Real-Life Efficacy of Tofacitinib in Various Situations in Ulcerative Colitis: A Retrospective Worldwide Multicenter Collaborative Study.

BACKGROUND AND AIMS: Tofacitinib (TFB) appears to be effective in the treatment of ulcerative colitis (UC); however, available real-world studies are limited by cohort size. TFB could be an option in the treatment of acute severe ulcerative colitis (ASUC). We aimed to investigate efficacy and safety of TFB in moderate-to-severe colitis and ASUC. METHODS: This retrospective, international cohort study enrolling UC patients with ≥6-week follow-up period was conducted from February 1 to July 31, 2022. Indications were categorized as ASUC and chronic activity (CA). Baseline demographic and clinical data were obtained. Steroid-free remission (SFR), colectomy, and safety data were analyzed. RESULTS: A total of 391 UC patients (median age 38 [interquartile range, 28-47] years; follow-up period 26 [interquartile range, 14-52] weeks) were included. A total of 27.1% received TFB in ASUC. SFR rates were 23.7% (ASUC: 26.0%, CA: 22.8%) at week 12 and 41.1% (ASUC: 34.2%, CA: 43.5%) at week 52. The baseline partial Mayo score (odds ratio [OR], 0.850; P = .006) was negatively associated with week 12 SFR, while biologic-naïve patients (OR, 2.078; P = .04) more likely achieved week 52 SFR. The colectomy rate at week 52 was higher in ASUC group (17.6% vs 5.7%; P < .001) and decreased with age (OR, 0.94; P = .013). A total of 67 adverse events were reported, and 17.9% resulted in cessation of TFB. One case of thromboembolic event was reported. CONCLUSIONS: TFB is effective in both studied indications. TFB treatment resulted in high rates of SFR in the short and long terms. Higher baseline disease activity and previous biological therapies decreased efficacy. No new adverse event signals were found.

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.

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.

Clinical benefits of oral capecitabine over intravenous 5-fluorouracyl regimen in case of neoadjuvant chemoradiotherapy followed by surgery for locally advanced rectal cancer.

Background: During the last decade, one of the most important treatment options for locally advanced, potencially resectable rectal tumours was neoadjuvant chemoradiotherapy (CRT) followed by surgery. Methods: Effects of the neoadjuvant treatment on surgical outcomes were retrospectively analysed in 185 patients with stage T2-T4 and N0-2, resectable rectal tumour among two patient groups defined by radiosensitizer agents. Group 1 (n = 94) involved radiotherapy (RT) with 50.4 Gy total dose (25 × 1.8 Gy + 3 × 1.8 Gy tumour bed boost), and intravenous 5-fluorouracil (5-FU) (350 mg/m2) with leucovorin (20 mg/m2) on the 1-5 and 21-25 days, while Group 2 (n = 91) RT and orally administrated capecitabine (daily 2 × 825 mg/m2) on RT days. Surgery was carried out after 8-10 weeks. Side effects, perioperative complications, type of surgery, number of removed regional lymph nodes, resection margins and tumour regression grade (TRG) were analysed. Results: More favourable side effects were observed in Group 2. Despite the same rate of diarrhoea (Group 1 vs. Group 2: 54.3% vs. 56.0%), Grade 2-3 diarrhoea ratio was lower (p = 0.0352) after capecitabine (Group 2). Weight loss occurred in 17.0% and 2.2% (p = 0.00067), while nausea and vomiting was described in 38.3% and 15.4% (p = 0.00045) with 5-FU treatment and capecitabine respectively. Anaemia was observed in 33.0% and 22.0% (p = 0.0941). Complete tumour regression occurred in 25.3% after oral- and 13.8% after intravenous treatment (p = 0.049). Ratio of sphincter preservation was higher with laparoscopy than open surgery (72.3% vs. 39.7%) (p = 0.00001). Conclusion: The study confirms advantages of neoadjuvant chemoradiotherapy with oral capecitabine for rectal tumours, such as more favourable side effect profile and overall clinical outcome, with increased rate of complete tumour regression.

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.

Mean arterial blood pressure values of complaint-free pregnant women in the first and second trimesters / Panaszmentes várandósok artériás nyomásértéke a várandósság elso és második trimeszterében

Introduction: The cardiovascular system of women adapts to pregnancy to maintain the growth of the fetus. Objective: The aim of this prospective study is to measure the mean arterial pressure of each gestational week. Hemo-dynamical changes in pregnancy are different in every trimester. Normally the mean arterial pressure decreases at the beginning of the pregnancy, and starts to increase in the third trimester. Method: We have examined 185 pregnant women between May 2020 and July 2020. We used a validated device, TensioMed Arteriograph 2020, which can monitor blood pressure parameters non-invasively. We measured the following parameters: mean arterial pressure, central systolic blood pressure, pulse wave velocity, ankle-brachial index. Results: We found that the mean arterial pressure and the central systolic blood pressure decrease from the 12th to the 15th week, and then start to rise. We did not find significant difference considering the ankle-brachial index and pulse wave velocity. Discussion: The change at the 15th gestational week is the result of circulatory redistribution, histological change when the placenta replaces the chorion. Thus, a high-flow and low-resistance blood flow is created. Compared to the reference values in non-pregnant women, we can say that the values vary significantly within the normal range. Conclusion: Hereafter, we would like to extend our studies to the third trimester as well as to include not only healthy pregnant women, but also pregnant women at risk of developing hypertension. This would create a Hungarian database, which could become a useful pillar in national prenatal care in screening for gestational hypertension.

Seasonal changes in proportion of cardiac surgeries associated with diabetes, smoking and elderly age.

BACKGROUND: Seasonal variations in the ambient temperature may affect the exacerbation of cardiovascular diseases. Our primary objective was to evaluate the seasonality of the monthly proportion of cardiac surgeries associated with diabetes, smoking and/or elderly age at a tertiary-care university hospital in East-Central Europe with a temperate climate zone. As a secondary objective, we also assessed whether additional factors affecting small blood vessels (smoking, aging, obesity) modulate the seasonal variability of diabetes. METHODS: Medical records were analyzed for 9838 consecutive adult patients who underwent cardiac surgery in 2007-2018. Individual seasonal variations of diabetes, smoking, and elderly patients were analyzed monthly, along with the potential risk factors for cardiovascular complication. We also characterized whether pairwise coexistence of diabetes, smoking, and elderly age augments or blunts the seasonal variations. RESULTS: Seasonal variations in the monthly proportion of cardiac surgeries associated with diabetes, smoking and/or elderly age were observed. The proportion of cardiac surgeries of non-elderly and smoking patients with diabetes peaked in winter (amplitude of change as [peak-nadir]/nadir: 19.2%, p<0.02), which was associated with increases in systolic (6.1%, p<0.001) and diastolic blood pressures (4.4%, p<0.05) and serum triglyceride levels (27.1%, p<0.005). However, heart surgery in elderly patients without diabetes and smoking was most frequently required in summer (52.1%, p<0.001). Concomitant occurrence of diabetes and smoking had an additive effect on the requirement for cardiac surgery (107%, p<0.001), while the simultaneous presence of older age and diabetes or smoking eliminated seasonal variations. CONCLUSIONS: Scheduling regular cardiovascular control in accordance with periodicities in diabetes, elderly, and smoking patients more than once a year may improve patient health and social consequences. TRIAL REGISTRATION: NCT03967639.

ONEST (Observers Needed to Evaluate Subjective Tests) suggests four or more observers for a reliable assessment of the consistency of histological grading of invasive breast carcinoma: A reproducibility study with a retrospective view on previous studies.

Histological grade is one of the most important prognosticators of breast cancer which is available for nearly all cases. It also makes part of several multivariable analysis derived combined prognostic profiles despite concerns about its reproducibility. The aims included a reproducibility study of grading in the light of a recently described statistical approach, ONEST (Observers Needed to Evaluate Subjective Tests) and review earlier reproducibility studies in the light of the ONEST analysis. Nine pathologists reviewed 50 core needle biopsies and 50 slides from different excision specimens and recorded the scores for gland (tubule) formation, nuclear pleomorphism and mitotic activity as well as histological grade. Overall percent agreement, Fleiss kappa and the intraclass correlation coefficient (ICC) were used for the analysis of reproducibility. ONEST data and curves were generated from 100 random permutations of the participants. ONEST suggested a minimum of 4 observers for the reliable evaluation of reproducibility for both the scored components and grade in either type of specimen. Our results suggested moderate or moderate to good reproducibility of grading (kappa values of 0.51 for excisions, and 0.54 for biopsies and ICCs of 0.70 and 0.69, respectively) with gland formation being the most and nuclear pleomorphism the worst consistently evaluated feature. In studies with sufficient participants (at least 4) and non-pairwise comparisons in the analysis, the reproducibility of histological grading is fair to moderate, whereas studies with fewer participants or pairwise kappa analysis suggest moderate to almost prefect agreement of the results. ONEST is a valuable complementation of reproducibility analyses.

Patterns of suicide deaths in Hungary between 1995 and 2017.

Hungary has had one of the highest suicide mortality rates in the world for decades. Investigating seasonality of suicide deaths is essential as its findings could be key elements in the prevention. In our study we have analyzed the seasonal effect in suicide mortality in relation to possible risk factors in Hungary during 1995-2017. Data on the numbers of suicide deaths were obtained from a published online database. Negative binomial regression was employed to investigate the effect of possible risk factors and seasonal and annual trends in suicide rates. The seasonal effect was further investigated, adding a significant risk factor from the "initial" negative binomial regression. The suicide risk was significantly (p < 0.001) higher in men than in women (incidence rate ratio: 3.48), and it increased with age and decreased with education level. Marriage was a protective factor against suicide. Annual suicide mortality declined significantly (p < 0.001 for trend) from 36.7 (95% confidence interval: 35.5-37.9) to 16.5 (15.7-17.3) per 100,000 persons per year during the study period. Significant seasonality was found in suicide rates with a peak in late June. Similar peaks were observed at each level of each risk factor. There were differences in peaks by suicide method. The peak of non-violent suicides was in early June; suicides committed by violent methods peaked half a month later. This study suggests that there was a significant seasonal effect on suicide deaths between 1995 and 2017, which remained significant even in the presence of each risk factor. To our knowledge, this has been the first study to investigate the seasonal pattern so extensively in Hungary. Our findings confirm that the environmental effects are involved in the etiology of suicide mortality.

The additional value of ONEST (Observers Needed to Evaluate Subjective Tests) in assessing reproducibility of oestrogen receptor, progesterone receptor, and Ki67 classification in breast cancer.

The reproducibility of assessing potential biomarkers is crucial for their implementation. ONEST (Observers Needed to Evaluate Subjective Tests) has been recently introduced as a new additive evaluation method for the assessment of reliability, by demonstrating how the number of observers impact on interobserver agreement. Oestrogen receptor (ER), progesterone receptor (PR), and Ki67 proliferation marker immunohistochemical stainings were assessed on 50 core needle biopsy and 50 excision samples from breast cancers by 9 pathologists according to daily practice. ER and PR statuses based on the percentages of stained nuclei were the most consistently assessed parameters (intraclass correlation coefficients, ICC 0.918-0.996), whereas Ki67 with 5 different theoretical or St Gallen Consensus Conference-proposed cut-off values demonstrated moderate to good reproducibility (ICC: 0.625-0.760). ONEST highlighted that consistent tests like ER and PR assessment needed only 2 or 3 observers for optimal evaluation of reproducibility, and the width between plots of the best and worst overall percent agreement values for 100 randomly selected permutations of observers was narrow. In contrast, with less consistently evaluated tests of Ki67 categorization, ONEST suggested at least 5 observers required for more trustful assessment of reliability, and the bandwidth of the best and worst plots was wider (up to 34% difference between two observers). ONEST has additional value to traditional calculations of the interobserver agreement by not only highlighting the number of observers needed to trustfully evaluate reproducibility but also by highlighting the rate of agreement with an increasing number of observers and disagreement between the better and worse ratings.

Comparison of Nottingham Prognostic Index, PREDICT and PrognosTILs in Triple Negative Breast Cancer -a Retrospective Cohort Study.

Triple-negative breast cancer (TNBC) represents a heterogenous subtype of breast cancer with generally poor prognosis. The prediction of its prognosis remains essential to clinicians in their therapeutical decision-making process. The aim of our study was to compare the validity of three multivariable analysis derived prognostic systems, the Nottingham Prognostic Index (NPI), PREDICT and PrognosTILs (a prognosticator including tumor infiltrating lymphocytes, TILs) in a series of TNBCs. Patients operated on with TNBC at the Department of Surgery, Bács-Kiskun County Teaching Hospital, Kecskemét between 2005 and 2016 were included. Clinical and pathological parameters and follow-up data were collected from medical charts. TILs were assessed retrospectively, following international recommendations. Estimated survivals of PrognosTILs, PREDICT and NPI were recorded and compared with real outcomes. Altogether 136 patients were included in this retrospective study. In univariate Cox analysis, type of surgery, pT, pN, stage, NPI and type of adjuvant therapy were the significant prognostic variables. The multivariate Cox-regression strengthened that NPI is an independent predictor of overall and disease-free survivals in TNBCs. The NPI, PREDICT and PrognosTILs could be compared directly only in a ROC curve analysis: the sensitivities and specificities of these predicting systems are rather similar with area under the curve values falling between 0.7 and 0.8, and NPI having the highest values. Our findings reflect the diverse prognosis of TNBC and highlight the difficulties of predicting its outcome. None of the three multivariable prognosticators is inferior to the others, the NPI can reliably be used for TNBCs.

Ultrasonographic Evaluation of Glycemic Control Effect on Placental Vascularization in Pregnancy with Type 1 Diabetes Mellitus.

AIMS: The aim of our study was to assess the effect of glycemic control on placental vascularization in pregnancies complicated by type 1 diabetes mellitus (T1DM) and to compare dataset of optimal/suboptimal glycemic control to normal placental 3-dimensional power Doppler (3-DPD) indices in 2nd and 3rd trimester. METHODS: Placental vascularization of pregnant women was prospectively evaluated by 3-DPD ((vascularization-index (VI); flow-index (FI); vascularization-flow-index (VFI)) ultrasound technique. The normal pregnancies (n=214) were compared to those complicated by T1DM (n=53) with optimal (HbA1C≤6%;≤ 42 mmol/mol) and suboptimal (HbA1C>6%;>42 mmol/mol) glycemic control. RESULTS: Pregnancies complicated by T1DM expressed lower placental vascularization indices as compared with normal pregnancies (adjusted odds ratio (AOR) for VI:0.86; FI:0.94; VFI:0.76). Placental 3-DPD indices have a significant correlation with HbA1C and optimal glycemic control is associated with lower placental perfusion (AOR for VI:1.64; FI:1.13; VFI:2.34). Short-term adverse neonatal outcome was predicted by lower 3-DPD indices (AORVI:0.83, AORFI:0.93, AORVFI:0.66, p<0.05 for each index). Besides the glycemic control, the pregestational body mass index (BMI), had significant influences on placental perfusion. CONCLUSIONS: VI displayed the best screening ability for suboptimal glycemic control with a sensitivity of 90.9%. The suboptimal glycemic control has a direct deteriorating effect on placental vasculature. Therefore the ultrasound examination could be an adjunct diagnostic modality for pregnant women with T1DM.

