Therapeutic plasma exchange (PLEX) is an adjunctive treatment for patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and kidney involvement. Little is known about the effect of PLEX on early changes in kidney function. This post-hoc analysis of the PEXIVAS trial investigated the effects of PLEX on changes in kidney function within 12 months. PEXIVAS was a randomized controlled trial recruiting 691 patients with ANCA-associated glomerulonephritis, of whom 349 underwent PLEX and 342 received no-PLEX. The primary outcomes of this post hoc study of PEXIVAS were change in estimated glomerular filtration rate (eGFR) from baseline and recovery of kidney function (defined as eGFR increase of 15ml/min/1.73m2 or more). Baseline eGFR was 21.7 ± 20.3 and 20.6 ± 18.7 ml/min/1.73m2 in the PLEX and no-PLEX groups, respectively. Mean improvements in eGFR at weeks two, four, and eight after initiation of therapy were greater for the PLEX vs. the no-PLEX groups. The greatest significant difference in recovery of kidney function in the PLEX compared to the no-PLEX groups was at week four (relative risk (RR): 1.41; 95% confidence interval:1.09-1.82). Increased eGFR or recovery of kidney function at week four were significantly associated with lower risk for end-stage kidney disease at week 52 (RR: 0.96: 0.95-0.97, and RR: 0.29: 0.16-0.52; respectively). Neither changes in eGFR nor recovery of kidney function differed by reduced- compared to standard-dose glucocorticoid group. Overall, our study indicates that PLEX improves early kidney function in patients with ANCA-associated glomerulonephritis.

• MeSH
• ANCA-asociované vaskulitidy * patofyziologie   terapie   farmakoterapie   komplikace   imunologie   diagnóza   MeSH
• dospělí MeSH
• glomerulonefritida * patofyziologie   imunologie   terapie   krev   MeSH
• glukokortikoidy * terapeutické užití   aplikace a dávkování   MeSH
• hodnoty glomerulární filtrace * MeSH
• ledviny * patofyziologie   účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• obnova funkce MeSH
• senioři MeSH
• výměna plazmy * 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
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

PURPOSE: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment. METHODS: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study. All patients were initially treated with high-dose systemic glucocorticoids. Rituximab was later administered to 29 of 42 corticoresistant patients. RESULTS: The CAS of the corticoresistant patients was significantly higher both before (p = 0.0001) and after (p = <0.0001) first-line treatment compared to the corticosensitive group. ROC analysis established the cut-point value as CAS ≥ 2.5 with a sensitivity of 96.3%, specificity of 57.5% and area under the curve of 82.8%. In 22 patients treated with rituximab, CAS gradually decreased to zero values without reactivation during extended follow-up. There was no difference in the TSI of corticosensitive and corticoresistant patients before or after first-line therapy. CONCLUSION: CAS ≥ 2, after first-line treatment, could be used as a corticoresistance marker. Corticoresistant patients should be subject to long-term follow-up for early detection of reactivation to reduce the delay to second-line treatment. Rituximab is a well-tolerated choice of second-line treatment and has a long-lasting effect on disease activity. Although TSI is a valuable biomarker of Graves' disease and TED activity, according to our results, TSI cannot be used as a marker of corticoresistance.

• MeSH
• dospělí MeSH
• glukokortikoidy terapeutické užití   MeSH
• Gravesova oftalmopatie * farmakoterapie   krev   MeSH
• imunoglobuliny stimulující tyreoideu krev   MeSH
• imunologické faktory terapeutické užití   MeSH
• léková rezistence * MeSH
• lidé středního věku MeSH
• lidé MeSH
• retrospektivní studie MeSH
• rituximab * terapeutické užití   MeSH
• senioři 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

Background: Low back pain (LBP) is one of the common musckloskeletal diseases and usual treated by epidural steroid injection (ESI). ESIs improve patients' quality of life, reduce lumbar radicular pain, and postpone spinal surgery. The mechanism of improvement is yet unscertain, perhaps involve type α collagen (COL2α) for bone maintenance, hence, we sought to investigate the role of injected steroids in bone healing focusing on the role of COL2α.Methods: All patients in this research were diagnosed by specialists based on their histories and clinical features and associated diseaeses or compiling therapy. Serum samples collected from LBP patients and control group for comparisons.Results: The present study found a significant (<0.0001) increase in the concentration of COL2α in patients with LBP after injection with ESI treatment compared with patients before injection and healthy individuals.Conclusion: ESI helps LBP sufferers by boosting COL2α, which repairs damaged tissues.

• MeSH
• biologické markery analýza   MeSH
• bolesti zad * farmakoterapie   MeSH
• glukokortikoidy aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• injekce epidurální * metody   MeSH
• klinická studie jako téma metody   MeSH
• kolagen typ II * aplikace a dávkování   farmakologie   terapeutické užití   MeSH
• lidé MeSH
• management bolesti metody   MeSH
• radikulopatie etiologie   farmakoterapie   MeSH
• regenerace kostí účinky léků   MeSH
• Check Tag
• lidé MeSH

INTRODUCTION: Glucocorticoids (GCs) are widely used as a treatment for rheumatoid arthritis (RA), leading to high cumulative doses in long-term treated patients. The impact of a high cumulative GC dose on the systemic inflammatory response in RA remains poorly understood. METHODS: We investigated long-treated patients with RA (n = 72, median disease duration 14 years) through blood counts and the serum levels of 92 inflammation-related proteins, and disease activity was assessed using the Simple Disease Activity Index (SDAI). Patients were grouped based on the cumulative GC dose, with a cut-off value of 20 g (low/high, n = 49/23). RESULTS AND DISCUSSION: Patients with a high cumulative GC dose within the active RA group had elevated serum levels in 23 inflammation-related proteins compared with patients with a low dose (cytokines/soluble receptors: CCL3, CCL20, CCL25, IL-8, CXCL9, IL-17A, IL-17C, IL-18, sIL-18R1, IL-10, sIL-10RB, OSM and sOPG; growth factors: sTGFα and sHGF; other inflammatory mediators: caspase 8, STAMBP, sCDCP1, sirtuin 2, 4E-BP1, sCD40, uPA and axin-1; pcorr < 0.05). In non-active RA, the high and low GC groups did not differ in analysed serum protein levels. Moreover, patients with active RA with a high GC dose had an increased white blood cell count, increased neutrophil-lymphocyte and platelet-lymphocyte ratios and a decreased lymphocyte-monocyte ratio compared with the low dose group (p < 0.05). This is the first study to report elevated serum levels in inflammation-related proteins and deregulated blood counts in patients with active RA with a high cumulative GC dose. The elevated systemic inflammation highlights the importance of improving care for patients receiving high cumulative GC doses.

• MeSH
• biologické markery krev   MeSH
• cytokiny krev   MeSH
• dospělí MeSH
• glukokortikoidy * aplikace a dávkování   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mediátory zánětu * krev   metabolismus   MeSH
• revmatoidní artritida * farmakoterapie   krev   imunologie   MeSH
• senioři MeSH
• zánět MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• antiflogistika nesteroidní farmakologie   klasifikace   terapeutické užití   MeSH
• antiflogistika * farmakologie   imunologie   klasifikace   terapeutické užití   MeSH
• antimetabolity farmakologie   klasifikace   terapeutické užití   MeSH
• glukokortikoidy aplikace a dávkování   farmakologie   škodlivé účinky   terapeutické užití   MeSH
• imunosupresiva * farmakologie   imunologie   klasifikace   terapeutické užití   MeSH
• imunosupresivní léčba klasifikace   metody   MeSH
• inhibitory kalcineurinu aplikace a dávkování   farmakologie   metabolismus   terapeutické užití   MeSH
• mTOR inhibitory aplikace a dávkování   farmakologie   klasifikace   terapeutické užití   MeSH
• nežádoucí účinky léčiv klasifikace   MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• alergeny imunologie   klasifikace   MeSH
• alergie * diagnóza   farmakoterapie   imunologie   patofyziologie   MeSH
• anafylaxe farmakoterapie   MeSH
• antagonisté leukotrienů farmakologie   klasifikace   terapeutické užití   MeSH
• antihistaminika farmakologie   klasifikace   terapeutické užití   MeSH
• bronchodilatancia farmakologie   klasifikace   terapeutické užití   MeSH
• desenzibilizace imunologická klasifikace   metody   MeSH
• glukokortikoidy farmakologie   klasifikace   terapeutické užití   MeSH
• imunoglobulin E imunologie   MeSH
• stabilizátory mastocytů farmakologie   terapeutické užití   MeSH
• Publikační typ
• přehledy MeSH

Resistance to glucocorticoids (GC), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-offunction experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GC-resistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GC against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL.

• MeSH
• antigeny CD9 * metabolismus   genetika   MeSH
• chemorezistence * genetika   MeSH
• dexamethason farmakologie   MeSH
• dítě MeSH
• glukokortikoidy * farmakologie   terapeutické užití   MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• pre-B-buněčná leukemie * farmakoterapie   metabolismus   genetika   patologie   MeSH
• předškolní dítě MeSH
• receptory glukokortikoidů metabolismus   genetika   MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Pacienti s nešpecifickými zápalovými ochoreniami čreva vykazujú významné odlišnosti vo fenotypových prejavoch ochorenia ako aj odpovedi na liečbu. Výrazná interindividuálna variabilita liečebnej odozvy viedla v posledných rokoch k výskumným iniciatívam zameraným na identifikáciu genetických markerov schopných prispieť k optimalizácii liečebných stratégií. Do klinickej praxe sa implementovalo napríklad vyšetrovanie prediktívnych markerov tiopurínmi-indukovanej myelosupresie. Na druhej strane, markery súvisiace s novšími liečebnými možnosťami, akou je napríklad biologická liečba, sa v bežnej praxi zatiaľ nevyužívajú. Článok ponúka prehľad pokrokov na poli farmakogenetiky IBD, sumarizuje známe farmakogenetické markery ako aj tzv. kandidátne gény a zaoberá sa ich perspektívnym využitím v personalizácii liečby IBD.

Patients with inflammatory bowel diseases show significant differences in phenotypic manifestation as well as responses to treatment. Significant interindividual variability in therapeutic response has led in recent years to research initiatives aimed at identifying genetic markers capable of optimizing the treatment. For example, investigation of predictive markers of thiopurine-induced myelosuppression has been implemented into clinical practice. On the other hand, markers related to new treatment options such as biological treatment are not yet used in common clinical practice. The article offers an overview of advances in the field of IBD pharmacogenetics, summarizes known pharmacogenetic markers as well as the candidate genes and their prospective use in the personalization of IBD treatment.

• MeSH
• dítě MeSH
• farmakogenetika * klasifikace   metody   MeSH
• genetické markery genetika   MeSH
• glukokortikoidy farmakologie   genetika   klasifikace   terapeutické užití   MeSH
• idiopatické střevní záněty * diagnóza   farmakoterapie   genetika   klasifikace   MeSH
• individualizovaná medicína metody   MeSH
• inhibitory TNF farmakologie   klasifikace   terapeutické užití   MeSH
• kyseliny aminosalicylové farmakologie   klasifikace   terapeutické užití   MeSH
• lidé MeSH
• mutace genetika   MeSH
• puriny farmakologie   klasifikace   terapeutické užití   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• dyslipidemie farmakoterapie   MeSH
• glukokortikoidy aplikace a dávkování   terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• infarkt myokardu bez ST elevací terapie   MeSH
• lidé MeSH
• myozitida chemicky indukované   diagnóza   farmakoterapie   MeSH
• nemoci svalů * chemicky indukované   diagnóza   farmakoterapie   MeSH
• senioři MeSH
• statiny * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

Allergic rhinitis is a common ailment in primary and acute care settings. Diagnosis is clinical, by means of history and physical examination. Referral to an allergist is considered when symptoms are difficult to manage and/or confirmation by means of further testing is desired. Management of allergic rhinitis should not be considered trivial, as multiple secondary effects can present as the course progresses. Several treatment modalities exist but should begin with glucocorticoid nasal sprays and systemic second- or third-generation antihistamines.

• MeSH
• alergická rýma * diagnóza   terapie   farmakoterapie   MeSH
• antihistaminika terapeutické užití   MeSH
• glukokortikoidy terapeutické užití   aplikace a dávkování   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH