Evaluation of novel biomarkers for early pregnancy outcome prediction†.

OBJECTIVE: To assess performance and discriminatory capacity of commercially available enzyme-linked immunosorbent assays of biomarkers for predicting first trimester pregnancy outcome in a multi-center cohort. DESIGN: In a case-control study at three academic centers of women with pain and bleeding in early pregnancy, enzyme-linked immunosorbent assays of biomarkers were screened for assay performance. Performance was assessed via functional sensitivity, assay reportable range, recovery/linearity, and intra-assay precision (%Coefficient of Variation). Top candidates were analyzed for discriminatory capacity for viability and location among 210 women with tubal ectopic pregnancy, viable intrauterine pregnancy, or miscarriage. Assay discrimination was assessed by visual plots, area under the curve with 95% confidence intervals, and measures of central tendency with two-sample t-tests. RESULTS: Of 25 biomarkers evaluated, 22 demonstrated good or acceptable assay performance. Transgelin-2, oviductal glycoprotein, and integrin-linked kinase were rejected due to poor performance. The best biomarkers for discrimination of pregnancy location were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 1, insulin-like growth factor binding protein 1, kisspeptin (KISS1), pregnancy-specific beta-1-glycoprotein 3, and beta parvin (PARVB). The best biomarkers for discrimination of pregnancy viability were pregnancy-specific beta-1-glycoprotein 9, pregnancy-specific beta-1-glycoprotein 3, EH domain-containing protein 3, KISS1, WAP four-disulfide core domain protein 2 (HE4), quiescin sulfhydryl oxidase 2, and pregnancy-specific beta-1-glycoprotein 1. CONCLUSION: Performance of commercially available enzyme-linked immunosorbent assays was acceptable for a panel of novel biomarkers to predict early pregnancy outcome. Of these, six and seven candidates demonstrated good discriminatory capacity of pregnancy location and viability, respectively, when validated in a distinct external population. Four markers demonstrated good discrimination for both location and viability.

Depletion of muscularis macrophages ameliorates inflammation-driven dysmotility in murine colitis model.

Previously, the presence of a blood-myenteric plexus barrier and its disruption was reported in experimentally induced colitis via a macrophage-dependent process. The aim of this study is to reveal how myenteric barrier disruption and subsequent neuronal injury affects gut motility in vivo in a murine colitis model. We induced colitis with dextran sulfate sodium (DSS), with the co-administration of liposome-encapsulated clodronate (L-clodronate) to simultaneously deplete blood monocytes contributing to macrophage infiltration in the inflamed muscularis of experimental mice. DSS-treated animals receiving concurrent L-clodronate injection showed significantly decreased blood monocyte numbers and colon muscularis macrophage (MM) density compared to DSS-treated control (DSS-vehicle). DSS-clodronate-treated mice exhibited significantly slower whole gut transit time than DSS-vehicle-treated animals and comparable to that of controls. Experiments with oral gavage-fed Evans-blue dye showed similar whole gut transit times in DSS-clodronate-treated mice as in control animals. Furthermore, qPCR-analysis and immunofluorescence on colon muscularis samples revealed that factors associated with neuroinflammation and neurodegeneration, including Bax1, Hdac4, IL-18, Casp8 and Hif1a are overexpressed after DSS-treatment, but not in the case of concurrent L-clodronate administration. Our findings highlight that MM-infiltration in the muscularis layer is responsible for colitis-associated dysmotility and enteric neuronal dysfunction along with the release of mediators associated with neurodegeneration in a murine experimental model.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high-throughput technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥0.80: lutropin subunit beta and serpin B8. While some of the markers had previously been implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high-throughput platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

Application of a Multiplex Platform to Identify Novel Biomarkers for Pregnancy Location and Viability.

Determining early pregnancy location and viability can be cumbersome, often requiring serial evaluations. This study aimed to identify novel biomarker candidates for pregnancy location and viability using a pseudodiscovery high through-put technique. This was a case-control study among patients presenting for early pregnancy assessment, including ectopic pregnancies, early pregnancy losses, and viable intrauterine pregnancies. For pregnancy location, ectopic pregnancy was considered "case" and non-ectopic considered "control." For pregnancy viability, viable intrauterine pregnancy was considered "case" and early pregnancy loss + ectopic pregnancy were considered "control." Using Proximity Extension Assay technology from Olink Proteomics, serum levels of 1012 proteins were compared separately for pregnancy location and viability. Receiver operator characteristic curves were generated to determine a biomarker's discriminative abilities. Analysis included 13 ectopic pregnancies, 76 early pregnancy losses, and 27 viable intrauterine pregnancies. For pregnancy location, 18 markers had an area under the curve (AUC) ≥ 0.80, with three being expressed more in ectopic compared to non-ectopic pregnancies: thyrotropin subunit beta, carbonic anhydrase 3, and DEAD (Asp-Glu-Ala-Asp) box polypeptide 58. For pregnancy viability, two markers had an AUC ≥ 0.80: lutropin subunit beta and serpin B8. While some of the markers were previously identified as implicated in early pregnancy physiology, others were from pathways not previously explored. Using a high through-put platform, a large number of proteins were screened as potential biomarkers for pregnancy location and viability, and twenty candidate biomarkers were identified. Further exploration of these proteins may facilitate validation as diagnostic tools for establishing early pregnancy diagnoses.

BRAF RNA is prognostic and widely expressed in lung adenocarcinoma.

Background: BRAF is a critical member of proliferation pathways in cancer, and a mutation is present in only 2-4% of lung adenocarcinomas (LADC). There is no data available on the expression pattern of BRAF RNA that might result in enhanced signalling and drug resistance. Methods: LADC tissue samples (n=64) were fixed and processed into paraffin blocks. Tissue microarrays (TMA) were constructed, and RNAScope® in situ hybridization (ISH) assay was performed for wild-type (WT) BRAF RNA. Apart from pathological assessment of tumor samples (grade, necrosis, vascular involvement and peritumoral infiltration), anti-programmed death ligand 1 (PD-L1) and anti-programmed death 1 (PD-1) immunohistochemistry and validation in public databases [The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA)] were carried out. Results: WT BRAF RNA is expressed in LADC, with no significant expressional difference between early-stage (I-II) and advanced-stage (III-IV) patients (P=0.317). Never smokers exhibited significantly increased BRAF expression (compared to current and ex-smokers, P<0.01) and tumor necrosis correlated significantly with BRAF expression (P=0.014). PD-L1 expression was assessed on tumor cells and immune cells, PD-1 expression was evaluated on immune cells. There was no significant difference in BRAF RNA expression between tumor cell PD-L1-high vs. low patients (P=0.124), but it was decreased in immune cell PD-L1-high patients (P=0.03). Kaplan-Meier survival analysis showed that high BRAF expression was associated with significantly decreased OS (P<0.01) and was an independent negative prognostic factor according to multivariate Cox hazard regression (P=0.024). TCGA validation cohort confirmed our findings regarding OS in early-stage patients (P=0.034). Conclusions: We found an increased expression of BRAF RNA in all stages in LADC. High BRAF expression was associated with tumor necrosis, distinct immune checkpoint biology and outcomes. We recommend further evaluating the potential of targeting overexpressed BRAF pathways in LADC.

Implication of the Gut Microbiome and Microbial-Derived Metabolites in Immune-Related Adverse Events: Emergence of Novel Biomarkers for Cancer Immunotherapy.

