Lung volume reduction surgery: a micro-costing analysis from a national tertiary referral Centre.

OBJECTIVES: Lung volume reduction surgery (LVRS) is a clinically effective palliation procedure for patients with chronic obstructive pulmonary disease (COPD). LVRS has recently been commissioned by the NHS England. In this study, a costing model was developed to analyse cost and resource implications of different LVRS procedures. METHODS: Three pathways were defined by their surgical procedures: bronchoscopic endobronchial valve insertion (EBV-LVRS), video assisted (VATS-LVRS), and robotic assisted LVRS (RATS-LVRS). The costing model considered use of hospital resources from the LVRS decision until 90-days after hospital admission. The model was calibrated with data obtained from an observational study, electronic health records, and expert opinion. Unit costs were obtained from the hospital finance department and reported in 2021-Euros. RESULTS: VATS-LVRS was associated with the lowest cost at €12,896 per patient. This compares to the costs of EBV-LVRS at €15,598 per patient and €13,305 per patient for RATS-LVRS. A large component of EBV-LVRS costs were accrued secondary to complications, including revision EBV-LVRS. CONCLUSIONS: This study presents a comprehensive model framework for the analysis of hospital-related resource use and costs for the three surgical modalities. In the future, service commissioning agencies, hospital management, and clinicians can use this framework to determine their modifiable resource use (composition of surgical teams, use of staff and consumables, planned length of stay, and revision rates for EBV-LVRS) and to assess the potential cost implications of changes in these parameters.

Monopolar diathermy versus a vessel-sealing device for reducing postoperative drain output after simple mastectomy: randomized clinical trial.

BACKGROUND: Electrosurgical devices are commonly used during mastectomy for simultaneous dissection and haemostasis, and can provide potential benefits regarding vessel and lymphatic ligation. The aim of this prospective RCT was to assess whether using a vessel-sealing device (LigaSure™) improves perioperative outcomes compared with monopolar diathermy when performing simple mastectomy. METHODS: Patients were recruited prospectively and randomized in a 1 : 1 manner to undergo simple mastectomy using either LigaSure™ or conventional monopolar diathermy at a single centre. The primary outcome was the number of days the drain remained in situ after surgery. Secondary outcomes of interest included operating time and complications. RESULTS: A total of 86 patients were recruited (42 were randomized to the monopolar diathermy group and 44 were randomized to the LigaSure™ group). There was no significant difference in the mean number of days the drain remained in situ between the monopolar diathermy group and the LigaSure™ group (7.75 days versus 8.23 days; P = 0.613) and there was no significant difference in the mean total drain output between the monopolar diathermy group and the LigaSure™ group (523.50 ml versus 572.80 ml; P = 0.694). In addition, there was no significant difference in the mean operating time between the groups, for simple mastectomy alone (88.25 min for the monopolar diathermy group versus 107.20 min for the LigaSure™ group; P = 0.078) and simple mastectomy with sentinel lymph node biopsy (107.20 min for the monopolar diathermy group versus 114.40 min for the LigaSure™ group; P = 0.440). CONCLUSION: In this double-blinded single-centre RCT, there was no difference in the total drain output or the number of days the drain remained in situ between the monopolar diathermy group and the LigaSure™ group. REGISTRATION NUMBER: EudraCT 2018-003191-13 BEAUMONT HOSPITAL REC 18/66.

Establishing an expert opinion framework for lung volume reduction in Ireland: a Delphi consensus technique.

BACKGROUND: Lung volume reduction (LVR) is an effective treatment option offered to patients with emphysema. There is no formalised LVR referral network in Ireland. A rigorous approach to agreeing and implementing a LVR referral framework in an Irish context is required. A Delphi process was used to provide a basis for a framework of multi-disciplinary teams (MDTs) which can provide LVR as a management option. A Delphi process offers a framework for understanding variations and developing a consensus from expert opinion. AIM: The aim of this study was to develop consensus on recommendations for LVR referral guidelines in an Irish context and provide a national scope based on current practice and evidence. DESIGN: In accordance with Guidance on Conducting and Reporting Delphi Studies, a consensus-building Delphi study was performed. Thirty-three statements informed from review of research literature were identified and presented to participants. Evaluation of the statements was performed by an expert panel using a 5-point Likert scale. ≥ 70% agreement was defined as consensus and items with a consensus rating of < 70% were revised during the process. In total, Delphi questionnaires were distributed to 18 experts with a response rate of 78% (n = 14) and a follow-up response-rate of 50% (n = 7). SETTING/PARTICIPANTS: The expert panel in Ireland consisted of representatives from respiratory medicine, cardiothoracic surgery and allied-health professionals with expertise in COPD care. RESULTS: Of the initial 33 statements in five dimensions, there were consensus regarding 31 statements. CONCLUSIONS: The 31 statements agreed through this Delphi study clarify a coherent direction for development of a LVR framework in Ireland. The Delphi study methodology described is a useful process to reach consensus among multi-disciplinary experts.

Validation and comparison of two new scoring systems for the prediction of complicated versus uncomplicated appendicitis.

OBJECTIVES: To validate the Atema and APSI scoring systems in the diagnosis of complicated vs uncomplicated appendicitis. To compare these scoring systems with computed tomography (CT) imaging alone to establish which method provides most accurate prediction of complicated vs uncomplicated appendicitis. METHODS: This was a retrospective review of a sample of 160 patients that underwent appendicectomy and CT imaging for suspected appendicitis between 2018 and 2021 in a tertiary university teaching hospital. Each scoring system was applied to all patients and results analysed and compared with the effectiveness of CT imaging, RESULTS: 32.5% (n = 52) were found to have complicated appendicitis and 67.5% (n = 108) uncomplicated appendicitis. Application of the Atema score to our cohort of patients resulted in a sensitivity 76.9% [CI (64.2, 87.5), specificity 58.7% [CI (48.9, 68.1)], PPV 47.1% [CI (40.5, 53.8) and NPV 84.2% [CI (76.0, 89.9)]. By comparison, the APSI yielded a sensitivity 50.9% [CI (36.6, 65.4)], specificity 76.1% [CI (67.0, 87.8)], PPV 50% [CI (39.2, 60.6)] and NPV 76% [CI (71.1, 81.7)]. Radiology prediction of complicated vs uncomplicated appendicitis with CT imaging showed sensitivity 46% [CI (32.2, 60.5)], specificity 79%; [CI (69.8, 86)], PPV 51% [CI (39.6, 62.5)] and NPV 75% [CI (69.8, 79.9)]. CONCLUSION: By comparing the APSI and Atema et al. scoring systems with CT reporting in our hospital, it appears that the Atema may confer some benefit in stratifying patient risk of complicated versus uncomplicated appendicitis. Further larger scale prospective studies are required.

Composite quality measures of abdominal surgery at a population level: systematic review.

BACKGROUND: Measurement of surgical quality at a population level is challenging. Composite quality measures derived from administrative and clinical information systems could support system-wide surgical quality improvement by providing a simple metric that can be evaluated over time. The aim of this systematic review was to identify published studies of composite measures used to assess the overall quality of abdominal surgical services at a hospital or population level. METHODS: A search was conducted in PubMed and MEDLINE for references describing measurement instruments evaluating the overall quality of abdominal surgery. Instruments combining multiple process and quality indicators into a single composite quality score were included. The identified instruments were described in terms of transparency, justification, handling of missing data, case-mix adjustment, scale branding and choice of weight and uncertainty to assess their relative strengths and weaknesses (PROSPERO registration: CRD42022345074). RESULTS: Of 5234 manuscripts screened, 13 were included. Ten unique composite quality measures were identified, mostly developed within the past decade. Outcome measures such as mortality rate (40 per cent), length of stay (40 per cent), complication rate (60 per cent) and morbidity rate (70 per cent) were consistently included. A major challenge for all instruments is the reliance of valid administrative data and the challenges of assigning appropriate weights to the underlying instrument components. A conceptual framework for composite measures of surgical quality was developed. CONCLUSION: None of the composite quality measures identified demonstrated marked superiority over others. The degree to which administrative and clinical data influences each composite measure differs in important ways. There is a need for further testing and development of these measures.

Hospital response to Activity-Based Funding and price incentives: Evidence from Ireland.

Activity-Based Funding (ABF) is a funding policy incentivising hospitals to deliver more efficient care. ABF can be complemented by additional price incentives to further drive hospital efficiency. In 2016, ABF was introduced for public patients admitted to Irish public hospitals. Additionally, a price incentive to perform laparoscopic cholecystectomy as day-case surgery was introduced in 2018. Private patient activity in public hospitals was subject to neither ABF nor price incentive. Using national Hospital In-Patient-Enquiry activity data 2013-2019, we evaluated the impact of ABF and the price incentive for laparoscopic cholecystectomy surgery in Ireland. We exploit variation in hospital payment for public and private patients treated in public acute Irish hospitals and employ a Propensity Score Matching Difference-in-Differences approach. We estimate the funding change impacts across outcomes measuring the proportion of day-case admissions and length of stay. We found no significant impact for either outcomes linked to ABF introduction. Similarly, no impacts linked to the price incentive were observed. It appears providers of laparoscopic cholecystectomy in Irish public hospitals did not react to the new funding mechanisms. The implementation of the funding policies did not improve hospital efficiency. Further strengthening of these new funding mechanisms are required to deliver more efficient care.

Patient and hospital-level factors associated with time to surgery after hip fracture in Ireland: Analysis of national audit data 2016-2020.

INTRODUCTION: In hip fracture care, time to surgery (TTS) is a commonly used quality indicator associated with patient outcomes including mortality. This study aimed to identify patient and hospital-level characteristics associated with TTS in Ireland. METHODS: National data from the Irish Hip Fracture Database (IHFD) (2016-2020) were analysed along with hospital-level characteristics obtained from a 2020 organisational survey. Generalised linear model regression was used to explore the association of TTS with case-mix, surgical details, hospital-level staffing and specific protocols recommended to expedite surgery. RESULTS: A total of 14,951 patients with surgically treated hip fracture from 16 hospitals were included (Mean age= 80.6 years (SD=8.8), 70.4% female). Mean TTS was 40.9 h (SD=60.3 h). Case-mix factors associated with longer TTS were male sex and higher American Society of Anaesthesiologists (ASA) grade. Other factors found to be associated with longer TTS included low pre-morbid mobility, inter-hospital transfer, weekday presentation, pre-operative medical physician assessment, intracapsular fracture type, arthroplasty surgery, general anaesthesia, consultant grade of surgeon and lower hospital-level orthopaedic surgical capacity. The oldest age-group and pre-fracture nursing home residence were associated with shorter TTS when adjusted for other case-mix factors. None of four explored protocols for expediting surgery were associated with TTS. CONCLUSION: Patients with more comorbidity experience longer surgical delay after hip fracture in Ireland, in line with international research. Low availability of senior orthopaedic surgeons in Ireland may be delaying hip fracture surgery. Pathway of presentation, including via inter-hospital transfer or hospital bypass, is an important factor that requires further exploration. Further research is required to identify successful system-level protocols and interventions that may expedite hip fracture surgery within this setting.

To develop, implement and evaluate an integrated care pathway for patients presenting with pneumothorax.

BACKGROUND AND PURPOSE: Pneumothorax is a common presentation to acute healthcare services in Ireland, however there is wide variation in management approaches between centres. There is robust evidence to demonstrate that ambulatory management of pneumothorax is feasible and safe. The purpose of this study was to evaluate whether the implementation of an integrated care pathway (ICP) for pneumothorax patients with a focus on ambulatory care would be economically beneficial for the healthcare system. METHODS: This study developed, implemented and evaluated an ICP for all patients presenting with pneumothorax, with a specific focus on ambulatory management for suitable patients. The ICP was designed to be utilised in the Irish healthcare setting, and was evaluated using a prospective multi-centre observational study, with a rigorous economic analysis at the centre of study design. MAIN FINDINGS: Implementation of the ICP resulted in a statistically significant reduction in inpatient length of stay of 2.84 days from 7.4 to 4.56 days (p = 0.001). The incremental per patient cost reduction of treating a patient according to the pneumothorax ICP was 2314 euro. There were no adverse events related to drain insertion at the study sites. CONCLUSIONS: This study demonstrates therefore that standardisation of care for pneumothorax patients with a focus on ambulatory management are economically beneficial for the publicly-funded healthcare service. It is envisaged that this work will be used to inform healthcare policy at a national level across Ireland.

Treatment of inborn errors of immunity patients with inflammatory bowel disease phenotype by allogeneic stem cell transplantation.

Patients with inborn errors of immunity (IEI) can suffer from treatment-refractory inflammatory bowel disease (IBD) causing failure to thrive and consequences of long-term multiple immunosuppressive treatments. Allogeneic haematopoietic stem cell transplantation (alloHSCT) can serve as a curative treatment option. In this single-centre retrospective cohort study we report on 11 paediatric and young adult IEI patients with IBD and failure to thrive, who had exhausted symptomatic treatment options and received alloHSCT. The cohort included chronic granulomatous disease (CGD), lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency, STAT3 gain-of-function (GOF), Wiskott-Aldrich syndrome (WAS), dedicator of cytokinesis 8 (DOCK8) deficiency and one patient without genetic diagnosis. All patients achieved stable engraftment and immune reconstitution, and gastrointestinal symptoms were resolved after alloHSCT. The overall survival was 11/11 over a median follow-up of 34.7 months. Graft-versus-host disease (GVHD) was limited to grade I-II acute GVHD (n = 5), one case of grade IV acute GVHD and one case of limited chronic GVHD. Since treatment recommendations are limited, this work provides a centre-specific approach to treatment prior to transplant as well as conditioning in IEI patients with severe IBD.

A comparison of four quasi-experimental methods: an analysis of the introduction of activity-based funding in Ireland.

BACKGROUND: Health services research often relies on quasi-experimental study designs in the estimation of treatment effects of a policy change or an intervention. The aim of this study is to compare some of the commonly used non-experimental methods in estimating intervention effects, and to highlight their relative strengths and weaknesses. We estimate the effects of Activity-Based Funding, a hospital financing reform of Irish public hospitals, introduced in 2016. METHODS: We estimate and compare four analytical methods: Interrupted time series analysis, Difference-in-Differences, Propensity Score Matching Difference-in-Differences and the Synthetic Control method. Specifically, we focus on the comparison between the control-treatment methods and the non-control-treatment approach, interrupted time series analysis. Our empirical example evaluated the length of stay impact post hip replacement surgery, following the introduction of Activity-Based Funding in Ireland. We also contribute to the very limited research reporting the impacts of Activity-Based-Funding within the Irish context. RESULTS: Interrupted time-series analysis produced statistically significant results different in interpretation, while the Difference-in-Differences, Propensity Score Matching Difference-in-Differences and Synthetic Control methods incorporating control groups, suggested no statistically significant intervention effect, on patient length of stay. CONCLUSION: Our analysis confirms that different analytical methods for estimating intervention effects provide different assessments of the intervention effects. It is crucial that researchers employ appropriate designs which incorporate a counterfactual framework. Such methods tend to be more robust and provide a stronger basis for evidence-based policy-making.

Geographic variation in hip fracture surgery rate, care quality and outcomes: a comparison between national registries in Ireland and Denmark.

Ireland and Denmark have similar hip fracture surgery rates but differences in care quality indicators and patterns of intracapsular fracture repair. Very high variation in total hip arthroplasty rate within both countries and higher observed early mortality in Denmark require further investigation. PURPOSE: To explore and compare geographic variation of hip fracture surgery rate, care quality and outcomes in Ireland and Denmark. METHODS: Patients aged ≥ 65 years with surgically treated hip fracture were included from the Irish Hip Fracture Database (years = 2017-2020, n = 12,904) and the Danish Multidisciplinary Hip Fracture Registry (years = 2016-2017, n = 12,924). The age and sex standardised rate of hip fracture surgery and the proportion of patients with seven process quality indicators, three surgery types and four outcomes were calculated. Systematic components of variation (SCV) were calculated based on hospital area (6 Irish hospital groups, 5 Danish regions). RESULTS: The age and sex standardised rate of hip fracture surgery per 1000 older population in 2017 was 4.7 (95% CI = 4.4-5.1) in Ireland and 5.3 (95% CI = 5.1-5.5) in Denmark. Ireland had lower rates of surgery within 36 h (59% versus 84%), nutritional assessment (27% versus 84%) and pre-discharge mobility recording (52% versus 92%). Patterns of intracapsular fracture repair also differed between countries (hemiarthroplasty: Ireland = 85%, Denmark = 52%). Both countries had very high variation for total hip arthroplasty (THA) provision (SCV Ireland = 10.6, Denmark = 97.9). Ireland had longer hospital stays (median 12 versus 7 days), but lower 7-day (1.0% versus 3.1%) and 14-day (2.0% versus 5.5%) mortality. CONCLUSION: Ireland and Denmark have similar hip fracture surgery rates, but differences in care quality, surgery patterns and outcomes. High variation in THA provision and observed differences in mortality require further exploration. In Ireland, there is scope for improvement regarding early surgery, mobility, nutrition assessment and improved post-discharge follow-up.

Is robotic lobectomy cheaper? A micro-cost analysis.

Higher capital costs and operating room costs associated with Lobectomy via Robot Assisted Thoracic Surgery (RATS) have previously been suggested as the principal contributors to the elevated overall cost. This study uses a micro-costing approach to a previous analysis of clinical outcomes of RATS, Video-Assisted Thoracic Surgery (VATS) and Open Lobectomy to evaluate the most significant cost drivers for the higher cost of robot-assisted lobectomy. A micro-costing model was developed to reflect the pathway of patients from day of surgery through the first 30 days following lobectomy. Costs were provided for RATS, VATS and Open approaches. Sensitivity analysis was performed specifically in the area of staff costs. A threshold sensitivity analysis of the overall cost components was also performed. Total cost per case for the RATS approach was €13,321 for the VATS approach €11,567, and for the Open approach €12,582. The overall cost differences were driven primarily by the elevated consumable costs associated with RATS Lobectomy. Capital costs account for a relatively small proportion of the per-case cost difference. This study presents a detailed analysis of the cost drivers for lobectomy, modelled for the three primary surgical approaches. We believe this is a useful tool for surgeons, hospital management, and service commissioning agencies to accurately and comprehensively determine where cost savings can be applied in their programme to improve the cost-effectiveness of RATS lobectomy.

Impact of COVID-19 on hip fracture care in Ireland: findings from the Irish Hip Fracture Database.

PURPOSE: To describe the impact of COVID-19 on hip fracture care during the first 6 months of the pandemic. METHODS: A secondary analysis of 4385 cases in the Irish Hip Fracture Database from 1st June 2019 to 31st August 2020 was conducted. RESULTS: Hip fracture admissions decreased by 15% during the study period (p < 0.001). Patient characteristics were largely unchanged as the majority of cases occurred in females over 80 years admitted from home. Adherence to many of the Irish Hip Fracture Standards (IHFS) changed following the COVID-19 pandemic. There was an increase in patients admitted to an orthopaedic ward from Emergency Department (ED) within 4 h from 27 to 36% (p < 0.001). However, the proportion of patients reviewed by a geriatrician reduced from 85% pre-COVID to 80% (p < 0.001). Fewer patients received a bone health assessment [90% from 95% (p < 0.001)] and specialist falls assessment [(82% from 88% (p < 0.001)]. No change was seen in time to surgery or incidence of pressure injuries. There was a significant decrease in length of stay from 18 to 14 days (p < 0.001). There was an increase in patients discharged home during the COVID-19 period and a decrease in patients discharged to rehabilitation, convalescence or nursing home care. There was no statistically significant change in mortality. CONCLUSION: Healthcare services were widely restructured during the pandemic, which had implications for hip fracture patients. There was a notable change in compliance with the IHFS. Multidisciplinary teams involved in hip fracture care should be preserved throughout any subsequent waves of the pandemic.

Impact of the COVID-19 pandemic on provision and outcomes of emergency abdominal surgery in Irish public hospitals.

BACKGROUND: The SARS-CoV-2 pandemic caused severe disruption to scheduled surgery in Ireland but its impact on emergency abdominal surgery (EAS) is unknown. AIMS: The primary objective was to identify changes in volume, length of stay (LOS), and survival outcomes following EAS during the pandemic. A secondary objective was to evaluate differences in EAS patient flow including admission source, ITU utilisation, discharge destination, and readmission rates. METHODS: Using a national administrative dataset, demographic, comorbidity, and patient flow data on 5611 patients admitted for EAS between 2018 and 2020 were extracted. Pre-pandemic and pandemic timeframes were compared using graphic and regression analyses, and bivariate logistic regression, adjusting for demographics and case-mix. RESULTS: There was a 19.9% decrease in EAS during the 2020 COVID-19 pandemic with no difference in comorbidity, nor in the commonest procedures. Most patients (92.4%) were admitted from home. In-hospital post-operative mortality was unchanged (7.6%). Patients over 80 comprised 16.3% of EAS pre-COVID, but 17.9% during COVID. Average total LOS reduced significantly by 4.9 days and 3.5 days during COVID-19 waves 1 (29 Feb 2020-30 June 2020) and 2 (1 July 2020-30 Nov 2020), respectively. During wave 1, pre-operative LOS reduced (1 day) and ICU LOS was significantly shorter (0.8 days), but similar change was not observed during wave 2. CONCLUSIONS: Significant improvements in patient flow following admission for EAS during the pandemic were observed. These changes were not associated with greater mortality nor increased readmission rates and offer important insights into optimal delivery of EAS services.

Neoadjuvant Short-Course Radiotherapy for Upper Third Rectal Tumors: Systematic Review and Individual Patient Data Metaanalysis of Randomized Controlled Trials.

BACKGROUND: There is no consensus on the use of neoadjuvant radiotherapy for tumors of the upper third of the rectum. Due to conflicting findings in high-quality trials and significant long-term side effects associated with neoadjuvant radiotherapy, the benefit of neoadjuvant radiotherapy for upper third rectal tumors is less certain than for lower two third rectal tumors. This metaanalysis compares oncological outcomes with neoadjuvant radiotherapy and surgery versus surgery alone for upper third rectal tumors. PATIENTS AND METHODS: PubMed, Embase, and the Cochrane library databases were searched. Randomized controlled trials (RCT) comparing neoadjuvant radiotherapy and surgery versus surgery alone for resectable rectal cancer were included. Individual patient data were sought from the principal investigator of each eligible trial for comparative data on patients with upper third rectal tumors. The main outcomes measured were survival outcomes, oncological outcomes, postoperative morbidity, and late toxicity. RESULTS: Individual patient data from two RCTs examining outcomes in 758 patients were obtained. Published data from one further RCT containing comparable data on upper third rectal tumors were included in analysis of local recurrence. In patients with curative surgery, there was no significant reduction in local recurrence or significant improvement in overall survival or disease-free survival with neoadjuvant radiotherapy (LR RR: 0.38, 95% CI 0.14-1.04, p = 0.06) (OS RR: 1.10, 95% CI 0.98-1.24, p = 0.11) (DFS RR: 1.11, 95% CI 0.97-1.26, p = 0.13). CONCLUSIONS: The benefit of neoadjuvant radiotherapy for upper third rectal tumors is not certain, and surgery alone for patients with potentially curative disease at preoperative staging may be sufficient.

