AIMS: To assess the efficacy and safety of switching from premixed insulin to a once-daily, fixed-ratio combination of insulin glargine 100 U/mL + lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D). METHODS: In this phase 4, 24-week, single-arm study, participants switched from once-daily or twice-daily premixed insulin to iGlarLixi (EudraCT number 2021-003711-25). Key inclusion criteria: ≥18 years; premixed insulin therapy for ≥3 months and < 10 years; ± 1-2 oral antidiabetic drugs (OADs); HbA1c ≥7.5% to ≤10.0%. The primary endpoint was the change in HbA1c from baseline to Week 24. Secondary endpoints included: participants achieving HbA1c <7% and change in body weight at Week 24, and safety. RESULTS: Overall, 162 participants switched to iGlarLixi (89.5% from twice-daily premixed insulin); mean duration of diabetes was 15.7 (standard deviation [SD]: 8.3) years. Mean baseline HbA1c (8.5%) reduced by least squares (LS) mean of 1.2% (95% confidence interval [CI]: -1.4, -1.1) at Week 24, and 37.6% of participants had achieved an HbA1c target of <7% (95% CI: 30.0, 45.7). LS mean body weight change from baseline to Week 24 was -1.0 kg (95% CI: -1.6, -0.5). Fasting and post-prandial plasma glucose decreased from baseline to Week 24 by 45.6 mg/dL (SD ± 52.4) and 67.6 mg/dL (SD ± 65.1), respectively. Confirmed symptomatic hypoglycaemia occurred in 38.3% of participants (ADA level 1: 35.8%; level 2: 15.4%; level 3: 0.0%). CONCLUSIONS: iGlarLixi initiation was associated with improved glycaemic control, without body weight gain or increased hypoglycaemia over 24 weeks.

• MeSH
• diabetes mellitus 2. typu * farmakoterapie   krev   MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• glykovaný hemoglobin analýza   MeSH
• hypoglykemie chemicky indukované   MeSH
• hypoglykemika * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• inzulin glargin * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• krevní glukóza účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada léků * MeSH
• peptidy * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• receptor pro glukagonu podobný peptid 2 MeSH
• rozvrh dávkování léků 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
• klinické zkoušky, fáze IV MeSH
• multicentrická studie MeSH

Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 109/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 109/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 109/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 109/L or ≥ 30 × 109/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 109/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients. Trial Registration: NCT03395210, EudraCT 2017-004012-19.

• MeSH
• aplikace orální MeSH
• dospělí MeSH
• idiopatická trombocytopenická purpura * farmakoterapie   MeSH
• inhibitory proteinkinas * škodlivé účinky   terapeutické užití   aplikace a dávkování   MeSH
• inhibitory tyrosinkinasy MeSH
• lidé středního věku MeSH
• lidé MeSH
• počet trombocytů MeSH
• proteinkinasa BTK * antagonisté a inhibitory   MeSH
• pyrazoly terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• pyrimidiny aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH

Fabry disease is an X-linked lysosomal storage disorder that causes accumulation of glycosphingolipids in body tissues and fluids, leading to progressive organ damage and life-threatening complications. It can affect both males and females and can be classified into classic or later-onset phenotypes. The disease severity in females ranges from asymptomatic to the more severe, classic phenotype. Most females are hemizygous and the X-linked inheritance is associated with variable X-activation pattern and residual enzymatic activity. The heterogeneity of clinical presentation in females requires different approaches to diagnosis and management than males. A European group of 7 physicians, experienced in the management of Fabry disease, convened to discuss patient perspectives and published guidelines. The experts discussed the need to focus on psychological treatment in relation to individual coping styles when monitoring targets, and the lack of data supporting the use of plasma globotriaosylsphingosine over enzyme activity in the diagnosis of these patients. It was suggested that the high phenotypic variability in female patients may be related to the dynamic nature of the X-chromosome inactivation process and further understanding of this process could help predict the progression of Fabry disease in females and facilitate timely intervention. Due to the range of disease severity they exhibit, female patients with Fabry disease may require a more individualized treatment approach than males. Despite current recommendations, the experts agreed that early disease-specific treatment initiation in high-risk females could improve clinical outcome.

• MeSH
• Fabryho nemoc * terapie   genetika   diagnóza   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

AIM: To evaluate the efficacy of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) using derived time-in-range (dTIR). METHODS: Participant-level data from LixiLan-L, LixiLan-O and LixiLan-G were pooled and dTIR (70-180 mg/dL), derived time-above-range (> 180 mg/dL) and derived time-below-range (dTBR; < 70 mg/dL) were calculated from participant seven-point self-monitored blood glucose profiles. RESULTS: This pooled analysis included data from 2420 participants receiving iGlarLixi (n = 1093), iGlar (n = 836), Lixi (n = 234) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA) (n = 257). Numerically greater improvements in least square (LS) means dTIR were seen from baseline to end of treatment (EOT) with iGlarLixi (25.7%) versus iGlar (15.8%), Lixi (11.7%) or GLP-1 RA (16.2%). At EOT, the mean (standard deviation) dTBR was 0.71% ± 3.4%, 0.61% ± 3.2%, 0.08% ± 1.0% and 0.0% ± 0.0% for iGlarLixi, iGlar, Lixi and GLP-1 RA, respectively. In a subgroup analysis, participants aged younger than 65 years (n = 1690) and 65 years or older (n = 713) showed numerically greater improvements in LS means dTIR from baseline to EOT with iGlarLixi versus iGlar, Lixi or GLP-1 RA. CONCLUSIONS: iGlarLixi achieved improvements in dTIR, with low dTBR values, providing further evidence to inform clinical outcomes with the use of iGlarLixi.

• MeSH
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• diabetes mellitus 2. typu * farmakoterapie   krev   MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• glykovaný hemoglobin analýza   metabolismus   účinky léků   MeSH
• hypoglykemika * terapeutické užití   MeSH
• inzulin glargin * terapeutické užití   MeSH
• krevní glukóza * účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• peptidy * terapeutické užití   aplikace a dávkování   MeSH
• randomizované kontrolované studie jako téma MeSH
• receptor pro glukagonu podobný peptid 2 MeSH
• selfmonitoring glykemie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• randomizované kontrolované studie MeSH

Fabry Registry data were analyzed among 83 agalsidase beta-treated patients with Fabry disease who switched to migalastat. Outcomes (estimated glomerular filtration rate [eGFR], urine protein-creatinine ratio [UPCR], plasma globotriaosylceramide [GL-3], plasma globotriaosylsphingosine [lyso-GL-3], interventricular septal wall thickness [IVST], left posterior wall thickness [LPWT], left ventricular mass index [LVMI]) were assessed using linear mixed models to estimate annual change over time in the pre- and postswitch periods. eGFR decreased throughout both periods (preswitch: -0.85 mL/min/1.73 m2/year; postswitch: -1.96 mL/min/1.73 m2/year; both p < 0.0001), with steeper decline postswitch (ppre/post = 0.01) in both classic and late-onset patients. UPCR increased significantly postswitch (ppre/post = 0.003) among classic patients and was stable in both periods among late-onset patients. GL-3 trajectories worsened postswitch across phenotypes (ppre/post = 0.0005 classic, 0.02 late-onset). LPWT was stable preswitch (0.07 mm/year, p = 0.25) and decreased postswitch (-0.51 mm/year, p = 0.0005; ppre/post = 0.0009), primarily among late-onset patients. IVST and LVMI slopes varied significantly by phenotype. Among classic patients, IVST and LVMI were stable and decreasing, respectively preswitch and increasing postswitch (ppre/post = 0.02 IVST, 0.01 LVMI). Among late-onset patients, IVST significantly decreased postswitch (ppre/post = 0.0003); LVMI was stable over time (ppre/post = 0.89). Ultimately, eGFR and GL-3 trajectories worsened postswitch across phenotypes, while UPCR and cardiac measures worsened among classic and stabilized/improved among late-onset patients. These findings indicate variability in long-term outcomes after switching from ERT to migalastat, underscoring the importance of careful monitoring.

• MeSH
• 1-deoxynojirimycin * analogy a deriváty   terapeutické užití   aplikace a dávkování   MeSH
• alfa-galaktosidasa * terapeutické užití   MeSH
• dospělí MeSH
• enzymová substituční terapie metody   MeSH
• Fabryho nemoc * farmakoterapie   MeSH
• glykolipidy MeSH
• hodnoty glomerulární filtrace * MeSH
• izoenzymy * terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• registrace * MeSH
• sfingolipidy krev   MeSH
• trihexosylceramidy metabolismus   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
• práce podpořená grantem MeSH

• MeSH
• diabetes mellitus 2. typu * farmakoterapie   MeSH
• fixní kombinace léků MeSH
• glykovaný hemoglobin analýza   účinky léků   metabolismus   MeSH
• hypoglykemika * terapeutické užití   MeSH
• inzulin glargin * terapeutické užití   aplikace a dávkování   MeSH
• krevní glukóza účinky léků   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• peptidy * terapeutické užití   aplikace a dávkování   MeSH
• receptor pro glukagonu podobný peptid 2 MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH

INTRODUCTION: Multiple daily injection insulin regimen (MDI) represents the most intensive insulin regimen used in the management of people with type 2 diabetes (PwT2D). Its efficacy regarding glycaemic control is counterbalanced by the increased risk of hypoglycaemia, frequently observed tendency to weight gain and necessity for frequent glucose monitoring. Recent introduction of novel antidiabetic medications with pleiotropic effects reaching far beyond the reduction of glycaemia (HbA1c), such as the glucagon-like peptide 1 receptor agonist (GLP-1 RA), has significantly widened the therapeutic options available for management of T2D. Consequently, there is currently a substantial number of PwT2D for whom the MDI regimen was initiated at a time when no other options were available. Yet, in present times, these individuals could benefit from simplified insulin regimens ideally taking advantage of the beneficial effects of the novel classes of antidiabetic medications. iGlarLixi (Suliqua®) is a once-daily fixed-ratio combination of basal insulin analogue glargine 100 U/ml and a GLP-1 RA lixisenatide. METHODS: Insulin therapy DE-intensificAtion with iglarLixi (IDEAL) is a six-centre, open-label, parallel-group, active comparator, phase IV randomised controlled trial with a 24-week active treatment period examining the efficacy and safety of MDI regimen de-intensification with once-daily administration of iGlarLixi versus MDI regimen continuation in PwT2D on a backgroud therapy with metformin ± sodium-glucose cotransporter 2 inhibitor. PLANNED OUTCOMES: The primary objective is to compare the effects of MDI therapy de-intensification with iGlarLixi versus MDI regimen continuation regarding glycaemic control (HbA1c). Secondary objectives include detailed evaluation of the effects of MDI regimen de-intensification with iGlarLixi on glycaemic control using standardised continuous glucose monitoring (CGM) metrics and self-monitoring of plasma glucose. Furthermore, body weight and body composition analysis, quality of life and safety profile are evaluated. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04945070.

• Publikační typ
• časopisecké články MeSH

Gain/amplification of 1q21 (≥3 copies), a chromosomal abnormality frequently observed in multiple myeloma, can negatively affect prognosis, due to its involvement in resistance to anti-myeloma therapy and disease progression. In this updated subgroup analysis of the randomized, Phase 3 IKEMA study (NCT03275285) in relapsed/refractory multiple myeloma (RRMM), we evaluated progression-free survival (PFS) and depth of response with the anti-CD38 antibody isatuximab plus carfilzomib-dexamethasone (Isa-Kd) versus Kd, in 1q21+ patients and related subgroups, at long-term follow-up (44.2 months). Our analysis included patients with 1q21+ (≥3 copies, with/without high-risk chromosomal abnormality [HRCA]), isolated 1q21+ (≥3 copies, without HRCA), gain(1q21) (3 copies, with/without HRCA), and amp(1q21) (≥4 copies, with/without HRCA). PFS benefit was achieved with Isa-Kd versus Kd in patients with 1q21+ (HR 0.58, 95% CI: 0.37-0.92), with isolated 1q21+ (HR 0.49, 95% CI: 0.27-0.92), with gain(1q21), or amp(1q21), consistent with the overall population and prior interim 1q21+ subgroup analyses. Median PFS with Isa-Kd versus Kd was 25.8 versus 16.2 months in 1q21+ patients and 38.2 versus 16.2 months in patients with isolated 1q21+. Clinically meaningful, higher rates of very good partial response or better, complete response or better (≥CR), minimal residual disease (MRD) negativity, and MRD negativity and ≥CR were reached with Isa-Kd versus Kd in patients with 1q21+, isolated 1q21+, gain(1q21), or amp(1q21). In Isa-Kd and Kd, the MRD negativity and ≥CR rate was 29.3% versus 15.4% in 1q21+ patients, 36.2% versus 12.9% in patients with isolated 1q21+, 27.9% versus 13.5% in patients with gain(1q21), and 31.3% versus 20.0% in patients with amp(1q21), respectively. In conclusion, addition of Isa to Kd in triplet combination therapy has shown PFS benefit and deeper responses, compared with Kd, in 1q21+ patients at higher risk of progression, including patients with isolated 1q21+, gain(1q21), and amp(1q21), thus supporting Isa-Kd an effective treatment option for patients with RRMM.

• MeSH
• chromozomální aberace MeSH
• dexamethason terapeutické užití   MeSH
• humanizované monoklonální protilátky * MeSH
• lidé MeSH
• mnohočetný myelom * MeSH
• oligopeptidy * MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The majority of cases of chronic kidney disease (CKD) worldwide are driven by the presence of type 2 diabetes (T2D), resulting in an increase in CKD rates over the past few decades. The existence of CKD alongside diabetes is associated with increased burden of cardiovascular disease and increased risk of death. Optimal glycaemic control is essential to prevent progression of CKD, but achieving glycaemic targets in people with CKD and diabetes can be challenging because of increased risk of hypoglycaemia and limitations on glucose-lowering therapeutic options. This review considers the challenges in management of T2D in people with impaired kidney function and assesses evidence for use of basal insulin analogues in people with CKD.

• MeSH
• chronická renální insuficience * komplikace   farmakoterapie   chemicky indukované   MeSH
• diabetes mellitus 2. typu * komplikace   farmakoterapie   chemicky indukované   MeSH
• hypoglykemie * chemicky indukované   prevence a kontrola   komplikace   MeSH
• hypoglykemika terapeutické užití   MeSH
• inzulin terapeutické užití   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

AIMS: To determine the current state of the use of reperfusion and adjunctive therapies and in-hospital outcomes in European Society of Cardiology (ESC) member and affiliated countries for patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS). METHODS AND RESULTS: ESC EurObservational Research Programme prospective international cohort study of admissions with STEMI within 24 h of symptom onset (196 centres; 26 ESC member and 3 affiliated countries). Of 11 462 patients enrolled, 448 (3.9%) had CS. Patients with compared to patients without CS, less frequently received primary percutaneous coronary intervention (PCI) (65.5% vs. 72.2%) and fibrinolysis (15.9% vs. 19.0), and more often had no reperfusion therapy (19.0% vs. 8.5%). Mechanical support devices (intraaortic ballon pump 11.2%, extracoporeal membrane oxygenation 0.7%, other 1.1%) were used infrequently in CS. Bleeding definition academic research consortium 2-5 bleeding complications (10.1% vs. 3.0%, P < 0.01) and stroke (4.2% vs. 0.9%, P < 0.01) occurred more frequently in patients with CS. In-hospital mortality was 10-fold higher (35.5% vs. 3.1%) in patients with CS. Mortality in patients with CS in the groups with PCI, fibrinolysis, and no reperfusion therapy were 27.4%, 36.6%, and 62.4%, respectively. CONCLUSION: In this multi-national registry, patients with STEMI complicated by CS less frequently receive reperfusion therapy than patients with STEMI without CS. Early mortality in patients with CS not treated with primary PCI is very high. Therefore, strategies to improve clinical outcome in STEMI with CS are needed.

• MeSH
• infarkt myokardu s elevacemi ST úseků * komplikace   diagnóza   terapie   MeSH
• kardiogenní šok etiologie   terapie   MeSH
• kardiologie * MeSH
• kohortové studie MeSH
• koronární angioplastika * metody   MeSH
• lidé MeSH
• prospektivní studie MeSH
• registrace MeSH
• reperfuze MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH