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1.
Acta Medica Peruana ; 39(2):104-113, 2022.
Article in Spanish | EMBASE | ID: covidwho-2067675

ABSTRACT

Objective: To identify demographic, clinical, laboratory and treatment characteristics associated with mortality in hospitalized patients with SARS-CoV-2 pneumonia in a Level I Hospital of Peruvian Social Security, at La Libertad Network. Material(s) and Method(s): Retrospective cohort study. Cox proportional hazards model was used, calculating crude and adjusted hazard ratios (HR), and the Kaplan-Meier estimator was used to evaluate the overall survival curve and for each factor. Result(s): Of the 158 patients, the diagnosis was confirmed in 79.11%. Nearly 70% (68.99%) were men, the global median age was 65 years (IQR: 52-77), and it was higher in deceased subjects 69 years old (IQR: 61-80 years). Little more than half of this population (53.80%) had comorbidities, such as high blood pressure (27.85%), obesity (22.78%), and diabetes mellitus (13.92%). The median duration of symptoms prior to admission was 9 days (IQR: 6-11 days). HRs were determined for oxygen saturation less than 80% on admission with 0.21 FIO2, leukocytosis with associated lymphopenia, oxygen requirement at 0.80 FIO2 on admission, and moderate-severe ARDS. Such values were 1.54, 1.98, 2.07 and 2.91, respectively. Conclusion(s): The development of moderate-severe ARDS on admission, leukocytosis associated with lymphopenia, less than 80% hypoxemia on admission at 0.21 FIO2, and high-flow oxygen requirement since admission with 0.80 FIO2, were the only risk factors for mortality. Copyright © 2022 by Begell House, Inc.

2.
American Journal of Transplantation ; 22(Supplement 3):948, 2022.
Article in English | EMBASE | ID: covidwho-2063503

ABSTRACT

Purpose: Currently there are no UNOS guidelines regarding the selection criteria required for simultaneous heart-kidney transplant recipients (SHKT). As of 2018 our center has begun performing these dual transplants for appropriate candidates. We report on the criteria devised to guide SHKT candidate selection at our institution and the subsequent clinical outcomes. Method(s): This is a single center, retrospective study of 26 patients who received SHKT at our institution from Dec 2018 to Oct 2021. A multidisciplinary team composed of heart and kidney transplant medical and surgical members determined appropriate recipient-donor SHKT candidate pairs. Selection criteria for SHKT was established by our kidney transplant group and included an evaluation for chronic kidney disease (CKD) or evidence of acute kidney injury (AKI) with a prolonged course or requiring renal replacement therapy (RRT). The surgery was conducted according to our institution's standardized protocols. The majority of patients received IL2-RA and methylprednisolone induction therapy, and all patients received triple immunosuppression therapy with prednisone, mycophenolate mofetil and tacrolimus. Adjustments in long term therapy were made in collaboration between the heart and kidney transplant teams. Result(s): From Dec 2018 to Oct 2021, 26 patients underwent SHKT at our institution. 24 patients (92%) carried a diagnosis of chronic kidney disease (CKD) as defined as an eGFR <60 ml/min/1.73m2 for at least 90 days on at least two separate tests. Clinical risk factors for CKD, the presence of proteinuria, and renal imaging data were also taken into consideration when determining a diagnosis of CKD. Two patients (8%) carried a diagnosis of stage III AKI for at least 4 weeks and required renal replacement therapy during their hospital course. Of our 26 patients, one patient received a DCD donor and 12 patients (46%) received hepatitis C donors. 25 patients (96%) received induction therapy with IL2-RA. During the first 3 months post-transplant, the only patient who received ATG had 7 severe infections;11 patients (44%) and 13 patients (52%) who received IL2 -RA had no infections and <= 4 mild infections, respectively. One patient died due to COVID 19 pneumonia complicated by multisystem organ failure. For a median follow up period of 410 (187-707) days, 8% patients in the IL2-RA induction cohort experienced a 2R/3A heart rejection, 8% patients remained on HD due to primary kidney graft nonfunction, and the survival rate was 96%. Conclusion(s): UNOS guidelines regarding selection criteria for SHKT are an important next step in the care of heart transplant candidates with kidney disease, particularly as the number of SHKT performed yearly increase. Compared to the literature, our data supports the use of standardized criteria for SHKT selection and the use of IL2- RA as an induction strategy with excellent patient survival.

3.
American Journal of Transplantation ; 22(Supplement 3):720, 2022.
Article in English | EMBASE | ID: covidwho-2063497

ABSTRACT

Purpose: Liver transplant recipients have a high risk of developing postoperative pulmonary complications. Pulmonary function tests (PFTs) are expensive and often incapable of predicting patients at risk or improving patient outcomes, thus a single-center implemented specific criteria to determine when a PFT is administered for the evaluation of patients for liver transplantation. The protocol recommends a PFT for patients with a history of chronic lung disease, recurrent pneumonia prior to transplant, symptomatic COVID-19 requiring hospitalization, tobacco abuse, alpha-1 antitrypsin positivity, or oxygen dependency. Method(s): We conducted a retrospective cohort study of consecutive adult patients (age greater than 18 years) who underwent deceased donor liver transplantation from January 1, 2020, to June 30, 2021. We analyzed results from pre-protocol (PRE) and post-protocol (POST) implementation. Result(s): There were a total of 215 patients in the study, 186 PRE and 29 POST protocol implementation. In the PRE group, 168 (90%) patients received PFTs compared to 12 (41%) in the POST group, p<0.001). There was no difference between the PRE and POST groups based on age in years (56 vs 55, p=0.713), male gender (65% vs 662%, p=0.83), White race (80% vs 86%, p=0.15), BMI (34 vs 28, p=0.107), or cold ischemic time in hours (5.7 vs 6, p=0.252). There was no difference in FVC (3.3 vs 3.0, p=0.84), FEV1 (2.6 vs 2.2, p=0.87), FEV1/FVC% (76.9 vs 74.4, p=0.47) and DLCO (16.4 vs 13.8, p=0.11). The postoperative variables were the same for both groups with time to extubation hours (25 vs 31, p=0.26), ICU length of stay days (8 vs 10, p=0.12), and transplant admission length of stay days (14.4 vs 17.4, p=0.36). Lastly, there was no difference between PRE and POST graft survival (p=0.69) or patient survival (p=0.08). Conclusion(s): This study demonstrates the successful implementation of a PFT protocol with a cost savings of roughly $38,000 in just three months with no impact on patient outcomes. Further research is indicated for broad-scale implementation.

4.
American Journal of Transplantation ; 22(Supplement 3):1069, 2022.
Article in English | EMBASE | ID: covidwho-2063450

ABSTRACT

Purpose: Increasing mismatch between kidneys available for transplant and the number of patients on the transplant wait list has led to research into novel sources of organs. One such source is kidneys from hepatitis C NAT positive deceased donors. This was previously deemed unforbidden territory due to the risk of disease transmission;however, with the development of direct-acting antiviral agents for effective treatment of Hepatitis C, this organ pool is now usable. Method(s): A retrospective analysis of outcomes of Hepatitis C NAT positive kidney transplants into Hepatitis C seronegative recipients was conducted at newly opened Appalachian transplant center. Due to insurance constraints, the criteria to initiate hepatitis C therapy was seroconversion to positive Hepatitis C PCR. Outcomes examined include median creatinine, glomerular filtration rate (GFR), liver function tests, recipient Hepatitis C seroconversion, concomitant Ebstein Barr virus (EBV), Cytomegalovirus (CMV) or polyoma hominis (BK) activation, morbidities and mortality. Result(s): Six transplants (of 15 total kidney transplants) from Hepatitis C NAT positive donors were performed in the first year of establishment. Male to female ratio was 2:1 and median patient age was 55.7 years (Range 42-73 years). Median follow-up was 10 months (Range 2-12 months). Diabetes and hypertensive nephrosclerosis were the most common causes of end stage renal disease at 40%. The average time on dialysis was 2.9 years (Range 1-6 years), the most common type being hemodialysis (67%) followed by peritoneal dialysis (33%). Average time on transplant waitlist was 5.57 months (Range 1.2-13.2 months). All patients seroconverted but with treatment, by 24 weeks all patients maintained undetectable viral loads. Patient survival rate was 83% with a death censored graft survival rate of 100%. One patient died due to respiratory failure from COVID-19 infection. Median creatinine and GFr were 1.96 mg/dL (Range 1.8 - 2.6 mg/dL) and 41.3 (Range 35.3 - 50) respectively. One case each of acute antibody and T cell mediated rejection was seen (6.7%), which were treated successfully. CMV, BK and EBV virus reactivation were seen in one patient each (6.7%). The most common complication was COVID-19 infection (50%) followed by neutropenia (33%). Conclusion(s): With the development of direct-acting antiviral agents offering complete cure of Hepatitis C, kidneys from Hepatitis C positive donors can be used for transplantation with excellent outcomes.

5.
American Journal of Transplantation ; 22(Supplement 3):992, 2022.
Article in English | EMBASE | ID: covidwho-2063425

ABSTRACT

Purpose: Lung transplant is the last resort for COVID-19 refractory ARDS. Dual organ transplant is seen as a relative contraindication at many institutions. We describe a case of simultaneous Lung-Kidney transplant (SLK) in a patient with COVID-19 ARDS. Method(s): A 24-year-old patient with no PMH presented to an outside hospital with a week of shortness of breath, cough, and fever. Despite treatment with Remdesivir and dexamethasone, the patient developed hypoxemic respiratory failure with acute renal injury requiring ICU care and intubation, V-V ECMO, and dialysis. Additionally, Intravenous and inhaled Aviptadil were given under emergency use authorization. While oxygenation improved, the patient could not be weaned off ECMO. With a LAS score of 90.29, the patient underwent an SLK transplant on HD 53, requiring standard induction and maintenance immunosuppression therapy. The patient was treated post-operatively for PGD as well as for subclinical AMR. After successful inpatient rehabilitation, the patient was discharged home after four months and had a one-month follow-up on room air and normal creatinine clearance. Result(s): Patients with pre-existing renal dysfunction who have undergone lung transplants have a significantly higher one- and three-year mortality than patients with normal GFR. The patient's survival after SLK was similar to isolated lung transplants at one and five years, according to an analysis of the UNOS/OPTN database. Still, dual organ transplant in the COVID-19 ARDS population is considered a contraindication at many centers, given these patients' critical illness and frailty. However, the frailty in this population is reversible due to the rapid onset of disease in an otherwise previously healthy younger population with minimal comorbidities. Thus, multiorgan transplantation should be considered in such a patient population. Our patient received Aviptadil as part of an EIND to stabilize patients and improve oxygenation while waiting on the transplant list. Conclusion(s): We propose that SLK transplantation should be considered for carefully selected patients with COVID-19 ARDS.

6.
American Journal of Transplantation ; 22(Supplement 3):1110, 2022.
Article in English | EMBASE | ID: covidwho-2063405

ABSTRACT

Purpose: Kidney transplantation has become the optimal treatment for end stage renal disease (ESRD), allowing dialysis free survival. Despite widespread availability of transplant programs;rural patients have limited access to transplantation due to several barriers including increased travel time and financial burden. We report outcomes after establishment of a kidney transplant program serving rural West Virginia. Method(s): A retrospective review of the first 15 kidney transplants performed at a newly established Appalachian transplant program was conducted. Primary outcomes measured were graft survival and function. Other outcomes included graft rejection, patient survival and complications. Data related to patient demographics, etiology of ESRD, type of renal replacement therapy, time on transplant waitlist and average travel to transplant center were also collected. Result(s): The first 15 kidneys transplanted had an overall death censored graft survival rate of 100%. Median patient age was 53 (Range 31- 73 years) and a median follow-up of 6 months (Range 1-13 months). The average time on dialysis for this cohort was 4 years (n=13, Range 1-6 years) and average time on waitlist was 4.06 months (Range 0.4-13.2 months). The most common type of dialysis was hemodialysis (77%) followed by peritoneal dialysis (15%). Two patients were predialysis. Diabetes with hypertension (20%), IgA nephropathy (13%) and diabetes without hypertension (13%) were the most common causes of ESRD. Median graft creatinine was 1.51 mg/dL (Range 1.26 - 1.83 mg/dL) with a glomerular filtration rate (GFR) at 51.38 (Range 41.86-70) at one year. One patient developed acute antibody mediated rejection and one developed borderline T cell mediated rejection (13.3%), which were successfully treated with steroids, plasmapheresis and immune globulin therapy. Two patients died (13.3 %);one from acute respiratory failure following coronavirus (COVID-19) infection and one from cardiac arrest secondary to myocarditis (possible COVID-19). Patients experienced COVID-19 infection at a rate of 13.3 %. The average distance patients had to travel was 94 miles (Range 12 - 164 miles) with a travel time of 1 hour and 52 minutes on average (Range 20 minutes - 2.5 hours) to reach the transplant center. Conclusion(s): We report comparable outcomes from our new rural transplant program despite several barriers to delivery of quality care to our population.

7.
American Journal of Transplantation ; 22(Supplement 3):472-473, 2022.
Article in English | EMBASE | ID: covidwho-2063355

ABSTRACT

Purpose: Acuity circles (AC) allocation was implemented on 2/4/2020 with a goal of removing DSA and region from liver allocation and broadening the distribution of livers, particularly for highly medically urgent candidates. Method(s): OPTN waitlist and transplant data was analyzed 18 months pre- (8/6/2018- 2/3/2020) and post- (2/4/2020-8/3/2021) AC implementation. Result(s): Post-policy, there were 448 more adult (age 18+ at listing) and 83 less pediatric (<18 at listing) waitlist additions, 570 more adult (age 18+ at transplant) and 4 less pediatric (<18 at transplant) deceased donor liver-alone transplants, and 121 less adult and 12 less pediatric removals for death or too sick. Transplant rates significantly increased overall post-policy, notably in the most medically urgent groups (Figure 1). The national median transplant score for adults remained unchanged at 28 and decreased from 35 to 30 for pediatric transplant recipients, likely due to the increased number of adolescents (age 12-17) transplanted at MELD scores under 29. There was a noticeable shift in the distribution of distance between donor hospital and transplant program, particularly for the most medically urgent groups where larger proportions of livers are coming from 250-500 NMs (Figure 2). Despite this change, median cold ischemia time increased only 11 minutes for adult recipients and 33 minutes for pediatric recipients post-policy. One year post transplant patient survival decreased from 94% pre-policy to 93% post-policy (p=0.02). Conclusion(s): Broader allocation increased transplant rates and livers are traveling longer distances for candidates with greater medical urgency with little effect on cold ischemia time and post-transplant survival. Unfortunately, AC implementation was followed shortly by COVID-19 making it difficult to parse out COVID-19 from potential policy effects. Metrics will continue to be monitored as more data become available. (Figure Presented).

