Safety and Immunogenicity of Respiratory Syncytial Virus Prefusion F Protein Vaccine when Co-administered with Adjuvanted Seasonal Quadrivalent Influenza Vaccine in Older Adults: A Phase 3 Randomized Trial.

BACKGROUND: We evaluated co-administration of adjuvanted seasonal quadrivalent influenza vaccine (FLU-aQIV) and respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) in ≥65-year-olds. METHODS: This phase 3, open-label trial randomized ≥65-year-olds to receive FLU-aQIV and RSVPreF3 OA concomitantly (Co-Ad) or sequentially, 1 month apart (Control). Primary objectives were to demonstrate the non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration in terms of hemagglutination inhibition (HI) titers for each FLU-aQIV strain and RSV-A and RSV-B neutralization titers, 1 month post-vaccination. Reactogenicity and safety were also assessed. RESULTS: Overall, 1045 participants were vaccinated (Co-Ad: 523; Control: 522). Non-inferiority of FLU-aQIV and RSVPreF3 OA co-administration versus sequential administration was demonstrated in terms of HI titers for the A/Victoria(H1N1), B/Victoria, and B/Yamagata influenza strains and RSV-A neutralization titers (upper limits [ULs] of 95% confidence intervals [CIs] for adjusted geometric mean titer [GMT] ratios [Control/Co-Ad] ≤1.50) but not for A/Darwin(H3N2) HI titers (95% CI UL = 1.53). The immune response to A/Darwin(H3N2) was further assessed post-hoc using a microneutralization assay; the post-vaccination adjusted GMT ratio (Control/Co-Ad) was 1.23 (95% CI: 1.06-1.42, ie, UL ≤1.50), suggesting an adequate immune response to A/Darwin(H3N2) following co-administration. RSV-B neutralization titers were comparable between groups (95% CI UL for adjusted GMT ratio ≤1.50). Solicited adverse events were mostly mild or moderate and transient; unsolicited and serious adverse event rates were balanced between groups. CONCLUSIONS: Adjuvanted FLU-aQIV and RSVPreF3 OA had acceptable reactogenicity/safety profiles when co-administered in ≥65-year-olds, without clinically relevant interference with the immune responses to either vaccine. CLINICAL TRIALS REGISTRATION: NCT05568797.

Evolving patterns and clinical outcome of genetic studies performed at diagnosis in acute myeloid leukemia patients: Real life data from the PETHEMA Registry.

BACKGROUND: There are no studies assessing the evolution and patterns of genetic studies performed at diagnosis in acute myeloid leukemia (AML) patients. Such studies could help to identify potential gaps in our present diagnostic practices, especially in the context of increasingly complex procedures and classifications. METHODS: The REALMOL study (NCT05541224) evaluated the evolution, patterns, and clinical impact of performing main genetic and molecular studies performed at diagnosis in 7285 adult AML patients included in the PETHEMA AML registry (NCT02607059) between 2000 and 2021. RESULTS: Screening rates increased for all tests across different time periods (2000-2007, 2008-2016, and 2017-2021) and was the most influential factor for NPM1, FLT3-ITD, and next-generation sequencing (NGS) determinations: NPM1 testing increased from 28.9% to 72.8% and 95.2% (p < .001), whereas FLT3-ITD testing increased from 38.1% to 74.1% and 95.9% (p < .0001). NGS testing was not performed between 2000-2007 and only reached 3.5% in 2008-2016, but significantly increased to 72% in 2017-2021 (p < .001). Treatment decision was the most influential factor to perform karyotype (odds ratio [OR], 6.057; 95% confidence interval [CI], 4.702-7.802), and fluorescence in situ hybridation (OR, 2.273; 95% CI, 1.901-2.719) studies. Patients ≥70 years old or with an Eastern Cooperative Oncology Group ≥2 were less likely to undergo these diagnostic procedures. Performing genetic studies were associated with a favorable impact on overall survival, especially in patients who received intensive chemotherapy. CONCLUSIONS: This unique study provides relevant information about the evolving landscape of genetic and molecular diagnosis for adult AML patients in real-world setting, highlighting the increased complexity of genetic diagnosis over the past 2 decades.

