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Összefoglaló. Bevezetés: Az antibiotikumok észszerű alkalmazása kulcsfontosságú a hatékonyságuk megőrzésében és a néhol kritikus méreteket öltő antibiotikumrezisztencia visszaszorításában. Célkitűzés: A hazai ambuláns antibiotikumfelhasználás jellemzőinek, trendjeinek bemutatása. Módszer: A 2010 és 2019 közötti időszakra vonatkozó, dobozszámban kifejezett ambuláns szisztémás antibiotikumfelhasználási adatokat – a WHO 2019. évi indexe alapján – „defined daily dose” (DDD – napi átlagdózis) egységbe konvertáltuk. Standardizált technikai egységünk a DDD/1000 fő/nap volt (DID). Az antibiotikumfelhasználás értékelésére nemzetközileg elfogadott minőségi indikátorokat alkalmaztunk. Eredmények: Az antibiotikumfelhasználás mértéke kismértékű ingadozást mutatott (min.: 12,9 DID, max.: 14,7 DID), viszont a szezonális ingadozás a teljes megfigyelt időszakban jelentős mértékű volt. A széles versus szűk spektrumú béta-laktámok és makrolidek felhasználási hányadosa évről évre tovább emelkedett (2010: 13,3 vs. 2019: 71,6), a fluorokinolonok alkalmazási aránya továbbra is meghatározó (2010: 14,3%, 2019: 14,5%). A vizsgált 12 minőségi indikátor közül a tanulmány nyitó évében 4, a tanulmány záró évében 6 indikátor esetében a legkedvezőtlenebbül teljesítő európai országok közé tartoztunk. Megbeszélés: A hazai antibiotikumalkalmazás mértéke európai mérce szerint nem magas, de csökkentésére látszik lehetőség; mintázata szuboptimális, és az évek során kedvezőtlen irányba változott. Következtetés: A kapott antibiotikumfelhasználási adatok s azok értelmezése alapján rendkívül sürgető morális kötelesség a szakmai és hatósági intervenciókra épülő hazai antibiotikumstratégia és -akcióterv mielőbbi kidolgozása, implementálása. Orv Hetil. 2022; 163(4): 140–149. Summary. Introduction: Prudent antibiotic use is an important tool to preserve their effectiveness as well as reverse and confine antibiotic resistance. Objective: To evaluate the trends and characteristics of Hungarian outpatient antibiotic use. Methods: Crude, package level antibiotic sales data for the period 2010–2019 were converted into DDD (defined daily dose) and were standardized for 1000 inhabitants and per year (ATC-DDD index, version 2019). Internationally validated drug-specific quality indicators were used to evaluate antibiotic use. Results: The scale of antibiotic use was stagnating with minimal fluctuation (min.: 12.9 DID, max.: 14.7 DID), and with high intra-year seasonality index. The ratio of the consumption of broad to narrow spectrum beta-lactams and macrolides increased gradually from year to year (2010: 13.3 vs. 2019: 71.6) and the relative consumption of fluoroquinolones is still remarkable (2010: 14.3%, 2019: 14.5%). Out of the twelve surveyed drug-specific quality indicators in the first and last year of analysis, we were ranked among the weakest European countries in the case of four and six indicators, respectively. Discussion: The scale of Hungarian outpatient antibiotic use is not high, in European comperison, but has some reserve capacity for reduction. The pattern of Hungarian antibiotic use is suboptimal and had further decreased quality through the years. Conclusion: Based on the recorded data of antibiotic use and their interpretation, the development of national antibiotic strategy (including both professional and authority interventions) is a pressing moral obligation. Orv Hetil. 2021; 163(4): 140–149.

Background In December 2019, pneumonia caused by coronavirus Disease-19 (COVID-19) occurred in Wuhan, Hubei Province, China. Currently, COVID-19 has spread worldwide. In accordance with the restrictions of the Hungarian Government, several epidemic hospitals and centers have been established in Hungary. The first infected patient was detected on 4th March, 2020 in our country, who was not a Hungarian citizen. The first patient died of pneumonia caused by COVID-19 was on 15th March. The Hungarian epidemic curve is flattened and more prolonged. We aimed to report our computer tomography (CT) findings in correlation with clinical status in patients with COVID-19 infection. Material and methods All patients with laboratory-identified Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection by real-time polymerase chain reaction (PCR) and who underwent chest CT were collected between March 26, 2020, and April 20, 2020, in our hospital. In our centre we had 107 PCR confirmed COVID-19 positive patients in this period. 52 patient (male: female 1:2, average age: 67.94) were admitted to our central epidemic hospital, according to their complains: fever, dyspnoea, hypoxaemia, altered mental status, comorbidity, sepsis or if patient isolation could not be performed. In case of every patient we took blood test, nasopharyngeal sample and a chest CT without contrast agent. In our CT report we used a score system to characterize the severity. Results The majority of infected patients had a history of exposure in nursing homes and mostly presented with fever and cough. The present study confirmed the findings about results of other researches. The COVID-19 pneumonia affected the elderly patients, caused hypoxia, cough and sepsis. On the CT scan, typical signs were seen in the cases of PCR confirmed patients. Conclusion The limitations of the present study include the low number of patients. Collectively, our results appear consistent with previous studies. Chest CT examination plays an important role in the diagnosis and estimation of the severity of the novel coronavirus pneumonia. Future research should examine strategically the features of the Hungarian population.

Here, we describe a scalable and automated, high-content microscopy -based mini-immunofluorescence assay (mini-IFA) for serological testing i.e., detection of antibodies. Unlike conventional IFA, which often relies on the use of cells infected with the target pathogen, our assay employs transfected cells expressing individual viral antigens. The assay builds on a custom neural network-based image analysis pipeline for the automated and multiplexed detection of immunoglobulins (IgG, IgA, and IgM) in patient samples. As a proof-of-concept, we employed high-throughput equipment to set up the assay for measuring antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with spike (S), membrane (M), and nucleo (N) proteins, and the receptor-binding domain (R) as the antigens. We compared the automated mini-IFA results from hundreds of patient samples to the visual observations of human experts and to the results obtained with conventional ELISA. The comparisons demonstrated a high correlation to both, suggesting high sensitivity and specificity of the mini-IFA. By testing pre-pandemic samples and those collected from patients with RT-PCR confirmed SARS-CoV-2 infection, we found mini-IFA to be most suitable for IgG and IgA detection. The results demonstrated N and S proteins as the ideal antigens, and the use of these antigens can serve to distinguish between vaccinated and infected individuals. The assay principle described enables detection of antibodies against practically any pathogen, and none of the assay steps require high biosafety level environment. The simultaneous detection of multiple Ig classes allows for distinguishing between recent and past infection.Public abstractThe manuscript describes a miniaturized immunofluorescence assay (mini-IFA) for measuring antibody response in patient blood samples. The automated method builds on machine-learning -guided image analysis with SARS-CoV-2 as the model pathogen. The method enables simultaneous measurement of IgM, IgA, and IgG responses against different virus antigens in a high throughput manner. The assay relies on antigens expressed through transfection and allows for differentiation between vaccine-induced and infection-induced antibody responses. The transfection-based antigen expression enables performing the assay at a low biosafety level laboratory and allows fast adaptation of the assay to emerging pathogens. Our results provide proof-of-concept for the approach, demonstrating fast and accurate measurement of antibody responses in a clinical and research set-up.

The aim of this study was to analyse characteristics of paediatric antibiotic use in ambulatory care in Hungary. Data on antibiotics for systemic use dispensed to children (0–19 years) were retrieved from the National Health Insurance Fund. Prescribers were categorised by age and specialty. Antibiotic use was expressed as the number of prescriptions/100 children/year or month. For quality assessment, the broad per narrow (B/N) ratio was calculated as defined by the European Surveillance of Antimicrobial Consumption (ESAC) network. Paediatric antibiotic exposure was 108.28 antibiotic prescriptions/100 children/year and was the highest in the age group 0–4 years. Sex differences had heterogenous patterns across age groups. The majority of prescriptions were issued by primary care paediatricians (PCP). The use of broad-spectrum agents dominated, co-amoxiclav alone being responsible for almost one-third of paediatric antibiotic use. Elderly physicians tended to prescribe less broad-spectrum agents. Seasonal variation was found to be substantial: antibiotic prescribing peaked in January with 16.6 prescriptions/100 children/month, while it was the lowest in July with 4 prescriptions/100 children/month. Regional variation was prominent with an increasing west to east gradient (max: 175.6, min: 63.8 prescriptions/100 children/year). The identified characteristics of paediatric antibiotic use suggest that prescribing practice should be improved.

Összefoglaló. Bevezetés: Az antibiotikumok észszerű alkalmazása kulcsfontosságú a hatékonyságuk megőrzésében és a néhol kritikus méreteket öltő antibiotikumrezisztencia visszaszorításában. Célkitűzés: A hazai ambuláns antibiotikumfelhasználás jellemzőinek, trendjeinek bemutatása. Módszer: A 2010 és 2019 közötti időszakra vonatkozó, dobozszámban kifejezett ambuláns szisztémás antibiotikumfelhasználási adatokat - a WHO 2019. évi indexe alapján - "defined daily dose" (DDD - napi átlagdózis) egységbe konvertáltuk. Standardizált technikai egységünk a DDD/1000 fő/nap volt (DID). Az antibiotikumfelhasználás értékelésére nemzetközileg elfogadott minőségi indikátorokat alkalmaztunk. Eredmények: Az antibiotikumfelhasználás mértéke kismértékű ingadozást mutatott (min.: 12,9 DID, max.: 14,7 DID), viszont a szezonális ingadozás a teljes megfigyelt időszakban jelentős mértékű volt. A széles versus szűk spektrumú béta-laktámok és makrolidek felhasználási hányadosa évről évre tovább emelkedett (2010: 13,3 vs. 2019: 71,6), a fluorokinolonok alkalmazási aránya továbbra is meghatározó (2010: 14,3%, 2019: 14,5%). A vizsgált 12 minőségi indikátor közül a tanulmány nyitó évében 4, a tanulmány záró évében 6 indikátor esetében a legkedvezőtlenebbül teljesítő európai országok közé tartoztunk. Megbeszélés: A hazai antibiotikumalkalmazás mértéke európai mérce szerint nem magas, de csökkentésére látszik lehetőség; mintázata szuboptimális, és az évek során kedvezőtlen irányba változott. Következtetés: A kapott antibiotikumfelhasználási adatok s azok értelmezése alapján rendkívül sürgető morális kötelesség a szakmai és hatósági intervenciókra épülő hazai antibiotikumstratégia és -akcióterv mielőbbi kidolgozása, implementálása. Orv Hetil. 2022; 163(4): 140-149.Prudent antibiotic use is an important tool to preserve their effectiveness as well as reverse and confine antibiotic resistance.To evaluate the trends and characteristics of Hungarian outpatient antibiotic use.Crude, package level antibiotic sales data for the period 2010-2019 were converted into DDD (defined daily dose) and were standardized for 1000 inhabitants and per year (ATC-DDD index, version 2019). Internationally validated drug-specific quality indicators were used to evaluate antibiotic use.The scale of antibiotic use was stagnating with minimal fluctuation (min.: 12.9 DID, max.: 14.7 DID), and with high intra-year seasonality index. The ratio of the consumption of broad to narrow spectrum beta-lactams and macrolides increased gradually from year to year (2010: 13.3 vs. 2019: 71.6) and the relative consumption of fluoroquinolones is still remarkable (2010: 14.3%, 2019: 14.5%). Out of the twelve surveyed drug-specific quality indicators in the first and last year of analysis, we were ranked among the weakest European countries in the case of four and six indicators, respectively.The scale of Hungarian outpatient antibiotic use is not high, in European comperison, but has some reserve capacity for reduction. The pattern of Hungarian antibiotic use is suboptimal and had further decreased quality through the years.Based on the recorded data of antibiotic use and their interpretation, the development of national antibiotic strategy (including both professional and authority interventions) is a pressing moral obligation. Orv Hetil. 2021; 163(4): 140-149.

Aims Subunit interactions at the cytoplasmic domain interface (CD-I) have recently been shown to control gating in inward rectifier potassium channels. Here we report the novel KCNJ2 variant p.Glu293Lys that has been found in a patient with Andersen-Tawil Syndrome type 1 (ATS1), causing amino acid substitution at the CD-I of the inward rectifier potassium channel subunit Kir2.1. Neither has the role of Glu293 in gating control been investigated, nor has a pathogenic variant been described at this position. This study aimed to assess the involvement of Glu293 in CD-I subunit interactions and to establish the pathogenic role of the p.Glu293Lys variant in ATS1. Methods and results The p.Glu293Lys variant produced no current in homomeric form and showed dominant negative effect over wild type (WT) subunits. Immunocytochemical labelling showed the p.Glu293Lys subunits to distribute in the subsarcolemmal space. Salt bridge prediction indicated the presence of an intersubunit salt bridge network at the CD-I of Kir2.1, with the involvement of Glu293. Subunit interactions were studied by the NanoBiT split reporter assay. Reporter constructs carrying NanoBiT tags on the intracellular termini produced no bioluminescent signal above background with the p.Glu293Lys variant in homomeric configuration and significantly reduced signals in cells co-expressing WT and p.Glu293Lys subunits simultaneously. Extracellularly presented reporter tags, however, generated comparable bioluminescent signals with heteromeric WT and p.Glu293Lys subunits and with homomeric WT channels. Conclusions Loss of function and dominant negative effect confirm the causative role of p.Glu293Lys in ATS1. Co-assembly of Kir2.1 subunits is impaired in homomeric channels consisting of p.Glu293Lys subunits and is partially rescued in heteromeric complexes of WT and p.Glu293Lys Kir2.1 variants. These data point to an important role of Glu293 in mediating subunit assembly, as well as in gating of Kir2.1 channels. Translational perspective Andersen-Tawil Syndrome (ATS) is a rare genetic disorder characterized by the triad of periodic paralysis, dysmorphic features and ventricular arrhythmias. Symptoms can be mild and atypical, therefore, genetic screening of affected families is pivotal. This study describes the p.Glu293Lys variant of KCNJ2 encoding the Kir2.1 ion channel subunit as pathogenic, thereby aiding genetic testing of ATS. The study also identifies disturbed interactions between the cytoplasmic domains of Kir2.1 subunits as the molecular mechanism of loss-of-function in the p.Glu293Lys variant. Targeting cytoplasmic domain interactions may represent a promising strategy for the development of Kir2.1 agonists.