BACKGROUND & AIMS: Homozygous Pi∗Z mutation in alpha-1 antitrypsin (Pi∗ZZ genotype) predisposes to pulmonary loss-of-function and hepatic gain-of-function injury. To facilitate selection into clinical trials typically targeting only 1 organ, we systematically evaluated an international, multicenter, longitudinal, Pi∗ZZ cohort to uncover natural disease course and surrogates for future liver- and lung-related endpoints. METHODS: Cohort 1 recruited 737 Pi∗ZZ individuals from 25 different centers without known liver comorbidities who received a baseline clinical and laboratory assessment as well as liver stiffness measurement (LSM). A follow-up interview was performed after at least 6 months. Cohort 2 consisted of 135 Pi∗ZZ subjects without significant liver fibrosis, who received a standardized baseline and follow-up examination at least 2 years later, both including LSM. RESULTS: During 2634 patient-years of follow-up, 39 individuals died, with liver and lung being responsible for 46% and 36% of deaths, respectively. Forty-one Pi∗ZZ subjects who developed a hepatic endpoint presented with significantly higher baseline liver fibrosis surrogates, that is, LSM (24 vs 5 kPa, P < .001) and aspartate aminotransferase-to-platelet ratio index (1.1 vs 0.3 units, P < .001). Liver-related endpoints within 5 years were most accurately predicted by LSM (area under the curve 0.95) followed by aspartate aminotransferase-to-platelet ratio index (0.92). Baseline lung parameters displayed only a moderate predictive utility for lung-related endpoints within 5 years (forced expiratory volume in the first second area under the curve 0.76). Fibrosis progression in those with no/mild fibrosis at baseline was rare and primarily seen in those with preexisting risk factors. CONCLUSIONS: Noninvasive liver fibrosis surrogates accurately stratify liver-related risks in Pi∗ZZ individuals. Our findings have direct implications for routine care and future clinical trials of Pi∗ZZ patients.

• MeSH
• alfa-1-antitrypsin * genetika   krev   MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• deficit alfa1-antitrypsinu * genetika   diagnóza   komplikace   MeSH
• dospělí MeSH
• elastografie MeSH
• genotyp MeSH
• homozygot MeSH
• jaterní cirhóza * genetika   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• mutace MeSH
• plíce patofyziologie   patologie   diagnostické zobrazování   MeSH
• plicní nemoci genetika   etiologie   diagnóza   MeSH
• progrese nemoci * MeSH
• rizikové faktory MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Už niekoľko desaťročí podiel seniorov v populácii vyspelých krajín rastie, a to aj pre predlžovanie života. To má byť spojené s napĺňaním jedného zo základných princípov geriatrie – s „pridávaním života rokom“, t. j. so zlepšovaním kvality života. Tá je medzi ľuďmi i v odbornej komunite hodnotená rôzne, multidimenzionálne. U nemalej časti starších ľudí pozorujeme stúpajúcu tendenciu akejsi „estetickej komponenty“ vnímania kvality vlastného života – aj seniori stále častejšie dbajú na svoj estetický vzhľad. V tzv. západnom svete je tento trend dokumentovaný dlhšie, v ostatných rokoch ho pozorujeme už aj na Slovensku. Moderná medicína ponúka viacero prístupov, ako naplniť očakávania seniorov, ktorí chcú zlepšiť vlastný pocit zo svojho vzhľadu. Z medicínskeho hľadiska budeme u seniorov aj v tomto prípade preferovať neinvazívne alebo miniinvazívne metódy. Predkladaná práca sa zaoberá možnosťami a obmedzeniami niektorých bežne dostupných minimálne invazívnych „antiageingových“ procedúr u starších ľudí.

For several decades, there has been an increase in the proportion of seniors in developed countries, one of the reasons of which is the prolongation of life expectancy. In accordance with one of the basic principles of geriatrics, it should be one’s aim to „add life to years“, meaning improving the quality of life of the elderly. Quality of life is evaluated differently among people and in the scientific community – it is multi-dimensional. Among a considerable number of elderly people, we observe a rising tendency of an „aesthetic component“ in the perception of the quality of their life – even seniors pay more attention to their aesthetic appearance. In the so-called Western world this trend has been observed for a long time, and in recent years so have we in Slovakia. Modern medicine offers several approaches to meet the expectations of seniors who want to improve perception of their appearance. From a medical point of view, we will prefer noninvasive or mini invasive methods for seniors. The presented work deals with the possibilities and limitations of some commonly available minimally invasive „anti-ageing“ procedures for seniors.

BACKGROUND AND PURPOSE: Diffuse gliomas, a heterogeneous group of primary brain tumors, have traditionally been stratified by histology, but recent insights into their molecular features, especially the IDH mutation status, have fundamentally changed their classification and prognosis. Current diagnostic methods, still predominantly relying on invasive biopsy, necessitate the exploration of noninvasive imaging alternatives for glioma characterization. MATERIALS AND METHODS: In this prospective study, we investigated the utility of the spherical mean technique (SMT) in predicting the IDH status and histologic grade of adult-type diffuse gliomas. Patients with histologically confirmed adult-type diffuse glioma underwent a multiparametric MRI examination using a 3T system, which included a multishell diffusion sequence. Advanced diffusion parameters were obtained using SMT, diffusional kurtosis imaging, and ADC modeling. The diagnostic performance of studied parameters was evaluated by plotting receiver operating characteristic curves with associated area under curve, specificity, and sensitivity values. RESULTS: A total of 80 patients with a mean age of 48 (SD, 16) years were included in the study. SMT metrics, particularly microscopic fractional anisotropy (μFA), intraneurite voxel fraction, and μFA to the third power (μFA3), demonstrated strong diagnostic performance (all AUC = 0.905, 95% CI, 0.835-0.976; P < .001) in determining IDH status and compared favorably with diffusional kurtosis imaging and ADC models. These parameters also showed a strong predictive capability for tumor grade, with intraneurite voxel fraction and μFA achieving the highest diagnostic accuracy (AUC = 0.937, 95% CI, 0.880-0.993; P < .001). Control analyses on normal-appearing brain tissue confirmed the specificity of these metrics for tumor tissue. CONCLUSIONS: Our study highlights the potential of SMT for noninvasive characterization of adult-type diffuse gliomas, with a potential to predict IDH status and tumor grade more accurately than traditional ADC metrics. SMT offers a promising addition to the current diagnostic toolkit, enabling more precise preoperative assessments and contributing to personalized treatment planning.

• MeSH
• difuzní magnetická rezonance metody   MeSH
• dospělí MeSH
• gliom * diagnostické zobrazování   patologie   MeSH
• isocitrátdehydrogenasa * genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• mutace MeSH
• nádory mozku * diagnostické zobrazování   patologie   MeSH
• prospektivní studie MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• stupeň nádoru 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: Large vessel carotid stenosis is a significant cause of ischaemic stroke. Indications for surgical revascularisation depend on the severity of the stenosis and clinical symptoms. However, mild symptoms such as TIA (Transient ischaemic attack), amaurosis fugax or minor stroke precede large strokes in only 15% of cases. AIM: The aim of this prospective study is to evaluate whether retinal perfusion is impacted in significant carotid stenosis. Automated retinal oximetry will be used to better assess perfusion in the post-stenotic basin. We presume the more stenotic the blood vessel, the more reduced the retinal perfusion is, resulting in adaptive changes such as greater arteriovenous saturation difference due to greater oxygen extraction. This could broaden the indication spectrum for revascularisation for carotid stenosis. METHODS: We plan to enroll yearly 50 patients with significant carotid stenosis and cross-examine them with retinal oximetry. The study group will provide stenotic vessels and, non-stenotic vessels will form the control group. Patients with significant carotid stenosis will undergo an MRI (Magnetic Resonnance imaging) examination to determine the presence of asymptomatic recent ischaemic lesions in the stenotic basin, and the correlation to oximetry parameters. STATISTICS: The stenosis severity and retinal oximetry parameters will be compared for study and control groups with a threshold of 70%, respectively 80% and 90% stenosis. Results will be then reevaluated with emphasis on MRI findings in the carotid basin. CONCLUSION: This prospective case control study protocol will be used to launch a multicentre trial assessing the relationship between significant carotid stenosis and retinal perfusion measured with automated retinal oximetry. Despite these differences, the findings indicate the potential of retinal oximetry for noninvasive real-time measurements of oxyhaemoglobin saturation in central nervous system vessels. Following calibration upgrade and technological improvement, verification retinal oximetry may potentially be applied to critically ill and anaesthesia care patients. The study on combined scanning laser ophthalmoscope and retinal oximetry supports the feasibility of the technique for oximetry analysis in newly born babies. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT06085612.

• MeSH
• lidé středního věku MeSH
• lidé MeSH
• oxymetrie * metody   MeSH
• prospektivní studie MeSH
• retina diagnostické zobrazování   patofyziologie   MeSH
• retinální cévy diagnostické zobrazování   patofyziologie   MeSH
• senioři MeSH
• stenóza arteria carotis * patofyziologie   chirurgie   komplikace   MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH

Arterial compliance (AC) is an important cardiovascular parameter characterizing mechanical properties of arteries. AC is significantly influenced by arterial wall structure and vasomotion, and it markedly influences cardiac load. A new method, based on a two-element Windkessel model, has been recently proposed for estimating AC as the ratio of the time constant T of the diastolic blood pressure decay and peripheral vascular resistance derived from clinically available stroke volume measurements and selected peripheral blood pressure parameters which are less prone to peripheral distortions. The aim of this study was to validate AC estimation using a virtual population generated by in silico model of the systemic arterial tree. In the second part of study, we analysed causal coupling between AC oscillations and variability of its potential determinants - systolic blood pressure and heart rate in healthy young human subjects. The pool of virtual subjects (n=3818) represented an extensive AC distribution. AC was estimated from the peripheral blood pressure curve and by the standard method from the aortic blood pressure curve. The proposed method slightly overestimated AC set in the model but both ACs were strongly correlated (r=0.94, p<0.001). In real data, we observed that AC dynamics was coupled with basic cardiovascular parameters variability independently of the autonomic nervous system state. In silico analysis suggests that AC can be reliably estimated by noninvasive method. The analysis of short-term AC variability together with its determinants could improve our understanding of factors involved in AC dynamics potentially improving assessment of AC changes associated with atherosclerosis process. Key words Arterial compliance, Cardiovascular model, Arterial blood pressure, Causal analysis, Volume-clamp photoplethysmography.

• MeSH
• arterie * fyziologie   MeSH
• cévní rezistence fyziologie   MeSH
• dospělí MeSH
• krevní tlak * fyziologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• modely kardiovaskulární * MeSH
• počítačová simulace * MeSH
• poddajnost MeSH
• srdeční frekvence fyziologie   MeSH
• tuhost cévní stěny fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• validační studie MeSH

BACKGROUND: Dexamethasone 6 mg in patients with severe COVID-19 has been shown to decrease mortality and morbidity. The effects of higher doses of corticosteroid, that would further increase anti-inflammatory effects, are uncertain. The objective of our study was to assess the effect of 20 mg dexamethasone vs. 6 mg dexamethasone intravenously in patients with moderate-to-severe acute respiratory distress syndrome (ARDS) and COVID-19. METHODS: In a multicenter, open-label, randomized trial conducted in nine hospitals in the Czech Republic, we randomized adult patients with ARDS and COVID-19 requiring high-flow oxygen, noninvasive or invasive mechanical ventilation to receive either intravenous high-dose dexamethasone (20 mg/day on days 1-5, 10 mg/day on days 6-10) or standard-dose dexamethasone (6 mg/d, days 1-10). The primary outcome was 28-day ventilator-free days. The five secondary outcomes were 60-day mortality, C-reactive protein dynamics, 14-day WHO (World Health Organization) Clinical Progression Scale score, adverse events and 90-day Barthel index. The long-term outcomes were 180- and 360-day mortality and the Barthel index. The planned sample size was 300, with interim analysis after enrollment of 150 patients. RESULTS: The trial was stopped due to a lack of recruitment, and the follow-up was completed in February 2023. Among 234 randomized patients of 300 planned patients, the primary outcome was available for 224 patients (110 high-dose and 114 standard-dose dexamethasone; median [interquartile range (IQR)] age, 59.0 [48.5-66.0] years; 130 [58.0%] were receiving noninvasive or invasive mechanical ventilation at baseline). The mean number of 28-day ventilator-free days was 8.9 (± 11.5) days for high-dose dexamethasone and 8.0 (± 10.7) days for standard-dose dexamethasone, with an absolute difference of + 0.81 days (95% CI - 2.12-3.73 days). None of the prespecified secondary outcomes, including adverse events, differed between the groups. CONCLUSIONS: Despite not reaching its prespecified enrollment, there was no signal to either benefit or harm high-dose dexamethasone over standard-dose dexamethasone in patients with COVID-19 and moderate-to-severe ARDS. Trial registration Trial registration: ClinicalTrials.gov Identifier: NCT04663555. Registered 10 December 2020, https://clinicaltrials.gov/study/NCT04663555?term=NCT04663555&rank=1 and EudraCT: 2020-005887-70.

• MeSH
• COVID-19 * mortalita   komplikace   MeSH
• dexamethason * aplikace a dávkování   terapeutické užití   MeSH
• farmakoterapie COVID-19 * MeSH
• lidé středního věku MeSH
• lidé MeSH
• SARS-CoV-2 MeSH
• senioři MeSH
• syndrom dechové tísně * farmakoterapie   mortalita   MeSH
• umělé dýchání * MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Česká republika MeSH

CONTEXT: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported. OBJECTIVE: To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions. METHODS: Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey. RESULTS: A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania. CONCLUSION: Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.

• MeSH
• buněčné jádro patologie   MeSH
• folikulární adenokarcinom * patologie   epidemiologie   diagnóza   MeSH
• lékařská praxe - způsoby provádění statistika a číselné údaje   MeSH
• lidé MeSH
• nádory štítné žlázy * epidemiologie   patologie   diagnóza   MeSH
• papilární karcinom štítné žlázy epidemiologie   patologie   diagnóza   MeSH
• papilární karcinom patologie   epidemiologie   diagnóza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Asie MeSH
• Evropa MeSH
• Oceánie MeSH
• Severní Amerika MeSH

Cíl: Cílem studie je vyhodnotit opakovatelnost měření neinvazivního break-up time (NIBUT) keratografem při jeho stanovení z jednoho, dvou či třech dílčích měření a doporučit pro praxi vhodnou metodiku. Dalším cílem je ověřit, zda opakovaná měření neovlivňují měřenou hodnotu. Materiál a metodika: Do studie bylo zařazeno 38 zdravých dobrovolníků (30 žen a 8 mužů) ve věku od 19 do 50 let, u každého bylo měřeno vždy jen jedno oko. Studie byla koncipována jako prospektivní. Po 15minutové adaptaci na podmínky vyšetřovny podstoupil každý účastník dvě série měření NIBUT (test, retest) na keratografu OCULUS 3. Minimální časový odstup obou sérií byl 10 minut, každá série obsahovala tři dílčí měření v odstupu přibližně 3 minuty. Výsledný NIBUT byl v každé sérii stanoven (A) jako první hodnota v dané sérii, (B) jako průměr prvních dvou nebo (C) všech tří měření v dané sérii. Opakovatelnost byla hodnocena Bland-Altmanovou analýzou a vyjádřena koeficientem opakovatelnosti. Sledován byl vždy pouze čas prvního roztržení slzného filmu. Výsledky: Statistická analýza neprokázala statisticky signifikantní rozdíly jak mezi dílčími měřeními NIBUT v jednotlivých sérií (p = 0,92, p = 0,81), tak při porovnání všech šesti měření (p = 0,95). Průměrné hodnoty dílčích měření se pohybovaly od 13,6 s do 14,4 s. Pro postupy A, B a C byly zjištěny koeficienty opakovatelnosti (po řadě) 15,0 s, 12,1 s a 10,0 s. Doplňující analýza pro 12 očí s nízkým NIBUT (< 10 s) prokázala statisticky signifikantně lepší opakovatelnost v této skupině, a to s koeficienty 7,0 s (metodika A), 6,0 s (B) a 4,6 s (C) . Závěr: Stanovení NIBUT ze tří po sobě jdoucích měření (s dostatečným, ideálně několikaminutovým odstupem) významně zlepšuje opakovatelnost. Přitom takto opakovaná měření NIBUT nemají významný vliv na měřenou hodnotu. Uvedenou metodiku měření NIBUT na keratografu lze doporučit pro použití v praxi.

Aim: The primary aim of this study is to evaluate the repeatability of noninvasive break-up time (NIBUT) measurement by keratograph when it is determined from one, two or three partial measurements, and to recommend a suitable methodology for practice. Another goal is to verify that repeated measurements do not affect the measured value. Material and Methods: Thirty-eight healthy volunteers (30 women and 8 men) aged between 19 and 50 years old were included in the study, in which only one eye of each volunteer was measured. The study was designed as a prospective one. Each subject adapted to the local conditions of the laboratory for 15 minutes and subsequently underwent two series of NIBUT measurements (test, retest) on an OCULUS 3 Keratograph. The minimum time interval between the two series was 10 minutes, in which each series contained three partial measurements approximately 3 three measurements in the given series. Repeatability was assessed by a Bland-Altman analysis and expressed as a repeatability coefficient. In every case, only the time of the first break-up of the tear film was monitored. Results: The statistical analysis did not show statistically significant differences both between partial measurements of NIBUT in the individual series (p = 0.92, p = 0.81) and when comparing all six measurements (p = 0.95). The mean values of the partial measurements ranged from 13.6 s to 14.4 s. The repeatability coefficients were found to be 15.0 s, 12.1 s and 10.0 s for methodologies A, B and C, respectively. A supplementary analysis for 12 eyes with low NIBUT (< 10 s) showed statistically significantly better repeatability in this group, with coefficients of 7.0 s (methodology A), 6.0 s (B) and 4.6 s (C). Conclusion: Determination of NIBUT from three consecutive measurements (with a sufficient interval of ideally a few minutes) significantly improves repeatability. Such repeated NIBUT measurements do not have a significant effect on the measured value. The mentioned methodology for measuring NIBUT on a keratograph can be recommended for use in practice.

