BACKGROUND: We investigated whether carotid intima-media thickness is associated with measures of cerebral blood flow (CBF), white matter hyperintensities, and brain volume in a biracial cohort of middle-aged individuals. METHODS: We performed a cross-sectional cohort study based on data from a multicenter, population-based study Coronary Artery Risk Development in Young Adults. Using linear and logistic regression, we estimated the association of the composite intima-media thickness measured in three segments of carotid arteries (common carotid artery, carotid artery bulb, and internal carotid artery) with volume (cm3) and CBF (mL/100 g/min) in the total brain and gray matter as well as volume of white matter hyperintensities (cm3). RESULTS: In the analysis, 461 participants (54% women, 34% African Americans) were included. Greater intima-media thickness was associated with lower CBF in gray matter (β=-1.36; p = .04) and total brain (β=-1.26; p = .04), adjusting for age, sex, race, education, and total brain volume. The associations became statistically nonsignificant after further controlling for cardiovascular risk factors. Intima-media thickness was not associated with volumes of total brain, gray matter, and white matter hyperintensities. CONCLUSIONS: This study suggests that lower CBF in middle age is associated with markers of atherosclerosis in the carotid arteries. This association may reflect early long-term exposure to traditional cardiovascular risk factors. Early intervention on atherosclerotic risk factors may modulate the trajectory of CBF as people age and develop brain pathology.

• MeSH
• běloši statistika a číselné údaje   MeSH
• bílá hmota diagnostické zobrazování   MeSH
• černoši nebo Afroameričané statistika a číselné údaje   MeSH
• intimomediální šíře tepenné stěny * MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mozek diagnostické zobrazování   MeSH
• mozkový krevní oběh * MeSH
• průřezové studie MeSH
• velikost orgánu MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Geografické názvy
• Spojené státy americké MeSH

Metastatic disease is the leading cause of death due to prostate cancer (PCa). Although the hypermethylated in cancer 1 (HIC1) gene has been observed to be epigenetically modified in PCa, its intrinsic role and mechanism in PCa metastasis still remain uncertain. Here, we show that hypermethylation of the HIC1 promoter markedly reduces its suppressive function in metastatic PCa tissues as compared with primary and adjacent normal prostate tissues, and is associated with poor patient survival. PCas in cancer-prone mice homozygous for a prostate-targeted Hic1 conditional knockout showed stronger metastatic behaviour than those in heterozygous mice, as a result of epithelial-mesenchymal transition (EMT). Moreover, impairment of HIC1 expression in PCa cells induced their migration and metastasis through EMT, by enhancing expression of Slug and CXCR4, both of which are critical to PCa metastasis; the CXCL12-CXCR4 axis promotes EMT by activating the extracellular signal-regulated kinase (ERK) 1/2 pathway. Taken together, our results suggest that evaluation of HIC1-CXCR4-Slug signalling may provide a potential predictor for PCa aggressiveness. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

• MeSH
• chemokin CXCL12 metabolismus   MeSH
• DNA nádorová genetika   MeSH
• epitelo-mezenchymální tranzice genetika   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé MeSH
• metastázy nádorů MeSH
• metylace DNA MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• nádorové buňky kultivované MeSH
• nádorové proteiny genetika   metabolismus   MeSH
• nádory prostaty genetika   metabolismus   patologie   MeSH
• prognóza MeSH
• promotorové oblasti (genetika) MeSH
• receptory CXCR4 metabolismus   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• rodina transkripčních faktorů Snail genetika   fyziologie   MeSH
• signální transdukce fyziologie   MeSH
• transkripční faktory Krüppel-like nedostatek   genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Morbidity and mortality from COVID-19 caused by novel coronavirus SARS-CoV-2 is accelerating worldwide, and novel clinical presentations of COVID-19 are often reported. The range of human cells and tissues targeted by SARS-CoV-2, its potential receptors and associated regulating factors are still largely unknown. The aim of our study was to analyze the expression of known and potential SARS-CoV-2 receptors and related molecules in the extensive collection of primary human cells and tissues from healthy subjects of different age and from patients with risk factors and known comorbidities of COVID-19. METHODS: We performed RNA sequencing and explored available RNA-Seq databases to study gene expression and co-expression of ACE2, CD147 (BSG), and CD26 (DPP4) and their direct and indirect molecular partners in primary human bronchial epithelial cells, bronchial and skin biopsies, bronchoalveolar lavage fluid, whole blood, peripheral blood mononuclear cells (PBMCs), monocytes, neutrophils, DCs, NK cells, ILC1, ILC2, ILC3, CD4+ and CD8+ T cells, B cells, and plasmablasts. We analyzed the material from healthy children and adults, and from adults in relation to their disease or COVID-19 risk factor status. RESULTS: ACE2 and TMPRSS2 were coexpressed at the epithelial sites of the lung and skin, whereas CD147 (BSG), cyclophilins (PPIA andPPIB), CD26 (DPP4), and related molecules were expressed in both epithelium and in immune cells. We also observed a distinct age-related expression profile of these genes in the PBMCs and T cells from healthy children and adults. Asthma, COPD, hypertension, smoking, obesity, and male gender status generally led to the higher expression of ACE2- and CD147-related genes in the bronchial biopsy, BAL, or blood. Additionally, CD147-related genes correlated positively with age and BMI. Interestingly, we also observed higher expression of CD147-related genes in the lesional skin of patients with atopic dermatitis. CONCLUSIONS: Our data suggest different receptor repertoire potentially involved in the SARS-CoV-2 infection at the epithelial barriers and in the immune cells. Altered expression of these receptors related to age, gender, obesity and smoking, as well as with the disease status, might contribute to COVID-19 morbidity and severity patterns.

• MeSH
• angiotensin-konvertující enzym 2 genetika   imunologie   MeSH
• basigin genetika   imunologie   MeSH
• bronchiální astma epidemiologie   genetika   imunologie   MeSH
• chronická nemoc epidemiologie   MeSH
• chronická obstrukční plicní nemoc epidemiologie   genetika   imunologie   MeSH
• COVID-19 epidemiologie   genetika   imunologie   MeSH
• dipeptidylpeptidasa 4 genetika   imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• exprese genu genetika   MeSH
• hypertenze epidemiologie   genetika   imunologie   MeSH
• kojenec MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• obezita epidemiologie   genetika   imunologie   MeSH
• předškolní dítě MeSH
• přirozená imunita imunologie   MeSH
• rizikové faktory MeSH
• SARS-CoV-2 genetika   imunologie   MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)-programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stage small-cell lung cancer. Combining checkpoint inhibition with cytotoxic chemotherapy may have a synergistic effect and improve efficacy. METHODS: We conducted this double-blind, placebo-controlled, phase 3 trial to evaluate atezolizumab plus carboplatin and etoposide in patients with extensive-stage small-cell lung cancer who had not previously received treatment. Patients were randomly assigned in a 1:1 ratio to receive carboplatin and etoposide with either atezolizumab or placebo for four 21-day cycles (induction phase), followed by a maintenance phase during which they received either atezolizumab or placebo (according to the previous random assignment) until they had unacceptable toxic effects, disease progression according to Response Evaluation Criteria in Solid Tumors, version 1.1, or no additional clinical benefit. The two primary end points were investigator-assessed progression-free survival and overall survival in the intention-to-treat population. RESULTS: A total of 201 patients were randomly assigned to the atezolizumab group, and 202 patients to the placebo group. At a median follow-up of 13.9 months, the median overall survival was 12.3 months in the atezolizumab group and 10.3 months in the placebo group (hazard ratio for death, 0.70; 95% confidence interval [CI], 0.54 to 0.91; P=0.007). The median progression-free survival was 5.2 months and 4.3 months, respectively (hazard ratio for disease progression or death, 0.77; 95% CI, 0.62 to 0.96; P=0.02). The safety profile of atezolizumab plus carboplatin and etoposide was consistent with the previously reported safety profile of the individual agents, with no new findings observed. CONCLUSIONS: The addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer resulted in significantly longer overall survival and progression-free survival than chemotherapy alone. (Funded by F. Hoffmann-La Roche/Genentech; IMpower133 ClinicalTrials.gov number, NCT02763579 .).

• MeSH
• doba přežití bez progrese choroby MeSH
• dvojitá slepá metoda MeSH
• etoposid aplikace a dávkování   MeSH
• Kaplanův-Meierův odhad MeSH
• karboplatina aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• malobuněčný karcinom plic farmakoterapie   mortalita   MeSH
• monoklonální protilátky aplikace a dávkování   škodlivé účinky   MeSH
• nádory plic farmakoterapie   mortalita   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Cieľ Adjuvantná chemoterapia založená na cisplatine (adjuvant cisplatin-based chemotherapy, ACT) je v súčasnosti akceptovaným štandardom pre kompletne resekované štádium II a III nemalobunko- vého karcinómu pľúc (non–small-cell lung cancer, NSCLC). Dôležité je dlhodobé sledovanie, aby sa dokumentoval pretrvávajúci úžitok a neskorá toxicita. V tejto publikácii podávame správu o aktuali- zovaných údajoch celkového prežitia (overall survival, OS) a prežitia špecificky súvisiaceho s ocho- rením (disease-specific survival, DSS). Pacienti a metódy Pacienti s kompletne resekovaným NSCLC štádia Ib (T2N0, n = 219) alebo II (T1-2N1, n = 263) boli randomizovaní na 4 cykly vinorelbín/cisplatina alebo na observáciu. Všetky analýzy efektivity boli vykonané na báze zámeru vyliečenia pacientov. Výsledky Medián sledovania pacientov bol 9,3 roka (rozmedzie od 5,8 do 13,8; zo sledovania sa 33 pacien- tov stratilo). Celkove 271 pacientov zo 482 randomizovaných pacientov zomrelo. ACT sústavne vykazuje prospešnosť (pomer rizík [hazard ratio, HR] = 0,78; 95% interval spoľahlivosti [confi- dence interval, CI] 0,61–0,99; p = 0,04). Bol prítomný trend k interakcii so štádiom ochorenia (p = 0,09; HR pre štádium II = 0,68; 95% CI 0,5–0,92; p = 0,01; štádium IB, HR = 1,03; 95% CI, 0,7–1,52; p = 0,87). Výsledkom ACT bolo signifikantné predĺženie DSS (HR = 0,73; 95% CI 0,55–0,97; p = 0,03). Observácia bola spojená so signifikantne vyšším rizikom úmrtia na karcinóm pľúc (p = 0,02). Medzi oboma ramenami nebol rozdiel v miere úmrtia z inej príčiny alebo z dôvodu druhého malígneho ochorenia. Záver Predĺžené sledovanie pacientov zo štúdie JBR.10 pokračuje vo vykazovaní úžitku v prežití pre rameno s adjuvantnou chemoterapiou. Ukazuje sa, že tento úžitok sa viaže na pacientov s N1. V ramene s chemoterapiou nebol pozorovaný žiadny nárast úmrtnosti z inej príčiny.

Adjuvant cisplatin-based chemotherapy (ACT) is now an accepted standard for completely resected stage II and III A non-small-cell lung cancer (NSCLC). Long-term follow-up is important to document persistent benefit and late toxicity. We report here updated overall survival (OS) and disease-specific survival (DSS) data. PATIENTS AND METHODS Patients with completely resected stage IB (T2N0, n = 219) or II (T1-2N1, n = 263) NSCLC were randomly assigned to receive 4 cycles of vinorelbine/cisplatin or observation. All efficacy analyses were performed on an intention-to-treat basis. Results Median follow-up was 9.3 years (range, 5.8 to 13.8; 33 lost to follow-up); there were 271 deaths in 482 randomly assigned patients. ACT continues to show a benefit (hazard ratio [HR], 0.78; 95% CI, 0.61 to 0.99; P = .04). There was a trend for interaction with disease stage (P = .09; HR for stage II, 0.68; 95% CI, 0.5 to 0.92; P = .01; stage IB, HR, 1.03; 95% CI, 0.7 to 1.52; P = .87). ACT resulted in significantly prolonged DSS (HR, 0.73; 95% CI, 0.55 to 0.97; P = .03). Observation was associated with significantly higher risk of death from lung cancer (P = .02), with no difference in rates of death from other causes or second primary malignancies between the arms. CONCLUSION Prolonged follow-up of patients from the JBR.10 trial continues to show a benefit in survival for adjuvant chemotherapy. This benefit appears to be confined to N1 patients. There was no increase in death from other causes in the chemotherapy arm.

• MeSH
• cisplatina MeSH
• dospělí MeSH
• financování organizované MeSH
• geny ras MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádory plic farmakoterapie   mortalita   patologie   MeSH
• nemalobuněčný karcinom plic farmakoterapie   mortalita   patologie   MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• sekundární malignity etiologie   MeSH
• senioři MeSH
• staging nádorů MeSH
• vinblastin analogy a deriváty   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinické zkoušky, fáze III MeSH
• srovnávací studie MeSH