8.
Chest ; 162(4):A925, 2022.
Article in English | EMBASE | ID: covidwho-2060729

ABSTRACT

SESSION TITLE: ECMO and ARDS in COVID-19 Infections SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/17/2022 12:15 pm - 1:15 pm PURPOSE: To compare characteristics and outcomes of COVID-19 patients with respiratory failure meeting ECMO eligibility criteria who received ECMO vs. conventional therapy (CT) alone. METHODS: Retrospective analysis of COVID-19 patients (admitted April 2020 -December 2021) meeting ECMO eligibility criteria (PaO2/FiO2 <50 for more than 3 hours, PaO2/FiO2 < 80 for more than 6 hours, or pH < 7.25 with a pCO2 of at least 60 mm Hg for more than 6 hours within the first 7 days of mechanical ventilation (MV)) was performed. All patients received optimal therapies according to current guidelines. Due to the criteria evolution over the course of the pandemic, two intensivists confirmed eligibility by independent chart review. Differences between CT and ECMO groups were analyzed using Chi-square, Fisher’s exact, and Wilcoxon rank-sum tests as appropriate. RESULTS: 62 patients met ECMO eligibility criteria, and 20 of them received CT alone. Reasons for not receiving ECMO included high BMI, comorbid conditions, improving gas exchange, or treatment team preference. CT patients had higher BMI (39.0 vs. 32.5, p=0.01), higher incidence of acute kidney injury (70% vs. 42.9%, p=0.05), and lower prevalence of current smoking (10% vs. 33%) compared to ECMO patients. In-hospital mortality for CT was 60% vs. 47.6% for ECMO (p= 0.36). Overall, CT patients had a significantly shorter duration of MV, ICU and hospital length of stay (LOS) than ECMO patients (18.0 vs. 41.0, 19.0 vs. 44.5, and 18.0 vs. 49 days respectively, p< 0.001). CT survivors had a shorter duration of MV, and shorter ICU and hospital LOS than ECMO survivors (23.5 vs. 44.5, 25.0 vs. 52.0, 31.5 vs. 56.0 days respectively, p <0.05). Among CT patients, survivors were younger (38.5 vs. 55, p=0.01), had higher P/F ratio (66.0 vs. 53.5, p=0.05), and lower pCO2 (71.5 vs. 86.0, p= 0.02) during the first week of MV than non-survivors. Respiratory acidosis was the principal ECMO eligibility criteria in 50% of CT survivors and 8.3% of non-survivors. CONCLUSIONS: The difference in mortality between ECMO-eligible patients treated with ECMO vs. CT alone didn’t reach statistical significance, possibly due to small sample size. ECMO was associated with a longer duration of MV, and ICU and hospital LOS. In CT patients, younger age and less severe oxygenation and ventilation abnormalities were associated with survival. Observed survival differences in relation to respiratory acidosis vs. hypoxemia as the main ECMO indication require confirmation. CLINICAL IMPLICATIONS: A significant number of patients meeting ECMO eligibility criteria survived with CT alone. ECMO is resource-intensive and is not universally available, especially at the peaks of the pandemic. We demonstrate characteristics of survivors receiving CT alone which may help further refine ECMO indications in COVID-19 patients. DISCLOSURES: No relevant relationships by Roman Melamed No relevant relationships by Ramiro Saavedra Romero No relevant relationships by Lynn Sipsey No relevant relationships by Ashley Stenzel No relevant relationships by David Tierney

9.
Chest ; 162(4):A319, 2022.
Article in English | EMBASE | ID: covidwho-2060563

ABSTRACT

SESSION TITLE: Critical Care in Chest Infections Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: During the COVID-19 pandemic, acute respiratory distress syndrome (ARDS) was a very common presentation. Many clinicians sought to rule out COVID-19 in those presenting with hypoxia and shortness of breath due to the importance of triage and quarantining infected individuals and those under investigation. As a result, delay in diagnosis of other viral and bacterial pathogens occurred. There is a known but rare overlapping of disease processes and sometimes even co-infections with COVID-19 and Pneumocystis jirovecii pneumonia (PJP) which made narrowing the differential challenging [1,2]. We present a case of a patient with known HIV who presented with typical features of COVID-19 and clinically worsened. Further investigation revealed PJP and AIDS. CASE PRESENTATION: A 55-year-old female with a past medical history of human immunodeficiency virus (HIV), previously controlled on highly active antiretroviral therapy (HAART), presented with shortness of breath, cough, and syncope. She required sedation and mechanical ventilation following significant hypoxia on admission. Chest radiograph and computed tomography (CT) were concerning for acute respiratory distress syndrome (ARDS) with diffuse bilateral ground glass opacities (Figure 1 and Figure 2) and she was found to be in septic shock requiring vasopressors. She presented during the COVID-19 pandemic and it was initially thought to be the cause of her condition, however she repeatedly tested negative via polymerase chain reaction (PCR). Through further investigation, it was found that her total cluster of differentiation 4 (CD4) cell count was 184/??L, posing a risk for opportunistic infections. Prior records indicated her last CD4 count was greater than 250/??L. Bronchoscopy showed progressively darker-tinged aliquots significant for diffuse alveolar hemorrhage that stained positive for Pneumocystis jirovecii pneumonia (PJP). She was treated with appropriate antimicrobial therapy, eventually weaned from ventilation, and transferred to the floor despite her high risk of morbidity and mortality [3]. DISCUSSION: This clinical case demonstrates PJP infection in an individual with features on imaging nearly identical to those of COVID-19 during the pandemic. There is a strong role in verifying CD4 count and HIV viral level in those affected with HIV with reported medication adherence who present with critical illness. There should be a low threshold to perform bronchoscopy in patients with ARDS and negative COVID-19 if no known source is identified. CONCLUSIONS: It is important to consider all causes of ARDS in patients who are immunocompromised with a low threshold to test for and treat uncommon causes, such as opportunistic infections, because the treatment should be directed at the underlying cause. Reference #1: Coleman, H., Snell, L., Simons, R., Douthwaite, S. and Lee, M., 2020. Coronavirus disease 2019 and Pneumocystis jirovecii pneumonia: a diagnostic dilemma in HIV. AIDS, 34(8), pp.1258-1260. Reference #2: Menon, A., Berg, D., Brea, E., Deutsch, A., Kidia, K., Thurber, E., Polsky, S., Yeh, T., Duskin, J., Holliday, A., Gay, E. and Fredenburgh, L., 2020. A Case of COVID-19 and Pneumocystis jirovecii Coinfection. American Journal of Respiratory and Critical Care Medicine, 202(1), pp.136-138. Reference #3: Dworkin, M., Hanson, D. and Navin, T., 2001. Survival of Patients with AIDS, after Diagnosis of Pneumocystis carinii Pneumonia, in the United States. The Journal of Infectious Diseases, 183(9), pp.1409-1412. DISCLOSURES: No relevant relationships by salah alandary No relevant relationships by Joella Lambert No relevant relationships by Joshua Lung

10.
ASAIO Journal ; 68(Supplement 3):61, 2022.
Article in English | EMBASE | ID: covidwho-2058514

ABSTRACT

Objective: The motto Cannulate, Extubate, Ambulate reflects the care ECMO patients receive at West Virginia University Medicine. Early mobility, crucial in our outcomes, especially with the COVID-19 population, is started with a Physical Therapist. This is followed by all team members participating in ECMO mobilization. This project examined the impact of mobilization for our COVID+ population placed on VV ECMO. Method(s): A WVU retrospective review was completed of COVID-19+ patients on ECMO between 3/2020 and 12/2021, determining survival to decannulation and discharge location. Mobility was examined for ECMOday of first active participation, first active transfer out of bed, and first ambulation. Further, PT sessions during cannulation, total PT, staff assist mobility while cannulated, and total number of sessions during admission. All patients who survived to discharge were included in survival rate, but those transferred to outside facilities for ECMO management were excluded from mobility and discharge location analyses. Result(s): Out of 91 patients, 70% successfully decannulated, and 98.4% survived to discharge. Mobilization began day 1 of ECMO, averaging 7.6 sessions/patient during their hospitalization. 88% performed their first active transfers with PT assist. Mobility sessions were also performed by Nursing/ECMO Specialists (3.6 times vs. 2.8 times). Total active mobilizations ranged 2-69 sessions, averaging 13.9 mobilizations during hospitalization. 60% of COVID-19 ECMO survivors were discharged home. Conclusion(s): Physical therapists lead mobility efforts, however, active involvement of nursing and ECMO Specialists is vital to provide continuity and repetition of mobility. Our results suggest teamwork improves patient survival and other important outcomes.

