OBJECTIVES: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder caused by increased platelet destruction and altered production. Despite the well-described pathophysiological background of immune dysregulation, current treatment guidelines consist of monotherapy with different drugs, with no tool to predict which patient is more suitable for each therapeutic modality. METHODS: In our study, we attempted to determine differences in the immune setting, comparing the patients' responses to administered therapy. During 12-month follow-up, we assessed blood count, antiplatelet autoantibodies, and T lymphocyte subsets in peripheral blood in 35 patients with ITP (newly diagnosed or relapsed disease). RESULTS: Our data show that the value of antiplatelet autoantibodies, the percentage of cytotoxic T lymphocytes, and the immunoregulatory index (IRI, CD4+ / CD8+ T cell ratio) differ significantly by treatment response. Responders have a higher IRI (median 2.1 vs. 1.5 in non-responders, P = 0.04), higher antiplatelet autoantibodies (median 58 vs. 20% in non-responders, P = 0.01) and lower relative CD8+ T cells count (P = 0.02) before treatment. DISCUSSION: The results suggest that immunological parameters (antiplatelet autoantibodies, relative CD8+ T cell count and IRI) could be used as prognostic tools for a worse clinical outcome in patients with ITP. CONCLUSION: These biomarkers could be utilized for stratification and eventually selection of treatment preferring combination therapy.
- MeSH
- autoprotilátky MeSH
- CD8-pozitivní T-lymfocyty MeSH
- idiopatická trombocytopenická purpura * diagnóza farmakoterapie MeSH
- lidé MeSH
- lymfocyty MeSH
- trombocytopenie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Léčba imunitní trombocytopenie (ITP) doznala v době pandemie COVID-19 některých změn. Kromě tradiční terapie první linie se v posledních letech dostává do popředí i terapie agonisty trombopoetinového receptoru a kombinace imunosupresivních terapií. I přesto se stále objevují výzvy v podobě refrakterních případů, které vyžadují agresivnější přístup či terapii novými preparáty mimo schválené indikace nebo v rámci studií. Probíhající pandemie COVID-19 a následný rozmach očkování jsou často jedinou dohledatelnou příčinou nových případů ITP diagnostikovaných v posledních dvou letech. Cílem tohoto článku je shrnout dosavadní léčebná doporučení a zároveň poukázat na nové terapeutické možnosti z posledních let, které zatím nejsou součástí platných guidelines.
Treatment of immune thrombocytopenia (ITP) underwent certain changes during the COVID-19 pandemic. In addition to traditional first-line therapy, thrombopoietin receptor agonists therapy and combination of immunosuppressants have achieved a stronger position in recent years. Nevertheless, there are still refractory cases that require a more aggressive approach or the administration of the new targeted drugs outside the approved indications or studies. The COVID-19 pandemic itself and the subsequent boom in vaccination are often the only unequivocal causes of new cases of ITP diagnosed in the previous two years. The aim of this article is to summarize the current treatment recommendations and highlight possible new therapeutic options according to our single-centre experience.
- Klíčová slova
- TPO mimetika,
- MeSH
- COVID-19 komplikace MeSH
- idiopatická trombocytopenická purpura * etiologie terapie MeSH
- imunosupresivní léčba metody MeSH
- lidé MeSH
- vakcíny proti COVID-19 škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Rilzabrutinib, an oral, reversible covalent inhibitor of Bruton's tyrosine kinase, may increase platelet counts in patients with immune thrombocytopenia by means of dual mechanisms of action: decreased macrophage (Fcγ receptor)-mediated platelet destruction and reduced production of pathogenic autoantibodies. METHODS: In an international, adaptive, open-label, dose-finding, phase 1-2 clinical trial, we evaluated rilzabrutinib therapy in previously treated patients with immune thrombocytopenia. We used intrapatient dose escalation of oral rilzabrutinib over a period of 24 weeks; the lowest starting dose was 200 mg once daily, with higher starting doses of 400 mg once daily, 300 mg twice daily, and 400 mg twice daily. The primary end points were safety and platelet response (defined as at least two consecutive platelet counts of ≥50×103 per cubic millimeter and an increase from baseline of ≥20×103 per cubic millimeter without the use of rescue medication). RESULTS: Sixty patients were enrolled. At baseline, the median platelet count was 15×103 per cubic millimeter, the median duration of disease was 6.3 years, and patients had received a median of four different immune thrombocytopenia therapies previously. All the treatment-related adverse events were of grade 1 or 2 and transient. There were no treatment-related bleeding or thrombotic events of grade 2 or higher. At a median of 167.5 days (range, 4 to 293) of treatment, 24 of 60 patients (40%) overall and 18 of the 45 patients (40%) who had started rilzabrutinib treatment at the highest dose met the primary end point of platelet response. The median time to the first platelet count of at least 50×103 per cubic millimeter was 11.5 days. Among patients with a primary platelet response, the mean percentage of weeks with a platelet count of at least 50×103 per cubic millimeter was 65%. CONCLUSIONS: Rilzabrutinib was active and associated with only low-level toxic effects at all dose levels. The dose of 400 mg twice daily was identified as the dose for further testing. Overall, rilzabrutinib showed a rapid and durable clinical activity that improved with length of treatment. (Funded by Sanofi; ClinicalTrials.gov number, NCT03395210; EudraCT number, 2017-004012-19.).
- MeSH
- aplikace orální MeSH
- idiopatická trombocytopenická purpura * farmakoterapie MeSH
- inhibitory proteinkinas * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- počet trombocytů MeSH
- proteinkinasa BTK antagonisté a inhibitory MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky, fáze I MeSH
- klinické zkoušky, fáze II MeSH
Multiple non-aggregatory functions of human platelets (PLT) are widely acknowledged, yet their functional examination is limited mainly due to a lack of standardized isolation and analytic methods. Platelet apheresis (PA) is an established clinical method for PLT isolation aiming at the treatment of bleeding diathesis in severe thrombocytopenia. On the other hand, density gradient centrifugation (DC) is an isolation method applied in research for the analysis of the mitochondrial metabolic profile of oxidative phosphorylation (OXPHOS) in PLT obtained from small samples of human blood. We studied PLT obtained from 29 healthy donors by high-resolution respirometry for comparison of PA and DC isolates. ROUTINE respiration and electron transfer capacity of living PLT isolated by PA were significantly higher than in the DC group, whereas plasma membrane permeabilization resulted in a 57% decrease of succinate oxidation in PA compared to DC. These differences were eliminated after washing the PA platelets with phosphate buffer containing 10 mmol·L-1 ethylene glycol-bis (2-aminoethyl ether)-N,N,N',N'-tetra-acetic acid, suggesting that several components, particularly Ca2+ and fuel substrates, were carried over into the respiratory assay from the serum in PA. A simple washing step was sufficient to enable functional mitochondrial analysis in subsamples obtained from PA. The combination of the standard clinical PA isolation procedure with PLT quality control and routine mitochondrial OXPHOS diagnostics meets an acute clinical demand in biomedical research of patients suffering from thrombocytopenia and metabolic diseases.
- Publikační typ
- časopisecké články MeSH
- MeSH
- bezvědomí etiologie MeSH
- císařský řez MeSH
- defibrilátory implantabilní MeSH
- dospělí MeSH
- fatální výsledek MeSH
- gestační diabetes MeSH
- hepatitida C komplikace MeSH
- kardiomyopatie * diagnóza farmakoterapie komplikace patofyziologie patologie terapie MeSH
- kardiopulmonální resuscitace MeSH
- komplikace porodu * diagnóza farmakoterapie patofyziologie patologie terapie MeSH
- lidé MeSH
- poporodní období MeSH
- srdeční selhání diagnóza farmakoterapie komplikace patofyziologie patologie terapie MeSH
- těhotenství s dvojčaty MeSH
- těhotenství MeSH
- uživatelé drog MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Cíl práce: Představit jednu z chirurgických metod v léčbě sestupu orgánů pánevního dna a její výsledky na základě dostupné literatury. Metodika: Literární zdroje byly vyhledány pomocí vyhledávače PubMed. Závěr: Sestup orgánů pánevního dna je častý problém postihující až 40 % ženské populace. Základní rizikové faktory jsou vaginální porod, zejména spojený s avulzním poraněním levátoru, rostoucí věk a obezita. Jednou z možností operační léčby je použití vlastních tkání pacientky. Bohužel je stále častou součástí těchto výkonů i hysterektomie. Děloha je však pouze pasivní orgán, který nehraje roli v etiologii sestupu. Ponechání dělohy zachovává původní fixační struktury a kompartmenty a poskytuje kvalitní tkáň ke kotvení stehů. Benigní a zejména maligní onemocnění dělohy a rizikové faktory jejich vzniku jsou kontraindikací k ponechání dělohy. Při sakrospinózní hysteropexi je děloha elevována nevstřebatelnými stehy k jednomu nebo oběma jmenovaným vazům. Závěry prací a metaanalýz ukazují srovnatelné anatomické a funkční výsledky při kratším operačním čase, snížené krevní ztrátě, rychlejší rekonvalescenci a nižší četnosti komplikací v porovnání s hysterektomií a apikální fixací za sakrouterinní vazy. V prospektivní randomizované studii je po sakrospinózní hysteropexi v dlouhodobém follow-up dosaženo významně nižšího počtu reoperací pro recidivu sestupu v apikálním kompartmentu. Jedná se o bezpečnou a efektivní operaci pro pacientky, které si přejí ponechat dělohu. Sakrospinózní hysteropexe je možnou alternativou v primární chirurgické léčbě sestupu pánevních orgánů.
Objective: To present a surgical treatment of pelvic organ prolapse and its outcomes according to the literature. Methods: PubMed database search. Conclusion: Pelvic organ prolapse is a common diagnosis with prevalence around 40% of female population. Vaginal delivery, especially with levator ani trauma, increasing age and obesity are the basic risk factors. Native tissue repair is a possible surgical treatment. Unfortunately, concomitant hysterectomy is still a very common procedure. It is established that uterus plays a passive role in pelvic organ prolapse. Sparing of the uterus keeps the original fixation structures and compartments intact and provides a solid tissue to anchor the stitches. Patients with benign and malign uterine diseases cannot have their uterus spared. In sacrospinous hysteropexy, nonabsorbable sutures are passed through the namesaked ligament on one or both sides to elevate the uterus. Several studies and their metaanalyses show comparable anatomical and functional outcomes with shorter operation time, decreased blood loss, faster recovery and lower complication rates in comparison with hysterectomy and uterosacral ligament fixation. In a prospective randomized control trial, sacrospinous hysteropexy provides significantly lower reoperation rate for apical compartment prolapse in a long-term follow-up. It is a safe and effective procedure for patients who wish to keep their uterus in place.
- Klíčová slova
- sakrospinózní hysteropexe, dělohu zachovávající výkon,
- MeSH
- gynekologické chirurgické výkony metody MeSH
- lidé MeSH
- prolaps pánevních orgánů * chirurgie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Toxic epidermal necrolysis (TEN) is a rare disease, which predominantly manifests as damage to the skin and mucosa. Antibiotics count among the most common triggers of this hypersensitive reaction. Patients with TEN are highly susceptible to infectious complications due to the loss of protective barriers and immunosuppressant therapy. The aim of this study was to investigate the potential relationship between antibiotics used before the development of TEN and early and late-onset infectious complications in TEN patients. In this European multicentric retrospective study (Central European Lyell syndrome: therapeutic evaluation (CELESTE)), records showed that 18 patients with TEN used antibiotics (mostly aminopenicillins) before the disease development (group 1), while in 21 patients, TEN was triggered by another factor (group 2). The incidence of late-onset infectious complications (5 or more days after the transfer to the hospital) caused by Gram-positive bacteria (especially by Enterococcus faecalis/faecium) was significantly higher in group 1 than in group 2 (82.4% vs. 35.0%, p = 0.007/pcorr = 0.014) while no statistically significant difference was observed between groups of patients with infection caused by Gram-negative bacteria, yeasts, and filamentous fungi (p > 0.05). Patients with post-antibiotic development of TEN are critically predisposed to late-onset infectious complications caused by Gram-positive bacteria, which may result from the dissemination of these bacteria from the primary focus.
- Publikační typ
- časopisecké články MeSH
Arterial thrombosis is a common complication in patients with Ph- myeloproliferative neoplasms (MPN). We searched for the risk factors of stroke in MPN patients from anagrelide registry. We analyzed the potential risk factors triggering a stroke/TIA event in 249 MPN patients with previous stroke (n = 168) or Transient Ischemic Attack (TIA) (n = 140), and in 1,193 MPN control subjects (without clinical history of thrombosis). These patients were registered in a prospective manner, providing a follow-up period after Anagrelide treatment. The median age of the patients in the experimental group was of 56 years of age (ranging from 34-76) and of 53 years of age (ranging from 26-74) in the control group (p < 0.001). Using a multivariate model, we determined the following as risk factors: JAK2V617F mutation (OR 2.106, 1.458-3.043, p = 0.006), age (OR 1.017/year, 1.005-1,029, p = 0.006), male gender (OR 1.419, 1.057-1.903, p = 0.020), MPN diagnosis (OR for PMF 0.649, 0.446-0.944, p = 0.024), BMI (OR 0.687 for BMI > 25, 0.473-0.999, p = 0.05) and high TAG levels (OR 1.734, 1.162-2.586, p = 0.008), all of which were statistically significant for CMP development. Concerning the risk factors for thrombophilia, only the antiphospholipid syndrome (OR 1.994, 1.017-3.91, p = 0.048) was noteworthy in a stroke-relevant context. There was no significant difference between the blood count of the patients prior to a stroke event and the control group, both of which were under a cytoreductive treatment. We found that age, male gender, JAK2V617F mutation, previous venous thrombosis, and hypertriglyceridemia represent independent risk factors for the occurrence of a stroke in Ph- MPN patients.
- MeSH
- cévní mozková příhoda etiologie MeSH
- chinazoliny terapeutické užití MeSH
- dospělí MeSH
- fibrinolytika terapeutické užití MeSH
- Janus kinasa 2 genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- myeloproliferativní poruchy komplikace genetika MeSH
- rizikové faktory MeSH
- senioři MeSH
- trombóza etiologie prevence a kontrola 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: Heparin-induced thrombocytopenia (HIT) is the most frequent drug-induced, immune-mediated thrombocytopenia. It is associated with significant morbidity and mortality. Anticoagulation with heparin must be stopped immediately and replaced by some suggested alternative - lepirudin, danaparoid or argatroban. Fondaparinux has been also successfully used in HIT. METHODS: We present a cohort of 10 patients diagnosed with HIT and treated in a university hospital in a period of four years. Diagnosis was based on Keeling ́s scoring system, screening immunologic test for HIT (STic EXPERT® HIT) and sandwich ELISA (detection of IgG/heparin-PF4 antibodies). While other alternative anticoagulants are not readily available in our hospital, we used fondaparinux in all cases. RESULTS: From 2014 to 2018, eight males and two females (mean age 67 years, range 46-86 years) were diagnosed with HIT in our hospital. This complication developed in 9 cases after low-molecular-weight heparin and in one after heparin flushes in hemodialysis. A drop-in platelet count developed in all patients, thrombotic complications in 7 and skin necrosis in 2 cases. Fondaparinux was used in all patients, including two cases with severe renal impairment, the dose was chosen individually. We observed complete platelet recovery in all cases. One patient died because of advanced malignancy, others did not have any complication. In 6 cases we switched to oral anticoagulation after platelet recovery. CONCLUSIONS: In our group of 10 HIT patients fondaparinux was shown to be both safe and effective, even in those with severe renal impairment. Additional studies are warranted to confirm this observation.
- MeSH
- antikoagulancia terapeutické užití MeSH
- fondaparinux terapeutické užití MeSH
- hemokoagulace účinky léků MeSH
- heparin nízkomolekulární škodlivé účinky MeSH
- inhibitory faktoru Xa terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- počet trombocytů MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- trombocytopenie chemicky indukované farmakoterapie 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
