SARS-CoV-2-Spike Antibody and T-Cell Responses Elicited by a Homologous Third mRNA COVID-19 Dose in Hemodialysis and Kidney Transplant Recipients.

The effect of a third vaccine dose (3D) of homologous mRNA vaccine on blood levels of SARS-CoV-2-receptor binding domain (RBD)-total antibodies was assessed in 40 hemodialysis patients (HD) and 21 kidney transplant recipients (KTR) at a median of 46 days after 3D. Anti-RBD antibodies were detected in 39/40 HD and 19/21 KTR. Overall, 3D boosted anti-RBD antibody levels (median: 58-fold increase). Neutralizing antibodies (NtAb) against the Wuhan-Hu-1, Delta, and Omicron variants were detected in 14, 13, and 11 out of 14 HD patients, and in 5, 5, and 4 out of 8 KTR patients, respectively. The median fold increase in NtAb titers in HD patients was 77, 28, and 5 and 56, 37, and 9 in KTR patients for each respective variant. SARS-CoV-2-S S-IFN-γ-producing CD8+ and CD4+ T-cell responses were detected in the majority of HD (35 and 36/37, respectively) and all KTR (16/16) patients at 3D. Overall, the administration of 3D boosted T-cell levels in both population groups. In conclusion, a homologous mRNA COVID-19 vaccine 3D exerts a booster effect on anti-RBD antibodies, NtAb binding to Wuhan-Hu-1, Delta, and Omicron variants, and SARS-CoV-2-S-IFN-γ-producing T cells in both HD and KTR patients. The magnitude of the effect was more marked in HD than KTR patients.

Dynamics of SARS-CoV-2-Spike-reactive antibody and T-cell responses in chronic kidney disease patients within 3 months after COVID-19 full vaccination.

Background: Little is known regarding the dynamics of antibody and T-cell responses in chronic kidney disease (CKD) following coronavirus disease 2019 (COVID-19) vaccination. Methods: Prospective observational cohort study including 144 participants on haemodialysis (HD) (n = 52) or peritoneal dialysis (PD) (n = 14), those undergoing kidney transplantation (KT) (n = 30) or those with advanced CKD (ACKD) not on dialysis and healthy controls (n = 18). Anti-Spike (S) antibody and T-cell responses were assessed at 15 days (15D) and 3 months (3M) after complete vaccination schedule. HD, PD and KT patients received mRNA vaccines (mRNA-123 and BNT162b2). Most ACKD patients received BNT162b2 (n = 23), or Ad26.COV.2.S (4). Most controls received BNT162b2 (n = 12), or Ad26.COV.2.S (n = 5). Results: Anti-S antibodies at 15D and 3M were detectable in 95% (48/50)/98% (49/50) of HD patients, 93% (13/14)/100% of PD patients, 67% (17/26)/75% (21/28) of KT patients and 96% (25/26)/100% (24/24) of ACKD patients. Rates for healthy controls were 81% (13/16)/100% (17/17). Previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2-S) infection was documented in four (7.7%) HD patients, two (14.3%) PD patients, two (6.7%) KT patients, one (5.55%) healthy control and in no ACKD patient. Antibody levels decreased at 3M in HD (P = .04), PD (P = .008) and ACKD patients (P = .0009). In KT patients, levels increased (P = .04) between 15D and 3M, although they were low at both time points.T-cell responses were detected in HD patients in 37 (80%) at baseline, 35 (70%) at 15D and 41 (91%) at 3M. In PD patients, T-cell responses appeared in 8 (67%) at baseline, 13 (93%) at 15D and 9 (100%) at 3M. In KT patients, T-cell responses were detected in 12 (41%) at baseline, 22 (84%) at 15D and 25 (96%) at 3M. In ACKD patients, T-cell responses were detected in 13 (46%) at baseline, 20 (80%) at 15D and 17 (89%) at 3M. None of healthy controls showed T-cell response at baseline, 10 (67%) at 15D and 8 (89%) at 3M. Conclusions: Most HD, PD and ACKD patients develop SARS-CoV-2-S antibody responses comparable to that of healthy controls, in contrast to KT recipients. Antibody waning at 3M was faster in HD, PD and ACKD patients. No differences in SARS-CoV-2 T-cell immunity responses were noticed across study groups.

COVID-19 Vaccination Improved Psychological Distress (Anxiety and Depression Scores) in Chronic Kidney Disease Patients: A Prospective Study.

The purpose of the study is to analyze the impact of vaccination against SARS-CoV-2 on anxiety and depression scores in patients with different modalities of chronic kidney disease. One hundred and seventeen renal patients (50 hemodialysis patients, 13 peritoneal dialysis patients, 32 kidney transplants, and 22 advanced chronic kidney disease patients at pre-dialysis care) were evaluated for depression, anxiety, health-related quality of life (HRQOL), and perceived fears and resources with standardized (Hospital Anxiety and Depression Scale (HADS)) and self-reported questionnaires. The measure points were before vaccination and 15 days after vaccination. The main finding of the study was that there was a decrease in the global mean of normal scores for anxiety and depression symptoms in chronic kidney disease patients post-vaccination. We did not find statistically significant differences in depression or anxiety scores, nor any HRQOL differences between the treatment groups. The three main fears reported by the participants at baseline were those of adverse effects, not getting the vaccine, and lack of information. These findings highlight the potential interest of assessing psychological variables related to the impact of vaccination against SARS-CoV-2. New studies will be required to assess the impact of comprehensive vaccine coverage and its psychological impact.

Epicardial cell shape and maturation are regulated by Wt1 via transcriptional control of Bmp4.

The epicardium plays a crucial role in embryonic heart development and adult heart repair; however, the molecular events underlying its maturation remain unknown. Wt1, one of the main markers of the embryonic epicardium, is essential for epicardial development and function. Here, we analyse the transcriptomic profile of epicardial-enriched cells at different stages of development and from control and epicardial-specific Wt1 knockout (Wt1KO) mice. Transcriptomic and cell morphology analyses of epicardial cells from epicardial-specific Wt1KO mice revealed a defect in the maturation process of the mutant epicardium, including sustained upregulation of Bmp4 expression and the inability of mutant epicardial cells to transition into a mature squamous phenotype. We identified Bmp4 as a transcriptional target of Wt1, thus providing a molecular basis for the retention of the cuboidal cell shape observed in the Wt1KO epicardium. Accordingly, inhibition of the Bmp4 signalling pathway both ex vivo and in vivo rescued the cuboidal phenotype of the mutant epicardium. Our findings indicate the importance of the cuboidal-to-squamous transition in epicardial maturation, a process regulated by Wt1.

[Detection of LADA-type diabetes in overweight diabetic patients. Is treatment with metformin suitable?]. / Detección de diabetes tipo LADA en pacientes diabéticos con exceso ponderal. 'Es adecuado el tratamiento con metformina?

OBJECTIVES: To detect type-1 LADA (latent auto-immune diabetes in adults) in adults with overweight. To describe the metabolic variations in these patients after metformin treatment. DESIGN: Observational, multi-centre study based on a series of cases. SETTING: Health centres in Barcelona province, Spain. PARTICIPANTS: Diabetic patients with overweight or obesity, diagnosed with diabetes for <2 years, aged between 35 and 65, and without clinical micro-macrovascular complications and without initial glycaemia-lowering drug treatment. INTERVENTION: Metformin administration (1700 mg/day). MEASUREMENTS: The metabolic control variable was HbA1c. Other variables measured were: body mass index (BMI), glucose in fast, insulinaemia, C-peptide, and insulin resistance (HOMA-IR). We determined ICA, GADAb and IA2Ab antibodies to diagnose LADA-type diabetes. RESULTS: In our sample of diabetics (N=103), we detected 3 type-1 LADA cases. These patients had higher levels of HbA1c, insulin and, especially, HOMA-IR. Metformin treatment for one year improved HbA1c in both groups (with and without type-1 LADA). However, the decrease in insulin one year afterwards was greater in type-1 LADA patients. CONCLUSIONS: The percentage of type-1 LADA in our sample made us wonder whether we should search for pancreatic antibodies more often in primary care. More studies on the prevalence of type-1 LADA in our country are needed, especially in diabetic patients with overweight. Type-1 LADA patients improved their metabolic control after metformin treatment and showed a drastic decrease in insulin levels. Further studies are needed to evaluate whether metformin improves metabolic control, even though it may not protect insulin reserves, and to contrast metformin with other drugs.

Detección de diabetes tipo LADA en pacientes diabéticos con exceso ponderal. ¿Es adecuado el tratamiento con metformina? / Detection of LADA-type diabetes in overweight diabetic patients. Is treatment with metformin suitable?

Objetivos. Detectar pacientes con diabetes tipo LADA (latent autoinmune diabetes of adult) tipo 1 en diabéticos adultos con sobrepeso y describir las variaciones metabólicas tras administrar metformina. Diseño. Estudio observacional, multicéntrico, basado en una serie de casos. Emplazamiento. Atención primaria, provincia de Barcelona. Participantes. Diabéticos con sobrepeso u obesidad, con diagnóstico de diabetes < 2 años, entre 35 y 65 años de edad, sin complicaciones microvasculares o macrovasculares ni tratamiento farmacológico inicial antidiabético. Intervención. Administración de metformina, 1.700 mg/día. Mediciones. La variable de control metabólico fue la hemoglobina glucosilada (HbA1c); otras variables fueron el índice de masa corporal (IMC), la glucemia en ayunas, la insulinemia, el péptido C y la valoración de la insulinorresistencia (HOMA-IR). Para el diagnóstico de diabetes tipo LADA se determinaron los anticuerpos ICA, anti-GAD y anti-IA2. Resultados. En la muestra de diabéticos estudiada (n = 103) se detectaron 3 casos de LADA tipo 1 (prevalencia del 2,9%; intervalo de confianza del 95%, 0,6-8,3%). Estos pacientes presentaron valores basales más elevados de HbA1c, insulina y sobre todo de HOMA-IR. El tratamiento con metformina mejoró la HbA1c en ambos grupos de pacientes (con o sin LADA de tipo 1). El descenso de la insulinemia al cabo de un año en los pacientes con LADA de tipo 1 fue más marcado que en el resto de diabéticos. Conclusiones. Dada su frecuencia, hay que reflexionar sobre si deberían buscarse con más frecuencia anticuerpos frente a células β pancreáticas en atención primaria. Los pacientes con LADA de tipo 1 presentaron buen control de la HbA1c en tratamiento con metformina y un drástico descenso de la insulina. Faltan estudios que evalúen si la metformina mejora el control glucémico, aunque tal vez no proteja la reserva insulínica, y confrontarla con otros fármacos

Objectives. To detect type-1 LADA (latent auto-immune diabetes in adults) in adults with overweight. To describe the metabolic variations in these patients after metformin treatment. Design. Observational, multi-centre study based on a series of cases. Setting. Health centres in Barcelona province, Spain. Participants. Diabetic patients with overweight or obesity, diagnosed with diabetes for <2 years, aged between 35 and 65, and without clinical micro-macrovascular complications and without initial glycaemia-lowering drug treatment. Intervention. Metformin administration (1700 mg/day). Measurements. The metabolic control variable was HbA1c. Other variables measured were: body mass index (BMI), glucose in fast, insulinaemia, C-peptide, and insulin resistance (HOMA-IR). We determined ICA, GADAb and IA2Ab antibodies to diagnose LADA-type diabetes. Results. In our sample of diabetics (N=103), we detected 3 type-1 LADA cases. These patients had higher levels of HbA1c, insulin and, especially, HOMA-IR. Metformin treatment for one year improved HbA1c in both groups (with and without type-1 LADA). However, the decrease in insulin one year afterwards was greater in type-1 LADA patients. Conclusions. The percentage of type-1 LADA in our sample made us wonder whether we should search for pancreatic antibodies more often in primary care. More studies on the prevalence of type-1 LADA in our country are needed, especially in diabetic patients with overweight. Type-1 LADA patients improved their metabolic control after metformin treatment and showed a drastic decrease in insulin levels. Further studies are needed to evaluate whether metformin improves metabolic control, even though it may not protect insulin reserves, and to contrast metformin with other drugs

Angina de pecho en relación con la toma de dipiridamol oral / Angina pectoris induced by oral dipyridamol

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