Immune checkpoint inhibitors (ICIs) have changed how we think about tumor management. Combinations of anti-programmed death ligand-1 (PD-L1) immunotherapy have become the standard of care in many advanced-stage cancers, including as a first-line therapy. Aside from improved anti-tumor immunity, the mechanism of action of immune checkpoint inhibitors (ICIs) exposes a new toxicity profile known as immune-related adverse effects (irAEs). This novel toxicity can damage any organ, but the skin, digestive and endocrine systems are the most frequently afflicted. Most ICI-attributed toxicity symptoms are mild, but some are severe and necessitate multidisciplinary side effect management. Obtaining knowledge on the various forms of immune-related toxicities and swiftly changing treatment techniques to lower the probability of experiencing severe irAEs has become a priority in oncological care. In recent years, there has been a growing understanding of an intriguing link between the gut microbiome and ICI outcomes. Multiple studies have demonstrated a connection between microbial metagenomic and metatranscriptomic patterns and ICI efficacy in malignant melanoma, lung and colorectal cancer. The immunomodulatory effect of the gut microbiome can have a real effect on the biological background of irAEs as well. Furthermore, specific microbial signatures and metabolites might be associated with the onset and severity of toxicity symptoms. By identifying these biological factors, novel biomarkers can be used in clinical practice to predict and manage potential irAEs. This comprehensive review aims to summarize the clinical aspects and biological background of ICI-related irAEs and their potential association with the gut microbiome and metabolome. We aim to explore the current state of knowledge on the most important and reliable irAE-related biomarkers of microbial origin and discuss the intriguing connection between ICI efficacy and toxicity.

Application of ultrasound elastography in obstetrics and gynecology / Ultrahang-elasztográfia alkalmazásának lehetoségei a szülészet-nogyógyászatban.

Összefoglaló. Az ultrahang-elasztográfia az elmúlt évek során egyre növekvo figyelmet kapott a lágyszövetek elaszticitásának vizsgálatában. A módszer használatát az teszi szükségessé, hogy egyes, a mechanikai tulajdonságaikban különbözo szövetek hasonló echogenitásúak lehetnek, valamint hogy egy adott szövet megváltozott struktúrája vagy mechanikai tulajdonsága nem minden esetben jár együtt a szövet hagyományos ultrahangképének megváltozásával. Az elmúlt évtizedben a deformációs és a nyírási ultrahang-elasztográfia vált széles körben elérhetové. Ezen új képalkotási technika egyre nagyobb szerepet tölt be a szülészeti-nogyógyászati ultrahang-diagnosztikában is. A nogyógyászatban szerephez juthat az endometriosis és az adenomyosis kimutatásában, valamint a benignus és a malignus cervicalis és ovarialis képletek elkülönítésében. A nogyógyászathoz hasonlóan a szülészetben is jelentos változást hozhat az ultrahang-elasztográfia: alkalmas lehet a szülésindukció sikerességének, a koraszülés bekövetkezésének és a praeeclampsia kialakulásának elorejelzésére. Orv Hetil. 2021; 162(18): 690-695. Summary. Ultrasound elastography has received significant attention for the assessment and measurement of soft tissue elastic properties in recent years. The advantage of ultrasound elastography lies in the fact that two different tissues can share similar echogenicities but may have other mechanical properties or, on the contrary, mechanical abnormalities of a designated tissue do not necessarily go hand in hand with an altered appearance on a conventional ultrasound image. In the last decade, strain and shear-wave elasticity imaging methods have become the most widely available among commercial ultrasound equipments. The importance of this new method expands rapidly also in the field of obstetrics and gynecology. Ultrasound elastography has a promising role in the diagnosis of endometriosis and adenomyosis and helps to differentiate benign and malignant cervical and ovarian lesions. The use in the prediction of the outcome of labor induction and preterm birth, and in the evaluation of preeclampsia are emerging. Orv Hetil. 2021; 162(18): 690-695.

Predictive Value of Biomechanical Mapping for Pelvic Organ Prolapse Surgery.

OBJECTIVE: This study examined biomechanical changes in pelvic floor after urogynecological surgery. METHODS: This multisite clinical study was designed to explore changes in tissue elasticity, pelvic support, and certain functions (contractive strength, muscle relaxation speed, muscle motility) after pelvic organ prolapse (POP) surgery. A biomechanical mapping of the pelvic floor was performed before and 4 to 6 months after the surgery. The biomechanical data for 52 parameters were acquired by vaginal tactile imaging for manually applied deflection pressures to vaginal walls and pelvic muscle contractions. The two-sample t-test (P < 0.05) was used to test the null hypothesis that presurgery data in group 1 (positive parameter change after surgery) and presurgery data in group 2 (negative parameter change after surgery) belonged to the same distribution. RESULTS: A total of 78 subjects with 255 surgical procedures were analyzed across 5 participating clinical sites. All 52 t-tests for group 1 versus group 2 had P value in the range from 4.0 × 10-10 to 4.3 × 10-2 associating all of the 52 parameter changes after surgery with the presurgical conditions. The P value of before and after surgery correlation ranged from 3.7 × 10-18 to 1.6 × 10-2 for 50 of 52 tests, with Pearson correlation coefficient ranging from -0.79 to -0.27. Thus, vaginal tactile imaging parameters strongly correlated weak pelvic floor presurgery with the positive POP surgery outcome of improved biomechanical properties. CONCLUSIONS: Pelvic organ prolapse surgery, in general, improves the biomechanical conditions and integrity of the weak pelvic floor. The proposed biomechanical parameters can predict changes resulting from POP surgery.

Comparison of novel single nucleotide polymorphisms of zinc transporters with zinc concentration in the human blood and vaginal tissues.

The most important proteins regulating cellular zinc homeostasis belong to two protein families of zinc transporters, the solute carrier family 30 (SLC30A) and solute carrier family 39 (SLC39A). We aimed to identify single nucleotide polymorphisms (SNPs) of the SLC30A and SLC39A genes and its association with blood and vaginal tissue zinc levels since vaginal tissue zinc level may play a role in vaginal remodeling and pathological conditions of the vagina. Blood and vaginal tissue samples were collected from women undergoing surgery for benign gynecological reasons. SNPs of twenty-four zinc transporters were determined by PCR/Sequence method, and the concentration of zinc was assessed by inductively coupled plasma optical emission spectrometry. Sequencing of selected exons revealed 16 SNPs, including five previously unidentified SNPs. Our data showed an association between the number of SNPs (more than six SNPs vs. less than six) per patient and high zinc vaginal tissue levels (67% vs. 33%, p < 0.01). The SLC39A4 SNP 590c A (rs17855765) was significantly more frequent in the group of women with high zinc vaginal tissue levels compared to the group without SNP (93% vs. 7%, p = 0.02). Also, our analysis revealed that the number of SNPs in SLC39A4 was significantly more frequent in patients with low zinc blood levels (76% vs. 24%, p = 0.01). Our findings indicate that different SNPs of the zinc transporter genes may have a significant effect on the blood and vaginal tissue zinc levels.

Incidence of haematological malignancies in adults in Szabolcs-Szatmár-Bereg county, Hungary. Analysis of data of a 36-year period / A felnottkori malignus hematológiai megbetegedések gyakorisága Szabolcs-Szatmár-Bereg megyében. 36 év adatainak elemzése.

INTRODUCTION: During a 36-year period (between January 1, 1983 and December 31, 2018), 5159 adult patients with newly diagnosed haematological malignancy were registered in the leukaemia/lymphoma registry of Szabolcs-Szatmár-Bereg county. AIM: The review of the incidence of different haematological malignancy in the authors' county, and the changes of incidence from time to time, the associated haematological malignancies, and familial occurrence of malignant haematological diseases. METHOD: Detailed analysis of the data of the registry, with statistical analysis of incidence. RESULTS: The incidence of Hodgkin disease and non-Hodgkin's lymphoma (1.49 and 7.12 new cases, respectively/100 000 inhabitants/year) was a little smaller, that of essential thrombocythaemia was larger than in the published data. The incidence of all other haematological malignancies corresponded to the data of the literature. The change of incidence of all malignant haematological diseases was similar to the published data. In the registry, there were 35 patients with two different malignant haematological diseases appearing simultaneously or successively. During the 36-year period, 88 families with haematological malignancies were recorded in the registry. CONCLUSION: With the exception of Hodgkin disease, non-Hodgkin's lymphoma, and essential thrombocythaemia, the incidence of other haematological malignancies corresponded to the data of the literature. The change of incidence in all entities was similar to that observed by other authors. The authors in their country do not know other published data related to associated malignant haematological diseases. The observed anteposition in familial haematological diseases of uncle/aunt and nephew/cousin, and anteposition in malignant haematological diseases of siblings are equally new in the literature. Orv Hetil. 2020; 161(34): 1400-1413.

Epidemiology, mortality and prevalence of colorectal cancer in ulcerative colitis patients between 2010-2016 in Hungary - a population-based study.

BACKGROUND: The incidence and prevalence of ulcerative colitis (UC) varies geographically. The risk of colorectal cancer (CRC) and possibly some other malignancies is increased among patients with UC. It is still debated if patients with UC are at a greater risk of dying compared with the general population. Our aim was to describe the epidemiology and mortality of the Hungarian UC population from 2010 to 2016 and to analyze the associated malignancies with a special focus on CRC. METHODS: This is an observational, descriptive, epidemiological study based on the National Health Insurance Fund social security databases from 2010 to 2016. All adult patients who had at least two events in outpatient care or at least two medication prescriptions, or at least one inpatient event with UC diagnosis were analyzed. Malignancies and CRC were defined using ICD-10 codes. We also evaluated the survival of patients suffering from UC compared with the general population using a 3 to 1 matched random sample (age, gender, geography) from the full population of Hungary. RESULTS: We found the annual prevalence of UC 0.24-0.34%. The incidence in 2015 was 21.7/100 000 inhabitants. Annual mortality rate was 0.019-0.023%. In this subpopulation, CRC was the most common cancer, followed by non-melanotic skin and prostate cancer. 8.5% of the UC incident subpopulation was diagnosed with CRC. 470 (33%) of the CRC patients died during the course of the study (25% of all deaths were due to CRC), the median survival was 9.6 years. UC patients had significantly worse survival than their matched controls (HR = 1.65, 95% CI: 1.56-1.75). SUMMARY: This is the first population-based study from Eastern Europe to estimate the different malignancies and mortality data amongst Hungarian ulcerative colitis patients. Our results revealed a significantly worse survival of patients suffering from UC compared to the general population.

Large-scale mortality gap between SLE and control population is associated with increased infection-related mortality in lupus.

OBJECTIVE: The aim of the present study was to analyse the incidence, prevalence, mortality and cause of death data of adult SLE patients and matched controls in a full-populational, nationwide, retrospective study. METHODS: This non-interventional study was based on database research of the National Health Insurance Fund of Hungary. A total of 7888 patients were included in the analyses, within which two subgroups of incident patients were created: the 'All incident SLE patients' group consisted of all incident SLE patients (4503 patients), while the 'Treated SLE patients' group contained those who received relevant therapy in the first 6 months after diagnosis (2582 patients). RESULTS: The median age of the SLE population was found to be 46.5 years (women 85%). The incidence rate was 4.86 and 2.78 per 100 000 inhabitants in the 'All incident SLE patients' and 'Treated SLE patients' groups, respectively. The standardized mortality ratio was 1.63 and 2.09 in the 'All incident SLE patients' and 'Treated SLE patients' groups, respectively. Overall survival was significantly lower (P < 0.001) in both groups than in the general population, with hazard ratio = 2.17 in the 'All incident SLE patients' group and hazard ratio = 2.75 in the 'Treated SLE patients' group. There was no significant difference between SLE and control deaths regarding cerebrovascular conditions as the cause of death. Generally, cancer-related deaths were less common, while haematological cancer and infection-related deaths were more common in SLE patients. CONCLUSION: Infections, especially sepsis, had the largest positive effect on top of the extra mortality of SLE. This highlights that SLE patients are at increased risk of infection-related death.

The effect of oral zinc supplementation on cervicovaginal lavage fluid zinc level.

OBJECTIVES: To investigate the effect of oral zinc supplementation on cervicovaginal lavage fluid (CVL) zinc level in pre and postmenopausal women. STUDY DESIGN: A prospective interventional cohort study was carried out by the enrollment of twelve premenopausal and ten postmenopausal women without significant gynecological conditions. Women received daily oral supplementation with 30 mg of zinc for two weeks. Clinical and demographic variables were stored in a dedicated database. Vaginal Health Index was calculated, and vaginal cytology was obtained. CVL and serum samples were collected in a standardized fashion before and after completion of the oral supplementation. Zinc and copper levels were measured by inductively coupled plasma optical emission spectrometry. Paired t-test was used to compare the before and after treatment results. RESULTS: Serum zinc levels increased significantly both in the pre and postmenopausal women (0.88 ± 0.17 vs. 1.06 ± 0.23, p < 0.01 and 0.83 ± 0.24 vs. 0.96 ± 0.33, p < 0.01) after two weeks of daily oral zinc supplementation. CVL zinc level was significantly higher in the premenopausal group compared to the postmenopausal group before and after supplementation (0.13 ± 0.05 vs. 0.06 ± 0.04, p < 0.01 and 0.10 ± 0.03 vs. 0.05 ± 0.01, p < 0.01). Zinc supplementation had no significant impact on the CVL zinc level in either group. Neither serum nor CVL copper levels were affected by the zinc supplementation. There was no significant correlation between serum and CVL zinc or copper levels. CONCLUSION: Daily oral supplementation with 30 mg of zinc had no significant impact on CVL zinc level despite a significant rise in serum zinc level.

The Effect of Vaginal Microablative Fractional CO2 Laser Treatment on Vaginal Cytology.

BACKGROUND AND OBJECTIVES: Most recently vaginal laser treatment was introduced as a new option for women with genitourinary syndrome of menopause, vaginal dryness. Our objective was to assess the effects of intravaginal CO2 laser treatment on vaginal cytology. STUDY DESIGN/MATERIALS AND METHODS: Fifty-two women with symptoms of vaginal dryness were enrolled and underwent vaginal laser treatment using a fractional CO2 laser. Patients received three vaginal laser treatments 4 weeks apart. Vaginal cytology was obtained before the first treatment and 4 weeks after each additional treatment. Vaginal dryness was assessed by using a Visual Analog Scale (VAS). RESULTS: Out of the 52 women enrolled, 34 were in menopause. Postmenopausal women had significantly lower vaginal maturation values (VMV) compared with premenopausal women at the baseline visit (mean ± standard deviation [SD], 42 ± 23 vs. 68 ± 13, P < 0.01). The vaginal dryness VAS was higher (worse) in postmenopausal women compared with premenopausal cases (mean ± SD, 5.7 ± 4 vs. 2.4 ± 3, P < 0.01). The VMV did not change significantly over time after vaginal laser treatment. However vaginal dryness VAS improved significantly after each treatment. Both in the premenopausal and postmenopausal groups, vaginal dryness scores improved significantly from baseline after the three treatments (postmenopausal 5.7 ± 4 vs. 1.6 ± 2.5, P < 0.01 and premenopausal 2.4 ± 3 vs. 0.2 ± 0.5, P < 0.01). Those patients who had improvement in VMV had significantly better (lower) dryness VAS compared with those women without an improvement in VMV after the three treatments (mean ± SD, 0.3 ± 0.8 vs. 1.6 ± 2.6, P = 0.04). CONCLUSIONS: Vaginal dryness VAS improved significantly in a cohort of premenopausal and postmenopausal women undergoing vaginal CO2 laser treatment despite no significant change in vaginal cytology. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Epidemiological data and utilization patterns of anti-TNF alpha therapy in the Hungarian ulcerative colitis population between 2012-2016.

Background: Anti-TNF therapy is efficacious in the maintenance of remission in ulcerative colitis (UC); however, long-term data on real-life use of these agents are lacking.Methods: This observational, retrospective, epidemiological study using the National Health Insurance Fund social security database aimed to understand patient characteristics and therapeutic patterns of anti-TNF therapy. Data of adult Hungarian, UC patients treated with anti-TNF agents (IFX-infliximab, ADA-adalimumab) between 2012 and 2016 were analyzed.Results: Five hundred and sixty-eight UC patients were identified. Approximately 70-80% of the patients reached maintenance therapy. A large proportion of patients stopped therapy after 10 to 12 months due to the reimbursement policy. Corticosteroid use decreased significantly after the initiation of biological therapy. The dose-escalation rate was 19.8% for ADA and 10.9% for IFX, respectively, and was performed earlier along the treatment timeline for patients on ADA. In the present study, the rate of primary non-response (PNR) was 11.6% and the rate of secondary loss of response (LOR) was 36.5%.Summary: Treatment length is in correspondence with the Hungarian reimbursement policies. The mandatory stop of treatment in the reimbursement policy is suboptimal in UC patients requiring biological therapy. The corticosteroid-sparing effect of biological therapy was demonstrated.

[Short-term efficacy of vaginal CO2 laser therapy as a treatment modality for genitourinary syndrome of menopause]. / A hüvelyi CO2-lézer-kezelés rövid távú hatásai a menopausalis genitourinalis szindróma tüneteire.

Introduction: Genitourinary syndrome of menopause (GSM) affects up to 40-57% of postmenopausal women. Intravaginal microablative fractional CO2 laser is a new proposal for the management of GSM, although the evidence of safety and efficacy of the procedure appears to be insufficient. Aim: The aim of the study was to assess the efficacy of fractional CO2 laser for the treatment of GSM at the Department of Obstetrics and Gynecology of the University of Debrecen. Method: Postmenopausal women with symptoms of GSM underwent three sessions of microablative fractional rejuvenation CO2 laser therapy at 4-6 weeks intervals. Vaginal health index (VHI) scores were completed before each treatment and at 6 weeks follow-up as an objective measurement and visual analog scale was used to assess subjective complaints. Statistical analysis included Student's paired two-sampling t-test for the measure of statistical significance using the standard cutoff for significance p<0.05. Results: 51 women participated (mean age 57.0 ± 9.9 y). Average VHI score was 14.0 ± 4.9 before treatment, 15.0 ± 4.7 after the first session, 18.2 ± 4.6 after the second treatment and 19.5 ± 4.9 at follow-up. The improvement of VHI score was statistically significant between all sessions. Average VAS score was 15.6 ± 14.1 before treatment, 9.0 ± 10.8 after the first session, 5.9 ± 9.2 after the second treatment and 3.4 ± 7.5 at follow-up. The improvement of VAS score was statistically also significant between all sessions. Conclusions: Our study suggests that the fractional CO2 laser is an effective and safe treatment of symptoms associated with GSM. Orv Hetil. 2019; 160(41): 1617-1622.

The Effect of Fractional CO2 Laser Treatment on the Symptoms of Pelvic Floor Dysfunctions: Pelvic Floor Distress Inventory-20 Questionnaire.

BACKGROUND AND OBJECTIVES: To assess the improvement on pelvic floor distress (PFD)-related urogenital symptoms using validated questionnaires after intravaginal CO2 laser treatment. STUDY DESIGN/MATERIALS AND METHODS: Forty postmenopausal women with genitourinary symptoms of menopause (GSM) were enrolled into this prospective cohort study and underwent vaginal laser treatment using MonaLisa Touch® fractional CO 2 laser system. Patients received three vaginal laser treatments with 360° probe 4 weeks apart. A three-component Pelvic Floor Distress Inventory (PFDI-20) validated questionnaire was filled out by each patient before each session and 4 weeks after the final treatment. Wilcoxon rank sum test was used to compare the before and after treatment scores. RESULTS: Pelvic Organ Prolapse Distress Inventory (POPDI-6) scores were not significantly different after the first treatment compared with baseline (mean ± standard deviation [SD], 21 ± 18 vs. 17 ± 15, P = 0.44). However, each subsequent treatment resulted in further, statistically significant improvement in symptom scores (14 ± 15, P = 0.03 and 13 ± 13, P = 0.01, after the second and third treatments, respectively). Similarly, Urinary Distress Inventory (UDI-6) scores were not significantly different after the first laser treatment (mean ± SD, 36 ± 25 vs. 29 ± 23, P = 0.36). After the second and third treatments there were significant improvement in the standardized scores (24 ± 20, P = 0.03 and 22 ± 21, P = 0.01). Colorectal-Anal Distress Inventory (CRADI-8) scores did not change significantly after three laser treatments. CONCLUSIONS: Three sessions of microablative fractional CO2 vaginal laser treatment significantly improves patient reported urinary and pelvic organ prolapse symptoms. Lasers Surg. Med. © 2019 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Socioeconomic status, health related behaviour, and self-rated health of children living in Roma settlements in Hungary.

OBJECTIVE: The poor health of Roma is well documented, but there is only limited data regarding the health of Roma children. The aim of this study was to describe the socioeconomic status, health related behaviour, and health of children living in segregated Roma settlements, and to compare the data with that of non-Roma children. METHODS: In March-April of 2011, a cross-sectional questionnaire-based survey among 11-year-old (211 boys and 252 girls) and 13-year-old (205 boys and 247 girls) children living in Roma settlements was performed (response rate: 91.5%). These data were compared with data from the Health Behaviour in School-Aged Children (HBSC) survey carried out in 2009/2010. RESULTS: The parents of Roma children were substantially less educated and less likely to be actively employed, and Roma children reported lower material welfare than non-Roma ones. The prevalence of consuming sweets and soft drinks at least 5 times per week was 1.5-2 times higher among Roma children. The prevalence of regular intense physical activity was higher at the age of 13 years among Roma boys, while physical inactivity was substantially higher in both age groups among Roma girls. Almost one quarter of Roma children and approximately 14% of non-Roma children had tried smoking at the age of 11. More Roma boys tried alcohol at the age of 11 than non-Roma ones. One in ten Roma children was obese in both age groups. The self-rated health status of Roma children was worse than that of non-Roma children. CONCLUSIONS: Children living in Roma settlements reported poorer socioeconomic conditions, higher consumption of sweets and soft drinks, earlier smoking and alcohol initiation, and worse self-rated health, but with some exceptions do not differ in fruit or vegetable consumption and BMI from general child population. To promote health of children living in Roma settlements, a multi-sector approach, special health education, plus social and health promotion programmes are needed.

Persistence to subcutaneous biological agents in Hungarian patients treated for inflammatory arthritis.

BACKGROUND: The aim of the study was to compare drug survival rate of subcutaneous tumor necrosis factor alpha inhibitors in rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis patients in Hungary. METHODS: This was a retrospective analysis using data collected from 5,647 patients over a period of 10 years who were treated with any of the following drugs: adalimumab (ADA), etanercept, certolizumab pegol (CZP), and golimumab (GLM). National Health Insurance Fund's hospital, drug reimbursement, and special reimbursement registry data have been used in this study. Drug survival rate was calculated according to Kaplan-Meier survival analysis. Propensity score matching was used to reduce the potential bias caused by the inhomogeneity resulting from demographic characteristics, patient pathways, or drug administration protocols. Both raw and propensity matched data were subject of pairwise comparison between the four subcutaneous therapies. RESULTS: The overall rate of persistence for the 4 biological therapies was between 53% and 61% after 1 year and between 14% and 19% after 4 years (follow-up time). Pairwise comparisons between therapies showed significant differences with GLM-treated patients showing longer median survival times than patients on other therapies. After propensity matching, these differences remained statistically significant between GLM and ADA or CZP over 4 years. CONCLUSION: Hungarian show longer persistence to GLM compared to ADA and CZP.