BACKGROUND: Heart transplantation (HTx) is an established therapeutic option for children with end-stage heart failure. Comprehensive pediatric nationwide HTx program was introduced in 2014 in the Czech Republic. The aim of this study was to evaluate its mid-term characteristics and outcomes and to compare them with international data. METHODS: Retrospective observational study, including all patients who underwent HTx from June 2014 till December 2022. Data from the institutional database were used for descriptive statistics and survival analyses. RESULTS: A total of 30 HTx were performed in 29 patients with congenital heart disease (CHD, N = 15, single ventricular physiology in 10 patients) and cardiomyopathy (CMP, N = 14). Ten patients were bridged to HTx by durable left ventricular assist devices (LVADs) for a mean duration of 104 (SD 89) days. There was one early and one late death during median follow-up of 3.3 (IQR 1.3-6.1) years. Survival probability at 5 years after HTx was 93%. Two patients underwent re-transplantation (one of them in an adult center). Significant rejection-free survival at 1, 3, and 6 years after HTx was 76%, 63%, and 63%, respectively. CONCLUSIONS: The introduced pediatric HTx program reflects the complexity of the treated population, with half of the patients having complex CHD and one-third being bridged to HTx by LVADs. Mid-term results are comparable to worldwide data. The data confirm the possibility of establishing a successful nationwide pediatric HTx program in a relatively small population country with well-developed pediatric cardiovascular care and other transplantation programs.
- MeSH
- dítě MeSH
- dospělí MeSH
- kardiomyopatie * MeSH
- lidé MeSH
- podpůrné srdeční systémy * MeSH
- retrospektivní studie MeSH
- srdeční selhání * chirurgie MeSH
- transplantace srdce * MeSH
- vrozené srdeční vady * MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Česká republika MeSH
BACKGROUND: Cardiac surgery invariably triggers acute kidney stress causing adverse renal outcomes. The AKITA study evaluated the efficacy and safety of RMC-035, a novel analogue of alpha-1-microglobulin, for reducing cardiac surgery-associated kidney injury. METHODS: In this randomised double-blind placebo-controlled phase 2a study, we randomly assigned (1:1) adult hospitalised patients undergoing open-chest cardiac surgery at high risk for acute kidney injury (AKI) at 21 sites in North America and Europe to receive either RMC-035 (1.3 or 0.65 mg/kg) or placebo (1:1) for 2 days (5 intravenous infusions), stratified by region and renal function. Eligible patients had at least one pre-defined AKI risk factor. Patients with severe renal impairment (estimated glomerular filtration rate [eGFR] <30 mL/min/1.73 m2) were excluded. The co-primary efficacy and safety endpoints were AKI (Kidney Disease: Improving Global Outcomes definition) within 72 h after surgery and nature, frequency, and severity of treatment-emergent adverse events (TEAEs). Secondary endpoints included eGFR and Major Adverse Kidney Events (MAKE) up to Day 90. Randomised patients who had received at least one dose of study drug were analysed for primary and safety analyses. Participants, investigators and sponsor were masked to treatment allocation. This study is registered at ClinicalTrials.gov (NCT05126303) and EudraCT (2021-004040-19). FINDINGS: Patient enrolment was stopped at interim analysis due to futility. Between March 31, 2022 and July 12, 2023, 177 patients (RMC-035: 89, placebo: 88) were randomised and treated. AKI rate for RMC-035 vs placebo was 50.6% (n = 45) and 39.8% (n = 35) (relative risk [RR]: 1.30, 90% confidence interval [90% CI]: 0.99, 1.71; p = 0.12). A short-lived creatinine increase was observed with the higher RMC-035 dose. Treatment with RMC-035 was associated with improved secondary renal outcomes at Day 90: placebo-adjusted eGFR change from baseline 4.3 mL/min/1.73 m2, 90% CI 0.51-8.12, p = 0.06; and MAKE 6.7% (n = 6) vs 15.9% (n = 14); RR: 0.41, 90% CI: 0.19, 0.88, p = 0.05. The most frequently reported TEAEs for RMC-035 were chills (30.3%), nausea (21.3%), anaemia (20.2%); and atrial fibrillation (29.5%), anaemia (20.5%), hypervolemia (14.8%) for placebo. The majority of TEAEs in both treatment groups were mild or moderate in severity. In the RMC-035 group, 26 (29.2%) patients experienced at least one severe or life-threatening TEAE and in the placebo group 16 (18.2%) patients. There were 4 deaths per treatment arm (one treatment-related, in placebo group). INTERPRETATION: In this proof-of-concept study, RMC-035 did not reduce AKI 72 h after cardiac surgery. Evaluations may have been confounded by a drug-induced transient creatinine increase in a subgroup of patients. RMC-035 was associated with improved secondary renal outcomes. These results merit further investigation and should be interpreted with caution, as the study was not powered for these outcomes. FUNDING: Guard Therapeutics.
- Publikační typ
- časopisecké články MeSH
Reconstruction of right ventricular outflow tract in patients with congenital heart disease in various age groups remains a controversial issue. Currently, a little is known about the fate of secondary and subsequent conduit. The aim of the study was to determine risk factors of conduit failure, evaluate long-term conduit survival, find out which type of conduit should be preferred in case of reoperations. We performed a retrospective analysis of a total of 249 records of valved conduit secondary and subsequent replacement in right ventricular outflow tract in 197 patients. Median follow-up was 5.7 years. The study endpoints were defined as conduit explants; balloon dilatation of the graft (excluding balloon dilatation of left/right pulmonary artery), transcatheter pulmonary valve implantation; heart transplantation or death of the patient. There were total of 21 deaths (11% mortality) among 197 patients during the follow-up, 2 patients underwent heart transplant, in 23 implanted conduits pulmonary angioplasty or/including transcatheter pulmonary valve implantation was afterwards performed due to graft failure, conduit had to be explanted in 46 cases. After 28 years follow-up, freedom from graft failure after 5 years was 77%, 48% after 10 years and 21% after 15 years. Reoperative right ventricular outflow tract reconstruction demonstrates good mid-term and acceptable long-term outcomes regardless of the type of conduit implanted. Worse long-term graft survival of secondary and further conduits is associated with younger age of the recipient at implantation, small size of the conduit, younger age of donor and male donor in case of allograft implantation.
- Publikační typ
- abstrakt z konference MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
nestr.
Wound care and wound treatment is a serious socio-economic problem. It has been shown in both Europe and the US that amniotic membrane (AM) grafting promotes and accelerates healing of non-healing wounds when compared to standard of care (SOC). We propose two prospective multicenter studies to introduce and standardize AM treatment with the aim of faster and more effective treatment of a wide range of wounds. Prospective Study 1 will assess the effect of frozen AM in the treatment of non-healing wounds in at least 80 patients suffering from non-healing wounds (venous leg ulcer, diabetic and pressure ulcer). Prospective randomized Study 2 (90 patients) will evaluate the efficacy of cryopreserved and dried AM by their application to ulcers related to peripheral artery disease and venous insufficiency, and comparing them with SOC. We will determine the effects of the particular steps of AM processing on the efficiency of the biologically active substances present in AM. The evaluation of the effects of AM (healing rate, length of treatment) will be independent of the treatment centers.
Léčba a péče o rány je vážným sociálně-ekonomickým problémem. V Evropě a v USA bylo prokázáno, že transplantace amniové membrány (AM) ve srovnání se standardní terapií výrazně urychluje hojení ran, u dlouhodobě se nehojících ran hojení navodí a zrychlí, sníží bolest. V projektu navrhujeme provedení dvou prospektivních multicentrických studií, jejichž podstatou je zavést a standardizovat léčbu pomocí AM s cílem rychlejší a účinnější léčby širokého spektra ran. Prospektivní Studie 1 vyhodnotí účinek zmrazené AM v léčbě dlouhodobě se nehojících ran u minimálně 80 pacientů trpících zejména bércovými, diabetickými a dekubitálními vředy. Prospektivní randomizovaná Studie 2 (90 pacientů) vyhodnotí efektivitu různých typů AM (zmrazená a sušená) na léčbu žilního, arteriálního nebo smíšeného vředu, a prokáže případné rozdíly v účinnosti zmrazené a sušené AM ve srovnání se standardní terapií. Souběžně určíme vliv jednotlivých kroků přípravy AM na aktivitu biologicky účinných látek. Hodnocení efektu aplikace allograftu AM (rychlost a délka hojení) bude probíhat nezávisle na léčebných centrech.
- Klíčová slova
- amniová membrána, amniotic membrane, nehojící se rány, Non-healing wounds, Allograft, allograft,
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
To compare the therapeutic efficacy of cryopreserved amniotic membrane (AM) grafts and standard of care (SOC) in treating nonhealing wounds (NHW) through a prospective multicenter clinical trial, 42 patients (76% polymorbid) with 54 nonhealing wounds of various etiologies (mainly venous) and an average baseline size of 20 cm2 were included. All patients were treated for at least 6 weeks in the center before they were involved in the study. In the SOC group, 29 patients (36 wounds) were treated. If the wound healed less than 20% of the baseline size after 6 weeks, the patient was transferred to the AM group (35 patients, 43 wounds). Weekly visits included an assessment of the patient's condition, photo documentation, wound debridement, and dressing. Quality of life and the pain degree were subjectively reported by patients. After SOC, 7 wounds were healed completely, 1 defect partially, and 28 defects remained unhealed. AM application led to the complete closure of 24 wounds, partial healing occurred in 10, and 9 remained unhealed. The degree of pain and the quality of life improved significantly in all patients after AM application. This study demonstrates the effectiveness of cryopreserved AM grafts in the healing of NHW of polymorbid patients and associated pain reduction.
- Publikační typ
- časopisecké články MeSH
This study aimed to evaluate the efficacy of cryopreserved amniotic membrane (AM) grafts in chronic wound healing, including the mean percentage of wound closure per one AM application, and to determine whether the healing efficiency differs between AM grafts obtained from different placentas. A retrospective study analyzing inter-placental differences in healing capacity and mean wound closure after the application of 96 AM grafts prepared from nine placentas. Only the placentas from which the AM grafts were applied to patients suffering from long-lasting non-healing wounds successfully healed by AM treatment were included. The data from the rapidly progressing wound-closure phase (p-phase) were analyzed. The mean efficiency for each placenta, expressed as an average of wound area reduction (%) seven days after the AM application (baseline, 100%), was calculated from at least 10 applications. No statistical difference between the nine placentas' efficiency was found in the progressive phase of wound healing. The 7-day average wound reduction in particular placentas varied from 5.70 to 20.99% (median from 1.07 to 17.75) of the baseline. The mean percentage of wound surface reduction of all analyzed defects one week after the application of cryopreserved AM graft was 12.17 ± 20.12% (average ± SD). No significant difference in healing capacity was observed between the nine placentas. The data suggest that if there are intra- and inter-placental differences in AM sheets' healing efficacy, they are overridden by the actual health status of the subject or even the status of its individual wounds.
- MeSH
- amnion * transplantace MeSH
- hojení ran MeSH
- kryoprezervace MeSH
- lidé MeSH
- placenta * MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Cíl: Představit použití lidské kryokonzervované amniové membrány (AM) v léčbě chronických ran, specifikovat indikační kritéria pro její aplikaci, protokol aplikace a metodiku převazů. Dalším cílem je seznámení se souhrnnými výsledky studie léčby chronických nehojících se ran pomocí AM a s predikcí zhojení dle dynamiky léčby. Materiály a metody: Standardizace léčby pomocí kryokonzervované AM proběhla v rámci multicentrické studie ve třech klinických centrech. Pacientům s chronickými ranami, kteří se nehojili v průměru po dobu 34 měsíců (minimálně šest týdnů), byla aplikována AM, s pravidelnými vizitami po sedmi dnech. Výsledky: Z 35 pacientů s 43 ranami různé etiologie, bylo po aplikaci AM zcela zhojeno 24 ran (56 %), 10 ran bylo zhojeno částečně (> 50 % plochy rány) (23 %), 9 ran (21 %) se zhojit nepodařilo. Během léčby AM zaznamenali pacienti silný analgetický účinek. Sledování dynamiky hojení vedlo ke stanovení predikčního intervalu pro posouzení schopnosti rány zhojit se pomocí AM na 10–12 týdnů. Závěr: Léčba chronických ran pomocí AM přináší prospěch indikovaným pacientům, jak v akceleraci hojení, tak ve zlepšení kvality života, a to zejména snížení bolesti v oblasti rány.
Objective: This work presents the use of human cryopreserved amniotic membrane (AM) in the treatment of chronic wounds, specifying the indication criteria for its application, application protocol, and wound dressing methodology. At the same time, it presents the summary results of the study of the treatment of chronic non-healing wounds using AM with the prediction of healing according to the dynamics of the treatment. Materials and methods: Standardization of treatment using cryopreserved AM took place within the framework of a multicentre study in three specialist centres. Patients with chronic wounds that did not heal for an average of 34 months (min. six weeks) were treated with AM, with regular visits every seven days. The AM application was carried out 1–2 times in 14 days. Results: Out of 35 patients with 43 wounds of various etiologies, 24 wounds (56%) were completely healed after AM application, 10 wounds were partially healed (> 50% of the wound area) (23%), 9 wounds (21%) failed to heal. During AM treatment, patients experienced a strong analgesic effect. Monitoring the dynamics of healing led to the establishment of a prediction interval for assessing the ability of the wound to heal using AM at 10–12 weeks. Conclusion: The treatment of chronic wounds using AM brings benefits to the indicated patients, both in the acceleration of healing and in the improvement of the quality of life, especially in the reduction of pain in the wound area.
- MeSH
- amnion * fyziologie MeSH
- biologické krytí * klasifikace MeSH
- hojení ran MeSH
- kryoprezervace metody MeSH
- lidé MeSH
- membrány fyziologie MeSH
- placenta fyziologie MeSH
- rány a poranění ošetřování terapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- multicentrická studie MeSH
- práce podpořená grantem MeSH
We evaluated the effect of the application of cryo-preserved amniotic membrane on the healing of 26 non-healing wounds (18 patients) with varying aetiologies and baseline sizes (average of 15.4 cm2 ), which had resisted the standard of care treatment for 6 to 456 weeks (average 88.8 weeks). Based on their average general responses to the application of cryo-preserved AM, we could differentiate three wound groups. The first healed group was characterised by complete healing (100% wound closure, maximum treatment period 38 weeks) and represented 62% of treated wounds. The wound area reduction of at least 50% was reached for all wounds in this group within the first 10 weeks of treatment. Exactly 19% of the studied wounds responded partially to the treatment (partially healed group), reaching less than 25% of closure in the first 10 weeks and 90% at maximum for extended treatment period (up to 78 weeks). The remaining 19% of treated wounds did not show any reaction to the AM application (unhealed defects). The three groups have different profiles of wound area reduction, which can be used as a guideline in predicting the healing prognosis of non-healing wounds treated with a cryo-preserved amniotic membrane.
- MeSH
- amnion * MeSH
- hojení ran * fyziologie MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
