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Objective: To improve outcomes of hemophagocytic lymphohistiocytosis (HLH), prompt recognition and treatment are necessary. A HLH multidisciplinary team was implemented at our institution, and we established an electronic order set to foster uniformity in the diagnostic approach. The goal of this study is to capture the impact of this diagnostic tool., Methods: This is a retrospective study analyzing the utilization of a HLH-specific order set since time of implementation in June 2019 through December 2022. The trends in the utilization of the order set by providers were analyzed to evaluate the awareness and effectiveness of this tool., Results: The order set was utilized 50 times, most commonly by hematology/oncology (50%) and infectious disease (26%). Utilization by providers on newly presenting patients included 4 times in the year 2019, 12 times in 2020, 16 times in 2021, and 18 times in 2022. Utilization was associated with the diagnosis of HLH in 9 patients (18%)., Conclusion: Implementation of an HLH-specific order set facilitated a systematic method to approach patients with suspected HLH. The utilization of the order set displayed an upward trend over time, indicating support of this tool among these providers. This tool can increase awareness and early identification of HLH., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Fever of unknown origin is a common presentation in children with an extensive differential diagnosis that encompasses multiple specialties. From a hematologic standpoint, the differential includes hyperinflammatory syndrome, such as hemophagocytic lymphohistiocytosis (HLH), among others. Due to the rarity of HLH and nonspecific symptoms at initial presentation, specialists are often consulted later in the disease progression, which complicates disease evaluation further. Cook Children's Medical Center (CCMC) has recently developed a multidisciplinary histiocytic disorder group that is often consulted on cases presenting with fever of unknown origin to increase awareness and potentially not miss new HLH cases. In this study, we examine the clinical presentation and workup of 13 patients consulted by the HLH work group at a single institution and describe the clinical course of 2 patients diagnosed with HLH. The goal of this project was to describe the formation of a disease-specific team and the development of a stepwise diagnostic approach to HLH. A review of the current diagnostic criteria for HLH may be warranted given findings of markers such as soluble IL2 receptor and ferritin as nonspecific and spanning multiple disciplines including rheumatology, infectious disease, and hematology/oncology., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Sustainability interventions were implemented at the Royal Brisbane and Women's Hospital (RBWH) following identification of inhaled anaesthetic gases as a target for reducing medical carbon emissions. This quality improvement study assessed and evaluated the impact of sustainability interventions on the environmental and financial cost of inhaled anaesthetic gas use in order to guide future initiatives and research in reducing carbon emissions from healthcare practice.Ethical exemption was granted from the RBWH Research Ethics Committee (EX/2021/QRBW/76078). Usage (bottles) and expenditure for desflurane and sevoflurane from January 2016 to December 2021 were obtained. Global warming potential and carbon dioxide equivalent (CO 2 e) were used to report environmental impact of volatile agents. Methods to estimate this were performed in Excel based on Campbell and Pierce methodology. An Environmental Protection Agency greenhouse gas equivalency calculator was used to convert CO 2 e to equivalent petrol carbon emissions and kilometres travelled by a typical passenger vehicle.The total number of bottles of sevoflurane and desflurane purchased between January 2016 and December 2021 decreased by 34.76% from 1991 to 1299. The number of desflurane bottles purchased decreased by 95.63% from 800 to 35 bottles. The number of sevoflurane bottles purchased increased by 6.13% from 1191 bottles to 1264 bottles. This was achieved by implementing quality improvement interventions such as staff education of desflurane-sparing practices, distribution of posters and progressive removal of desflurane from operating theatres. Total carbon emission from volatile anaesthetics equalled 2326 tonnes CO 2 e. Combined desflurane and sevoflurane emissions decreased by 87.88%. In 2016, desflurane made up 92.39% of the annual CO 2 e, which steadily decreased to 33.36% in 2021. Combined sevoflurane and desflurane usage costs decreased by 58.33%.Substantial reductions in carbon emissions from volatile anaesthetics demonstrate the significant degree to which environmentally sustainable practices have been implemented. Applying desflurane-sparing practice can heavily limit anaesthetic drug expenditure and contribution to environmental waste. This is important given the global health sector's challenge to optimise patient outcomes in the face of global climate change crisis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There are sparse data on the long-term and late effects of hematopoietic cell transplantation (HCT) for sickle cell disease (SCD)., Objective: This study aims to establish an international registry of long-term outcomes post-HCT for SCD and demonstrate the feasibility of recruitment at a single site in the United States., Methods: The Sickle Cell Transplantation Evaluation of Long-Term and Late Effects Registry (STELLAR) was designed to enroll patients with SCD ≥1 year post-HCT, their siblings without SCD, and nontransplanted controls with SCD to collect web-based participant self-reports of health status and practices by using the Bone Marrow Transplant Survivor Study (BMTSS) surveys, health-related quality of life (HRQOL) using the Patient-Reported Outcomes Measurement Information System (PROMIS) Pediatric Profile-25 or Pediatric Profile-29 survey, chronic graft-versus-host disease (cGVHD) using the symptom scale survey, daily pain using an electronic pain diary, the economic impact of HCT using the financial hardship survey, sexual function using the PROMIS Sexual Function SexFSv2.0 survey, and economic productivity using the American Time Use Survey (ATUS). We also piloted retrieval of clinical data previously submitted to the Center for International Blood and Marrow Transplant Research (CIBMTR); recorded demographics, height, weight, blood pressure, waist and hip circumferences, timed up and go (TUG) test, and handgrip test; and obtained blood for metabolic screening, gonadal function, fertility potential, and biorepository of plasma, serum, RNA, and DNA., Results: Of 100 eligible post-HCT patients, we enrolled 72 (72%) participants aged 9-38 (median 17) years. We also enrolled 19 siblings aged 5-32 (median 10) years and 28 nontransplanted controls with SCD aged 4-46 (median 22) years. Of the total 119 participants, 73 (61%) completed 85 sets of surveys and 41 (35%) contributed samples to the biorepository. We completed ATUS interviews of 28 (24%) participants. We successfully piloted retrieval of data submitted to the CIBMTR and expanded recruitment to multiple sites in the United States, Canada, the United Kingdom, and Nigeria., Conclusions: It is feasible to recruit subjects and conduct study procedures for STELLAR in order to determine the long-term and late effects of HCT for SCD., International Registered Report Identifier (irrid): DERR1-10.2196/36780., (©Lakshmanan Krishnamurti, Staci D Arnold, Ann Haight, Allistair Abraham, Gregory MT Guilcher, Tami John, Nitya Bakshi, Shalini Shenoy, Karen Syrjala, Paul L Martin, Sonali Chaudhury, Gretchen Eames, Olusola Festus Olowoselu, Matthew Hsieh, Josu De La Fuente, Kimberly A Kasow, Elizabeth Stenger, Anne Mertens, Fuad El-Rassi, Peter Lane, Bronwen E Shaw, Lillian Meacham, David Archer. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 06.07.2022.)

Purpose: Patients undergoing stem-cell transplants endure prolonged hospitalizations and aggressive medical treatments. This combination can quickly evolve into loss of functional strength and physical debilitation. We aimed to promote independent patient activity during hospitalizations, to improve compliance with prescribed physical therapy (PT) sessions, and to focus those sessions on resistance and endurance exercises., Methods: We used the Institute for Healthcare Improvement Model of Improvement as our quality improvement (QI) framework, and we implemented an initiative called Exercise is Medicine. The initiative included three key components: (1) educating staff and caregivers about the importance of early ambulation, (2) incorporating the Miles in Motion (MiM) program to encourage patients' daily activity, and (3) eliminating barriers to allow for higher completion rates of prescribed PT sessions. Data were collected for the completion rate of PT sessions, rate of high-frequency PT sessions, participation in the MiM program, and 1-minute sit-to-stand test scores on admission and discharge., Results: Before intervention, 42% of patients required high-frequency PT because of significant debilitation, which decreased to 17% after intervention. The completion rate of PT sessions increased from 71% to 87%. By discharge, 79% of patients improved their 1-minute sit-to-stand test scores and 21% returned to baseline score, indicating stable or improved functional strength, and 92% of patients participated in MiM., Conclusion: The Exercise is Medicine initiative facilitated positive changes with patients showing stable or improved functional strength and endurance and increased participation in independent activity during inpatient stays., Competing Interests: Jessica MungerEmployment: TempusStock and Other Ownership Interests: Tempus Ashraf MohamedConsulting or Advisory Role: AllMed Healthcare Management, Medical Consultant NetworkSpeakers' Bureau: NovartisNo other potential conflicts of interest were reported.

Background: The optimum preparative regimen for unrelated donor marrow transplantation in patients with severe aplastic anaemia remains to be established. We investigated whether the combination of fludarabine, anti-thymocyte globulin, and total body irradiation (TBI) would enable reduction of the cyclophosphamide dose to less than 200 mg/kg while maintaining engraftment and having a survival similar to or better than that with standard regimens using a cyclophosphamide dose of 200 mg/kg (known to be associated with significant organ toxicity) for unrelated donor transplantation for severe aplastic anaemia. We have previously shown that cyclophosphamide at 150 mg/kg resulted in excess toxicity and its omission (0 mg/kg) resulted in unacceptable graft failure (three of three patients had secondary graft failure). Here we report results for the 50 mg/kg and 100 mg/kg cohorts., Methods: In a multicentre phase 1-2 study, patients (aged ≤65 years) with severe aplastic anaemia, adequate organ function, and an unrelated adult marrow donor HLA matched at the allele level for HLA A, B, C, and DRB1 or mismatched at a single HLA locus received bone marrow grafts from unrelated donors. All patients received anti-thymocyte globulin (rabbit derived 3 mg/kg per day, intravenously, on days -4 to -2, or equine derived 30 mg/kg per day, intravenously, on days -4 to -2), fludarabine (30 mg/m(2) per day, intravenously, on days -5 to -2), and TBI (2 Gy). Cyclophosphamide dosing started at 150 mg/kg and was de-escalated in steps of 50 mg/kg (to 100 mg/kg, 50 mg/kg, and 0 mg/kg). The primary endpoint was the selection of the optimum cyclophosphamide dose based on assessments of graft failure (primary or secondary), toxicity, and early death during 100 days of follow-up after the transplant; this is the planned final analysis for the primary endpoint. This trial is registered with ClinicalTrials.gov, number NCT00326417., Findings: 96 patients had bone marrow transplant. At day 100, 35 (92%) of 38 patients were engrafted and alive in the cyclophosphamide 50 mg/kg cohort and 35 (85%) of 41 in the 100 mg/kg cohort. Cyclophosphamide 50 mg/kg and 100 mg/kg resulted in posterior means for fatality without graft failure of 0·7% (credible interval 0-3·3) and 1·4% (0-4·9), respectively. Three patients (8%) had graft failure with cyclophosphamide 50 mg/kg and six (15%) with cyclophosphamide 100 mg/kg. Four (11%) patients had major regimen-related toxicity with cyclophosphamide 50 mg/kg and nine (22%) with cyclophosphamide 100 mg/kg. The most common organ toxicity was pulmonary (grade 3 or 4 dyspnoea or hypoxia including mechanical ventilation), and occurred in three (8%) and four (10%) patients given cyclophosphamide 50 mg/kg and 100 mg/kg, respectively., Interpretation: Cyclophosphamide at 50 mg/kg and 100 mg/kg with TBI 2 Gy, fludarabine, and anti-thymocyte globulin results in effective conditioning and few early deaths after unrelated donor transplantation for severe aplastic anaemia. These doses of cyclophosphamide provide a framework for further regimen optimisation strategies., Funding: US National Heart, Lung, and Blood Institute and National Cancer Institute., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: Leukocyte adhesion deficiency is a rare primary immune disorder caused by defects of the CD18 beta-integrin molecule on immune cells. The condition usually presents in early infancy and is characterized by deep tissue infections, leukocytosis with impaired formation of pus, and delayed wound healing. Allogeneic hematopoietic stem-cell transplantation offers the possibility of curative therapy, and with patient numbers at any individual center being limited, we surveyed the transplant experience at 14 centers worldwide., Methods: The course of 36 children with a confirmed diagnosis of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research., Results: At a median follow-up of 62 months (extending to 14 years), the overall survival rate was 75%. Myeloablative conditioning regimens were used in 28 patients, and reduced-intensity conditioning in 8 patients, with no deaths in this subgroup. Survival rates after matched family donor and unrelated donor transplants were similar, with 11 of 14 matched family donor and 12 of 14 unrelated donor recipients alive; mortality was greatest after haploidentical transplants, after which 4 of 8 children did not survive. Twenty-seven transplant recipients were alive, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases., Conclusions: Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients.

Sixty-three patients who had undergone a BMT at age < or = 18 years were evaluated cross-sectionally to determine cardiac function as well as the long-term prevalence, types, severity, and risk factors of cardiac abnormalities. Patients were > or = 1 year post-BMT and were evaluated by history, resting ECG, echocardiography (ECHO), exercise treadmill test, chest X-ray, pulmonary function tests and review of past cardiac studies. Patients were assigned a New York Heart Association (NYHA) class based on an activity and cardiac symptoms questionnaire. Pretransplant preparative regimens included high-dose cyclophosphamide (CY) and total body/lymphoid irradiation (n = 38), CY in combination with other chemotherapy (n = 22), and other drug combinations (n = 3). Forty patients (63.5%) had received prior anthracyclines (median 307 mg/m2). Patients' ages ranged from 1.9 to 32 years (median 10.9 years) with median follow-up of 3.3 years (range 1-16.3 years). Twenty-six patients (41.3%) had a cardiac abnormality detected at follow-up. In 21 patients the abnormal finding had not been present at the pre-BMT evaluation. Ten patients (16.4%) had resting ECG abnormalities. Left ventricular ejection fraction (LVEF) by ECHO was mildly decreased to 50-54% in three patients and markedly decreased to 40% in one patient. Only one patient (1.7%) developed a mildly abnormal shortening fraction of 27%. All patients with ECHO abnormalities were asymptomatic. Twenty-three of 31 patients > or = 9 years of age (74%) who underwent a treadmill exercise test had a borderline or abnormal response to exercise. There was no correlation between demographic factors, previous therapy, preparative regimen or length of follow-up with the post-BMT ECG, ECHO and treadmill abnormalities. Overall, eight patients (12.7%) were symptomatic and NYHA class II or III, and all had abnormal exercise tests. The presence of symptoms and NYHA class were predictors for oxygen consumption during exercise (P = 0.03 and 0.02, respectively) and tended to predict overall treadmill results also. Late cardiac abnormalities do occur following BMT in childhood and thus, there is a clear need for continued, serial long-term cardiac evaluation in transplant survivors. Evaluations should include exercise stress testing to detect inadequate cardiac output as well as oxygen consumption during exercise.