Comparative Outcomes for Mature T and NK/T-cell Lymphomas in People with and without HIV and to AIDS-Defining Lymphomas

There are no studies comparing the prognosis for mature T-cell lymphoma (TCL) in people with human immunodeficiency virus (PWH) to people without HIV (PWoH) and to AIDS-defining B-cell lymphomas (A-BCL) in the modern antiretroviral therapy (ART) era. NA-ACCORD and COMPLETE are cohorts that enroll patients diagnosed with HIV and TCL, respectively. In our study 52, 64, 101, 500 and 246 PWH with histological confirmation of TCL, primary CNS, Burkitt's, diffuse large B-cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL) respectively and 450 TCL without HIV were eligible for analysis. At the time of TCL diagnosis, Anaplastic large-cell lymphoma (ALCL) was the most common TCL subtype within PWH. While PWH with TCL diagnosed between 1996-2009, experienced a low 5-year survival probability at 0.23 (95% CI: 0.13, 0.41), we observed a marked improvement in their survival when diagnosed between 2010-2016 (0.69; 95% CI: 0.48, 1; p=0.04) in contrast to TCL among PWoH (0.45; 95% CI: 0.41, 0.51; p=0.53). Similarly, PWH with ALCL diagnosed between 1996-2009 were associated with a conspicuously inferior 5-year survival probability (0.17; 95% CI: 0.07, 0.42) and consistently lagged behind A-BCL subtypes such as Burkitt's (0.43; 95% CI:0.33, 0.57; p=0.09) and DLBCL (0.17; 95% CI: 0.06, 0.46; p=0.11) and behind HL (0.57; 95% CI: 0.50, 0.65; p <0.0001). Despite a small number, those diagnosed between 2010-2016, experienced a remarkable improvement in survival (0.67; 95% CI: 0.3, 1) in comparison to PWoH (0.76; 95% CI: 0.66, 0.87; p=0.58). Thus, our analysis confirms improved overall survival for aggressive B and T-cell malignancies among PWH in the last decade.

Gastrointestinal Adenocarcinoma Incidence and Survival Trends in South Australia, 1990–2017

Background & Aims: Globally, there has been a concerning rise in the incidence of young-onset cancers. The aim of this study was to provide trends in the incidence and survival of gastrointestinal adenocarcinomas (oesophagus, stomach, pancreas, and colorectal) in South Australia over a 27-year period. Methods: This is a cross-sectional analysis of a prospective longitudinal database including all cases of gastrointestinal adenocarcinomas prospectively reported to the South Australian (State) Cancer Registry from 1990 to 2017. Results: A total of 28,566 patients diagnosed with oesophageal, stomach, pancreatic, or colorectal adenocarcinoma between 1990 and 2017 were included in the study. While the overall incidence for gastrointestinal adenocarcinomas in individuals >50 years has decreased since 2000 (IRR of 0.97 (95% CI 0.94–1.00; p = 0.06)) compared to 1990–1999, the rate amongst individuals aged 18–50 has significantly increased (IRR 1.41 (95% CI 1.27–1.57; p <0.001)) during the same reference time period. Although noted in both sexes, the rate of increase in incidence was significantly greater in males (11.5 to 19.7/100,000; p <0.001). The overall survival from adenocarcinomas across all subsites improved in the >50-year cohort in the last decade (HR 0.89 (95% CI 0.86–0.93; p <0.001)) compared to 1990–1999. In individuals aged 18–50 years, there has only been a significant improvement in survival for colorectal cancer (HR 0.82 (95% CI 0.68–0.99; p <0.04)), but not the other subsites. A lower overall survival was noted for males in both age cohorts (18–50 years—HR 1.24 (95% CI 1.09–1.13; p <0.01) and >50 years—HR 1.13 (95% CI 1.10–1.16; p <0.001), respectively) compared to females. Conclusions: This study from South Australia demonstrates a significant increase in young-onset gastrointestinal adenocarcinomas over the last 28 years, with a greater increase in the male sex. The only significant improvement in survival in this cohort has been noted in colorectal cancer patients.

High-risk multiple myeloma: how to treat at diagnosis and relapse?

Patients with multiple myeloma have experienced a great improvement in survival over the past century because of the introduction of novel therapeutic strategies. However, a subgroup of patients with poorer outcomes than expected is considered high risk and identified by the presence of patient- and disease-based factors such as frailty, extramedullary disease, cytogenetic abnormalities, or even relapses occurring earlier than expected according to the baseline factors. Although the management of patients with high-risk features is not well established because of the lack of specific trials in this subgroup of patients and because of their underrepresentation in the clinical trials, treatment should be planned on 2 pillars: (1) poor prognosis with the presence of high-risk features can be at least improved or even abrogated by achieving a deep and sustained response over time, and (2) this can most likely be obtained through using the best therapeutic options and in a response-adapted way. Some clinical trials that have been planned or are ongoing include only patients with high-risk features, using the most effective therapies (proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies) as well as chimeric antigen receptor T cells and T-cell engagers that will unravel what the best therapeutic approach will be to overcome the poor prognosis of the presence of high-risk features.

Psychosocial and financial issues after hematopoietic cell transplantation

With improvement in survival after hematopoietic cell transplantation (HCT), it has become important to focus on survivors' psychosocial issues in order to provide patient-centered care across the transplant continuum. The goals of this article are to describe updates in the literature on certain psychosocial domains (emotional/mental health and social/financial) in HCT survivors, offer a brief overview of the status of the screening and management of these complications, and identify opportunities for future practice and research. An evidence-based approach to psychosocial care can be broken down as primary (promoting health, raising awareness, and addressing risk factors), secondary (screening and directing early pharmacological and nonpharmacological interventions), and tertiary (rehabilitating, limiting disability, and improving quality of life) prevention. Implementing such an approach requires close coordination between multiple stakeholders, including transplant center staff, referring hematologist/oncologists, and other subspecialists in areas such as palliative medicine or psychiatry. Innovative models of care that leverage technology can bring these stakeholders together to fulfill unmet needs in this area by addressing barriers in the delivery of psychosocial care.

P-P55 CT-PET use in potentially resectable pancreatic cancer

Background CT-PET has become increasingly used in the diagnostic pathway for pancreatic cancer (PC)and was introduced into National Guidelines (NICE) in 2018 in the United Kingdom. It can improve the diagnosis of metastatic disease, though some believe it is not significantly better than a staging CT and MRI, and there are concerns that it can significantly delay the treatment pathway for patients, without adding benefit. Methods A retrospective national study undertaken by 26/27 specialist pancreatic resectional centres in the United Kingdom. All adult patients listed for pancreatoduodenectomy for suspected PC were included. Baseline demographics, length of pathway (days from MDT to surgery), number and type of investigations, interventions (ERCP or PTC) and associated complications were recorded, in addition to the operation performed and 12-month survival. Patients undergoing neoadjuvant chemotherapy were excluded. Results 1709 cases were entered from 2017-2020. 155 patients were excluded due to neoadjuvant chemotherapy, with 8 further patients excluded due to incomplete data entry. The median age was comparable for patients undergoing CT-PET (68 years IQR 60.0-73.0) and those who did not undergo CT PET (68 years IQR 60.0-74.0). 363/1546 patients (23.5%) underwent a pre-operative CT-PET. There was a significantly longer pathway with CT-PET (56 vs 42 days, p &lt; 0.001) and a non-significant tendency towards an increased bypass rate with CT-PET (9.9% vs. 7.8%, p = 0.065), and no improvement in survival (1-year survival 76.9% vs 75.7%, p = 0.712). Conclusions There is a statistically significant increase in the length of pathway with CT-PET, without any improvement in bypass rate or one year survival compared the no-CT-PET group. CT-PET undoubtedly has benefits but should be used selectively rather as standard investigation for all patients as failed to demonstrate survival improvement.

Abstract 12436: App-Based EMS to ED Communication May Improve Survival to Discharge Rates for OHCA Survivors

Background: Survival rates for Out-of-Hospital Cardiac Arrest (OHCA) remain low despite advances in therapeutics. Although it seems intuitive, there is little evidence to support a benefit from early activation of emergency services at receiving hospitals from improved Emergency Medical Services provider (EMS) communication. We hypothesize that early, app-based communication from EMS in the field to in-hospital providers may improve survival to discharge rates. Methods: We utilized the General Devices Company, Inc. e-BridgeTM mobile application. EMS Providers were trained to use the app and dedicated devices and staff were stationed to monitor EMS transmissions to the emergency department (ED). A single-center, retrospective observational study was conducted on patients transferred to our institution for resuscitated OHCA. We identified 45 cases with OHCA admitted to our institution between February and July 2020 that utilized the app. We excluded interfacility transfers as well as patients certified deceased on the field. Given that standard, radio-based communication with EMS occurs 5 minutes prior to presentation, we used 5 minutes as the cutoff between our standard and intervention groups. Results: Of 45 cases, 29 had established communication using the app prior to 5 minutes, with the remaining 16 being considered in the standard group. We noted that 24% of patients (7 of 29) with early EMS notification survived to discharge compared to 0 of the 16 patients in the standard group. There was also an improvement in door-admission times from the ED to appropriate care units in this group (156 versus 228 minutes). Conclusion: Implementation of app-based communication between EMS providers and in-hospital providers with GPS tracking led to a trend to improvement in survival to discharge as well as time to admission from the ED in patients admitted for OHCA.

Abstract 12097: The Impact of a High-Performance Cardiopulmonary Resuscitation Protocol on Survival From Out-of-Hospital Cardiac Arrests Witnessed by Paramedics

Introduction: Some emergency medical services (EMS) have shown increases in survival from out-of-hospital cardiac arrest (OHCA) following the implementation of a high-performance cardiopulmonary resuscitation (CPR) protocol. Despite this, little is known about the effect of high-performance CPR on OHCA witnessed by EMS personnel. Methods: We performed a retrospective cohort study of adult, EMS-witnessed OHCA patients of medical etiology from a population-based registry in Victoria, Australia. Patients treated after the introduction of a high-performance CPR protocol and training program between February 2019 and January 2020 were compared to historical controls between January 2015 and January 2019. The effect of the intervention on survival to hospital discharge was examined using logistic regression models adjusted for temporal and arrest factors. Results: A total of 1,561 and 420 EMS-witnessed OHCA patients were treated in the control and intervention periods, respectively. Baseline characteristics were similar across control and intervention periods, including the median age of cases (69 vs. 69 years, p=0.97), male sex (65.2% vs. 60.5%, p=0.08) and initial shockable arrests (33.7% vs. 29.3%, p=0.09). Resuscitation interventions were similar across groups, except for the use of mechanical CPR which declined during the intervention period (17.0% vs. 10.7%, p<0.001). Unadjusted survival to hospital discharge was similar across control and intervention periods for the overall population (29.4% vs. 32.1%, p=0.27), but significantly higher during the intervention period for initial shockable arrests (66.6% vs. 76.9%, p=0.03). After adjustment for confounders, cases in the intervention period were associated with a 43% increase (adjusted odds ratio [AOR] 1.43; 95% CI: 1.05, 1.94; p=0.02) in the risk-adjusted odds of survival to hospital discharge or a 79% increase (AOR 1.79, 95% CI: 1.09, 2.95; p=0.02) for initial shockable arrests. Conclusions: The implementation of a high-performance CPR quality improvement intervention was associated with significant improvement in survival from EMS witnessed OHCA. Efforts to monitor and improve CPR performance could yield further improvements in patient outcomes.

Abstract 11336: Experience with an Institutional Guideline on Extracorporeal Cardiopulmonary Resuscitation for Refractory in Hospital and Out of Hospital Cardiac Arrest

Aim: To compare survival rates in patients with refractory cardiac arrest treated with extracorporeal cardiopulmonary resuscitation (ECPR) before and after implementation of an action card.The primary outcome was survival to discharge, and secondary outcomes were low-flow time and rate of cerebral complications. Methods: Retrospective evaluation of 37 patients treated with ECPR for refractory cardiac arrest. Information was obtained through medical records. Patients were categorized into two groups - before (BA) and after (AA) introduction of an action card. The card entailed inclusion and exclusion criteria used to evaluate the benefit of ECPR for any individual patient. Results: There were no statistically significant differences in baseline characteristics between the groups.After the introduction of the action card, survival to discharge increased from 6.7 % to 18.2 % suggesting a trend toward improved survival, despite this finding being statistically insignificant (p = 0.629).Low-flow time was reduced from 100 (12-195) minutes to 66 (30-195) minutes and the upper extreme was reduced from 195 to 153 minutes, but this was not statistically significant (p = 0.334).Cerebral factors contributed to significantly fewer deaths in AA compared with BA (p = 0.0022). Conclusion: There was no statistically significant improvement in survival rates nor a reduction in low-flow time after the implementation of an action card for the use of ECPR in patients with refractory CA. However, cerebral causes factored in fewer deaths and several patients survived despite meeting potential exclusion criteria outlined in local and international guidelines.

Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate

Background Vibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and septic shock. Mesenchymal stem cells (MSCs) are currently used to treat infectious and inflammatory diseases. Therefore, this study aimed to evaluate the immune-modulating effects of the LPS‐MSC‐conditioned medium (CM) on V. cholerae LPS immunization in a murine model. Methods After preconditioning MSCs with LPS, mice were immunized intraperitoneally on days 0 and 14 with the following combinations: LPS + LPS-MSC-CM; detoxified LPS (DLPS) + MSC-CM; LPS + MSC sup; LPS; LPS-MSC-CM; MSC supernatant (MSC sup); and PBS. The mouse serum and saliva samples were collected to evaluate antibody (serum IgG and saliva IgA) and cytokine responses (TNF-α, IL-10, IL-6, TGF-β, IL-4, IL-5, and B-cell activating factor (BAFF)). Results The LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P < 0.001). TNF-α levels, in contrast to IL-10 and TGF-β, were reduced significantly in mice receiving the LPS + LPS-MSC-CM compared to mice receiving only LPS. IL-4, IL-5, and BAFF levels significantly increased in mice receiving increased doses of LPS + LPS-MSC-CM compared to those who received only LPS. The highest vibriocidal antibody titer (1:64) was observed in LPS + LPS-MSC-CM-immunized mice and resulted in a significant improvement in survival in infant mice infected by V. cholerae O1. Conclusions The LPS-MSC-CM modulates the immune response to V. cholerae LPS by regulating inflammatory and anti-inflammatory responses and inducing vibriocidal antibodies, which protect neonate mice against V. cholerae infection.