14 research outputs found
Változások az őssejt-transzplantációhoz társult thromboticus microangiopathia diagnosztikus kritériumrendszerében
Absztrakt:
Az őssejt-transzplantációhoz társult thromboticus microangiopathia egy
multifaktoriális szövődmény transzplantáció után. Incidenciája a különböző
diagnosztikus kritériumrendszerek miatt nagyon eltérő az irodalomban. A
thromboticus microangiopathia aktivitását jelző klinikai paraméterek, így a
laktátdehidrogenáz-emelkedés, a hematológiai paraméterek és a vesefunkció
változásai az őssejt-transzplantáció után nem specifikusak. A
patomechanizmusában a klasszikus és az alternatív út diszregulációjának egyaránt
szerepe lehet, azonban a komplex patomechanizmus pontosan még nem ismert. A
jövőben a komplement paraméterek, köztük a terminális komplement út aktivációs
komplex monitorozása segítheti a klinikusokat a gyors és pontos diagnózisban, a
kezelésre szoruló betegek optimális kiválasztásában, a terápia várható
hatékonyságának előrejelzésében és eredményességének monitorizálásában. A
közlemény a thromboticus microangiopathia diagnosztikus kritériumrendszereinek
és a terápiás lehetőségeinek változásait, valamint a hazai gyermek betegekben
szerzett tapasztalatokat mutatja be. Orv Hetil. 2017; 158(27): 1043–1050.
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Abstract:
Hematopoietic stem cell transplantation associated thrombotic microangiopathy is
a multifactorial complication, and has variable incidence in study populations
due to different diagnostic criteria. The diversity of activity parameters, like
elevated laktát-dehidrogenáz, hematological parameters and kidney function are
not specific variables after stem cell transplantation. Dysregulation of the
classical and alternative pathway can play an important role in the
pathomechanism of thrombotic microangiopathy, but the understanding of the role
of complement activation under transplantation conditions requires further
investigation. Monitoring of complement parameters, including terminal
complement pathway activation complex during transplantation may help physicians
to improve diagnostic strategy, to evaluate therapeutical options and to predict
and follow up efficacy of complement blockade methods and supportive therapy.
This review focuses on the development of diagnostic criteria and therapeutical
options in thrombotic microangiopathy, and presents some preliminary findings
while using different diagnostic criteria in pediatric patients. Orv Hetil.
2017; 158(27): 1043–1050
Korszakváltás a gyermekkori szerzett csontvelő-elégtelenséggel járó kórképek kezelésében Magyarországon = Change in paradigm in the treatment of pediatric acquired bone marrow failure syndromes in Hungary
Absztrakt:
Bevezetés: A gyermekkori szerzett csontvelő-elégtelenségek
ritka, kezelés nélkül halálos betegségek. Egységes diagnosztikájukat és
terápiájukat európai munkacsoport felügyeli. A munkacsoport bevezette a
hypocellularis gyermekkori refrakter cytopenia entitást, melyet csökkentett
intenzitású kondicionálással transzplantálva lényegesen jobb túlélési
eredményeket kaptak. Célkitűzés: A protokollhoz csatlakozás
előtt és az azóta eltelt 5 évben kezelt betegek eredményeinek ismertetése.
Módszer: A 2013 és 2017 között eltelt 5 évben a Magyar
Gyermekonkológiai Hálózat 8 központjában 55 gyermeket kezeltünk (súlyos
aplasticus anaemia: 9, myelodysplasticus szindróma: 41, juvenilis myelomonocyter
leukaemia: 5). Súlyos aplasticus anaemiában 7 esetben végeztünk
őssejt-transzplantációt, egy esetben antithymocytaglobulin-kezelést, egy beteg a
diagnózis előtt meghalt. Myelodysplasiában 37 esetben végeztünk
transzplantációt, 4 esetben a szoros megfigyelést választhattuk. E
transzplantációk 54%-a (20 eset) csökkentett intenzitású kondicionálással
történt. A juvenilis myelomonocyter leukaemiában szenvedő 5 betegnél
transzplantáció történt. Eredmények: A diagnózis és a kuratív
kezelés között eltelt idő medián 92 (3–393) nap volt, súlyos aplasticus anaemia
esetén 28 (3–327) nap. Akut graft versus host betegség II–IV. fokozatú
súlyossággal 22,6%, III–IV. fokozatú súlyossággal 6,8%-ban jelentkezett, míg
betegeink 11,2%-a krónikus graft versus host betegségben szenvedett. A súlyos
aplasticus anaemiával kezelt 8 beteg mindegyike teljes remisszióban él (100%). A
myelodysplasia miatt transzplantált betegek becsült túlélése 85,1%, juvenilis
myelomonocyter leukaemiában 75%. A medián követési idő 30,4 (1,1–62,5) hónap
volt. Jelen eredményeinket összevetettük az 1992 és 2012 között kezelt betegek
eredményeivel. A túlélés az új szemlélet nyomán jelentősen javult, súlyos
aplasticus anaemiában trendszerűen 70%-ról 100%-ra (p = 0,133),
myelodysplasticus szindrómában szignifikánsan 31,3%-ról 85,1%-ra (p = 0,000026).
Következtetés: Paradigmaváltás történt a gyermekkori
szerzett csontvelő-elégtelenségek kezelésében, a betegcsoport túlélése
szignifikánsan növekedett. Orv Hetil. 2018; 159(42): 1710–1719.
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Abstract:
Introduction: Acquired bone marrow failures are rare but fatal
diseases in childhood. Since 2013, Hungary has been participating as a full
member in the work of the European Working Group on uniform diagnostics and
therapy in patients with acquired bone marrow failure syndromes. Hypocellular
refractory cytopenia of childhood has been emphasized as a frequent entity,
transplanted by reduced intensity conditioning with excellent outcomes.
Aim: To analyse and compare the results of treatment before
and after our joining. Method: A total of 55 patients have been
treated in the 8 centres of the Hungarian Pediatric Oncology Network during 5
years between 2013 and 2017 (severe aplastic anemia: 9, myelodysplastic
syndrome: 41, juvenile myelomonocytic leukemia: 5 patients). Allogeneic
hematopoietic stem cell transplantation was performed in severe aplastic anemia
in 7 cases, while antithymocyte globulin was administered in one case and one
patient died before diagnosis. In patients with myelodysplastic syndromes, watch
and wait strategy was applied in 4, while transplantation in 37 cases. Reduced
intensity conditioning was used in 54 percent of these cases. Transplantation
was the treatment of choice in all 5 patients with juvenile myelomonocytic
leukemia. Results: In the whole patient cohort, the time from
diagnosis to treatment was median 92 (3–393) days, while in severe aplastic
anemia median 28 (3–327) days only. Grade II–IV acute graft versus host disease
occurred in 22.6%, grade III–IV in 6.8% and chronic in 11.2%. All the patients
treated with severe aplastic anemia are alive and in complete remission (100%).
The overall estimated survival rate is 85.1% in myelodysplastic syndrome, while
75% in juvenile myelomonocytic leukemia. The median follow-up was 30.4
(1.1–62.5) months. There was a remarkable increase in overall survival comparing
the data before (1992–2012) and after (2013) joining the international group,
70% vs. 100% (p = 0.133) in severe aplastic anemia and 31.3% vs. 85.1% (p =
0.000026) in myelodysplastic syndrome. Conclusion: Due to a
change in the paradigm of the conditioning regimen in hypocellular refractory
cytopenia of childhood, the overall survival rate has significantly increased.
Orv Hetil. 2018; 159(42): 1710–1719
Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017
Background
Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout.
Methods
The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function.
Findings
Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function.
Interpretation
Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI
Performance of the beta-glucan test for the diagnosis of invasive fusariosis and scedosporiosis: a meta-analysis
The (1→3)-β-D-glucan (BDG) is a component of the fungal cell wall that can be detected in serum and used as an adjunctive tool for the diagnosis of invasive mold infections (IMI) in patients with hematologic cancer or other immunosuppressive conditions. However, its use is limited by modest sensitivity/specificity, inability to differentiate between fungal pathogens, and lack of detection of mucormycosis. Data about BDG performance for other relevant IMI, such as invasive fusariosis (IF) and invasive scedosporiosis/lomentosporiosis (IS) are scarce.
The objective of this study was to assess the sensitivity of BDG for the diagnosis of IF and IS through systematic literature review and meta-analysis. Immunosuppressed patients diagnosed with proven or probable IF and IS, with interpretable BDG data were eligible. A total of 73 IF and 27 IS cases were included. The sensitivity of BDG for IF and IS diagnosis was 76.7% and 81.5%, respectively. In comparison, the sensitivity of serum galactomannan for IF was 27%. Importantly, BDG positivity preceded the diagnosis by conventional methods (culture or histopathology) in 73% and 94% of IF and IS cases, respectively. Specificity was not assessed because of lacking data. In conclusion, BDG testing may be useful in patients with suspected IF or IS. Combining BDG and galactomannan testing may also help differentiating between the different types of IMI
Geotrichum capitatum/Saprochaete capitata fertőzés első hazai esete egy immunszupprimált gyermekben = First Hungarian report of Geotrichum capitatum/Saprochaete capitata infection in an immunocompromised child
Leukaemiás betegekben esetenként rossz prognózisú, ritka, opportunista gombafertőzések is kialakulhatnak. Magyarországon Geotrichum capitatum okozta gombafertőzést a korábbiakban még nem írtak le. Esetbemutatásunkkal a G. capitatum okozta gombafertőzésre szeretnénk ráirányítani a figyelmet. A másfél éves, akut myeloid leukaemiás leánygyermeket testvér donoros csontvelő-transzplantáció után 120 nappal kialakult recidíva miatt kezeltük. A kemoterápia megkezdését követő 11. napon magas, hullámzó lázmenete indult, mely kombinált, széles spektrumú antibiotikum- és gombaellenes (pozakonazol-) terápia mellett sem szűnt. A súlyosbodó légúti tünetei miatt elvégzett mellkas-CT-vizsgálat invazív gombainfekció gyanúját vetette fel. Hemokultúrából G. capitatum fertőzés igazolódott. Az empirikusan alkalmazott liposzómás amfotericin B kezelést a nemzetközi tapasztalatok alapján vorikonazollal egészítettük ki, állapotjavulást azonban nem észleltünk. Az alapbetegség progressziója miatt a beteget néhány nap múlva elvesztettük. A G. capitatum, újabb nevén Saprochaete capitata egy ubiquitaer sarjadzó gomba, mely elsősorban leukaemiás betegeknél okozhat rossz prognózisú fertőzést. Ennek tünetei elsősorban a bőrben és a légutakban jelentkezhetnek. Felismerésében elengedhetetlen a kórokozó pontos identifikálása, mivel a szokásos diagnosztikai tesztek nem adnak specifikus reakciót. Kezelésében a kevés nemzetközi tapasztalat alapján az amfotericin B és a vorikonazol kombinációja játszhat elsődleges szerepet, a kórkép azonban adekvát kezelés mellett is 50%-ban letális. A G. capitatum okozta első hazai eset leírásával az immunszupprimált betegekben kialakuló ritka, rossz prognózisú fertőzést előidéző opportunista gombafajnak a jelentőségére hívjuk fel a figyelmet. Orv Hetil. 2023; 164(26): 1034–1038. | Patients with leukemia may occasionally suffer from rare opportunistic fungal infections with poor prognosis. Fungal
infection caused by Geotrichum captitatum has not yet been described in Hungary. With this case report, we would
like to draw attention to the fungal infection caused by G. capitatum. The 1.5-year-old girl with acute myeloid leukemia was treated for relapse diagnosed +120 days after a sibling donor bone marrow transplantation. High-grade,
fluctuating fever began 11 days after the start of chemotherapy which did not decrease despite combined treatment
with broad-spectrum antibiotics and antifungals (posaconasole). Due to worsening respiratory symptoms, a chest
CT-scan was performed, raising suspicion of an invasive fungal infection. Blood culture confirmed G. capitatum
infection. Initial empiric treatment with liposomal amphotericin B was combined with voriconazole based on international experience. However, we did not observe any improvement, and a few days later the patient passed away due
to progression of the underlying disease. G. capitatum (presently known as Saprochaete capitata) is an ubiquitous
yeast that can cause an infection with a poor prognosis, mainly in patients with leukemia. Its symptoms primarily appear in the skin and respiratory tract. The accurate identification of this pathogen is essential because the standard
diagnostic tests do not give a specific reaction. Based on the limited international experience, the combination of
amphotericin B and voriconazole can play a fundamental role in the treatment, however, even with adequate therapy 50% of the cases are fatal. By describing the first Hungarian case caused by G. capitatum, we draw attention to the
importance of this rare, opportunistic fungal species with a poor prognosis that develops in immunosuppressed patients
Evaluation of Isolation Area, Myocardial Injury and Left Atrial Function Following High-Power Short-Duration Radiofrequency or Second-Generation Cryoballoon Ablation for Atrial Fibrillation
This randomized study aims to compare the left atrial (LA) lesion size, function, and tissue damage following pulmonary vein isolation (PVI) by high-power short-duration (HPSD) radiofrequency (RF) and second-generation cryoballoon (CB2) ablation. We enrolled 40 patients with paroxysmal atrial fibrillation who underwent PVI by HPSD RF (n = 21) or CB2 (n = 19). Every patient underwent LA CT angiography and transthoracic echocardiography (TTE) to assess the LA anatomy and function. Biomarker levels (hs-cTnT, hs-CRP, LDH) were compared pre- and post-procedurally. Pre- and post-ablation high-density mapping (HDM) was performed. The isolation area was defined under 0.2 mV bipolar voltage (low voltage area, LVA). We calculated the post-PVI LVA/LA surface ratio using LA CT-HDM merge images. At 3-month follow-up, TTE was performed to assess the changes in LA function. Post-ablation hs-cTnT level was significantly higher in the RF group (RF: 1249 ± 469 ng/L, CB2: 995 ± 280 ng/L, p = 0.024). Post-PVI hs-CRP (RF: 9.53 ± 10.30 mg/L, CB2: 12.36 ± 5.76 mg/L, p = 0.034) and LDH levels (RF: 349.9 ± 65.6 U/L, CB2: 451.6 ± 91.3 U/L, p p = 0.022). LA function did not change significantly after the PVI procedure. Our data indicate that second-generation cryoballoon ablation produces a significantly larger LA lesion size compared to “point-by-point” HPSD radiofrequency. Both techniques preserve LA function. The myocardial component of tissue loss appears to be higher using HPSD radiofrequency ablation, with less collateral damage
Sikeres autológ haemopoeticus őssejt-transzplantáció gyermekkori, súlyos, terápiarezisztens Crohn-betegségben. Az első hazai beteg esetének ismertetése | Successful autologous haemopoietic stem cell transplantation in severe, therapy-resistant childhood-onset Crohn’s disease. Report on the first case in Hungary
A Crohn-betegség pontos oka ismeretlen, így terápiája sem megoldott. Kezelésében az infliximab jelentős áttörést jelentett, a mindennapi gyakorlatban azonban vannak olyan betegek, akik a kombinált immunszuppresszív, illetve biológiai terápia ellenére sem kerülnek remisszióba. Ezekben az esetekben új esélyt jelenthet az őssejt-transzplantáció. A szerzők egy 15 éves fiúgyermek történetét mutatják be, akinél 2008 februárjában súlyos Crohn-betegséget (aktivitási index [PCDAI]: 82,5 – maximumérték: 100) kórisméztek. Konzervatív kezelésének 3 éve alatt a kombinált terápia (immunszuppresszió, antibiotikum, infliximab) ellenére sem került tartós remisszióba. Az ígéretes külföldi esetközlések nyomán autológ őssejt-transzplantációt végeztek, amely a Crohn-betegség remisszióját eredményezte. Egy évvel az őssejt-transzplantáció után az alapbetegség relapsusa jelentkezett, amely a korábbiakhoz képest lényegesen enyhébb, konzervatív terápiával uralható formában zajlott. A szerzők tudomása szerint hazánkban még nem végeztek őssejt-transzplantációt terápiarezisztens Crohn-betegség kezeléseként, amely – noha végleges gyógyulást nem jelentett – terápiás alternatíva lehet súlyos, refrakter esetekben. Orv. Hetil., 2014, 155(20), 789–792.
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The biological therapy of Crohn’s disease, such as infliximab is a powerful approach in the therapy of inflammatory bowel diseases. However, in some patients with aggressive disease course, even a combined immunosuppressive therapy will not result in permanent remission. Hematopoietic stem cell transplantation has emerged as a new potential therapeutic tool for inflammatory bowel diseases. The authors report the case of a 15-year-old boy with severe Crohn’s disease resistant to combined immunosuppressive therapy. After a 3-years course of unsuccessful conventional therapy including infliximab, autologous hematopoietic stem cell transplantation was performed which resulted in a complete remission. One year after transplantation the patient has relapsed, but he could be treated effectively with conventional therapy regiments. To the best of knowledge of the authors, this is the first report in Hungary presenting hematopoietic stem cell therapy in patient with severe Crohn’s disease. Orv. Hetil., 2014, 155(20), 789–792
Antithymocyte Globuline Therapy and Bradycardia in Children
In antithymocyte globulin (ATG) treated patients occasionally bradycardia has been noticed. Therefore, we retrospectively analyzed the occurrence of bradycardia in ATG-treated children. Using medical records between 2007 and 2012 we identified children undergoing a combined therapy with ATG and glucocorticoids (ATG group, n = 22). The incidence of bradycardia was compared to that registered in children treated with glucocorticoids alone (glucocorticoid alone group, n = 21). Heart rates (HR) were registered before and on days 0-3, 4-7 and 8-14 after the ATG or steroid administration. The rate of bradycardic episodes was higher during ATG therapy than in the steroid alone group, while severe bradycardia occurred only in the ATG group (97 versus 32, p = 0.0037, and 13 versus 0, p = 0.0029, respectively). There was an interaction between the time and treatment group on HR (p = 0.046). Heart rates in ATG and steroid alone groups differed significantly on day 0-3 and day 4-7 (p = 0.046, p = 0.006, respectively). Within the ATG group HR was lower on days 4-7 compared to the days before and the days 8-14 values (p < 0.001, 95%CI: 0.020-0.074). These findings indicate that transient asymptomatic bradycardia is probably more common with ATG therapy than previously reported. HR should be closely monitored during and after ATG therapy
Early Increase in Complement Terminal Pathway Activation Marker sC5b-9 Is Predictive for the Development of Thrombotic Microangiopathy after Stem Cell Transplantation
Hematopoietic stem cell transplantation (HSCT)-associated thrombotic microangiopathy (TA-TMA) is a multifactorial complication, and its prediction is largely unresolved. Our aim was to analyze changes of complement profile after HSCT to identify potential markers of TA-TMA development. Thirty-three consecutive pediatric patients (9.6 +/- 4.4 years old) who underwent allogeneic HSCT due to malignant (n = 17) or nonmalignant (n = 16) indications were included in this study. Graft-versus-host disease (GVHD) was diagnosed using Glucksberg criteria, viral reactivation was monitored, 5 different TA-TMA diagnostic criteria were applied, and all important clinical and laboratory parameters of TA-TMA activity were registered. Complement pathway activities, components and terminal pathway activation marker (sC5b-9) levels were systematically measured before transplantation and on days 28, 56, and 100 after HSCT. During the first 100 days after HSCT, 1 of 33 patients died (day 50, multiple organ failure), whereas 10 subjects met the criteria for TA-TMA, typically on day 61 (range, 16 to 98 days). TA-TMA was preceded by acute GVHD in 3 of 10 patients, by viral reactivation in 2 of 10, or by both in 4 of 10 cases. Baseline sC5b-9 levels did not differ in patients without (200 [interquartile range, 144 to 266] ng/mL), or with (208 [interquartile range, 166 to 271] ng/mL) subsequent TA-TMA; however, on day 28 significant differences were observed (201 [interquartile range, 185 to 290] ng/mL versus 411 [interquartile range, 337 to 471] ng/mL; P = .004). Importantly, all 10 patients with TMA showed increase in sC5b-9 level from baseline level to day 28, whereas in patients without TMA the same tendency was observed for only 9 of 23 patients (P = .031). No additional complement parameters were closely associated with the development of TA-TMA. Development of TA-TMA occurred in 30% of our patients, typically after GVHD and/or viral reactivation. However, early raise of sC5b-9 activation marker was predictive for later development of TA-TMA, and should therefore be considered as an alarming sign necessitating a careful monitoring of all TA-TMA activity markers. Further studies enrolling a higher number of patients are necessary to determine if terminal pathway activation is an independent predictor of TA-TMA