Miklós Garami

Semmelweis University | SOTE · Second Department of Pediatrics

Background Paediatric patients are often exposed to subtherapeutic levels or treatment failure of β-lactams, and prolonged infusion may be beneficial. We aimed to investigate the efficacy and safety of extended infusion (EI; defined as ≥3 h) or continuous infusion vs. short, intermittent infusion (SI; defined as ≤60 min) of β-lactams in patients <2...

Background: Hypovitaminosis D is associated with oncogenesis, and the initial level of Vitamin D may play a role in determining long-term prognosis, relapse-free survival (RFS) and overall survival (OS). The purpose of our study was to follow up pediatric cancer patients for a long time in terms of their baseline Vitamin D level and disease outcome...

Objective This study aimed to evaluate the association between the location (supratentorial or infratentorial) of brain tumors and the development of depression and anxiety in childhood cancer survivors. Understanding the risk factors for the development of depression and anxiety disordersin these patients is crucial for early diagnosis and success...

Nowadays, whole-body vibration (WBV) has become increasingly popular as an additional therapy in the intervention of patients with cerebral palsy (CP). However, the impact of WBV remains a subject of debate. Consequently, a systematic review and meta-analysis were undertaken to evaluate the effects of WBV on the musculoskeletal system in children w...

As medical knowledge expands and targeted therapies emerge, there is newfound hope for treating congenital disorders and tumour-related syndromes that so far had been treated with surgeries, resulting temporary relief only. This article presents cutting-edge research and treatments for some of the most complex pediatric skin conditions. We demonstr...

Plexiform neurofibromas occurring in approximately 20–50% of all neurofibromatosis type-1 (NF1) cases are histologically benign tumors, but they can be fatal due to compression of vital structures or transformation to malignant sarcomas or malignant peripheral nerve sheath tumors. All sizeable plexiform neurofibromas are thought to result from an e...

Cyclophosphamide, an oxazaphosphorine prodrug is frequently used in treatment of neuroblastoma, which is one of the most prevalent solid organ malignancies in infants and young children. Cytochrome P450 2B6 (CYP2B6) is the major catalyst and CYP2C19 is the minor enzyme in bioactivation and inactivation pathways of cyclophosphamide. CYP-mediated met...

Background: The international, multicenter registry LOGGIC Core BioClinical Data Bank aims to enhance the understanding of tumor biology in pediatric low-grade glioma (pLGG) and provide clinical and molecular data to support treatment decisions and interventional trial participation. Hence, the question arises whether implementation of RNA sequenc...

Background The utility of routine extensive molecular profiling of pediatric tumors is a matter of debate due to the high number of genetic alterations of unknown significance or low evidence and the lack of standardized and personalized decision support methods. Digital drug assignment (DDA) is a novel computational method to prioritize treatment...

Orally administered, small-molecule anticancer drugs with tumor-specific cellular protein targets (OACD) have revolutionized oncological pharmacotherapy. Nevertheless, the differences in exposure to these drugs in the systemic circulation and extravascular fluid compartments have led to several cases of therapeutic failure, in addition to posing un...

Knowledge of the complexity of the gut microbiota is expanding, and its importance in physiological processes and disease development is widely studied. The aim of this review is to present the most relevant and recent research on the associations between gut microbiota and oncologic disease. Recently, a number of associations between the gut micro...

Background The EUROCARE-5 study revealed disparities in childhood cancer survival among European countries, giving rise to important initiatives across Europe to reduce the gap. Extending its representativeness through increased coverage of eastern European countries, the EUROCARE-6 study aimed to update survival progress across countries and years...

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain1–4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage5–8. By contrast, mutations that activate WNT signalling lea...

Background: Our previous work has shown a correlation between lower vitamin D levels in children with cancer and adverse prognosis. It suggests that supplying vitamin D is reasonable. VDR expression in childhood solid tumors has been linked to tumor characteristics and patient survival in only a few studies. Methods: For this study, 177 children...

