This study investigates the diagnostic accuracy of liver fat fraction (FF) and other biomarkers in differentiating metabolic dysfunction‐associated steatohepatitis (MASH) from non‐MASH conditions in a cohort of 127 liver transplant patients using 1H MRS and machine learning techniques. Receiver operating characteristic analysis identified FF as the most significant predictor, achieving an area under the curve (AUC) > 0.96 for distinguishing MASH from non‐steatosis and non‐MASH metabolic dysfunction‐associated steatotic liver disease (MASLD). Secondary biomarkers, including insulinemia and elastography, showed moderate discriminatory power (AUC = 0.7–0.8) and contributed to refining classification decisions within a decision tree model. The decision tree analysis, validated with 10‐fold cross‐validation and independent testing, demonstrated robust sensitivity and specificity, with FF contributing 60%–70% to decision‐making. Secondary splits, such as insulinemia (~16.21 μIU/mL) and elastography (~8 kPa), provided additional discriminatory power, particularly in cases with borderline FF values. Non‐significant biomarkers, such as waist circumference and signals of diallylic protons resonating at 2.8 ppm, were excluded due to low discriminatory performance (AUC < 0.7). Compared to the general population (~5.8% prevalence), MASH was significantly more common in liver transplant recipients (~30%–50%). In patients with FF > 5.3%, the positive predictive value (PPV) for MASH ranged from 88% to 97%, more than twice the PPV observed in the general population (approximately 60%). These findings align with existing literature validating MRI‐derived proton density fat fraction as a reliable biomarker for hepatic steatosis. However, liver fat percentage alone is insufficient for MASH diagnosis. Secondary biomarkers, particularly insulinemia and elastography, enhanced classification accuracy near the FF threshold of 5.3%. This multiparametric approach significantly improves diagnostic accuracy and addresses the elevated risk and unique clinical needs of liver transplant recipients. Overall, these results underscore the clinical utility and precision of MR spectroscopy as a noninvasive biomarker for MASH diagnosis in liver transplant patients.

Machine learning identifies liver fat fraction (FF) measured by 1H MR spectroscopy, insulinemia, and elastography as robust, non-invasive biomarkers for diagnosing steatohepatitis in liver transplant patients, validated through decision tree analysis. Compared to the general population (~5.8% prevalence), MASH is significantly more common in liver transplant recipients (~30%-50%). In patients with FF > 5.3%, the positive predictive value for MASH ranged up to 97%, more than twice the value observed in the general population.

• Klíčová slova
• biomarkers, decision trees, liver fat, liver transplantation, machine learning, magnetic resonance spectroscopy, metabolic dysfunction‐associated steatohepatitis, metabolic syndrome,
• MeSH
• dospělí MeSH
• elastografie MeSH
• játra * patologie   diagnostické zobrazování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• strojové učení * MeSH
• transplantace jater * MeSH
• ztučnělá játra * diagnóza   diagnostické zobrazování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Orthotopic liver transplantation (OLT) has greatly improved short-term survival for end-stage liver disease. However, cardiovascular events (CVE) still pose a significant threat to long-term post-transplant health. Aim of this study is to assess the occurrence of long-term cardiovascular events and whether it relates to new-onset diabetes after liver transplantation (NODALT). METHODS: We conducted a multicentric retrospective analysis of adult OLT recipients with regular follow-up visits spanning from January 1995 to December 2020. Data collection included anamnestic, clinical, anthropometric, and laboratory data from two centers. NODALT was diagnosed following ADA guidelines. The primary outcome was incident CVE (a composite of fatal and non-fatal stroke and myocardial infarction). CVE occurrence was analyzed in relation to NODALT diagnosis, along with clinical characteristics associated with its development. RESULTS: Ninety-three eligible Caucasian patients, with a median age of 57.0 years (IQR: 49.0-62.0, 69.9% male), were enrolled. Over the median follow-up period of 100.5 months, 29 patients (31.2%) developed NODALT, and 14 patients (15.1%) developed any CVE, with 9 being in the NODALT group. A significant association between NODALT and cardiovascular complications was confirmed by both generalized estimating equation (OR 5.31; 95% CI 1.59-17.72, p = 0.006) and Kaplan-Meier analysis (log-rank = 0.046). Metabolic syndrome and impaired fasting glucose were identified as baseline risk factors for the incident NODALT (OR 5.75; 95% CI 1.44-22.92, p = 0.013 and OR 7.29; 95% CI 1.46-36.41, p = 0.015, respectively). CONCLUSIONS: Post-OLT cardiovascular events are less frequent than previously reported but are notably linked to NODALT, highlighting the interplay between metabolic syndrome and impaired fasting glucose.

• Klíčová slova
• Cardiovascular disease, Impaired fasting glucose, Long-term outcomes, Metabolic syndrome, Morbidity, Mortality, Myocardial infarction, New-onset diabetes after liver transplantation, Orthotopic liver transplantation, Preventive strategies, Stroke,
• MeSH
• diabetes mellitus * epidemiologie   etiologie   MeSH
• dospělí MeSH
• kardiovaskulární nemoci * epidemiologie   etiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• transplantace jater * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Plasma circulating donor-derived cell-free DNA (ddcfDNA) can be used to noninvasively monitor acute rejection of heart transplants (HTx). This study utilized digital droplet PCR to analyze ddcfDNA concentrations (measured in copies per milliliter) and the fractional abundance (%ddcfDNA) to differentiate between donor and recipient DNA on the basis of single nucleotide polymorphism (SNP) homozygosity. Seventy-seven patients participated in a study, providing 300 plasma samples. Both markers, mean ddcfDNA (cp/mL) and %ddcfDNA, showed similar decreasing trends following the HTx, (R2 < 0.2; p < 0.001). Significantly higher levels of ddcfDNA (cp/mL) and %ddcfDNA were observed during episodes of acute rejection (AR) compared to non-rejection samples (p < 0.001). Additionally, antibody-mediated rejection (AMR) was associated with increased %ddcfDNA levels compared to non-rejection and to acute cellular rejection samples (p < 0.001 and p < 0.01). A logistic regression model identified %ddcfDNA as an early predictor of AMR risk 10-19 days post-heart transplant (odds ratio 158, p < 0.02). Performance analysis established an optimal %ddcfDNA threshold of 0.125% for AMR detection, correctly identifying all patients without subsequent AMR. These findings suggest that early %ddcfDNA measurements post-HTx can accurately identify individuals unlikely to develop AMR during the first posttransplant year.

• Klíčová slova
• SNP, biomarker, cfDNA, rejection, transplantation,
• MeSH
• biologické markery * krev   MeSH
• časná diagnóza MeSH
• dárci tkání * MeSH
• dospělí MeSH
• isoprotilátky * imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• přežívání štěpu MeSH
• prognóza MeSH
• rejekce štěpu * diagnóza   etiologie   krev   MeSH
• rizikové faktory MeSH
• transplantace srdce * škodlivé účinky   MeSH
• volné cirkulující nukleové kyseliny * krev   genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery * MeSH
• isoprotilátky * MeSH
• volné cirkulující nukleové kyseliny * MeSH

OBJECTIVE: To compare the impact of sleeve gastrectomy (SG) on kidney function, comorbidities, and kidney transplant (KT) rates in KT candidates with obesity with a nonsurgical cohort. METHODS: Twenty-one KT candidates with body mass index (BMI) above 35 kg/m2 underwent SG between February 26, 2021, and October 27, 2023, and were compared with 19 who did not have SG. The secondary endpoints included changes in BMI, requirements for antihyperglycemic and antihypertension medications, and preemptive KT rates. RESULTS: The mean estimated glomerular filtration rate (eGFR) increased from a pre-SG baseline of 16.7±5.4 to 23.5±8.3 and 23.5±8.6 mL/min per 1.73 m2 at 2 and 6 months after SG (P=.002 and .02, respectively), whereas it remained unchanged in the non-SG cohort: 13.8±3.4, 14.3±5.1, and 14.8±6.4 mL/min per 1.73 m2 at the pre-evaluation period, 2 months, and 6 months. A higher baseline eGFR correlated with an improvement in eGFR after SG. The BMI and insulin requirements decreased only in the SG cohort. During the follow-up period of 5.1±4.6 months, 5 (23.8%) patients in the SG cohort and no patient in the non-SG cohort underwent preemptive KT. CONCLUSION: Pretransplant SG improves kidney function and may consequently increase rates of preemptive KT in candidates not yet on dialysis. These findings need to be confirmed by prospective studies with a well-matched cohort.

• MeSH
• dospělí MeSH
• gastrektomie * metody   MeSH
• hodnoty glomerulární filtrace fyziologie   MeSH
• index tělesné hmotnosti MeSH
• ledviny patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita * chirurgie   komplikace   MeSH
• transplantace ledvin * statistika a číselné údaje   metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in kidney transplant (KT) recipients have not been adequately studied. METHODS: We retrospectively examined the effects of GLP-1 RA on mortality, kidney outcomes and metabolic parameters in KT recipients with type 2 diabetes mellitus (T2DM) treated versus not treated with GLP-1 RA. A reference group of KT recipients not treated with GLP-1 RA was used for comparison. Data were analyzed using analysis of variance, χ2 tests, and generalized estimating equation models. GLP-1 RA was used as a time-dependent model in Cox regression modeling. For survival analysis, the final model fitting was stratified by race-ethnicity. RESULTS: Seventy-seven KT recipients with T2DM were treated with GLP-1 RA for at least 12 months. Reference group included 2094 patients not on GLP-1 RA. The mean (SD) age at transplant was 57.9 (9.5) and 60.8 (9.5) years for the treatment and reference groups, respectively. Median follow-up time from the index date for mortality was 1.5 (IQR 0.99, 2.4) in the treatment and 5.8 (IQR 3.4, 9.1) years in the reference group. GLP-1 RA use was associated with improved survival (P = .049), decreased urine albumin to creatinine ratio (net reduction of 10.62 mg/g per year, P = .003), slower estimated glomerular filtration rate decline (1.04 vs 1.56 mL/min/1.73 m2 per year, P = .04), and lower troponin levels. CONCLUSIONS: GLP-1 RA in KT recipients with T2DM was associated with reduced mortality, and improved kidney function compared to the reference group. Larger, prospective studies are needed to fully evaluate the risks and benefits of GLP-1 RA therapy in KT recipients.

