Non-contrast cardiac magnetic resonance imaging after SARS-CoV2 infection or vaccination in asymptomatic adolescents: Insights from the EnIGMA study

Background: Myocarditis after SARS-CoV2 infection or vaccination is rare, but seems to be relatively more frequent in young population. Cardiac magnetic resonance (CMR) T2 weighted sequences have the potential to detect subclinical myocarditis. However, there is paucity of data on the potential myocardial involvement after SARS-CoV2 infection or vaccination in asymptomatic adolescents. Purpose(s): To evaluate the presence of subclinical myocardial damage in adolescents who were infected with SARS-CoV2 or vaccinated against SARS-CoV2 using non-contrast CMR imaging. Method(s): Asymptomatic adolescents enrolled in the Early ImaginG Markers of unhealthy lifestyles in Adolescents (EnIGMA) project were scanned using a 3-Tesla CMR scanner between March 2021 and October 2021. CMR scans included CINE imaging and myocardial T2-mapping sequences. SARS-CoV2 IgG antibody testing was performed in capillary blood samples, and date of confirmed SARS-CoV2 infection and/or vaccination if any was collected. Participants were assigned to three different groups according to SARS-CoV2 status: Group 1 (non-infected and nonvaccinated), Group 2 (infected and non-vaccinated), and Group 3 (vaccinated, independently of past infection status). CMR images were analyzed by experienced observers blinded to adolescent's SARS-CoV2 status. ANOVA and multiple regression analysis, together with correlation coefficients, were used to study between-group differences and associations among variables of interest. Result(s): A total of 115 adolescents with a mean age of 16.0 years (standard deviation (SD)=0.4), 54% girls, completed the CMR study and SARSCoV2 data successfully, and were assigned to Group 1 (n=72), Group 2 (n=22), and Group 3 (n=21). Left and right ventricular ejection fraction (LVEF/RVEF) did not significantly differ among groups: Mean LVEF was 62.8% (SD=4.1), 63.0% (SD=3.7) and 60.9% (SD=3.9) [p=0.12] and mean RVEF was 56.5% (SD=4.2), 56.5% (SD=5.5) and 54.5% (SD=5.1) [p=0.23] in Groups 1, 2 and 3, respectively. Similarly, there were no between-group significant differences in myocardial T2 relaxation values: Mean T2 values were 44.1 ms (SD=2.2), 44.1 ms (SD=1.8) and 44.4 ms (SD=1.9) in Groups 1, 2, and 3, respectively (p=0.63) (Figure 1). No differences were found either after adjusting for age and gender. Median time (interquartile range) from date of infection or vaccination to CMR acquisition was 133 (121) days and 28 (38) days in Group 2 and Group 3, respectively. No correlation between time from infection/vaccination to CMR acquisition and T2 values was detected (Figure 2). Conclusion(s): This observational study did not find evidence of subclinical myocardial involvement after SARS-CoV2 infection or vaccination in asymptomatic adolescents, as assessed with T2-mapping magnetic resonance imaging.

Effect of N-acetyl cysteine in a patient cohort with severe or very severe COVID-19 pneumonia

Introduction: COVID-19, as of 9 June 2020, had been responsible for 404,396 deaths worldwide. Throughout the pandemic, IRCU and ICU directly cared for patients with severe or very severe respiratory failure due to COVID19 pneumonia. Objective(s): To determine if N-acetyl-cysteine (NAC) could be associated with lower mortality risk. Methodology: 1141 patients from March to May 2020 admitted to the ICU and IRCU of the Fundacion Jimenez Diaz were analysed. Patients with <3 days of hospital admission and those with CURB-65 equal to or <0 were excluded. A multivariate regression logistics models have been used to respond to our hypothesis and investigate the relationship between each variable and the mortality. Result(s): Of all patients analyzed, 44% received treatment with NAC associated with other drugs according to established protocols. Of these, 55% were male, most non-smokers with a mean age of 74.43 years. In table 2 we describe statistically significant predictive parameters associated with a decreased risk of mortality in severe or very severe patients with an area AUC of 0.80 Conclusion(s): Adjuvant treatment with NAC in severe or very severe COVID-19 pneumonia is associated with a significantly lower risk of mortality by 30% in elderly patients, principally males, and with associated co-morbidities.

[Evaluation of the effectiveness of the new perioperative model to recover surgical activity during the COVID-19 pandemic]. / Evaluación de la efectividad del nuevo modelo perioperatorio para recuperar la actividad quirúrgica durante la pandemia de COVID-19.