11.
ASAIO Journal ; 68(Supplement 3):66, 2022.
Article in English | EMBASE | ID: covidwho-2058241

ABSTRACT

Purpose: We report the clinical outcomes of an Adult Respiratory ECMO (VV-ECMO) program that was rapidly established in a community hospital within a 4-week period. The program was launched in response to increasing patients presenting with acute respiratory failure due to COVID-19. Method(s): Our institution supported urgent preparedness to add VVECMO therapy to our established, nurse-run Adult VA-ECMO program. ICU nurses were trained to run VV-ECMO through interdisciplinary collaboration with neonatal-pediatric ECMO nurses, cardiac perfusionists, providers (NP, PA), respiratory therapists, and physicians. Retrospective data of VV-ECMO therapy was collected between November 2020 and June 2022. Result(s): 29 patients with ARDS due to COVID-19 received VV-ECMO. Of the 29 patients were 23 males and 6 females, of median age 48 (31-59) years and median body mass index (BMI) 31.4 kg/m2 (20.5-49.2). The mean duration of VV-ECMO was 970 hours (44.1 days) and the longest run time was 2752 hours (114.6 days). Patient survival rate to VV-ECMO explant was 66%. Patient survival to discharge with a return to pre-ECMO functional capacity was 55%, defined as supplemental oxygen requirements less than 3L nasal cannula and rehabilitating to activities of daily living. Conclusion(s): In the setting of the COVID-19 pandemic, an Adult VV-ECMO program was rapidly developed and executed in an advanced community hospital system. Our VV-ECMO program results are comparable to programs at major academic centers, with survival rates on par with statistics reported by the ELSO registry. Additionally, our outcomes demonstrate that a nurse-run VV-ECMO program can be both feasible and successful.

12.
ASAIO Journal ; 68(Supplement 3):26, 2022.
Article in English | EMBASE | ID: covidwho-2058110

ABSTRACT

Background: Mortality for patients receiving extracorporeal membrane oxygenation (ECMO) for COVID-19 has increased over time. We investigated the association between immunomodulators and mortality for patients receiving ECMO for COVID-19. Method(s): We analysed the Extracorporeal Life Support Organisation Registry from Jan 1, 2020 through Dec 31, 2021, comparing in-hospital mortality and the overall survival since ECMO initiation of patients who did and did not receive immunomodulators (selective interleukin blockers, corticosteroids, janus-kinase inhibitors, convalescent plasma, and intravenous immunoglobulins) before or during ECMO, by using logistic regression and Cox regression. We calculated the propensity scores, and applied the overlap-weightage method to account for confounding factors. We conducted sensitivity analyses including regression models using inverse propensity score weightage method, models adjusted by propensity score, and unadjusted models to ensure robustness of results. A subgroup analysis on patients receiving corticosteroids was conducted. Result(s): 7180 patients were included in the final analysis. Immunomodulators were associated with increased mortality (OR: 1.168, 95%CI: 1.059-1.289, p=0.0020) and shorter survival since ECMO (HR: 1.05, 95%- CI: 1.078, 95%CI: 1.007-1.154, p=0.031). Similarly, corticosteroids were associated with a significant increase in mortality (OR: 1.302, 95%-CI: 1.180-1.437, p<0.0001) and shorter survival (HR: 1.221, 95%-CI: 1.139- 1.308, p<0.0001). Sensitivity analyses did not significantly change the overall results. Conclusion(s): Immunomodulators and corticosteroids, in particular, were associated with a significant increase in mortality amongst patients receiving ECMO for COVID-19, even after adjusting for potential confounding variables. Further studies are required to evaluate the timing of immunomodulators and understand the possible mechanisms behind this association.

13.
Ter Arkh ; 94(7): 827-835, 2022 Aug 12.
Article in Russian | MEDLINE | ID: covidwho-2044341

ABSTRACT

AIM: The primary objective of the interim analysis of the MULTISPECT study was to evaluate the short-term efficacy of the treatment and long-term outcomes in cohorts of primary and pretreated patients with multiple myeloma (MM) receiving treatment in actual clinical practice in various regions of the Russian Federation. Secondary objectives were a description of the main characteristics of patients; analysis of the most commonly used therapy regimens of the 1st and later lines and the sequence of their changes; evaluation of the response to therapy. Additional objectives included evaluation of the effect of the new COVID-19 coronavirus infection on the course of MM in patients. MATERIALS AND METHODS: The study is an observational retrospective-prospective multicenter cohort study. For its implementation, a structured database of patients with MM was used, provided by hematologists of the centers affiliated for the study. RESULTS: The study included 1,294 patients (cohort 1 806, cohort 2 488). In both cohorts, patients aged 6069 years were in the majority. 3 lines of therapy (L1, L2, L3) were used for cohort 1; in cohort 2, the 4th line of therapy was also used in 2 patients. The therapy regimens were analyzed for 290 (22.41%) of all patients in the study. Responses to therapy were analyzed for 214 patients of cohort 1 and 109 patients of cohort 2. Autologous and allogeneic hematopoietic stem cell transplantations were carried out for a limited proportion of patients in both cohorts. At the end of the study and upon presentation of its results, the status of patients was the following: 96% of patients in cohort 1 and 89% in cohort 2 were alive. The therapy regimens in both cohorts were characterized by variability. The most commonly used regimens in each of the lines of therapy have been identified. The most used therapy regimen in patients with MM of both cohorts was the VCD-regime. Rd-regime in cohort 1 and RD-regime in cohort 2 were the second most frequent used regimens. In patients of both cohorts, the therapy regimens including Bortezomib were most often used. CONCLUSION: The variety of therapy regimens used to treat MM in actual clinical practice may be due to the factors of availability of new medicines and updated recommendations for the treatment of the disease. Further, in the context of this study, a more detailed analysis of the efficacy of certain therapy regimens in the 1st and later lines on progression free survival and overall survival of MM patients should be carried out.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/epidemiology , Multiple Myeloma/therapy , Bortezomib/therapeutic use , Retrospective Studies , Cohort Studies , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/therapy , Transplantation, Autologous/methods , Hematopoietic Stem Cell Transplantation/methods , Treatment Outcome , Disease-Free Survival
14.
Journal of the Intensive Care Society ; 23(1):3, 2022.
Article in English | EMBASE | ID: covidwho-2043051

ABSTRACT

Introduction: Previous studies on acute respiratory distress syndrome (ARDS) relate trajectories to initial degree of hypoxia1,2 Further work is required to deduce whether previous ARDS frameworks are applicable to COVID-19 ARDS patients. Objectives: How does hypoxia progression influence outcomes in non-COVID ARDS patients and does this differ from COVID-19 ARDS patients? Methods: Mechanically ventilated patients that met the Berlin ARDS Criteria1 were selected from the Medical Information Mart for Intensive Care (MIMIC) database.3 Daily blood gas and ventilatory settings were analysed, from the point of intubation to death or discharge, allowing longitudinal analysis with high granularity. Our primary outcome was how the trajectory of patients was dependent on their hypoxia progression. Secondary outcomes included how base characteristics and initial clinical parameters affect trajectory and outcomes. Comparative analysis was performed between the results of this study and a previous large COVID-19 ARDS study4 Results: 1,575 ICU admissions were included in the study. All results report this study first followed by the COVID-19 study.4 Overall survival rate was higher (70.2% vs 57.7%);less patients had initial moderate or severe hypoxia (54.5% vs 76.8%);less patients had worsening of hypoxia over the first 7 days (18.9% vs 31.8%);and more patients improved their hypoxia status (33.1% vs 23.5%). This study showed a smaller proportion of hypoxia nonresolvers compared to the COVID study (32.6% vs 57.9%). However, non-resolvers in the two studies had similar survival rates (58.6% vs 60.4%). Length of ICU stay (LOS) and duration of invasive mechanical ventilation (IMV) was significantly less in this study compared to the COVID-19 study regardless of hypoxia resolver status. Conclusions: Non-COVID ARDS patients have a more predictable natural history and trajectory compared to COVID-19 ARDs patients. Respiratory failure occurs less frequently and is quicker to resolve, resulting in a lower proportion of hypoxia non-resolvers. However hypoxia non-resolvers of both populations have similar survival outcomes. Despite this, COVID ARDS patient have much longer ICU length of stay and length of ventilation which has significant implications for provision of critical care resources. Further analysis of the impact of COVID-19 therapies on these outcomes is needed.

15.
British Journal of Surgery ; 109:vi56, 2022.
Article in English | EMBASE | ID: covidwho-2042556

ABSTRACT

Background: Thymic epithelial tumours (TET) are rare thoracic cancers with reported annual incidence of 1.3-3.2 per million. TETs are histologically classified as thymomas or thymic carcinomas. Thymomas are slow-growing tumours that comprise the majority of lesions found in the anterior mediastinum. They can be associated with autoimmune disorders such as Myasthenia Gravis. Contrast CT is the standard for diagnosis. Surgery is treatment of choice depending on resectability of the tumour. The Masaoka-Koga staging system is correlated with overall survival and is utilised post-surgical resection to guide adjuvant treatment. Case Presentation: A 50-year-old male presented with cough, shortness of breath, myalgia, sore throat, and reduced sense of smell that was diagnosed as COVID-19. CT chest and abdomen showed a large heterogeneous mediastinal mass (11cm) invading the innominate vein and left upper lobe with two left pleural deposits, and diaphragmatic disease. CT biopsy confirmed thymoma. MDT recommended surgery due to patient age and resectability of tumour with post-operative chemotherapy. The sites of disease necessitated a left thoracotomy and median sternotomy. The pleural and diaphragmatic deposits were resected, followed by left upper lobe anatomical dissection enbloc with invaded pericardium, phrenic and vagus nerve, followed by median sternotomy to resect the thymic mass along with the innominate vein. Final staging was stage IVA thymoma (B2 and B3) (T3N0M1aR0). A CT scan at 1 year showed no recurrence despite patient declining adjuvant chemotherapy. Conclusion: Surgical resection is a viable treatment option for patients with stage IVA thymoma who present with resectable primary and metastatic disease.

16.
British Journal of Surgery ; 109:vi40-vi41, 2022.
Article in English | EMBASE | ID: covidwho-2042553

ABSTRACT

Aim: Immune checkpoint inhibitors (ICIs) have been shown to prolong survival in patients that have locally advanced stage III/IV and metastatic non-small cell lung cancer (NSCLC). The role that salvages surgery plays in persistent localised disease and unresponsive synchronous cancer following treatment with a course of ICIs is not yet fully clear. We present a case series of nine patients with stage III/ IV NSCLC that underwent surgical resection after treatment with the ICI, pembrolizumab. Method: Six cases underwent salvage surgery after downstaging of the primary cancer following pembrolizumab treatment and three patients had resection of contralateral lung nodules that were unresponsive to ICI therapy. Three of the cases were open thoracotomies, 3 were robotic-assisted and 2 were video-assisted. One case was converted to open due to pulmonary artery involvement. Results: There was complete, successful macroscopic resection in all cases with each showing histological evidence for active cancer cells. One patient died of COVID pneumonitis in the community within 60 days of surgery. All other patients are alive with no evidence of localised disease or of any disease reoccurrence within 3-18 months of their surgery. Conclusions: Our case series demonstrates the potential for salvage pulmonary resection in select patients with advanced stage NSCLC who have persistent localised disease or unresponsive synchronous cancer after treatment with the ICI, pembrolizumab. Salvage surgery in this group of patients is safe and pragmatic despite high levels of post-immunotherapy hilar fibrosis. Further studies will be required in order to assess overall survival rates.

17.
Kidney International Reports ; 7(9):S508-S509, 2022.
Article in English | EMBASE | ID: covidwho-2041721

ABSTRACT

Introduction: Because of the limited donor pool, transplants are being done across the blood group and even HLA incompatibility barriers. But this comes at the cost of increased immunosuppression and the side effects. Effect of this intensified immunosuppression on the incidence of post transplant infections and the type of infection has not been studied extensively. Methods: We retrospectively analysed the incidence of infection in ABO incompatible transplants (ABOi) and compared it with propensity matched cohort of ABO compatible transplants(ABOc) over the same timeframe i.e. 2011 to April 2019. using hospital eHIS record system. Patients were matched with 1:2 ratio (ABOi: ABOc) for age (<60yr, >60yrs),sex, number of previous transplants, pretransplant infections, history of prior immunosuppression, diabetic status, NODAT, and induction agent used. Desensitization protocol for ABO incompatible transplant includes rituximab with double filtration plasmapheresis, plasmapharesis or immunoadsorption to target anti blood group titre of 8. Patient with high immunological risk (e.g.second transplant, HLA incompatible) receive ATG induction while others receive basiliximab induction. Valganciclovir prophylaxis was given only in patients with ATG induction. Results: [Formula presented] [Formula presented] During the study period 89 patients underwent ABOi transplants which were compared with 178 ABOc transplants. (Table1)Mean follow up duration was 50.45months (SD 26.8) in ABOi group and 49.47months (SD28.7) in ABOc group. 17% patients lost to follow up with their last follow up being more than 2 years before. Incidence of overall infections was similar in both the groups (59% (43/89) Vs 44.3% (79/178);p=0.6). (Table2) Incidence of urinary tract infections(UTI)was significantly more in ABOi group vs ABOc group.(23.5% (21/89) vs 11.79% (21/178);p=0.019). Cytomegalovirus infections (CMV) were significantly more in ABOi group 12.3% (11/89) as compared to ABOc group 5% (9/187) (p=0.04). All the patients with CMV infection were CMV IgG positive pretransplant except 2, one from ABOc group who was CMV IgG negative and another from ABOi group who’s pretransplant CMV serology was unavailable. There was no significant difference in incidence of fungal infection, pneumocystis infection, diarrheal infections (other than CMV),pneumonia (other than CMV, PCP, fungal), Herpes, BKV infection. Incidence of post-transplant tuberculosis (3.3% (3/89) Vs 2.8% (5/178);p=1.0) and SARS COV2 infections (12.3% (11/89) vs 9% (16/178);p=0.39 was similar in both the groups. Patient survival was similar in both the groups i.e.95.5% but death censored graft loss was significantly more in ABOi group 0.9% (8/89) as compared ABOc group 0.3% (5/178) p=0.03. Reason of graft loss in all the patients was immunological and not infection. Infection was cause for death in three ABOi patients and four ABOc patients. Conclusions: Overall incidence of infections in ABOi transplants was similar to Abo compatible transplant. Incidence of UTIs and CMV infections were significantly higher in ABOi group. No conflict of interest

18.
Annals of Oncology ; 33:S1427-S1428, 2022.
Article in English | EMBASE | ID: covidwho-2041570

ABSTRACT

Background: AAP or ENZ added to ADT improves outcomes for mHSPC. Any benefit of combining ENZ & AAP in this disease setting is uncertain. Methods: STAMPEDE is a multi-arm, multi-stage (MAMS), platform protocol conducted at 117 sites in the UK & Switzerland. 2 trials with no overlapping controls randomised mHSPC patients (pts) 1:1 to ADT +/- AAP (1000mg od AA + 5mg od P) or AAP + ENZ (160mg od). Treatment was continued to progression. From Jan 2016 docetaxel 75mg/m2 3-weekly with P 10mg od was permitted + ADT. Using meta-analysis methods, we tested for evidence of a difference in OS and secondary outcomes (as described previously: failure-free, metastatic progression-free, progression-free & prostate cancer specific survival) across the 2 trials using data frozen 3 Jul 2022. All confidence intervals (CI) 95%. Restricted mean survival times (RMST) restricted to 84 months (m). Results: Between Nov 2011 & Jan 2014, 1003 pts were randomised ADT +/- AAP & between Jul 2014 & Mar 2016, 916 pts were randomised ADT +/- AAP + ENZ. Randomised groups were well balanced across both trials. Pt cohort: age, median 68 years (yr), IQR 63, 72;PSA prior to ADT, median 95.7 ng/ml, IQR 26.5, 346;de novo 94%, relapsed after radical treatment, 6%. In AAP + ENZ trial, 9% had docetaxel + ADT. OS benefit in AAP + ENZ trial, HR 0.65 (CI 0.55‒0.77) p = 1.4×10-6;in AAP trial, HR 0.62 (0.53, 0.73) p = 1.6×10-9. No evidence of a difference in treatment effect (interaction HR 1.05 CI 0.83‒1.32, p = 0.71) or between-trial heterogeneity (I2 p = 0.70). Same for secondary end-points. % (CI) of pts reporting grade 3-5 toxicity in 1st 5 yr: AAP trial, ADT: 38.5 (34.2-42.8), + AAP: 54.4 (50.0-58.8);AAP + ENZ trial, ADT: 45.2 (40.6 – 49.8), + AAP + ENZ: 67.9 (63.5 – 72.2);most frequently increased with AAP or AAP + ENZ = liver derangement, hypertension. At 7 yr in AAP trial (median follow-up: 95.8m), % (CI) pts alive with ADT: 30 (26, 34) versus with ADT + AAP: 48 (43, 52);RMST: ADT: 50.4m, ADT + AAP: 60.6m, p = 6.6 x 10-9. Conclusions: ENZ + AAP need not be combined for mHSPC. Clinically important improvements in OS when adding AAP to ADT are maintained at 7 yr. Clinical trial identification: NCT00268476. Legal entity responsible for the study: Medical Research Council Clinical Trials Unit at University College London. Funding: Cancer Research UK, Medical Research Council, Janssen, Astellas. Disclosure: G. Attard: Financial Interests, Personal, Invited Speaker: Janssen, Astellas, AstraZeneca;Financial Interests, Personal, Advisory Board: Janssen, Astellas, Novartis, Bayer, AstraZeneca, Pfizer, Sanofi, Sapience, Orion;Financial Interests, Personal, Royalties, Included in list of rewards to discoverers of abiraterone: Institute of Cancer Research;Financial Interests, Institutional, Research Grant: Janssen, Astellas;Non-Financial Interests, Principal Investigator: Janssen, Astellas;Non-Financial Interests, Advisory Role: Janssen, AstraZeneca. W.R. Cross: Financial Interests, Personal, Invited Speaker, Speaker fee: Myriad Genetics, Janssen, Astellas;Financial Interests, Personal, Advisory Board, Advisory Board fee: Bayer;Financial Interests, Institutional, Research Grant, Research grant: Myriad Genetics. S. Gillessen: Financial Interests, Personal, Advisory Board, 2018: Sanofi, Roche;Financial Interests, Personal, Advisory Board, 2018, 2019: Orion;Financial Interests, Personal, Invited Speaker, 2019 Speaker's Bureau: Janssen Cilag;Financial Interests, Personal, Advisory Board, 2020: Amgen;Financial Interests, Personal, Invited Speaker, 2020: ESMO;Financial Interests, Personal, Other, Travel Grant 2020: ProteoMEdiX;Financial Interests, Institutional, Advisory Board, 2018, 2019, 2022: Bayer;Financial Interests, Institutional, Advisory Board, 2020: Janssen Cilag, Roche, MSD Merck Sharp & Dohme, Pfizer;Financial Interests, Institutional, Advisory Board, 2018: AAA International, Menarini Silicon Biosystems;Financial Interests, Institutional, Advisory Board, 2019, 2020: Astellas Pharma;Financial Interests, Institutional, Advisory B ard, 2019: Tolero Pharmaceuticals;Financial Interests, Personal, Invited Speaker, 2021, 2022: SAKK, DESO;Financial Interests, Institutional, Advisory Board, 2021: Telixpharma, BMS, AAA International, Novartis, Modra Pharmaceuticas Holding B.V.;Financial Interests, Institutional, Other, Steering Committee 2021: Amgen;Financial Interests, Institutional, Advisory Board, 2021, 2022: Orion, Bayer;Financial Interests, Personal, Invited Speaker, 2021: SAKK, SAKK, SAMO - IBCSG (Swiss Academy of Multidisciplinary oncology);Financial Interests, Personal, Advisory Board, 2021: MSD Merck Sharp & Dhome;Financial Interests, Personal, 2021: RSI (Televisione Svizzera Italiana);Financial Interests, Institutional, Invited Speaker, 2021: Silvio Grasso Consulting;Financial Interests, Institutional, Other, Faculty activity 2022: WebMD-Medscape;Financial Interests, Institutional, Advisory Board, 2022: Myriad genetics, AstraZeneca;Financial Interests, Institutional, Invited Speaker, 2022: TOLREMO;Financial Interests, Personal, Other, Travel support 2022: AstraZeneca;Financial Interests, Institutional, Funding, 2021, Unrestricted grant for a Covid related study as co-investigator: Astellas;Non-Financial Interests, Advisory Role, 2019: Menarini Silicon Biosystems, Aranda;Non-Financial Interests, Advisory Role, Continuing: ProteoMediX. C. Pezaro: Financial Interests, Personal, Advisory Board, Ad board Dec 2020: Advanced Accelerator Applications;Financial Interests, Personal, Advisory Board, Aug 2021: Astellas;Financial Interests, Personal, Advisory Board, Oct 2021: Bayer;Financial Interests, Personal, Invited Speaker, Sept-Oct 2020: AstraZeneca;Financial Interests, Personal, Invited Speaker, Oct 2020: Janssen;Financial Interests, Personal, Advisory Board, July-Sept 2022: Pfizer. Z. Malik: Financial Interests, Personal, Advisory Board, advisry board for new hormonal therapy for breast cancer: sanofi;Financial Interests, Institutional, Invited Speaker, research grant for CHROME study: sanofi;Other, Other, support to attend meetings or advisory boards in the past: Astellas,Jaansen,Bayer;Other, Other, Sponsorship to attend ASCO meeting 2022: Bayer. M.R. Sydes: Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training sessions for clinicians (no discussion of particular drugs): Janssen;Financial Interests, Personal, Invited Speaker, Speaker fees at clinical trial statistics training session for clinicians (no discussion of particular drugs): Eli Lilly;Financial Interests, Institutional, Research Grant, Educational grant and drug for STAMPEDE trial: Astellas, Janssen, Novartis, Pfizer, Sanofi;Financial Interests, Institutional, Research Grant, Educational grant and biomarker costs for STAMPEDE trial: Clovis Oncology. L.C. brown: Financial Interests, Institutional, Research Grant, £170k educational grant for the FOCUS4-C Trial from June 2017 to Dec 2021: AstraZeneca;Financial Interests, Institutional, Funding, Various grants awarded to my institution for work undertaken as part of the STAMPEDE Trial: janssen pharmaceuticals;Non-Financial Interests, Other, I am a member of the CRUK CERP funding advisory panel and my Institution also receive grant funding from CRUK for the STAMPEDE and FOCUS4 trials: Cancer Research UK. M.K. Parmar: Financial Interests, Institutional, Full or part-time Employment, Director at MRC Clinical Trials Unit at UCL: Medical Research Council Clinical Trials Unit at UCL;Financial Interests, Institutional, Research Grant: AstraZeneca, Astellas, Janssen, Clovis;Non-Financial Interests, Advisory Role, Euro Ewing Consortium: University College London;Non-Financial Interests, Advisory Role, rEECur: University of Birmingham;Non-Financial Interests, Advisory Role, CompARE Trial: University of Birmingham. N.D. James: Financial Interests, Personal, Advisory Board, Advice around PARP inhibitors: AstraZeneca;Financial Interests, Personal, Advisory Board, Prostate cancer therapies: Janssen, Clovis, Novartis;Financial Interests, Institutional, Expert Testimony, Assisted with submissions regarding licencing for abiraterone: Janssen;Financial Interests, Personal, Advisory Board, Docetaxel: Sanofi;Financial Interests, Institutional, Expert Testimony, Providing STAMPEDE trial data to facilitate licence extensions internationally for docetaxel: Sanofi;Financial Interests, Personal, Advisory Board, Bladder cancer therapy: Merck;Financial Interests, Personal, Advisory Board, Advice around novel hormone therapies for prostate cancer: Bayer;Financial Interests, Personal, Invited Speaker, Lecture tour in Brazil August 2022 - speaking on therapy for advanced prostate cancer: Merck Sharp & Dohme (UK) Limited;Financial Interests, Institutional, Invited Speaker, Funding for STAMPEDE trial: Janssen, Astellas;Financial Interests, Institutional, Invited Speaker, Funding for RADIO trial bladder cancer: AstraZeneca. All other authors have declared no conflicts of interest.

19.
Annals of Oncology ; 33:S1050, 2022.
Article in English | EMBASE | ID: covidwho-2041544

ABSTRACT

Background: The value of increased HER2 gene copy number (GCN) in NSCLC is unclear. In this study we defined its frequency and characterized a cohort of patients harboring it. Methods: Patients with stage IIIB/IV NSCLC enrolled in the Gustave Roussy MSN study (NCT02105168) between Oct. 2009 and Feb. 2016 were screened by FISH (positivity defined as HER2 GCN to centromeres ratio ≥ 2) and tested for other molecular alterations. Descriptive analyses of clinical-pathological data were performed, progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier method. Results: HER2 FISH tested positive in 22 of 250 screened patients (9%). Median age was 60 years (range 47-80), 68% (n=15) were male, 91% (n=20) were current or former tobacco smokers (median exposure 47 pack-year), 64% (n=14) had adenocarcinoma, 18% (n=4) squamous cell and 18% (n=4) large cell carcinoma. 91% (n=20) had an ECOG PS of 0 or 1. Stage IV with extra-thoracic involvement was the most common clinical presentation (64%, n=14). Overall, 95% of patients (n=21) had 1 or 2 metastatic sites at diagnosis (bone 32%, lung 27%, nodes 18%, liver 18%, brain 18%). In 9 patients (41%) 12 concurrent molecular alterations were detected: 5 KRAS mutation (3 G12C, 1 G12D, 1 G61H), 2 HER2 exon 20 insertion, 1 EGFR exon 19 deletion, 1 BRAF V600E mutation, 1 ALK rearrangement, 1 FGFR1 and 1 MET amplification. 18 patients received first-line platinum-based chemotherapy, with 33% (95% CI 16-56) objective response rate and 83% (95% CI 61-94) disease control rate. After a median follow-up of 28 months (95% CI 23-45), median PFS and OS were 5.9 (95% CI 3.4-11.0) and 15.3 (95% CI 10.3-NR) months, respectively. Median PFS was longer in patients with higher GCN. As further line of treatment, 5 patients received trastuzumab: 4 in combination with chemotherapy and 1 as monotherapy, with 1 stabilization of disease as best response. 3 patients received nivolumab (1 partial response and 1 stable disease) and 3 a targeted therapy (anti ALK, EGFR, BRAF). Conclusions: Increased HER2 GCN was found in 9% of patients with unresectable NSCLC, was not correlated to particular clinical characteristics, but frequently occurred with other molecular alterations. Its clinical actionability and the correlation with protein expression deserve further characterization. Clinical trial identification: NCT02105168. Legal entity responsible for the study: Gustave Roussy. Funding: Has not received any funding. Disclosure: M. Tagliamento: Other, Personal, Other, Travel grants: Roche, Bristol-Myers Squibb, AstraZeneca, Takeda, Eli Lilly;Other, Personal, Writing Engagements, Honoraria as medical writer: Novartis, Amgen. E. Auclin: Financial Interests, Personal, Advisory Board: Amgen, Sanofi. E. Rouleau: Financial Interests, Institutional, Advisory Board: AstraZeneca, Roche, Amgen, GSK;Financial Interests, Institutional, Invited Speaker: Clovis, BMS;Financial Interests, Institutional, Funding, Data base: AstraZeneca. A. Bayle: Non-Financial Interests, Institutional, Other, Principal/Sub-Investigator of Clinical Trials: AbbVie, Adaptimmune, Adlai Nortye USA Inc, Aduro Biotech, Agios Pharmaceuticals, Amgen, Argen-X Bvba, Astex Pharmaceuticals, AstraZeneca Ab, Aveo, Basilea Pharmaceutica International Ltd, Bayer Healthcare Ag, Bbb Technologies Bv, BeiGene, BicycleTx Ltd, Non-Financial Interests, Institutional, Research Grant: AstraZeneca, BMS, Boehringer Ingelheim, GSK, INCA, Janssen Cilag, Merck, Novartis, Pfizer, Roche, Sanofi;Financial Interests, Institutional, Other, drug supplied: AstraZeneca, Bayer, BMS, Boehringer Ingelheim, GSK, MedImmune, Merck, NH TherAGuiX, Pfizer, Roche. F. Barlesi: Financial Interests, Personal, Advisory Board: AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly Oncology, F. Hoffmann–La Roche Ltd, Novartis, Merck, Mirati, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis, Seattle Genetics, Takeda;Non-Financial Interests, Principal Investigator: AstraZeneca, BMS, Merck, Pierre Fabre, F. Hoffmann-La Roche Ltd. D. Planchard: Financial I terests, Personal, Advisory Board: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Samsung, Celgene, AbbVie, Daiichi Sankyo, Janssen;Financial Interests, Personal, Invited Speaker: AstraZeneca, Novartis, Pfizer, priME Oncology, Peer CME, Samsung, AbbVie, Janssen;Non-Financial Interests, Principal Investigator, Institutional financial interests: AstraZeneca, BMS, Merck, Novartis, Pfizer, Roche, Daiichi Sankyo, Sanofi-Aventis, Pierre Fabre;Non-Financial Interests, Principal Investigator: AbbVie, Sanofi, Janssen. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, EISAI, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche;Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda;Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI;Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS;Financial Interests, Institutional, Research Grant, COVID research Grant: Amgen;Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. All other authors have declared no conflicts of interest.

20.
Annals of Oncology ; 33:S1022-S1023, 2022.
Article in English | EMBASE | ID: covidwho-2041543

ABSTRACT

Background: OSE2101 (Tedopi) is an anticancer vaccine that increased overall survival (OS) (HR 0.59, p=0.017) versus Standard of Care Chemotherapy in the population of interest (PoI N=118) of patients with IO secondary resistance after sequential CT-IO (ESMO 2021 #47LBA). The Net Treatment Benefit (NTB) is an original method combining efficacy and safety endpoints to test the overall improvement in health outcome between 2 treatments (Buyse M. Stat Med 2010). NTB was assessed in the overall population (N=219) from whom OS improvement of OSE2101 (HR 0.86, p=0.35) was lower than in PoI. Methods: NTB was tested by comparing prioritized outcomes using Generalized Paired Wise Comparisons (GPC). The prioritized outcomes were OS, then time to worsening ECOG (threshold=2 months) followed by severe adverse events, progression free survival (shorter vs. longer than 2 months) and Quality of Life (threshold=5 points on Global Health Status of EORTC-QLQC30). Analysis was stratified using the 3 strata of the study (histology, best response to 1rst line, line of prior IO) and enrollment time (before vs during COVID-19). Sensitivity analyses used no stratification, different thresholds of clinical relevance and PoI. Results: In the primary analysis (1088 pairs), NTB was 19% and reached statistical significance in favor of OSE2101 (p=0.035). In unstratified analysis (11120 pairs), NTB was 11% (p=0.188). In the PoI (388 pairs), NTB was 22% (p stratified=0.074) and 28% (p=0.014) in unstratified analysis (3040 pairs). Although the primary analysis was statistically positive, results were not consistent in some sensitivity analyses due to the limited sample size and the impact of stratification factors. Conclusions: An overall improvement in health outcome was observed with OSE2101 in the overall population of advanced NSCLC after IO failure with a NTB of 19% over SoC. In PoI with IO secondary resistance after CT-IO, the NTB was 22%. Post-hoc analyses are ongoing intended to explain the variability of NTB and will be detailed. Clinical trial identification: EudraCT: 2015-003183-36;NCT02654587. Editorial acknowledgement: We thank Pierre Attali (Medical Expert, MD) for his support in the writing of the . Legal entity responsible for the study: Ose Immunotherapeutics. Funding: Ose Immunotherapeutics. Disclosure: M.E. Buyse: Financial Interests, Personal, Officer, Chief Scientific Officer: IDDI;Financial Interests, Personal, Invited Speaker, Board Member: CluePoints;Financial Interests, Personal, Stocks/Shares: IDDI, CluePoints. F. Montestruc: Financial Interests, Personal, Member of the Board of Directors, CEO of the Company: eXYSTAT SAS;Financial Interests, Institutional, Other, Statistician Consultant: AbbVie, Biocodex, Geneuro, Gensight, Guerbet, Imcheck, Ose Immunotherapeutics, Pfizer, Takeda;Non-Financial Interests, Personal, Other, Statistician Consultant and Training: Institut Pasteur. J. Chiem: Financial Interests, Personal, Full or part-time Employment: IDDI. V. Deltuvaite-Thomas: Financial Interests, Personal, Full or part-time Employment: IDDI. S. Salvaggio: Financial Interests, Personal, Full or part-time Employment, Working as a statistician: International Drug Development Institute. M.R. Garcia Campelo: Financial Interests, Personal, Advisory Role: Roche/Genentech, MSD Oncology, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, Janssen Oncology;Financial Interests, Personal, Speaker’s Bureau: Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Novartis, Takeda, Boehringer Ingelheim, MSD Oncology, Sanofi/Aventis, Janssen Oncology, Amgen;Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Roche/Genentech, MSD Oncology, Pfizer. F. Cappuzzo: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, PharmaMar, Mirati, Novocure, OSE, and MSD;Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, BMS, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, Mirati, PharmaMar, Novocure, OSE, Galecto and MS . S. Viteri Ramirez: Financial Interests, Personal, Advisory Board: Merck Healthcare KGAA Germany, Bristol Myers Squibb S.A. U, Puma Biotechnology;Financial Interests, Personal, Invited Speaker: Takeda Farmaceutica España SA, MSD de España SA, AstraZeneca Farmaceutica Spain, Roche Farma SA;Financial Interests, Personal, Expert Testimony: Reddy Pharma Iberia SAU. W. Schuette: Financial Interests, Personal, Other, Honoraria: Roche, MSD, Novartis;Financial Interests, Personal, Advisory Role: Roche, MSD, Novartis. A. Zer: Financial Interests, Personal, Invited Speaker: Roche, BMS, MSD, Takeda, Pfizer, Novartis;Financial Interests, Personal, Advisory Board: AstraZeneca, Steba, Oncohost;Financial Interests, Personal, Stocks/Shares: Nixio;Financial Interests, Institutional, Research Grant: BMS. S. Comis: Financial Interests, Personal, Full or part-time Employment: Ose Immunotherapeutics. B. Vasseur: Financial Interests, Personal, Full or part-time Employment: Ose Immunotherapeutics;Financial Interests, Personal, Other, Actions: Ose Immunotherapeutics. R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Seattle Genetics, Pfizer, Takeda, Regeneron, MSD, Bristol Myers-Squibb, PharmaMar, Bayer;Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim, Foundation Medicine;Financial Interests, Personal, Expert Testimony: Novartis;Financial Interests, Personal and Institutional, Invited Speaker: Roche, AstraZeneca, MSD, Amgen, Celon Pharma, Pfizer, Novartis, Brsitol Myers-Squibb, Eli Lilly, Loxo;Financial Interests, Invited Speaker: BeiGene, Ardigen, Ose Immunotherapeutics;Financial Interests, Personal and Institutional, Other, Subinvestigator and ad hoc Consultant: PDC* line Pharma;Non-Financial Interests, Institutional, Product Samples: Novartis, Pfizer, AstraZeneca, Roche;Other, Travel: Roche, Bristol Myers-Squibb, AstraZeneca. G. Giaccone: Financial Interests, Personal, Advisory Board: Novartis;Financial Interests, Institutional, Research Grant: Karyopharm. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, EISAI, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. E. Felip: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Glaxo Smith Kline, Janssen, Medical Trends, Merck Sharp & Dohme, Pfizer, Puma, Sanofi, Takeda, Merck Serono, Peptomyc, Regeneron, Syneos Health, F. Hoffmann-La Roche;Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Medscape, Merck Sharp & Dome, Peervoice, Pfizer, Springer, Touch Medical, Amgen, F. Hoffmann-La Roche, Janssen, Medical Trends, Merck Serono;Financial Interests, Personal, Invited Speaker, Independent member: Grifols;Financial Interests, Institutional, Invited Speaker, Clinical Trial: F. Hoffmann-La Roche Ltd, Merck Sharp & Dohme Corp, AstraZeneca AB, Daiichi Sankyo Inc, Exelixis Inc, Merck KGAA, Janssen Cilag International NV, GlaxoSmithKline Research & Development Limited, AbbVie Deutschland GmbH & Co KG, Novartis Farmaceutica SA, Bayer Consumer Care AG, Takeda Pharmaceuticals International, Boehringer Ingelheim International GmbH, Pfizer S.L.U., Amgen Inc, Bristol-Myers Squibb International Corporation (BMS), Mirati Therapeutics Inc;Non-Financial Interests, Leadership Role, President Elect (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica);Non-Financial Interests, Member, Member of ESMO Nominating Committee and Compliance Committee: ESMO;Non-Financial Interests, Leadership Role, Member of Board of Directors and the Executive Committee (2017-Sept 2021): IASLC (International Association for the Study of Lung Cancer);Non-Fina cial Interests, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform). All other authors have declared no conflicts of interest.

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