Seasonal variation in childhood mortality.

Aim: This ecological study was carried out to determine the cyclic trends in the rate of perinatal and infant mortality and among children aged under 15 years who died in traffic accidents or from drowning, respiratory disease or cancer.Methods: Monthly data on the numbers of live births, perinatal and infant deaths, and deaths from respiratory disease, cancer, traffic accidents, accidental drowning, and submersion in children aged under 15 years were obtained from the Hungarian nationwide population register. The data were aggregated over the study period and cyclic trends were investigated using the Walter-Elwood and negative binomial regression methods.Results: Significant double-peak (May and November) trends were found in mortality rates for perinatal and infant deaths, respectively. Additionally, significant (p-value < .001) seasonal variation in monthly mortality rates for deaths from respiratory diseases was observed with a peak in February, and a significant single peak was observed in mortality rates in July in both deaths from traffic accidents and drowning among children aged 0-14 years. However, there was no seasonal variation in monthly mortality rates for deaths from childhood cancer.Conclusions: Since cyclic trends in mortality suggest some effect of environmental factors in etiology, we might speculate that perinatal mortality may have been related to respiratory infections. A significant single peak was observed in mortality rates in July in both deaths from traffic accidents and drowning among children aged 0-14 years which could be related to environmental factors, such as temperature, air masses, and fronts. However, there was no seasonal variation in monthly mortality rates for deaths from childhood cancer. All of these novel findings could prove useful in preventive strategies, but further cohort studies are needed to investigate this hypothesis.What is knownSeasonality in infant mortality is known.What is newA significant cyclic trend was found in infants' mortality, with a peak in deaths in winter during the post-perinatal period and double peaks in May and November during the perinatal period, which might be associated with respiratory syncytial virus infections.Winter-peak cyclic trends were observed in both preterm and low birthweight mortality.A significant cyclic trend was observed in mortality, with a peak in deaths from traffic accidents and drowning in July for children aged 0-14 years, but seasonal variation was not found in monthly deaths from childhood cancer.

Seasonal variation of mortality from external causes in Hungary between 1995 and 2014.

OBJECTIVE: To analyze trends in external mortality in Hungary between 1995 and 2014 by sex. METHODS: Data on the numbers of deaths due to external causes were obtained from the published nationwide population register. Negative binomial regression was applied to investigate the yearly trends in external-cause mortality rates. Cyclic trends were investigated using the Walter-Elwood method. RESULTS: Suicide and accidents accounted for approximately 84% of the all-external-cause of deaths in Hungary. Annual suicide, unintentional falls and traffic accidents mortality declined significantly (p-value for annual trend: p < 0.001) from 30.5 (95% CI: 29.5-31.5) to 15.8 (15.1-16.5), from 31.2 (30.2-32.2) to 12.2 (11.7-12.8) and from 17.2 (16.4-18) to 5.4 (5-5.8) per 100 000 persons per year, respectively, during the study period. A significant declining trend in annual mortality was also found for assault, cold/heating-related accidents and accidents caused by electric current. However, the declining trend for drowning-related accidents was significant only for males. Significant winter-peak seasonality was found in the mortality rates from accidental falls, cold/heat-related accidents, other accidents caused by submersion/obstruction and other causes. Seasonal trends with a peak from June to July were observed in death rates from suicide/self-harm, accidental drowning/submersion and accidents caused by electric current. A significant seasonal variation with a peak in September was revealed in the mortality due to traffic accidents. CONCLUSIONS: This Hungarian study suggests that there was a significant seasonal effect on almost all kinds of deaths from external causes between 1995 and 2014. Environmental effects are involved in the aetiology of suicide and accidents.

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).

Adverse perinatal outcome in teenage pregnancies: an analysis of a 5-year period in Southeastern Hungary.

OBJECTIVE: To determine the risks of adverse perinatal outcomes of teenage mothers. MATERIAL AND METHODS: A retrospective analysis was performed on teenage mothers (under 20 years of age) who delivered in the period of 2010-2014 at the Department of Obstetrics and Gynecology, University of Szeged (study group). All mothers who delivered in Hungary during the same period were studied as a control group. The following parameters were analyzed: demographic data of the mothers, maternal complications, perinatal outcome and congenital malformations of the newborns. The binominal test, Student's t-test and Poisson's regression were applied using STATA 9.0 (StataCorp, College Station, TX, USA) statistical software (p < .05 was considered to be statistically significant). RESULTS: During this 5-year period, 12,845 births were recorded at the Department, of these 274 (2.1%) were teenage pregnancies with 275 newborns. The offsprings of teenage mothers had significantly lower mean birth weight (3110.2 ± 564.03 g versus 3247 g), higher rate of congenital malformations (8.0 versus 5.0%) and higher admission to neonatal intensive care unit (12.4 versus 8.0%) than the infants in the control group. CONCLUSIONS: Younger maternal age was significantly associated with lower mean birth weight, higher risk of congenital malformations, and increased admission rate to neonatal intensive care unit.

Examination of the vascularization of fetal kidney with three-dimensional power Doppler technique in pregnancies complicated by increased maternal blood pressure.

The goal of this study was to investigate the fetal renal vascularization during the third trimester of gestation and the perinatal outcome in pregnancies diagnosed with hypertension. Depending on the medical history, the cases were divided into two groups: chronic hypertension (CHT) group and gestational hypertension (GHT) group. The vascularization and the volume of kidneys were observed in prenatal period by three-dimensional ultrasound. We monitored gestations and perinatal complications. Renal volume and vascularization were detected in 45 cases complicated by GHT and 21 cases with CHT during the 20-month study period. The alteration in fetal renal volume and vascularization may be an in utero cause of subsequent intrauterine and neonatal complications, such as cesarean section because of fetal distress (36%), perinatal infection (24%), treatment in neonatal intensive care unit (39%), or increased perinatal mortality (1%) in affected cases. The results demonstrate that fetuses with depressed vascularization of medullae had 1.5 times the risk of an abnormal outcome compared with the control group. The volume of kidneys had a strong correlation with their vascularization. Detailed ultrasound examinations of renal parenchyma appear to be useful for the prenatal diagnosis of intrauterine hypoxia, allowing the detection of potential pathological fetal conditions in utero.

Infliximab biosimilar CT-P13 therapy is effective in maintaining endoscopic remission in ulcerative colitis - results from multicenter observational cohort.

BACKGROUND: CT-P13, the first biosimilar monoclonal antibody to infliximab (IFX), has previously been confirmed to be efficacious in inducing mucosal healing in ulcerative colitis (UC) patients. The aim of this study was to evaluate the efficacy of CT-P13 therapy in maintaining mucosal healing in UC. METHODS: CT-P13 trough levels, antibody positivity, serum inflammatory markers as CRP level, fecal calprotectin at weeks 14 and 54, concomitant steroid and azathioprine therapy at the time of induction therapy and at weeks 14 and 54, previous use of anti TNF drug and the need of dose intensification as possible predictive factors for mucosal healing at week 54 were evaluated in this prospective study. RESULTS: 61 patients had already completed the 54-week treatment period. Mucosal healing was shown in 65.5 % and 62.1 %, complete mucosal healing was present in 31% and 38 % at week 14 and 54, respectively. The median values of CRP, leukocytes, thrombocytes, and albumin showed significant difference between baseline and week 54. Serum antibody positivity was proved in 6.5 % and 19.7 % of cases at week 14 and 54, respectively. CONCLUSION: Our study confirmed the long-term efficacy of CT-P13 therapy on mucosal healing in UC.

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.