• MeSH
• augmentace alveolárního výběžku metody   MeSH
• časové faktory MeSH
• dentální technologie MeSH
• hodnocení rizik MeSH
• lidé MeSH
• podpěry zubní normy   MeSH
• zubní náhrada ve spojení s implantáty * metody   MeSH
• zubní náhrady úplné okamžité MeSH
• zubní protéza - design MeSH
• Check Tag
• lidé MeSH

• MeSH
• infekční nemoci MeSH
• nemoci nosu MeSH
• otorinolaryngologické nemoci MeSH
• sinusitida MeSH
• zánět čelistní dutiny MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• otorinolaryngologie
• infekční lékařství

• MeSH
• akutní nemoc MeSH
• antibakteriální látky terapeutické užití   MeSH
• hodnocení rizik MeSH
• infekce získané v komunitě MeSH
• management nemoci MeSH
• sinusitida farmakoterapie   imunologie   MeSH
• zánět čelistní dutiny farmakoterapie   imunologie   MeSH
• Publikační typ
• sborníky MeSH
• Geografické názvy
• Francie MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• otorinolaryngologie
• alergologie a imunologie

The growing use of medical devices (e.g., vascular grafts, stents, and cardiac catheters) for temporary or permanent purposes that remain in the body's circulatory system demands a reliable and multiparametric approach that evaluates the possible hematologic complications caused by these devices (i.e., activation and destruction of blood components). Comprehensive in vitro hemocompatibility testing of blood-contacting implants is the first step towards successful in vivo implementation. Therefore, extensive analysis according to the International Organization for Standardization 10993-4 (ISO 10993-4) is mandatory prior to clinical application. The presented flow loop describes a sensitive model to analyze the hemostatic performance of stents (in this case, neurovascular) and reveal adverse effects. The use of fresh human whole blood and gentle blood sampling are essential to avoid the preactivation of blood. The blood is perfused through a heparinized tubing containing the test specimen by using a peristaltic pump at a rate of 150 mL/min at 37 °C for 60 min. Before and after perfusion, hematologic markers (i.e., blood cell count, hemoglobin, hematocrit, and plasmatic markers) indicating the activation of leukocytes (polymorphonuclear [PMN]-elastase), platelets (β-thromboglobulin [β-TG]), the coagulation system (thombin-antithrombin III [TAT]), and the complement cascade (SC5b-9) are analyzed. In conclusion, we present an essential and reliable model for extensive hemocompatibility testing of stents and other blood-contacting devices prior to clinical application.

• MeSH
• beta-thromboglobulin metabolismus   MeSH
• biologické markery metabolismus   MeSH
• biologické modely * MeSH
• cévní protézy * MeSH
• heparin farmakologie   MeSH
• imunitní systém metabolismus   MeSH
• komplement metabolismus   MeSH
• krevní oběh účinky léků   fyziologie   MeSH
• krevní obraz MeSH
• krevní plazma MeSH
• lidé MeSH
• odběr vzorku krve MeSH
• pankreatická elastasa metabolismus   MeSH
• stenty MeSH
• testování materiálů metody   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• audiovizuální média MeSH
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The prognosis for patients with relapsed and/or refractory (R/R) non-Hodgkin's lymphoma (NHL) or acute lymphoblastic leukaemia (ALL) remains poor, with existing treatments having significant side effects. Developed for the treatment of these cancers, AFM11 is a tetravalent, bispecific humanised recombinant antibody construct (TandAb®) designed to bind to human CD19 and CD3 and lead to the activation of T cells inducing apoptosis and killing of malignant B cells. METHODS: Two open-label, multicentre, dose-escalation phase 1 studies evaluated the safety, pharmacokinetics and activity of AFM11 in patients with R/R CD19-positive B cell NHL (AFM11-101) and in patients with CD19 + B-precursor Philadelphia-chromosome negative ALL (AFM11-102). Adverse events (AEs) were assessed and recorded; imaging (NHL) or bone marrow assessment (ALL) were used to evaluate response. Additional pharmacodynamic assays undertaken included cytokine release analysis and B-cell and T-cell depletion. RESULTS: In AFM11-101, 16 patients with R/R NHL received AFM11 in five different dose cohorts. Of which, 14 experienced drug-related treatment-emergent AEs (TEAEs) [including five serious AEs (SAEs)], five patients experienced dose-limiting toxicity (DLT) and ten patients discontinued the study. The high number of neurological events led to a decrease in infusion frequency during the study. No objective response to treatment was observed. In AFM11-102, 17 patients with R/R ALL received AFM11 in six different dose cohorts. Thirteen patients experienced drug-related TEAEs (including four SAEs), DLTs occurred in two patients and five patients discontinued the study. An objective response was recorded in three patients. The maximum tolerated dose could not be determined in either study due to early termination. CONCLUSIONS: AFM11 treatment was associated with frequent neurological adverse reactions that were severe in some patients. In ALL, some signs of activity, albeit short-lived, were observed whereas no activity was observed in patients with NHL; therefore, further clinical development was terminated. TRIAL REGISTRATION: NCT02106091 . Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL. Registered April 2014. NCT02848911 . Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL. Registered July 2016.

• MeSH
• antitumorózní látky * škodlivé účinky   MeSH
• cytokiny MeSH
• dospělí MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• nehodgkinský lymfom * farmakoterapie   patologie   MeSH
• protilátky bispecifické * farmakologie   terapeutické užití   MeSH
• T-lymfocyty MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH

BACKGROUND: The early repolarization (ER) pattern is associated with an increased risk of arrhythmogenic sudden death. However, strategies for risk stratification of patients with the ER pattern are not fully defined. OBJECTIVES: This study sought to determine the role of electrophysiology studies (EPS) in risk stratification of patients with ER syndrome. METHODS: In a multicenter study, 81 patients with ER syndrome (age 36 ± 13 years, 60 males) and aborted sudden death due to ventricular fibrillation (VF) were included. EPS were performed following the index VF episode using a standard protocol. Inducibility was defined by the provocation of sustained VF. Patients were followed up by serial implantable cardioverter-defibrillator interrogations. RESULTS: Despite a recent history of aborted sudden death, VF was inducible in only 18 of 81 (22%) patients. During follow-up of 7.0 ± 4.9 years, 6 of 18 (33%) patients with inducible VF during EPS experienced VF recurrences, whereas 21 of 63 (33%) patients who were noninducible experienced recurrent VF (p = 0.93). VF storm occurred in 3 patients from the inducible VF group and in 4 patients in the noninducible group. VF inducibility was not associated with maximum J-wave amplitude (VF inducible vs. VF noninducible; 0.23 ± 0.11 mV vs. 0.21 ± 0.11 mV; p = 0.42) or J-wave distribution (inferior, odds ratio [OR]: 0.96 [95% confidence interval (CI): 0.33 to 2.81]; p = 0.95; lateral, OR: 1.57 [95% CI: 0.35 to 7.04]; p = 0.56; inferior and lateral, OR: 0.83 [95% CI: 0.27 to 2.55]; p = 0.74), which have previously been demonstrated to predict outcome in patients with an ER pattern. CONCLUSIONS: Our findings indicate that current programmed stimulation protocols do not enhance risk stratification in ER syndrome.

• MeSH
• časové faktory MeSH
• dospělí MeSH
• elektrokardiografie metody   MeSH
• fibrilace komor komplikace   diagnóza   patofyziologie   MeSH
• incidence MeSH
• lidé MeSH
• míra přežití trendy   MeSH
• náhlá srdeční smrt epidemiologie   etiologie   prevence a kontrola   MeSH
• následné studie MeSH
• prediktivní hodnota testů MeSH
• převodní systém srdeční patofyziologie   MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

Plant growth and architecture is regulated by the polar distribution of the hormone auxin. Polarity and flexibility of this process is provided by constant cycling of auxin transporter vesicles along actin filaments, coordinated by a positive auxin-actin feedback loop. Both polar auxin transport and vesicle cycling are inhibited by synthetic auxin transport inhibitors, such as 1-N-naphthylphthalamic acid (NPA), counteracting the effect of auxin; however, underlying targets and mechanisms are unclear. Using NMR, we map the NPA binding surface on the Arabidopsis thaliana ABCB chaperone TWISTED DWARF1 (TWD1). We identify ACTIN7 as a relevant, although likely indirect, TWD1 interactor, and show TWD1-dependent regulation of actin filament organization and dynamics and that TWD1 is required for NPA-mediated actin cytoskeleton remodeling. The TWD1-ACTIN7 axis controls plasma membrane presence of efflux transporters, and as a consequence act7 and twd1 share developmental and physiological phenotypes indicative of defects in auxin transport. These can be phenocopied by NPA treatment or by chemical actin (de)stabilization. We provide evidence that TWD1 determines downstream locations of auxin efflux transporters by adjusting actin filament debundling and dynamizing processes and mediating NPA action on the latter. This function appears to be evolutionary conserved since TWD1 expression in budding yeast alters actin polarization and cell polarity and provides NPA sensitivity.

