Response to COVID-19 vaccination post CAR T therapy in patients with non-Hodgkin lymphoma and multiple myeloma

COVID-19 adversely affects individuals with cancer. Several studies have found that seroconversion rates among patients with hematologic malignancies are suboptimal when compared to patients without cancer. Patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are immunocompromised due to impaired humoral and cellular immunity in addition to prescribed immunosuppressive therapy. Chimeric antigen receptor T-cell (CAR T) therapy is now widely used for NHL and MM, but little is known about seroconversion rates after COVID-19 vaccination among these populations. We evaluated SARS-CoV-2 spike-binding IgG antibody levels following COVID-19 vaccination among NHL and MM CAR T therapy recipients. Out of 104 CAR T infusions, 19 patients developed known COVID-19 infection post-CAR T. We tested 17 patients that received CAR T for antibody spike titers post COVID-19 vaccination, only 29 % (n=5) were able to mount a clinically relevant antibody response (>250 IU/mL). Clinical Practice Points : Approximately one-third of patients with NHL and multiple myeloma following COVID-19 vaccination and CAR T therapy were able to mount an immune response using the strictest criteria for vaccination immunogenicity in our relatively small sample. Even though patients that receive CAR T have impaired humoral response, COVID-19 vaccination may still benefit this population and perhaps boosters should follow immune reconstitution.

Response to COVID-19 Vaccination Post-CAR T Therapy in Patients With Non-Hodgkin Lymphoma and Multiple Myeloma.

COVID-19 adversely affects individuals with cancer. Several studies have found that seroconversion rates among patients with hematologic malignancies are suboptimal when compared to patients without cancer. Patients with non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are immunocompromised due to impaired humoral and cellular immunity in addition to prescribed immunosuppressive therapy. Chimeric antigen receptor T-cell (CAR T) therapy is now widely used for NHL and MM, but little is known about seroconversion rates after COVID-19 vaccination among these populations. We evaluated SARS-CoV-2 spike-binding IgG antibody levels following COVID-19 vaccination among NHL and MM CAR T therapy recipients. Out of 104 CAR T infusions, 19 patients developed known COVID-19 infection post-CAR T. We tested 17 patients that received CAR T for antibody spike titers post COVID-19 vaccination, only 29 % (n = 5) were able to mount a clinically relevant antibody response (>250 IU/mL).

Intelligent tutoring systems for word problem solving in COVID-19 days: could they have been (part of) the solution?

The COVID-19 pandemic led to the lockdown of schools in many countries, forcing teachers and students to carry out educational activities remotely. In the case of mathematics, developing remote instruction based on both synchronous and asynchronous technological solutions has proven to be an extremely complex challenge. Specifically, this was the case in topics such as word problem solving, as this domain requires intensive supervision and feedback from the teacher. In this piece of research, we present an evaluation of how technology is employed in the teaching of mathematics, with particular relevance to learning during the pandemic. For that purpose, we conducted a systematic review, revealing the almost complete absence of experiments in which the use of technology is not mediated by the teacher. These results reflect a pessimistic vision within the field of mathematics education about the possibilities of learning when the student uses technology autonomously. Bringing good outcomes out of a bad situation, the pandemic crisis may represent a turning point from which to start directing the research gaze towards technological environments such as those mediated by artificial intelligence. As an example, we provide a study illustrating to what extent intelligent tutoring systems can be cost-effective compared to one-to-one human tutoring and mathematic learning-oriented solutions for intensive supervision in the teaching of word problem solving, especially appropriate for remote settings. Despite the potential of these technologies, the experience also showed that student socioeconomic level was a determining factor in the participation rate with an intelligent tutoring system, regardless of whether or not the administration guaranteed students' access to technological resources during the COVID-19 situation.

Intelligent tutoring systems for word problem solving in COVID-19 days: could they have been (part of) the solution?

The COVID-19 pandemic led to the lockdown of schools in many countries, forcing teachers and students to carry out educational activities remotely. In the case of mathematics, developing remote instruction based on both synchronous and asynchronous technological solutions has proven to be an extremely complex challenge. Specifically, this was the case in topics such as word problem solving, as this domain requires intensive supervision and feedback from the teacher. In this piece of research, we present an evaluation of how technology is employed in the teaching of mathematics, with particular relevance to learning during the pandemic. For that purpose, we conducted a systematic review, revealing the almost complete absence of experiments in which the use of technology is not mediated by the teacher. These results reflect a pessimistic vision within the field of mathematics education about the possibilities of learning when the student uses technology autonomously. Bringing good outcomes out of a bad situation, the pandemic crisis may represent a turning point from which to start directing the research gaze towards technological environments such as those mediated by artificial intelligence. As an example, we provide a study illustrating to what extent intelligent tutoring systems can be cost-effective compared to one-to-one human tutoring and mathematic learning-oriented solutions for intensive supervision in the teaching of word problem solving, especially appropriate for remote settings. Despite the potential of these technologies, the experience also showed that student socioeconomic level was a determining factor in the participation rate with an intelligent tutoring system, regardless of whether or not the administration guaranteed students' access to technological resources during the COVID-19 situation.

Axicabtagene ciloleucel as first-line therapy in high-risk large B-cell lymphoma: the phase 2 ZUMA-12 trial.

High-risk large B-cell lymphoma (LBCL) has poor outcomes with standard first-line chemoimmunotherapy. In the phase 2, multicenter, single-arm ZUMA-12 study (ClinicalTrials.gov NCT03761056) we evaluated axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, as part of first-line treatment in 40 patients with high-risk LBCL. This trial has completed accrual. The primary outcome was complete response rate (CRR). Secondary outcomes were objective response rate (ORR), duration of response (DOR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), assessment of safety, central nervous system (CNS) relapse and blood levels of CAR T cells and cytokines. The primary endpoint in efficacy-evaluable patients (n = 37) was met, with 78% CRR (95% confidence interval (CI), 62-90) and 89% ORR (95% CI, 75-97). As of 17 May 2021 (median follow-up, 15.9 months), 73% of patients remained in objective response; median DOR, EFS and PFS were not reached. Grade ≥3 cytokine release syndrome (CRS) and neurologic events occurred in three patients (8%) and nine patients (23%), respectively. There were no treatment-related grade 5 events. Robust CAR T-cell expansion occurred in all patients with a median time to peak of 8 days. We conclude that axi-cel is highly effective as part of first-line therapy for high-risk LBCL, with a manageable safety profile.

Recomendaciones para una conducta temprana en el manejo clínico de los pacientes con Covid-19

Hasta abril de 2020, se contabilizaba una cifra cercana a los dos millones de contagiados con SARS-Cov-2 [1], diseminándose a centenares de países en todo el mundo. El impacto se ha visto reflejado en todos los estratos sociales, afectando a los más carenciados y ha develado las grandes debilidades de las estructuras sanitarias frente a pandemias, en la gran mayoría de los gobiernos. En el mes de diciembre de 2019 aparecen los primeros pacientes con neumonía viral en Wuhan, China. Epidemiológicamente, todos los pacientes habían visitado el mercado de productos exóticos de dicha ciudad. A fines del mismo mes, un joven médico oftalmólogo de Wuhan describe, virtualmente, a siete pacientes con sintomatología similar al SARS y recomienda a sus amigos usar equipos de protección, por este hecho fue castigado por las autoridades policiales y más tarde fallecería por COVID-19. En la primera semana de enero, 2020, las autoridades chinas anuncian que han identificado un nuevo coronavirus (Co-V) en los pacientes que estaban siendo tratados por neumonía viral. Until April 2020, there was about two million people infected with SARS-Cov-2 [1], spreading to hundreds of countries around the world. The impact has been reflected in all social strata, affecting the neediest people and has revealed the great weaknesses of health structures to face the pandemics in the majority of governments. In December 2019, the first patients with viral pneumonia appear in Wuhan, China. Epidemiologically, all the patients had visited the market with exotic products in that city. At the end of the same month, a young ophthalmologist from Wuhan virtually describes seven patients with symptoms similar to SARS and recommends his friends to wear protective equipment, for this fact he was punished by the police authorities and later died by COVID- 19. In the first week of January, 2020, Chinese authorities announce that they have identified a new coronavirus (Co-V) in patients who were being treated for viral pneumonia. A correct diagnosis of infected people is important in the present pandemic;it is based on three fundamental aspects: clinic, complementary examinations and imaging

[Variables associated with mortality in a selected sample of patients older than 80 years and with some degree of functional dependence hospitalized for COVID-19 in a Geriatrics Service]. / Variables asociadas con mortalidad en una población de pacientes mayores de 80 años y con algún grado de dependencia funcional, hospitalizados por COVID-19 en un Servicio de Geriatría.

OBJECTIVE: The SARS-CoV-2 pandemic conditions high mortality rates in hospitalized elderly. Currently, a few studies include octogenarian patients and none of them analyze the impact of functional status on this health outcome. Our objective is to describe the characteristics of patients older than 80 years hospitalized for coronavirus disease 2019 (COVID-19), to determine the mortality rate and to identify associated factors. MATERIAL AND METHODS: Prospective observational study carried out on patients over 80 years admitted for COVID-19 in a Geriatrics Service. Sociodemographic, clinical, functional, mental, analytical, radiological, therapeutic and healthcare variables were collected. The factors associated with in-hospital lethality were analyzed by bivariate analysis. RESULTS: 58 cases with laboratory-confirmed COVID-19 were included, mean age 88.3 ± 5.4 years, 69% women, 65.5% moderate-severe cognitive impairment and previous Barthel index 40.66 ± 36. The main symptoms were fever (60,3%), dyspnea (53.4%) and deterioration of functional condition (50%). The most frequent comorbidities were cardiovascular disease (75.9%), hypertension (HT) (74.1%) and chronic kidney disease (CKD) (50%). A mortality rate of 41,4% was detected and the associated factors were: severe functional dependence (OR = 3.8 [1.2-12.2]), moderate-severe cognitive impairment (OR = 4.9 [1-25.4]) and CKD (OR = 3.2 [1.1-9.7]). CONCLUSION: High mortality rates are observed in older patients hospitalized for COVID-19, with a higher risk of dying in those with severe functional dependence or cognitive impairment. These findings reinforce the value of Geriatric Assessment to develop strategies to adapt diagnostic and therapeutic decision-making and to optimize care for elderly patients in the event of a new epidemic outbreak.