There is growing body of evidence supporting the role of germline mutations in the pathogenesis of pediatric central nervous system (CNS) tumors, and the widespread use of next‐generation sequencing (NGS) panels facilitates their detection. Variants of the MUTYH gene are increasingly recognized as suspected germline background of various extraintes...

We report on children with cancer in Hungary suffering from COVID-19, surveying a 13-months-long period of time. We performed a retrospective clinical trial studying the medical documentation of children treated in seven centers of the Hungarian Pediatric Oncology-Hematology Group. About 10% of children admitted to tertiary hemato-oncological cente...

Introduction Standards for chemotherapy against choroid plexus tumors (CPT) have not yet been established. Methods CPT-SIOP-2000 (NCT00500890) was an international registry for all CPT nesting a chemotherapy randomization for high-risk CPT with Carboplatin/Etoposide/Vincristine (CarbEV) versus Cyclophosphamide/Etoposide/Vincristine (CycEV). Patien...

Background: Only few data are available on treatment-associated behavior of distinct rare CNS-embryonal tumor entities previously treated as "CNS-primitive neuroectodermal tumors" (CNS-PNET). Respective data on specific entities, including CNS neuroblastoma, FOXR2 activated (CNS NB-FOXR2), and embryonal tumor with multi-layered rosettes (ETMR) are...

Sonic hedgehog medulloblastoma encompasses a clinically and molecularly diverse group of cancers of the developing central nervous system. Here, we use unbiased sequencing of the transcriptome across a large cohort of 250 tumors to reveal differences among molecular subtypes of the disease, and demonstrate the previously unappreciated importance of...

Intravenous administration of lipid-based nanodrugs can cause hypersensitivity, also known as infusion reactions (IRs), that can be attenuated by slow infusion in adult patients. We studied the role of infusion rate and complement (C) activation in IRs in pediatric patients treated with Abelcet, and also in anesthetized rats. IRs were observed in 6...

Cancer is one of the leading causes of death for children; however, appropriate nutritional status can positively affect survival. The aim of this study was to determine to what extent malnutrition risk screening and intensified nutrition support, provided by a professional team, promoted disease progression and survival in pediatric patients with...

The Hungarian Pediatric Oncology Network provides centralized treatment and population-based registration for cases of childhood cancer since 1973. We collected and analized data on late mortality, secondary malignancies and cardiac diseases in survivors (> 5 years) of childhood cancer to evaluate long-term risks. We extracted all solid tumour case...

Objective: Our aims were to compare the vitamin D status of children with and without cancer and to examine the possible correlation between vitamin D levels in children with cancer before initiating treatment and prognosis. Method: We compared the data of 173 children with cancer with those of 569 children without cancer. Results: We measured a si...

Despite continuing advances in therapeutic strategies, survival of childhood medulloblastoma (MB) patients has reached a plateau in the past decade. Current clinical approaches divide patients into average- and high-risk treatment categories, although this categorization does not take patient heterogeneity into account. Advanced genomics has initia...

A neuroblastoma a gerinc két ol-dalán lévő szimpatikus ideglánc gang lion jaiban, valamint a mellékvese velő állo mányában jelentkező malignus tumor. A 18 hónapos kor után megjele-nő neuroblastoma disszeminált formája a legrosszabb indulatú gyermekkori da-ganatok közé tartozik. A neuroblastoma a gyermekkori tumorok 8-10%-át teszi ki, Magyarországon...

Rationale: Cancer is a leading cause of death for children, however, appropriate nutritional status can positively affect the outcome of the disease. The aim of this study was to determine whether intensified nutrition support had an effect on the disease progression in paediatric patients with solid tumours.

Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of p...

The survival of children treated with Ewing sarcoma at Semmelweis University were investigated. Pediatric patients with Ewing sarcoma treated at Semmelweis University from 2001 through 2013 were analyzed in terms of overall survival and clinical factors (age, primary localization and extent of the tumor, time interval from primary complaints to dia...

Children with medulloblastoma (MB) are predisposed for negative cognitive sequela, which has been widely identified in this population. The purpose of the present study was to explore cognitive deficits and psychopathological symptoms and analyse their relation among MB survivors. The Wechsler Intelligence Scale for Children and the Mini Internatio...

Choroid plexus tumors (CPT) comprise choroid plexus papilloma (CPP, WHO grade I), atypical choroid plexus papilloma (aCPP, WHO grade II), and choroid plexus carcinoma (CPC, WHO grade III). CPT from 20 nations were prospectively recruited into the CPT-SIOP-2000 study (01/2000–03/2010, n=129, median follow-up 7.4 years) and the CPT-SIOP registry (04/...

Célkitűzés:A gyermekkori medulloblasztóma (MB) túlélői a késői neurokognitív deficitek tekintetében különösen veszélyeztetettek. Vizsgálatunk célja, hogy feltárjuk ezeket a kognitív deficiteket és azonosítsuk a rizikótényezőket egy homogén betegcsoportban. Módszer: Mintánkat 34 fő, MB diagnózissal kezelt gyermek alkotta. Az intelligenciaprofiljuk f...

A Magyar Gyermekonkológiai Hálózat megalakulása, 1971 óta működteti a gyermekkori daganatos betegségek hazai nyilvántartását végző Országos Gyermektumor Regisztert (OGYR). Történelmileg kiemelendő, hogy alapításával Magyarország messze megelőzte korát, hiszen Európában harmadik országos gyermekonkológiai regiszterként jött létre.

A neuroblastoma egy gyermekkori rosszindulatú idegrendszeri betegség. Viszonylag ritka, a daganatos betegek 5-10 százalékát érinti, vagyis évente 15-20 esettel találkozunk. A gyermek kilátásai a daganat stádiumától és a kockázati besorolástól függenek. A kis kockázatú gyermekek ötéves túlélése meghaladja a 95%-ot, nagy kockázat esetén ez körülbelül...

Survival for childhood central nervous system (CNS) tumours varies across Europe, partly because of the difficulty of distinguishing malignant from non-malignant disease. This study examines bias in CNS tumours survival analysis to obtain the reliable and comparable survival figures. We analysed survival data for about 15,000 children (age <15) dia...

The Hungarian Childhood Cancer Registry, a population-based national registry of the Hungarian Paediatric Haemato-Oncology Network founded in 1971, monitors the incidence and mortality of childhood cancer. Our aims were to carry out a longitudinal study to investigate the trends and spatial inequalities of incidence and survival of leukaemia, and t...

Aims: First proof to show that (-)-deprenyl/selegiline (DEP), the first selective inhibitor of MAO-B, later identified as the first β-phenylethylamine (PEA)-derived synthetic catecholaminergic activity enhancer (CAE) substance and (2R)-1-(1-benzofuran-2-yl)-N-propylpentane-2-amine (BPAP), the tryptamine-derived presently known most potent, selecti...

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medic...

Background: High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, eto...

Purpose: Neutropenia is a common complication from chemotherapy, limiting optimal dosing and treatment. Lipegfilgrastim is a long-acting granulocyte colony-stimulating factor developed for the management of chemotherapy-induced neutropenia. The objectives of this phase 1, multinational, open-label, single-arm study were to characterize the pharmac...

A 2,5 éves kisfiú súlyos, elesett állapotban, ileus gyanúja miatt került felvételre osztályunkra. Idõre, császármetszéssel, 4050 gramm súllyal született. Perinatális anamnézise negatív volt, fejlõdése problémamentesen zajlott. Felvételét megelõzõ hetekben székrekedés jelentkezett. A területileg il-letékes kórházból kifejezett haspuffadás, hasi fáj-...

Background: Pineoblastoma is a rare pineal region brain tumor. Treatment strategies have reflected those for other malignant embryonal brain tumors. Patients and methods: Original prospective treatment and outcome data from international trial groups were pooled. Cox regression models were developed considering treatment elements as time-depende...

We recently reported that atypical teratoid rhabdoid tumors (ATRTs) comprise at least two transcriptional subtypes with different clinical outcomes; however, the mechanisms underlying therapeutic heterogeneity remained unclear. In this study, we analyzed 191 primary ATRTs and 10 ATRT cell lines to define the genomic and epigenomic landscape of ATRT...

Gyermekgyógyászati Továbbképző Szemle, Interjú Hatvan évvel az alapítás után ez a folyóiratszám cikksorozatot közöl a Kórház korábbi munkatársaitól. A szám vendégszerkesztője Péter professzor, aki korábban 20 éven át főigazgatóként irányította az intézményt, majd vezetésében további 7 évig orvos-igazgatóként működött közre. Az intézmény és a személ...

Ependymomas are common pediatric brain tumors that originate from the ependyma and characterized by poor prognosis due to frequent recurrence. However, the current WHO grading system fails to accurately predict outcome. In a retrospective study, we analyzed 54 intracranial pediatric ependymomas and found a significantly higher overall survival in s...

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Recently, by utilizing DNA methylation, it has been demonstrated that a large proportion of institutionally-diagnosed CNS-PNETs...

Treatment strategies for childhood pineoblastoma have been adapted from those for other brain tumors. To analyze the impact of different treatment elements, treatment and outcome data from international trial groups were pooled, and Cox regression models were developed considering treatment elements as time-dependent covariates. 140 patients aged 0...

Background: Evaluation of prognostic factors in high risk stage 4 neuroblastoma (HRNBL) patients (pts) treated with busulfan-melphalan (BUMEL) within HR-NBL1/SIOPEN. Methods: Between 2002-2009 (prior antiGD2 immunotherapy) BUMEL was given to 475 pts (275 males) in 149 centres / 20 countries. Pts < 1year (yr) had MYCN amplification (MNA). After indu...

Background. More than 90% of patients with diffuse intrinsic pontine glioma (DIPG) will die within 2 years of diagnosis. Patients deteriorate rapidly during the disease course, which severely impairs their quality of life. To date, no specific research on this clinically important subject has been conducted. This study aimed to compile an inventory...

The embryonal tumor with abundant neuropil and true rosettes is a rare and highly malignant variant of embryonal brain tumors. It usually affects infants and young children under the age of 4 years and exhibits a very aggressive course with a dismal prognosis. For the 68 cases reported to date the mean age at diagnosis was 25.42 months (range 3-57...

Bevezetés Az elmúlt 15 évben több, mint 90 000 kohorsz vizsgálat jelent meg, mely a D-vitamin-hiány és a daganatos megbetegedések közötti összefüggést vizsgálta. A témát az teszi fontossá, hogy egyes fel-nõttkori daganatos betegségekben már leírtak összefüggést a malignitás kialakulása és a D-vitamin -hiány között, valamint mindezek alapján java-so...

BACKGROUND: Ependymomas are the third most common CNS tumors in children. To date, extent of resection and patient age are the most important prognostic factors. To refine treatment strategies and improve patient outcome molecular markers are needed. Recently, the prognostic impact of tenascin-C (TNC) expression and gain of chromosome 1q have been...

Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 an...

Objectives: Valproic acid (VPA)-induced adverse effects, which are sometimes serious in children, can be associated with alterations in VPA metabolism. VPA-evoked toxicity is attributed to both the parent compound and its unsaturated metabolites, primarily formed by the cytochrome P450 (CYP)2C9 enzyme. Thus, patients' CYP2C9-status may account for...

Rhabdoid brain tumours, also called atypical teratoid rhabdoid tumours, are lethal childhood cancers with characteristic genetic alterations of SMARCB1/hSNF5. Lack of biological understanding of the substantial clinical heterogeneity of these tumours restricts therapeutic advances. We integrated genomic and clinicopathological analyses of a cohort...

Childhood cancers are rare disorders. The average annual age-standardized incidence is 149/1000000 (0-14 yrs). Diagnosis of childhood brain tumors, despite the specific localization and advanced imaging techniques can cause difficulties. In recent years, due to better early recognition, the number of surgically removable brain tumors is increasing....