• Klíčová slova
• slzný film, break-up time test, opakovatelnost měření, keratograf OCULUS 3,
• MeSH
• diagnostické techniky oftalmologické * klasifikace   přístrojové vybavení   MeSH
• prospektivní studie MeSH
• rohovka diagnostické zobrazování   fyziologie   patologie   MeSH
• syndromy suchého oka * diagnostické zobrazování   diagnóza   MeSH
• Publikační typ
• práce podpořená grantem MeSH

AIMS: There is increasing evidence that plaque instability in the extracranial carotid artery may lead to an increased stroke risk independently of the degree of stenosis. We aimed to determine diagnostic accuracy of vulnerable and stable plaque using noninvasive imaging modalities when compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis. METHODS AND RESULTS: Medline Ovid, Embase, Cochrane Library, and Web of Science were searched for diagnostic accuracy of noninvasive imaging modalities (CT, MRI, US) in the detection of 1) vulnerable/stable plaque, and 2) vulnerable/stable plaque characteristics, compared to histology. The quality of included studies was assessed by QUADAS-2 and univariate and bivariate random-effect meta-analyses were performed. We included 36 vulnerable and 5 stable plaque studies in the meta-analysis, and out of 211 plaque characteristics from remaining studies, we classified 169 as vulnerable and 42 as stable characteristics (28 CT, 120 MRI, 104 US characteristics). We found that MRI had high accuracy [90% (95% CI: 82-95%)] in the detection of vulnerable plaque, similar to CT [86% (95% CI: 76-92%); P > 0.05], whereas US showed less accuracy [80% (95% CI: 75-84%); P = 0.013]. CT showed high diagnostic accuracy in visualizing characteristics of vulnerable or stable plaques (89% and 90%) similar to MRI (86% and 89%; P > 0.05); however, US had lower accuracy (77%, P < 0.001 and 82%, P > 0.05). CONCLUSION: CT and MRI have a similar, high performance in detecting vulnerable carotid plaques, whereas US showed significantly less diagnostic accuracy. Moreover, MRI visualized all vulnerable plaque characteristics allowing for a better stroke risk assessment. REGISTRATION: PROSPERO ID CRD42022329690.

• MeSH
• aterosklerotický plát * diagnostické zobrazování   MeSH
• hodnocení rizik MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   MeSH
• nemoci arterie carotis diagnostické zobrazování   MeSH
• počítačová rentgenová tomografie metody   MeSH
• stenóza arteria carotis diagnostické zobrazování   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH

BACKGROUND & AIMS: α1-Antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the 'Pi∗Z' variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation, and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown. METHODS: Liver-related parameters were assessed in a multinational cohort of 760 adults with severe AATD (Pi∗ZZ genotype) and available liver phenotyping, of whom 344 received augmentation therapy and 416 did not. Liver fibrosis was evaluated noninvasively via the serum test AST-to-platelet ratio index and via transient elastography-based liver stiffness measurement. Histologic parameters were compared in 15 Pi∗ZZ adults with and 35 without augmentation. RESULTS: Compared with nonaugmented subjects, augmented Pi∗ZZ individuals displayed lower serum liver enzyme levels (AST 71% vs 75% upper limit of normal, P < .001; bilirubin 49% vs 58% upper limit of normal, P = .019) and lower surrogate markers of fibrosis (AST-to-platelet ratio index 0.34 vs 0.38, P < .001; liver stiffness measurement 6.5 vs 7.2 kPa, P = .005). Among biopsied participants, augmented individuals had less pronounced liver fibrosis and less inflammatory foci but no differences in AAT accumulation were noted. CONCLUSIONS: The first evaluation of AAT augmentation on the Pi∗ZZ-related liver disease indicates liver safety of a widely used treatment for AATD-associated lung disease. Prospective studies are needed to confirm the beneficial effects and to demonstrate the potential efficacy of exogenous AAT in patients with Pi∗ZZ-associated liver disease.

• MeSH
• deficit alfa1-antitrypsinu * komplikace   farmakoterapie   MeSH
• dospělí MeSH
• fenotyp MeSH
• genotyp MeSH
• jaterní cirhóza etiologie   MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH