COVID-19 mortality prediction in Hungarian ICU settings implementing random forest algorithm.

The emergence of newer SARS-CoV-2 variants of concern (VOCs) profoundly changed the ICU demography; this shift in the virus's genotype and its correlation to lethality in the ICUs is still not fully investigated. We aimed to survey ICU patients' clinical and laboratory parameters in correlation with SARS-CoV-2 variant genotypes to lethality. 503 COVID-19 ICU patients were included in our study beginning in January 2021 through November 2022 in Hungary. Furthermore, we implemented random forest (RF) as a potential predictor regarding SARS-CoV-2 lethality among 649 ICU patients in two ICU centers. Survival analysis and comparison of hypertension (HT), diabetes mellitus (DM), and vaccination effects were conducted. Logistic regression identified DM as a significant mortality risk factor (OR: 1.55, 95% CI 1.06-2.29, p = 0.025), while HT showed marginal significance. Additionally, vaccination demonstrated protection against mortality (p = 0.028). RF detected lethality with 81.42% accuracy (95% CI 73.01-88.11%, [AUC]: 91.6%), key predictors being PaO2/FiO2 ratio, lymphocyte count, and chest Computed Tomography Severity Score (CTSS). Although a smaller number of patients require ICU treatment among Omicron cases, the likelihood of survival has not proportionately increased for those who are admitted to the ICU. In conclusion, our RF model supports more effective clinical decision-making among ICU COVID-19 patients.

Circulating microRNAs correlate with structural and functional MRI parameters in patients with multiple sclerosis.

Introduction: Circulating microRNAs are promising biomarkers for multiple sclerosis (MS). Our aim was to correlate serum microRNA levels with various magnetic resonance imaging (MRI) parameters. Methods: We recruited 50 MS patients and measured cervical spine and cerebral white matter lesions together with regional brain volumes. Microstructural changes in the white matter were investigated with diffusion tensor imaging. Magnetic resonance spectroscopy was performed to measure cerebral metabolites. Functional connectivity within the default mode network was examined with resting-state functional MRI. On the day of the MRI measurements, we collected serum samples and carried out quantitative analysis of ten pre-selected microRNAs using droplet digital PCR. Results: Serum level of miR-143.3p could differentiate between MS subtypes and had lower levels in progressive MS types. We found significant associations between microRNA levels and MRI measures: (1) higher miR-92a.3p and miR-486.5p levels were associated with greater total white matter lesion volumes within the cervical spine, (2) decreased miR-142.5p levels was associated with reduced total creatinine concentration and (3) miR-92a.3p, miR-142.5p and miR-486.5p levels were associated with functional connectivity strengths between specific nodes of the default mode network. Specifically, we found a negative association between miR-92a.3p and miR-486.5p levels and connectivity strength between the lateral temporal cortex and posterior inferior parietal lobule, and a positive association between miR-142.5p level and connectivity strength between the retrosplenial cortex and temporal pole. However, miRNA levels were not associated with regional brain volumes. Conclusion: We provide here further evidence that circulating microRNAs may show correlation with both structural and functional neuroimaging outcomes in patients with MS.

Diagnostic accuracy of SARS-CoV-2 Panbio™ rapid antigen diagnostic tests in a 4,440-case clinical follow-up.

