BACKGROUND: Drug survival, defined as the length of time from initiation to discontinuation of a given therapy, allows comparisons between drugs, helps to predict patient's likelihood of remaining on a specific treatment, and achieving the best decision for each patient in daily clinical practice. OBJECTIVE: The aim of this study was to provide data on drug survival of secukinumab, ixekizumab, brodalumab, guselkumab, tildrakizumab, and risankizumab in a large international cohort, and to identify clinical predictors that might have an impact on the drug survival of these drugs. METHODS: This was a retrospective, multicentric, multi-country study that provides data of adult patients with moderate to severe psoriasis who started treatment with an interleukin (IL)-17 or IL-23 inhibitor between 1 February 2015 and 31 October 2021. Data were collected from 19 distinct hospital and non-hospital-based dermatology centers from Canada, Czech Republic, Italy, Greece, Portugal, Spain, and Switzerland. Kaplan-Meier estimator and proportional hazard Cox regression models were used for drug survival analysis. RESULTS: A total of 4866 treatment courses (4178 patients)-overall time of exposure of 9500 patient-years-were included in this study, with 3164 corresponding to an IL-17 inhibitor (secukinumab, ixekizumab, brodalumab) and 1702 corresponding to an IL-23 inhibitor (guselkumab, risankizumab, tildrakizumab). IL-23 inhibitors had the highest drug survival rates during the entire study period. After 24 months of treatment, the cumulative probabilities of drug survival were 0.92 (95% confidence interval [CI] 0.89-0.95) for risankizumab, 0.90 (95% CI 0.88-0.92) for guselkumab, 0.80 (95% CI 0.76-0.84) for brodalumab, 0.79 (95% CI 0.76-0.82) for ixekizumab, and 0.75 (95% CI 0.73-0.77) for secukinumab. At 36 months, only guselkumab [0.88 (95% CI 0.85-0.91)], ixekizumab [0.73 (95% CI 0.70-0.76)], and secukinumab [0.67 (95% CI 0.65-0.70)] had more than 40 patients at risk of drug discontinuation. Only two drugs had more than 40 patients at risk of drug discontinuation at 48 months, with ixekizumab demonstrating to have a higher cumulative probability of drug survival [0.71 (95% CI 0.68-0.75)] when compared with secukinumab [0.63 (95% CI 0.60-0.66)]. Secondary failure was the main cause for drug discontinuation. According to the final multivariable model, patients receiving risankizumab, guselkumab, and ixekizumab were significantly less likely to discontinue treatment than those receiving secukinumab. Previous exposure to biologic agents, absent family history of psoriasis, higher baseline body mass index (BMI), and higher baseline Psoriasis Area and Severity Index (PASI) were identified as predictors of drug discontinuation. CONCLUSION: The cumulative probability of drug survival of both IL-17 and IL-23 inhibitors was higher than 75% at 24 months, with risankizumab and guselkumab demonstrating to have overall cumulative probabilities ≥ 90%. Biological agent chosen, prior exposure to biologic agents, higher baseline BMI and PASI values, and absence of family history of psoriasis were identified as predictors for drug discontinuation. Risankizumab, guselkumab, and ixekizumab were less likely to be discontinued than secukinumab.

• MeSH
• dospělí MeSH
• inhibitory interleukinu MeSH
• interleukin-17 * MeSH
• interleukin-23 MeSH
• lidé MeSH
• psoriáza * farmakoterapie   MeSH
• retrospektivní studie MeSH
• stupeň závažnosti nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Pandemie v podobně onemocnění COVID-19 rychle změnila klinický obraz světa. Symptomy se často dostavují plíživě a maskují dramatické klinické scénáře. Na oddělení akutního příjmu byl dopraven 52letý muž s perzistentní bolestí na hrudi, dyspnoe a hypoxií. Stěžoval si rovněž na kašel a horečku (38 °C) přetrvávající už čtyři dny bez jakéhokoli klinického zlepšení při užívání paracetamolu. Nazofaryngeální stěr byl pozitivní na přítomnost viru SARS-CoV-2. Vyšetření výpočetní tomografií s vysokým rozlišením (high-resolution computed tomography, HRCT) ukázalo typický obraz oboustranného zápalu plic v souvislosti s onemocněním COVID-19. Během pobytu v nemocnici došlo ke zhoršení klinického stavu pacienta a CT angiografické vyšetření plic prokázalo bilaterální masivní akutní plicní embolii. Byla zahájena léčba nefrakcionovaným heparinem.

COVID-19 pandemic changed quickly world's clinical picture. Symptoms often are sneaky, hiding dramatic clinical scenarios. A 52-year-old man was sent to the Emergency Department with persistent chest pain, dyspnea and hypoxia. He also complained of cough and fever (38 °C) since four days without clinical improvements by paracetamol. Nasopharyngeal swab was positive for SARS-CoV-2. High resolution computer tomography (HRCT) showed typical CT pattern of bilateral COVID-19 pneumonia. During hospital stay clinical worsening occurred and a CT pulmonary angiography revealed a bilateral massive acute pulmonary embolism. The patient was treated with unfractionated heparin.

• MeSH
• COVID-19 * diagnostické zobrazování   komplikace   MeSH
• CT angiografie MeSH
• heparin nízkomolekulární terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní embolie diagnostické zobrazování   farmakoterapie   komplikace   MeSH
• počítačová rentgenová tomografie MeSH
• rentgendiagnostika hrudníku MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Koronární píštěle představují vzácnou anatomickou anomálii; incidence těchto píštělí ústících do levé komory srdeční je nízká. Hypertrofie hrotu levé komory je poměrně vzácným projevem hypertrofické kardiomyopatie, někdy je spojena s přítomností koronární píštěle. Popisujeme případ koronární mikropíštěle ústící do levé komory a spojené s apikální hypertrofickou kardiomyopatií, která se poprvé projevila jako akutní koronární syndrom v podobě infarktu myokardu bez elevací úseku ST (NSTEMI).

Coronary fistulae are rare anatomic anomalies and those ones draining in left ventricle have low incidence. Apical hypertrophy of left ventricle is a relatively rare manifestation of hypertrophic cardiomyopathy, sometimes associated with coronary fistulae. We show the case of a coronary microfistulae draining on left ventricle associated with an apical hypertrophic cardiomyopathy which manifested for the first time as an acute coronary syndrome non-ST elevation myocardial infarction (NSTEMI).

• MeSH
• akutní koronární syndrom * etiologie   terapie   MeSH
• cévní píštěle diagnóza   komplikace   MeSH
• hypertrofická kardiomyopatie diagnóza   patofyziologie   MeSH
• lidé MeSH
• nemoci koronárních tepen diagnóza   komplikace   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Tetranucleotide Short Tandem Repeats (STRs) for human identification and common use in forensic cases have recently been used to address the population genetics of the North-Eastern Mediterranean area. However, to gain confidence in the inferences made using STRs, this kind of analysis should be challenged with changes in three main aspects of the data, i.e. the sizes of the samples, their distance across space and the genetic background from which they are drawn. AIM: To test the resilience of the gradients previously detected in the North-Eastern Mediterranean to the enlargement of the surveyed area and population set, using revised data. SUBJECTS AND METHODS: STR genotype profiles were obtained from a publicly available database (PopAffilietor databank) and a dataset was assembled including >7000 subjects from the Arabian Peninsula to Scandinavia, genotyped at eight loci. Spatial principal component analysis (sPCA) was applied and the frequency maps of the nine alleles which contributed most strongly to sPC1 were examined in detail. RESULTS: By far the greatest part of diversity was summarised by a single spatial principal component (sPC1), oriented along a SouthEast-to-NorthWest axis. The alleles with the top 5% squared loadings were TH01(9.3), D19S433(14), TH01(6), D19S433(15.2), FGA(20), FGA(24), D3S1358(14), FGA(21) and D2S1338(19). These results confirm a clinal pattern over the whole range for at least four loci (TH01, D19S433, FGA, D3S1358). CONCLUSIONS: Four of the eight STR loci (or even alleles) considered here can reproducibly capture continental arrangements of diversity. This would, in principle, allow for the exploitation of forensic data to clarify important aspects in the formation of local gene pools.

• MeSH
• frekvence genu * MeSH
• genetická variace * MeSH
• genotyp * MeSH
• mikrosatelitní repetice * MeSH
• populační genetika MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• severní Afrika MeSH
• Střední východ MeSH
• Středomoří MeSH

Human forensic STRs used for individual identification have been reported to have little power for inter-population analyses. Several methods have been developed which incorporate information on the spatial distribution of individuals to arrive at a description of the arrangement of diversity. We genotyped at 16 forensic STRs a large population sample obtained from many locations in Italy, Greece and Turkey, i.e. three countries crucial to the understanding of discontinuities at the European/Asian junction and the genetic legacy of ancient migrations, but seldom represented together in previous studies. Using spatial PCA on the full dataset, we detected patterns of population affinities in the area. Additionally, we devised objective criteria to reduce the overall complexity into reduced datasets. Independent spatially explicit methods applied to these latter datasets converged in showing that the extraction of information on long- to medium-range geographical trends and structuring from the overall diversity is possible. All analyses returned the picture of a background clinal variation, with regional discontinuities captured by each of the reduced datasets. Several aspects of our results are confirmed on external STR datasets and replicate those of genome-wide SNP typings. High levels of gene flow were inferred within the main continental areas by coalescent simulations. These results are promising from a microevolutionary perspective, in view of the fast pace at which forensic data are being accumulated for many locales. It is foreseeable that this will allow the exploitation of an invaluable genotypic resource, assembled for other (forensic) purposes, to clarify important aspects in the formation of local gene pools.

• MeSH
• genetická variace genetika   MeSH
• genotyp MeSH
• lidé MeSH
• mikrosatelitní repetice genetika   MeSH
• modely genetické * MeSH
• populační genetika * MeSH
• soudní genetika * MeSH
• zeměpis MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Středomoří MeSH