OBJECTIVE: The aim of the study was the assessment of adherence to antiretroviral (ARV) treatment in a population of people living with HIV (PWH), improving the awareness of PWH, drawing attention to the risk of developing HIV drug resistance and subsequent treatment failure. METHODS: The basic cohort consisted of PWH followed up long-term at the HIV centre of the University Hospital Pilsen. Adherence to treatment was assessed by ARV levels. Nucleoside analogs were determined in urine by high pressure liquid chromatography (HPLC), in relation to clinical data, viral load (HIV RNA), and absolute CD4 and CD8 T cell counts. To assess mental and physical state of the patients, a modified SF-36 questionnaire was used to measure social relationships, education and ability to relax. RESULTS: From a group of 131 PWH, 18 (13.7%) with zero levels and 113 (86.3%) with any detectable ARV levels were followed for 6-12 months. A statistically significant lower viral load was demonstrated in patients who adhered to the treatment at the time of the test as indicated by ARV levels in the urine. CD4 T lymphocyte values in adherent patients were, as expected, statistically significantly higher. A significant difference for CD8 T lymphocyte was not demonstrated. A survey assessed subjective factors influencing the degree of adherence. PWH consider important: quality care enabling trust, low risk of developing opportunistic infections, self-sufficiency, quality of sleep, managing leisure activities, and good family relationships. Quality of life evaluation and satisfaction in the monitored areas were similar in both groups of PWH. CONCLUSIONS: Non-adherence leads to deterioration of CD4 and viral load levels and may be the cause of the development of HIV drug resistance and treatment failure on the part of the patient. PWH with zero or low urinary nucleoside levels were repeatedly instructed about the need for regular and sustained medication use. Regular checks with a laboratory examination service are needed to detect early emergence of resistance and side effects of the treatment, which are initially only detectable in the laboratory.

• MeSH
• adherence k farmakoterapii * psychologie   MeSH
• dospělí MeSH
• HIV infekce * farmakoterapie   psychologie   MeSH
• kohortové studie MeSH
• kvalita života * MeSH
• látky proti HIV * terapeutické užití   moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet CD4 lymfocytů MeSH
• virová nálož MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Persistent selective T-lymphocytopenia is found both in SCID and congenital athymia. Without molecular diagnosis, it is challenging to determine whether HCT or thymus transplantation ought to be performed. Ex vivo T-lymphopoiesis assays have been proposed to assist clinical decision-making for genetically undefined patients. We investigated 20 T-lymphocytopenic patients, including 13 patients awaiting first-line treatment and 7 patients with failed immune reconstitution after previous HCT or thymus transplantation. Whilst developmental blocks in ex vivo T-lymphopoiesis indicated hematopoietic cell-intrinsic defects, successful T-lymphocyte differentiation required careful interpretation, in conjunction with clinical status, immunophenotyping, and genetic investigations. Of the 20 patients, 13 proceeded to treatment, with successful immune reconstitution observed in 4 of the 6 patients post-HCT and 4 of the 7 patients after thymus transplantation, the latter including two patients who had previously undergone HCT. Whilst further validation and standardization are required, we conclude that assessing ex vivo T-lymphopoiesis during the diagnostic pathway for genetically undefined T-lymphocytopenia improves patient outcomes by facilitating corrective treatment choice.

• MeSH
• buněčná diferenciace MeSH
• dítě MeSH
• imunofenotypizace MeSH
• kojenec MeSH
• lidé MeSH
• lymfopenie * imunologie   MeSH
• lymfopoéza * genetika   MeSH
• mladiství MeSH
• předškolní dítě MeSH
• primární imunodeficience terapie   genetika   imunologie   MeSH
• T-lymfocyty * imunologie   MeSH
• thymus imunologie   MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 109/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 109/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 109/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 109/L or ≥ 30 × 109/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 109/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients. Trial Registration: NCT03395210, EudraCT 2017-004012-19.

• MeSH
• aplikace orální MeSH
• dospělí MeSH
• idiopatická trombocytopenická purpura * farmakoterapie   MeSH
• inhibitory proteinkinas * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• inhibitory tyrosinkinasy MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet trombocytů MeSH
• proteinkinasa BTK * antagonisté a inhibitory   MeSH
• pyrazoly terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• pyrimidiny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie 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
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH

BACKGROUND: The present study aimed to investigate the prognostic and predictive roles of Hb/RDW ratio in patients with mRCC treated with first-line immunotherapy combinations (TKI plus ICI or ICI plus ICI). MATERIALS AND METHODS: We performed a sub-analysis of a multicenter retrospective observational study (ARON-1 project) involving patients with mRCC treated with first-line immunotherapy combinations. RESULTS: Three hundred and twenty-nine patients were enrolled, 244 males and 85 females. Median age was 65.5 years. The prognostic impact of the Hb/RDW ratio on PFS and OS was observed in the whole population examined. Hb/RDW ratio had a correlation with neutrophil-to-lymphocyte ratio (NLR), a blood inflammatory parameter. CONCLUSION: Hb/RDW ratio is a new inflammatory prognostic factor, easy to use in daily clinical practice.

• MeSH
• dospělí MeSH
• erytrocytární znaky MeSH
• hemoglobiny * analýza   metabolismus   MeSH
• imunoterapie * metody   MeSH
• inhibitory kontrolních bodů terapeutické užití   MeSH
• karcinom z renálních buněk * farmakoterapie   terapie   krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory ledvin * farmakoterapie   terapie   krev   patologie   mortalita   imunologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři 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
• multicentrická studie MeSH
• pozorovací studie MeSH

WBP1L is a broadly expressed transmembrane adaptor protein involved in regulating hematopoietic stem cell function and T cell development. It interacts with NEDD4-family E3 ubiquitin ligases and regulates important chemokine receptor CXCR4. Using tandem affinity purification coupled with mass spectrometry, we identified novel WBP1L interactions with the IFNγ receptor and the Cullin-RING ubiquitin ligases CRL1β-TrCP1/2. We found that WBP1L interaction with the IFNγ receptor serves to downregulate proximal IFNγ receptor signaling in female macrophages, while the interaction with CRL1β-TrCP1/2 ubiquitin ligases regulates WBP1L protein levels. Disrupting this interaction, as well as inhibiting proteasome activity or neddylation, increased WBP1L protein levels, demonstrating that CRL1β-TrCP1/2 ubiquitin ligases regulate WBP1L protein abundance. These data provide important insights into the mechanisms controlling WBP1L function.

• MeSH
• adaptorové proteiny signální transdukční metabolismus   MeSH
• HEK293 buňky MeSH
• hematopoéza * MeSH
• lidé MeSH
• makrofágy metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• myši MeSH
• proteiny s repetitivními sekvencemi beta-transducinu metabolismus   MeSH
• signální transdukce MeSH
• ubikvitinligasy * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• tranzitorní abnormální myelopoéza,
• MeSH
• Downův syndrom * diagnóza   komplikace   MeSH
• kazuistiky jako téma MeSH
• leukocytóza krev   patofyziologie   MeSH
• lidé MeSH
• multiorgánové selhání * diagnóza   etiologie   MeSH
• myelopoéza imunologie   MeSH
• myeloproliferativní poruchy diagnóza   etiologie   klasifikace   MeSH
• novorozenec nedonošený MeSH
• novorozenec MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• přehledy MeSH

Ischemic stroke is a common and serious condition. Timely restoration of cerebral perfusion is crucial for improving patient outcomes and reducing economic impacts. For three decades, alteplase has been the only established pharmacological treatment, often combined with endovascular therapy. Tenecteplase, a newer generation of fibrinolytic therapy, is recommended by the ESO 2023 guidelines as a suitable alternative to alteplase, particularly if treatment is initiated within 4.5 hours of symptom onset. Tenecteplase offers higher fibrin specificity, lower binding to PAI-1, and a longer plasma half-life compared to alteplase, allowing for single bolus administration. Clinical studies have shown that tenecteplase 0.25 mg/kg achieves better recanalization and clinical improvement without increased risk of bleeding. It is equally effective and safe as alteplase, with meta-analyses indicating improved recanalization and clinical outcomes at a lower risk of bleeding. Tenecteplase is a suitable alternative for treating iNCMP, especially within 4.5 hours of symptom onset. Its single bolus administration simplifies hospital management and improves the logistics of transporting patients to specialized centers.

• MeSH
• fibrinolýza účinky léků   MeSH
• ischemická cévní mozková příhoda * diagnóza   farmakoterapie   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• reperfuze klasifikace   metody   MeSH
• tenektepláza * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• tkáňový aktivátor plazminogenu farmakologie   terapeutické užití   MeSH
• trombolytická terapie klasifikace   metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

An imbalance in coagulation is associated with cardiovascular events. For prevention and treatment, anticoagulants, currently mainly xabans and gatrans, are used. The purpose of the present study was to provide a head-to-head comparison since there are no studies directly evaluating these novel anticoagulants. An additional aim was to find whether selected anthropological and biochemical factors can affect their anticoagulant properties as they are used in fixed doses. In this cross-sectional study, blood from 50 generally healthy donors was collected, and coagulation responses to dabigatran, argatroban, rivaroxaban, and apixaban, at a concentration of 1 μM, were analyzed. Heparin was used as a positive control. Prothrombin time (PT) expressed as international normalized ratio (INR) and activated partial thromboplastin time (aPTT) were measured and compared. Rivaroxaban was the most active according to PT/INR while argatroban according to aPTT. The ex vivo anticoagulant effect measured by INR correlated inversely with body mass index (BMI) in all four anticoagulants tested. Shortening of aPTT was associated with higher cholesterol and triglyceride levels. No sex-related differences were observed in response to the anticoagulant treatments. As this was an ex vivo study and pharmacokinetic factors were not included, the influence of BMI is of high therapeutic importance.

• MeSH
• antikoagulancia * farmakologie   MeSH
• arginin * analogy a deriváty   MeSH
• dabigatran farmakologie   MeSH
• dospělí MeSH
• hemokoagulace * účinky léků   MeSH
• index tělesné hmotnosti MeSH
• INR MeSH
• kyseliny pipekolové * farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• parciální tromboplastinový čas MeSH
• protrombinový čas MeSH
• průřezové studie MeSH
• pyrazoly farmakologie   MeSH
• pyridony farmakologie   farmakokinetika   MeSH
• rivaroxaban * farmakologie   MeSH
• sulfonamidy farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

OBJECTIVES: To evaluate the base excess response during acute in vivo carbon dioxide changes. DESIGN: Secondary analysis of individual participant data from experimental studies. SETTING: Three experimental studies investigating the effect of acute in vivo respiratory derangements on acid-base variables. SUBJECTS: Eighty-nine (canine and human) carbon dioxide exposures. INTERVENTIONS: Arterial carbon dioxide titration through environmental chambers or mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: For each subject, base excess was calculated using bicarbonate and pH using a fixed buffer power of 16.2. Analyses were performed using linear regression with arterial dioxide (predictor), base excess (outcome), and studies (interaction term). All studies show different baselines and slopes for base excess across carbon dioxide titrations methods. Individual subjects show substantial, and potentially clinically relevant, variations in base excess response across the hypercapnic range. Using a mathematical simulation of 10,000 buffer power coefficients we determined that a coefficient of 12.1 (95% CI, 9.1-15.1) instead of 16.2 facilitates a more conceptually appropriate in vivo base excess equation for general clinical application. CONCLUSIONS: In vivo changes in carbon dioxide leads to changes in base excess that may be clinically relevant for individual patients. A buffer power coefficient of 16.2 may not be appropriate in vivo and needs external validation in a range of clinical settings.

• MeSH
• acidobazická rovnováha * fyziologie   MeSH
• dospělí MeSH
• hyperkapnie patofyziologie   metabolismus   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• oxid uhličitý * metabolismus   MeSH
• poruchy acidobazické rovnováhy patofyziologie   metabolismus   MeSH
• psi MeSH
• umělé dýchání MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• psi MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Referrals to emergency services are frequently made for acute appendicitis and renal colic. This conundrum of patients with acute appendicitis and right ureteral stones frequently presents itself to emergency physicians. The hematological parameters of patients suffering from acute appendicitis and right ureteral stones were compared in this study. From May 2022 to April 2023 the patients who applied to emergency department were reviewed retrospectively. Of these patients, age, sex, complete blood test results including white blood cell, procalcitonin and C-reactive protein were recorded. The platelet to lymphocyte ratio and the neutrophil to lymphocyte ratio were calculated by dividing the platelet count by the lymphocyte, and the neutrophil count by the lymphocyte count, respectively. We used the receiver operating characteristic curves to assess the diagnostic efficacy of hematological markers. There were 106 patients in the study. The mean age of the patients was 43.83 ± 15.82 years. The significant difference was found for age, white blood cell, neutrophil, lymphocyte, neutrophil to lymphocyte ratio, platelet to lymphocyte ratio and monocyte between groups. The white blood cell and neutrophil to lymphocyte ratio have the biggest area than the other parameters in the receiver operating characteristic curves. Patients with acute appendicitis have a high level of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio than ureteral stones. Further studies are needed to define the diagnostic efficacy of hematological markers for acute appendicitis and ureteral stones.

• MeSH
• akutní nemoc MeSH
• apendicitida * krev   diagnóza   MeSH
• biologické markery * krev   MeSH
• dospělí MeSH
• kameny v močovodu * krev   diagnóza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet leukocytů MeSH
• retrospektivní studie MeSH
• ROC křivka MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH