, overweight, and obese patients, respectively. Relative to normal weight patients, underweight (OR 1.32, 95% CI 0.89-1.98; p = 0.171) and overweight/obese patients (OR 1.10, 95% CI 0.86-1.42; p = 0.446) did not have an increase risk in mortality. There was also no difference in duration of MV, PICU and hospital LOS between all three weight categories. Included studies were heterogeneous and lacked standardized nutritional categorization. Sensitivity analysis including only studies that used BMI z-scores as nutritional classification (n = 5) revealed that underweight patients had higher odds of mortality compared to patients with normal weight (OR 1.61, 95% CI 1.35-1.92; p < 0.001); studies that used percentiles as classification did not reveal any differences in mortality. Sensitivity analysis including only studies containing mixed PICU cohorts (i.e., excluding specialized cohorts e.g., congenital heart surgeries, burns) revealed higher mortality odds in underweight patients (OR 1.53, 95% CI 1.25-1.87; p < 0.001) and overweight/obese patients (OR 1.51, 95% CI 1.14-2.01; p = 0.004) relative to normal weight patients. CONCLUSIONS: Our systematic review did not reveal any association between PICU admission BMI status and outcomes in critically ill children. Further investigation with standardized nutrition status classification on admission, stratified by patient subgroups, is needed to clarify the association between nutritional status and clinical outcomes of PICU patients.

Psychosocial impact of the COVID-19 pandemic on paediatric healthcare workers.

INTRODUCTION: Frontline healthcare workers (HCWs) exposed to coronavirus disease 2019 (COVID-19) are at risk of psychological distress. This study evaluates the psychological impact of COVID-19 pandemic on HCWs in a national paediatric referral centre. METHODS: This was a survey-based study that collected demographic, work environment and mental health data from paediatric HCWs in the emergency, intensive care and infectious disease units. Psychological impact was measured using the Depression, Anxiety, Stress Scale-21. Multivariate regression analysis was performed to identify risk factors associated with psychological distress. RESULTS: The survey achieved a response rate of 93.9% (430 of 458). Of the 430 respondents, symptoms of depression, anxiety and stress were reported in 168 (39.1%), 205 (47.7%) and 106 (24.7%), respectively. Depression was reported in the mild (47, 10.9%), moderate (76, 17.7%), severe (23, 5.3%) and extremely severe (22, 5.1%) categories. Anxiety (205, 47.7%) and stress (106, 24.7%) were reported in the mild category only. Collectively, regression analysis identified female sex, a perceived lack of choice in work scope/environment, lack of protection from COVID-19, lack of access to physical activities and rest, the need to perform additional tasks, and the experience of stigma from the community as risk factors for poor psychological outcome. CONCLUSION: A high prevalence of depression, anxiety and stress was reported among frontline paediatric HCWs during the COVID-19 pandemic. Personal psychoneuroimmunity and organisational prevention measures can be implemented to lessen psychiatric symptoms. At the national level, involving mental health professionals to plan and coordinate psychological intervention for the country should be considered.

Use of an Electronic Feeds Calorie Calculator in the Pediatric Intensive Care Unit.

Strategies to improve nutritional management are associated with better outcomes in pediatric intensive care units. We implemented a calorie-based protocol that integrated an electronic feeds calculator and stepwise feeds increment algorithm. METHODS: Using a pretest-posttest design, we compared the effectiveness of the calorie-based protocol with an existing fluid-based protocol in a quality improvement project. The main outcome measure was the proportion of patients prescribed with the appropriate amount of calories (defined as 90%-110% of calculated energy requirements). Nurses were surveyed on their satisfaction with the new calorie-based protocol. We compared consecutive patients enrolled in the calorie-based protocol over 21 months with retrospective data of patients in the fluid-based protocol. χ 2 and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. RESULTS: We enrolled 75 and 92 patients in the fluid-based (pre) and calorie-based (post) protocols, respectively. Both groups did not differ in their age, reasons for pediatric intensive care units admissions, length of stay, duration of mechanical ventilation, and risks of mortality. The frequency of appropriate feeds prescription increased (16.0% versus 33.7%, P = 0.002). The new protocol significantly reduced the time from protocol initiation to full feeds (median: 18.0 hours, interquartile range = 18.0-27.5 versus median: 12.8 hours, interquartile range = 12.0-16.0, P < 0.001). The satisfaction surveys (n = 63) revealed favorable nursing perceptions. CONCLUSIONS: The use of a calorie-based protocol with an electronic calculator led to an improvement in the accuracy of the prescribed feeds and the time required to attain full enteral feeding. Nursing perceptions regarding the protocol were positive.

Systematic Review of the Effect of Topical Application of Human Breast Milk on Early Umbilical Cord Separation.

OBJECTIVE: To evaluate the efficacy of topical application of human breast milk to reduce umbilical cord separation time. DATA SOURCES: We used a three-step search strategy. First, we searched six electronic databases from inception through July 16, 2018: PubMed, Cochrane, CINAHL, Embase, Scopus, and ProQuest Dissertations and Theses Global. We used the following search terms: infant, newborn, baby, babies, colostrum, breast milk expression, breast milk, breastmilk, mother milk, human milk, umbilical cord, and umbilicus. We included published trials in English without any time limit to optimize the search. Second, we searched for ongoing clinical trials and grey literature. Last, we conducted a manual review of the reference lists of the identified articles. STUDY SELECTION: From 1,303 articles initially screened, eight articles reporting seven randomized controlled trials (RCTs) were included in the systematic review and meta-analysis. DATA EXTRACTION: Two independent reviewers used a standardized extraction form to extract data from eligible articles. We evaluated the quality of individual and overall evidence according to risk of bias and the Grade of Recommendation, Assessment, Development, and Evaluation (GRADE) system. DATA SYNTHESIS: Allocation concealment was not clearly identified in any of the studies. In only two trials were participants and personnel blinded to the intervention group, and in none was the assessment of outcomes blinded. The overall quality of evidence was very low for RCTs according to the GRADE criteria. We found a significant reduction in time to cord separation with the topical application of human breast milk (z = 6.22, p < .001), with a mean difference of -1.01 day (95% confidence interval [-1.3,-0.690]) compared with dry cord care. Incidence of omphalitis was not significantly different (risk ratio = 0.82, 95% confidence interval [0.57, 1.18], z = 1.06, p = .29) between human breast milk and dry cord care groups. CONCLUSION: Topical application of human breast milk is an effective and safe way to reduce cord separation time. Given that the overall quality of the included RCTs was very low, further well-designed trials are needed.

Characteristics and Outcomes of Long-Stay Patients in the Pediatric Intensive Care Unit.

Long-stay patients in the PICU have a higher risk of mortality as compared with non-long-stay patients. We aim to describe mortality and characteristics of long-stay patients and to determine the risk factors for mortality in these children. Total 241 (4.8%) long-stay admissions were identified. Mortality of long-stayers was 48/241 (20%). Higher severity-of-illness score at admission, need for organ support therapies, number of nosocomial infections, and bloodstream nosocomial infection were associated with a higher mortality in long-stay patients in the PICU. Based on multivariate analysis, oncologic diagnosis as a preexisting comorbidity is a strong independent predictor of mortality for long-stay patients.

Perceptions of Pediatric Critical Care Nurses on the Initiation of a Nursing-Led Feeding Protocol.

BACKGROUND: Critically ill children frequently receive inadequate nutritional support. Feeding protocols have been shown to facilitate optimal nutritional care. PURPOSE: We aim to determine the perceptions of critical care nurses with regard to the implementation of a feeding protocol as well as to their preferred teaching methods before introducing this protocol in our pediatric intensive care unit (PICU). We hypothesize that nursing experience and educational level are factors that predict readiness to adopt this protocol. METHODS: All PICU nurses were invited to participate in an online survey to investigate their perceptions on protocol implementation and on preferred teaching methods. Statistical analysis was performed using simple logistic regression and the Fisher exact test. Statistical significance was taken as p < .05. RESULTS: Seventy-four nurses completed the survey. Fifty-four (73%) had nursing degrees. Mean duration of PICU experience was 6.2 years (5th, 95th percentile: 1, 15). Three quarters of participants (74%, n = 55) felt that they did not have sufficient knowledge regarding feeding protocols, and 86% (n = 64) expressed that they were keen to implement a feeding protocol. There was no association between readiness to adopt the feeding protocol with years of ICU experience (OR = 0.99, 95% CI [0.84, 1.18]) and educational level (OR = 1.43, 95% CI [0.31, 6.68]). The preferred teaching methods were bedside teaching (61%), didactic lectures (51%), and the distribution of protocol manuals (50%). PICU nurses felt that the advantages of a feeding protocol included standardization of practice, optimization of patient's nutritional intake, earlier initiation of feeding, increased patient safety, and the extension of nursing roles. Perceived disadvantages included inapplicability of the feeding protocol to all patients, lack of flexibility in feeding management, increased confusion, and doctors placing little value on the feeding protocol. CONCLUSIONS: This study found that nursing experience and level of education do not significantly affect the readiness of nurses to adopt a feeding protocol. Medical and nursing teams should not shy away from introducing a new protocol although their nurses have little experience or prior knowledge of that protocol. Future studies to investigate the impact of tailoring of educational needs before introduction of a new protocol are necessary to study the overall effectiveness of this teaching before introducing a new protocol in the ICU.

Unusual presentation of myeloid sarcoma in a case of acute promyelocytic leukemia with a cryptic PML-RARA rearrangement involving multiple sites including the atrium.

Myeloid sarcoma is an extramedullary tumor mass composed of immature myeloid cells. Myeloid sarcoma may develop de novo, concurrently with acute myeloid leukemia (AML), or at relapse. Although myeloid sarcoma can occur at any site, myeloid sarcoma involving the heart is extremely rare. Reported here is the case of a 30-year-old man, initially diagnosed with acute promyelocytic leukemia (APL) in bone marrow, who presented later with myeloid sarcoma at multiple anatomical sites (left scapula, thoracic vertebra, right atrium, and supraclavicular mass) in multiple relapses. Conventional cytogenetic studies performed on the atrial sample revealed a karyotype with additional material on the short arm of chromosome 7, at 7p22. Fluorescence in situ hybridization studies confirmed a cryptic PML-RARA fusion on the short arm of chromosome 7, as well as a second fusion on one copy of chromosome 15. With the fourth and latest relapse, molecular cytogenetic studies performed on interphase nuclei of the myeloid sarcoma specimen (a supraclavicular mass) showed evidence of six related abnormal clones with a PML-RARA fusion, suggesting clonal evolution. This represents a rare case of APL with a cryptic PML-RARA rearrangement presenting as myeloid sarcoma at multiple relapses and involving multiple anatomical sites, including cardiac atrium.