• MeSH
• Arabidopsis genetika   metabolismus   MeSH
• biologický transport genetika   fyziologie   MeSH
• kyseliny indoloctové metabolismus   MeSH
• mikrofilamenta metabolismus   MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• proteiny vázající takrolimus genetika   metabolismus   MeSH
• regulace genové exprese u rostlin genetika   fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• akutní myeloidní leukemie genetika   MeSH
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mutace MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• transportní proteiny genetika   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for most children with juvenile myelomonocytic leukemia (JMML). Novel therapies controlling the disorder prior to HSCT are needed. We conducted a phase 2, multicenter, open-label study to evaluate the safety and antileukemic activity of azacitidine monotherapy prior to HSCT in newly diagnosed JMML patients. Eighteen patients enrolled from September 2015 to November 2017 were treated with azacitidine (75 mg/m2) administered IV once daily on days 1 to 7 of a 28-day cycle. The primary end point was the number of patients with clinical complete remission (cCR) or clinical partial remission (cPR) after 3 cycles of therapy. Pharmacokinetics, genome-wide DNA-methylation levels, and variant allele frequencies of leukemia-specific index mutations were also analyzed. Sixteen patients completed 3 cycles and 5 patients completed 6 cycles. After 3 cycles, 11 patients (61%) were in cPR and 7 (39%) had progressive disease. Six of 16 patients (38%) who needed platelet transfusions were transfusion-free after 3 cycles. All 7 patients with intermediate- or low-methylation signatures in genome-wide DNA-methylation studies achieved cPR. Seventeen patients received HSCT; 14 (82%) were leukemia-free at a median follow-up of 23.8 months (range, 7.0-39.3 months) after HSCT. Azacitidine was well tolerated and plasma concentration--time profiles were similar to observed profiles in adults. In conclusion, azacitidine monotherapy is a suitable option for children with newly diagnosed JMML. Although long-term safety and efficacy remain to be fully elucidated in this population, these data demonstrate that azacitidine provides valuable clinical benefit to JMML patients prior to HSCT. This trial was registered at www.clinicaltrials.gov as #NCT02447666.

• MeSH
• azacytidin škodlivé účinky   MeSH
• dítě MeSH
• dospělí MeSH
• juvenilní myelomonocytární leukemie * farmakoterapie   genetika   MeSH
• lidé MeSH
• metylace DNA MeSH
• mutace MeSH
• transplantace hematopoetických kmenových buněk * MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

CONTEXT: Adrenal gland imaging is recommended by the current guidelines for the workup of primary aldosteronism (PA). However, its diagnostic performance has not been established in large, multiethnic cohorts of patients who undergo adrenal vein sampling (AVS) and adrenalectomy. OBJECTIVE: This work aims to assess the diagnostic accuracy of cross-sectional adrenal imaging. METHODS: This international multicenter study took place in tertiary referral centers. A total of 1625 PA patients seeking surgical cure were enrolled in an international study involving 19 centers in North America, Europe, Asia, and Australia. Of these, 1311 (81%) had imaging data available and 369 (23%), who received a final diagnosis of surgically cured unilateral PA, were examined. Patients underwent AVS and imaging by computed tomography and/or magnetic resonance imaging. The accuracy of detection of unilateral PA at imaging was estimated by the area under the receiver operator characteristics curve using cure (biochemical and/or full clinical success) as the reference at follow-up after unilateral adrenalectomy. RESULTS: In the cohort of 1311 patients with imaging data available, 34% and 7% of cases showed no detectable or bilateral nodules, respectively. Imaging did not detect the culprit adrenal in 28% of the surgically cured unilateral PA patients. Moreover, the clinical outcome did not differ significantly between the imaging-positive and imaging-negative patients. CONCLUSION: Cross-sectional imaging did not identify a lateralized cause of disease in around 40% of PA patients and failed to identify the culprit adrenal in more than one-fourth of patients with unilateral PA.

• MeSH
• adrenalektomie metody   MeSH
• aldosteron krev   MeSH
• dospělí MeSH
• hyperaldosteronismus diagnostické zobrazování   patologie   chirurgie   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nadledviny krevní zásobení   diagnostické zobrazování   MeSH
• počítačová rentgenová tomografie MeSH
• retrospektivní studie MeSH
• senzitivita a specificita MeSH
• vény MeSH
• výsledek terapie 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
• práce podpořená grantem MeSH
• Geografické názvy
• Asie MeSH
• Austrálie MeSH
• Evropa MeSH
• Severní Amerika MeSH