• Klíčová slova
• diabetes mellitus, glucagon-like peptide-1 receptor agonist, kidney transplantation, post-transplant diabetes mellitus,
• MeSH
• agonisté receptoru pro glukagonu podobný peptid 1 * MeSH
• diabetes mellitus 2. typu * farmakoterapie   mortalita   komplikace   MeSH
• hypoglykemika * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace ledvin * mortalita   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• agonisté receptoru pro glukagonu podobný peptid 1 * MeSH
• hypoglykemika * MeSH

BACKGROUND: Expression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in "failed repair" states. We hypothesized that the phenomenon of failed repair could be associated with deterioration and failure in kidney transplants. METHODS: We defined injury-induced transcriptome states in 4,502 kidney transplant biopsies injury-induced gene sets and classifiers previously developed in transplants. RESULTS: In principal component analysis (PCA), PC1 correlated with both acute and chronic kidney injury and related inflammation and PC2 with time posttransplant. Positive PC3 was a dimension that correlated with epithelial remodeling pathways and anticorrelated with inflammation. Both PC1 and PC3 correlated with reduced survival, with PC1 effects strongly increasing over time whereas PC3 effects were independent of time. In this model, we studied the expression of 12 "new" gene sets annotated in single-nucleus RNA-sequencing studies of epithelial cells with failed repair in native kidneys. The new gene sets reflecting epithelial-mesenchymal transition correlated with injury PC1 and PC3, lower estimated glomerular filtration rate, higher donor age, and future failure as strongly as any gene sets previously derived in transplants and were independent of nephron segment of origin and graft rejection. CONCLUSION: These results suggest 2 dimensions in the kidney transplant response to injury: PC1, AKI-induced changes, failed repair, and inflammation; and PC3, a response involving epithelial remodeling without inflammation. Increasing kidney age amplifies PC1 and PC3. TRIAL REGISTRATION: INTERCOMEX (ClinicalTrials.gov NCT01299168); Trifecta-Kidney (ClinicalTrials.gov NCT04239703). FUNDING: Genome Canada; Natera, Inc.; and Thermo Fisher Scientific.

• Klíčová slova
• Molecular diagnosis, Nephrology, Organ transplantation, Transplantation,
• MeSH
• akutní poškození ledvin * patologie   genetika   MeSH
• analýza hlavních komponent MeSH
• biopsie MeSH
• dospělí MeSH
• epitelo-mezenchymální tranzice genetika   MeSH
• epitelové buňky * patologie   metabolismus   MeSH
• ledviny patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• průřezové studie MeSH
• rejekce štěpu * patologie   genetika   MeSH
• senioři MeSH
• transkriptom MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

Intravenous immunoglobulins (IVIG) are commonly used in peri-transplant desensitization, but evidence supporting their efficacy is limited. We conducted a prospective, randomized single-center, open-label, Phase IIIb non-inferiority clinical pilot trial to compare the efficacy of IVIG (administered at a dose of 3 × 0.5 g/kg) versus no IVIG, in conjunction with rabbit anti-thymocyte globulin (5-7 mg/kg) induction, in pre-sensitized patients with donor-specific antibodies who had negative pre-transplantation Flow- and CDC-crossmatches, between July 2020 and November 2022. The primary endpoint was the rate of efficacy failure, defined as biopsy-proven rejection within 12-month post-transplant. Secondary endpoints included the incidence of rejection at protocol biopsies, evaluated by histology and biopsy-based transcripts diagnostics. Of the screened patients, 53 (72.6%) were excluded due to crossmatch positivity. Ten patients were randomized to the IVIG+, and 7 to the IVIG-arm. The trial was prematurely terminated due to futility at interim analysis. In the IVIG-arm, 3 patients (43%) experienced the primary endpoint compared to none in the IVIG+ arm (p = 0.026). MMDx identified one molecular ABMR in the IVIG+ and 2 in the IVIG-arm in 12-month protocol biopsies. There was one graft loss in the IVIG-arm. The results of this pilot study, although not definitive, do not support the use of IVIG-sparing regimens in HLA-incompatible kidney transplantation (NCT04302805). This study is registered on ClinicalTrials.gov under the identifier NCT04302805.

• Klíčová slova
• HLA-incompatible transplantation, IVIG, desensitization, induction, kidney transplantation,
• MeSH
• antilymfocytární sérum * terapeutické užití   aplikace a dávkování   MeSH
• desenzibilizace imunologická * metody   MeSH
• dospělí MeSH
• intravenózní imunoglobuliny * terapeutické užití   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pilotní projekty MeSH
• prospektivní studie MeSH
• rejekce štěpu * prevence a kontrola   imunologie   MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antilymfocytární sérum * MeSH
• intravenózní imunoglobuliny * MeSH

The aim of this prospective study was to assess the duration of culture-viable SARS-CoV-2 and to monitor the emergence of mutations in a cohort of 23 kidney transplant recipients (KTRs) from June 2022 to June 2023. Combined nares/oropharyngeal swabs were collected weekly starting as soon as possible after symptom onset. The time from symptom onset to a negative culture was 11 days (interquartile range, 8-14), while the time to negative reverse transcriptase quantitative polymerase chain reaction was 18 days (interquartile range, 15-30). Beyond the first swab, 21.7% had a positive culture, and 8.7% replicated viable virus for longer than 30 days. T cell depletion (rate ratio, 2.5; 95% confidence interval [95% CI], 1.9-3.3; P < .001) and time from transplantation (rate ratio, 0.93; 95% CI, 0.90-0.97; P = .006) were associated with the time of viable virus shedding. A cycle threshold value of 24.2 demonstrated a 91.3% negative predictive value of viability (95% credible interval [95% CrI], 76-100). The odds of viability decreased by 69% per week of infection (odds ratio, 0.31; 95% CrI, 0.12-0.76). Overall, ribonucleic acid sequencing did not show accelerated molecular evolution though mutation rate could be increased in molnupiravir-treated KTRs. In conclusion, viable SARS-CoV-2 is eliminated rapidly, the risk of virus evolution is low, and prolonged self-isolation is generally unnecessary for most KTRs.

• Klíčová slova
• SARS-CoV-2, immunodeficiency, immunosuppression, infectiousness, kidney transplantation, public health, virus evolution, virus viability,
• MeSH
• COVID-19 * virologie   epidemiologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• molekulární evoluce * MeSH
• mutace MeSH
• příjemce transplantátu * MeSH
• prospektivní studie MeSH
• SARS-CoV-2 * genetika   izolace a purifikace   fyziologie   MeSH
• senioři MeSH
• transplantace ledvin * MeSH
• vylučování virů * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

The maximal donor age for lung transplantation (LTx) remains controversial, despite favorable outcomes with donors ≥70 years. We report our experience with LTx from donors ≥80 years. Donor/recipient characteristics and short-term postoperative outcome were retrospectively analyzed across two centers between 2016 and 2023. Seventeen patients underwent single (n=2) or double (n=15) LTx from octo- or nonagenarian donors with a median age of 83 years (range 80-94). Most donors were non-smoking females with intracerebral bleeding. Last donor PaO2/FiO2 ratio was 440 mmHg. Three recipients developed PGD3 at 72 h. Median ICU and hospital stay were 11 and 29 days, respectively. Five patients showed minimal (A1) ACR at one month post-LTx. Two patients developed CLAD. One- and three-year survival rates were 84% and 70%. Our case series indicates that LTx from well-selected octo- and nonagenarian donors is a valuable option to expand the donor pool.

• Klíčová slova
• aging, donor age, lung transplantation,
• MeSH
• dárci tkání * MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• transplantace plic * metody   MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

The preservation of donor lungs and the effort to safely extend ischemic time while maintaining function is an important topic that the transplant community has been addressing for a long time. Recent publications, mainly from the Toronto team, have fundamentally influenced the existing standard of optimal preservation conditions, and their results provide a scientific basis for the shift from ice preservation to con-trolled hypothermia. Optimal preservation conditions are a necessary prerequisite for the safe extension of ischemic time. This brings additional potential for the development of the field and the possibility to improve the availability of lung transplantations and their outcomes. This review summarizes the key findings in the area of donor lung preservation from the first experimental attempts conducted 30 years ago to recent studies and discusses the various aspects that the change in preservation standard has influenced or is likely to influence.

• Klíčová slova
• Lung transplantation, donor lung preservation, ischemic time,
• MeSH
• chlazení MeSH
• dárci tkání MeSH
• led MeSH
• lidé MeSH
• transplantace plic * MeSH
• uchovávání orgánů * metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• led MeSH