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Post-transplant lymphoproliferative disorder is a life-threatening complication of immunosuppression following transplantation mediated by failure of T cells to control Epstein-Barr virus (EBV)-infected and transformed B cells. Typically, a modification or reduction of immunosuppression is recommended, but insufficiently defined thus far. In order to help delineate this, we characterized EBV-antigen-specific T cells and lymphoblastoid cell lines from healthy donors and in patients with a kidney transplant in the absence or presence of the standard immunosuppressants tacrolimus, cyclosporin A, prednisolone, rapamycin, and mycophenolic acid. Phenotypes of lymphoblastoid cell-lines and T cells, T cell-receptor-repertoire diversity, and T-cell reactivity upon co-culture with autologous lymphoblastoid cell lines were analyzed. Rapamycin and mycophenolic acid inhibited lymphoblastoid cell-line proliferation. T cells treated with prednisolone and rapamycin showed nearly normal cytokine production. Proliferation and the viability of T cells were decreased by mycophenolic acid, while tacrolimus and cyclosporin A were strong suppressors of T-cell function including their killing activity. Overall, our study provides a basis for the clinical decision for the modification and reduction of immunosuppression and adds information to the complex balance of maintaining anti-viral immunity while preventing acute rejection. Thus, an immunosuppressive regime based on mTOR inhibition and reduced or withdrawn calcineurin inhibitors could be a promising strategy for patients with increased risk of or manifested EBV-associated post-transplant lymphoproliferative disorder.
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Infecções por Vírus Epstein-Barr , Transtornos Linfoproliferativos , Humanos , Herpesvirus Humano 4 , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico , Calcineurina/genética , Inibidores de MTOR , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Transtornos Linfoproliferativos/tratamento farmacológico , Transtornos Linfoproliferativos/etiologia , Transtornos Linfoproliferativos/prevenção & controle , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Sirolimo/farmacologia , Sirolimo/uso terapêutico , Prednisolona/farmacologia , Prednisolona/uso terapêutico , Serina-Treonina Quinases TORRESUMO
BACKGROUND: Patients in haemodynamic shock are in need for an intensive care treatment. Invasive haemodynamic monitoring is state of the art for these patients. However, evolved, non-invasive blood pressure monitoring devices offer advanced functions like the assessment of central blood pressure and arterial stiffness. We analysed the feasibility of two oscillometric blood pressure devices in patients with shock. METHODS: We performed a monocentre prospective study, enrolling 57 patients admitted to the intensive care unit (ICU), due to septic and/or cardiogenic shock. We assessed invasive and non-invasive peripheral and central blood pressure <24 hours and 48 hours after admission on the ICU. Additional haemodynamic parameters such as pulse wave velocity (PWV), augmentation pressure and augmentation index were obtained through Mobil-o-Graph PWA (IEM) and SphygmoCor XCEL (AtCor Medical). RESULTS: A complete haemodynamic assessment was successful in all patients (48) with the Mobil-o-Graph 24 hours PWA and in 29 patients with the SphygmoCor XCEL (P = .001), when cases of death or device malfunction were excluded. Reasons for failure were severe peripheral artery disease, haemodynamic instability, oedema and agitation. Invasive blood pressure showed a sufficient correlation with both devices; however, large differences between invasive and non-invasive techniques were recorded in Bland-Altmann analysis (P < .05 for all parameters). PWV differed between the two devices. CONCLUSION: Non-invasive peripheral blood pressure measurement remains a rescue technique. However, non-invasive assessment of arterial stiffness and central blood pressure is possible in patients with septic or cardiogenic shock. Further studies are required to assess their clinical significance for patients in shock.
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Determinação da Pressão Arterial/métodos , Pressão Sanguínea/fisiologia , Monitorização Hemodinâmica/métodos , Choque/fisiopatologia , Rigidez Vascular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Determinação da Pressão Arterial/instrumentação , Estudos de Viabilidade , Feminino , Monitorização Hemodinâmica/instrumentação , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Oscilometria/instrumentação , Oscilometria/métodos , Estudos Prospectivos , Análise de Onda de Pulso , Choque Cardiogênico/fisiopatologia , Choque Séptico/fisiopatologiaRESUMO
BACKGROUND/AIM: Peritonitis rates in peritoneal dialysis (PD) vary considerably not only across countries but also between centers in the same country. Patient education has been shown to significantly reduce infection rates but up till now training lacks standardization with patients being trained using different methods and media (e.g., illustrations, videos). As a result, patients may be insufficiently experienced in performing PD, which might be one of the causes for high peritonitis rates. To address these issues, we developed a PD training program based on virtual reality (VR). METHODS: To become acquainted with the PD procedure, patients are equipped with a VR headset and controllers. They are presented with a virtual PD set, which simulates the feeling of sitting in front of a real PD set. The patient is enabled to run through the program as often as necessary to become familiarized with the whole PD procedure. The aim is to standardize, facilitate, and accelerate the individual learning process. To compare the effect of the applied training method to traditional training, a randomized controlled trial is underway. CONCLUSION: Previous studies on the effectiveness of learning showed that VR training applications are superior to traditional methods, such as text- or video-based training. However, no study has been undertaken in the context of dialysis. We believe that the implementation of VR training programs in clinical practice will be beneficial in improving the patient's proficiency, and thereby the quality and safety of PD.
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Educação de Pacientes como Assunto/métodos , Diálise Peritoneal , Realidade Virtual , Feminino , Humanos , Masculino , Educação de Pacientes como Assunto/organização & administraçãoRESUMO
Background: Mono and combined reactivation of latent viruses occurs frequently under immunosuppressive therapy in kidney transplant patients. Recently, monitoring torque teno virus (TTV) reactivation came more into focus as a potential biomarker for immune status. The surrogate characteristics of TTV reactivation on acute rejection, and the combined reactivation with other latent viruses such as cytomegalovirus (CMV), human BK virus (BKV), Epstein-Barr virus (EBV), and human herpes virus-6A (HHV-6A) on allograft function, are unknown so far. Methods: Blood samples from 93 kidney transplant recipients obtained during the first post-transplant year were analyzed for TTV/BKV/CMV/EBV/HHV-6A load. Clinical characteristics, including graft function [glomerular filtration rate (GFR)], were collected in parallel. Results: TTV had the highest prevalence and viral loads at 100% and a mean of 5.72â copies/ml (cp/ml) (log10). We found 28.0%, 26.9%, 7.5%, and 51.6% of simultaneous reactivation of TTV with BKV, CMV, EBV, and HHV-6, respectively. These combined reactivations were not associated with a significantly reduced estimated GFR at month 12. Of interest, patients with lower TTV loads <5.0â cp/ml (log10) demonstrated not only a higher incidence of acute rejection, but also an unexpected significantly earlier occurrence and higher incidence of BKV and HHV-6A reactivation. Correlations between TTV loads, other latent viruses, and immunosuppressive medication were only significant from 6â months after transplant. Conclusion: We were able to observe and support previously introduced TTV load thresholds predicting kidney allograft rejection. However, due to a possible delayed relation between immunosuppressive medication and TTV viral load adaptation, the right time points to start using TTV as a biomarker might need to be further clarified by other and better designed studies.
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PURPOSE: To evaluate the feasibility of diffusion-tensor (DT) imaging at 3 T for functional assessment of transplanted kidneys. MATERIALS AND METHODS: This study was approved by the local ethics committee; written informed consent was obtained. Between August 2009 and October 2010, 40 renal transplant recipients were prospectively included in this study and examined with a clinical 3-T magnetic resonance (MR) imager. An echo-planar DT imaging sequence was performed in coronal orientation by using five b values (0, 200, 400, 600, 800 sec/mm(2)) and 20 diffusion directions. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were determined for the cortex and medulla of the transplanted kidney. Relationships between FA, ADC, and allograft function, determined by the estimated glomerular filtration rate (eGFR), were assessed by using Pearson correlation coefficient. ADC and FA were compared between patients with good or moderate allograft function (group A; eGFR > 30 mL/min/1.73 m(2)) and patients with impaired function (group B; eGFR ≤ 30 mL/min/1.73 m(2)) by using a student t test. P < .05 indicated a statistically significant difference. RESULTS: Mean FA of the renal medulla and cortex was significantly higher in group A (0.39 ± 0.06 and 0.17 ± 0.4) compared with group B (0.27 ± 0.05 and 0.14 ± 0.03) (P < .001 and P = .009, respectively). Mean ADCs of renal cortex and medulla were significantly higher in group A than in group B (P = .007 and P = .01, respectively). In group B, mean medullary FA was significantly lower in patients whose renal function did not recover (0.22 ± 0.02) compared with those with stable allograft function at 6 months (0.29 ± 0.05, P < .001). There was significant correlation between eGFR and medullary FA (r = 0.65, P < .001), cortical ADC (r = 0.43, P = .003), and medullary ADC (r = 0.35, P = .01). CONCLUSION: DT imaging is a promising noninvasive technique for functional assessment of renal allografts. FA values in the renal medulla exhibit a good correlation with renal function.
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Imagem de Difusão por Ressonância Magnética/métodos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Nefropatias/etiologia , Nefropatias/patologia , Transplante de Rim/efeitos adversos , Transplante de Rim/patologia , Adulto , Estudos de Viabilidade , Feminino , Humanos , Testes de Função Renal/métodos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do TratamentoRESUMO
Human herpesvirus 6 (HHV-6) is a common opportunistic pathogen in kidney transplant recipients. Two distinct species of HHV-6, HHV-6A and HHV-6B, have been identified, of which the latter seems to be dominant. However, it is unclear whether they increase the likelihood of other viral reactivations. We characterized a multi-centre cohort of 93 patients along nine study visits for viral load. We tested for the following viruses: HHV-6A and HHV-6B, the herpesviruses cytomegalovirus (CMV) and Epstein-Barr virus (EBV) and the polyomavirus BK (BKV). We detected HHV-6A viral load in 48 (51.6%) patients, while the incidence of HHV-6B was much lower, being detected in 6 (6.5%) patients. The incidence of HHV-6A was higher than of BKV, CMV and EBV. HHV-6A also demonstrated higher viral loads than the rest of viruses. There was a non-significant trend of association between HHV-6A and HHV-6B as co-infection, whereas no increased incidence of other viruses among patients with HHV-6A reactivation was observed. There was no negative effect of high HHV-6A (>10,000â copies/ml) load on markers of renal graft and hepatic function or blood count twelve months post-transplant. In contrast to previously published data, our results show a clear dominance of HHV-6A in peripheral blood when compared to HHV-6B, with higher incidence and viral load levels. Despite the high HHV-6A loads observed, we did not identify any negative effects on posttransplant outcome.
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It has recently been shown that von Willebrand factor (VWF) multimers contribute to immunothrombosis in Coronavirus disease 2019 (COVID-19). Since COVID-19 is associated with an increased risk of autoreactivity, the present study investigates, whether the generation of autoantibodies to ADAMTS13 contributes to this finding. In this observational prospective controlled multicenter study blood samples and clinical data of patients hospitalized for COVID-19 were collected from April to November 2020. The study included 156 individuals with 90 patients having confirmed COVID-19 of mild to critical severity. 30 healthy individuals and 36 critically ill ICU patients without COVID-19 served as controls. ADAMTS13 antibodies occurred in 31 (34.4%) COVID-19 patients. Antibodies occurred more often in critically ill COVID-19 patients (55.9%) than non-COVID-19 ICU patients and healthy controls (5.6% and 6.7%; p < 0.001), respectively. Generation of ADAMTS13 antibodies in COVID-19 was associated with lower ADAMTS13 activity (56.5%, interquartile range (IQR) 21.25 vs. 71.5%, IQR 24.25, p = 0.0041), increased disease severity (severe or critical in 90% vs. 62.3%, p = 0.019), and a trend to higher mortality (35.5% vs. 18.6%, p = 0.077). Median time to antibody development was 11 days after first positive SARS-CoV-2-PCR specimen. Gel analysis of VWF multimers resembled the constellation in patients with TTP. The present study demonstrates for the first time, that generation of ADAMTS13 antibodies is frequent in COVID-19, associated with lower ADAMTS13 activity and increased risk of an adverse disease course. These findings provide a rationale to include ADAMTS13 antibodies in the diagnostic workup of SARS-CoV-2 infections.
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Autoanticorpos , COVID-19 , Humanos , Estado Terminal , Estudos Prospectivos , Fator de von Willebrand , SARS-CoV-2 , Proteína ADAMTS13RESUMO
To compare minimally invasive video-assisted parathyroidectomy (MIVAP) versus conventional surgery for renal hyperparathyroidism (rHPT). Between 2006 and 2020, 53 patients underwent MIVAP and 182 underwent conventional parathyroidectomy for rHPT at the Kliniken Essen-Mitte and Knappschaftskrankenhaus Bochum, respectively. Two propensity score-matched groups were retrospectively analyzed: the MIVAP group (VG; n = 53) and the conventional group (CG; n = 53). To assess long-term results, the patients were questioned prospectively (VG; n = 17, and CG; n = 26). The VG had a smaller incision (2.8 vs. 4.8 cm), shorter operation duration (81.0 vs. 13.9 min), and shorter duration of stay (2.4 vs. 5.7 days) (p < 0.0001) but a smaller drop in parathyroid hormone (PTH) postoperatively (81.3 vs. 85.5%. p = 0.022) than the CG. The conversion rate was 9.4% (n = 5). The VG had better Patient Scar Assessment Scale (PSAS) scores (10.8 vs. 11.7 p = 0.001) but worse SF-12 health survey scores (38.7 vs. 45.8 for physical health and 46.7 vs. 53.4 for mental health) (p < 0.0001). The PTH level at follow-up was higher in the VG (162.7 vs. 59.1 ng/l, p < 0.0001). There were no differences in morbidity, number of removed parathyroid glands, disease persistence, late rHPT relapse and need for repeat surgery between groups. MIVAP was superior to conventional parathyroidectomy regarding aesthetic outcomes and cost effectiveness. Conventional surgery showed better control of PTH levels and health scores on follow-up than MIVAP, without any impact on rHPT relapse and need for repeat surgery.Trail registration number and date of registration: DRKS00022545 on 14.12.2020.
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Hiperparatireoidismo , Paratireoidectomia , Humanos , Hiperparatireoidismo/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Paratireoidectomia/métodos , Recidiva , Estudos Retrospectivos , Cirurgia Vídeoassistida/métodosRESUMO
Blood pressure (BP) shows a seasonal variation with higher levels at lower temperatures. Many hypertensives, however, report on BP disturbances rather in association with acutely changing weather conditions than with absolute temperatures. To date, the impact of changing meteorological parameters on hypertensive episodes remains elusive. We performed a retrospective time series regression analysis on 203,703 patients in three hospitals in Germany between 2010 and 2018, of whom 7362 patients were admitted for hypertensive disease. Numbers of daily admissions for hypertension were associated with metereological data obtained from three nearby weather stations. Data comprised temperature (mean, maximal, minimal and range within 24 h), athmospheric pressure, and precipitation. Changes of these parameters were calculated over a two and three day period. There was an inverse correlation between maximal daily temperature and the number of admissions for hypertensive disease, which remained significant both after adjustment for seasonality and week day in a spline model and in a constrained distributed lag model. A decrease of maximal temperature by 5 °C was associated with a 3% increase of risk for admission for hypertension and vice versa. There were no significant effects of precipitation and athmospheric pressure on the number of admissions. With regard to all observed metereological parameters, neither the change within two, nor within three days was consistently associated with the number of daily admissions. High temperatures are associated with lower numbers of hypertensive episodes requiring hospital admission. In contrast to the subjective perception of many hypertensive patients, however, acutely changing weather conditions are not associated with a higher risk of hypertensive emergency.
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Hipertensão , Tempo (Meteorologia) , Hospitalização , Hospitais , Humanos , Hipertensão/epidemiologia , Estudos Retrospectivos , Estações do Ano , TemperaturaRESUMO
BACKGROUND Morbidity and mortality rates are high for patients returning to dialysis after renal graft failure. Keeping failed kidney transplants in situ with concomitant minimization or withdrawal of immunosuppression is standard of care in many transplant centers. It is unclear, however, whether the resulting allospecific immune response can cause a microinflammatory milieu. The present work investigated the impact of allograft nephrectomy on systemic inflammation, erythropoiesis, and donor-specific antibodies (DSA). MATERIAL AND METHODS We performed a retrospective analysis evaluating C-reactive protein (CRP), hemoglobin concentration (Hb), ferritin, iron substitution dosages, erythropoietin dosages, and DSA in 92 transplant recipients with allograft failure, of whom 49 did not (Group A) and 43 did undergo transplant nephrectomy (Group B). Blood samples and clinical data were obtained 3-6 months after returning to dialysis. We additionally assessed outcome of kidney re-transplantation in a 10-year follow-up. RESULTS There was no significant difference in Hb concentrations, ferritin concentrations, CRP concentrations, iron, and EPO substitution dosages between the 2 groups. Patients undergoing nephrectomy had a significantly higher prevalence of DSA (65.1% vs 38.8%, P<0.0001). In the 10-year follow-up, 3 patients (12%) of Group B and none in Group A had allograft failure after primary successful re-transplantation. CONCLUSIONS Keeping a kidney graft in situ after returning to dialysis did not lead to an increase in microinflammation. Although DSA develops in more than 50% of patients after an allograft nephrectomy, the outcome of a renal re-transplantation seems to be unaffected. Thus, both strategies are feasible options in kidney transplant recipients after return to dialysis.
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Eritropoese , Rejeição de Enxerto , Inflamação , Transplante de Rim , Aloenxertos , Anticorpos , Ferritinas , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Ferro , Nefrectomia , Complicações Pós-Operatórias , Estudos RetrospectivosRESUMO
Background: Despite recent advances and refinements in perioperative management of kidney transplantation (KT), early renal graft injury (eRGI) remains a critical problem with serious impairment of graft function as well as short- and long-term outcome. Serial monitoring of peripheral blood innate immune cells might be a useful tool in predicting post-transplant eRGI and graft outcome after KT. Methods: In this prospective study, medical data of 50 consecutive patients undergoing KT at the University Hospital of Leipzig were analyzed starting at the day of KT until day 10 after the transplantation. The main outcome parameter was the occurrence of eRGI and other outcome parameters associated with graft function/outcome. eRGI was defined as graft-related complications and clinical signs of renal IRI (ischemia reperfusion injury), such as acute tubular necrosis (ATN), delayed graft function (DGF), initial nonfunction (INF) and graft rejection within 3 months following KT. Typical innate immune cells including neutrophils, natural killer (NK) cells, monocytes, basophils and dendritic cells (myeloid, plasmacytoid) were measured in all patients in peripheral blood at day 0, 1, 3, 7 and 10 after the transplantation. Receiver operating characteristics (ROC) curves were performed to assess their predictive value for eRGI. Cutoff levels were calculated with the Youden index. Significant diagnostic immunological cutoffs and other prognostic clinical factors were tested in a multivariate logistic regression model. Results: Of the 50 included patients, 23 patients developed eRGI. Mean levels of neutrophils and monocytes were significantly higher on most days in the eRGI group compared to the non-eRGI group after transplantation, whereas a significant decrease in NK cell count, basophil levels and DC counts could be found between baseline and postoperative course. ROC analysis indicated that monocytes levels on POD 7 (AUC: 0.91) and NK cell levels on POD 7 (AUC: 0.92) were highly predictive for eRGI after KT. Multivariable analysis identified recipient age (OR 1.53 (95% CI: 1.003−2.350), p = 0.040), recipient body mass index > 25 kg/m2 (OR 5.6 (95% CI: 1.36−23.9), p = 0.015), recipient cardiovascular disease (OR 8.17 (95% CI: 1.28−52.16), p = 0.026), donor age (OR 1.068 (95% CI: 1.011−1.128), p = 0.027), <0.010), deceased-donor transplantation (OR 2.18 (95% CI: 1.091−4.112), p = 0.027) and cold ischemia time (CIT) of the renal graft (OR 1.005 (95% CI: 1.001−1.01), p = 0.019) as clinically relevant prognostic factors associated with increased eRGI following KT. Further, neutrophils > 9.4 × 103/µL on POD 7 (OR 16.1 (95% CI: 1.31−195.6), p = 0.031), monocytes > 1150 cells/ul on POD 7 (OR 7.81 (95% CI: 1.97−63.18), p = 0.048), NK cells < 125 cells/µL on POD 3 (OR 6.97 (95% CI: 3.81−12.7), p < 0.01), basophils < 18.1 cells/µL on POD 10 (OR 3.45 (95% CI: 1.37−12.3), p = 0.02) and mDC < 4.7 cells/µL on POD 7 (OR 11.68 (95% CI: 1.85−73.4), p < 0.01) were revealed as independent biochemical predictive variables for eRGI after KT. Conclusions: We show that the combined measurement of immunological innate variables (NK cells and monocytes on POD 7) and specific clinical factors such as prolonged CIT, increased donor and recipient age and morbidity together with deceased-donor transplantation were significant and specific predictors of eRGI following KT. We suggest that intensified monitoring of these parameters might be a helpful clinical tool in identifying patients at a higher risk of postoperative complication after KT and may therefore help to detect andby diligent clinical managementeven prevent deteriorated outcome due to IRI and eRGI after KT.
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Ubiquitous microthromboses in the pulmonary vasculature play a crucial role in the pathogenesis of COVID-19 associated acute respiratory distress syndrome (ARDS). Excess of Willebrand factor (vWf) with intravascular multimer formation was identified as a key driver of this finding. Plasma exchange (PLEX) might be a therapeutic option to restore the disbalance between vWf and ADAMTS13. We report the effects of PLEX on vWf, ADAMTS13, inflammatory cytokines and parameters of ventilation. We investigated 25 patients, who were on mechanical ventilation for COVID-19 pneumonia with ARDS at two German university hospitals. All patients received PLEX as an ultima ratio measure for refractory ARDS. VWf antigen (vWf:Ag), ADAMTS13 activity, a cytokine panel mirroring the inflammatory situation and clinical parameters were assessed before and after three to six PLEX therapies with fresh frozen plasma. Before the PLEX sequence there was an excessive release of vWf:Ag (425.4 ± 167.5%) and mildly reduced ADAMTS13 activity (49.7 ± 23.3%). After the PLEX series, there was a significant increase of ADAMTS13 activity to 62.4 ± 17.7% (p = 0.029) and a significant decrease of vWf:Ag to 336.1 ± 138.2% (p = 0.041) resulting in a 63% improvement of the ADAMT13/vWf:Ag ratio from 14.5 ± 10.0 to 23.7 ± 14.6, p = 0.024. Comparison of parameters before and after individual PLEX sessions (n = 35) revealed a mean reduction of vWf from 387.8 ± 165.1 to 213.2 ± 62.3% (p = 0.001) and an increase of ADAMTS13 activity from 60.4 ± 20.1 to 70.5 ± 14.0% (p = 0.001). Parallelly, monocyte chemotactic protein-1 and interleukin-18 decreased significantly (p = 0.034 each). Along the PLEX sequence lactate dehydrogenase (p = 0.001), C-reactive protein (p = 0.001), and positive end expiratory pressure (p = 0.01) significantly decreased accompanied by an improvement of Horovitz index (p = 0.001). PLEX restores the disbalance between ADAMTS13 and vWf:Ag, a driver of immunothrombosis. Moreover, it reduces the inflammatory state and is associated with a benefit of ventilation parameters. These findings render a further rationale to regard PLEX as a therapeutic option in severe COVID-19.
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COVID-19 , Troca Plasmática , Fator de von Willebrand , Proteína ADAMTS13/metabolismo , COVID-19/terapia , Estado Terminal/terapia , Humanos , Inflamação/terapia , Fator de von Willebrand/metabolismoRESUMO
Healthcare workers are at substantially increased risk for infection with SARS-CoV-2. Successful vaccination constitutes a crucial prerequisite to protect this group during the pandemic. Since post vaccination antibody monitoring is not standard of care in all healthcare institutions, data on risk factors of impaired vaccine induced immune response are urgently required. Moreover, there are no data on cellular immune responses in humoral low responders so far. Anti-SARS-CoV-2 spike IgG was assessed after vaccination with BNT162b2 in 1386 employees of three hospitals of a German healthcare provider. Concentrations were compared to those of 45 convalescent employees. Vaccine-induced cellular immunity was measured in employees with reduced humoral response by assessment of frequencies of SARS-CoV-2-reactive CD4+ and CD8+ T cell. Anti-SARS-CoV-2 spike IgG were detected in 99.9% of 1386 healthcare workers after completed vaccination. The median antibody concentration was significantly higher after vaccination than after infection with SARS-CoV-2 (p = 0.0001). 10 subjects (0.7%) generated an IgG concentration < 100 IU/ml, and only two persons (0.1%, solid organ recipients) did not produce detectable antibodies at all. T cell responses of those subjects with submaximal or lacking humoral response were comparable to employees with maximal antibody titers. 50% of those individuals with impaired or lacking humoral immune response were on immunosuppression. Vaccination to SARS-CoV-2 with BNT162b2 is very effective in healthcare workers yielding a seroconversion rate of 99.9%. Immunosuppression is the most important risk factor of an impaired immune response. There was no case of vaccination failure without immunosuppression. Thus, post vaccination antibody monitoring is highly recommendable in those employees with immunosuppression.
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COVID-19 , Vacinas , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Pessoal de Saúde , Humanos , Imunidade Humoral , Imunoglobulina G , SARS-CoV-2 , VacinaçãoRESUMO
BACKGROUND: Low-density lipoprotein apheresis is not specific to lipoproteins but removes immunoglobulins as well. It remains elusive, whether protective SARS-CoV-2 antibodies after vaccination from COVID-19 are eliminated as well. METHODS: A cross-sectional case-control study on 55 patients undergoing weekly lipoprotein apheresis and 21 patients with comparable comorbidities and epidemiology not undergoing apheresis. SARS-CoV-2 IgG was assessed in all patients prior to apheresis and in 38 patients both before and after apheresis. RESULTS: SARS-CoV-2 IgG concentrations before a session of lipoprotein apheresis were comparable to control patients not undergoing apheresis(1727 IU/ml, IQR 365-2500) vs. 1652 IU/ml,(IQR408.8-2500), p = 0.78). SARS-CoV-2 IgG concentrations were reduced by lipoprotein apheresis from 1656 IU/ml(IQR 540.5-2500) prior to 1305 IU/ml (IQR 449-2500) afterwards(p < 0.0001). CONCLUSION: Lipoprotein apheresis removes SARS-CoV-2 IgG. The average elimination rate was 21.2%. In the present population of patients undergoing apheresis once weekly, however, the elimination did not lead to inferior concentrations compared to patients not undergoing lipoprotein apheresis.
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Remoção de Componentes Sanguíneos , COVID-19 , Humanos , SARS-CoV-2 , Estudos de Casos e Controles , Estudos Transversais , COVID-19/terapia , Lipoproteínas , Lipoproteínas LDL , Imunoglobulina GRESUMO
Simultaneous pancreas and kidney transplantation (SPK) is an accepted treatment for diabetic patients with renal failure, and is associated with increased survival and quality of life for recipients. There are only a few publications on the outcomes of simultaneous pancreas-kidney retransplantation (Re-SPK) after previous SPK and the loss of function of both grafts. A total of 55 patients with type 1 diabetes mellitus underwent pancreas retransplantation at our center between January 1994 and March 2021. Twenty-four of these patients underwent Re-SPK after a previous SPK. All 24 operations were technically feasible. Patient survival rate after 3 months, 1 year, and 5 years was 79.2%, 75%, and 66.7%, respectively. The causes of death were septic arterial hemorrhage (n = 3), septic multiorgan failure (n = 2), and was unknown in one patient. Pancreas and kidney graft function after 3 months, 1 year, and 5 years were 70.8% and 66.7%, 66.7% and 62.5%, and 45.8% and 54.2%, respectively. Relaparotomy was performed in 13 out of 24 (54.2%) patients. The results of our study show that Re-SPK, after previously performed SPK, is a technical and immunological challenge, associated with a significantly increased mortality and complication rate; therefore, the indication for Re-SPK should be very strict. Careful preoperative diagnosis is indispensable.
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OBJECTIVES: Histidine-tryptophan-ketoglutarate and University of Wisconsin solutions are currently used for pancreas graft preservation. Our hypothesis was whether the use of histidine-tryptophan-ketoglutarate solution is associated with worse pancreas graft survival than University of Wisconsin solution, in general and after prolonged cold ischemic time of ≥12 hours. MATERIALS AND METHODS: This retrospective study investigated the impact of static cold storage in histidine-tryptophan-ketoglutarate (n = 133) versus University of Wisconsin (n = 107) solution on outcomes of 240 pancreas transplant procedures. Patient and graft survival rates were compared after 1, 3, and 5 years in both groups. Serum lipase, amylase, and C-reactive protein levels and incidence of surgical complications were evaluated at postoperative week 1. A subgroup analysis of 96 grafts (52 with histidine-tryptophanketoglutarate/44 with University of Wisconsin) with pancreas graft cold ischemic time ≥12 hours was also performed. RESULTS: At mean follow-up of 75.2 ± 9.9 months, both groups demonstrated comparable short- and long-term patient survival. Overall, pancreas graft survival was slightly better in the histidine-tryptophan-ketoglutarate group (Kaplan-Meier analysis, log-rank P = .013). However, the subgroup analysis of grafts with cold ischemic time ≥12 hours showed slightly better pancreatic graft survival in the University of Wisconsin group, although not significantly (log-rank P = .95). Serum lipase and C-reactive protein levels at postoperative week 1 were higher in the histidinetryptophan-ketoglutarate group. Surgical complications were comparable. Multivariable Cox regression analysis identified neither solution as a risk factor affecting patient and graft survival. CONCLUSIONS: Although a direct comparison between histidine-tryptophan-ketoglutarate and University of Wisconsin showed better pancreas graft survival with histidine-tryptophan-ketoglutarate, the multivariable analysis showed that the perfusion solution does not significantly influence patient and graft survival. However, in the analysis of transplants with cold ischemic time ≥12 hours, pancreas graft survival was slightly better in the University of Wisconsin group, although not significantly.
Assuntos
Histidina , Soluções para Preservação de Órgãos , Adenosina , Alopurinol/efeitos adversos , Proteína C-Reativa , Isquemia Fria/efeitos adversos , Glucose/efeitos adversos , Glutationa , Humanos , Insulina/efeitos adversos , Lipase , Soluções para Preservação de Órgãos/efeitos adversos , Pâncreas , Rafinose/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Triptofano , Universidades , WisconsinRESUMO
BACKGROUND: De novo donor-specific antibodies (DSA) are associated with an increased risk of antibody-mediated rejection and a substantial reduction of allograft survival. We hypothesized that detection of DSA should prompt a biopsy even in the absence of proteinuria and loss of estimated glomerular filtration rate (eGFR). However, data on a population without proteinuria or loss of kidney function is scant, and this is the main novelty of our study design. METHODS: Single center retrospective analysis on biopsy findings after detection of de novo DSA. One-hundred-thirty-two kidney and pancreas-kidney transplant recipients were included. Eighty-four of these patients (63.6%) underwent allograft biopsy. At the time of biopsy n = 50 (59.5%) had a protein/creatinine ratio (PCR) > 300 mg/g creatinine and/or a loss of eGFR ≥ 10 ml/min in the previous 12 months, whereas 40.5% did not. Diagnosis of rejection was performed according to Banff criteria. RESULTS: Seventy-seven (91.7%) of the biopsies had signs of rejection (47.6% antibody mediated rejection (ABMR), 13.1% cellular, 20.2% combined, 10.7% borderline). Among subjects without proteinuria or loss of eGFR ≥ 10 ml/min/a (n = 34), 29 patients (85.3%) showed signs of rejection (44.1% antibody mediated (ABMR), 14.7% cellular, 11.8% combined, 14.7% borderline). CONCLUSION: The majority of subjects with de novo DSA have histological signs of rejection, even in the absence of proteinuria and deterioration of graft function. Thus, it appears reasonable to routinely perform an allograft biopsy after the detection of de novo DSA.
Assuntos
Transplante de Rim , Biópsia , Rejeição de Enxerto/diagnóstico , Sobrevivência de Enxerto , Antígenos HLA , Humanos , Isoanticorpos , Rim , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , TransplantadosRESUMO
BACKGROUND: Transplant recipients are prone to developing severe infections because of immunosuppression. Therefore, studying the manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in transplant recipients is of particular importance. METHODS: One hundred twelve transplant patients consecutively visiting the outpatient department of 2 German transplant centers were included in this study after providing written informed consent. The patients were interviewed about coronavirus disease 2019 (COVID-19) symptoms and history. Nasopharyngeal swabs were analyzed by SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR). SARS-CoV-2 IgG and IgA were measured concomitantly in patient sera by enzyme-linked immunosorbent assay. RESULTS: The risk of severe COVID-19 according to 2 recent scores differed among the analyzed patients. All patients were well educated about their presumed higher risk of a severe COVID-19 and described performing self-isolation wherever possible. Nevertheless, 20 patients reported contact with someone suspected of having COVID-19 or who tested positive shortly thereafter (18%). Despite this relatively high exposure, no clinically relevant case of COVID-19 was reported. Though SARS-CoV-2 IgG and IgA were found in 3 patients (3%); 2 patients were asymptomatic and only 1 had mild COVID-19 symptoms and positive RT-PCR 4 weeks earlier. There were no occult SARS-CoV-2 infections, as demonstrated by negative PCR tests. CONCLUSION: Despite the high exposure level, the incidence of COVID-19 remained very low. Because of the differences in COVID-19 risk, balancing risk exposure and quality of life should be recommended.
Assuntos
COVID-19/diagnóstico , Transplantados/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , COVID-19/epidemiologia , COVID-19/virologia , Feminino , Alemanha/epidemiologia , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos , Prevalência , RNA Viral/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Risco , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificaçãoRESUMO
OBJECTIVE: To quantify renal allograft perfusion in recipients with stable allograft function and acute decrease in allograft function using nonenhanced flow-sensitive alternating inversion recovery (FAIR)-TrueFISP arterial spin labeling (ASL) MR imaging. METHODS: Following approval of the local ethics committee, 20 renal allograft recipients were included in this study. ASL perfusion measurement and an anatomical T2-weighted single-shot fast spin-echo (HASTE) sequence were performed on a 1.5-T scanner (Magnetom Avanto, Siemens, Erlangen, Germany). T2-weighted MR urography was performed in patients with suspected ureteral obstruction. Patients were assigned to three groups: group a, 6 patients with stable allograft function over the previous 4 months; group b, 7 patients with good allograft function who underwent transplantation during the previous 3 weeks; group c, 7 allograft recipients with an acute deterioration of renal function. RESULTS: Mean cortical perfusion values were 304.8 +/- 34.4, 296.5 +/- 44.1, and 181.9 +/- 53.4 mg/100 ml/min for groups a, b and c, respectively. Reduction in cortical perfusion in group c was statistically significant. CONCLUSION: Our results indicate that ASL is a promising technique for nonenhanced quantification of cortical perfusion of renal allografts. Further studies are required to determine the clinical value of ASL for monitoring renal allograft recipients.