BACKGROUND: In patients with multiple myeloma (MM) free light chain-induced cast nephropathy is a serious complication associated with poor survival. High-cut-off (HCO) hemodialysis can reduce the amount of serum free light chains (sFLC), but data on its impact on clinical outcome is limited and contradictory. To gain further insights we collected real world data from two major myeloma and nephrology centers in Austria and the Czech Republic. METHODS: Sixty-one patients with MM and acute kidney injury, who were treated between 2011 and 2019 with HCO hemodialysis and bortezomib-based MM therapy, were analyzed. RESULTS: The median number of HCO hemodialysis sessions was 11 (range 1-42). Median glomerular filtration rate at diagnosis was 7 ± 4.2 ml/min/1.73m2. sFLC after the first HCO hemodialysis decreased by 66.5% and by 89.2% at day 18. At 3 and 6 months, 26 (42.6%) and 30 (49.2%) of patients became dialysis-independent. CONCLUSION: The widely used strategy combining HCO hemodialysis and bortezomib-based antimyeloma treatment is dissatisfactory for half of the patients undergoing it and clearly in need of improvement.

• MeSH
• akutní poškození ledvin * diagnóza   terapie   MeSH
• bortezomib škodlivé účinky   MeSH
• dialýza ledvin škodlivé účinky   MeSH
• lehké řetězce imunoglobulinů MeSH
• lidé MeSH
• mnohočetný myelom * komplikace   diagnóza   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Background: Thrombotic microangiopathy (TMA) significantly affects kidney graft survival, but its pathophysiology remains poorly understood. Methods: In this multicenter, retrospective, case-control paired study designed to control for donor-associated risks, we assessed the recipients' risk factors for de novo TMA development and its effects on graft survival. The study group consists of patients with TMA found in case biopsies from 2000 to 2019 (n = 93), and the control group consists of recipients of paired kidney grafts (n = 93). Graft follow-up was initiated at the time of TMA diagnosis and at the same time in the corresponding paired kidney graft. Results: The TMA group displayed higher peak panel-reactive antibodies, more frequent retransplantation status, and longer cold ischemia time in univariable analysis. In the multivariable regression model, longer cold ischemia times (odds ratio, 1.18; 95% confidence interval [CI], 1.01-1.39; P = 0.043) and higher peak pretransplant panel-reactive antibodies (odds ratio, 1.03; 95% CI, 1.01-1.06; P = 0.005) were found to be associated with increased risk of de novo TMA. The risk of graft failure was higher in the TMA group at 5 y (hazard ratio [HR], 3.99; 95% CI, 2.04-7.84; P < 0.0001). Concomitant rejection significantly affected graft prognosis at 5 y (HR, 6.36; 95% CI, 2.92-13.87; P < 0.001). De novo TMA associated with the active antibody-mediated rejection was associated with higher risk of graft failure at 5 y (HR, 3.43; 95% CI, 1.69-6.98; P < 0.001) compared with other TMA. Conclusions: Longer cold ischemia and allosensitization play a role in de novo TMA development, whereas TMA as a part of active antibody-mediated rejection was associated with the highest risk for premature graft loss.

• Publikační typ
• časopisecké články MeSH

Liver stiffness (LS) is a novel non-invasive parameter widely used in clinical hepatology. LS correlates with liver fibrosis stage in non-cirrhotic patients. In cirrhotic patients it also shows good correlation with Hepatic Venous Pressure Gradient (HVPG). Our aim was to assess the contribution of liver fibrosis and portal hypertension to LS in patients with advanced liver cirrhosis. Eighty-one liver transplant candidates with liver cirrhosis of various aetiologies underwent direct HVPG and LS measurement by 2D shear-wave elastography (Aixplorer Multiwave, Supersonic Imagine, France). Liver collagen content was assessed in the explanted liver as collagen proportionate area (CPA) and hydroxyproline content (HP). The studied cohort included predominantly patients with Child-Pugh class B and C (63/81, 77.8%), minority of patients were Child-Pugh A (18/81, 22.2%). LS showed the best correlation with HVPG (r=0.719, p< 0.001), correlation of LS with CPA (r=0.441, p< 0.001) and HP/Amino Acids (r=0.414, p< 0.001) was weaker. Both variables expressing liver collagen content showed good correlation with each other (r=0.574, p<0.001). Multiple linear regression identified the strongest association between LS and HVPG (p < 0.0001) and weaker association of LS with CPA (p = 0.01883). Stepwise modelling showed minimal increase in r2 after addition of CPA to HVPG (0.5073 vs. 0.5513). The derived formula expressing LS value formation is: LS = 2.48 + (1.29 x HVPG) + (0.26 x CPA). We conclude that LS is determined predominantly by HVPG in patients with advanced liver cirrhosis whereas contribution of liver collagen content is relatively low.

• MeSH
• dospělí MeSH
• elastografie MeSH
• jaterní cirhóza metabolismus   patologie   patofyziologie   chirurgie   MeSH
• játra chemie   diagnostické zobrazování   patologie   chirurgie   MeSH
• kolagen analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• portální hypertenze diagnóza   patofyziologie   chirurgie   MeSH
• portální tlak * MeSH
• prediktivní hodnota testů MeSH
• prospektivní studie MeSH
• senioři MeSH
• transplantace jater MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Plectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; PleΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the PleΔIEC colon.

• MeSH
• desmozomy genetika   metabolismus   MeSH
• dospělí MeSH
• keratiny metabolismus   MeSH
• kolitida metabolismus   prevence a kontrola   MeSH
• kolon patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• plektin genetika   metabolismus   MeSH
• senioři MeSH
• střevní sliznice metabolismus   patologie   MeSH
• ulcerózní kolitida metabolismus   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND AND AIMS: Patients after endoscopic treatment of Barrett's esophagus (BE) related neoplasia (BORN) should enter endoscopic surveillance with biopsies to detect persistent or recurrent neoplasia or intestinal metaplasia (IM). Probe-based confocal laser endomicroscopy (pCLE) serves as a virtual biopsy and could replace standard biopsies. However, the role of pCLE in patients after endoscopic treatment of BORN has not been systematically assessed. The aim of this study was to compare pCLE with biopsies in detecting persistent/recurrent IM/neoplasia. METHODS: A single center, prospective and pathologist-blinded study was performed. Patients after endoscopic treatment of BORN (endoscopic resection or dissection, radiofrequency ablation) underwent surveillance endoscopy with pCLE followed by biopsies. RESULTS: A total of 56 patients were enrolled: initial diagnoses were low-grade dysplasia (LGD) in 24 patients (43%), high-grade dysplasia (HGD) in 12 patients (21%) and early adenocarcinoma (EAC) in 20 patients (36%). Only one patient (2%) experienced recurrent neoplasia (LGD), which was diagnosed by pCLE only. Twenty patients (35.7%) experienced persistent/recurrent IM, diagnosed by both pCLE and biopsies in 17 patients (17/30, 85%) and by pCLE only in 3 pts (3/30, 15%). Sensitivity, specificity, positive and negative predictive values to diagnose recurrent/persistent IM did not differ significantly between pCLE and biopsies; diagnostic accuracy was 100% (95%CI 93.6-100) for pCLE and 94.6 (95%CI 85.1-98.9%) for biopsies, p=0.25. In patients with IM detected by both tested methods, pCLE detected significantly more goblet cells (median 43 per patient) than biopsies (median 12 per patient), p=0.01. CONCLUSION: pCLE is at least as effective as standard biopsies in the detection of persistent/recurrent IM after endoscopic treatment of BORN.

• MeSH
• Barrettův syndrom patologie   chirurgie   MeSH
• biopsie MeSH
• časové faktory MeSH
• dospělí MeSH
• ezofagektomie * škodlivé účinky   MeSH
• ezofágoskopie * škodlivé účinky   MeSH
• konfokální mikroskopie * MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru * MeSH
• nádory jícnu patologie   chirurgie   MeSH
• prediktivní hodnota testů MeSH
• prospektivní studie MeSH
• radiofrekvenční ablace * MeSH
• reprodukovatelnost výsledků MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• stupeň nádoru MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH

BACKGROUND: The rs58542926 polymorphism in transmembrane 6 superfamily member 2 (TM6SF2) is a genetic factor predisposing to nonalcoholic fatty liver disease. We aimed to explore the effect of recipient and donor TM6SF2 rs58542926 genotypes on liver graft fat content after liver transplantation. METHODS: Steatosis was evaluated in liver biopsies from 268 adult recipients. The influence of recipient and donor TM6SF2 genotypes, patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 genotypes, and nongenetic factors on the steatosis grade assessed 6-30 months after transplantation was analyzed by ordinal logistic regression. RESULTS: The presence of the TM6SF2 c.499A allele in the donor (P = 0.014), PNPLA3 c.444G allele in the donor (P < 0.001), posttransplant body mass index (P < 0.001), and serum triglycerides (P = 0.047) independently predicted increased liver fat content on multivariable analysis, whereas noncirrhotic liver disease, as an indication for liver transplantation, was associated with lower risk of steatosis (P = 0.003). The effects of the donor TM6SF2 A and PNPLA3 G alleles were additive, with an odds ratio of 4.90 (95% confidence interval, 2.01-13.00; P < 0.001), when both minor alleles were present compared with an odds ratio of 2.22 (95% confidence interval, 1.42-3.61; P = 0.002) when only one of these alleles was present. CONCLUSIONS: The donor TM6SF2 c.499A allele is an independent risk factor of liver graft steatosis after liver transplantation that is additive to the effects of donor PNPLA3 c.444G allele.

• MeSH
• alely MeSH
• alografty patologie   MeSH
• biopsie MeSH
• dárci tkání statistika a číselné údaje   MeSH
• dospělí MeSH
• genotypizační techniky statistika a číselné údaje   MeSH
• játra patologie   MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipasa genetika   MeSH
• membránové proteiny genetika   MeSH
• mladý dospělý MeSH
• následné studie MeSH
• nealkoholová steatóza jater diagnóza   epidemiologie   genetika   patologie   MeSH
• pooperační komplikace diagnóza   epidemiologie   genetika   patologie   MeSH
• prevalence MeSH
• příjemce transplantátu statistika a číselné údaje   MeSH
• rizikové faktory MeSH
• stupeň závažnosti nemoci MeSH
• transplantace jater škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• dospělí MeSH
• kožní nemoci vrozené   diagnóza   genetika   MeSH
• lidé MeSH
• missense mutace genetika   MeSH
• prsty ruky patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH

BACKGROUND: Cytomegalovirus (CMV) disease represents a serious complication in liver transplant (OLT) recipients. CMV prophylaxis reduces incidence of CMV disease in the early post-transplant period (on-prophylaxis disease, OPD) but may postpone its manifestation after the completion of prophylaxis. Post-prophylaxis disease (PPD) incidence after prophylaxis cessation may be modified by genetic factors. METHODS: We analyzed impact of IL28B rs1297986 variants on CMV disease incidence in 743 adult OLT recipients receiving universal prophylaxis. RESULTS: One hundred and forty-four (19.4%) patients had at least one CMV disease episode. One hundred and two of them (70.8%) had at least one OPD and 36 (25%) patients had PPD, six (4.2%) patients had both. The rate of IL28B T allele carriers was lower in PPD group (38.9%) in comparison with OPD group (66.7%, P = 0.005) and group without CMV disease (61.4%, P = 0.009). The impact of IL28B genotype on the risk of CMV OPD was significant neither in the allelic (TT + CT vs CC, P = 0.32) nor in the recessive model (TT vs CT + CC, P = 0.79). Contrarily, in the PPD group, T allele (TT + CT vs CC) had a protective effect, OR 0.4 (95% CI 0.2-0.8, P = 0.008). Further risk factors of PPD were age <55 years and valganciclovir prophylaxis, whereas the risk factors of OPD were age <55 years, cyclosporine A therapy and pre-transplant CMV serostatus (donor +/recipient -). CONCLUSIONS: IL28B rs12979860 T allele carriers had a lower risk of CMV PPD.

• MeSH
• alely MeSH
• antivirové látky terapeutické užití   MeSH
• cytomegalovirové infekce genetika   prevence a kontrola   MeSH
• dárci tkání MeSH
• dospělí MeSH
• ganciklovir terapeutické užití   MeSH
• genotyp MeSH
• incidence MeSH
• interferony genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• příjemce transplantátu MeSH
• senioři MeSH
• transplantace jater * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Accommodation in ABO-incompatible (ABOi) transplantation and subclinical antibody-mediated rejection in HLA-incompatible (HLAi) transplantation share several morphological similarities. Because the clinical long-term outcomes differ, we hypothesized different molecular processes involved in ABOi transplantation and subclinical antibody-mediated rejection. METHODS: Using Illumina Human HT-12 v4 Expression BeadChips, the whole transcriptome was evaluated based on 3-month protocol C4d+ biopsies in otherwise stable ABOi and HLAi kidney grafts, as well as in C4d-negative HLA-compatible grafts exhibiting normal histological findings. Top differently regulated genes were further validated using real-time quantitative polymerase chain reaction in another patient cohort and complement regulatory proteins by immunohistochemistry. RESULTS: In the case of genes involved in immune response-related biological processes, ABOi and HLAi cohorts had similar transcriptomic profiles to C4d-negative controls. The majority of deregulated genes in the ABOi and HLAi groups consisted of metallothioneins and epithelial transporter genes. Increased expression of epithelial transporters (SLC4A1, SLC4A9, SLC17A3, SLC12A3, and SLC30A2) and class 1 metallothioneins (MT1F, MT1G, and MT1X) in HLAi transplantation was validated by real-time quantitative polymerase chain reaction. In comparison to controls, both incompatible cohorts were characterized by the upregulation of intrarenal complement regulatory genes. CD46 and CD59 transcripts were increased in the ABOi cohort, whereas CD46 solely in HLAi group, and CD59 protein expression was similar in both incompatible groups. CONCLUSIONS: Several epithelial transporters and metallothioneins discriminate subclinical antibody-mediated rejection in HLAi transplantation from accommodation in ABOi transplantation, which suggest different involved downstream mechanisms and increased risk of injury in HLAi settings. Metallothioneins with their antioxidative properties may help to attenuate the inflammation response induced by donor-specific anti-HLA antibody binding.

• MeSH
• ABO systém krevních skupin imunologie   MeSH
• alografty imunologie   metabolismus   patologie   MeSH
• biologické markery metabolismus   MeSH
• biopsie MeSH
• dospělí MeSH
• HLA antigeny imunologie   MeSH
• isoprotilátky imunologie   MeSH
• ledviny imunologie   metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové transportní proteiny metabolismus   MeSH
• metalothionein metabolismus   MeSH
• mladý dospělý MeSH
• následné studie MeSH
• nekompatibilita krevních skupin diagnóza   imunologie   patologie   MeSH
• přežívání štěpu imunologie   MeSH
• rejekce štěpu diagnóza   imunologie   patologie   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• stanovení celkové genové exprese MeSH
• transplantace ledvin škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH

Intimal arteritis is known to be a negative prognostic factor for kidney allograft survival. Isolated v-lesion (IV) is defined as intimal arteritis with minimal tubulointerstitial inflammation (TI). Although the Banff classification assesses IV as T cell-mediated rejection (TCMR), clinical, and prognostic significance of early IV (early IV, eIV) with negative C4d and donor-specific antibodies (DSA) remains unclear. To help resolve if such eIV truly represents acute rejection, a molecular study was performed. The transcriptome of eIV (n=6), T cell-mediated vascular rejection with rich TI (T cell-mediated vascular rejection, TCMRV, n=4) and non-rejection histologic findings (n=8) was compared using microarrays. A total of 310 genes were identified to be deregulated in TCMRV compared with eIV. Gene enrichment analysis categorized deregulated genes to be associated primarily with T-cells associated biological processes involved in an innate and adaptive immune and inflammatory response. Comparison of deregulated gene lists between the study groups and controls showed only a 1.7% gene overlap. Unsupervised hierarchical cluster analysis revealed clear distinction of eIV from TCMRV and showed similarity with a control group. Up-regulation of immune response genes in TCMRV was validated using RT-qPCR in a different set of eIV (n=12) and TCMRV (n=8) samples. The transcriptome of early IV (< 1 month) with negative C4d and DSA is associated with a weak immune signature compared with TCMRV and shows similarity with normal findings. Such eIV may feature non-rejection origin and reflect an injury distinct from an alloimmune response. The present study supports use of molecular methods when interpreting kidney allograft biopsy findings.

• MeSH
• alografty MeSH
• arteritida genetika   MeSH
• dospělí MeSH
• genová ontologie MeSH
• lidé MeSH
• průřezové studie MeSH
• rejekce štěpu diagnóza   genetika   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• stanovení celkové genové exprese metody   MeSH
• studie případů a kontrol MeSH
• transkriptom * MeSH
• transplantace ledvin metody   MeSH
• tunica intima metabolismus   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH