BACKGROUND: The rate of immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) plays the principal role in the development of serious post-transplant complications. However, the post-transplantation course has a significant impact on shaping the immune system of the recipient, per se, thus representing risk factors for subsequent unfavorable outcomes. The predictive power of an interferon gamma (IFNγ) release assay (IGRA) on graft-versus-host disease (GVHD) or hematological relapse in recipients of allo-HSCT treated with post-transplantation cyclophosphamide and the impact of these complications on the restoration of cellular immune responsiveness was evaluated. STUDY DESIGN: A prospective observational study in which 62 adult patients with myeloid hematological malignancies who underwent allo-HSCT with a myeloablative conditioning regimen combined with post-transplantation cyclophosphamide were enrolled. Clinical data were collected and the IGRA was performed before commencement of the conditioning regimen and for 12 months post-allo-HSCT. Multivariate Cox regression and logistic regression models with backward stepwise analyses were used to calculate the predictive values for acute or chronic GVHD, or hematological relapse. RESULTS: Pre-transplantation and early post-transplantation IGRA values and other selected covariables (age, diagnosis, relapse risk, conditioning type, pre-T lymphocyte count, and donor sex), enabled prediction of the 12-month incidence of chronic GVHD with positive and negative predictive values of 75 % and 88 %, respectively. However, the IGRA did not improve the predictive value for acute GVHD or hematological relapse. Patients with myelodysplastic syndrome (MDS) had a significantly lower pre-transplant IGRA value (p = 0.021) and a delayed IFNγ response in IGRA, post-HSCT, than patients with acute myeloid leukemia (AML) (p = 0.015 and p = 0.0063 for 3 and 4 months post-HSCT, respectively). CONCLUSIONS: The IGRA can be used to monitor the recovery of total cellular immunity, post-HSCT and it has shown potential for use in personalized post-transplantation care. In the multivariate backward stepwise logistic regression model, pre-and early post-transplantation IGRA values showed potential for predicting chronic GVHD. Patients with MDS had a significantly lower pre-transplantation IGRA value and delayed IFNγ response in IGRA, post-HSCT, than patients with AML.
- MeSH
- chronická nemoc MeSH
- cyklofosfamid * terapeutické užití MeSH
- dospělí MeSH
- hematologické nádory terapie MeSH
- homologní transplantace MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- myeloablativní agonisté terapeutické užití MeSH
- nemoc štěpu proti hostiteli * diagnóza prevence a kontrola etiologie MeSH
- příprava pacienta k transplantaci * metody MeSH
- prospektivní studie MeSH
- senioři MeSH
- test pomocí interferonu gama MeSH
- transplantace hematopoetických kmenových buněk * škodlivé účinky MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
OBJECTIVE: Patients with deep-seated arteriovenous malformations (AVMs) have a higher rate of unfavorable outcome and lower rate of nidus obliteration after primary stereotactic radiosurgery (SRS). The aim of this study was to evaluate and quantify the effect of AVM location on repeat SRS outcomes. METHODS: This retrospective, multicenter study involved 505 AVM patients managed with repeat, single-session SRS. The endpoints were nidus obliteration, hemorrhage in the latency period, radiation-induced changes (RICs), and favorable outcome. Patients were split on the basis of AVM location into the deep (brainstem, basal ganglia, thalamus, deep cerebellum, and corpus callosum) and superficial cohorts. The cohorts were matched 1:1 on the basis of the covariate balancing score for volume, eloquence of location, and prescription dose. RESULTS: After matching, 149 patients remained in each cohort. The 5-year cumulative probability rates for favorable outcome (probability difference -18%, 95% CI -30.9 to -5.8%, p = 0.004) and AVM obliteration (probability difference -18%, 95% CI -30.1% to -6.4%, p = 0.007) were significantly lower in the deep AVM cohort. No significant differences were observed in the 5-year cumulative probability rates for hemorrhage (probability difference 3%, 95% CI -2.4% to 8.5%, p = 0.28) or RICs (probability difference 1%, 95% CI -10.6% to 11.7%, p = 0.92). The median time to delayed cyst formation was longer with deep-seated AVMs (deep 62 months vs superficial 12 months, p = 0.047). CONCLUSIONS: AVMs located in deep regions had significantly lower favorable outcomes and obliteration rates compared with superficial lesions after repeat SRS. Although the rates of hemorrhage in the latency period and RICs in the two cohorts were comparable, delayed cyst formation occurred later in patients with deep-seated AVMs.
- MeSH
- dospělí MeSH
- intrakraniální arteriovenózní malformace * chirurgie radioterapie MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- radiochirurgie * metody MeSH
- reoperace MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
The emergence of biofilm-induced drug tolerance poses a critical challenge to public healthcare management. Pseudomonas aeruginosa, a gram-negative opportunistic bacterium, is involved in various biofilm-associated infections in human hosts. Towards this direction, in the present study, a combinatorial approach has been explored as it is a demonstrably effective strategy for managing microbial infections. Thus, P. aeruginosa has been treated with cuminaldehyde (a naturally occurring phytochemical) and gentamicin (an aminoglycoside antibiotic) in connection to the effective management of the biofilm challenges. It was also observed that the test molecules could show increased antimicrobial activity against P. aeruginosa. A fractional inhibitory concentration index (FICI) of 0.65 suggested an additive interaction between cuminaldehyde and gentamicin. Besides, a series of experiments such as crystal violet assay, estimation of extracellular polymeric substance (EPS), and microscopic images indicated that an enhanced antibiofilm activity was obtained when the selected compounds were applied together on P. aeruginosa. Furthermore, the combination of the selected compounds was found to reduce the secretion of virulence factors from P. aeruginosa. Taken together, this study suggested that the combinatorial application of cuminaldehyde and gentamicin could be considered an effective approach towards the control of biofilm-linked infections caused by P. aeruginosa.
- MeSH
- antibakteriální látky * farmakologie MeSH
- benzaldehydy * farmakologie MeSH
- biofilmy * účinky léků MeSH
- cymeny farmakologie MeSH
- faktory virulence MeSH
- gentamiciny * farmakologie MeSH
- lidé MeSH
- mikrobiální testy citlivosti * MeSH
- Pseudomonas aeruginosa * účinky léků fyziologie MeSH
- synergismus léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Fingolimod is a first-in-class, orally administered drug indicated for the treatment of relapsing-remitting multiple sclerosis. It acts as an immunomodulator, is classified as a "disease-modifying therapy", and its main mechanism of action is the modulation of sphingosine-1-phosphate receptors. In this prospective pilot study, whole blood concentrations of fingolimod and fingolimod phosphate obtained during routine health care were measured. In this study, we aimed to determine whether therapeutic monitoring of fingolimod and fingolimod phosphate concentrations can help personalise pharmacotherapy for patients with multiple sclerosis. METHOD: The study group consisted of 73 patients treated with oral fingolimod (0.5 mg) once daily. Blood samples were collected between July 2021 and January 2022. The whole blood concentrations of fingolimod and fingolimod phosphate were analysed using ultra-high-performance liquid chromatography-tandem mass spectrometry. The relationship between the measured concentrations and the absolute peripheral blood lymphocyte count was evaluated. RESULTS: Fingolimod concentrations ranged from 0.61 to 6.21 μg/L, and fingolimod phosphate concentrations from 0.48 to 4.28 μg/L. Significantly higher concentrations of the active metabolite, fingolimod phosphate, and a significantly higher fingolimod phosphate/fingolimod concentration ratio were observed in women. The sum of fingolimod and fingolimod phosphate concentrations was significantly higher in the subgroup of patients with a lower absolute peripheral blood lymphocyte count. CONCLUSION: Although all patients were treated with the same dose of fingolimod (0.5 mg orally daily), a 10-fold difference was observed in the achieved whole blood concentrations of fingolimod and fingolimod phosphate. This wide inter-individual variability may lead to potential toxicity or suboptimal concentrations, with the risk of further deterioration in the clinical condition of patients with multiple sclerosis. Therefore, fingolimod is a suitable candidate for therapeutic drug monitoring, including monitoring patient adherence to treatment.
- MeSH
- dospělí MeSH
- fingolimod hydrochlorid * krev aplikace a dávkování farmakologie MeSH
- imunosupresiva * krev aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- monitorování léčiv metody MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- relabující-remitující roztroušená skleróza farmakoterapie krev MeSH
- roztroušená skleróza farmakoterapie krev MeSH
- tandemová hmotnostní spektrometrie 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
Kazuistika popisuje léčbu agresivní formy Crohnovy choroby s perianálními a mimostřevními projevy komplikovanou podezřením na tuberkulózu a později chirurgickou léčbou bronchoalveolárního karcinomu. Pacientka byla úspěšně léčena subkutánním infliximabem, který vedl ke slizničnímu zhojení a sanaci perianální nemoci.
The case report describes the treatment of an aggressive form of Crohn's disease with perianal and extraintestinal manifestations, complicated by suspected tuberculosis and later by surgical treatment of bronchoalveolar carcinoma. The patient was successfully treated with subcutaneous infliximab, which led to mucosal healing and resolution of the perianal disease.