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) Rapid Antigen Detection Testing (RADT) has been subjected to several evaluations in reference to diagnostic accuracy, ranging from small scale up to large population studies including nation-wide community-based studies. All confirmed the diagnostic accuracy of the tests which were strongly dependent upon the infection's population prevalence. In our retrospective study, parallel SARS-CoV-2 Panbio™ RADT assay, including real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) tests, were aimed to evaluate diagnostic performance regarding the rapid antigen diagnostic testing. Out of 4,440 paired tests, 609 samples tested positive using RT-qPCR, resulting in a prevalence of 13.7%. Panbio detected 251 (5.7%) positive tested samples. Overall sensitivity was 41.2% (95% CI 37.4-45.2%) and overall specificity was 99.7% (95% CI 99.4-99.8%). Positive predictive value (PPV) was 95.1% (95% CI 91.8-97.1%) and the negative predictive value (NPV) was 91.4% (95% CI 90.5-92.2%). RADT sensitivity increased with stratification in reference to the results according to PCR Cycle threshold (Ct) and presence of the symptoms considerably influenced PPV and NPV. Sensitivity in the group of Ct values ≤ 20 was 91.2%, 68.6% within the Ct range of 20-25, 47.9% in the group of Ct values between 25 and 30, and 12.6% in the group of Ct values between 30 and 35. A follow-up of the positive cases aligned with RT-qPCR testing and comparison of the general population enrolled in the testing in which the fatal cases occurred enabled us to estimate real clinical diagnostic performance regarding the SARS-CoV-2 Panbio RADT. Based upon our results, we recommend the SARS-CoV-2 Panbio RADT tests be carried out as the primary test, without parallel PCR testing, only among high population prevalence rates of the infection and to be used for symptomatic individuals with average or low severe disease developmental risk. In the case of high risk regarding the development of severe infection complications, a parallel SARS-CoV-2 RT-qPCR is needed to be carried out to attain proper diagnostic accuracy and avoid delaying appropriate medical care.

Novel Molecular Approaches to the Understanding of Pathophysiologal Mechanisms Acting in Human Embryos: An Editorial.

Infertility is a rapidly evolving global health problem [...].

Initial Renal Function (eGFR) Is a Prognostic Marker of Severe Acute Pancreatitis: A Cohort-Analysis of 1,224 Prospectively Collected Cases.

Background: Acute pancreatitis (AP) is a life-threatening disease. We aimed to explore the prognostic relevance of renal function based on estimated glomerular filtration rate (eGFR). Methods: A prospective registry of AP patients was established by the Hungarian Pancreatic Study Group. Data of 1,224 consecutive patients were collected between 2012 and 2017. Patients were divided into 3 groups according to their eGFR measured within 24 h of hospitalization: normal renal function: >90 mL/min, mild to moderate renal functional impairment: 30-90 mL/min and severe renal dysfunction: <30 mL/min. Associations of eGFR with outcome (survival, length of hospitalization, AP severity, blood glucose), inflammatory markers (erythrocyte sedimentation rate, white blood cell count), anemia and organ failure (heart, kidney, liver) were analyzed. Results: Death, longer hospitalization and severe AP, but not the cause of AP, were significantly associated with lower eGFR. The inflammatory markers (CRP, WBC count) but not anemia (Hb, Htk) were closely associated with severe renal dysfunction. Renal function was associated with heart and renal failure but not with other complications of AP such as respiratory failure, local pancreatic complications, diabetes or peptic ulcer. eGFR was not associated with liver damage (ALAT, γ-GT) or liver function (serum bilirubin) although biliary complications, alcohol and metabolic syndrome were the most common etiologies of AP. Conclusions: Our study suggests a useful prognostic value of initial eGFR in AP patients. Even mild eGFR reduction predicted mortality, severity of AP and the length of hospitalization. Thus, precise evaluation of renal function should be considered for assessing AP severity and outcome.

NGS-Based Application for Routine Non-Invasive Pre-Implantation Genetic Assessment in IVF.

Although non-invasive pre-implantation genetic testing for aneuploidy (NIPGT-A) is potentially appropriate to assess chromosomal ploidy of the embryo, practical application of it in a routine IVF centre have not been started in the absence of a recommendation. Our objective in this study was to provide a comprehensive workflow for a clinically applicable strategy for NIPGT-A based on next-generation sequencing (NGS) technology with the corresponding bioinformatic pipeline. In a retrospective study, we performed NGS on spent blastocyst culture media of Day 3 embryos fertilised with intracytoplasmic sperm injection (ICSI) with quality score on morphology assessment using the blank culture media as background control. Chromosomal abnormalities were identified by an optimised bioinformatics pipeline applying copy number variation (CNV) detecting algorithm. In this study, we demonstrate a comprehensive workflow covering both wet- and dry-lab procedures supporting a clinically applicable strategy for NIPGT-A that can be carried out within 48 h, which is critical for the same-cycle blastocyst transfer. The described integrated approach of non-invasive evaluation of embryonic DNA content of the culture media can potentially supplement existing pre-implantation genetic screening methods.

Impact of the COVID‒19 pandemic on ophthalmic outpatient care at the Ophthalmology Department of the New St. John's Hospital, Budapest / A COVID-19-pandémia hatása a szemészeti járóbeteg-szakellátásra az Új Szent János Kórházban, Budapesten.

Összefoglaló. Bevezetés: Az új típusú koronavírus-járvány (COVID-19) az egészségügyi ellátóhálózatot egy eddig ismeretlen helyzet elé állította. A nemzetközi adatok alapján a szemészeti járóbeteg-ellátásban jelentos változások alakultak ki. Célkituzés: Felmérni a COVID-19-járvány okozta kvantitatív és kvalitatív változásokat az Észak-Közép-budai Centrum, Új Szent János Kórház és Szakrendelo Szemészeti Osztályának járóbeteg-szakellátásában. Módszer: A pandémia elso hullámában (2020. április 1-30.) mért járóbeteg-forgalmi adatokat hasonlítottuk össze a megelozo év azonos periódusában rögzített adatokkal. A betegek demográfiai jellemzoi mellett megvizsgáltuk a sürgosségi besorolásukat, valamint a panaszokhoz kötheto fodiagnózis-csoportok eloszlását. Rögzítettük a telemedicina keretein belül történt ellátások számát. Eredmények: 2020 vizsgált idoszakában 916, míg az elozo év azonos hónapjában 2835 járóbeteg-eset került rögzítésre. A 2020-as idoszakban a törvényi szabályozás szerint sürgos panaszokkal jelentkezo betegek aránya nem változott (p = 0,38), azonban a szakorvosi megítélés szerint sürgos panaszokkal érkezo betegek aránya nott (p<0,001) az elozo évhez viszonyítva. A zöld hályog, kötohártya-gyulladás, árpa, sérülés és nedves típusú maculadegeneratio miatt ellátásra jelentkezo betegek aránya szignifikánsan nott (p<0,001 mind), míg a szürke hályog, a száraz típusú maculadegeneratio, egyéb, a szemhéj és a könnyutak betegségei, utóhályog miatt és a szemészeti betegség nélkül érkezok aránya csökkent (p<0,001 mind). A telemedicina keretei között ellátott betegek száma 2020-ban közel a tizenötszörösére emelkedett 2019-hez képest (p<0,001). Következtetés: A COVID-19-pandémia elso hulláma során markáns betegszámcsökkenést regisztráltunk a szemészeti járóbeteg-szakellátásban. Több fodiagnózis-csoport esetén számolhatunk jelentos terápiavesztéssel és halasztott ellátási igény jelentkezésével. Az adatok kiértékelése segítséget nyújthat az elkövetkezo években az ellátási folyamat proaktív átszervezésében, a humáneroforrás-szükségletek jobb tervezésében, valamint a teleoftalmológiai ellátás fejlesztésében. Orv Hetil. 2021; 162(6): 203-211. INTRODUCTION: The COVID-19 pandemic put the healthcare network in a hitherto unknown situation. The ophthalmic outpatient care changed internationally. OBJECTIVE: To assess the quantitative and qualitative changes of the outpatient specialty care at the Ophthalmology Department of the North-Central-Buda Center, New St. John's Hospital and Clinic, through the pandemic. METHOD: Outpatient service data during the first wave of the pandemic (April 2020) were compared with those in April 2019. Patient demographics, emergency classification, distribution of the main diagnostic groups (associated with complaints) and services provided via telemedicine were collected. RESULTS: There were 2835 patient visits in 2019 and 916 in 2020. For 2020, the proportion of patients with emergency classification according to legal regulations did not change (p = 0.38), however, using the ophthalmologist's classification increased (p<0.001) significantly. The proportion of patients with glaucoma, conjunctivitis, chalazeon, injury and wet macular degeneration increased (p<0.001 all), while the proportion of patients with cataract, dry macular degeneration, other diseases, other adnexal diseases, secondary cataract and without ophthalmic pathology decreased significantly (p<0.001 for all). Patient number using telemedicine treatment was about 15× of those treated in 2019 (p<0.001). CONCLUSION: During the first wave of the pandemic, a marked decrease in ophthalmic outpatient care volume was recorded. In the case of several main diagnosis groups, significant therapy loss and a delayed need for care could be expected. Evaluation of the data helps in the upcoming years in proactive reorganization of the care process, in better planning of human resource needs, and in improvement of teleophthalmology care. Orv Hetil. 2021; 162(6): 203-211.

Translating Scientific Knowledge to Government Decision Makers Has Crucial Importance in the Management of the COVID-19 Pandemic.

In times of epidemics and humanitarian crises, it is essential to translate scientific findings into digestible information for government policy makers who have a short time to make critical decisions. To predict how far and fast the disease would spread across Hungary and to support the epidemiological decision-making process, a multidisciplinary research team performed a large amount of scientific data analysis and mathematical and socioeconomic modeling of the COVID-19 epidemic in Hungary, including modeling the medical resources and capacities, the regional differences, gross domestic product loss, the impact of closing and reopening elementary schools, and the optimal nationwide screening strategy for various virus-spreading scenarios and R metrics. KETLAK prepared 2 extensive reports on the problems identified and suggested solutions, and presented these directly to the National Epidemiological Policy-Making Body. The findings provided crucial data for the government to address critical measures regarding health care capacity, decide on restriction maintenance, change the actual testing strategy, and take regional economic, social, and health differences into account. Hungary managed the first part of the COVID-19 pandemic with low mortality rate. In times of epidemics, the formation of multidisciplinary research groups is essential for policy makers. The establishment, research activity, and participation in decision-making of these groups, such as KETLAK, can serve as a model for other countries, researchers, and policy makers not only in managing the challenges of COVID-19, but in future pandemics as well.

Small Interfering RNAs Are Highly Effective Inhibitors of Crimean-Congo Hemorrhagic Fever Virus Replication In Vitro.

Crimean-Congo hemorrhagic fever virus (CCHFV) is one of the prioritized diseases of the World Health Organization, considering its potential to create a public health emergency and, more importantly, the absence of efficacious drugs and/or vaccines for treatment. The highly pathogenic characteristic of CCHFV restricts research to BSL-4 laboratories, which complicates effective research and developmental strategies. In consideration of antiviral therapies, RNA interference can be used to suppress viral replication by targeting viral genes. RNA interference uses small interfering RNAs (siRNAs) to silence genes. The aim of our study was to design and test siRNAs in vitro that inhibit CCHFV replication and can serve as a basis for further antiviral therapies. A549 cells were infected with CCHFV after transfection with the siRNAs. Following 72 h, nucleic acid from the supernatant was extracted for RT Droplet Digital PCR analysis. Among the investigated siRNAs we identified effective candidates against all three segments of the CCHF genome. Consequently, blocking any segment of CCHFV leads to changes in the virus copy number that indicates an antiviral effect of the siRNAs. In summary, we demonstrated the ability of specific siRNAs to inhibit CCHFV replication in vitro. This promising result can be integrated into future anti-CCHFV therapy developments.

First experiences with Navilas® 577s micropulse laser in the treatment of diabetic maculopathy / Elso tapasztalataink diabeteses maculopathia Navilas® 577s mikropulzuslézer-készülékkel történo kezelésével.

Összefoglaló. Bevezetés és célkituzés: A Navilas® 577s mikropulzuslézerrel végzett kezelés biztonságosságának és hatásosságának vizsgálata diabeteses maculaoedemában. Módszer: Retrospektív vizsgálatunkba diabeteses maculaoedema miatt gondozott és legalább 6 hónapos utánkövetéssel rendelkezo, korábban Navilas® 577s mikropulzuslézer-kezelésen átesett 28 beteg 46 szemét válogattuk be. Minden szemen optikaikoherencia-tomográfia (OCT) vastagsági térkép navigált, nonkontakt, küszöb alatti mikropulzuslézer-kezelés történt egy alkalommal. A kezelést megelozoen és az azt követo 6. hónapban rögzítettük a látóélesség, a centrális retinavastagság értékeit és az éreredetu endothelialis növekedési faktort (VEGF) gátló injekciók számát. A követési ido végén megvizsgáltuk a szemfenéki képnek a digitális fundusfotográfia és az átmetszeti OCT-képek segítségével észlelheto változásait. Eredmények: A vizsgált szemek közül 30 esetben a lézerkezelést korábbi centrális maculaoedema miatt VEGF-gátló injekciós kezelés elozte meg, míg 16 szem esetében primer lézerkezelés történt. A Navilas® 577s mikropulzuslézer-kezelést követoen 6 hónappal sem a látóélesség, sem a centrális maculavastagság nem változott szignifikánsan egyik csoportban sem (p>0,05). Ugyanakkor a korábban injekciós kezelésben részesült szemek esetében a lézerkezelést megelozo 6 hónapban adott injekciók száma az átlagos 2,63 ± 1,18 értékrol átlagosan 0,5 ± 0,73 értékre csökkent (p<0,001). A fundusfotókon és az átmetszeti OCT-scaneken a lézerkezelést követoen egyetlen szem esetében sem találtunk látható pigmentelváltozásokat vagy hegesedést. Következetetés: Megfigyeléseink szerint a Navilas® 577s mikropulzuslézer-kezelés biztonságos a diabeteses maculaoedemás betegek kezelésében, továbbá a VEGF-gátlóval kezelt szemeken szerepet játszhat az injekciók számának csökkentésében. Orv Hetil. 2020; 161(49): 2078-2085. INTRODUCTION AND OBJECTIVE: To assess the safety and efficacy of Navilas® 577s micropulse subthreshold laser in the treatment of non-center involved diabetic macular edema. METHOD: In this retrospective study, we included 46 eyes of 28 patients with diabetic macular edema, who were treated at least 6 months ago with Navilas® 577s micropulse laser. Laser treatment was navigated by optical coherence tomography (OCT) macular thickness map in subthreshold micropulse mode at one occasion. Data from visual acuity testing, retinal thickness, and the number of anti-vascular endothelial growth factor (VEGF) injections needed 6 months before and after treatment were registered. At the end of the follow-up, digital fundus photography and OCT radial scans were performed to evaluate any possible anatomical changes. RESULTS: 30 eyes had previous anti-VEGF treatment for central macular edema, and in 16 eyes we performed the laser as primary treatment. At the end of the follow-up, no significant visual acuity or central retinal thickness change were observed (p>0.05). On the other hand, in the anti-VEGF pretreated group the number of injections decreased significantly from 2.63 ± 1.18 to 0.5 ± 0.73 (p<0.001). We did not find any pigmentary changes or visible signs of scaring on final fundus photography pictures or OCT radial scans. CONCLUSION: Navilas® 577s subthreshold microsecond laser proved to be a safe option in the treatment of diabetic macular edema. It can be very useful in anti-VEGF treated eyes by decreasing the number of injections needed. Orv Hetil. 2020; 161(49): 2078-2085.

Label-Free Semiquantitative Liquid Chromatography-Tandem Mass Spectrometry Proteomics Analysis of Laryngeal/Hypopharyngeal Squamous Cell Carcinoma on Formalin-Fixed, Paraffin-Embedded Tissue Samples - a Pilot Study.

Squamous cell carcinoma (SCC) of the head and neck region is the sixth most frequent malignancy with high mortality rate. Due to its poor prognosis it is considered a growing public health problem worldwide inspite of existing treatment modalities. Thus, early diagnosis of new diseases and recurrences is emerging on one hand, but on the other hand troublesome in the lack of reliable tumor markers in this field. The rapid development of proteomics has opened new perspectives in tumor marker discovery. Liquid chromatography/mass spectrometry (LC/MS) as the gold standard in proteomics enables the semi-quantitative analysis of proteins within various tissues. Abundance differences between tumor and normal tissue also can be interpreted as tumor specific changes. The aim of this study was to identify potential tumor markers of laryngeal/hypopharyngeal SCC by revealing abundance changes between cancerous and the surrounding phenotypically healthy tissue. After separating the phenotypically cancerous and healthy parts of formalin-fixed paraffin-embedded tissues, each sample underwent protein recovery process and tryptic digestion for label-free semi-quantitative LC/MS analysis. Eight proteins showed significantly higher abundance in tumor including tenascin, transmembrane emp24 domain-containing protein 2, cytoplasmic dynein light chain 1, coactosin-like protein, small proline-rich protein 2D, nucleolin, U5 small nuclear RNP 200-kDa helicase and fatty aldehyde dehydrogenase. Desmoglein-1 and keratin type I cytoskeletal 9 were down-regulated in tumor. Using Ingenuity Pathway Analysis we mapped the signaling pathways these proteins play role in regarding other tumors. Based on these findings these proteins may serve as promising biomarkers in the fight against laryngeal/hypopharyngeal SCCs.

Author Correction: Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Visualization of mucosal field in HPV positive and negative oropharyngeal squamous cell carcinomas: combined genomic and radiology based 3D model.

The aim of this study was to visualize the tumor propagation and surrounding mucosal field in radiography-based 3D model for advanced stage HNSCC and combine it with HPV genotyping and miRNA expression characterization of the visualized area. 25 patients with T1-3 clinical stage HNSCC were enrolled in mapping biopsy sampling. Biopsy samples were evaluated for HPV positivity and miR-21-5p, miR-143, miR-155, miR-221-5p expression in Digital Droplet PCR system. Significant miRNA expression differences of HPV positive tumor tissue biopsies were found for miR-21-5p, miR-143 and miR-221-5p compared to the HPV negative tumor biopsy series. Peritumoral mucosa showed patchy pattern alterations of miR-21-5p and miR-155 in HPV positive cases, while gradual change of miR-21-5p and miR-221-5p was seen in HPV negative tumors. In our study we found differences of the miRNA expression patterns among the HPV positive and negative tumorous tissues as well as the surrounding mucosal fields. The CT based 3D models of the cancer field and surrounding mucosal surface can be utilized to improve proper preoperative planning. Complex evaluation of HNSCC tissue organization field can elucidate the clinical and molecular differentiation of HPV positive and negative cases, and enhance effective organ saving therapeutic strategies.

Characteristics of Patients Referred To A Specialized Headache Clinic.

Headache is a common problem with great effect both on the individual and on the society. Recent studies raised the possibility of increasing rate of specialty referrals, inappropiate treatment and advanced imaging for simple headache. The aim of our study was to analyze the characteritics of patients (including duration of symptoms, headache type, brain imaging, treatment) referred to our specialized headache clinic between 01/01/2014 and 01/01/2015 by their general practitioners and primary care neurologists due to chronic/treatment-resistant headache syndromes. 202 patients (mean age 53.6 ± 17.6 years) were evaluated in our clinic (102 females, mean age 50.14 ± 16.11 years and 100 males, mean age 57 ± 18.1 years). Migraine (84/202) and tension-type (76/202) were the most common syndromes. 202 plain brain CT, 60 contrast-enhanced CT and 128 MRI were carried out by their general practitioners or other healthcare professioners including neurologists before referral to our headache centre. Despite of extensive brain imaging appropiate treatment was started less than 1/3 of all patients and significant proportion received benzodiazepines or opioid therapy. Furthermore, more than 10% of referred patients presented with secondary headache including one meningitis. The management of headache is still a challenge for primary care physicians leading to medical overuse. Vast majority of our patients should not be referred to our specialized headache clinic as they had uncomplicated headache or other underlying conditions than pain.

Analysis of COVID-19-Related RT-qPCR Test Results in Hungary: Epidemiology, Diagnostics, and Clinical Outcome.

Background: Effective testing is an essential tool for controlling COVID-19. We aimed to analyse the data from first-wave PCR test results in Hungary's Southern Transdanubian region to improve testing strategies. Methods: We performed a retrospective analysis of all suspected COVID-19 cases between 17 March and 8 May 2020, collecting epidemiological, demographic, clinical and outcome data (ICU admission and mortality) with RT-qPCR test results. Descriptive and comparative statistical analyses were conducted. Results: Eighty-six infections were confirmed among 3,657 tested patients. There was no difference between the positive and negative cases in age and sex distribution; however, ICU admission (8.1 vs. 3.1%, p = 0.006) and in-hospital mortality (4.7 vs. 1.6%, p = 0.062) were more frequent among positive cases. Importantly, none of the initially asymptomatic patients (n = 20) required ICU admission, and all survived. In almost all cases, if the first test was negative, second and third tests were performed with a 48-h delay for careful monitoring of disease development. However, the positive hit rate decreased dramatically with the second and third tests compared to the first (0.3 vs. 2.1%, OR = 0.155 [0.053-0.350]). Higher E-gene copy numbers were associated with a longer period of PCR positivity. Conclusion: In our immunologically naïve suspected COVID-19 population, coronavirus infection increased the need for intensive care and mortality by 3-4 times. In the event of the exponential phase of the pandemic involving a bottleneck in testing capacity, a second or third test should be reconsidered to diagnose more coronavirus infections.

Early seizures after ischemic stroke: focus on thrombolysis.

INTRODUCTION: Stroke is a significant underlying cause of epilepsy. Seizures due to ischemic stroke (IS) are generally categorized into early seizures (ESs) and late seizures (LSs). Seizures in thrombolysis situations may raise the possibility of other etiology than IS. AIM: We overtook a systematic review focusing on the pathogenesis, prevalence, risk factors, detection, management, and clinical outcome of ESs in IS and in stroke/thrombolysis situations. We also collected articles focusing on the association of recombinant tissue-type plasminogen activator (rt-PA) treatment and epileptic seizures. RESULTS: We have identified 37 studies with 36,775 participants. ES rate was 3.8% overall in patients with IS with geographical differences. Cortical involvement, severe stroke, hemorrhagic transformation, age (<65 years), large lesion, and atrial fibrillation were the most important risk factors. Sixty-one percent of ESs were partial and 39% were general. Status epilepticus (SE) occurred in 16.3%. 73.6% had an onset within 24 h and 40% may present at the onset of stroke syndrome. Based on EEG findings seizure-like activity could be detected only in approximately 18% of ES patients. MRI diffusion-weighted imaging and multimodal brain imaging may help in the differentiation of ischemia vs. seizure. There are no specific recommendations with regard to the treatment of ES. CONCLUSION: ESs are rare complications of acute stroke with substantial burden. A significant proportion can be presented at the onset of stroke requiring an extensive diagnostic workup.

Tyrosine Kinase Inhibitor Imatinib Mesylate Alters DMBA-Induced Early Onco/Suppressor Gene Expression with Tissue-Specificity in Mice.

Tyrosine kinases play crucial roles in cellular development and tumorigenesis. Tyrosine kinase inhibitors (TKIs) are effective and widely used drug molecules in targeted cancer therapies. Altered expressions of protooncogenes and tumor suppressor genes after DMBA (7,12-dimethylbenz[a]anthracene) treatment have been described as early markers of tumor induction; however their tissue-specific effects remain still unclear. Our study was aimed at examining the short-term possible antineoplastic and chemopreventive effects of a TKI compound (imatinib mesylate) on a DMBA-induced mouse tumor model. In addition, we also investigated the tissue-specific expressions of Hras, Kras, Myc, and Trp53 genes in the brain, bone marrow, spleen, liver, abdominal lymph nodes, thymus, lungs, and kidneys, respectively. 24 hours after the imatinib mesylate injection, we observed significant Kras downregulation in the bone marrow and lung of the DMBA-treated mice. Moreover, the mRNA expression of Myc was also found to be decreased significantly in the spleen. Interestingly, while Trp53 expression was significantly increased in the lung, it was decreased in the other tissues. However, there was also a tendency in the decreased Myc level in the bone marrow, brain, kidneys, lungs, and lymph nodes and in the decreased Hras level in the bone marrow, kidneys, and lungs, although no significant differences were observed. Our findings indicate rapid tissue-specific impact of imatinib mesylate on DMBA-induced gene expression in vivo, supporting the chemopreventive potential of imatinib mesylate in cancer.

Prognostic role of HPV infection in esophageal squamous cell carcinoma.

BACKGROUND: The aims of this study were to evaluate whether HPV infection has a prognostic role in patients with esophageal squamous cell carcinoma who underwent oncological treatment and also to compare the heat shock proteins (Hsp) 90, 27 and 16.2 and growth hormone-releasing hormone receptor (GHRH-R) expression patterns of the pre-treatment tumor biopsies with the HPV status and with the oncological response. METHODS: Pre-treatment tumor biopsies of 74 patients with locally advanced esophageal squamous cell carcinoma were processed retrospectively. The presence of HPV was detected by chromogenic in situ hybridization. Hsp and GHRH-R expressions were determined using immunohistochemistry. Following neoadjuvant or definitive radiochemotherapy, the patients were restaged according to the Response Evaluation Criteria in Solid Tumors. The correlation between the HPV status, response to treatment and Hsp and GHRH-R expressions were evaluated. RESULTS: Fourteen (19%) patients were HPV-positive. These patients were more likely to respond poorly to multimodal therapy (71.4% were non-responders vs. 28.6% responders) and had shorter survival compared to HPV-negative patients (mean survival of 8 months vs. 11 months), although the difference was not significant. A significantly higher number of HPV-positive patients expressed Hsp 90 and 16.2 at high levels (93 and 79%, respectively) than at low levels (Chi-Square p = 0.019 and p = 0.031). Higher levels of Hsp expressions were associated with poorer response to therapy and worse overall survival. No correlation was found between GHRH-R expression and the HPV status, nor between GHRH-R expression and the treatment response of the examined samples. CONCLUSIONS: We found that HPV infection was associated with poor response to oncological treatment and decreased overall survival, and therefore proved to be a negative prognostic factor in patients with esophageal squamous cell carcinoma. There was a linear correlation between levels of Hsp 90 and 16.2 expression and HPV positivity.

[Orbital compartment syndrome. The most frequent cause of blindness following facial trauma]. / Orbitakompartment-szindróma. Arcot ért trauma következtében leggyakrabban vakságot okozó állapot.

INTRODUCTION: Although orbital compartment syndrome is a rare condition, it is still the most common cause of blindness following simple or complicated facial fractures. Its pathomechanism is similar to the compartment syndrome in the limb. Little extra fluid (blood, oedema, brain, foreign body) in a non-space yielding space results with increasingly higher pressures within a short period of time. Unless urgent surgical intervention is performed the blocked circulation of the central retinal artery will result irreversible ophthalmic nerve damage and blindness. Aim, material and method: A retrospective analysis of ten years, 2007-2017, in our hospital among those patients referred to us with facial-head trauma combined with blindness. RESULTS: 571 patients had fractures involving the orbit. 23 patients become blind from different reasons. The most common cause was orbital compartment syndrome in 17 patients; all had retrobulbar haematomas as well. 6 patients with retrobulbar haematoma did not develop compartment syndrome. Compartment syndrome was found among patient with extensive and minimal fractures such as with large and minimal haematomas. Early lateral canthotomy and decompression saved 7 patients from blindness. CONCLUSION: We can not predict and do not know why some patients develop orbital compartment syndrome. Compartment syndrome seems independent from fracture mechanism, comminution, dislocation, amount of orbital bleeding. All patients are in potential risk with midface fractures. We have a high suspicion that orbital compartment syndrome has been somehow missed out in the recommended textbooks of our medical universities and in the postgraduate trainings. Thus compartment syndrome is not recognized. Teaching, training and early surgical decompression is the only solution to save the blind eye. Orv Hetil. 2017; 158(36): 1410-1420.

Comparative miRNA Expression Profile Analysis of Squamous Cell Carcinoma and Peritumoral Mucosa from the Meso- and Hypopharynx.

BACKGROUND/AIM: The role of microRNAs (miRNA) in carcinogenesis is related to their genome-regulatory function. The aim of the present study was to identify and compare miRNA expression signatures of meso- and hypopharynx squamous cell cancers in consideration of the cancer field hypothesis. PATIENTS AND METHODS: Thirteen snap-frozen biopsy series of tumors and peritumoral tissues from the meso- and hypopharynx were analyzed regarding their miRNA expression with quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Significant miRNA expression changes of miR-21, -27a, -34a, -143 and -146a were found in peritumoral tissues that were dependent from the tumor location and the distance from the primary tumor site. CONCLUSION: miRNA expression analysis was found to be appropriate for molecular segregation of tumor location and peritumoral tissue segments, and appears to be a promising marker for cancer field characterization.