BACKGROUND: Perianal fistulas of Crohn's disease (CD) create a significant burden on patients' lives. However, the efficacy and safety of adipose-derived mesenchymal stem cell treatment are contradicting, and real-world evidence is lacking. AIMS: To examine the usability of darvadstrocel therapy in managing perianal CD. METHODS: We enrolled patients with CD and perianal fistulas in this retrospective multicenter study. The primary outcome was perianal clinical remission (defined as all treated fistulas closed) at weeks 26 and 52. Secondary outcomes were clinical response rates (≥ 1 fistulas closed), perianal activity (PDAI), patient satisfaction, and adverse events. Data were recorded at baseline and weeks 12, 26 and 52. Prediction of primary outcomes was performed by logistic regression. RESULTS: Overall, among 223 patients (male/female ratio: 0.48), perianal clinical remission was achieved in 78.2% and 62.3% until weeks 26 and 52. Baseline PDAI score (OR 0.75), number of fistulas (OR 0.28) and the number of weeks after preparation for surgery (OR 0.98) were associated with treatment failure. The clinical response rates were 84.8% and 79.8% at weeks 26 and 52. Improvement of subjective perianal symptoms was achieved in 77.8% and 78.4% of patients, respectively. Adverse events occurred in 13.5% of patients; perianal abscesses and proctalgia were the most frequently reported. CONCLUSION: Effectiveness data were higher than in clinical trials. The safety profile was reassuring, and patients' satisfaction was high. Appropriate patient selection, fistula preparation and expertise may help to achieve treatment success.

• MeSH
• Crohnova nemoc * terapie   komplikace   MeSH
• dospělí MeSH
• indukce remise MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• rektální píštěl * terapie   etiologie   MeSH
• retrospektivní studie MeSH
• spokojenost pacientů MeSH
• transplantace mezenchymálních kmenových buněk * metody   škodlivé účinky   MeSH
• výsledek terapie 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
• multicentrická studie MeSH

PURPOSE: To determine the optimal daunorubicin dose and number of 7 + 3 induction cycles in newly diagnosed AML, this randomized controlled trial compared a once daily dose of 60 mg/m2 with 90 mg/m2 daunorubicin in the first 7 + 3 induction and one versus two cycles of 7 + 3 induction. PATIENTS AND METHODS: Patients age 18-65 years with newly diagnosed AML were randomly assigned to 60 versus 90 mg/m2 daunorubicin once daily plus cytarabine. Patients with marrow blasts below 5% on day 15 after first induction were randomly assigned to receive a second induction cycle or no second induction cycle. RESULTS: Eight hundred and sixty-four patients with a median age of 52 years were randomly assigned. After a preplanned interim analysis showing no significant difference in response between 60 and 90 mg/m2, all consecutive patients received 60 mg/m2 daunorubicin once daily. The proportion of good early responders was 44% versus 48% (P = .983) with a composite complete remission (CRc) rate of 90% versus 89% after induction (P = .691); the 3-year relapse-free survival (RFS) after 60 versus 90 mg/m2 once daily was 54% versus 50% (P = .561), and the 3-year overall survival (OS) was 65% versus 58% (P = .242). Among 389 good responders, CRc rates at the end of induction were 87% after single induction and 85% after double induction. The 3-year RFS was 51% versus 60% (hazard ratio [HR], 1.3; P = .091), and the 3-year OS was 76% versus 75% after single versus double induction (HR, 1.0; P = .937). CONCLUSION: The use of 90 mg/m2 daunorubicin once daily in the context of classical 7 + 3 induction does not significantly improve early response and does not lead to higher remission rates or longer survival than 60 mg/m2 once daily. In patients with a good early response after first induction, a second induction has only a limited impact on RFS and does not result in an OS benefit.

• MeSH
• akutní myeloidní leukemie * farmakoterapie   mortalita   MeSH
• antibiotika antitumorózní aplikace a dávkování   MeSH
• cytarabin * aplikace a dávkování   MeSH
• daunomycin * aplikace a dávkování   MeSH
• dospělí MeSH
• indukce remise MeSH
• indukční chemoterapie * metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• protokoly antitumorózní kombinované chemoterapie * terapeutické užití   aplikace a dávkování   MeSH
• rozvrh dávkování léků MeSH
• senioři 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
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

Stratified and precision nutrition refers to disease management or prevention of disease onset, based on dietary interventions tailored to a person's characteristics, biology, gut microbiome, and environmental exposures. Such treatment models may lead to more effective management of inflammatory bowel disease (IBD) and reduce risk of disease development. This societal position paper aimed to report advances made in stratified and precision nutritional therapy in IBD. Following a structured literature search, limited to human studies, we identified four relevant themes: (a) nutritional epidemiology for risk prediction of IBD development, (b) food-based dietary interventions in IBD, (c) exclusive enteral nutrition (EEN) for Crohn's disease (CD) management, and (d) pre- and probiotics for IBD management. There is scarce literature upon which we can make recommendations for precision or stratified dietary therapy for IBD, both for risk of disease development and disease management. Certain single-nucleotide polymorphisms related to polyunsaturated fatty acid (PUFA) metabolism may modify the effect dietary PUFA have in increasing the risk of IBD development. Non-colonic CD, mild-to-moderate CD, and high microbiota richness may predict success of EEN and may be used both for prediction of treatment continuation, but also for early cessation in nonresponders. There is currently insufficient evidence to make recommendations for precision or stratified dietary therapy for patients with established IBD. Despite the great interest in stratified and precision nutrition, we currently lack data to support conclusive recommendations. Replication of early findings by independent research groups and within structured clinical interventions is required.

• MeSH
• Crohnova nemoc * terapie   MeSH
• dítě MeSH
• idiopatické střevní záněty * terapie   MeSH
• indukce remise MeSH
• lidé MeSH
• pomocný zdravotnický personál MeSH
• translační biomedicínský výzkum MeSH
• veřejné mínění MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: STARDUST, a phase 3b randomised trial, compared ustekinumab therapeutic strategies in patients with Crohn's disease (CD) using early endoscopic assessment and treat-to-target (T2T) versus standard of care (SoC). AIM: To assess the efficacy of ustekinumab extended treatment in a long-term extension (LTE) of up to 104 weeks with dosing adapted according to clinical, biomarker and endoscopy outcomes. METHODS: Adults with moderately-to-severely active CD received intravenous ustekinumab approximating 6 mg/kg at Week 0 and subcutaneous ustekinumab 90 mg at Week 8. At Week 16, 440 ≥70-point responders were randomised to T2T or SoC and 323 entered the LTE. At Week 48, a unified, protocol-defined ustekinumab dose frequency escalation/de-escalation was applied based on achieving endoscopic remission and corticosteroid-free clinical remission. Achieving corticosteroid-free clinical remission and biomarker remission at consecutive visits determined ustekinumab dosing frequency. Dichotomous variables were analysed using non-responder imputation. RESULTS: Among patients who entered the LTE, 7.7%, 48.6% and 43.7% received doses every 4, 8 and 12 weeks, respectively. Ustekinumab dose frequency was escalated in 23.5% and de-escalated in 19.7%. Endoscopic response and remission rates were 28.9% and 10.73% (all randomised) and 39.3% and 14.6% (patients entering the LTE), respectively, at Week 104. Clinical remissiona rates at week 104 were 50.2% (all randomised) and 68.4% (patients entering the LTE). There were no new safety signals. CONCLUSION: STARDUST LTE is the first interventional ustekinumab efficacy study to show a favourable benefit-risk profile with preservation of clinical and endoscopic outcomes through Week 104 using flexible, algorithm-driven dose adjustment including de-escalation.

• MeSH
• biologické markery analýza   MeSH
• Crohnova nemoc * farmakoterapie   MeSH
• dospělí MeSH
• gastrointestinální endoskopie MeSH
• indukce remise MeSH
• lidé MeSH
• ustekinumab * terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH

The best donor option for acute myeloid leukemia (AML) patients lacking an HLA-matched donor has remained intensively debated. We herein report the results of a large retrospective registry study comparing hematopoietic cell transplantation (HCT) outcomes between double-unit umbilical cord blood transplantation (dCBT, n = 209) versus 9/10 HLA-matched unrelated donor (UD) with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (UD 9/10, n = 270) in patients with AML in first complete remission (CR1). Inclusion criteria consisted of adult patient, AML in CR1 at transplantation, either peripheral blood stem cells (PBSC) from UD 9/10 with PTCy as GVHD prophylaxis or dCBT without PTCy, transplantation between 2013 and 2021, and no in vivo T-cell depletion. The 180-day cumulative incidence of grade II-IV acute GVHD was 29% in UD 9/10 versus 44% in dCBT recipients (p = .001). After adjustment for covariates, dCBT recipients had a higher non-relapse mortality (HR = 2.35, 95% CI: 1.23-4.48; p = .01), comparable relapse incidence (HR = 1.12, 95% CI: 0.67-1.86; p = .66), lower leukemia-free survival (HR = 1.5, 95% CI: 1.01-2.23; p = .047), and lower overall survival (HR = 1.66, 95% CI: 1.08-2.55; p = .02) compared with patients receiving UD 9/10 HCT. In summary, our results suggest that transplantation outcomes are better with UD 9/10 with PTCy-based GVHD prophylaxis than with dCBT for AML patients in CR1. These data might support the use of UD 9/10 with PTCy-based GVHD prophylaxis over dCBT in AML patients lacking an HLA-matched donor.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   MeSH
• cyklofosfamid * terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli * prevence a kontrola   etiologie   mortalita   MeSH
• nepříbuzný dárce * MeSH
• registrace MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk MeSH
• transplantace kmenových buněk z pupečníkové krve * 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

We assessed outcomes of allogeneic transplantation (HSCT) in favorable risk AML in CR1 over 3 time periods. 1850 patients were included, 2005 to 2009- 222, 2010 to 2014 -392, and 2015 to 2021-1236; 526 with t (8:21), 625 with inv (16), and 699 with NPM1mutFLT3WT. Patients transplanted in 2015-2021 were older (p < 0.0001) with more patients ≥60 years of age (p < 0.0001). The most frequent diagnosis in 2015-2021 was NPM1mutFLT3WT vs. t (8:21) in the 2 earlier periods, (p < 0001). Haploidentical transplants (Haplo) increased from 5.9% to 14.5% (p < 0.0001). Graft-versus-host disease (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) was more frequent in 2015-2021 vs. the other 2 periods (p < 0.0001). On multivariate analysis, incidence of total chronic GVHD was reduced in HSCTs performed ≥2015 vs. those performed in 2005-2009, hazard ratio (HR) = 0.74 (95% CI 0.56-0.99, p = 0.046) and GVHD-free, relapse-free survival (GRFS) improved for patients transplanted from 2010-2014 vs. those transplanted in 2005-2009, HR = 0.74 (95% CI 0.56-0.98, p = 0.037). Other HSCT outcomes did not differ with no improvement ≥2015. LFS, OS, and GRFS were inferior in patients with t (8:21) with HR = 1.32 (95% CI 1.03-1.68, p = 0.026), HR = 1.38 (95% CI 1.04-1.83, p = 0.027) and HR = 01.25 (95% CI 1.02-1.53, p = 0.035), respectively. In conclusion, this retrospective analysis of HSCT in patients with favorable risk AML, transplanted over 16 years showed an increased number of transplants in patients ≥60 years, from Haplo donors with PTCy. Most importantly, 3-year GRFS improved ≥2010 and total chronic GVHD reduced ≥2015, with no significant change in other HSCT outcomes.

• MeSH
• akutní myeloidní leukemie * terapie   MeSH
• alografty MeSH
• dospělí MeSH
• homologní transplantace metody   MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli prevence a kontrola   etiologie   MeSH
• nukleofosmin MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * metody   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
• multicentrická studie MeSH

OBJECTIVE: Because 66/68 joint counts are not always performed in routine care, we aimed to determine which of the modified 28-joint disease activity index for psoriatic arthritis (DAPSA28) or 28-joint disease activity score with C-reactive protein (DAS28-CRP) should be preferred for monitoring disease activity in psoriatic arthritis (PsA) when the original DAPSA (66/68 joints) is not available. METHODS: Prospectively collected real-world data of European bionaive patients with PsA initiating a first tumor necrosis factor inhibitor were pooled. Remission and response status were evaluated at 6 months by remission (DAPSA ≤ 4, DAPSA28 ≤ 4, and DAS28-CRP < 2.6), response (75% improvement for DAPSA and DAPSA28), and combined EULAR good/moderate responses for DAS28-CRP. Logistic regression analyses on multiple imputed data were used to identify baseline predictors. RESULTS: Remission and response cohorts included 3,159 and 1,866 patients, respectively. The 6-month proportions achieving remission/response were DAPSA (27%/44%), DAPSA28 (28%/44%), and DAS28-CRP (59%/80%). Of 14 possible baseline predictors, 11 predicted both DAPSA and DAPSA28 remission (8 of which also predicted their response, indicated by "*"): longer disease duration*, male sex*, and higher CRP* were positive, whereas older age*, higher body mass index*, patient fatigue*, and global, physician global, health assessment questionnaire score*, and tender and swollen* joint counts were negative predictors. Eight and five of these predicted DAS28-CRP remission and response, respectively. CONCLUSION: In patients with PsA, DAPSA28 should be preferred over DAS28-CRP as a substitute for DAPSA when 66/68 joint counts are not available because of the large overlap in remission and response status and in predictors between DAPSA and DAPSA28.

• MeSH
• antirevmatika terapeutické užití   MeSH
• biologické markery krev   MeSH
• C-reaktivní protein * analýza   MeSH
• dospělí MeSH
• indukce remise * MeSH
• inhibitory TNF terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• psoriatická artritida * farmakoterapie   krev   MeSH
• senioři MeSH
• stupeň závažnosti nemoci * MeSH
• TNF-alfa antagonisté a inhibitory   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
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

We compared transplantation (HSCT) outcomes in AML patients undergoing HSCT with post-transplant cyclophosphamide (PTCy) in first complete remission from 1065 young (<35 years) haploidentical (Haplo) donors (yHaplo) vs. 147 old (≥35 years) mismatched unrelated donors (oMMUD) (first comparison) and from 271 young (<35 years) MMUD (yMMUD) vs. 1315 old (≥35 years) Haplo donors (oHaplo) (second comparison). Acute graft-versus-host disease (aGVHD) grades II-IV were significantly lower in the yHaplo vs. oMMUD group (HR = 0.62, p = 0.007). There were no significant differences in chronic GVHD, non-relapse mortality (NRM), relapse incidence, leukemia-free survival, overall survival, and GVHD-free and relapse-free survival. As for the second comparison, more patients in the oHaplo group had de novo AML, 86.6% vs. 81.9% in the yMMUD group (p = 0.044), while myeloablative conditioning was used more frequently in the yMMUD group, 53.3% vs. 46.8% in the oHaplo group (p = 0.049). aGVHD grades II-IV and NRM were significantly lower in the yMMUD vs. oHaplo group (HR = 0.69, p = 0.013 and HR = 0.60, p = 0.022). All other transplant outcomes did not differ. In conclusion, HSCT from young alternative donors (<35 years) results in a lower incidence of grades II-IV aGVHD. In addition, NRM is lower in HSCT from yMMUD compared to HSCT from oHaplo.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   MeSH
• cyklofosfamid * terapeutické užití   MeSH
• dítě MeSH
• dospělí MeSH
• haploidentická transplantace metody   MeSH
• homologní transplantace metody   MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli MeSH
• nepříbuzný dárce * MeSH
• přežití po terapii bez příznaků nemoci MeSH
• příprava pacienta k transplantaci metody   MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Geografické názvy
• Evropa MeSH

Jedním z největších objevů v diabetologii posledních desetiletí je možnost dosažení remise DM 2. typu. DM 2. typu bylo podobně jako ostatní typy diabetu dlouho považováno za chronické, progredující a nevyléčitelné onemocnění. Jako první prokázaly možnosti remise DM 2. typu metody bariatrické chirurgie. V posledních letech ale přibývají studie, které dokládají možnosti dosažení remise také pomocí dietních intervencí jako je nízkoenergetická, středomořská, ketogenní dieta nebo přerušované lačnění. Klíčovým mechanismem dosažení remise DM 2. typu je redukce hmotnosti. Článek se zabývá jednotlivými metodami dosažení remise DM 2. typu a v závěru shrnuje praktická doporučení pro jejich aplikaci v klinické praxi.

One of the biggest breakthroughs in diabetes of the last decades is the possibility of achieving remission of type 2 DM. Type 2 DM, like other types of diabetes, has long been considered a chronic, progressive, and incurable disease. Bariatric surgery was the first to demonstrate the possibility of remission of type 2 DM. In recent years, however, an increasing number of studies have demonstrated that remission can also be achieved with dietary interventions such as low-calorie, Mediterranean, ketogenic diets or intermittent fasting. Weight reduction is a key mechanism for achieving remission of type 2 DM. The article reviews the different methods of achieving remission of type 2 DM and concludes with practical recommendations for their application in clinical practice.

• Klíčová slova
• studie DIRECT, studie DIADEM-I, studie LOOK AHEAD,
• MeSH
• bariatrická chirurgie metody   MeSH
• časové faktory MeSH
• diabetes mellitus 2. typu * diagnóza   metabolismus   patofyziologie   MeSH
• dietoterapie klasifikace   metody   MeSH
• hmotnostní úbytek * MeSH
• indukce remise * metody   MeSH
• inzulin terapeutické užití   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• Check Tag
• lidé MeSH

An increasing number of older patients with acute myeloid leukemia (AML) are offered an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Normally, older patients have older matched related donors (MRD). Matched unrelated donors (MUD) are an important alternative, but it remains unclear whether a younger MUD is associated with better outcomes, especially in the context of post-transplant cyclophosphamide (PTCy). We compared outcomes of patients older than 50 years with AML in first complete remission (CR1) and receiving a first HSCT from a 10/10 MUD aged younger than 40 years to those receiving a graft from a MRD aged older than 50 years, using PTCy and with well-known transplant conditioning intensity (TCI) score. A total of 345 consecutive patients were included and classified according to TCI score as low, intermediate, or high. On multivariable analysis in the TCI-intermediate/high group, MUD was associated with better graft-versus-host disease-free, relapse-free survival, lower non-relapse mortality and lower relapse incidence. For patients receiving a TCI-low regimen, outcomes are independent on the type of donor. In patients with AML in CR1, older than 50 years and receiving a TCI-intermediate/high conditioning regimen using PTCy, a MUD younger than 40 years is preferable over a MRD older than 50 years.

• MeSH
• akutní myeloidní leukemie * terapie   mortalita   farmakoterapie   patologie   MeSH
• cyklofosfamid * terapeutické užití   aplikace a dávkování   MeSH
• dospělí MeSH
• homologní transplantace MeSH
• indukce remise * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nemoc štěpu proti hostiteli etiologie   MeSH
• nepříbuzný dárce MeSH
• příprava pacienta k transplantaci * metody   MeSH
• prognóza MeSH
• senioři MeSH
• transplantace hematopoetických kmenových buněk * metody   MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH