The value of PLA2R antigen and IgG subclass staining relative to anti-PLA2R seropositivity in the differential diagnosis of membranous nephropathy.

BACKGROUND: The diagnostic performance of PLA2R and IgG subclass staining of kidney biopsies relative to anti-PLA2R seropositivity in the differentiation of primary and secondary membranous nephropathy (pMN, sMN) was examined. Besides PLA2R staining - which has a lower specificity than anti-PLA2R antibody serology - there is insufficient knowledge to decide which IgG1-4 subtype immunohistological patterns (IgG4-dominance, IgG4-dominance/IgG1-IgG4-codominance or IgG4-dominance/IgG4-codominance with any IgG subtype) could be used to distinguish between pMN and sMN. METHODS: 87 consecutive Hungarian patients (84 Caucasians, 3 Romas) with the biopsy diagnosis of MN were classified clinically as pMN (n = 63) or sMN (n = 24). The PLA2R and IgG subclass staining was part of the diagnostic protocol. Anti-PLA2R antibodies were determined by an indirect immunofluorescence test in 74 patients with disease activity. RESULTS: For pMN, the sensitivity of anti-PLA2R seropositivity was 61.1%, and the specificity was 90.0%; and similar values for PLA2R staining were 81.0%, and 66.7%, respectively. In all stages of pMN, IgG4-dominance was the dominant subclass pattern, while the second most frequent was IgG3/IgG4-codominance. The sensitivity and specificity scores were: IgG4-dominance 52.2% and 91.7%, IgG4-dominance/IgG3-IgG4-codominance 76.2% and 87.5%, IgG4-dominance/IgG1-IgG4-codominance 64.2% and 75%, and IgG4-dominance/codominance with any IgG subclass 92.1% and 70.8%, respectively. Anti-PLA2R seropositivity, glomerular PLA2R, and IgG4-dominance/codominance significantly correlated with each other. The IgG4 subclass was rarely encountered in sMN. CONCLUSION: In our series, IgG4-dominance had the highest specificity in the differentiation of MN, just as high as that for anti-PLA2R seropositivity. The specificity values of PLA2R staining and IgG4-dominance/codominance with any IgG subclass or IgG4-dominance/IgG1-IgG4 codominance were ≤ 75%. Apart from IgG4 dominance, IgG4-dominance/IgG3-IgG4-codominance also had good statistical value in differentiating pMN from sMN. As IgG subclass switching during the progression of pMN was not the feature of our cohort, pMN in Hungarian patients is presumed to be an IgG4-related disorder right from the start. Although anti-PLA2R seropositivity has become the cornerstone for diagnosing pMN, if a kidney biopsy evaluation is conducted, besides the staining of PLA2R antigen, the evaluation of IgG subclasses provides relevant information for a differential diagnosis. Even in cases with IgG4-dominance, however, malignancy should be thoroughly checked.

The impact of the COVID-19 pandemic on suicide rates in Hungary: an interrupted time-series analysis.

BACKGROUND: From 2010 to 2019, suicide mortality fell steadily and substantially in Hungary: the declining trend remained stable, and the suicide rate decreased by more than one-third which was remarkable even from an international perspective. However, despite the declining trend, regional inequalities have always characterised the distribution of suicide mortality in Hungary. Following these favourable trends, COVID-19 appeared in Hungary on the 4th of March 2020 which might lead to an increase in suicides. We aimed to investigate this hypothesis in Hungary by gender, age, educational attainment, and region, as well. METHODS: To test whether the pandemic changed the declining trend of Hungarian suicide rates, the observed number of suicides during March-December 2020 (pre-vaccination period) was compared with the expected numbers (without the appearance of COVID-19). An interrupted time-series analysis was conducted by negative binomial regression using monthly data from January 2010 to February 2020 (pre-pandemic period). RESULTS: Suicide mortality increased significantly compared to the trend during the pre-pandemic period: overall (by 16.7%), among males (18.5%), in the age group 35-49 years (32.8%), and among vocational school graduates (26.1%). Additionally, significant growths in suicide rates were detected in the two regions (Central Hungary and Central Transdanubia) with the lowest COVID mortality rates (by 27.3% and 22.2%, respectively). CONCLUSIONS: Our study revealed reversed trend in suicide mortality during the pre-vaccination period compared to the pre-pandemic period in Hungary. There were significant differences in the pattern of suicide rates by gender, age group, educational attainment, and region during the pre-vaccination period in Hungary, which might be attributed to the socio-economic effects of the COVID-19 pandemic. These findings could prove useful in preventive strategies as the identification of groups at higher risk may be important for suicide prevention; however, further investigations are needed to explore the reasons.

Seasonal variation of cancer mortality in Hungary between 1984 and 2013.

Aims: Despite decreasing trends, Hungary is the leader in cancer mortality among European countries. We examined the seasonal variation of cancer mortality in Hungary between 1984 and 2013. Methods: Hungarian monthly cancer mortality and population data were used in the analysis. The Walter-Elwood method was used to determine seasonal variation in both mortality rates and proportionate mortality. Results: Significant winter-peak seasonality was found in all-cancer mortality. A similar seasonal trend with a peak from November to January was observed in death rates from colorectal, lung, female breast, prostate, bladder, brain, lymphoid and hematopoietic cancers. However, no more cyclical variation was identified in the mortality rates from other cancers. In addition, significant seasonal variation in proportionate mortality was shown for all cancer sites examined, with a peak in August or September. Conclusions: This study presents the seasonality pattern of different types of cancer mortality which might be related to environmental factors (e.g. infections).

Annual and seasonal trends in mortality rates from cardiovascular diseases in Hungary between 1984 and 2013.

OBJECTIVES: The aim of this study was to investigate annual and seasonal trends in mortality rates from cardiovascular diseases in Hungary between 1984 and 2013. METHODS: Annual and monthly mortality and population data were obtained from the Hungarian Central Statistical Office. The annual mortality data by gender and age were available for the following disease classifications of the circulatory system: all cardiovascular diseases, all diseases of the heart, hypertension, coronary heart disease, and cerebrovascular diseases. Six age groups were defined for both sexes. Negative binomial regression was carried out to analyse annual trends in age-standardized mortality rates. The Walter-Elwood method was used to identify seasonal variation using monthly numbers of deaths. RESULTS: Significant decreases in annual mortality rates for all cardiovascular diseases were found, but not for hypertension. Age-standardized death rates were higher for men for all causes, except for hypertension. The greatest sex difference in the average risk of death was observed in the middle-aged groups. The greatest percentage decrease in death rates during the study period was seen for both sexes in the under 35 age group. The lowest percentage change was observed among people aged over 75. Significant seasonality was found in monthly death rates from all causes, with a peak in February. CONCLUSIONS: In spite of a decreasing trend in the annual mortality rates for cardiovascular diseases, the Hungarian mortality rate is still high. Moreover, this study demonstrated a significant winter peak in mortality from cardiovascular diseases over a thirty-year period.

Use of placental vascularization indices and uterine artery peak systolic velocity in early detection of pregnancies complicated by gestational diabetes, chronic or gestational hypertension, and preeclampsia at risk.

AIM: We aimed to investigate correlations between uterine artery peak systolic velocity (AUtPSV), and placental vascularization in groups of normal blood pressure (NBP) and hypertensive disorders of pregnancy (chronic hypertension (CHT), gestational hypertension (GHT) and preeclampsia (PE)) alone or in combination with gestational diabetes mellitus (GDM), and hypothesized that AUtPSV rises when GDM complicates pregnancy hypertension. METHODS: Placental 3-dimensional power Doppler indices, such as vascularization index (VI), flow index (FI), and vascularization-flow index (VFI), and uterine artery peak systolic velocity (AUtPSV) were measured in CHT (N=43), CHT+GDM (N=15), GHT (N=57), GHT+GDM (N=23) and PE (N=17) pregnancies, and compared to NBP (N=109). Correlations were analyzed between vascularization indices, AUtPSV, pregestational BMI and adverse pregnancy outcome rates. RESULTS: In our results VI was higher in CHT (P=0.010), while FI was lower in CHT (P=0.009), GHT and PE (P=0.001) compared to NBP. In case of VFI, significant difference was found between CHT and GHT (P=0.002), and NBP and PE (P=0.001). FI was found prognostic for umbilical pH and neonatal birth weight. Pre-gestational BMI was significantly higher in GHT+GDM compared to GHT, and in CHT+GDM compared to the CHT group. As for AUtPSV, significant difference was found between NBP and CHT (P=0.012), NBP and CHT+GDM (P=0.045), NBP and GHT+GDM (P=0.007), NBP and PE (P=0.032), and GHT and GHT+GDM (P=0.048) groups. CONCLUSION: Our study revealed that vascularization indices and AUtPSV show significant differences due to gestational pathology, and can be useful in detection of pregnancies at risk.

[Evaluation of anatomic and prognostic stages of breast cancer according to the 8th edition of the TNM staging system - Retrospective analysis based on data from deceased patients once diagnosed with breast cancer]. / Emlorákok TNM-8 szerinti anatómiai és prognosztikai stádiumainak retrospektív vizsgálata elhunyt, valaha emlorákos betegek adatai alapján.

INTRODUCTION: The 8th edition of the Tumor-Node-Metastasis (TNM) based staging of breast cancer introduces a prognostic stage influenced by biomarkers along the traditional T, N and M categories. AIM: To retrospectively assess stage influencing prognostic variables; and the anatomic and prognostic stages on the basis of the overall survival (OS) of a cohort of deceased patients once diagnosed with breast cancer. METHOD: We included patients with known causes of death certified at the Bács-Kiskun County Teaching Hospital and having a history of breast cancer diagnosed on a resection specimen at the same institution. Prognostic factors were obtained from the histopathological reports. Statistics included one-way ANOVA, Dunn's post hoc test and Kaplan-Meier curve analyses. RESULTS: The 303 patients grouped as breast cancer related death (n = 168) or unrelated (n = 135) showed significant differences in most stage defining prognostic factors and the anatomic and prognostic stages. Significant differences in 5-year OS were observed between pT and pN categories, histological grades and estrogen receptor statuses. Except for stages I and II, significant differences were found between both different anatomic and prognostic stages (p<0.001). Stage IV is by definition uniform, but we identified survival differences between biomarker based subgroups: triple negative carcinomas had worse OS than estrogen receptor positive and HER2 negative carcinomas. CONCLUSIONS: Our analysis based on real survival data suggests that the prognostic stages separate patients according to OS similarly to the anatomic stages. The results validate the prognostic stages, but also suggest that separating stage IV disease according to biomarkers makes sense. Orv Hetil. 2017; 158(35): 1373-1381.

[Examination of placental three-dimensional power Doppler indices and perinatal outcome in pregnancies complicated by intrauterine growth restriction]. / A háromdimenziós power Doppler-indexek és a perinatalis kimenetel vizsgálata méhen belüli növekedési restrikcióval szövodött terhességekben.

INTRODUCTION: Development of intrauterine growth restriction (IUGR) can be traced back to maternal or fetal factors, but in many cases we find placental factors (reduced placental circulation) in the background. AIM: Our aim was to examine whether the reduced placental bloodperfusion and vascularity show any correlation with cesarean section frequency and the clinical outcome in IUGR pregnancies. The aim of the present study was also to use a properly calibrated and reproducible method for evaluating placental blood flow, that can later be incorporated into the routine examination. METHOD: 254 women were recruited in our prospective case-control study. The 3 dimensional power Doppler (3DPD) ultrasound indices; vascularisation index (VI), flow index (FI) and vascularization flow index (VFI) were measured on each participant. RESULTS: Median VI was 3.7% (interquartile range [IQR] 3.2%-4.2%) in the IUGR group and 10.1% (IQR 8.6%-10.9%) in the control group (p = 0.001). Median FI value was 40.0 (IQR 39.7-42.5) in the IUGR group and 45.1 (IQR 44.1-53.1) in the control group (p = 0.012). Median VFI was 2.2 (IQR 2.1-2.4) in the IUGR group and 4.8 (IQR 4.4-5.3) in the control. CONCLUSIONS: The 3DPD indices may be useful for examining changes in circulation in IUGR pregnancies to characterize the underlying pathology. Orv Hetil. 2017; 158(26): 1008-1013.

INTERNET AND STROKE AWARENESS IN THE YOUNG HUNGARIAN POPULATION.

BACKGROUND: Although stroke mortality rate in Hungary has tapered off over the last years, it is still twice the European average. This statistic is alarming and a coordinated response is needed to deal with this situation when considering new ways of communication. There are currently more than 300 websites in Hungarian related to stroke prevention, acute stroke treatment, recovery and rehabilitation. AIMS AND/OR HYPOTHESIS: We sought to identify base level of stroke knowledge of the Hungarian students and the efficiency with which the knowledge disseminated by internet is actually utilized. METHODS: We surveyed 321 high-school and university students to determine their ability to extract specific information regarding stroke from Hungarian websites. The base level of knowledge was established by asking 15 structured, close-ended questions. After completing the questionnaire, students were asked to search individually on stroke in the internet where all the correct answers were available. After a 25-min search session they answered the same questionnaire. We recorded and analyzed all their internet activity during the search period. RESULTS: The students displayed a fair knowledge on the basics of stroke but their results did not change significantly after the 25-min search (53 +/- 13% vs. 63 +/- 14%). Only correct information given on demographic facts improved significantly. Most of the students used very simple search strategies and engines and only the first 5-10 web-pages were visited. CONCLUSION: Analysis of the most often visited web-pages revealed that although stroke-related Hungarian web-based resources contain almost all the important and required information the unsuitable structure, lack of simplicity and verbosity hinder their effective public utilization.

Is mucosal healing more common than clinical remission in ulcerative colitis? - Is it the truth or only a myth coming from the studies?

BACKGROUND: The most important goals of the recent therapies of ulcerative colitis (UC) are to induce and maintain clinical remission and to achieve mucosal healing (MH). Rate of endoscopic remission has been shown to be higher than that of clinical remission in large trials like ULTRA and PURSUIT. The aim of our study was to evaluate the correlation between clinical and endoscopic disease activities of UC defined by activity scores. METHODS: Clinical and endoscopic activities were evaluated in 100 consecutive UC patients. Clinical activities were defined by two activity indices: the Rachmilewitz Activity Index (CAI) and the partial Mayo score. Colonoscopies and patient enrollments were performed by two experienced gastroenterologists and endoscopists. They graded the findings both according to the endoscopic part of the Rachmilewitz Endoscopic Activity Index (EI) and the Mayo endoscopic subscore. MH was defined as Mayo endoscopic subscore and EI of 0. Histological activity was scored by Riley score. RESULTS: Clinical and endoscopic activities showed strong correlations using both scoring systems (p = 0.0029 and p = 0.0001). Endoscopic disease activity also correlated with the histological activity (p ≥ 0.001). Significant correlation was shown between the clinical activity and MH (p = 0.0012 and p ≥ 0.001). No association was showed with the extension of the disease and clinical or endoscopic activity. CONCLUSION: Assessment of MH is very important for guiding therapy and for evaluation of remission in patients with UC. Our result showed good correlation between the clinical, endoscopic, and histological activities of UC focusing on the importance of evaluating the endoscopic activity of the patients.

Antibody and cell-mediated immune response to whole virion and split virion influenza vaccine in patients with inflammatory bowel disease on maintenance immunosuppressive and biological therapy.

OBJECTIVE: Influenza vaccination is recommended for inflammatory bowel disease (IBD) patients on immunosuppressive therapy. The objective was to evaluate the antibody and cell-mediated immune response to the split and whole virion influenza vaccine in patients with IBD treated with anti-TNF-α and immunosuppressive therapy. PATIENTS AND METHODS: One hundred and fifty-six immunocompromised IBD patients were vaccinated. Fifty-three patients (control group) refused vaccination. Split virion vaccine and whole virion vaccine were used. Serum samples were obtained for pre- and postimmunization antibody titers to influenza vaccine (A/California/7/2009 [H1N1], A/Victoria/361/2011 [H3N2], B/Wisconsin/1/2010-like B/Hubei-Wujiagang/158/2009). Cell-mediated response was evaluated using an interferon (INF)-γ, interleukine (IL)-2 and tumor necrosis factor (TNF)-α ELISA. RESULTS: Postimmunization titers of both influenza subtypes increased significantly after the administration of split virion vaccines compared to the controls and to those who received whole virion vaccine. The antibody titers of Influenza B also increased significantly in patients immunized with split vaccine and treated with anti-TNF-α therapy. After influenza vaccination, the level of serum IL-2 significantly decreased. No serious side effects developed occurred after influenza vaccination, and the influenza-like symptoms did not differ significantly between vaccinated versus control patients. The relapse of the disease was observed in only 10% of the patients and was more common in vaccinated than in control subjects. CONCLUSION: Split virion vaccines seem to be more effective than whole virion vaccines. Measuring the antibody responses is worthwhile in patients treated with immunosuppressants to determine the efficacy of influenza vaccination.

The use of regression methods for the investigation of trends in suicide rates in Hungary between 1963 and 2011.

PURPOSE: Suicide rates in Hungary have been analyzed from different aspects in recent decades. However, only descriptive rates have been reported. The aim of our epidemiological study was to characterize the pattern of annual rates of suicide in Hungary during the period 1963-2011 by applying advanced statistical methods. METHODS: Annual suicide rates per 100,000 population (>6 years) for gender, age group and suicide method were determined from published frequency tables and reference population data obtained from the Hungarian Central Statistical Office. Trends and relative risks of suicide were investigated using negative binomial regression models overall and in stratified analyses (by gender, age group and suicide method). Joinpoint regression analyses were additionally applied to characterize trends and to find turning points during the period 1963-2011. RESULTS: Overall, 178,323 suicides (50,265 females and 128,058 males) were committed in Hungary during the investigated period. The risk of suicide was higher among males than females overall, in all age groups and for most suicide methods. The annual suicide rate exhibited a significant peak in 1982 and remained basically constant after 2006. Different segmented patterns were observed for the suicide rates in the various age groups. CONCLUSIONS: Suicide rates revealed segmented linear pattern. This is the first detailed trend analysis with risk estimates obtained via joinpoint and negative binomial regression methods simultaneously for age-specific suicide frequencies in Hungary.

Trends in infant mortality rates in Hungary between 1963 and 2012.

AIM: This study investigated annual and seasonal death trends for infants of <1 year of age in Hungary between 1963 and 2012 and analysed commonly accepted risk factors. METHODS: Data on the numbers of live births and infant deaths were obtained from the published nationwide population register. Negative binomial regression was applied to investigate the yearly trends in rates and also the effect of possible risk factors - low birthweight, maternal education and sex - on infant mortality. Cyclic trends were investigated using logistic regression. RESULTS: Annual infant mortality declined significantly (p < 0.001) from 42.9 to 4.9 per 1000 live births per year during the study period and significantly increased (p < 0.001) in the low birthweight group and lower maternal education groups. A significant (p < 0.001) cyclic trend in mortality was revealed, with a peak in deaths in late February for all infants and a double peak, in May and November, in the group of cases who died during the early neonatal period. CONCLUSION: This Hungarian study suggests that there was a significant seasonal effect on neonatal and infant mortality at the end of winter between 1963 and 2012. We speculate that this may have been related to respiratory infections.

[On-site fine-needle aspiration cytology of thyroid nodules. Quality assurance of the Bethesda System for Reporting Thyroid Cytopathology (2008)]. / Pajzsmirigygöbök vékonytu-aspirációs citológiai vizsgálata. A Bethesda-rendszer (2008) minoségbiztosítása.

INTRODUCTION: The methods available for the diagnosis of thyroid nodules include physical examination, imaging, laboratory and fine-needle aspiration cytology tests. AIM: The aim of this study was to determine the quality assurance of fine-needle aspiration cytology of thyroid nodules. METHOD: Cytology results were rated to 6 categories according to the Bethesda System for Reporting Thyroid Cytopathology (2008) (I. nondiagnostic; II. benign; III. atypia of undetermined significance; IV. follicular neoplasia; V. suspicious for malignancy; VI. malignant). All cytology reports were compared with the final histology diagnosis. RESULTS: A total of 1384 patient with thyroid nodule underwent fine-needle aspiration biopsy cytology. Smears were classified I. inadequate in 214 (15.9%); II. benign 986; III. atypical 56; IV. follicular neoplasm 41; V. suspicious for malignancy 18; VI. malignant 33 cases. Two hundred and twenty seven (16.8%) of the cases were operated and histologically verified. The positive predictive value in the benign category was 98.25% and in the malignant 88.46%. The sensitivity of the follicular neoplasm was 66.67%. CONCLUSION: The results suggest that fine-needle aspiration cytology of thyroid nodules using the Bethesda System for Reporting Thyroid Cytopathology has a high diagnostic accuracy. The auditing values of the results meet the proposed threshold values.

Immunogenicity of a 2009 pandemic influenza virus A H1N1 vaccine, administered simultaneously with the seasonal influenza vaccine, in children receiving chemotherapy.

BACKGROUND: No examination of simultaneous vaccination against pandemic H1N1 and the seasonal influenza virus strains, in children with cancer receiving chemotherapy, are yet published. We investigated the immunogenicity of a whole-virion, inactivated, adjuvanted pandemic H1N1, and seasonal influenza vaccines administered simultaneously to children with cancer undergoing chemotherapy. PROCEDURE: We prospectively enrolled 27 pediatric patients receiving therapy for various types of cancer. All received influenza vaccination once in a seasonal risk period. We checked hemaglutination-inhibition (HAI) antibody titers in the sera of patients before, and 21-28 days after vaccination. Seroprotective titer was defined as an antibody titer ≥ 40, and seroresponse as ≥ 4-fold increase in antibody titers after vaccination. RESULTS: The pre- and post-vaccination seroprotective rates were H1N1: 33-48%, H3N2: 56-78%, B: 0-15% for seasonal influenza, and for pandemic H1N1: 15-37%. The seroresponse rates for seasonal influenza H1N1, H3N2, and B were 22%, 37%, and 22%, respectively, and 30% for the pandemic H1N1 vaccine. CONCLUSIONS: Whole-virion, inactivated, adjuvanted vaccine for the pandemic H1N1 Influenza A virus and the seasonal influenza vaccines were found safe and partially immunogenic in children with cancer receiving chemotherapy. The only determinants of responsiveness were lymphocyte count and serum immunoglobulin-G. Only influenza B vaccine elicited significant differences in differences in pre- and post-vaccination seroprotective rates. The response to vaccination for pandemic H1N1 is as effective as other vaccines, however administration of a single vaccine during chemotherapy is more comfortable for pediatric cancer patients.

[Liquid-based cervical cytology ThinPrep screening in Hungary]. / A folyadékalapú méhnyakrákszurés eredménye Magyarországon.

INTRODUCTION: Liquid-based cervical cytology has been developed as an alternative for conventional Papanicolaou cervical cytology. AIM: The aim of this study was to determine the quality assurance of liquid-based cervical cytology. METHOD: 4573 cervical cytology smears were classified according to the Bethesda (2001) system. Human papilloma virus infection was detected and subtyped from reflex test using real-time polymerase chain reaction. RESULTS: 4573 smears were classified according to the Bethesda (2001) system. Negative diagnosis was made in 2323 cases (50.8%), non neoplastic in 2017 cases (44.1%), and positive for intraepithelial lesions or malignancy in 233 cases (5.1%). Unsatisfactory smear for diagnosis was found in 43 cases (0.9%), low-grade squamous intraepithelial lesion in 87 cases (1.9%), high-grade squamous intraepithelial lesion in 24 cases (0.5%), and carcinoma in 23 cases (0.5%). Fifty-nine of the cases were histologically verified and 4 falsely negative cases were detected. The sensitivity, specificity and the positive predictive value were 93.2%, 100% and 100%, respectively. Compared to an identical time periods of the previous three years, the low- and high-grade squamous intraepithelial lesion increased from 0.82% to 2.51%. Eighty one human papilloma virus tests were performed with a positive predictive value of 99%. CONCLUSIONS: The auditing values of the liquid-bases cervical cytology results meet the proposed threshold values. Liquid-bases cervical cytology is an alternative cervical cytology and it seems to be significantly better than conventional Papanicolaou cervical cytology in all parameters.

The impact of the first year of COVID-19 pandemic on suicides in a collection of 27 EU-related countries.

Disasters, including epidemics, have a characteristic course, both in terms of the specific events and the human reactions to them. However, it is difficult to predict whether the COVID-19 pandemic will eventually lead to an increase in suicide rates. We aimed to provide a general pattern of the change in suicide rates in the countries linked to the European Union by direct comparison of the years 2019 and 2020 by gender and age group, grouped according to the predominant religions. Overall, 27 countries were included in the analysis. Incidence rate ratios and their 95% confidence intervals were calculated to characterise annual changes in the incidence of suicide deaths. In almost two-thirds of the countries studied, suicide rates did not increase. The largest increases were observed in Catholic-majority and 'mixed' Catholic-Protestant countries, but this was significant only for the oldest age group (over 65 years). This increase was even more marked within some Catholic-majority countries (Hungary, Ireland, and Spain) during the first months of the pandemic. There was no statistically significant increase overall in the suicide death rates in Europe. However, the pattern of suicide rates has changed significantly in some countries, and by age group and religion, respectively.

An intra- and interobserver reproducibility analysis of the Ki-67 proliferation marker assessment on core biopsies of breast cancer patients and its potential clinical implications.

OBJECTIVE: The Ki-67 proliferation index has received an important role in treatment tailoring and molecular classification of estrogen receptor-positive breast carcinomas. The aim was to analyze the reproducibility of assessing proliferation on the basis of Ki-67 immunohistochemistry. METHODS: Thirty core biopsy samples of breast cancer patients were analyzed after immunostaining with B56, SP6 and MIB-1 monoclonal Ki-67 antibodies. All samples were evaluated twice and independently by 3 pathologists, with each observer performing his daily routine practice. The ratio of Ki-67-positive cells was estimated with 5% accuracy. Correlation was calculated for the results of each investigator for all pairs of antibodies and for the results of each antibody for all pairs of investigators. Ki-67 scores were divided into categories of either 4 quarters or into 3 groups reflecting the St. Gallen consensus recommendations with 15 and 30% as cutoff values. The reproducibility of classifying the tumors into these categories was assessed with ĸ statistics. RESULTS: Altogether, 540 evaluations were made. Good to excellent correlation (Spearman's and Pearson's coefficient range 0.74-0.92 and 0.73-0.93, respectively) was noted for the pairwise comparison of antibodies by observer and of observers by antibody. The inter- and intraobserver reproducibility of the Ki-67 score classification into equal quarters (1-25, 26-50, 51-75 and 76-100%) or into 3 categories with cutoffs at 15 and 30% was fair to poor in the middle categories, but moderate to substantial in the low and high ranges. Interobserver differences in practice potentially impacted on less consistent classification. CONCLUSION: Our results indicate that the three different Ki-67 antibodies tested do not substantially influence the reproducibility of the estimated proliferation rates. Although reproducibility is better in the clinically more relevant distinction of high versus low proliferation, without standardization, the current practice of Ki-67 assessment in many laboratories does not allow proper and consistent therapeutic decision-making.

[Quality assurance of rapid on-site evaluation of CT-guided fine-needle aspiration cytology of lung nodules]. / A CT-vezérelt vékonytu-aspirációs citológiai vizsgálat minoségbiztosítása a tüdodaganatok diagnosztikájában.

INTRODUCTION: The methods available for the diagnosis of lung cancer include radiologic, cytologic and pathologic procedures. AIMS: The aim of this study was to determine the quality assurance of CT guided fine needle aspiration cytology of lung nodules. METHODS: Cytology results were rated to 4 categories (positive; suspicious; negative; not representative). All cytology reports were compared with the final histology diagnosis. RESULTS: A total of 128 patients underwent CT-guided percutaneous fine-needle aspiration biopsy cytology (63 males; 65 females; mean age 62.8 years). Smears were adequate in 99 cases and inadequate in 29 cases. The average diameter of the nodules was 3.28 cm. Thirty three (25.6%) of the cases were histologically verified and 2 falsely negative and 2 falsely positive cases were detected. The sensitivity and the positive predictive value were 88.8% and 88.8%, respectively. Pneumothorax developed in 7 (5.4%) cases. CONCLUSION: These results suggest that CT-guided transthoracic fine needle aspiration cytology has a high diagnostic accuracy and an acceptable complication rate. The auditing valves of the results meet the proposed threshold values.

Impact of neoadjuvant FLOT treatment of advanced gastric and gastroesophageal junction cancer following surgical therapy.

Introduction: Therapeutic treatment for advanced-stage (T2-T4) gastroesophageal junction (GEJ) and gastric cancer involves neoadjuvant chemotherapy with subsequent surgical intervention. Method: Neoadjuvant oncological treatment for GEJ and gastric cancer previously consisted of the intravenous administration of epirubicin, cisplatin and fluorouracil (ECF) or epirubicin, cisplatin and capecitabine (ECX) combination (Group 1). The new protocol (FLOT, F: 5-FU, L: leucovorin, O: oxaliplatin, T: docetaxel), included patients with resectable GEJ and gastric cancer who had a clinical stage cT2 or higher nodal positive cN+ disease (Group 2). Between 31 December 2008 and 31 October 2022, the effect of different oncological protocols in terms of surgical outcomes in cases of T2-T4 tumours were retrospectively evaluated. Results of randomly assigned patients from the earlier ECF/ECX protocol (n = 36) (Group 1) and the new FLOT protocol (n = 52) (Group 2) were compared. Effect of different neoadjuvant therapies on tumour regression, types of possible side effects, type of surgery, and oncological radicality of surgical procedures were analysed. Results: When comparing the two groups, we found that in case of the FLOT neoadjuvant chemotherapy (Group 2, n = 52), complete regression was achieved in 13.95% of patients, whereas in the case of ECF/ECX (Group 1, n = 36), complete regression occurred in only 9.10% of patients. Furthermore, in the FLOT group, the mean number of lymph nodes removed was slightly higher (24.69 vs. 20.13 in the ECF/ECX group). In terms of the safety resection margin (proximal), no significant difference was found between the two treatment groups. Nausea and vomiting were the most common side effects. The occurrence of diarrhea was significantly higher in the FLOT group (p = 0.006). Leukopenia and nausea occurred more commonly with the old protocol (Group 1). The rate of neutropenia was lower following FLOT treatment (p = 0.294), with the lack of grade II and III cases. Anaemia occured at a significantly higher rate (p = 0.036) after the ECF/ECX protocol. Conclusions: As a result of the FLOT neoadjuvant oncological protocol for advanced gastro-esophageal junction and gastric cancer, the rate of complete tumour regression increased significantly. The rate of side effects was also appreciably lower following the FLOT protocol. These results strongly suggest a significant advantage of the FLOT neoadjuvant treatment used before surgery.

ONEST (Observers Needed to Evaluate Subjective Tests) Analysis of Stromal Tumour-Infiltrating Lymphocytes (sTILs) in Breast Cancer and Its Limitations.

Tumour-infiltrating lymphocytes (TILs) reflect antitumour immunity. Their evaluation of histopathology specimens is influenced by several factors and is subject to issues of reproducibility. ONEST (Observers Needed to Evaluate Subjective Tests) helps in determining the number of observers that would be sufficient for the reliable estimation of inter-observer agreement of TIL categorisation. This has not been explored previously in relation to TILs. ONEST analyses, using an open-source software developed by the first author, were performed on TIL quantification in breast cancers taken from two previous studies. These were one reproducibility study involving 49 breast cancers, 23 in the first circulation and 14 pathologists in the second circulation, and one study involving 100 cases and 9 pathologists. In addition to the estimates of the number of observers required, other factors influencing the results of ONEST were examined. The analyses reveal that between six and nine observers (range 2-11) are most commonly needed to give a robust estimate of reproducibility. In addition, the number and experience of observers, the distribution of values around or away from the extremes, and outliers in the classification also influence the results. Due to the simplicity and the potentially relevant information it may give, we propose ONEST to be a part of new reproducibility analyses.