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1.
Hemodial Int ; 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33709483

RESUMO

INTRODUCTION: Fluid management is an important goal of dialysis treatment. The accurate assessment of fluid status is still a challenge for clinical nephrologists. Bioimpedance analysis (BIA) has been proposed as an objective tool to assess hydration. METHODS: This was a prospective randomized controlled study to compare hydration status measured by clinical assessment compared to BIA using a body composition monitor (BCM). The primary outcome was defined as the decline of cardiac biomarker N-terminal pro brain natriuretic peptide (NT-proBNP) from baseline to the end of the study. FINDINGS: About 281 chronic hemodialysis patients were assessed for eligibility, and 132 patients provided written informed consent to participate (65 BIA group, 67 clinical group). Predialytic NT-proBNP, and decline of NT-proBNP were similar in both groups. The amount of overhydration (2.18 ± 2.11 L vs. 1.29 ± 1.97 L; p 0.016) and the number of patients with severe overhydration (46.0% vs. 30.6%, p = 0.04) were significantly higher in the BIA group at the end of the study. Fluid accumulation in the interdialytic period was significantly lower in the clinical group (p = 0.013). Adverse events occurred more often in the BIA group (p = 0.032). The cumulative number of hypovolemic events was significantly higher in the BIA group (p = 0.002). DISCUSSION: Fluid management by BIA does not lead to a better cardiac outcome (appraised by surrogate markers) than fluid management by careful clinical assessment. Adapting the dry weight according to BIA results increases the risk of adverse events, especially hypovolemic episodes. Careful clinical fluid assessment is important for optimal care of chronic hemodialysis patients.

2.
Br J Clin Pharmacol ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620734

RESUMO

AIMS: Calcineurin inhibitors (CNI) have a small therapeutic window, and drug monitoring is required. Pharmacokinetic monitoring does not correlate sufficiently with clinical outcome. Therefore, the expression of nuclear factor of activated T cells (NFAT)-regulated genes in the peripheral blood has been suggested as a potentially useful immune monitoring tool to optimize CNI therapy. NFAT-regulated gene expression (RGE) was evaluated in renal allograft recipients as predictive biomarker to detect patients at risk of acute rejection or infections. METHODS: NFAT-RGE (interleukin-2, interferon-γ, granular-macrophage colony-stimulating factor) was evaluated by quantitative real-time polymerase chain reaction in whole blood samples at day 7, day 14, month 1, 3, and 6 after transplantation in 64 de novo renal allograft recipients from 3 European centres. Immunosuppression consisted of tacrolimus (Tac), mycophenolic acid, and corticosteroids. RESULTS: Tac concentrations (C0 and C1.5) correlated inversely with NFAT-RGE (P < .01). NFAT-RGE showed a high interindividual variability (1-61%). Patients with high residual gene expression (NFAT-RGE ≥30%) were at the increased risk of acute rejection in the following months (35 vs. 5%, P = .02), whereas patients with low residual gene expression (NFAT-RGE <30%) showed a higher incidence of viral complications, especially cytomegalovirus and BK virus replication (52.5 vs. 10%, P = .01). CONCLUSIONS: NFAT-RGE was confirmed as a potential noninvasive early predictive biomarker in the immediate post-transplant period to detect patients at risk of acute rejection and infectious complications in Tac-treated renal allograft recipients. Monitoring of NFAT-RGE may provide additional useful information for physicians to achieve individualized Tac treatment.

3.
Rheumatol Int ; 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33222006

RESUMO

To study the impact of glucocorticoid maintenance dose and treatment duration on outcomes in patients with AAV (ANCA-associated vasculitis) with emphasis on infectious complications. A total of 130 AAV patients from two German vasculitis centers diagnosed between August 2004 and January 2019 treated with cyclophosphamide and glucocorticoids for induction therapy and glucocorticoids for maintenance therapy were retrospectively enrolled. We investigated the influence of glucocorticoid maintenance therapy on patient survival, time to relapse, kidney function, infectious complications and irreversible physical damage. The patients were divided into the following groups: patients treated according to the predefined reduction scheme (< 7.5 mg) or patients treated with glucocorticoids ≥ 7.5 mg after 6 months. Compared to patients receiving < 7.5 mg glucocorticoids after 6 months, patients receiving [Formula: see text] 7.5 mg had an increased rate of infectious episodes per patient (1.7 vs. 0.6; p < 0.001), including urinary tract infection (p = 0.007), pneumonia (p = 0.003), opportunistic pneumonia (p = 0.022) and sepsis (p = 0.008). Especially pneumonia during the first 24 months after disease onset [hazard ratio, 3.0 (95% CI 1.5 - 6.1)] led to more deaths from infection (p = 0.034). Glucocorticoid maintenance therapy after 6 months had no impact on relapse rate or patient survival and decline in kidney function was comparable. Glucocorticoid maintenance therapy with [Formula: see text] 7.5 mg after 6 months is associated with more severe infectious complications leading to an increased frequency of deaths from infection. Glucocorticoid maintenance therapy has no effect on time to relapse or patient survival and should therefore be critically revised throughout the aftercare of AAV patients.

4.
Sci Rep ; 10(1): 19117, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33154421

RESUMO

Podocyte injury has recently been described as unifying feature in idiopathic nephrotic syndromes (INS). Puumala hantavirus (PUUV) infection represents a unique RNA virus-induced renal disease with significant proteinuria. The underlying pathomechanism is unclear. We hypothesized that PUUV infection results in podocyte injury, similar to findings in INS. We therefore analyzed standard markers of glomerular proteinuria (e.g. immunoglobulin G [IgG]), urinary nephrin excretion (podocyte injury) and serum levels of the soluble urokinase plasminogen activator receptor (suPAR), a proposed pathomechanically involved molecule in INS, in PUUV-infected patients. Hantavirus patients showed significantly increased urinary nephrin, IgG and serum suPAR concentrations compared to healthy controls. Nephrin and IgG levels were significantly higher in patients with severe proteinuria than with mild proteinuria, and nephrin correlated strongly with biomarkers of glomerular proteinuria over time. Congruently, electron microcopy analyses showed a focal podocyte foot process effacement. suPAR correlated significantly with urinary nephrin, IgG and albumin levels, suggesting suPAR as a pathophysiological mediator in podocyte dysfunction. In contrast to INS, proteinuria recovered autonomously in hantavirus patients. This study reveals podocyte injury as main cause of proteinuria in hantavirus patients. A better understanding of the regenerative nature of hantavirus-induced glomerulopathy may generate new therapeutic approaches for INS.

5.
BMJ Open ; 10(10): e032286, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051226

RESUMO

INTRODUCTION: Peritoneal fenestration is an effective preventive method for reducing the rate of lymphatic complications in kidney transplantation (KTx). The size of the fenestration plays an important role in its effectiveness. A large peritoneal window is no longer indicated, due to herniation and difficulties in performing biopsies. Small preventive fenestration is effective but will be closed too early. The aim of this study is to evaluate whether metal clips around the edges of a small fenestration result in optimal effects with minimum fenestration size. METHODS AND ANALYSIS: This trial has been initiated in July 2019 and is expected to last for 2 and a half years. All patients older than 18 years, who receive kidneys from deceased donors, will be included. The kidney recipients will be randomly allocated to either a control arm (small fenestration alone) or an intervention arm (small fenestration with clipping). All fenestrations will be round, maximum 2 cm, and close to the kidney hilum. Clipping will be performed with eight metal clips around the peritoneal window (360°) in every 45° in an oblique position. The primary endpoint is the incidence of symptomatic post-KTx lymphatic complications, which require interventional treatment within 6 months after KTx. Secondary endpoints are intraoperative and postoperative outcomes, including blood loss, operation time, severity grade of lymphocele/lymphorrhea and relative symptoms. ETHICS AND DISSEMINATION: This protocol study received approval from the Ethics Committee of the University of Heidelberg (Registration Number S-318/2017). A Standard Protocol Items: Recommendations for Interventional Trials checklist is available for this protocol. The results will be disseminated through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT03682627).

7.
Front Immunol ; 11: 1886, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983110

RESUMO

Delayed graft function (DGF) occurs in a significant proportion of deceased donor kidney transplant recipients and was associated with graft injury and inferior clinical outcome. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of human leukocyte antigen (HLA) antibodies. 1,724 patients who received a deceased donor kidney transplant during 2008-2017 and on whom a pre-transplant serum sample was available were studied. Graft survival during the first 3 post-transplant years was analyzed by multivariable Cox regression. Pre-transplant predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections in the first 3 post-transplant months were determined by multivariable logistic regression. Donor age ≥50 years, simultaneous pre-transplant presence of HLA class I and II antibodies, diabetes mellitus as cause of end-stage renal disease, cold ischemia time ≥18 h, and time on dialysis >5 years were associated with increased risk of DGF, while the risk was reduced if gender of donor or recipient was female or the reason for death of donor was trauma. DGF alone doubled the risk for graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (hazard ratio HR=4.75, P < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P < 0.001) were present pre-transplant. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections, including antibody-mediated rejections, increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1, whereas patients with both DGF and rejection showed the lowest rate of good kidney function, especially when organs from ≥65-year-old donors were used. In this new era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Measures to prevent the strong negative impact of DGF on outcome are necessary, especially during organ allocation for presensitized patients.

9.
Clin Exp Rheumatol ; 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32573411

RESUMO

OBJECTIVES: An imbalance between CD4+-regulatory T-cells (Tregs) and CD4+-responder T-cells (Tresps) correlates with active disease flares in systemic lupus erythematosus (SLE) patients. Both cell subsets consist of highly proliferating Tregs/Tresps expressing inducible T-cell co-stimulatory molecule (ICOS) and less proliferating ICOS--Tregs/Tresps. METHODS: Six-colour-flow-cytometric analysis was used to examine the effect of ICOS+- and ICOS--Treg/Tresp cell differentiation on the composition of the total CD4+-T-helper cell pool with ICOS+- and ICOS--Tregs/Tresps. Functionality of Tregs was examined using suppression assays. RESULTS: In 83 healthy volunteers, the ratio of ICOS+-Tregs/ICOS+-Tresps increased significantly with age, while that of ICOS--Tregs/ICOS--Tresps did not change. In 86 SLE patients (SLEDAI <7), disease activity was associated with an age-independently increased ratio of both ICOS+-Tregs/ICOS+-Tresps and ICOS--Tregs/ICOS--Tresps. In these patients, the functional activity of ICOS+-Tregs, but not of ICOS--Tregs, was preserved. In 13 markedly active disease patients (SLEDAI >7), the percentage of both ICOS+-Tregs and ICOS+-Tresps, was strongly increased within total CD4+-T-helper cells. However, the increased ratio of ICOS+-Tregs/ICOS+-Tresps was not maintained in these patients, due to terminal differentiation and accumulation of naïve cells within total ICOS+-Tregs. Despite increased differentiation of both ICOS--Tregs and ICOS--Tresps, the percentage of ICOS--Tregs increased within CD4+-T-helper cells, while that of ICOS--Tresps decreased, resulting in a significantly increased ratio of ICOS--Tregs/ICOS--Tresps independent of age. CONCLUSIONS: Our data reveal a crucial role of Treg immune senescence for the occurrence of disease flares in SLE patients, with ICOS+-Treg cells being most affected.

10.
Kidney Int ; 98(4): 1044-1052, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32450154

RESUMO

The randomized, controlled STOP-IgAN trial in patients with IgA nephropathy (IgAN) and substantial proteinuria showed no benefit of immunosuppression added on top of supportive care on renal function over three years. As a follow-up we evaluated renal outcomes in patients over a follow-up of up to ten years in terms of serum creatinine, proteinuria, end-stage kidney disease (ESKD), and death. The adapted primary endpoint was the time to first occurrence of a composite of death, ESKD, or a decline of over 40% in the estimated glomerular filtration rate (eGFR) compared to baseline at randomization into STOP-IgAN. Data were analyzed by Cox-regression models. Follow-up data were available for 149 participants, representing 92% of the patients originally randomized. Median follow-up was 7.4 years (inter quartile range 5.7 to 8.3 years). The primary endpoint was reached in 36 of 72 patients randomized to supportive care and 35 of 77 patients randomized to additional immunosuppression (hazard ratio 1.20; 95% confidence interval 0.75 to 1.92). ESKD occurred in 17 of the patients with supportive care and in 20 of the patients with additional immunosuppression. Additionally, the rates of eGFR loss over 40% and annual eGFR loss did not differ between groups. Two patients died with supportive care and three with additional immunosuppression. Thus, within the limitations of a retrospective study, over a follow-up of up to ten years, and using an adapted primary endpoint, we failed to detect differences in key clinical outcomes in IgAN patients randomized to receive added immunosuppression on top of supportive care versus supportive care alone.

11.
BMC Nephrol ; 21(1): 179, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32410664

RESUMO

BACKGROUND: Peritoneal ultrafiltration (pUF) in refractory heart failure (HF) reduces the incidence of decompensation episodes, which is of particular significance as each episode incrementally adds to mortality. Nevertheless, there are insufficient data about which patient cohort benefits the most. The objective of this study was to compare pUF in HFrEF and HFpEF, focusing on functional status, hospitalizations, surrogate endpoints and mortality. METHODS: This study involves 143 patients, who could be classified as either HFpEF (n = 37, 25.9%) or HFrEF (n = 106, 74.1%) and who received pUF due to refractory HF. RESULTS: Baseline eGFR was similar in HFrEF (23.1 ± 10.6 mg/dl) and HFpEF (27.8 ± 13.2 mg/dl). Significant improvements in NYHA class were found in HFpEF (3.19 ± 0.61 to 2.72 ± 0.58, P <  0.001) and HFrEF (3.45 ± 0.52 to 2.71 ± 0.72, P <  0.001). CRP decreased in HFrEF (19.4 ± 17.6 mg/l to 13.7 ± 21.4 mg/l, P = 0.018) and HFpEF (33.7 ± 52.6 mg/l to 17.1 ± 26.3 mg/l, P = 0.004). Body weight was significantly reduced in HFrEF (81.1 ± 14.6 kg to 77.2 ± 15.6 kg, P = 0.003) and HFpEF (86.9 ± 15.8 kg to 83.1 ± 15.9 kg, P = 0.005). LVEF improved only in HFrEF (25.9 ± 6.82% to 30.4 ± 12.2%, P = 0.046). BCR decreased significantly in HFrEF and HFpEF (55.7 ± 21.9 to 34.3 ± 17.9 P > 0.001 and 50.5 ± 68.9 to 37.6 ± 21.9, P = 0.006). Number of hospitalization episodes as well as number of hospitalization days decreased significantly only in HFpEF (total number 2.88 ± 1.62 to 1.25 ± 1.45, P <  0.001, days 40.4 ± 31.7 to 18.3 ± 22.5 days, P = 0.005). CONCLUSIONS: pUF offers various benefits in HFpEF and HFrEF, but there are also substantial differences. In particular, hospitalization rates were found to be significantly reduced in HFpEF patients, indicating a greater medical and economical advantage. However, LVEF was only found to be improved in HFrEF patients. While pUF can now be regarded as an option to supplement classical HF therapy, further studies are desirable to obtain specifications about pUF in HFpEF, HFmEF and HFrEF patients.

12.
Transpl Int ; 33(8): 849-857, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32337766

RESUMO

In several deceased donor kidney allocation systems, organs from elderly donors are allocated primarily to elderly recipients. The Eurotransplant Senior Program (ESP) was implemented in 1999, and since then, especially in Europe, the use of organs from elderly donors has steadily increased. The proportion of ≥60-year-old donors reported to the Collaborative Transplant Study (CTS) by European centers has doubled, from 21% in 2000-2001 to 42% in 2016-2017. Therefore, in the era of organ shortage it is a matter of debate whether kidney organs from elderly donors should only be allocated to elderly recipients or whether <65-year-old recipients can also benefit from these generally as "marginal" categorized organs. To discuss this issue, a European Consensus Meeting was organized by the CTS on April 12, 2018, in Heidelberg, in which 36 experts participated. Based on available evidence, it was unanimously concluded that kidney organs from 65- to 74-year-old donors can also be allocated to 55- to 64-year-old recipients, especially if these organs are from donors with no history of hypertension, no increased creatinine, no cerebrovascular death, and no other reasons for defining a marginal donor, such as diabetes or cancer.

13.
Transplant Proc ; 52(3): 722-730, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32143866

RESUMO

CONTEXT: Studies on the surgical outcome in living kidney donors mainly report perioperative complications with short follow-up. OBJECTIVE: The objectives of this study are to evaluate the long-term surgical outcome in living kidney donors and to identify donors with an increased risk for a complicated postoperative course. BASIC PROCEDURES: A prospectively collected database of 496 living kidney donors at the Department of General, Visceral, and Transplantation Surgery of the Ruprecht Karls University Heidelberg was retrospectively analyzed in a retrospective, observational single-center study. RESULTS: The median follow-up time was 37 months. The perioperative severe complication (Clavien-Dindo IIIb) rate was 2.8%, the early postoperative (PO) severe complication rate (1-3 months post operation) was 0.7%, and the late PO severe complication rate (> 3 months post operation) was 8.4%. In multivariate analyses, male sex was associated with higher overall perioperative complication rate (odds ratio [OR], 1.930; P = .005) as well as higher rate of late PO complications (OR, 2.243; P = .014). An increased body mass index was associated with a higher late and severe (Clavien-Dindo ≥ IIIb) PO complication rate (OR, 1.107; P = .009 and OR, 1.105; P = .008, respectively). CONCLUSIONS AND RELEVANCE: Long-term surgery-associated severe complications occur in 8.4% of kidney donors. Older age is associated with an increased operative time, greater intraoperative blood loss, and longer PO hospital stay. Male donors and donors with an increased body mass index have a higher risk for a complicated PO course after kidney donation. Within a shared decision-making process before living kidney donation, special awareness should be brought to these facts.


Assuntos
Transplante de Rim/métodos , Doadores Vivos , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Coleta de Tecidos e Órgãos/efeitos adversos , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Rim/cirurgia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
14.
Medicine (Baltimore) ; 99(10): e19335, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150070

RESUMO

BACKGROUND: Pancreas graft quality directly affects morbidity and mortality rates after pancreas transplantation (PTx). The criteria for pancreas graft allocation are restricted, which has decreased the number of available organs. Suitable pancreatic allografts are selected based on donor demographics, medical history, and the transplant surgeon's assessment of organ quality during procurement. Quality is assessed based on macroscopic appearance, which is biased by individual experience and personal skills. Therefore, we aim to assess the histopathological quality of unallocated pancreas organs to determine how many unallocated organs are potentially of suitable quality for PTx. METHODS AND ANALYSIS: This is a multicenter cross-sectional explorative study. The demographic data and medical history of donor and cause of rejection of the allocation of graft will be recorded. Organs of included donors will be explanted and macroscopic features such as weight, color, size, and stiffness will be recorded by 2 independent transplant surgeons. A tissue sample of the organ will be fixed for further microscopic assessments. Histopathologic assessments will be performed as soon as a biopsy can be obtained. We will evaluate up to 100 pancreata in this study. RESULT: This study will evaluate the histopathological quality of unallocated pancreas organs from brain-dead donors to determine how many of these unallocated organs were potentially suitable for transplantation based on a histopathologic evaluation of organ quality. CONCLUSION: The comprehensive findings of this study could help to increase the pancreas graft pool, overcome organ shortage, reduce the waiting time, and also increase the number of PTx in the future. Registration number: ClinicalTrials.gov: NCT04127266.


Assuntos
Morte Encefálica/patologia , Pâncreas/patologia , Doadores de Tecidos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/métodos , Distribuição de Qui-Quadrado , Protocolos Clínicos , Estudos Transversais , Alemanha , Sobrevivência de Enxerto , Humanos , Transplante de Pâncreas/métodos , Doadores de Tecidos/provisão & distribução , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/tendências
15.
J Virol ; 94(10)2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32102884

RESUMO

The Epstein-Barr virus (EBV) causes human cancers, and epidemiological studies have shown that lytic replication is a risk factor for some of these tumors. This fits with the observation that EBV M81, which was isolated from a Chinese patient with nasopharyngeal carcinoma, induces potent virus production and increases the risk of genetic instability in infected B cells. To find out whether this property extends to viruses found in other parts of the world, we investigated 22 viruses isolated from Western patients. While one-third of the viruses hardly replicated, the remaining viruses showed variable levels of replication, with three isolates replicating at levels close to that of M81 in B cells. We cloned one strongly replicating virus into a bacterial artificial chromosome (BAC); the resulting recombinant virus (MSHJ) retained the properties of its nonrecombinant counterpart and showed similarities to M81, undergoing lytic replication in vitro and in vivo after 3 weeks of latency. In contrast, B cells infected with the nonreplicating Western B95-8 virus showed early but abortive replication accompanied by cytoplasmic BZLF1 expression. Sequencing confirmed that rMSHJ is a Western virus, being genetically much closer to B95-8 than to M81. Spontaneous replication in rM81- and rMSHJ-infected B cells was dependent on phosphorylated Btk and was inhibited by exposure to ibrutinib, opening the way to clinical intervention in patients with abnormal EBV replication. As rMSHJ contains the complete EBV genome and induces lytic replication in infected B cells, it is ideal to perform genetic analyses of all viral functions in Western strains and their associated diseases.IMPORTANCE The Epstein-Barr virus (EBV) infects the majority of the world population but causes different diseases in different countries. Evidence that lytic replication, the process that leads to new virus progeny, is linked to cancer development is accumulating. Indeed, viruses such as M81 that were isolated from Far Eastern nasopharyngeal carcinomas replicate strongly in B cells. We show here that some viruses isolated from Western patients, including the MSHJ strain, share this property. Moreover, replication of both M81 and of MSHJ was sensitive to ibrutinib, a commonly used drug, thereby opening an opportunity for therapeutic intervention. Sequencing of MSHJ showed that this virus is quite distant from M81 and is much closer to nonreplicating Western viruses. We conclude that Western EBV strains are heterogeneous, with some viruses being able to replicate more strongly and therefore being potentially more pathogenic than others, and that the virus sequence information alone cannot predict this property.


Assuntos
Linfócitos B/virologia , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Replicação Viral/fisiologia , Animais , Linfócitos B/patologia , Linhagem Celular , Clonagem Molecular , DNA Viral , Modelos Animais de Doenças , Genoma Viral , Células HEK293 , Herpesvirus Humano 4/crescimento & desenvolvimento , Herpesvirus Humano 4/isolamento & purificação , Humanos , Neoplasias Nasofaríngeas/virologia , Transativadores/genética
16.
J Clin Invest ; 130(5): 2364-2376, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31990685

