Regional effects of the COVID-19 pandemic and policy responses in Hungary

Relevance. The new coronavirus pandemic (COVID-19) has brought major changes to everyday life and economy in 2020. The impacts of the pandemic are still difficult to measure and interpret. This paper analyses the key socio-economic factors that shaped the course of the pandemic and its regional effects in Hungary.Research objective. The aim of this paper is to provide a secondary data-based analysis of regional disparities in Hungary as well as the implications of the coronavirus pandemic and the related policy responses.Data and methodology. The analysis consisted of the three stages: first, we processed the official epidemiologic data related to the coronavirus pandemic and the territorial patterns of infections as well as the data on the socio-economic impacts of the lockdown (on retail trade, employment, tourism, local governments’ revenues, etc). Second, we collected the data related to the socio-economic effects of the pandemic and revealed the territorial impacts of the crisis. Finally, we evaluated the government’s measures and interventions introduced in the first wave of the pandemic in terms of their efficiency.Results. Our results demonstrate that while the epicentre of the pandemic was the capital city and its surrounding area, the socio-economic impacts of containment measures implemented by the Hungarian government were felt across the whole country. In some areas, the lockdown measures could have been unreasonably tight as no reasonable justification for these restrictions was provided. Therefore, territorial monitoring and development of regionally differentiated policies are the main tasks in preparation for further waves of the pandemic. In our opinion, it is necessary to devise an action plan that would regulate the protocols of prevention and protection in connection with the regional focal points (hospitals, nursing homes, schools, etc.) and their immediate surroundings.Conclusions. Although territorial aspects have been taken into account by the government in their efforts to contain the pandemic in Hungary, they have been given significantly less attention in terms of socio-economic support. Thus, as the article makes clear, it is important to devise and implement regionally differentiated policies of containment as well as socio-economic protection measures

Appendicitis képében jelentkező akut promyelocytás leukaemia kiújulása allogén csontvelő-transzplantációt követően

Az akut myeloid leukaemia ellátása primeren hematológiai feladat, relapsusa során is ritka a sebészeti szövődmény. Esettanulmányunkban egy 46 éves férfi beteget mutatunk be, akinél rutinvérvétel során felfedezett akut promyelocy- tás leukaemia miatt történt hematológiai kezelés. Alapbetegsége komplett molekuláris remisszióba jutott, ezt köve- tően fenntartó kezeléseket kapott, de betegsége kiújult. Reindukciós kezelést követően fehérvérsejtszáma normalizá- lódott, de nem jutott molekuláris remisszióba. További kezelés után a férfi testvérétől gyűjtött őssejttel allogén csontvelő-transzplantáció történt. Közel egy éve molekuláris remisszióban volt a beteg, amikor jelentkeztek jobb al- hasi panaszai neutropenia, a C-reaktív protein magas értéke és pozitív hasi ultrahang mellett. Akutan laparoszkópos módszerrel távolítottuk el a láthatóan gyulladt féregnyúlványt. A hisztológiai feldolgozás során az akut promyelocytás leukaemia manifesztációja igazolódott. Tekintettel arra, hogy közben csontvelői relapsus is kialakult, újabb reinduk- ciós kezelés, és másik testvérétől vett őssejtekkel ismételten allogén csontvelő-transzplantáció történt. Az általunk ismert irodalomban appendicitis képében jelentkező akut promyelocytás leukaemia relapsusáról nem találtunk közle- ményt, ezért tartottuk esetünket publikációra érdemesnek

Circulating microRNAs as minimal residual disease biomarkers in childhood acute lymphoblastic leukemia

Treatment stratification based on bone marrow minimal residual disease (MRD) at set time points has resulted in considerably improved survival in pediatric acute lymphoblastic leukemia (ALL). Treatment response is assessed using bone marrow samples. MicroRNAs (miRs) easily traffic among fluid spaces and are more stable than most other RNA classes. We examined the role of circulating miRs as putative less invasive MRD biomarkers.In an exploratory experiment, expression of 46 preselected miRs was studied in platelet-free blood plasma samples of 15 de novo, 5 relapsed ALL patients and 10 controls by Custom TaqMan Array Advanced MicroRNA Card. Based on their high expression in ALL compared to controls, and on the reduction observed along the induction therapy, four miRs were selected for further analyses: miR-128-3p, -181a-5p, -181b-5p and 222-3p. Their expression was measured by qPCR at 4 time points in 27 de novo ALL patients treated in the ALL IC-BFM 2009 study.The expression of all 4 miRs significantly decreased over the first week of therapy (miR-128-3p: log2 fold change - 2.86; adjusted p 3.6 × 10-7; miR-181b-5p: log2 fold change - 1.75; adjusted p 1.48 × 10-2; miR-181a-5p: log2 fold change -1.33; adjusted p 3.12 × 10-2; miR-222-3p: log2 fold change - 1.25; adjusted p 1.66 × 10-2). However, no significant further reduction in miR expression was found after the 8th day of therapy. Measured drop in expression of 2 miRs at day 8 strongly correlated with day 15 bone marrow flow cytometry MRD results (miR-128-3p: Pearson's r = 0.88, adjusted p = 2.71 × 10-4; miR-222-3p: r = 0.81, adjusted p = 2.99 × 10-3).In conclusion, these circulating miRs might act as biomarkers of residual leukemia. MiR-128-3p and miR-222-3p in blood predict day 15 flow cytometry MRD results 7 days earlier. Although, their sensitivity falls behind that of bone marrow flow cytometry MRD at day 15

Pharmacogenetics of the Central Nervous System—Toxicity and Relapse Affecting the CNS in Pediatric Acute Lymphoblastic Leukemia

Despite improving cure rates in childhood acute lymphoblastic leukemia (ALL), therapeutic side effects and relapse are ongoing challenges. These can also affect the central nervous system (CNS). Our aim was to identify germline gene polymorphisms that influence the risk of CNS events. Sixty single nucleotide polymorphisms (SNPs) in 20 genes were genotyped in a Hungarian non-matched ALL cohort of 36 cases with chemotherapy related acute toxic encephalopathy (ATE) and 544 controls. Five significant SNPs were further analyzed in an extended Austrian-Czech-NOPHO cohort (n = 107 cases, n = 211 controls) but none of the associations could be validated. Overall populations including all nations’ matched cohorts for ATE (n = 426) with seizure subgroup (n = 133) and posterior reversible encephalopathy syndrome (PRES, n = 251) were analyzed, as well. We found that patients with ABCB1 rs1045642, rs1128503 or rs2032582 TT genotypes were more prone to have seizures but those with rs1045642 TT developed PRES less frequently. The same SNPs were also examined in relation to ALL relapse on a case-control matched cohort of 320 patients from all groups. Those with rs1128503 CC or rs2032582 GG genotypes showed higher incidence of CNS relapse. Our results suggest that blood-brain-barrier drug transporter gene-polymorphisms might have an inverse association with seizures and CNS relapse

A gyermekkori koronavírus-fertőzést követő sokszervi gyulladás diagnosztikája és kezelése

A SARS-CoV-2-fertőzés ritka gyermekkori szövődménye a sokszervi gyulladás, angol terminológiával paediatric inflammatory multisystem syndrome (PIMS). Két vagy több szerv érintettségével járó, súlyos tünetekkel induló betegségről van szó, amelynek tünetei átfedést mutatnak a Kawasaki-betegséggel, a toxikus sokk szindrómával és a makrofágaktivációs szindrómával. A PIMS-betegek intenzív terápiás osztályon vagy intenzív terápiás háttérrel rendelkező intézményben kezelendők, ahol biztosítottak a kardiológiai ellátás feltételei is. A szükséges immunterápia a klinikai prezentációtól függ. A jelen közleményben a szerzők a releváns nemzetközi irodalom áttekintését követően ajánlást tesznek a PIMS diagnosztikai és terápiás algoritmusára. Orv Hetil. 2021; 162(17): 652-667. Summary. Pediatric inflammatory multisystem syndrome (PIMS) is a rare complication of SARS-CoV-2 infection in children. PIMS is a severe condition, involving two or more organ systems. The symptoms overlap with Kawasaki disease, toxic shock syndrome and macrophage activation syndrome. PIMS patients should be treated in an intensive care unit or in an institution with an intensive care background, where cardiological care is also provided. The required specific immunotherapy depends on the clinical presentation. In this paper, after reviewing the relevant international literature, the authors make a recommendation for the diagnostic and therapeutic algorithm for PIMS. Orv Hetil. 2021; 162(17): 652-667

Single-Cell Sequencing: Biological Insight and Potential Clinical Implications in Pediatric Leukemia

SIMPLE SUMMARY: Leukemia is the most common type of childhood malignancy. While the clinical management of pediatric acute leukemia, especially acute lymphoblastic leukemia, underwent a remarkable improvement during the past decades, a subset of the patients still experience relapse and succumb to their disease. Emergence or repositioning of targeted therapies aided by the comprehensive characterization of single leukemic cells using advanced sequencing approaches may provide novel opportunities for therapeutic intervention in these patients. In our review, we summarize the status quo of single-cell-sequencing studies in pediatric leukemia, provide an overview of the current landscape of targeted agents applicable in this disease group, and highlight options for ways single-cell sequencing could further support the decision making related to the clinical management of pediatric leukemia. ABSTRACT: Single-cell sequencing (SCS) provides high-resolution insight into the genomic, epigenomic, and transcriptomic landscape of oncohematological malignancies including pediatric leukemia, the most common type of childhood cancer. Besides broadening our biological understanding of cellular heterogeneity, sub-clonal architecture, and regulatory network of tumor cell populations, SCS can offer clinically relevant, detailed characterization of distinct compartments affected by leukemia and identify therapeutically exploitable vulnerabilities. In this review, we provide an overview of SCS studies focused on the high-resolution genomic and transcriptomic scrutiny of pediatric leukemia. Our aim is to investigate and summarize how different layers of single-cell omics approaches can expectedly support clinical decision making in the future. Although the clinical management of pediatric leukemia underwent a spectacular improvement during the past decades, resistant disease is a major cause of therapy failure. Currently, only a small proportion of childhood leukemia patients benefit from genomics-driven therapy, as 15–20% of them meet the indication criteria of on-label targeted agents, and their overall response rate falls in a relatively wide range (40–85%). The in-depth scrutiny of various cell populations influencing the development, progression, and treatment resistance of different disease subtypes can potentially uncover a wider range of driver mechanisms for innovative therapeutic interventions

The ortho effect in directed C-H activation.

The success of transition metal-catalysed ortho-directed C-H activation is often plagued by the effects of undesirable interactions between the directing group (DG) and other groups introduced into the aromatic core of the substrate. In particular, when these groups are in neighbouring positions, their interactions can affect profoundly the efficacy of the C-H activation by transition metals. In this work we introduce a simple substrate-only-based model to interpret the influence of steric hindrance of a group in ortho position to the DG in directed ortho-C-H bond activation reactions, and coined the term Ortho Effect (OE) for such situations. We consider simple descriptors such as torsion angle and torsional energy to predict and explain the reactivity of a given substrate in directed C-H activation reactions. More than 250 examples have been invoked for the model, and the nature of the ortho effect was demonstrated on a wide variety of structures. In order to guide organic chemists, we set structural and energetic criteria to evaluate a priori the efficiency of the metalation step which is usually the rate-determining event in C-H activations, i.e. we provide a simple and general protocol to estimate the reactivity of a potential substrate in C-H activation. For borderline cases these criteria help set the minimum reaction temperature to obtain reasonable reaction rates. As an example for the practical applicability of the model, we performed synthetic validations via palladium-catalysed 2,2,2-trifluoroethylation reactions in our lab. Furthermore, we give predictions for the necessary reaction conditions for several selected DGs