OBJECTIVE: Central neurocytomas (CNs) are uncommon intraventricular tumors, and their rarity renders the risk-to-benefit profile of stereotactic radiosurgery (SRS) unknown. The aim of this multicenter, retrospective cohort study was to evaluate the outcomes of SRS for CNs and identify predictive factors. METHODS: The authors retrospectively analyzed a cohort of patients with CNs treated with SRS at 10 centers between 1994 and 2018. Tumor recurrences were classified as local or distant. Adverse radiation effects (AREs) and the need for a CSF shunt were also evaluated. RESULTS: The study cohort comprised 60 patients (median age 30 years), 92% of whom had undergone prior resection or biopsy and 8% received their diagnosis based on imaging alone. The median tumor volume and margin dose were 5.9 cm3 and 13 Gy, respectively. After a median clinical follow-up of 61 months, post-SRS tumor recurrence occurred in 8 patients (13%). The 5- and 10-year local tumor control rates were 93% and 87%, respectively. The 5- and 10-year progression-free survival rates were 89% and 80%, respectively. AREs were observed in 4 patients (7%), but only 1 was symptomatic (2%). Two patients underwent post-SRS tumor resection (3%). Prior radiotherapy was a predictor of distant tumor recurrence (p = 0.044). Larger tumor volume was associated with pre-SRS shunt surgery (p = 0.022). CONCLUSIONS: Treatment of appropriately selected CNs with SRS achieves good tumor control rates with a reasonable complication profile. Distant tumor recurrence and dissemination were observed in a small proportion of patients, which underscores the importance of close post-SRS surveillance of CN patients. Patients with larger CNs are more likely to require shunt surgery before SRS.

• MeSH
• biopsie MeSH
• dítě MeSH
• doba přežití bez progrese choroby MeSH
• dospělí MeSH
• Kaplanův-Meierův odhad MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nádory mozku patologie   chirurgie   MeSH
• následné studie MeSH
• neurocytom patologie   chirurgie   MeSH
• prediktivní hodnota testů MeSH
• předškolní dítě MeSH
• radiochirurgie škodlivé účinky   metody   MeSH
• radioterapie škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• shunty pro odvod mozkomíšního moku statistika a číselné údaje   MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Pancreatic cancer has the worst prognosis among all cancers. Cancer screening of body fluids may improve the survival time prognosis of patients, who are often diagnosed too late at an incurable stage. Several studies report the dysregulation of lipid metabolism in tumor cells, suggesting that changes in the blood lipidome may accompany tumor growth. Here we show that the comprehensive mass spectrometric determination of a wide range of serum lipids reveals statistically significant differences between pancreatic cancer patients and healthy controls, as visualized by multivariate data analysis. Three phases of biomarker discovery research (discovery, qualification, and verification) are applied for 830 samples in total, which shows the dysregulation of some very long chain sphingomyelins, ceramides, and (lyso)phosphatidylcholines. The sensitivity and specificity to diagnose pancreatic cancer are over 90%, which outperforms CA 19-9, especially at an early stage, and is comparable to established diagnostic imaging methods. Furthermore, selected lipid species indicate a potential as prognostic biomarkers.

• MeSH
• antigen CA-19-9 krev   MeSH
• ceramidy krev   MeSH
• lidé MeSH
• lipidomika metody   MeSH
• lysofosfatidylcholiny krev   MeSH
• metabolismus lipidů genetika   MeSH
• multivariační analýza MeSH
• nádorové biomarkery krev   genetika   MeSH
• nádory slinivky břišní krev   diagnóza   mortalita   patologie   MeSH
• proporcionální rizikové modely MeSH
• senzitivita a specificita MeSH
• sfingomyeliny krev   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking. METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed. RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group. CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

• MeSH
• délka operace MeSH
• délka pobytu MeSH
• frakční průtoková rezerva myokardu * MeSH
• Kaplanův-Meierův odhad MeSH
• kardiovaskulární nemoci epidemiologie   MeSH
• koronární angioplastika škodlivé účinky   metody   MeSH
• koronární bypass * škodlivé účinky   MeSH
• koronární stenóza mortalita   chirurgie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• reoperace MeSH
• senioři MeSH
• stenty MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• hodnocení ekvivalence MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• srovnávací studie MeSH

BACKGROUND: BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). METHODS: We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10(-5)) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 % confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 % CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10(-12)). CONCLUSIONS: On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.

• MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace MeSH
• nádory prsu u mužů genetika   patologie   MeSH
• nádory prsu genetika   patologie   MeSH
• protein BRCA1 genetika   MeSH
• protein BRCA2 genetika   MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

• MeSH
• dárci tkání statistika a číselné údaje   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• perfuze * metody   přístrojové vybavení   MeSH
• přežívání štěpu * MeSH
• senioři MeSH
• terapeutická hypotermie metody   MeSH
• transplantace jater * metody   škodlivé účinky   MeSH
• uchovávání orgánů * metody   MeSH
• výsledek terapie 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
• pozorovací studie MeSH