Background: We report a successful wound treatment of a chronic ulcer with bone exposure using a somehow forgotten technique of creating burr holes into the bone. Most clinics would promote flap surgery to cover wounds with bone exposure, however, in some cases invasive surgery is not mandatory. We bring up an alternative treatment for such cases. Case: We report a case of chronic ulcers on both lower extremities in a 43-year-old Caucasian male. He suffers from a leukocytoclastic vasculitis and sarcoidosis which is medicated by immunosuppressive medication. The patient‘s wounds were initially treated with mechanical debridement and split-thickness skin grafts, however, his wounds tended to worsen the more they were manipulated and finally resulted in tibial bone exposure. After levelling up his immune suppressive drugs, the wounds finally stabilized but didn’t heal after several weeks of follow-up. The wound was ultimately treated by placing burr holes in the underlying cortical bone. Conclusion: Chronic ulcers with bone exposure at the lower leg are challenging to treat. They often require local or free flap surgery. In some cases, because of underlying systemic disease, it is mandatory to stay away from invasive flap surgery. With this case, we like to put under attention an old technique of decorticating the exposed bone to promote secondary wound healing. It has been described mainly for scalp injuries, however, we have proven the viability of this technique for pretibial wounds as well.

• MeSH
• bércové vředy chirurgie   etiologie   patologie   terapie   MeSH
• dospělí MeSH
• imunosupresiva škodlivé účinky   MeSH
• komorbidita MeSH
• lidé MeSH
• poranění dolní končetiny chirurgie   komplikace   patologie   terapie   MeSH
• terapie neúspěšná MeSH
• tibie * chirurgie   patologie   zranění   MeSH
• záchrana končetiny metody   MeSH
• zákroky plastické chirurgie * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Infliximab selectively targets recently activated effector cells and, as an induction agent, might enable the safe elimination of mycophenolate from maintenance immunosuppression in kidney transplantation. METHODS: This is a phase II international multicenter open-label single-arm confidence interval (CI)-based clinical trial of the BIO-DrIM EU consortium aimed at assessing the efficacy and safety of rabbit antithymocyte globulin and infliximab induction in kidney transplantation. Sixty-seven primary kidney transplant recipients at low risk (panel-reactive antibodies <20%, no donor-specific antibodies [DSA]) received rabbit antithymocyte globulin (2 × 1.5 mg/kg, postoperative days 0 and 1) and infliximab (5 mg/kg, postoperative day 2), followed by mycophenolate-free tacrolimus-based immunosuppression for 12 mo. The primary endpoint was efficacy failure, defined as a composite of acute rejection, graft loss, or poor graft function (estimated glomerular filtration rate <40 mL/min) at 12 mo and was based on the endpoint of the comparator study. Additionally, a historical propensity-matched control cohort was established. RESULTS: Primary endpoint occurred in 22 of 67 patients (32.84%), with upper bound of an exact 1-sided 95% CI of 43.47%, which met the predefined criteria (efficacy failure of <40% and upper-bound 95% CI of <50%) and was similar in the historical matched cohort. By 12 mo, 79.1% of patients remained on the study protocol. Lower rates of BK replication (6% versus 22.4%; P = 0.013) but higher rates of de novo DSAs (11.9% versus 1.5%; P = 0.039) were observed in the study cohort. CONCLUSIONS: A similar efficacy of the study immunosuppression regimen to the comparator study and the historical matched cohort was found. However, a higher de novo DSA emergence points to an increased risk of antibody-mediated rejection (NCT04114188).

• MeSH
• antilymfocytární sérum * MeSH
• imunosupresiva škodlivé účinky   MeSH
• imunosupresivní léčba MeSH
• infliximab škodlivé účinky   MeSH
• inhibitory enzymů MeSH
• lidé MeSH
• přežívání štěpu MeSH
• protilátky MeSH
• rejekce štěpu prevence a kontrola   MeSH
• takrolimus * škodlivé účinky   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH

V článku sa uvádza prehľad súčasného stavu poznatkov o imunoterapii spektra ochorení neuromyelitis optica (NMOSD, neuromyelitis optica spectrum disorders). Zneschopnenie pri NMOSD je následkom atakov a relapsov choroby, na ktoré sa sústreďuje liečba. Diagnostickým biomarkerom ochorenia sú autoprotilátky proti aquaporínu 4 (AQP4-IgG), ktoré zohrávajú dôležitú úlohu v patogenéze poškodenia astrocytov. Nedávny pokrok v chápaní NMOSD viedol k vývoju nových terapií a overeniu ich účinnosti v randomizovaných kontrolovaných štúdiách. Pre pacientov s pozitívnymi protilátkami proti AQP4 boli schválené nové imunoterapie, ktoré majú potenciál znížiť aktivitu ochorenia redukciou relapsov, sú to ekulizumab, ravulizumab, inebilizumab a satralizumab.

The article provides an overview of the current state of knowledge about neuromyelitis optica spectrum disorder (NMOSD) immunotherapy. Therapy focuses on the relapses that determine disability in NMOSD. Autoantibodies against aquaporin 4 (AQP4-IgG) are a diagnostic biomarker of the disease and have an important role in the pathogenesis of damage to astrocytes. Recent advances in the understanding of NMOSD have led to the development of new therapies and validation of their effectiveness in randomized controlled trials. New immunotherapies have been approved for patients with positive AQP4-igG antibodies, with the potential to reduce the number of relapses, namely eculizumab, ravulizumab, inebilizumab and satralizumab.

• MeSH
• akvaporin 4 imunologie   MeSH
• B-lymfocyty účinky léků   MeSH
• imunosupresiva farmakologie   klasifikace   škodlivé účinky   terapeutické užití   MeSH
• imunoterapie klasifikace   metody   MeSH
• inhibitory interleukinu-6 farmakologie   klasifikace   terapeutické užití   MeSH
• inhibitory komplementu farmakologie   klasifikace   terapeutické užití   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• lymfocytární deplece metody   MeSH
• monoklonální protilátky farmakologie   klasifikace   terapeutické užití   MeSH
• neuromyelitis optica * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

• MeSH
• imunosupresiva škodlivé účinky   MeSH
• inhibitory kalcineurinu * škodlivé účinky   MeSH
• lidé MeSH
• prognóza MeSH
• takrolimus škodlivé účinky   MeSH
• transplantace ledvin škodlivé účinky   MeSH
• trombotické mikroangiopatie * etiologie   chemicky indukované   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• úvodníky MeSH

BACKGROUND: Treatment with cladribine tablets (CladT), an immune reconstitution therapy for relapsing multiple sclerosis (RMS), involves two short courses of treatment in Year 1 and Year 2. Most patients achieve sustained efficacy with CladT, but a small proportion may experience new disease activity (DA). Following completion of the indicated dose, physicians may have questions relating to the long-term management of these patients. Since the EU approval of CladT over 5 years ago, real-world evidence (RWE) is increasing and may provide some insights and guidance for clinical practice. We describe a systematic literature review (SLR) of RWE and provide expert opinions relating to six questions regarding the long-term use of CladT. METHODS: Pertinent clinical questions were developed by a steering committee (SC) of 14 international multiple sclerosis (MS) experts regarding breakthrough DA in Year 1, new DA after 2 years or more of treatment, long-term management of stable patients, and whether additional courses of CladT may be required or safe. An SLR was performed in EMBASE and PubMed using the population, intervention, comparators, outcomes, study design (PICOS) framework to identify relevant studies within the last 15 years. Searches of key congress proceedings for the last 2-3 years were also performed. Following review of the results and RWE, the SC drafted and agreed on expert opinion statements for each question. RESULTS: A total of 35 publications reporting RWE for CladT were included in this review. In the real world, breakthrough DA in Year 1 is of low incidence (1.1-21.9%) but can occur, particularly in patients switching from anti-lymphocyte trafficking agents. In most patients, this DA did not lead to treatment discontinuation. Reported rates of DA after the full therapeutic effect of CladT has been achieved (end of Year 2, 3 or 4) range from 12.0 to 18.7% in the few studies identified. No RWE was identified to support management decisions for stable patients in Year 5 or later. Views among the group were also diverse on this question and voting on expert opinion statements was required. Only two studies reported the administration of additional courses of CladT, but detailed safety outcomes were not provided. CONCLUSIONS: RWE for the long-term use of CladT in the treatment of RMS is increasing, however, gaps in knowledge remain. Where possible, the RWE identified through the SLR informed expert statements, but, where RWE is still lacking, these were based solely on experiences and opinion, providing some guidance on topics and questions that occur in daily clinical practice. More real-world studies with longer-term follow-up periods are needed and highly anticipated.

• MeSH
• imunosupresiva škodlivé účinky   MeSH
• kladribin * škodlivé účinky   MeSH
• lidé MeSH
• lymfocyty MeSH
• recidiva MeSH
• roztroušená skleróza * MeSH
• tablety farmakologie   MeSH
• znalecký posudek MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• systematický přehled MeSH

BACKGROUND: Multiple sclerosis (MS) negatively affects health-related quality of life (HRQoL). OBJECTIVE: To evaluate HRQoL in people with highly active relapsing MS treated with cladribine tablets (CladT; 3.5 mg/kg cumulative dose over 2 years) in CLARIFY-MS. METHODS: Changes in the MS quality of life (MSQoL)-54 scores were analysed using a repeated mixed-effects linear model. Subgroup analyses were performed for participants who were pretreatment-naïve and those pretreated with disease-modifying therapies (DMTs) before initiating CladT. Safety and tolerability of CladT were also assessed. RESULTS: MSQoL-54 physical (mean change = 4.86; 95% confidence interval (CI) = 3.18, 6.53) and mental health (4.80; 95% CI = 3.13, 6.46) composite scores (primary endpoints) showed significant improvement at Month 24 versus Baseline (p < 0.0001). Changes in the MSQoL-54 scores were consistent across the pretreatment-naïve and DMT-pretreated subgroups. No new severe or opportunistic infections occurred. Most post-baseline lymphopenia events were Grade 1-2 in severity. Transient Grade-3 lymphopenia was observed in 19.7% (95/482) of participants. Grade-4 lymphopenia was not observed. CONCLUSIONS: CladT treatment significantly improved the mean MSQoL-54 physical and mental health composite scores over 2 years. CladT efficacy in HRQoL, relapse rates and Expanded Disability Status Scale scores demonstrates its multidimensional effects in MS treatment.

• MeSH
• imunosupresiva škodlivé účinky   MeSH
• kladribin škodlivé účinky   MeSH
• kvalita života MeSH
• lidé MeSH
• lymfopenie * chemicky indukované   farmakoterapie   MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• tablety terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

IMPORTANCE: Natalizumab cessation is associated with a risk of rebound disease activity. It is important to identify the optimal switch disease-modifying therapy strategy after natalizumab to limit the risk of severe relapses. OBJECTIVES: To compare the effectiveness and persistence of dimethyl fumarate, fingolimod, and ocrelizumab among patients with relapsing-remitting multiple sclerosis (RRMS) who discontinued natalizumab. DESIGN, SETTING, AND PARTICIPANTS: In this observational cohort study, patient data were collected from the MSBase registry between June 15, 2010, and July 6, 2021. The median follow-up was 2.7 years. This was a multicenter study that included patients with RRMS who had used natalizumab for 6 months or longer and then were switched to dimethyl fumarate, fingolimod, or ocrelizumab within 3 months after natalizumab discontinuation. Patients without baseline data were excluded from the analysis. Data were analyzed from May 24, 2022, to January 9, 2023. EXPOSURES: Dimethyl fumarate, fingolimod, and ocrelizumab. MAIN OUTCOMES AND MEASURES: Primary outcomes were annualized relapse rate (ARR) and time to first relapse. Secondary outcomes were confirmed disability accumulation, disability improvement, and subsequent treatment discontinuation, with the comparisons for the first 2 limited to fingolimod and ocrelizumab due to the small number of patients taking dimethyl fumarate. The associations were analyzed after balancing covariates using an inverse probability of treatment weighting method. RESULTS: Among 66 840 patients with RRMS, 1744 had used natalizumab for 6 months or longer and were switched to dimethyl fumarate, fingolimod, or ocrelizumab within 3 months of natalizumab discontinuation. After excluding 358 patients without baseline data, a total of 1386 patients (mean [SD] age, 41.3 [10.6] years; 990 female [71%]) switched to dimethyl fumarate (138 [9.9%]), fingolimod (823 [59.4%]), or ocrelizumab (425 [30.7%]) after natalizumab. The ARR for each medication was as follows: ocrelizumab, 0.06 (95% CI, 0.04-0.08); fingolimod, 0.26 (95% CI, 0.12-0.48); and dimethyl fumarate, 0.27 (95% CI, 0.12-0.56). The ARR ratio of fingolimod to ocrelizumab was 4.33 (95% CI, 3.12-6.01) and of dimethyl fumarate to ocrelizumab was 4.50 (95% CI, 2.89-7.03). Compared with ocrelizumab, the hazard ratio (HR) of time to first relapse was 4.02 (95% CI, 2.83-5.70) for fingolimod and 3.70 (95% CI, 2.35-5.84) for dimethyl fumarate. The HR of treatment discontinuation was 2.57 (95% CI, 1.74-3.80) for fingolimod and 4.26 (95% CI, 2.65-6.84) for dimethyl fumarate. Fingolimod use was associated with a 49% higher risk for disability accumulation compared with ocrelizumab. There was no significant difference in disability improvement rates between fingolimod and ocrelizumab. CONCLUSION AND RELEVANCE: Study results show that among patients with RRMS who switched from natalizumab to dimethyl fumarate, fingolimod, or ocrelizumab, ocrelizumab use was associated with the lowest ARR and discontinuation rates, and the longest time to first relapse.

• MeSH
• dimethyl fumarát škodlivé účinky   MeSH
• dospělí MeSH
• fingolimod hydrochlorid * terapeutické užití   MeSH
• imunologické faktory škodlivé účinky   MeSH
• imunosupresiva škodlivé účinky   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   MeSH
• natalizumab škodlivé účinky   MeSH
• recidiva MeSH
• relabující-remitující roztroušená skleróza * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH

Multiple sclerosis (MS) is a chronic neurodegenerative disease that affects the central nervous system (CNS). Currently, MS treatment is limited to several Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved medications that slow disease progression by immunomodulatory action. Fingolimod and siponimod have similar mechanisms of action, and consequently, their therapeutic effects may be comparable. However, while fingolimod is mainly used for relapsing-remitting MS (RRMS), siponimod, according to EMA label, is recommended for active secondary progressive MS (SPMS). Clinicians and scientists are analysing whether patients can switch from fingolimod to siponimod and identifying the advantages or disadvantages of such a switch from a therapeutic point of view. In this review, we aim to discuss the therapeutic effects of these two drugs and the advantages/disadvantages of switching treatment from fingolimod to siponimod in patients with the most common forms of MS, RRMS and SPMS.

• MeSH
• chronicko-progresivní roztroušená skleróza * farmakoterapie   chemicky indukované   MeSH
• fingolimod hydrochlorid škodlivé účinky   MeSH
• hodnocení rizik MeSH
• imunosupresiva škodlivé účinky   MeSH
• lidé MeSH
• neurodegenerativní nemoci * chemicky indukované   farmakoterapie   MeSH
• recidiva MeSH
• roztroušená skleróza * farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Maintaining of remission early in the disease course of Crohn's disease (CD) is essential and has major impact on the future prognosis. This study aimed to identify baseline predictors to develop model allowing stratification of patients who will not benefit from long-term azathioprine (AZA) treatment and will require more intensive therapy. METHODS: This study was designed to develop clinical prediction rule using retrospective data analysis of pediatric CD patients included in prospective inception cohort. Clinical relapse was defined as necessity of re-induction of remission. Sequence of Cox models was fitted to predict risk of relapse. RESULTS: Out of 1190 CD patients from 13 European centers, 441 were included, 50.3% patients did not experience clinical relapse within 2 years of AZA treatment initiation. Median time to relapse was 2.11 (CI 1.59-2.46) years. Of all the tested parameters available at diagnosis, six were significant in multivariate analyses: C-reactive protein (p = 0.038), body mass index Z-score >0.8 SD (p = 0.002), abnormal sigmoid imaging (p = 0.039), abnormal esophageal endoscopy (p = 0.005), ileocolonic localization (p = 0.023), AZA dose in specific age category (p = 0.031). CONCLUSIONS: Although the possibility of predicting relapse on AZA treatment appears limited, we developed predictive model based on six baseline parameters potentially helpful in clinical decision. IMPACT: The possibility of predicting relapse on AZA treatment appears to be possible but limited. We identified six independent predictors available at diagnosis of early AZA/6-MP treatment failure in pediatric CD patients. Using combination of these factors, a model applicable to clinical practice was created. A web-based tool, allowing estimation of individual relapse risk in pediatric CD patients on a particular therapeutic regimen, has been developed.

• MeSH
• azathioprin terapeutické užití   škodlivé účinky   MeSH
• Crohnova nemoc * komplikace   diagnóza   farmakoterapie   MeSH
• dítě MeSH
• imunosupresiva terapeutické užití   škodlivé účinky   MeSH
• indukce remise MeSH
• lidé MeSH
• prospektivní studie MeSH
• recidiva MeSH
• retrospektivní studie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Immunosuppression after kidney transplantation is mainly guided via plasma tacrolimus trough level, which cannot sufficiently predict allograft rejection and infection. The plasma load of the non-pathogenic and highly prevalent torque teno virus (TTV) is associated with the immunosuppression of its host. Non-interventional studies suggest the use of TTV load to predict allograft rejection and infection. The primary objective of the current trial is to demonstrate the safety, tolerability and preliminary efficacy of TTV-guided immunosuppression. METHODS: For this purpose, a randomised, controlled, interventional, two-arm, non-inferiority, patient- and assessor-blinded, investigator-driven phase II trial was designed. A total of 260 stable, low-immunological-risk adult recipients of a kidney graft with tacrolimus-based immunosuppression and TTV infection after month 3 post-transplantation will be recruited in 13 academic centres in six European countries. Subjects will be randomised in a 1:1 ratio (allocation concealment) to receive tacrolimus either guided by TTV load or according to the local centre standard for 9 months. The primary composite endpoint includes the occurrence of infections, biopsy-proven allograft rejection, graft loss, or death. The main secondary endpoints include estimated glomerular filtration rate, graft rejection detected by protocol biopsy at month 12 post-transplantation (including molecular microscopy), development of de novo donor-specific antibodies, health-related quality of life, and drug adherence. In parallel, a comprehensive biobank will be established including plasma, serum, urine and whole blood. The date of the first enrolment was August 2022 and the planned end is April 2025. DISCUSSION: The assessment of individual kidney transplant recipient immune function might enable clinicians to personalise immunosuppression, thereby reducing infection and rejection. Moreover, the trial might act as a proof of principle for TTV-guided immunosuppression and thus pave the way for broader clinical applications, including as guidance for immune modulators or disease-modifying agents. TRIAL REGISTRATION: EU CT-Number: 2022-500024-30-00.

• MeSH
• dospělí MeSH
• imunosupresiva škodlivé účinky   MeSH
• imunosupresivní léčba MeSH
• kvalita života MeSH
• lidé MeSH
• rejekce štěpu diagnóza   prevence a kontrola   MeSH
• takrolimus škodlivé účinky   MeSH
• Torque teno virus * MeSH
• transplantace ledvin * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH