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Introduction While surgical interventions for temporomandibular joint (TMJ) ankylosis are well-documented, there is lack of consensus regarding the ideal approach in pediatric patients. Surgical interventions include gap arthroplasty, interpositional arthroplasty, or total joint reconstruction. Methods A systematic review of PubMed (Jan 1, 1990-Jan 1, 2017) and Scopus (Jan 1, 1990-Jan 1, 2017) was performed and included studies in English with at least one patient under the age of 18 diagnosed with TMJ ankylosis who underwent surgical correction. Primary outcomes of interest included surgical modality, preoperative maximum interincisal opening (MIO) (MIOpreop), postoperative MIO (MIOpostop), ΔMIO (ΔMIO = MIOpostop - MIOpreop), and complications. Results Twenty-four case series/reports with 176 patients and 227 joints were included. By independent sample t tests MIOpostop (mm) was greater for gap arthroplasty (30.18) compared to reconstruction (27.47) (t = 4.9, P = 0.043), interpositional arthroplasty (32.87) compared to reconstruction (t = 3.25, P = 0.002), but not for gap compared to interpositional (t = -1.9, P = 0.054). ΔMIO (mm) was greater for gap arthroplasty (28.67) compared to reconstruction (22.24) (t = 4.2, P = 0.001), interpositional arthroplasty (28.33) compared to reconstruction (t = 3.27, P = 0.002), but not for interpositional compared to gap (t = 0.29, P = 0.33). Weighted-average follow-up time was 28.37 months (N = 164). 4 of 176 (2.27%) patients reported development of re-ankylosis. There was no significant difference in occurrence of re-ankylosis between interventions. Conclusions Given the technical ease of gap arthroplasty and nonsignificant differences in ΔMIO, MIOpostop, or occurrence of re-ankylosis between gap and interpositional arthroplasty, gap arthroplasty should be considered for primary ankylosis repair in pediatric patients, with emphasis on postoperative physiotherapy to prevent recurrent-ankylosis.

Background: Acellular dermal matrices (ADMs) were first incorporated into direct-to-implant (DTI) breast reconstruction by the senior author in 2001 and have since become foundational to implant-based reconstruction. ADM composition has evolved recently and now includes perforated types, which some speculate decrease the likelihood of seroma. The authors performed a retrospective review of perforated (P-ADM) and nonperforated (NP-ADM) ADM-assisted direct-to-implant breast reconstruction patients to evaluate differences in complication rates. Methods: Retrospective review of direct-to-implant breast reconstruction patients operated on by a single surgeon (CAS) from 2011 to 2018 was conducted. Patient and operative characteristics, including ADM type, were recorded. A propensity score matching algorithm accounting for potentially confounding variables was developed, followed by univariate analysis to evaluate the association between ADM perforation and postoperative complications. Results: The review began with 409 patients (761 breasts). Following exclusion of patients with missing demographic information, lack of ADM in their reconstruction, and follow-up times of less than 4 weeks, 364 patients (680 breasts) were included for analysis. A total of 530 (77.94%) and 150 (22.06%) breasts received NP-ADM and P-ADM, respectively. After propensity score matching, there were 294 breasts, composed of equal numbers of P-ADM and NP-ADM recipients. Univariate analysis showed no association between ADM type and any postoperative complication. Conclusions: The complication profile of direct-to-implant breast reconstruction appears to be unaffected by the use of P-ADM or NP-ADM. Current understanding of the association between ADM type and clinical outcomes would benefit from multi-institution, prospective, randomized trials.

It is presently considered the standard of care to perform many routine intra-abdominal operations using a minimally invasive approach. The authors recently identified a racial disparity in access to a laparoscopic approach to inguinal hernia repair, cholecystectomy, appendectomy, and colectomy. The present study further evaluates this patient cohort to assess the relationship between the race and postoperative complications and test the mediating effect of the selected surgical approach.After institutional review board approval, patients in the American College of Surgeons National Surgical Quality Improvement Program database who underwent inguinal hernia repair, cholecystectomy, appendectomy, or colectomy in 2016 were identified. Patient demographics, including the self-reported race and ethnicity, as well as clinical, operative, and postoperative variables were recorded. After the exclusion of cases associated with diagnoses of cancer, a 4:1 propensity score matching algorithm generated a clinically balanced cohort of patients of white and black self-reported race. The mediating effect of an open approach to surgery on the relationship between black self-reported race and postoperative complications was evaluated via a series of regressions.There were 41,340 unilateral inguinal hernia repairs, 3182 bilateral inguinal hernia repairs, 60,444 cholecystectomies, 50,523 appendectomies, and 58,012 colectomies included in the database in 2017. Exclusion of cases associated with cancer and subsequent propensity score matching returned 17,540 unilateral hernia repairs, 890 bilateral hernia repairs, 23,865 cholecystectomies, 11,660 appendectomies, and 12,320 colectomies. On mediation analysis, any complication, severe complication, and death were significant when regressed on black self-reported race (any: odds ratio [OR] = 1.210, 95% confidence interval [CI] = 1.132-1.291, P 0.001; severe: OR = 1.352, 95% CI = 1.245-1.466, P 0.001; death: OR = 1.358, 95% CI = 1.000-1.818, P = 0.044), and open surgery was a significant mediator in the incidence of any complication and severe complication (any: OR = 1.180, 95% CI = 1.105-1.260, P 0.001 and severe: OR = 1.307, 95% CI = 1.203-1.418, P 0.001).These findings underscore the importance of access to a minimally invasive approach to surgery. However, other factors may contribute to racial disparities in postoperative complications after common abdominal operations.

Introduction: Prognosis for adult B-cell Acute Lymphoblastic Leukaemia (B-ALL) is poor and there is currently no licensed CD19 Chimeric Antigen Receptor (CAR) therapeutic. We developed a novel CD19 CAR (CAT-41BBz CAR) with a fast off-rate, designed to result in more physiological T-cell activation, reduce toxicity and improve engraftment. We describe updated data from the Phase I ALLCAR19 (NCT02935257) study of AUTO1 in relapsed/refractory adult B-ALL. Methods: Manufacturing: AUTO1 utilises non-mobilised autologous leukapheresate. The first 6 products were generated using a standard dynabead/WAVE bioreactor process and subsequent products using a semi-automated closed process. Study design: Patients aged >16y underwent lymphodepletion with fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) followed by split dose CAR T-cell infusion (Day 0: if ≥20% Bone Marrow (BM) blasts, infuse 10 x 106 CAR T-cells; if Results: As of 13 May 2020, 24 patients have been leukapheresed, 23 products manufactured and 19 patients received at least 1 dose of AUTO1. The median age was 43y (range 18-62), 26% had prior blinatumomab, 47% had prior inotuzumab ozogamicin and 63% had prior hematopoietic stem cell transplantation (HSCT). At the time of pre-conditioning, 42% had ≥50% BM blasts. No patients experienced ≥Grade 3 CRS (Lee criteria), 3/19 (16%) experienced Grade 3 ICANS that swiftly resolved with steroids. Of 19 infused patients, 16/19 (84%) achieved Minimal Residual Disease (MRD) negative complete response (CR). Currently 6 patients have died, none related to AUTO1. 11/19 (58%) patients remain on study and continue in MRD negative remission at a median follow up of 12.2 months (range 0.6-24.4m). To date, only 2 patients underwent HSCT whilst in remission. For all treated patients, the event-free survival (EFS) at 6 months was 62% and 76% for those whose products were manufactured using the closed process. Patients exhibited robust CAR expansion (mean peak CAR T levels 716,769 copies/µg DNA). Conclusions: AUTO1 has a tolerable safety profile in adult patients with r/r B-ALL despite high disease burden. Early data shows high remission rates with 84% achieving MRD negative CR. This preliminary data supports the further development of AUTO1 as a standalone treatment in patients with r/r B-ALL. Data from additional patients and longer follow up will be presented. Furthermore, data from extension cohorts of patients with low- and high- grade B-cell Non-Hodgkin's lymphoma and chronic lymphocytic leukaemia will be presented. Figure Disclosures Roddie: Celgene: Honoraria; Gilead: Honoraria; Novartis: Honoraria. O'Reilly:Gilead: Honoraria; Novartis: Honoraria, Other: Travel support. Hartley:ADC Therapeutics: Consultancy, Current equity holder in publicly-traded company, Research Funding. Linch:Autolus: Consultancy. Pule:UCLB: Patents & Royalties; Mana Therapeutics: Other: entitled to share of revenue from patents filed by UCL; Autolus: Current Employment, Other: owns stock in and receives royalties, Patents & Royalties. Peggs:Autolus: Consultancy.

Background: Sepsis is an uncommon occurrence after appendectomy, but the morbidity and mortality of patients who develop sepsis after appendectomy remains exceedingly high. The purpose of ...

Laparoscopy has become the standard of care for the majority of cases for inguinal hernia repair, cholecystectomy, appendectomy, and colectomy due to the shortened patient recovery time compared to open surgery. This study sought to determine if there exists racial disparity in access to a laparoscopic approach to these common surgeries. This was an IRB-approved retrospective study utilizing data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Individuals who underwent inguinal hernia repair, cholecystectomy, appendectomy, and colectomy in 2016 were identified. Information on self-reported race and ethnicity and other demographic and pre-operative clinical covariates were recorded. Propensity matching was conducted to evaluate the association between race and a laparoscopic approach to surgery. There were 44,522, 60,444, 50,523, and 58,012 cases of inguinal hernia repair, cholecystectomy, appendectomy, and colectomy identified, respectively. Of these patients, 8.38, 8.76, 6.69, and 9.02% self-identified as black, respectively. Confounding effects of variables other than race were balanced by propensity matching. After propensity matching, there were 7460, 10,574, 10,470, and 6758 cases of hernia repair, cholecystectomy, colectomy, and appendectomy, respectively. On univariate (Chi square) analysis with laparoscopic surgery as the primary outcome, black race was significantly associated with lower likelihood of undergoing a minimally-invasive surgical approach in all four surgical procedures under investigation (33.86% of white patients and 21.69% of black patients, p

Introduction: 2nd generation CD19 CAR T cells show unprecedented efficacy in B-ALL, but several challenges remain: (1) scaling manufacture to meet patient need and (2) feasibility of generating products from lymphopenic patients post allogeneic stem cell transplant (allo-SCT). To overcome these issues we propose: (1) use of the CliniMACS Prodigy (Miltenyi Biotec), a semi-automated cGMP platform that simplifies CAR T cell manufacture and (2) the use of matched donor T cells to overcome the challenge posed by patient lymphopenia, albeit this may come with a heightened risk of graft versus host disease (GvHD). CARD (NCT02893189) is a Phase I study of matched donor derived CD19 CAR T cells generated on the CliniMACS Prodigy in 14 adult patients with relapsed/refractory (r/r) B ALL following allo-SCT. We additionally explore the requirement for lymphodepletion (LD) in the allogeneic CAR T cell setting and report on the incidence of GvHD with this therapy. Methods: Manufacturing: CARD utilises non-mobilised matched donor leucapheresate to manufacture 2nd generation CD19CAR T cells using a closed CliniMACS® Prodigy/ TransACTTM process. Study design: Eligible subjects are aged 16-70y with r/r B ALL following allo SCT. Study endpoints include feasibility of CD19CAR T cell manufacture from allo-SCT donors on the CliniMACS Prodigy and assessments of engraftment and safety including GvHD. To assess the requirement for LD prior to CD19CAR T cells in lymphopenic post-allo-SCT patients, the study is split into Cohort 1 (no LD) and Cohort 2 (fludarabine (30 mg/m2 x3) and cyclophosphamide (300mg/m2 x3)). To mitigate for the potential GvHD risk, cell dosing on study mirrors conventional donor lymphocyte infusion (DLI) schedules and is based on total CD3+ (not CAR T) cell numbers: Dose 1=1x106/kg CD3+ T cells; Dose 2= 3x106/kg CD3+ T cells; Dose 3= 1x107/kg CD3+ T cells. Results: As of 26 July 2019, 17 matched allo SCT donors were leukapheresed and 16 products were successfully manufactured and QP released. Patient demographics are as follows: (1) median patient age was 43y (range 19-64y); (2) 4/17 had prior blinatumomab and 5/17 prior inotuzumab ozogamicin; (3) 7/17 had myeloablative allo SCT and 10/17 reduced intensity allo SCT of which 6/17 were sibling donors and 12/17 were matched unrelated donors. No patients with haploidentical transplant were enrolled. To date, 12/16 patients have received at least 1 dose of CD19CAR T cells: 7/16 on Cohort 1 and 5/16 on Cohort 2 (2/16 are pending infusion on Cohort 2 and 2/16 died of fungal infection prior to infusion). Median follow-up for all 12 patients is 22.9 months (IQR 2.9-25.9; range 0.7 - 25.9). At the time of CAR T cell infusion, 7/12 patients were in morphological relapse with >5% leukemic blasts. Despite this, CD19CAR T cells were administered safely: only 2/12 patients experienced Grade 3 CRS (UPenn criteria), both in Cohort 1, which fully resolved with Tocilizumab and corticosteroids. No patients experienced ≥Grade 3 neurotoxicity and importantly, no patients experienced clinically significant GvHD. In Cohort 1 (7 patients), median peak CAR expansion by flow was 87 CD19CAR/uL blood whereas in Cohort 2 (5 patients to date), median peak CAR expansion was 1309 CD19CAR/uL blood. This difference is likely to reflect the use of LD in Cohort 2. CAR T cell persistence by qPCR in Cohort 1 is short, with demonstrable CAR in only 2/7 treated patients at Month 2. Data for Cohort 2 is immature, but this will also be reported at the meeting in addition to potential mechanisms underlying the short persistence observed in Cohort 1. Of the 10 response evaluable patients (2/12 pending marrow assessment), 9/10 (90%) achieved flow/molecular MRD negative CR at 6 weeks. 2/9 responders experienced CD19 negative relapse (one at M3, one at M5) and 3/9 responders experienced CD19+ relapse (one at M3, one at M9, one at M12). 4/10 (40%) response evaluable patients remain on study and continue in flow/molecular MRD negative remission at a median follow up of 11.9 months (range 2.9-25.9). Conclusions: Donor-derived matched allogeneic CD19 CAR T cells are straightforward to manufacture using the CliniMACS Prodigy and deliver excellent early remission rates, with 90% MRD negative CR observed at Week 6 in the absence of severe CAR associated toxicity or GvHD. Peak CAR expansion appears to be compromised by the absence of LD and this may lead to a higher relapse rate. Updated results from Cohorts 1 and 2 will be presented. Disclosures Roddie: Novartis: Consultancy; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. O'Reilly:Kite Gilead: Honoraria. Farzaneh:Autolus Ltd: Equity Ownership, Research Funding. Qasim:Autolus: Equity Ownership; Orchard Therapeutics: Equity Ownership; UCLB: Other: revenue share eligibility; Servier: Research Funding; Bellicum: Research Funding; CellMedica: Research Funding. Linch:Autolus: Membership on an entity's Board of Directors or advisory committees. Pule:Autolus: Membership on an entity's Board of Directors or advisory committees. Peggs:Gilead: Consultancy, Speakers Bureau; Autolus: Membership on an entity's Board of Directors or advisory committees.

Introduction: In adults, prognosis for B-ALL is poor, patients are more vulnerable to CD19 CAR immunotoxicity and there is currently no CD19 CAR therapeutic with acceptable toxicity and durable efficacy. We have developed a novel second generation CD19CAR (CAT-41BBz CAR), with a faster off-rate but equivalent on rate than the FMC63-41BBz CAR (Kd 116 nM vs 0.9 nM, T1/2 9s vs 4.2 hours) designed to result in more physiological T-cell activation, reduce toxicity and improve engraftment. Preliminary paediatric clinical data of this novel CD19 CAR (AUTO1) supports this assertion. We here describe preliminary data from ALLCAR19 (NCT02935257), a multi-centre, Phase I clinical study of AUTO1 as therapy for r/r adult B-ALL. Methods: Manufacturing: AUTO1 utilises non-mobilised autologous leucapheresate. The first 6 trial products were generated using a standard dynal bead/WAVE Bioreactor process and subsequent products using a semi-automated closed process. Study design: ALLCAR19 is a phase I/II study recruiting subjects 16-65y with r/r B ALL. Lymphodepletion with fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) is followed by split dose CAR T cell infusion (Day 0: if ≥20% BM blasts, infuse 10 x 106 CAR T cells ; if Results: As of 24 July 2019, 16 patients have been leukaphresed, 14 products manufactured (one failed leukaphresis and one currently in manufacture) and 13 patients have received at least 1 dose of AUTO1. Of the 16 patients, median age was 35.5 (range 18-63), 10/16 (63%) had prior blinatumomab or inotuzumab ozogamicin and 12/16 (75%) had prior HSCT. At the time of pre-conditioning, 9/13 (69%) patients were in morphological relapse with >5% leukemic blasts of which 6/13 (46%) had ≥50% blast. 9/13 patients (69%) received the total target split dose of 410 x 106 CAR T cells while 1/13 patients (8%) received a reduced split total dose of 51.3 x 106 CAR T cells due to manufacturing constraints. 3/13 patients (23%) received only a first dose of 10 x 106 CAR T cells. The dose was administered safely to date: No patients experienced ≥Grade 3 CRS (using Lee criteria) and only 1/13 (8%) experienced Grade 3 neurotoxicity (dysphasia) that resolved swiftly with steroids. All patients had robust CAR expansion (median peak expansion 172 CAR/uL blood). Of the 13 patients dosed (1/13 pending 28 day follow up), 10/12 (83%) achieved MRD negative CR at 1 month and all patients had ongoing CAR T cell persistence at last follow up. Two patients experienced CD19 negative relapse (one at M3, one at M6), 1 patient died on D17 before first response evaluation, 1 died in molecular CR from sepsis, and 1 died from persistent disease. Currently, 7/12 remain on study and continue in flow/molecular MRD negative remission with a median follow up of 9.0 months (range 1.2-14.8). Conclusions: AUTO1 delivers excellent early remission rates with initial data showing 83% MRD negative CR and robust CAR expansion and persistence. Despite high tumour burden, the safety profile compares favourably to other CD19 CARs, with no cases of severe CRS and only one case of Gr3 neurotoxicity. This is consistent with experience in the paediatric cohort. Updated results will be presented. Disclosures Roddie: Novartis: Consultancy; Gilead: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau. O'Reilly:Kite Gilead: Honoraria. Farzaneh:Autolus Ltd: Equity Ownership, Research Funding. Linch:Autolus: Membership on an entity's Board of Directors or advisory committees. Pule:Autolus: Membership on an entity's Board of Directors or advisory committees. Peggs:Gilead: Consultancy, Speakers Bureau; Autolus: Membership on an entity's Board of Directors or advisory committees.