Human microRNA sequencing and cytomegalovirus infection risk after kidney transplantation.

Cytomegalovirus (CMV)-seropositive kidney transplant recipients (KTRs) with detectable CMV-specific cell-mediated immunity according to the QuantiFERON-CMV assay (QTF-CMV) are expected to have adequate immune protection. Nevertheless, a proportion of patients still develop CMV infection. Human microRNAs (hsa-miRNAs) are promising biomarkers owing to their high stability and easy detection. We performed whole blood miRNA sequencing in samples coincident with the first reactive QTF-CMV after transplantation or cessation of antiviral prophylaxis to investigate hsa-miRNAs differentially expressed according to the occurrence of CMV infection. One-year incidence of CMV viremia was 55.0% (median interval from miRNA sequencing sampling of 29 days). After qPCR validation, we found that hsa-miR-125a-5p was downregulated in KTRs developing CMV viremia within the next 90 days (ΔCt: 7.9 ± 0.9 versus 7.3 ± 1.0; P = .011). This difference was more evident among KTRs preemptively managed (8.2 ± 0.9 versus 6.9 ± 0.8; P < .001), with an area under the receiver operating characteristic curve of 0.865. Functional enrichment analysis identified hsa-miR-125a-5p targets involved in cell cycle regulation and apoptosis, including the BAK1 gene, which was significantly downregulated in KTRs developing CMV viremia. In conclusion, hsa-miR-125a-5p may serve as biomarker to identify CMV-seropositive KTRs at risk of CMV reactivation despite detectable CMV-CMI.

Predictive value of fecal calprotectin and lactoferrin levels for negative outcomes in Clostridioides difficile infection.

PURPOSE: We investigated the role of fecal calprotectin (FC) and lactoferrin (FL) as predictive biomarkers in Clostridioides difficile infection (CDI). METHODS: We assembled a prospective cohort including all patients with a laboratory-confirmed CDI diagnosis between January and December 2017. FL and FC levels were measured at diagnosis by commercial ELISA and EIA kits. We investigated the diagnostic accuracy of FC and FL to predict CDI recurrence and severity (study outcomes) and explored optimal cut-off values in addition to those proposed by the manufacturers (200 µg/g and 7.2 µg/mL, respectively). RESULTS: We included 170 CDI cases (152 first episodes and 18 recurrences). The rates of recurrence (first episodes only) and severity (entire cohort) were 9.2% (14/152) and 46.5% (79/170). Both FL and FC levels were significantly higher in patients who developed study outcomes. Optimal cut-off values for FC and FL to predict CDI recurrence were 1052 µg/g and 6.0 µg/mL. The optimal cut-off value for FC yielded higher specificity (60.9%) and positive predictive value (PPV) (16.9%) than that proposed by the manufacturer. Regarding CDI severity, the optimal cut-off value for FC (439 µg/g) also provided higher specificity (43.9%) and PPV (54.1%) than that of the manufacturer, whereas the optimal cut-off value for FL (4.6 µg/mL) resulted in an improvement of PPV (57.5%). CONCLUSION: By modifying the thresholds for assay positivity, the measurement of FC and FL at diagnosis is useful to predict recurrence and severity in CDI. Adding these biomarkers to current clinical scores may help to individualize CDI management.

Post-transplant dynamics and clinical significance of CMV-specific neutralizing antibodies in kidney transplant recipients treated with T-cell-depleting agents.

We measured cytomegalovirus (CMV)-specific antibodies that neutralize epithelial cell infection (CMV-AbNEIs) in 101 CMV-seropositive kidney transplant recipients (KTRs) at baseline and post-transplant months 3 and 6. All the patients received antithymocyte globulin and 3-month valganciclovir prophylaxis. There were no significant differences in pre-transplant AbNEIs titers between KTRs that developed or did not develop any-level CMV infection or the composite of high-level infection and/or disease. One-year CMV infection-free survival was comparable between KTRs with or without pre-transplant CMV-AbNEIs. No differences were observed by months 3 and 6 either. We observed no protective role for CMV-AbNEIs among CMV-seropositive KTRs undergoing T-cell-depleting induction.

Comparison of intracellular cytokine staining versus an ELISA-based assay to assess CMV-specific cell-mediated immunity in high-risk kidney transplant recipients.

The best method for monitoring cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) among high-risk kidney transplant (KT) recipients remains uncertain. We assessed CMV-CMI by intracellular cytokine staining (ICS) by flow cytometry and a commercial interferon (IFN)-γ release assay (QuantiFERON®-CMV [QTF-CMV]) at posttransplant months 3, 4, and 5 in 53 CMV-seropositive KT recipients that had received induction therapy with antithymocyte globulin (ATG) and a 3-month course of valganciclovir prophylaxis. The discriminative capacity (areas under receiver operating characteristics curve [auROCs]) and diagnostic accuracy to predict immune protection against CMV infection from the discontinuation of prophylaxis to month 12 were compared between both methods. There was significant although moderate correlations between CMV-specific IFN-γ-producing CD8+ T-cell counts enumerated by ICS and IFN-γ levels by QTF-CMV at months 3 (rho: 0.493; p = 0.005) and 4 (rho: 0.440; p = 0.077). The auROCs for CMV-specific CD4+ and CD8+ T-cells by ICS were nonsignificantly higher than that of QTF-CMV (0.696 and 0.733 vs. 0.678; p = 0.900 and 0.692, respectively). The optimal cut-off of ≥0.395 CMV-specific CD8+ T-cells yielded a sensitivity of 86.4%, specificity of 54.6%, positive predictive value of 79.2% and negative predictive value of 66.7% to predict protection. The corresponding estimates for QTF-CMV (IFN-γ levels ≥0.2 IU/mL) were 78.9%, 37.5%, 75.0%, and 42.9%, respectively. The enumeration of CMV-specific IFN-γ-producing CD8+ T-cells at the time of cessation of prophylaxis performed slightly better than the QTF-CMV assay to predict immune protection in seropositive KT recipients previously treated with ATG.

Proof of concept of a new device for the insertion of peripheral venous catheters in aseptic conditions.

According to the recommendations by the World Health Organization, the insertion of a peripheral venous catheter (PVC) must be an aseptic procedure while using non-sterile gloves. To overcome this apparent contradiction we have invented and patented (WO/2021/123482) a new device to be used during PVC insertion. The device permits the PVC placement in the vein while avoiding to directly touch the catheter with the fingertips. A total of 16 PVCs were inserted in the veins of a venipuncture anatomic training model while the operator was wearing non-sterile gloves. The gloves had been previously contaminated by embedding the fingertips in an agar plate inoculated with Staphylococcus epidermidis. Following insertion, the PVCs were sterilely removed and deposited on a bacterial culture plate. The tip cultures of PVCs that had been inserted with or without the use of the device were compared. Eight out of eight cultures (100.0%) were positive for S. epidermidis when the PVC had been inserted without using the device, whereas only one out of eight (12.5%) was positive when the device had been used. The single positive tip culture in the latter group corresponded to an insertion in which the operator had inadvertently touched the sterile part of the device while manipulating it. In conclusion, an auxiliary novel device allows the aseptic insertion of PVCs while the operator is wearing non-sterile gloves. Regulatory institutions should consider to recommend the insertion of PVCs by means of devices aimed at avoiding the contamination of the catheter.

Dynamics of Human Anelloviruses in Plasma and Clinical Outcomes Following Kidney Transplantation.

BACKGROUND: Torque teno virus, the major member of the genus Alphatorquevirus , is an emerging biomarker of the net state of immunosuppression after kidney transplantation. Genetic diversity constitutes a main feature of the Anelloviridae family, although its posttransplant dynamics and clinical correlates are largely unknown. METHODS: The relative abundance of Alphatorquevirus , Betatorquevirus , and Gammatorquevirus genera was investigated by high-throughput sequencing in plasma specimens obtained at various points during the first posttransplant year (n = 91 recipients). Total loads of all members of the Anelloviridae family were also quantified by an "in-house" polymerase chain reaction assay targeting conserved DNA sequences (n = 195 recipients). In addition to viral kinetics, clinical study outcomes included serious infection, immunosuppression-related adverse event (opportunistic infection and cancer)' and acute rejection. RESULTS: Alphatorquevirus DNA was detected in all patients at every point, with an increase from pretransplantation to month 1. A variable proportion of recipients had detectable Betatorquevirus and Gammatorquevirus at lower frequencies. At least 1 change in the predominant genus (mainly as early transition to Alphatorquevirus predominance) was shown in 35.6% of evaluable patients. Total anelloviruses DNA levels increased from baseline to month 1, to peak by month 3 and decrease thereafter, and were higher in patients treated with T-cell depleting agents. There was a significant albeit weak-to-moderate correlation between total anelloviruses and TTV DNA levels. No associations were found between the predominant Anelloviridae genus or total anelloviruses DNA levels and clinical outcomes. CONCLUSIONS: Our study provides novel insight into the evolution of the anellome after kidney transplantation.

Impact of polymorphisms in genes orchestrating innate immune responses on replication kinetics of Torque teno virus after kidney transplantation.

Background: Torque teno virus (TTV) DNAemia has been proposed as a surrogate marker of immunosuppression after kidney transplantation (KT), under the assumption that the control of viral replication is mainly exerted by T-cell-mediated immunity. However, Tthe impact on post-transplant TTV kinetics of single genetic polymorphisms (SNPs) in genes orchestrating innate responses remains unknown. We aimed to characterize the potential association between 14 of these SNPs and TTV DNA levels in a single-center cohort of KT recipients. Methods: Plasma TTV DNAemia was quantified by real-time PCR in 221 KT recipients before transplantation (baseline) and regularly through the first 12 post-transplant months. We performed genotyping of the following SNPs: CTLA4 (rs5742909, rs231775), TLR3 (rs3775291), TLR9 (rs5743836, rs352139), CD209 (rs735240, rs4804803), IFNL3 (rs12979860, rs8099917), TNF (rs1800629), IL10 (rs1878672, rs1800872), IL12B (rs3212227) and IL17A (rs2275913). Results: The presence of the minor G allele of CD209 (rs4804803) in the homozygous state was associated with undetectable TTV DNAemia at the pre-transplant assessment (adjusted odds ratio: 36.96; 95% confidence interval: 4.72-289.67; p-value = 0.001). After applying correction for multiple comparisons, no significant differences across SNP genotypes were observed for any of the variables of post-transplant TTV DNAemia analyzed (mean and peak values, areas under the curve during discrete periods, or absolute increments from baseline to day 15 and months 1, 3, 6 and 12 after transplantation). Conclusion: The minor G allele of CD209 (rs4804803) seems to exert a recessive protective effect against TTV infection in non-immunocompromised patients. However, no associations were observed between the SNPs analyzed and post-transplant kinetics of TTV DNAemia. These negative results would suggest that post-transplant TTV replication is mainly influenced by immunosuppressive therapy rather than by underlying genetic predisposition, reinforcing its clinical application as a biomarker of adaptive immunity.

Adolescent pregnancies and adherence to puerperal consultation. / Gestações na adolescência e adesão à consulta puerperal.

OBJECTIVE: to determine the profile of pregnancies and prevalence of adherence to puerperal consultation among adolescent puerperal women compared to non-adolescent puerperal women served in an outpatient clinic of a teaching hospital in the rural area of Minas Gerais. METHOD: cross-sectional study nested in a cohort of puerperal women; non-probabilistic sample, by convenience; adolescent pregnancy - dependent variable; sociodemographic, clinical and obstetric - independent variables. It employed its own instrument, tested by means of a pilot test. Prevalence ratios and confidence intervals were calculated; chi-square and Fisher's exact tests were applied, considering a significance level of 5%, and Poisson regression with robust variance. RESULTS: we interviewed 121 puerperal women, of which 18.2% (22) were adolescents, and observed among them low educational level (p<0.001); fewer pregnancies with pathologies (p=0.016); predominance of primiparous women (p<0.001), and higher rates of normal delivery (p=0.032). The prevalence of adherence to puerperal consultation was 34.7% and 31.8% for adolescents. There were no differences regarding adherence and age of puerperal women. CONCLUSION: adolescents did not present negative obstetric and neonatal outcomes, although a lower educational level was observed. Association was found between early age and absence of diseases during pregnancy and higher rates of normal vaginal deliveries. Adherence to puerperal return visit was slightly lower, but without statistical significance.(1) Adolescent puerperal women had low educational level. (2) Association between early age and absence of diseases during pregnancy. (3) There were higher rates of normal vaginal deliveries among adolescents. (4) Adolescents did not present negative obstetric and neonatal outcomes. (5) There were no differences regarding adherence and age of puerperal women.

Influence of single-nucleotide polymorphisms in TLR3 (rs3775291) and TLR9 (rs352139) on the risk of CMV infection in kidney transplant recipients.

Risk stratification for cytomegalovirus (CMV) infection after kidney transplantation (KT) remains to be determined. Since endosomal toll-like receptors (TLRs) are involved in viral sensing, we investigated the impact of common single-nucleotide polymorphisms (SNPs) located within TLR3 and TLR9 genes on the occurrence of overall and high-level (≥1,000 IU/ml) CMV infection in a cohort of 197 KT recipients. Homozygous carriers of the minor allele of TLR3 (rs3775291) had higher infection-free survival compared with reference allele carriers (60.0% for TT versus 42.3% for CC/CT genotypes; P-value = 0.050). Decreased infection-free survival was observed with the minor allele of TLR9 (rs352139) (38.2% for TC/CC versus 59.3% for TT genotypes; P-value = 0.004). After multivariable adjustment, the recessive protective effect of the TLR3 (rs3775291) TT genotype was confirmed (adjusted hazard ratio [aHR]: 0.327; 95% CI: 0.167-0.642; P-value = 0.001), as was the dominant risk-conferring effect of TLR9 (rs352139) TC/CC genotypes (aHR: 1.865; 95% CI: 1.170-2.972; P-value = 0.009). Carriers of the TLR9 (rs352139) TC/CC genotypes showed lower CMV-specific interferon-γ-producing CD4+ T-cell counts measured by intracellular cytokine staining compared with the TT genotype (median of 0.2 versus 0.7 cells/µl; P-value = 0.003). In conclusion, TLR3/TLR9 genotyping may inform CMV infection risk after KT.

Genetic polymorphisms in TLR3, IL10 and CD209 influence the risk of BK polyomavirus infection after kidney transplantation.

Genetic determinants of BK polyomavirus infection after kidney transplantation remain poorly investigated. We assessed the potential impact of 13 different single nucleotide polymorphisms within genes mainly involved in innate immune responses on the risk of BKPyV viremia in 204 KT recipients. After a median follow-up of 1121.5 days, the cumulative incidence of any-level BKPyV viremia was 24.5% (50/204). There was a significant association between the minor T allele of TLR3 (rs3775291) SNP and the development of BKPyV viremia (adjusted hazard ratio [aHR]: 2.16; 95% confidence interval [CI]: 1.08-4.30; P value = 0.029), whereas the minor G allele of CD209 (rs4804803) SNP exerted a protective role (aHR: 0.54; 95% CI: 0.29-1.00; P value = 0.050). A higher incidence of BKPyV viremia was also observed for the minor G allele of IL10 (rs1800872) SNP, although the absence of BKPyV events among homozygotes for the reference allele prevented multivariable analysis. The BKPyV viremia-free survival rate decreased with the increasing number of unfavorable genotypes (100% [no unfavorable genotypes], 85.4% [1 genotype], 70.9% [2 genotypes], 52.5% [3 genotypes]; P value = 0.008). In conclusion, SNPs in TLR3, CD209 and IL10 genes play a role in modulating the susceptibility to any-level BKPyV viremia among KT recipients.

Tocilizumab therapy in SARS-CoV-2 pneumonia: A matched retrospective cohort analysis.

Background: The effect of immunomodulatory therapy with tocilizumab for coronavirus disease 2019 (COVID-19) in real-life clinical practice remains controversial. Methods: Single-center retrospective matched cohort analysis including 47 consecutive patients treated with intravenous tocilizumab for severe COVID-19 pneumonia ("TCZ group"), matched by age, comorbidities, time from symptoms onset and baseline SpO2/FiO2 ratio with 47 patients receiving standard of care alone ("SoC group"). Results: There were no significant differences between the TCZ and SoC groups in the rate of clinical improvement (hospital discharge and/or a decrease of ≥2 points on a six-point ordinal scale) by day 7 (51.1% [24/47] versus 48.9% [23/47]; P-value = 1.000). No differences were observed at day 14 in terms of clinical improvement (72.3% versus 76.6%; P-value = 0.791), all-cause mortality (10.6% versus 12.8%; P-value = 1.000), and the composite of invasive mechanical ventilation and/or death (25.5% versus 23.4%; P-value = 1.000) either. Patients in the TCZ group had a more rapid normalization of C-reactive protein levels. Conclusions: No apparent benefit was observed in patients with severe COVID-19 treated with tocilizumab as compared to a matched retrospective cohort.

Antecedentes: El efecto del tratamiento inmunomodulador con tocilizumab en la COVID-19 sigue siendo controvertido. Métodos: Estudio unicéntrico de cohortes retrospectivas pareadas que incluyó a 47 pacientes con COVID-19 grave tratados con tocilizumab intravenoso («grupo TCZ¼), emparejados por edad, comorbilidades mayores, evolución de síntomas y cociente SpO2/FiO2 basal con 47 pacientes que recibieron tratamiento estándar únicamente («grupo SoC¼). Resultados: No observamos diferencias significativas entre los grupos de TCZ y SoC en la tasa de mejoría clínica (alta hospitalaria y/o descenso de ≥ 2 puntos en una escala ordinal de 6 puntos) al día 7 (51,1% [24/47] vs. 48,9% [23/47]; P = 1,000). Tampoco hubo diferencias al día 14 en las tasas de mejoría clínica (72,3% vs. 76,6%; P = 0,791), mortalidad (10,6% vs. 12,8%; P = 1,000) o en el compuesto de ventilación mecánica invasiva y/o muerte (25,5% vs. 23,4%; P = 1,000). Los pacientes en el grupo de TCZ presentaron una normalización más rápida de la proteína C reactiva. Conclusiones: Respecto a una cohorte retrospectiva pareada, no detectamos un beneficio asociado al tratamiento con tocilizumab en pacientes con neumonía por COVID-19.

Tocilizumab therapy in SARS-CoV-2 pneumonia: A matched retrospective cohort analysis / Tocilizumab en el tratamiento de la neumonía por SARS-CoV-2: análisis de una cohorte retrospectiva pareada

Background:The effect of immunomodulatory therapy with tocilizumab for coronavirus disease 2019 (COVID-19) in real-life clinical practice remains controversial.Methods:Single-center retrospective matched cohort analysis including 47 consecutive patients treated with intravenous tocilizumab for severe COVID-19 pneumonia (“TCZ group”), matched by age, comorbidities, time from symptoms onset and baseline SpO2/FiO2 ratio with 47 patients receiving standard of care alone (“SoC group”).Results:There were no significant differences between the TCZ and SoC groups in the rate of clinical improvement (hospital discharge and/or a decrease of ≥2 points on a six-point ordinal scale) by day 7 (51.1% [24/47] versus 48.9% [23/47]; P-value=1.000). No differences were observed at day 14 in terms of clinical improvement (72.3% versus 76.6%; P-value=0.791), all-cause mortality (10.6% versus 12.8%; P-value=1.000), and the composite of invasive mechanical ventilation and/or death (25.5% versus 23.4%; P-value=1.000) either. Patients in the TCZ group had a more rapid normalization of C-reactive protein levels.Conclusions:No apparent benefit was observed in patients with severe COVID-19 treated with tocilizumab as compared to a matched retrospective cohort. (AU)

Antecedentes:El efecto del tratamiento inmunomodulador con tocilizumab en la COVID-19 sigue siendo controvertido.Métodos:Estudio unicéntrico de cohortes retrospectivas pareadas que incluyó a 47 pacientes con COVID-19 grave tratados con tocilizumab intravenoso («grupo TCZ»), emparejados por edad, comorbilidades mayores, evolución de síntomas y cociente SpO2/FiO2 basal con 47 pacientes que recibieron tratamiento estándar únicamente («grupo SoC»).Resultados:No observamos diferencias significativas entre los grupos de TCZ y SoC en la tasa de mejoría clínica (alta hospitalaria y/o descenso de ≥ 2 puntos en una escala ordinal de 6 puntos) al día 7 (51,1% [24/47] vs. 48,9% [23/47]; P=1,000). Tampoco hubo diferencias al día 14 en las tasas de mejoría clínica (72,3% vs. 76,6%; P=0,791), mortalidad (10,6% vs. 12,8%; P=1,000) o en el compuesto de ventilación mecánica invasiva y/o muerte (25,5% vs. 23,4%; P=1,000). Los pacientes en el grupo de TCZ presentaron una normalización más rápida de la proteína C reactiva.Conclusiones:Respecto a una cohorte retrospectiva pareada, no detectamos un beneficio asociado al tratamiento con tocilizumab en pacientes con neumonía por COVID-19. (AU)

Analysis of the factors predicting clinical response to tocilizumab therapy in patients with severe COVID-19.

BACKGROUND: Controversy remains about the efficacy of tocilizumab (TCZ) for the treatment of severe COVID-19. We aimed to analyze the profile of TCZ-respondent patients. METHODS: We retrospectively analyzed a cohort of patients with severe COVID-19 who received off-label TCZ after recommendation by a local committee and were admitted to the University Hospital "12 de Octubre" until May 2020. The primary end point was a significant clinical improvement (SCI) on day 14 after administration of TCZ. Factors independently related to SCI were analyzed by multivariate logistic regression models. RESULTS: Of 428 (63.3%) patients treated with TCZ, 271 (63.3%) experienced SCI. After adjustment for factors related to unfavorable outcomes, TCZ administration within the first 48 hours from admission (odds ratio [OR]: 1.98, 95% confidence Interval [95% CI]: 1.1-3.55; P = 0.02) and ALT levels >100 UI/L at day 0 (OR: 3.28; 95% CI: 1.3-8.1; P = 0.01) were independently related to SCI. The rate of SCI significantly decreased according to the time of TCZ administration: 70.2% in the first 48 hours from admission, 58.5% on days 3-7, and 45.1% after day 7 (P = 0.03 and P = 0.001, respectively). CONCLUSION: TCZ improves the prognosis of patients with COVID-19 the most if treatment starts within the first 48 hours after admission.

Tocilizumab therapy in SARS-CoV-2 pneumonia: A matched retrospective cohort analysis.

BACKGROUND: The effect of immunomodulatory therapy with tocilizumab for coronavirus disease 2019 (COVID-19) in real-life clinical practice remains controversial. METHODS: Single-center retrospective matched cohort analysis including 47 consecutive patients treated with intravenous tocilizumab for severe COVID-19 pneumonia ("TCZ group"), matched by age, comorbidities, time from symptoms onset and baseline SpO2/FiO2 ratio with 47 patients receiving standard of care alone ("SoC group"). RESULTS: There were no significant differences between the TCZ and SoC groups in the rate of clinical improvement (hospital discharge and/or a decrease of ≥2 points on a six-point ordinal scale) by day 7 (51.1% [24/47] versus 48.9% [23/47]; P-value=1.000). No differences were observed at day 14 in terms of clinical improvement (72.3% versus 76.6%; P-value=0.791), all-cause mortality (10.6% versus 12.8%; P-value=1.000), and the composite of invasive mechanical ventilation and/or death (25.5% versus 23.4%; P-value=1.000) either. Patients in the TCZ group had a more rapid normalization of C-reactive protein levels. CONCLUSIONS: No apparent benefit was observed in patients with severe COVID-19 treated with tocilizumab as compared to a matched retrospective cohort.

Human pegivirus type 1 infection in kidney transplant recipients: Replication kinetics and clinical correlates.

BACKGROUND: Increasing evidence suggests that infection with the nonpathogenic human pegivirus type 1 (HPgV-1) exerts a clinical benefit in human immunodeficiency virus (HIV) patients, which could be attributable to immunomodulatory effects. Whether this impact can be extrapolated to kidney transplantation (KT) remains largely unknown. METHODS: We measured plasma HPgV-1 RNA by real-time polymerase chain reaction targeting the 5' untranslated region at various points (pretransplantation, day 7, months 1, 3, 6, and 12) in 199 KT recipients. Study outcomes included posttransplant serious infection, immunosuppression-related adverse event (opportunistic infection and/or de novo cancer), and acute graft rejection. RESULTS: HPgV-1 infection was demonstrated in 52 (26.1%) patients, with rates increasing from 14.7% at baseline to 19.1% by month 12 (p-value = .071). De novo infection occurred in 13.8% of patients with no detectable HPgV-1 RNA before transplantation. Double-organ (liver-kidney or kidney-pancreas) transplantation (odds ratio [OR]: 5.62; 95% confidence interval [CI]: 1.52-20.82) and donation after brain death (OR: 2.21; 95% CI: 1.00-4.88) were associated with posttransplant HPgV-1 infection, whereas pretransplant hypertension was protective (OR: 0.23; 95% CI: 0.09-0.55). There were no significant differences in the incidence of study outcomes according to HPgV-1 status. Plasma HPgV-1 RNA levels at different points did not significantly differ between patients that subsequently developed outcomes and those remaining free from these events. No correlation between HPgV-1 RNA and immune parameters or torque teno virus DNA load was observed either. CONCLUSION: Unlike patients living with HIV, HPgV-1 infection does not seem to influence patient or graft outcomes after KT.

Role of cytomegalovirus infection after kidney transplantation on the subsequent risk of atherosclerotic and thrombotic events.

Background and aims: Whether cytomegalovirus (CMV) infection increases the risk of cardiovascular complications after kidney transplantation (KT) through different indirect effects remains controversial. Methods: We analyzed the incidence of post-transplant atherosclerotic (PAEs) and thrombotic events (PTEs) in 465 KT recipients according to the previous exposure to any level or high-level (≥1,000 IU/mL) CMV viremia (either asymptomatic or clinical disease) by means of landmark analysis beyond days 30, 180 and 360 after transplantation. Proportional hazards models were constructed with death and graft loss as competing risks. Results: After a median of 722 days, the cumulative incidences of PAE and PTE were 6.0% each. Most PAEs (53.6%) occurred beyond post-transplant day 360, whereas most PTEs (60.7%) were diagnosed between days 30-180.The incidence of PAE beyond day 180 was higher among patients with previous CMV viremia compared to those without (two-year rates: 4.7% versus 0.4%; P-value = 0.035). This difference was more pronounced in recipients developing high-level viremia (6.3% versus 0.7%, respectively; P-value = 0.013). After multivariate adjustment for age, pre-transplant cardiovascular risk, antiplatelet and statin therapy and graft function, however, associations were not maintained either for any-level (hazard ratio [HR]: 1.84; 95% confidence interval [CI]: 0.48-7.05) or high-level CMV viremia (HR: 2.84; 95% CI: 0.78-10.36). No significant differences were found in the remaining landmark analyses (days 30 or 360) or for the outcome of PTE either. Conclusions: Our study does not support that CMV infection independently contributes to the risk of PAE or PTE after KT.

Gestações na adolescência e adesão à consulta puerperal / Adolescent pregnancies and adherence to puerperal consultation / Embarazos en adolescentes y adherencia a la consulta puerperal

Resumo Objetivo: identificar o perfil das gestações e prevalência de adesão à consulta puerperal entre puérperas adolescentes comparadas a não adolescentes, assistidas em um ambulatório de hospital de ensino do interior de Minas Gerais. Método: estudo transversal aninhado a uma coorte de puérperas; amostra não probabilística, por conveniência; gestação na adolescência - variável dependente; sociodemográficas, clínicas e obstétricas - variáveis independentes. Utilizado instrumento próprio, testado mediante piloto. Calculadas razões de prevalência e intervalos de confiança; aplicados testes qui-quadrado e exato de Fisher, considerando nível de significância de 5%, e regressão de Poisson com variância robusta. Resultados: entrevistadas 121 puérperas, 18,2% (22) adolescentes, verificou-se entre elas baixa escolaridade (p<0,001); menor número de gestações cursando com patologias (p = 0,016); predomínio de primíparas (p<0,001) e maiores índices de parto normal (p = 0,032). A prevalência de adesão à consulta puerperal foi de 34,7% e de 31,8% para adolescentes. Não houve diferenças em relação à adesão e idade das puérperas. Conclusão: adolescentes não apresentaram desfechos obstétricos e neonatais negativos, embora tenha sido observada menor escolaridade. Identificou-se associação entre idade precoce e ausência de doenças na gestação e maiores índices de partos vaginais normais. A adesão ao retorno puerperal apresentou-se pouco inferior, porém sem significância estatística.

Abstract Objective: to determine the profile of pregnancies and prevalence of adherence to puerperal consultation among adolescent puerperal women compared to non-adolescent puerperal women served in an outpatient clinic of a teaching hospital in the rural area of Minas Gerais. Method: cross-sectional study nested in a cohort of puerperal women; non-probabilistic sample, by convenience; adolescent pregnancy - dependent variable; sociodemographic, clinical and obstetric - independent variables. It employed its own instrument, tested by means of a pilot test. Prevalence ratios and confidence intervals were calculated; chi-square and Fisher's exact tests were applied, considering a significance level of 5%, and Poisson regression with robust variance. Results: we interviewed 121 puerperal women, of which 18.2% (22) were adolescents, and observed among them low educational level (p<0.001); fewer pregnancies with pathologies (p=0.016); predominance of primiparous women (p<0.001), and higher rates of normal delivery (p=0.032). The prevalence of adherence to puerperal consultation was 34.7% and 31.8% for adolescents. There were no differences regarding adherence and age of puerperal women. Conclusion: adolescents did not present negative obstetric and neonatal outcomes, although a lower educational level was observed. Association was found between early age and absence of diseases during pregnancy and higher rates of normal vaginal deliveries. Adherence to puerperal return visit was slightly lower, but without statistical significance.

Resumen Objetivo: identificar el perfil de embarazos y la prevalencia de adherencia a las consultas puerperales entre madres adolescentes frente a las no adolescentes, atendidas en un hospital clínico universitario en el interior de Minas Gerais (Brasil). Método: estudio transversal anidado en un grupo de puérperas; muestra no probabilística, por conveniencia; embarazo adolescente - variable dependiente; variables sociodemográficas, clínicas y obstétricas- variables independientes. Se utilizó instrumento propio, prueba piloto. Se calcularon razones de prevalencia e intervalos de confianza; Se aplicaron las pruebas chi-cuadrado y exacta de Fisher, considerando un nivel de significancia del 5%, y regresión de Poisson con varianza robusta. Resultados: se entrevistaron a 121 puérperas, el 18,2% (22) eran adolescentes, siendo confirmado entre ellas una baja escolaridad (p<0,001); menor número de embarazos con patologías (p = 0,016); predominando las primíparas (p<0,001) y mayores tasas de parto normal (p = 0,032). La prevalencia de adherencia a la consulta puerperal fue del 34,7% y de 31,8% en adolescentes. No hubo diferencias en cuanto a la adherencia y la edad de las puérperas. Conclusión: las adolescentes no presentaron resultados obstétricos y neonatales negativos, aunque se observó menor escolaridad. Se identificó una asociación entre la edad precoz y la ausencia de enfermedades durante el embarazo y mayores tasas de partos vaginales normales. La adherencia al retorno puerperal fue ligeramente inferior, pero sin significación estadística.

Cultural adaptation and assessment of the reliability of the Special Needs Kids Questionnaire for the Brazilian context.

OBJECTIVE: To carry out the cultural adaptation of the Special Needs Kids Questionnaire into Brazilian Portuguese and assess its reliability. METHODS: Methodological study conducted between September 2019 and June 2020 from the stages of translation, back-translation, content validation, semantic validation and pilot test. Content Validation Index, Cronbach's Alpha Coefficient and Intraclass Correlation Coefficient were calculated. RESULTS: After the second round, the adapted version had a Content Validation Index greater than 0.80 in all items and was considered understandable by the mothers. The pilot test included 89 mothers of children born prematurely from the Neonatal Intensive Care Unit in the test and 44 in the retest. All items had Cronbach's Alpha greater than 0.70. Of the 20 items, 15 showed moderate reliability, three high and two weak. CONCLUSION: The instrument proved to be reliable and has the potential to identify the fragmentation and discontinuity of the care received.

T cell-mediated response to SARS-CoV-2 in liver transplant recipients with prior COVID-19.

Whether immunosuppression impairs severe acute respiratory syndrome coronavirus 2-specific T cell-mediated immunity (SARS-CoV-2-CMI) after liver transplantation (LT) remains unknown. We included 31 LT recipients in whom SARS-CoV-2-CMI was assessed by intracellular cytokine staining (ICS) and interferon (IFN)-γ FluoroSpot assay after a median of 103 days from COVID-19 diagnosis. Serum SARS-CoV-2 IgG antibodies were measured by ELISA. A control group of nontransplant immunocompetent patients were matched (1:1 ratio) by age and time from diagnosis. Post-transplant SARS-CoV-2-CMI was detected by ICS in 90.3% (28/31) of recipients, with higher proportions for IFN-γ-producing CD4+ than CD8+ responses (93.5% versus 83.9%). Positive spike-specific and nucleoprotein-specific responses were found by FluoroSpot in 86.7% (26/30) of recipients each, whereas membrane protein-specific response was present in 83.3% (25/30). An inverse correlation was observed between the number of spike-specific IFN-γ-producing SFUs and time from diagnosis (Spearman's rho: -0.418; p value = .024). Two recipients (6.5%) failed to mount either T cell-mediated or IgG responses. There were no significant differences between LT recipients and nontransplant patients in the magnitude of responses by FluoroSpot to any of the antigens. Most LT recipients mount detectable-but declining over time-SARS-CoV-2-CMI after a median of 3 months from COVID-19, with no meaningful differences with immunocompetent patients.