INTRODUCTION: It is hypothesized that systemically administered antibiotics penetrate wound sites more effectively during negative pressure wound therapy (NPWT). However, there is a lack of clinical data from patients who receive NPWT for deep sternal wound infection (DSWI) after open-heart surgery. Here, we evaluated vancomycin penetration into exudate in this patient group. PATIENTS AND METHODS: For this prospective observational study, we enrolled 10 consecutive patients treated with NPWT for post-sternotomy DSWI. On the first sampling day, serum and exudate samples were synchronously collected at 0 (pre-dose), 0.5, 1, 2, 3 and 6 h after vancomycin administration. On the following three consecutive days, additional samples were collected, only before vancomycin administration. RESULTS: The ratio of average vancomycin concentration in wound exudate to in serum was higher for free (unbound) (1.51 ± 0.53) than for total (bound + unbound) (0.91 ± 0.29) concentration (p = 0.049). The percentage of free vancomycin was higher in wound exudate than serum (0.79 ± 0.19 vs. 0.46 ± 0.16; p = 0.04). Good vancomycin wound penetration was maintained on the following three days (vancomycin trough exudate-to-serum concentration ratio > 1). The total hospital stay was significantly longer in patients with DSWI (46 ± 11.6 days) versus without DSWI (14 ± 11.7 days) (p < 0.001). There was no in-hospital or 90-day mortality. Two patients experienced late DSWI recurrence. All-cause mortality was 4.8% during a median follow-up of 2.5 years. CONCLUSION: Vancomycin effectively penetrates wound exudate in patients receiving NPWT for DSWI after open-heart surgery.The protocol for this study was registered at ClinicalTrials.gov on July 16, 2024 (NCT06506032).
- MeSH
- antibakteriální látky * farmakokinetika aplikace a dávkování MeSH
- exsudáty a transsudáty metabolismus mikrobiologie MeSH
- infekce chirurgické rány * MeSH
- kardiochirurgické výkony * škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- senioři MeSH
- sternotomie * škodlivé účinky MeSH
- sternum chirurgie MeSH
- terapie ran pomocí řízeného podtlaku * metody MeSH
- vankomycin * aplikace a dávkování farmakokinetika MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
BACKGROUND: Advances in paediatric type 1 diabetes management and increased use of diabetes technology have led to improvements in glycaemia, reduced risk of severe hypoglycaemia, and improved quality of life. Since 1993, progressively lower HbA1c targets have been set. The aim of this study was to perform a longitudinal analysis of HbA1c, treatment regimens, and acute complications between 2013 and 2022 using data from eight national and one international paediatric diabetes registries. METHODS: In this longitudinal analysis, we obtained data from the Australasian Diabetes Data Network, Czech National Childhood Diabetes Register, Danish Registry of Childhood and Adolescent Diabetes, Diabetes Prospective Follow-up Registry, Norwegian Childhood Diabetes Registry, England and Wales' National Paediatric Diabetes Audit, Swedish Childhood Diabetes Registry, T1D Exchange Quality Improvement Collaborative, and the SWEET initiative. All children (aged ≤18 years) with type 1 diabetes with a duration of longer than 3 months were included. Investigators compared data from 2013 to 2022; analyses performed on data were pre-defined and conducted separately by each respective registry. Data on demographics, HbA1c, treatment regimen, and event rates of diabetic ketoacidosis and severe hypoglycaemia were collected. ANOVA was performed to compare means between registries and years. Joinpoint regression analysis was used to study significant breakpoints in temporal trends. FINDINGS: In 2022, data were available for 109 494 children from the national registries and 35 590 from SWEET. Between 2013 and 2022, the aggregated mean HbA1c decreased from 8·2% (95% CI 8·1-8·3%; 66·5 mmol/mol [65·2-67·7]) to 7·6% (7·5-7·7; 59·4mmol/mol [58·2-60·5]), and the proportion of participants who had achieved HbA1c targets of less than 7% (<53 mmol/mol) increased from 19·0% to 38·8% (p<0·0001). In 2013, the aggregate event rate of severe hypoglycaemia rate was 3·0 events per 100 person-years (95% CI 2·0-4·9) compared with 1·7 events per 100 person-years (1·0-2·7) in 2022. In 2013, the aggregate event rate of diabetic ketoacidosis was 3·1 events per 100 person-years (95% CI 2·0-4·8) compared with 2·2 events per 100 person-years (1·4-3·4) in 2022. The proportion of participants with insulin pump use increased from 42·9% (95% CI 40·4-45·5) in 2013 to 60·2% (95% CI 57·9-62·6) in 2022 (mean difference 17·3% [13·8-20·7]; p<0·0001), and the proportion of participants using continuous glucose monitoring (CGM) increased from 18·7% (95% CI 9·5-28·0) in 2016 to 81·7% (73·0-90·4) in 2022 (mean difference 63·0% [50·3-75·7]; p<0·0001). INTERPRETATION: Between 2013 and 2022, glycaemic outcomes have improved, parallel to increased use of diabetes technology. Many children had HbA1c higher than the International Society for Pediatric and Adolescent Diabetes (ISPAD) 2022 target. Reassuringly, despite targeting lower HbA1c, severe hypoglycaemia event rates are decreasing. Even for children with type 1 diabetes who have access to specialised diabetes care and diabetes technology, further advances in diabetes management are required to assist with achieving ISPAD glycaemic targets. FUNDING: None. TRANSLATIONS: For the Norwegian, German, Czech, Danish and Swedish translations of the abstract see Supplementary Materials section.
- MeSH
- diabetes mellitus 1. typu * epidemiologie krev farmakoterapie MeSH
- dítě MeSH
- glykovaný hemoglobin * analýza MeSH
- hypoglykemie epidemiologie MeSH
- hypoglykemika * terapeutické užití MeSH
- kojenec MeSH
- krevní glukóza * analýza MeSH
- lidé MeSH
- longitudinální studie MeSH
- mladiství MeSH
- předškolní dítě MeSH
- registrace * statistika a číselné údaje MeSH
- regulace glykemie statistika a číselné údaje metody MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Fructobacillus, a Gram-positive, non-spore-forming, facultative anaerobic bacterium, belongs to the fructophilic lactic acid bacteria (FLAB) group. The group's name originates from fructose, the favored carbon source for its members. Fructobacillus spp. are noteworthy for their distinctive traits, captivating the interest of scientists. However, there have been relatively few publications regarding the isolation and potential utilization of these microorganisms in the industry. In recent years, F. tropaeoli has garnered interest for its promising role in the food and pharmaceutical sectors, although the availability of isolates is rather limited. A more comprehensive understanding of Fructobacillus is imperative to evaluate their functionality in the industry, given their unique and exceptional properties. Our in vitro study on Fructobacillus tropaeoli KKP 3032 confirmed its fructophilic nature and high osmotolerance. This strain thrives in a 30% sugar concentration, shows resistance to low pH and bile salts, and exhibits robust autoaggregation. Additionally, it displays significant antimicrobial activity against foodborne pathogens. Evaluating its probiotic potential, it aligns with EFSA recommendations in antibiotic resistance, except for kanamycin, to which it is resistant. Further research is necessary, but preliminary analyses confirm the high probiotic potential of F. tropaeoli KKP 3032 and its ability to thrive in the presence of high concentrations of fructose. The results indicate that the isolate F. tropaeoli KKP 3032 could potentially be used in the future as a fructophilic probiotic, protective culture, and/or active ingredient in fructose-rich food.
- MeSH
- antibakteriální látky farmakologie MeSH
- fruktosa metabolismus MeSH
- koncentrace vodíkových iontů MeSH
- ovocné a zeleninové šťávy * mikrobiologie MeSH
- pomerančovník čínský mikrobiologie chemie MeSH
- potravinářská mikrobiologie MeSH
- probiotika * izolace a purifikace MeSH
- RNA ribozomální 16S genetika MeSH
- žlučové kyseliny a soli metabolismus MeSH
- Publikační typ
- časopisecké články MeSH
Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.
- MeSH
- alfa-galaktosidasa * aplikace a dávkování terapeutické užití MeSH
- dospělí MeSH
- enzymová substituční terapie * metody MeSH
- Fabryho nemoc * farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- polyethylenglykoly aplikace a dávkování MeSH
- rekombinantní proteiny * aplikace a dávkování terapeutické užití MeSH
- rozvrh dávkování léků MeSH
- senioři MeSH
- sfingolipidy krev MeSH
- trihexosylceramidy krev MeSH
- výsledek terapie 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
- klinické zkoušky, fáze III MeSH
- multicentrická studie MeSH
- práce podpořená grantem 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
- 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
- protinádorová antibiotika aplikace a dávkování MeSH
- protokoly protinádorové 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
CssRS is a two-component system that plays a pivotal role in mediating the secretion stress response in Bacillus subtilis. This system upregulates the synthesis of membrane-bound HtrA family proteases that cope with misfolded proteins that accumulate within the cell envelope as a result of overexpression or heat shock. Recent studies have shown the induction of CssRS-regulated genes in response to cell envelope stress. We investigated the induction of the CssRS-regulated htrA promoter in the presence of different cell wall- and membrane-active substances and observed induction of the CssRS-controlled genes by glycopeptides (vancomycin and teicoplanin), polymyxins B and E, certain β-lactams, and detergents. Teicoplanin was shown to elicit remarkably stronger induction than vancomycin and polymyxin B. Teicoplanin and polymyxin B induced the spxO gene expression in a CssRS-dependent fashion, resulting in increased activity of Spx, a master regulator of disulfide stress in Bacillus subtilis. The CssRS signaling pathway and Spx activity were demonstrated to be involved in Bacillus subtilis resistance to teicoplanin and polymyxin B.
- MeSH
- antibakteriální látky * farmakologie MeSH
- Bacillus subtilis * genetika účinky léků metabolismus MeSH
- bakteriální proteiny * genetika metabolismus MeSH
- polymyxin B * farmakologie MeSH
- promotorové oblasti (genetika) MeSH
- regulace genové exprese u bakterií * účinky léků MeSH
- signální transdukce MeSH
- teikoplanin * farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
Investigation determines the beneficial effect of bergaptol against gestational diabetes (GD). Gestational diabetes was induced in female rats and treated them with bergaptol 20 and 40 mg/kg for eighteen days. Effect of bergaptol was assessed on blood glucose and insulin level in GD rat. Inflammatory mediators and oxidative stress parameters were also assessed in GD rats. Moreover, mRNA expression of INSR, NF-kappaB, Akt and GSK-3beta were assessed in the GD rats by qRT-PCR method. In silico network pharmacology study was performed, along with gene ontology and egg pathway to assessed the targets of bergaptol, molecular docking study was also performed for the confirmation of possible pathway involved in the management of GD. Blood glucose and insulin level was significantly reduces in the blood bergaptol treated group than GD group of rats. Treatment with bergaptol ameliorates the altered level of mediators of inflammation and oxidative stress parameters in GD rats. There was significant reduction in the mRNA expression of NF-kappaB and GSK-3beta and increase in expression of INSR and Akt in the tissue homogenate of bergaptol treated GD rats. Docking study shows effective binding strength of bergaptol individually with INSR, NF-kappaB, Akt and GSK-3beta-protein targets. In conclusion, data of investigation suggest that bergaptol improves the sensitivity of insulin receptor in GD, as it reduces parameters of oxidative stress and inflammatory mediators by regulating INSR/NF-kappaB/Akt/GSK-3beta pathway. Key words Gestational diabetes, Bergaptol, Insulin resistance, Inflammation, Oxidative stress.
- MeSH
- experimentální diabetes mellitus * farmakoterapie metabolismus MeSH
- gestační diabetes * farmakoterapie metabolismus MeSH
- inzulinová rezistence * fyziologie MeSH
- kinasa glykogensynthasy 3beta metabolismus MeSH
- krevní glukóza metabolismus účinky léků MeSH
- krysa rodu rattus MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- receptor inzulinu metabolismus MeSH
- signální transdukce účinky léků MeSH
- simulace molekulového dockingu * MeSH
- těhotenství MeSH
- zánět farmakoterapie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- amnion MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- kyselina askorbová aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- neúspěšná terapie MeSH
- popálení oka * diagnostické zobrazování farmakoterapie patologie MeSH
- tetracykliny aplikace a dávkování MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- arteria iliaca * patofyziologie MeSH
- heparin nízkomolekulární farmakologie terapeutické užití MeSH
- heparin farmakologie klasifikace terapeutické užití MeSH
- kazuistiky jako téma MeSH
- lidé MeSH
- novorozenci extrémně nezralí MeSH
- novorozenec MeSH
- trombóza * diagnóza farmakoterapie patofyziologie prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- Publikační typ
- přehledy MeSH
Úvod: Trombotické příhody jsou v novorozeneckém věku relativně vzácná onemocnění. Vyskytují se zpravidla jako komplikace jiného onemocnění nebo jeho léčby, přičemž významným rizikovým faktorem jsou infekce, porodní komplikace a zavedení katétru do žilního či tepenného řečiště. Současná doporučení pro léčbu a profylaxi trombóz u dětí vycházejí z 9. konsenzu ACCP a aktuálních doporučení ASH a ISTH. Lékem volby jsou pro iniciální léčbu hepariny (nefrakcionovaný heparin (UFH) a nízkomolekulární hepariny (LMWH)). Strategie léčby u novorozenců se v některých aspektech od léčby starších dětí odlišuje. Jde zejména o vyšší dávkování LMWH a rozdílnou délku léčby. Soubor a metodika: Tato práce mapuje trombotické příhody u dětí od narození do 28 dnů věku, které byly diagnostikovány a léčeny na novorozeneckých pracovištích ve spolupráci s Oddělením dětské hematologie a biochemie FN Brno v letech 2011–2023. Výsledky: Ve sledovaném období bylo pro trombotickou příhodu léčeno 19 dětí v novorozeneckém věku. V souboru je 11 chlapců a 8 dívek o hmotnosti 780–4 600 g, jen čtyři děti byly nedonošené (narozené dříve než v 37. týdnu gravidity). Trombotická příhoda byla diagnostikována ve věku 0–22 dní. V našem souboru převažují žilní trombotické příhody (84 %), nejčastěji trombózy mozkových splavů (42 %). Kromě jedné dívky byli všichni pacienti léčeni podáváním LMWH, zpravidla nejprve ve formě kontinuální infuze a následně byli převedeni na podkožní aplikaci. Jedna pacientka byla po iniciální léčbě LMWH léčena v rámci klinické studie dabigatranem. Medián trvání léčby byl 66 dnů, v rozmezí 0–105 dní. Plné regrese trombotických změn bylo dosaženo u 63 % pacientů, alespoň parciální regrese trombózy pak u 84 %. Komplikace léčby jsme nezaznamenali, celkově byla léčba pacienty i rodiči dobře tolerována. Závěr: Diagnostika trombotických příhod v novorozeneckém věku vyžaduje zkušené personální obsazení, zázemí laboratoří a zobrazovacích metod. Léčba těchto onemocnění patří do rukou dětského hematologa. Lékem volby pro iniciální léčbu jsou v současnosti nízkomolekulární hepariny. Správně zvolená léčba vede spolu s řešením obvykle přítomného základního onemocnění u většiny pacientů k regresi trombotických změn bez dlouhodobých následků.
Introduction: Thrombotic events are a relatively rare disease in the neonatal period. They usually occur as a complication of another disease or its treatment, with infection, childbirth complications and the insertion of a catheter into a vessels being an important risk factor. Current recommendations for the treatment and prophylaxis of thrombosis in newborns are based on the 9th ACCP consensus and the recent recommendations of ASH and ISTH. Heparins (unfractionated heparin (UFH) and low molecular weight heparin (LMWH)) are the drug of choice for initial treatment. The treatment strategy for newborns differs in some aspects from the treatment of older children. It is mainly a higher dosage of LMWH and a different duration of treatment. Cohort and methods: This work maps thrombotic events in children from birth to 28 days of age, diagnosed and treated in neonatal units in cooperation with the Department of Pediatric Hematology and Biochemistry University Hospital Brno from 2011 to 2023. Results: In the observed period, 19 children in newborn age were treated for a thrombotic event. There were 11 boys and 8 girls treated, weight from 780 up to 4 600 g, only four children were premature (born before the 37th week of pregnancy). A thrombotic event was diagnosed at 0-22 days of age. In our group, venous thrombotic events predominate (84%), with most frequent cerebral sinovenous thrombosis (42%). All but one patient were treated with low-molecular-weight heparins. In most of the cases, the treatment was initiated via continuous infusion, later converted to standard subcutaneous administration. One patient was treated with dabigatran in a clinical trial after initial LMWH treatment. The median duration of treatment was 66 days, with a range of 0-105 days. Full regression of thrombotic changes was achieved in 63% of patients, at least partial regression of thrombosis in 84%. We did not notice any treatment complications. The treatment was well tolerated by patients and parents. Conclusion: Diagnosis of thrombotic events in the neonatal period requires experienced personnel, laboratory background and imaging methods. The treatment should be managed by a paediatric haematologist. Low molecular weight heparins are currently the drug of choice for initial treatment. A well guided therapy combined with the treatment of often underlying diseases has a high probability of thrombosis regression.