RESUMO

BACKGROUNDPreclinical experiments have shown that donor blood cells, modified in vitro by an alkylating agent (modified immune cells [MICs]), induced long-term specific immunosuppression against the allogeneic donor.METHODSIn this phase I trial, patients received either 1.5 × 106 MICs per kg BW on day -2 (n = 3, group A), or 1.5 × 108 MICs per kg BW on day -2 (n = 3, group B) or day -7 (n = 4, group C) before living donor kidney transplantation in addition to post-transplantation immunosuppression. The primary outcome measure was the frequency of adverse events (AEs) until day 30 (study phase) with follow-up out to day 360.RESULTSMIC infusions were extremely well tolerated. During the study phase, 10 treated patients experienced a total of 69 AEs that were unlikely to be related or not related to MIC infusion. No donor-specific human leukocyte antigen Abs or rejection episodes were noted, even though the patients received up to 1.3 × 1010 donor mononuclear cells before transplantation. Group C patients with low immunosuppression during follow-up showed no in vitro reactivity against stimulatory donor blood cells on day 360, whereas reactivity against third-party cells was still preserved. Frequencies of CD19+CD24hiCD38hi transitional B lymphocytes (Bregs) increased from a median of 6% before MIC infusion to 20% on day 180, which was 19- and 68-fold higher, respectively, than in 2 independent cohorts of transplanted controls. The majority of Bregs produced the immunosuppressive cytokine IL-10. MIC-treated patients showed the Immune Tolerance Network operational tolerance signature.CONCLUSIONMIC administration was safe and could be a future tool for the targeted induction of tolerogenic Bregs.TRIAL REGISTRATIONEudraCT number: 2014-002086-30; ClinicalTrials.gov identifier: NCT02560220.FUNDINGFederal Ministry for Economic Affairs and Technology, Berlin, Germany, and TolerogenixX GmbH, Heidelberg, Germany.

17.
J Clin Periodontol ; 47(1): 19-29, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31603565

RESUMO

AIM: To assess the prevalence and severity of periodontitis in patients with moderate chronic kidney disease (CKD) and comparing the results with the self-reported periodontitis awareness of the study subjects. MATERIAL AND METHODS: The periodontal status of 270 patients with moderate CKD randomly selected from a cohort of 5,217 subjects participating in the prospective observational German Chronic Kidney Disease (GCKD) project was analysed by recording bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL). Furthermore, the awareness of the study subjects of their periodontal conditions was evaluated by a self-reported questionnaire. RESULTS: 24.4% of the CKD study patients showed no or only mild signs of periodontal disease, 47.6% displayed moderate and 27% severe periodontitis. Questionnaire data revealed that 62.3% of the study subjects with severe periodontitis were not aware of the presence of the disease, 44.4% denied having received any systematic periodontal therapy so far, although 50% of them indicated to visit their dentist regularly for professional tooth cleanings. CONCLUSION: While the clinical study data confirm an increased prevalence of periodontitis in CKD patients, their self-reported awareness of periodontitis was low.


Assuntos
Doenças Periodontais , Periodontite , Insuficiência Renal Crônica , Humanos , Perda da Inserção Periodontal , Estudos Prospectivos
18.
J Biomed Mater Res B Appl Biomater ; 108(1): 67-72, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30897297

RESUMO

Incidence of wound complications after kidney transplantation (KTx) is still considerable. Here, we report the impact of prophylactic absorbable polyglactin (Vicryl®) mesh reinforcement on the incidence of short-term post-KTx wound complications. Sixty-nine patients were analyzed; 23 with and 46 without preventive onlay mesh reinforcement. Surgical site infections (SSI) were seen in six (26%) patients in the mesh group and in 17 (37%) patients in no-mesh group. A lower, but not statistically significant, rate of early postoperative wound complications occurred in the mesh group. Wound complications were observed in seven (30%) patients in the mesh group and in 23 (50%) patients in the no-mesh group. There was no association between mesh placement and SSI incidence (odds ratios [OR] 0.60, 95% confidence interval [CI] 0.20-1.82, p = 0.369) and wound complications (OR 0.44, 95% CI 0.15-1.26, p = 0.126). Therefore, we conclude that mesh reinforcement does not increase the risk of SSI and overall wound complications. Long-term outcomes have to be evaluated in a randomized trial setting. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:67-72, 2020.

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