INTRODUCTION: The first wave of the COVID-19 pandemic caused the cancellation of elective interventions. After the improvement of the epidemiological situation, new models of care were applied in hospitals to restart the programmed surgical activity. The aim was to evaluate the effectiveness of the organizational model established to recover surgical activity during the transition period of the COVID-19 pandemic. METHODS: Retrospective observational study comparing patients who underwent schedule surgery from September 1 until October 31, 2020, study group, with a control group of the same period of time corresponding to the year 2019 at the General Hospital from the Vall d'Hebron University Hospital. RESULTS: The total population included 1,825 patients, 888 in the study group and 937 in the control group. Global surgical activity decreased 6.43% during the study period compared to the same period in 2019, with a 25.5% decrease in cancer surgeries. Seven patients became infected with SARS-CoV-2 during their hospital stay. In hospital mortality was 0.9% in the study group compared to 0.7% in control group (p=0.8). The survival rate in cancer patients at 90 days was lower in the study group (95.7% vs 98.7%; p=0.02). CONCLUSIONS: The change in the management model during the transition period of the COVID-19 pandemic allowed the recovery of programmed surgical activity to levels similar to those existing prior to the pandemic with a greater impact on cancer surgery.

Quantification of stress and depression level posed by COVID-19 in first-line healthcare workers

After pandemic, healthcare workers experienced a series of emotional and psychological disturbances that could impact their mental well-being. In this study, the feasibility of morphological characteristics of photoplethysmographic (PPG) waveform to quantify stress and depression level posed by COVID-19 in first-line healthcare workers is explored. Results show that higher stress and depression level are moderately correlated with large systolic amplitude and parameters that might indicate early wave reflection. These results suggest that an arterial stiffness, quantified with PPG morphological characteristics, could provide valuable information in assessing mental health.

A phase 1/2 trial of lurbinectedin (L) in combination with pembrolizumab (P) in relapsed small cell lung cancer (SCLC): The LUPER study

Background: L is a novel anticancer agent that inhibits trans-activated transcription and modulates the tumor microenvironment. L is approved by the FDA for metastatic SCLC patients (pts) with progressive disease (PD) on or after platinum-based chemotherapy (CT). The LUPER study is assessing the safety, tolerability, and preliminary efficacy of L+P as second-line regimen for SCLC pts after failure of platinum- based CT. Phase 1 data are presented here. Methods: In this phase 1/2 trial (NCT04358237), adult pts with histologically confirmed SCLC, PD to a previous CT-containing regimen (≥4 weeks before study initiation), no prior exposure to immunotherapy, ECOG PS of 0-1, and measurable disease as per RECIST 1.1 are eligible. Pts with treated, stable, and asymptomatic brain metastases (BMs) are allowed. A 3+3 dose-escalation was done to determine the recommended phase 2 dose (RP2D) of L+P. L was dosed at 2.4 mg/m2 and 3.2 mg/m2 IV Q3W in the dose level (DL)1 and 2, respectively, in combination with fixed dose of P (200 mg IV Q3W). The RP2D was the highest DL at which 0/3 pts or ≤1/6 pts experienced dose-limiting toxicities (DLTs) during the first cycle. Treatment was administered until PD, unacceptable toxicity, or consent withdrawal. Secondary endpoints include safety as per CTCAE 5.0, preliminary efficacy, and pharmacokinetics. Results: Thirteen pts were enrolled across 3 hospitals in Spain (DL1, n = 7;DL2, n = 6). Median age was 66 (range 43-78) years, 46.2% were female, 61.5% had ECOG PS of 1, 38.5% had platinum-free interval < 90 days, 30.8% had LDH > upper normal limit, and 15.4% had BMs. One DLT (G3 asthenia) and one G4 neutropenia lasting > 3 days (controlled with G-CSF prophylaxis upon C2, without requiring dose delay or modification) occurred in the DL1. No DLT were reported in the DL2. The RP2D was identified as 3.2 mg/m2 L and 200 mg P IV Q3W. At data cutoff (Jan 21, 2022), 5 (38.4%) pts remained on treatment (1 pt in DL1 discontinued due to COVID-19 in cycle 1). Median duration of treatment was 2.1 (0-11.8) months, 5 (38.5%) pts had ≥8 cycles, and median relative dose intensity of L and P were 91.1% and 95.7%, respectively. Immune-related AEs (G2 pneumonitis;G3 ALT increased) led to P discontinuation in 2 (15.4%) pts. Responses were shown in both DLs, with ORR of 30.8% (1 confirmed complete response and 3 partial responses);3 pts had stable disease (SD;including 1 patient with SD > 12 weeks) and 5 (38.5%) pts experienced PD. Conclusions: This is the first report to demonstrate a manageable safety profile and preliminary efficacy of second-line L+P for relapsed SCLC pts. This combination warrants further confirmation in the ongoing expansion phase 2.

Severity of Covid-19 Clinical Outcomes and Mortality in Multiple Myeloma Patients over Year 1 of the Pandemic

Introduction In the first weeks of the Covid-19 pandemic when healthcare systems in many areas were overstretched, we documented that hospital mortality in multiple myeloma (MM) patients infected by Sars-Cov-2 was 50% higher than in age matched Covid-19 patients without cancer. In the following months, the pressure on healthcare systems in Spain continued although it did not reach the extreme levels of the first weeks of the pandemic. In this study, we proposed to determine if the severity of Covid-19 outcomes in MM patients has changed over the first year of the pandemic. Patients and methods The Spanish MM Collaborative Group (Pethema-GEM) conducted a survey at national level on plasma cell disorder patients infected by SARS-Cov-2 between March 2020 and February 2021. Sixty-six (69%) out of 96 contacted healthcare centers, from all 17 regions in Spain, reported 502 patients. Data on Covid-19 acute and post-acute phase outcomes (hospitalization, oxygen requirements, severity of symptoms and mortality) were reported first in May 2020 (Martinez-Lopez et al, BCJ 2021) and updated in February 2021. In this study, we compared outcome occurrence between two study periods: P1, a period of extreme stress for the healthcare system in Spain, from March to mid-June 2020;and a second period, P2, up to mid-February 2021 with a sustained but lower burden on the national health care system. Results Among the 451 patients with plasma cell disorders and a Sars-Cov-2 infection documented with an rRT-PCR positive test, 377 (84%) were MM patients, 15 SMM (3%), 40 MGUS (9%) and 19 amyloidosis (4%). The number of MM weekly reported cases was 57% (95%CI, 48-65) lower in P2 (188 cases in 35 weeks) compared to P1 (189 cases in 15 weeks), p<0.001. The mean (SD) age and the proportion of men did not differ between P1 and P2, respectively 69.8 (10.9) vs 68.6 (11.0) years, p=0.6, and 53.3% vs 59.6%, p=0.2. MM patients with active or progressive disease at time of Covid-19 diagnosis were 24% in P1 and 34% in P2, p=0.05;patients on active treatment were more frequent in P1, 89%, than in P2, 79%, p=0.01. MM treatment was withheld in 78% and 82% of patients, p=0.4. Covid-19 treatment changed over time: MM inpatients received more remdesivir and corticoids in the second period (3% vs 31% p<0.001, and 49% vs 73%, p<0.001, respectively). In P1, 90% of the reported MM patients were hospitalized compared to 71% in P2, p<0.001. Thirty-one and 41% of patients did not require oxygen support during P1 and P2, respectively;non-invasive ventilation in 19% and 14%, and mechanical ventilation in 7% and 8%, p=0.12. Overall, acute clinical Covid-19 severity was reduced from P1 to P2: 75% to 51%, p<0.001: moderate/severe pneumonia was reduced from 68% to 36%, p<0.001 but severe distress syndrome increased from 7% to 15%, p=0.03. However, mortality in all reported patients was 30.7% in P1 vs 26.1% in P2, p=0.3;and no differences in mortality were observed in hospitalized patients, 32.2% in P1 and 35.3% in P2, p=0.6. We performed a multivariable adjustment with the predictors identified in our previous study (BCJ 2021) and confirmed that inpatient mortality was similar in both study periods, odds ratio (OR) 0.99 (95%CI 0.59-1.66). Independently of the study period, an increased mortality was observed in men (OR 1.81, 1.08-3.05), patients over 65 (OR 2.40, 1.33-4.36), and patients with active or progressive disease (OR 2.12, 1.24-3.62). The severity of Covid-19 clinical outcomes -besides mortality, was associated with increased age but not with active or progressive disease. Conclusions Although COVID-19 clinical severity has decreased over the first year of the pandemic in multiple myeloma patients, mortality remains high with no change between the initial weeks of the pandemic and the following months. Prevention and vaccination strategies should be strengthened in this vulnerable population, particularly in patients with active or progressive disease at time of Covid-19 diagnosis. Disclosures: Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfi er: Consultancy;Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Mateos: Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees;Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees;Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees;Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees;Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees;AbbVie: Honoraria;Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Bluebird bio: Honoraria;GSK: Honoraria;Oncopeptides: Honoraria. López-Muñoz: Amgen: Consultancy. Sureda: GSK: Consultancy, Honoraria, Speakers Bureau;Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche: Other: Support for attending meetings and/or travel;Mundipharma: Consultancy;Bluebird: Membership on an entity's Board of Directors or advisory committees;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;MSD: Consultancy, Honoraria, Speakers Bureau;BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau;Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Lahuerta: Celgene, Takeda, Amgen, Janssen and Sanofi: Consultancy;Celgene: Other: Travel accomodations and expenses. San-Miguel: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen, Karyopharm, Merck Sharpe & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, Takeda: Consultancy, Other: Advisory board.