A Randomized Clinical Trial Evaluating the Efficacy and Quality of Life of Antibiotic-only Treatment of Acute Uncomplicated Appendicitis: Results of the COMMA Trial.

OBJECTIVE: Evaluate the efficacy and quality of life associated with conservative treatment of acute uncomplicated appendicitis. SUMMARY BACKGROUND DATA: Conservative management with antibiotics only has emerged as a potential treatment option for acute uncomplicated appendicitis. However the reported failure rates are highly variable and there is a paucity of data in relation to quality of life. METHODS: Symptomatic patients with radiological evidence of acute, uncomplicated appendicitis were randomized to either intravenous antibiotics only or undergo appendectomy. RESULTS: One hundred eighty-six patients underwent randomization. In the antibiotic-only group, 23 patients (25.3%) experienced a recurrence within 1 year following randomization. There was a significantly better EQ-VAS quality of life score in the surgery group compared with the antibiotic-only group at 3 months (94.3 vs 91.0, P < 0.001) and 12 months postintervention (94.5 vs 90.4, P < 0.001). The EQ-5D-3L quality-of-life score was significantly higher in the surgery group indicating a better quality of life (0.976 vs 0.888, P < 0.001). The accumulated 12-month sickness days was 3.6 days shorter for the antibiotics only group (5.3 vs 8.9 days; P < 0.01). The mean length of stay in both groups was not significantly different (2.3 vs 2.8 days, P = 0.13). The mean total cost in the surgery group was significantly higher than antibiotics only group (€4,816 vs €3,077, P < 0.001). CONCLUSIONS: Patients with acute, uncomplicated appendicitis treated with antibiotics only experience high recurrence rates and an inferior quality of life. Surgery should remain the mainstay of treatment for this commonly encountered acute surgical condition.

Unstimulated apheresis for chimeric antigen receptor manufacturing in pediatric/adolescent acute lymphoblastic leukemia patients.

Autologous unstimulated leukapheresis product serves as starting material for a variety of innovative cell therapy products, including chimeric antigen receptor (CAR)-modified T-cells. Although it may be reasonable to assume feasibility and efficiency of apheresis for CAR-T cell manufacture, several idiosyncrasies of these patients warrant their separate analysis: target cells (mononuclear cells [MNC] and T-cells) are relatively few which may instruct the selection of apheresis technology, low body weight, and, hence, low total blood volume (TBV) can restrict process and product volume, and patients may be in compromised health. We here report outcome data from 46 consecutive leukaphereses in 33 unique pediatric patients performed for the purpose of CD19-CAR-T-cell manufacturing. Apheresis targets of 2×109 MNC/1×109 T-cells were defined by marketing authorization holder specification. Patient weight was 8 to 84 kg; TBV was 0.6 to 5.1 L. Spectra Optia apheresis technology was used. For 23 patients, a single apheresis sufficed to generate enough cells and manufacture CAR-T-cells, the remainder required two aphereses to meet target dose and/or two apheresis series because of production failure. Aphereses were technically feasible and clinically tolerable without serious adverse effects. The median collection efficiencies for MNC and T-cells were 53% and 56%, respectively. In summary, CAR apheresis in pediatric patients, including the very young, is feasible, safe and efficient, but the specified cell dose targets can be challenging in smaller children. Continuous monitoring of apheresis outcomes is advocated in order to maintain quality.