Immune response after SARS-CoV-2 vaccination in patients with inflammatory immune-mediated diseases receiving immunosuppressive treatment.

BACKGROUND: Real world data on the response to the SARS-CoV-2 vaccine in patients with immunomediated diseases (IMIDs) treated with immunesuppressants is of great interest because vaccine response may be impaired. The main aim was to study the humoral and cellular immune response after SARS-CoV-2 vaccination in patients with IMIDs treated with immunosuppressants. The secondary aim was to describe the frequency of SARS-CoV-2 infections after vaccination in these patients. MATERIAL AND METHODS: This is an observational study including 86 patients with IMIDs. All patients were treated with biologic or targeted synthetic disease-modifying antirheumatic drugs [b/tsDMARDs: TNF inhibitors (TNFi), rituximab, anti-interleukin 6 receptor (anti-IL6R) or JAK inhibitors (JAKi)]. Demographic and clinical information were collected. After 4-6 weeks of 2nd and 3rd vaccine doses, humoral response was assessed using the Thermo Scientific ELiA SARS-CoV-2-Sp1 IgG Test. Also, in patients with serum SARS-CoV-2 antibody levels under 100UI/ml, cellular response was analyzed using the QuantiFERON SARS-CoV-2 Starter Pack. RESULTS: A total of 86 patients under b/tsDMARDs and 38 healthy controls were included. Most patients received TNFi (45 with TNFi, 31 with rituximab, 5 with anti-IL6R and 5 with JAKi). SARS-CoV-2 antibodies (Ab) were present in an 86% of patients with IMIDs and in 100% healthy controls (p = 0.017). However, 12 (14%) patients had undetectable SARS-CoV-2 Ab levels, all treated with rituximab. In addition, SARS-CoV-2 Ab (IU/ml) were statistically lower in patients (Mdn (IQR): 59.5 (17-163) in patients vs 625 (405-932) in controls, p < 0.001). Patients treated with rituximab had lower Ab levels than those treated with TNFi and controls (p < 0.001). The cellular response to SARS-CoV-2 vaccine was evaluated in 30 patients. Eleven patients had a positive cellular response, being more frequent in patients treated with rituximab (p = 0.03). SARS-CoV-2 infection was reported in 43% of patients and 34% of controls after vaccination. Only 6 (7%) patients required hospitalization, most of whom treated with rituximab (67%). CONCLUSION: SARS-CoV-2 antibody levels were lower in patients than in controls, especially in patients treated with rituximab. A cellular response can be detected despite having a poor humoral response. Severe infections in vaccinated patients with IMIDs are rare, and are observed mainly in patients treated with rituximab.

Detection of specific RBD+ IgG+ memory B cells by flow cytometry in healthcare workers and patients with inborn errors of immunity after BNT162b2 m RNA COVID-19 vaccination.

Introduction: Inborn errors of immunity (IEI) are a heterogeneous group of diseases caused by intrinsic defects of the immune system. Estimating the immune competence of immunocompromised patients for an infection risk assessment or after SARS-CoV-2 vaccination constituted a challenge. Methods: The aim of this study was to determine the humoral responses of patients with IEI through a comprehensive analysis of specific receptor-binding domain-positive (RBD+) IgG+ memory B cells (MBCs) by flow cytometry, together with routine S-specific IgG antibodies and QuantiFERON SARS-CoV-2 (T-cell response), before the vaccine and 3 weeks after a second dose. Results and discussion: We first analyzed the percentage of specific RBD+ IgG+ MBCs in healthy healthcare workers. Within the control group, there was an increase in the percentage of specific IgG+ RBD+ MBCs 21 days after the second dose, which was consistent with S-specific IgG antibodies.Thirty-one patients with IEI were included for the pre- and post-vaccination study; IgG+ RBD+ MBCs were not evaluated in 6 patients due to an absence of B cells in peripheral blood. We detected various patterns among the patients with IEI with circulating B cells (25, 81%): an adequate humoral response was observed in 12/25, consider by the detection of positive S-specific IgG antibodies and the presence of specific IgG+ RBD+ MBCs, presenting a positive T-cell response; in 4/25, very low S-specific IgG antibody counts correlated with undetectable events in the IgG+ RBD+ MBC compartment but with positive cellular response. Despite the presence of S-specific IgG antibodies, we were unable to detect a relevant percentage of IgG+ RBD+ MBCs in 5/25; however, all presented positive T-cell response. Lastly, we observed a profound failure of B and T-cell response in 3 (10%) patients with IEI, with no assessment of S-specific IgG antibodies, IgG+ RBD+ MBCs, and negative cellular response. The identification of specific IgG+ RBD+ MBCs by flow cytometry provides information on different humoral immune response outcomes in patients with IEI and aids the assessment of immune competence status after SARS-CoV-2 mRNA vaccine (BNT162b2), together with S-specific IgG antibodies and T-cell responses.

Clinical validation of the Allen's Cognitive Level Screen in acquired brain injury.

BACKGROUND: The evaluation of functional cognition is a central concern in clinical practice. However, there are few standardized or validated tools, and many of them take too long, requiring screening tests. AIMS: To explore the convergent validity of the ACLS-5 with other cognitive screening test and functional independence test in a sample of people with acquired brain injury. Moreover, to examine the prediction of ACLS-5 on functioning and cognitive performance outcomes. MATERIALS AND METHODS: A cross-sectional design was applied following the guidelines of the STROBE checklist. A consecutive sample of people with acquired brain injury was recruited from rehabilitation centers. A cognitive screening test and daily living activity tests were implemented, such as ACLS-5, MoCA, Barthel, and FIM+FAM. Data were analyzed using non-parametric methods. In addition, a structural analysis and simple regression models were performed. RESULTS: Eighty patients with chronic acquired brain injury, with a mean age of 52, were recruited. All tests are significantly related to the ACLS-5 score, a moderate effect size for MoCA (ρ = 0.36), and a strong effect size for the other two (ρ > 0.50). CONCLUSIONS: ACLS-5 predicts functional and cognitive performance quickly and effectively, optimizing assessment time and avoiding mental fatigue or physical exhaustion.

Consumo de tabaco durante el tercer trimestre de embarazo y factores asociados a su mantenimiento / Tobacco consumption during the third trimester of pregnancy and factors associated with its maintenance

Objetivo: Conocer el consumo de tabaco en el último trimestre de la gestación por parte de las mujeres embarazadas, los factores asociados al mantenimiento, la exposición al humo ambiental del tabaco (HAT) en el hogar y la actitud de los/las profesionales durante el seguimiento del embarazo.Sujetos y método: Estudio descriptivo transversal realizado mediante entrevista personal a las gestantes, a partir de la semana 32, que acudieron a consultas de control prenatal a 10 centros de atención primaria de Cantabria durante el periodo comprendido entre junio de 2018 y junio de 2019. El cuestionario diseñado ad hoc constaba de 6 preguntas. Se compararon variables sociodemográficas, obstétricas y relacionadas con el consumo.Resultados: La muestra fue de 274 gestantes, y la prevalencia de fumadoras antes de la gestación del 31,4% (n= 86). Dejó de fumar el 60,5% (n= 52), y el 28,8% (n= 15) abandonó el consumo en la etapa preconcepcional o al conocer el embarazo. Logró la abstinencia sin ayuda profesional el 94,2% (n= 49).En el tercer trimestre continuaba fumando el 12,4% de las mujeres (n= 34), y al 23,5% de ellas no se les ofertó ayuda para dejar de fumar.Fueron predictores de abstinencia un nivel de estudios universitarios superior (p <0,001) y que la pareja no fumara (p <0,01). En los hogares de las fumadoras, la exposición al HAT fue mayor (p <0,001).Conclusiones: La mayoría de las gestantes que dejan de fumar lo hacen sin ayuda. El nivel de estudios es un predictor de abstinencia. Las que no han logrado dejarlo tienen el riesgo añadido de estar más expuestas al HAT. Si la pareja fuma, la embarazada tiene menos probabilidades de abandonar el consumo; por tanto, las estrategias de ayuda durante el embarazo se deberían potenciar y revisar, incluyendo en los programas de deshabituación a parejas y convivientes fumadores para incrementar su eficacia y disminuir los daños asociados al tabaquismo.  (AU)

Objective: To know the tobacco consumption in the last trimester of pregnancy, the factors associated with maintenance, exposure to environmental tobacco smoke in the home and the attitude of the professionals during the follow-up of the pregnancy.Subjects and method: Descriptive cross-sectional study carried out, by means of a personal interview with pregnant women, starting at week 32, who attended prenatal check-ups at 10 Primary Health Care Centers in Cantabria (Spain) during the period June 2018-June 2019. The ad hoc designed questionnaire consisted of 6 questions. Sociodemographic, obstetric and consumption-related variables were compared. Results: The sample consisted of 274 women, and the prevalence of smokers before pregnancy was 31.4% (86). 60.5% (n= 52) stopped smoking, of which 28.8% (n= 15) abandoned consumption in the preconception stage or when knowing the pregnancy. 94.2% (n= 49) achieved abstinence without professional help. In the third trimester, 12.4% (n= 34) continued to smoke; 23.5% of them were not offered help to quit smoking. Predictors of abstinence were a higher level of university studies (p <0.001) and that the couple wouldn’t smoke (p <0.01). Exposure to environmental tobacco smoke was higher in smokers’ homes (p <0.001).Conclusions: Most pregnant women who quit smoking do so without help. Educational level is a predictor of abstinence. Those who have not been able to quit smoking have the added risk of being more exposed to second-hand smoke. If the couple is a smoker, the pregnant woman is less likely to quit smoking, so the strategies to help them during pregnancy should be strengthened and reviewed, including smoking couples and cohabitants in smoking cessation programs to increase their effectiveness and decrease the harms associated with smoking. (AU)

PIM kinases mediate resistance of glioblastoma cells to TRAIL by a p62/SQSTM1-dependent mechanism.

Glioblastoma (GBM) is the most common and aggressive brain tumor and is associated with poor prognosis. GBM cells are frequently resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and finding new combinatorial therapies to sensitize glioma cells to TRAIL remains an important challenge. PIM kinases are serine/threonine kinases that promote cell survival and proliferation and are highly expressed in different tumors. In this work, we studied the role of PIM kinases as regulators of TRAIL sensitivity in GBM cells. Remarkably, PIM inhibition or knockdown facilitated activation by TRAIL of a TRAIL-R2/DR5-mediated and mitochondria-operated apoptotic pathway in TRAIL-resistant GBM cells. The sensitizing effect of PIM knockdown on TRAIL-induced apoptosis was mediated by enhanced caspase-8 recruitment to and activation at the death-inducing signaling complex (DISC). Interestingly, TRAIL-induced internalization of TRAIL-R2/DR5 was significantly reduced in PIM knockdown cells. Phospho-proteome profiling revealed a decreased phosphorylation of p62/SQSTM1 after PIM knockdown. Our results also showed an interaction between p62/SQSTM1 and the DISC that was reverted after PIM knockdown. In line with this, p62/SQSTM1 ablation increased TRAIL-R2/DR5 levels and facilitated TRAIL-induced caspase-8 activation, revealing an inhibitory role of p62/SQSTM1 in TRAIL-mediated apoptosis in GBM. Conversely, upregulation of TRAIL-R2/DR5 upon PIM inhibition and apoptosis induced by the combination of PIM inhibitor and TRAIL were abrogated by a constitutively phosphorylated p62/SQSTM1S332E mutant. Globally, our data represent the first evidence that PIM kinases regulate TRAIL-induced apoptosis in GBM and identify a specific role of p62/SQSTM1Ser332 phosphorylation in the regulation of the extrinsic apoptosis pathway activated by TRAIL.

Pythium solare sp. nov., a new pathogen of green beans in Spain.

A new disease causing wilt and death of adult plants of Phaseolus vulgaris was discovered in plastic-house crops of southeast Spain in 2004. The causal agent was shown to be a Pythium species with a unique type of oogonium ornamentation different from any of the described species. Zoospores were not observed, but globose or subglobose hyphal swellings, intercalary or terminal, were frequently found. Moreover, the ribosomal ITS region showed a unique sequence, significantly different (>14%) from any other known species of Pythium. This paper describes and illustrates the morphology of the new Pythium species and its pathogenicity to green beans. Its taxonomic position and phylogenetic relationships with other Pythium species are discussed.