BACKGROUND: Better risk-stratification of patients with chronic lymphocytic leukemia (CLL) and identification of subsets of ultra-high-risk (HR)-CLL patients are crucial in the contemporary era of an expanded therapeutic armamentarium for CLL. METHODS: A multivariate patient similarity network and clustering was applied to assess the prognostic values of routine genetic, laboratory, and clinical factors and to identify subsets of ultra-HR-CLL patients. The study cohort consisted of 116 HR-CLL patients (F/M 36/80, median age 63 yrs) carrying del(11q), del(17p)/TP53 mutations and/or complex karyotype (CK) at the time of diagnosis. RESULTS: Three major subsets based on the presence of key prognostic variables as genetic aberrations, bulky lymphadenopathy, splenomegaly, and gender: profile (P)-I (n = 34, men/women with CK + no del(17p)/TP53 mutations), P-II (n = 47, predominantly men with del(11q) + no CK + no del(17p)/TP53 mutations), and P-III (n = 35, men/women with del(17p)/TP53 mutations, with/without del(11q) and CK) were revealed. Subanalysis of major subsets identified three ultra-HR-CLL groups: men with TP53 disruption with/without CK, women with TP53 disruption with CK and men/women with CK + del(11q) with poor short-term outcomes (25% deaths/12 mo). Besides confirming the combinations of known risk-factors, the used patient similarity network added further refinement of subsets of HR-CLL patients who may profit from different targeted drugs. CONCLUSIONS: This study showed for the first time in hemato-oncology the usefulness of the multivariate patient similarity networks for stratification of HR-CLL patients. This approach shows the potential for clinical implementation of precision medicine, which is especially important in view of an armamentarium of novel targeted drugs.

• MeSH
• chronická lymfatická leukemie diagnóza   epidemiologie   genetika   terapie   MeSH
• dospělí MeSH
• hodnocení rizik MeSH
• individualizovaná medicína metody   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• mutační analýza DNA MeSH
• neuronové sítě (počítačové) MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• rozhodovací stromy MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• shluková analýza 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
• práce podpořená grantem MeSH

We aimed to detect the levels of T-lympho-cyte subsets and serum tumour markers in patients with non-small cell lung cancer (NSCLC) before chemotherapy, and to investigate the predictive value of their combined detection for the prognosis of NSCLC patients undergoing chemotherapy. The clinical data of 110 NSCLC patients treated with chemotherapy from January 2019 to February 2021 were analysed retrospectively. All patients were followed up for one year and divided into good prognosis group (surviving cases) and poor prognosis group (deceased cases). The predictive value of T-lymphocyte subsets combined with serum tumour markers for prognosis was analysed. The proportions of patients with tumour-node-metastasis stages III-IV, lymph node metastasis and poor differentiation were higher in the poor prognosis group than those in the good prognosis group (P < 0.05). Cox regression analysis revealed that high expression of CD4+ and CEA represented protective factors for poor prognosis of NSCLC patients undergoing chemotherapy [odds ratio (OR) < 1, P < 0.05], while high expression of CA125 was a risk factor (OR > 1, P < 0.05). All the areas under the receiver operating characteristic curves of single indicator detection (CD4+, CEA and CA125 levels) and their combined detection for prediction of the poor prognosis of NSCLC patients undergoing chemotherapy were > 0.70, which was highest in the case of combined detection. T-lymphocyte subsets and serum tumour markers are closely related to the prognosis of NSCLC patients undergoing chemotherapy, and their combined detection is of high predictive value.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery * krev   MeSH
• nádory plic * farmakoterapie   krev   patologie   MeSH
• nemalobuněčný karcinom plic * farmakoterapie   krev   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři MeSH
• T-lymfocyty - podskupiny * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

AIMS: Screening logs have the potential to appraise the actual prevalence and distribution of predefined patient subsets, avoiding selection biases, which are inevitably and potentially present in randomised trials and real-world registries, respectively. We aimed to assess the prevalence of high bleeding risk (HBR) characteristics in the real world and the external validity of the MASTER DAPT trial. METHODS AND RESULTS: All consecutive patients who underwent percutaneous coronary intervention (PCI) for at least two consecutive weeks across 65 sites participating in the trial were entered into a screening log. Of 2,847 consecutive patients, 1,098 (38.6 %) were HBR and 109 (9.9 %) consented for trial participation. PRECISE-DAPT score ≥ 25 was the most frequent HBR feature, followed by advanced age, use of oral anticoagulation (OAC) and anaemia. Compared with consecutive HBR patients, consenting patients were older (≥ 75 years: 69 % versus 62 %, absolute standardized difference [SD] 0.16), more frequently male (78 % versus 71 %, absolute SD 0.18), had higher use of OAC (38 % versus 20 %, absolute SD 0.39), treatment with steroids or nonsteroidal anti-inflammatory drugs (10 % versus 5 %, SD 0.16), and prior cerebrovascular events (10 % versus 6 %, absolute SD 0.18) but lower PRECISE DAPT score ≥ 25 (54 % versus 66 %, absolute SD 0.24). CONCLUSIONS: The HBR criteria distribution differed between consecutive versus selectively included HBR patients, suggesting the existence of selection biases in the trial population.

• MeSH
• antikoagulancia škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• duální protidestičková léčba škodlivé účinky   metody   MeSH
• hodnocení rizik MeSH
• inhibitory agregace trombocytů * škodlivé účinky   terapeutické užití   MeSH
• koronární angioplastika * MeSH
• krvácení * chemicky indukované   epidemiologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výběr pacientů MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

The natural history of hypertrophic cardiomyopathy (HCM) is extremely heterogeneous. Many patients remain asymptomatic throughout life, some develop severe symptoms of heart failure, but others die suddenly, often in the absence of previous symptoms and at a young age. Therefore, identification of those patients at high risk of sudden death represents a major clinical problem and has become an even greater challenge since the implantable cardioverter-defibrillator (ICD) has proved to be highly effective in preventing sudden death in HCM. Patients who have survived a cardiac arrest, or one or more episodes of sustained ventricular tachycardia, are considered to be at high risk and are candidates for an ICD. However, this patient subset represents a small proportion of the HCM population. The greatest difficulty concerns the identification of high risk patients who are candidates for primary prevention of sudden death with a prophylactic ICD. Decisions are based on generally accepted clinical markers which are associated with increased risk, including: family history of sudden death, extreme left ventricular (LV) wall thickness ( > or =30 mm), nonsustained ventricular tachycardia on Holter monitoring, unexplained (non-neurocardiogenic) syncope particularly in young patients, and hypotensive blood pressure response to exercise. Patients with end-stage HCM or a LV apical aneurysm represent important arrhythmogenic subsets also associated with substantially increased risk. Multiple or single strong risk markers are associated with increased sudden death risk and justify consideration for a prophylactic ICD.

• MeSH
• defibrilátory implantabilní MeSH
• dospělí MeSH
• hypertrofická kardiomyopatie mortalita   terapie   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• multivariační analýza MeSH
• náhlá srdeční smrt epidemiologie   MeSH
• následné studie MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• rizikové faktory MeSH
• senioři MeSH
• synkopa mortalita   terapie   MeSH
• věkové rozložení MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

BACKGROUND AND AIMS: We previously identified subsets of patients with NAFLD with different metabolic phenotypes. Here we align metabolomic signatures with cardiovascular disease (CVD) and genetic risk factors. APPROACH AND RESULTS: We analyzed serum metabolome from 1154 individuals with biopsy-proven NAFLD, and from four mouse models of NAFLD with impaired VLDL-triglyceride (TG) secretion, and one with normal VLDL-TG secretion. We identified three metabolic subtypes: A (47%), B (27%), and C (26%). Subtype A phenocopied the metabolome of mice with impaired VLDL-TG secretion; subtype C phenocopied the metabolome of mice with normal VLDL-TG; and subtype B showed an intermediate signature. The percent of patients with NASH and fibrosis was comparable among subtypes, although subtypes B and C exhibited higher liver enzymes. Serum VLDL-TG levels and secretion rate were lower among subtype A compared with subtypes B and C. Subtype A VLDL-TG and VLDL-apolipoprotein B concentrations were independent of steatosis, whereas subtypes B and C showed an association with these parameters. Serum TG, cholesterol, VLDL, small dense LDL5,6 , and remnant lipoprotein cholesterol were lower among subtype A compared with subtypes B and C. The 10-year high risk of CVD, measured with the Framingham risk score, and the frequency of patatin-like phospholipase domain-containing protein 3 NAFLD risk allele were lower in subtype A. CONCLUSIONS: Metabolomic signatures identify three NAFLD subgroups, independent of histological disease severity. These signatures align with known CVD and genetic risk factors, with subtype A exhibiting a lower CVD risk profile. This may account for the variation in hepatic versus cardiovascular outcomes, offering clinically relevant risk stratification.

• MeSH
• apolipoproteiny B MeSH
• fosfolipasy metabolismus   MeSH
• játra patologie   MeSH
• kardiovaskulární nemoci * epidemiologie   etiologie   MeSH
• lipoproteiny VLDL MeSH
• myši MeSH
• nealkoholová steatóza jater * patologie   MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• rizikové faktory MeSH
• triglyceridy metabolismus   MeSH
• VLDL-cholesterol metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

The study was designed to develop a simple risk stratification score for primary therapy with an implantable cardioverter-defibrillator (ICD). BACKGROUND: Current guidelines recommend primary ICD therapy in patients with a low ejection fraction (EF). However, the benefit of the ICD in the low EF population may not be uniform. METHODS: Best-subset proportional-hazards regression analysis was used to develop a simple clinical risk score for the end point of all-cause mortality in patients allocated to the conventional therapy arm of MADIT (Multicenter Automatic Defibrillator Implantation Trial)-II after excluding a pre-specified subgroup of very high-risk (VHR) patients (defined by blood urea nitrogen [BUN] >or=50 mg/dl and/or serum creatinine >or=2.5 mg/dl). The benefit of the ICD was then assessed within risk score categories and separately in VHR patients. RESULTS: The selected risk score model comprised 5 clinical factors (New York Heart Association functional class >II, age >70 years, BUN >26 mg/dl, QRS duration >0.12 s, and atrial fibrillation). Crude mortality rates in the conventional group were 8% and 28% in patients with 0 and >or=1 risk factors, respectively, and 43% in VHR patients. Defibrillator therapy was associated with a 49% reduction in the risk of death (p < 0.001) among patients with >or=1 risk factors (n = 786), whereas no ICD benefit was identified in patients with 0 risk factors (n = 345; hazard ratio 0.96; p = 0.91) and in VHR patients (n = 60; hazard ratio 1.00; p > 0.99). CONCLUSIONS: Our data suggest a U-shaped pattern for ICD efficacy in the low-EF population, with pronounced benefit in intermediate-risk patients and attenuated efficacy in lower- and higher-risk subsets.

• MeSH
• defibrilátory implantabilní MeSH
• dysfunkce levé srdeční komory etiologie   mortalita   terapie   MeSH
• hodnocení rizik metody   MeSH
• hodnocení výsledků zdravotní péče MeSH
• infarkt myokardu komplikace   terapie   MeSH
• Kaplanův-Meierův odhad MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhlá srdeční smrt epidemiologie   prevence a kontrola   MeSH
• proporcionální rizikové modely MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a prototypical complex disease with polygenic architecture playing an important role in determining susceptibility to develop the disease (and its complications) in subjects exposed to modifiable lifestyle factors. A current challenge is to quantify the degree of the individual's genetic risk using genetic risk scores (GRS) capturing the results of genome-wide association studies while incorporating possible ethnicity- or population-specific differences. METHODS: This study included three groups of T2DM (T2DM-I, N = 1,032; T2DM-II, N = 353; and T2DM-III, N = 399) patients and 2,481 diabetes-free subjects. The status of the microvascular and macrovascular diabetes complications were known for the T2DM-I patients. Overall, 21 single nucleotide polymorphisms (SNPs) were analyzed, and selected subsets were used to determine the GRS (both weighted - wGRS and unweighted - uGRS) for T2DM risk predictions (6 SNPs) and for predicting the risks of complications (7 SNPs). RESULTS: The strongest T2DM markers (P < 0.0001) were within the genes for TCF7L2 (transcription factor 7-like 2), FTO (fat mass and obesity associated protein) and ARAP1 (ankyrin repeat and PH domain 1). The T2DM-I subjects with uGRS values greater (Odds Ratio, 95 % Confidence Interval) than six had at least twice (2.00, 1.72-2.32) the risk of T2DM development (P < 0.0001), and these results were confirmed in the independent groups (T2DM-II 1.82, 1.45-2.27; T2DM-III 2.63, 2.11-3.27). The wGRS (>0.6) further improved (P < 0.000001) the risk estimations for all three T2DM groups. The uGRS was also a significant predictor of neuropathy (P < 0.0001), nephropathy (P < 0.005) and leg ischemia (P < 0.0005). CONCLUSIONS: If carefully selected and specified, GRS, both weighted and unweighted, could be significant predictors of T2DM development, as well as the diabetes complications development.

• MeSH
• celogenomová asociační studie MeSH
• diabetes mellitus 2. typu * komplikace   genetika   MeSH
• gen pro FTO genetika   MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus MeSH
• komplikace diabetu * MeSH
• lidé MeSH
• rizikové faktory MeSH
• T-buňky - transkripční faktor 1 genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Obezita je spojena s nízkou zánětlivou aktivitou a představuje rizikový faktor závažných kardiovaskulárních a metabolických onemocnění. U revmatoidní artritidy je výskyt kardiovaskulárních onemocnění dvakrát vyšší než v běžné populaci. Revmatoidní artritida bývá spojena s nepříznivým metabolickým stavem - chronický zánět a nedostatek pohybu způsobují úbytek svalové hmoty a zvýšenou akumulaci tukové tkáně. Tento stav se označuje jako revmatoidní kachexie nebo sarkopenická obezita a vyskytuje se u jedinců se zvýšeným, ale převážně také s normálním indexem tělesné hmotnosti. Obezita ovlivňuje u revmatoidní artritidy mnoho aspektů. Pravděpodobně může představovat rizikový faktor pro vznik séronegativní formy onemocnění. Obézní pacienti s revmatoidní artritidou mají obvykle aktivnější průběh onemocnění a horší kvalitu života. Na druhé straně ale existuje několik dokladů o tom, že obézní pacienti s revmatoidní artritidou mají méně kloubních erozí a pomalejší strukturální progresi. Vyšší výskyt kardiovaskulárních onemocnění a zvýšená mortalita u revmatoidní artritidy nejsou pravděpodobně přímo závislé na výši indexu tělesné hmotnosti, ale na zánětlivé aktivitě onemocnění. Ukazuje se naopak, že ohroženější skupinou jsou velmi hubení pacienti. Cílem této práce je shrnout vztah mezi obezitou, závažností revmatoidní artritidy a profilem kardiovaskulárního rizika v kontextu nových poznatků o roli adipokinů v patogenezi metabolických a zánětlivých onemocnění. Klíčová slova: revmatoidní artritida, obezita, tuková tkáň, mortalita, zánět, adipokiny

Obesity is associated with low inflammatory activity and is a risk factor for severe cardiovascular and metabolic diseases. The occurrence of cardiovascular diseases in rheumatoid arthritis is two times higher than in the general population. Rheumatoid arthritis is associated with an unfavourable metabolic condition - chronic inflammation, and lack of exercise causes loss of muscle mass and increased accumulation of adipose tissue. This condition is referred to as rheumatoid cachexia or sarcopenic obesity and occurs in individuals with increased or mainly with normal body mass index. Obesity in rheumatoid arthritis affects many aspects. It can be a potential risk factor for seronegative subset of the disease. Obese patients with rheumatoid arthritis tend to have more active disease course and worse quality of life. On the other hand, there is some evidence that obese patients with rheumatoid arthritis have less joint erosions, and slower structural progression. The higher incidence of cardiovascular disease and increased mortality in rheumatoid arthritis are probably not directly dependent on the body mass index, but rather dependent on the inflammatory activity of the disease. On the contrary, very thin patients appear to be the more vulnerable group. The aim of this review is to summarize the relationship between obesity, the severity of rheumatoid arthritis and cardiovascular risk profile in the context of new knowledge on the role of adipokines in the pathogenesis of metabolic and inflammatory diseases. Key words: rheumatoid arthritis, obesity, adipose tissue, mortality, inflammation, adipokines

• MeSH
• adipokiny farmakokinetika   škodlivé účinky   MeSH
• cytokiny farmakokinetika   škodlivé účinky   MeSH
• financování organizované MeSH
• hodnocení rizik MeSH
• index tělesné hmotnosti MeSH
• kardiovaskulární nemoci diagnóza   epidemiologie   MeSH
• lidé MeSH
• mortalita MeSH
• obezita diagnóza   epidemiologie   etiologie   MeSH
• revmatoidní artritida komplikace   MeSH
• sarkopenie imunologie   patofyziologie   patologie   MeSH
• tuková tkáň imunologie   metabolismus   MeSH
• zánět imunologie   prevence a kontrola   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

It is unknown if brief episodes of device-detected atrial fibrillation (AF) increase thromboembolic event (TE) risk. METHODS AND RESULTS: TRENDS was a prospective, observational study enrolling patients with > or = 1 stroke risk factor (heart failure, hypertension, age > or = 65 years, diabetes, or prior TE) receiving pacemakers or defibrillators that monitor atrial tachycardia (AT)/AF burden (defined as the longest total AT/AF duration on any given day during the prior 30-day period). This time-varying exposure was updated daily during follow-up and related to TE risk. Annualized TE rates were determined according to AT/AF burden subsets: zero, low (<5.5 hours [median duration of subsets with nonzero burden]), and high (> or = 5.5 hours). A multivariate Cox model provided hazard ratios including terms for stroke risk factors and time-varying AT/AF burden and antithrombotic therapy. Patients (n=2486) had at least 30 days of device data for analysis. During a mean follow-up of 1.4 years, annualized TE risk (including transient ischemic attacks) was 1.1% for zero, 1.1% for low, and 2.4% for high burden subsets of 30-day windows. Compared with zero burden, adjusted hazard ratios (95% CIs) in the low and high burden subsets were 0.98 (0.34 to 2.82, P=0.97) and 2.20 (0.96 to 5.05, P=0.06), respectively. CONCLUSIONS: The TE rate was low compared with patients with traditional AF with similar risk profiles. The data suggest that TE risk is a quantitative function of AT/AF burden. AT/AF burden > or = 5.5 hours on any of 30 prior days appeared to double TE risk. Additional studies are needed to more precisely investigate the relationship between stroke risk and AT/AF burden.

• MeSH
• analýza rozptylu MeSH
• cévní mozková příhoda epidemiologie   etiologie   MeSH
• defibrilátory implantabilní MeSH
• fibrilace síní MeSH
• financování organizované MeSH
• intrakraniální embolie epidemiologie   etiologie   MeSH
• lidé MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• rozdělení chí kvadrát MeSH
• senioři MeSH
• tranzitorní ischemická ataka epidemiologie   etiologie   MeSH
• trombolytická terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• multicentrická studie MeSH

DNA mismatch repair (MMR) deficiency is one of the best understood forms of genetic instability in colorectal cancer (CRC). CRC is routinely cured by 5-fluorouracil (5-FU)-based chemotherapy, with a prognostic effect and resistance to such therapy conferred by MMR status. In this study, we aimed to analyse the effect of genetic variants in classical coding regions or in less-explored predicted microRNA (miRNA)-binding sites in the 3' untranslated region (3'UTR) of MMR genes on the risk of CRC, prognosis and the efficacy of 5-FU therapy. Four single nucleotide polymorphisms (SNPs) in MMR genes were initially tested for susceptibility to CRC in a case-control study (1095 cases and 1469 healthy controls). Subsequently, the same SNPs were analysed for their role in survival on a subset of patients with complete follow-up. Two SNPs in MLH3 and MSH6 were associated with clinical outcome. Among cases with colon and sigmoideum cancer, carriers of the CC genotype of rs108621 in the 3'UTR of MLH3 showed a significantly increased survival compared to those with the CT + TT genotype (log-rank test, P = 0.05). Moreover, this polymorphism was also associated with an increased risk of relapse or metastasis in patients with heterozygous genotype (log-rank test, P = 0.03). Patients carrying the CC genotype for MSH6 rs1800935 (D180D) and not undergoing 5-FU-based chemotherapy showed a decreased number of recurrences (log-rank test, P = 0.03). No association with CRC risk was observed. We provide the first evidence that variations in potential miRNA target-binding sites in the 3'UTR of MMR genes may contribute to modulate CRC prognosis and predictivity of therapy.

• MeSH
• dospělí MeSH
• enzymy opravy DNA genetika   MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• Kaplanův-Meierův odhad MeSH
• kolorektální nádory genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• oprava chybného párování bází DNA genetika   MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol 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
• práce podpořená grantem MeSH