Incidence, risk factors, and outcomes of second neoplasms in patients with acute promyelocytic leukemia: the PETHEMA-PALG experience.

The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA "chemotherapy based" and "chemotherapy free" protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8-231.1): 43.3 (range: 2.8-113.9) for s-MDS/AML and 61.7 (range: 7.1-231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p < 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.

CD8+ NKs as a potential biomarker of complete response and survival with lenalidomide plus R-GDP in the R2-GDP-GOTEL trial in recurrent/refractory diffuse large B cell lymphoma.

Background: Diffuse large B cell lymphoma (DLBCL) is the most common non-Hodgkin lymphoma worldwide. DLBCL is an aggressive disease that can be cured with upfront standard chemoimmunotherapy schedules. However, in approximately 35-40% of the patients DLBCL relapses, and therefore, especially in this setting, the search for new prognostic and predictive biomarkers is an urgent need. Natural killer (NK) are effector cells characterized by playing an important role in antitumor immunity due to their cytotoxic capacity and a subset of circulating NK that express CD8 have a higher cytotoxic function. In this substudy of the R2-GDP-GOTEL trial, we have evaluated blood CD8+ NK cells as a predictor of treatment response and survival in relapsed/refractory (R/R) DLBCL patients. Methods: 78 patients received the R2-GDP schedule in the phase II trial. Blood samples were analyzed by flow cytometry. Statistical analyses were carried out in order to identify the prognostic potential of CD8+ NKs at baseline in R/R DLBCL patients. Results: Our results showed that the number of circulating CD8+ NKs in R/R DLBCL patients were lower than in healthy donors, and it did not change during and after treatment. Nevertheless, the level of blood CD8+ NKs at baseline was associated with complete responses in patients with R/R DLBCL. In addition, we also demonstrated that CD8+ NKs levels have potential prognostic value in terms of overall survival in R/R DLBCL patients. Conclusion: CD8+ NKs represent a new biomarker with prediction and prognosis potential to be considered in the clinical management of patients with R/R DLBCL. Clinical trial registration: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-001620-29 EudraCT, ID:2014-001620-29.

Omicron SARS-CoV-2 infection management and outcomes in patients with hematologic disease and recipients of cell therapy.

Introduction: Scarce real-life data exists for COVID-19 management in hematologic disease (HD) patients in the Omicron era. Purpose: To assess the current clinical management and outcome of SARS-CoV-2 infection diagnosed, identify the risk factors for severe outcomes according to the HD characteristics and cell therapy procedures in a real-world setting. Methods: A retrospective observational registry led by the Spanish Transplant Group (GETH-TC) with 692 consecutive patients with HD from December 2021 to May 2023 was analyzed. Results: Nearly one-third of patients (31%) remained untreated and presented low COVID-19-related mortality (0.9%). Nirmatrelvir/ritonavir was used mainly in mild COVID-19 cases in the outpatient setting (32%) with a low mortality (1%), while treatment with remdesivir was preferentially administered in moderate-to-severe SARS-CoV-2 infection cases during hospitalization (35%) with a mortality rate of 8.6%. The hospital admission rate was 23%, while 18% developed pneumonia. COVID-19-related mortality in admitted patients was 14%. Older age, autologous hematopoietic stem cell transplantation (SCT), chimeric antigen receptor T-cell therapy, corticosteroids and incomplete vaccination were factors independently associated with COVID-19 severity and significantly related with higher rates of hospital admission and pneumonia. Incomplete vaccination status, treatment with prior anti-CD20 monoclonal antibodies, and comorbid cardiomyopathy were identified as independent risk factors for COVID-19 mortality. Conclusions: The results support that, albeit to a lower extent, COVID-19 in the Omicron era remains a significant problem in HD patients. Complete vaccination (3 doses) should be prioritized in these immunocompromised patients. The identified risk factors may help to improve COVID-19 management to decrease the rate of severe disease, ICU admissions and mortality.

Decoding the historical tale: COVID-19 impact on haematological malignancy patients-EPICOVIDEHA insights from 2020 to 2022.

Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020-2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

Barreras de acceso a la telemedicina en tiempos de COVID-19, un desafío profesional y gubernamental / Barriers to Access to Telemedicine during COVID-19, a Professional and Governmental Challenge / Barreiras no acesso à telemedicina em tempos de COVID-19, um desafio profissional e governamental

Estimada Editora: La pandemia secundaria a la infección por SARS-CoV-2 (COVID-19) aisló durante meses al mundo y produjo un impacto en las cifras de morbilidad y mortalidad. Al 27 de agosto de 2021 se han reportado a nivel mundial 215,047,649 casos y 4,480,486 muertes. En Colombia, para la misma fecha se reportaron 4,899,085 casos y 124,567 muertes (1). Entre las medidas sanitarias para disminuir la propagación de la infección se implementó el aislamiento obligatorio, condición que impulsó a todos los sectores a generar transformaciones. Para el caso del sistema de salud, entre sus estrategias se generó una rápida implementación de la telemedicina (TM). El término TM se introdujo en 1970 como la "curación a distancia", definida por la Organización Mundial de la Salud (OMS) como "la prestación de servicios de atención médica mediante el uso de tecnologías de la información y la comunicación para realizar un diagnóstico, tratamiento y prevención de enfermedades" (2). Los objetivos de la TM son mejorar la calidad del servicio de salud, reducción de los costos de transporte, disminución de los tiempos de espera para la atención y brindar mayor oportunidad de atención a zonas geográficas distantes. Sumado a lo anterior, en el contexto de la pandemia permitió disminuir la exposición a la infección en los pacientes y profesionales en salud (3,4).

Dear editor: The pandemic caused by SARS-CoV-2 (COVID-19) infection isolated the world for months and impacted morbidity and mortality rate figures. 215,047,649 cases and 4,480,486 deaths have been reported worldwide as of August 27, 2021. In Colombia, 4,899,085 cases and 124,567 deaths were reported as of the same date (1). Mandatory isolation was among the health measures to reduce propagation. This situation drove all sectors to transform. With respect to the health care system, telemedicine (TM) was quickly implemented as one of its strategies. The term TM was introduced in 1970 as "healing at a distance," defined by the World Health Organization as "The delivery of health care services using information and communication technologies for diagnosis, treatment and prevention of disease" (2). The objectives of TM are to improve the quality of health care services, reduce transportation costs, reduce wait times and provide more opportunities to attend to geographically distant areas. In addition to the above, it allowed decreasing patients and health care professionals' exposure to the infection in pandemic context (3,4).

Cara Editora: A pandemia secundária à infecção por SARS-CoV-2 (COVID-19) isolou o mundo por meses e teve um impacto nos números de morbidade e mortalidade. Até 27 de agosto de 2021, 215.047.649 casos e 4.480.486 mortes foram relatados em todo o mundo. Na Colômbia, para a mesma data, foram notificados 4.899.085 casos e 124.567 óbitos (1). Entre as medidas sanitárias para reduzir a propagação do contágio, foi implementado o isolamento obrigatório, condição que levou todos os setores a gerar transformações. No caso do sistema de saúde, uma de suas estratégias foi a rápida implantação da telemedicina (TM). O termo TM foi introduzido em 1970 como "cura à distância", definido pela Organização Mundial da Saúde como "a prestação de serviços de saúde por meio do uso de tecnologias de informação e comunicação para realizar diagnóstico, tratamento e prevenção de doenças" (2). Os objetivos do TM são melhorar a qualidade dos serviços de saúde, reduzir os custos de transporte, diminuir os tempos de espera para atendimento e proporcionar maior oportunidade de atendimento em áreas geográficas distantes. Além do exposto, no contexto da pandemia, permitiu reduzir a exposição à infecção em pacientes e profissionais de saúde (3,4).

Factores asociados con somnolencia diurna excesiva en estudiantes de Medicina de una institución de educación superior de Bucaramanga / Factors Associated with Excessive Daytime Sleepiness in Medical Students of a Higher Education Institution of Bucaramanga

RESUMEN Introducción: La somnolencia diurna excesiva (SDE) puede llegar a interferir en el desempeño académico y profesional, debido a que las personas afectadas tienden a quedarse dormidas en situaciones que exigen un alto nivel de atención. Los estudiantes de Medicina representan una población en riesgo de SDE, dada la exigencia académica de numerosas horas de estudio, debido al gran número de créditos por asignatura contenidos en el plan de estudios del programa académico, las prácticas docentes asistenciales y los turnos nocturnos, que pueden generar privación o déficit acumulado del sueño. Por esta razón, es importante estimar la prevalencia de SDE y los factores asociados en estudiantes de Medicina de una institución de educación superior (IES) de Bucaramanga, con el objetivo de implementar estrategias de prevención primaria que disminuyan la presentación de este problema y mejoren la calidad de vida y el desempeño académico de los estudiantes. Material y métodos: Estudio transversal analítico observacional, con una muestra poblacional de 458 estudiantes de Medicina matriculados en el segundo semestre de 2015 en la Universidad Autónoma de Bucaramanga (UNAB), quienes respondieron a 4 cuestionarios: variables sociodemográficas, escala de somnolencia de Epworth, índice de calidad del sueño de Pittsburg (ICSP) e índice de higiene del sueño (IHS). Se realizó el análisis bivariable y multivariable en busca de asociación con SDE. Resultados: Los estudiantes tenían una media de edad de 20,3 arios; de los 458 encuestados, el 62,88% eran mujeres. Se estableció que el 80,75% de los participantes tenían SDE y el 80,55%, una percepción negativa de la calidad del sueño (OR = 1,91;IC95%, 1,11-3,29; p = 0,019). En el análisis multivariable, se encontró que el hecho de estar cursando ciencias clínicas disminuye el riesgo de SDE respecto a quienes estaban cursando el ciclo básico. Además, se observó que una puntuación > 15 en el IHS aumenta de manera significativa el riesgo de padecer SDE. Conclusiones: Aunque es frecuente encontrar SDE en los estudiantes de Medicina, solo un pequeño porcentaje de ellos sufren la forma severa de este trastorno del sueño. Estar cursando asignaturas del ciclo básico se asocia con mayor riesgo de SDE, por lo cual es importante que los comités curriculares de las IES evalúen regularmente la cantidad de horas de trabajo supervisado e independiente que realizan los estudiantes de Medicina. Finalmente, es importante emprender campañas orientadas a mejorar la percepción de riesgo sobre el uso de bebidas energizantes de los estudiantes universitarios y realizar, desde el ingreso al programa académico, recomendaciones sobre los hábitos de higiene del sueño.

ABSTRACT Introduction: Excessive daytime sleepiness (EDS) can interfere with academic and professional performance, as affected individuals tend to fall asleep in situations that demand a high level of alertness. Medical students are often a population at risk of suffering from EDS due to the demanding number of study hours, the significant number of credits per subject in the academic curriculum, practical teaching sessions and hospital night shifts, which can lead to sleep deprivation or sleep debt. It is for these reasons that it is important to estimate the prevalence of EDS and its associated factors in medical students of a Higher Education Institution (HEI) in Bucaramanga, in order to implement early prevention strategies to reduce the occurrence of this problem and to improve the students' quality of life and academic performance. Material and methods: An observational, cross-sectional analytical study with a population sample of 458 medical students enrolled in the second semester of 2015 at the Universidad Autonomade Bucaramanga (UNAB), who completed four questionnaires: Sociodemographic Variables, Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index and Sleep Hygiene Index (SHI). A bivariate and multivariate analysis was performed to identify any correlations with EDS. Results: Mean student age was 20.3 years and 62.88% of the 458 respondents were women. We were able to establish that 80.75% of participants suffered from EDS and 80.55% had a negative perception of their sleep quality (OR=1.91; 95% CI, 1.11-3.29; p =0.019). In the multivariate analysis, it was found that the risk of EDS is lower in the clinical sciences than in the basic cycle. Furthermore, it was noted that a score higher than 15 in the Sleep Hygiene Index significantly increases the risk of suffering from EDS. Conclusions: Although EDS is very common in medical students, only a small percentage present the most severe form of this sleep disorder. Being enrolled in basic cycle subjects is associated with a higher risk of suffering EDS, so it is important for the curriculum committees of higher education institutions to regularly evaluate the number of hours of supervised and independent work performed by medical students. Finally, it is important to implement campaigns aimed at improving university students' perception of the risk of taking energy drinks and to establish sleep hygiene recommendations from the start of the academic programme.