Colorectal Cancer and Screening Awareness, Beliefs and Attitudes

The World Health Organization predicts that colorectal carcinoma (CRC) will be the second most common cause of tumor-related mortality in 2018. The standardized mortality rate was the highest in Hungary (followed by Croatia) within the member states of the European Union in 2015. In Hungary, the second most common cause of death is CRC, a great challenge for public health. In countries running an effective campaign against smoking, CRC has become the most common malignant tumor, overtaking lung carcinoma. According to recent Hungarian data, 5 841 and 4 776 newly diagnosed CRC cases were recorded in 2015 among males and females, respectively; and CRC was responsible for 5 841 fatalities in 2017. In CRC, 70% of the cases are sporadic, 10-30% run in the family, and 7% is accompanied by diseases where the development of CRC is almost inevitable. In Hungary, most of the diagnosed cases are advanced (stages 3 or 4) where the yield of a curative therapy is humble. An approach to fixing this issue might be the introduction of CRC screening for people above 50 years of age as a proxy for the operating sporadic screening model. Although the preparations of the regular screening have been progressing for many years, the program has not been launched until the submission of this thesis. The initial step of the screening program would be the invitation of 1.8 million potential attendees between 50 and 75 years by volunteer family doctors or screening centers. Adenomatous polyps are present in 5-10% of the general population, which spikes up to 20-25% among those above 50 years and of average risk of CRC. The length of the preclinical period of CRC supports the idea of screening because the multistep adenoma-CRC sequence embraces a 10-15-year period. The incidence of adenomas is the highest between 55 and 65 years, whereas that of CRC is the highest between 65 and 75 years. The primary objective of CRC screening is the detection and removal of adenomas in average-risk persons and the early recognition of asymptomatic lesions, thereby providing better opportunities for curative therapy. The application of standard screening optimizes costs of care compared to the burden imposed by the management of advanced CRC. Data from the opportunistic CRC screening revealed a very low attendance rate (32%), for which several restraining factors are responsible. Besides, the rationale for carrying out this study is supported by the fact that knowledge of and attitude towards CRC have not been surveyed and published in Hungary

Menthol can be safely applied to improve thermal perception during physical exercise : a meta-analysis of randomized controlled trials

Menthol is often used as a cold-mimicking substance to allegedly enhance performance during physical activity, however menthol-induced activation of cold-defence responses during exercise can intensify heat accumulation in the body. This meta-analysis aimed at studying the effects of menthol on thermal perception and thermophysiological homeostasis during exercise. PubMed, EMBASE, Cochrane Library, and Google Scholar databases were searched until May 2020. Menthol caused cooler thermal sensation by weighted mean difference (WMD) of - 1.65 (95% CI, - 2.96 to - 0.33) and tended to improve thermal comfort (WMD = 1.42; 95% CI, - 0.13 to 2.96) during physical exercise. However, there was no meaningful difference in sweat production (WMD = - 24.10 ml; 95% CI, - 139.59 to 91.39 ml), deep body temperature (WMD = 0.02 °C; 95% CI, - 0.11 to 0.15 °C), and heart rate (WMD = 2.67 bpm; 95% CI - 0.74 to 6.09 bpm) between the treatment groups. Menthol improved the performance time in certain subgroups, which are discussed. Our findings suggest that different factors, viz., external application, warmer environment, and higher body mass index can improve menthol's effects on endurance performance, however menthol does not compromise warmth-defence responses during exercise, thus it can be safely applied by athletes from the thermoregulation point of view

A Nissen-féle fundoplicatio sikeressége és az azt befolyásoló faktorok. Eredmények a Pécsi Tudományegyetemen az indikációk és tünetek függvényében = Effectivity of the Nissen fundoplication and the influencing factors of the success. Results at the Medical Centre of Pécs depending on the indications and symptoms

Absztrakt: Bevezetés: A gastrooesophagealis refluxbetegség a fejlett országokban a leggyakoribb gastrointestinalis betegségek közé tartozik. Terápiájában a konzervatív kezelés mellett dedikált esetekben ma is nagy szerep jut a sebészeti beavatkozásoknak. Célkitűzés: Vizsgálatunk célja a Pécsi Tudományegyetem Sebészeti Klinikáján 2007 és 2014 között Nissen-féle fundoplicatión átesett betegek műtéti és 6 hónapos követéses eredményeinek feldolgozása, irodalmi eredményekkel való összehasonlítása (quality control) és a sikerességet befolyásoló faktorok (elsősorban a pszichiátriai társbetegség dokumentált jelenléte és antidepresszánsszedés) felderítése volt. Módszer: 166 beteg összesen 183 műtéti és posztoperatív adatai kerültek kigyűjtésre a Pécsi Tudományegyetem betegadatbázisából. Statisztikai analízis: Az adatok elemzése leíró statisztikával – relatív gyakoriság – és odds ratióval 95%-os valószínűségi szinttel történt. Eredmények: Vizsgálatunk kimutatta, hogy a primer fundoplicatiók leggyakoribb indikációja a protonpumpagátló (PPI)-refrakteritással társuló hiatus hernia volt (54%). A reoperációk indikációi gyakoriság tekintetében jelentős eltéréseket mutattak az irodalmi adatokhoz képest, azonban a reoperációs ráta centrumunkban (8%) megfelelt a nemzetközi tapasztalatoknak (5–10%). A műtétet követően a betegek 62%-ának volt valamilyen panasza. A puffadás kivételével ezek gyakoribbak voltak a nők körében. Operáció után 93,67% tapasztalt valamilyen szintű javulást a refluxos tüneteiben. Ismételt PPI-kezelésre 37%-nak volt szüksége 6 hónapon belül. Különböző posztoperatív beavatkozásokra az esetek 9%-ában került sor. A női nem és pszichiátriai társbetegség rontotta, az utóbbi esetben az antidepresszánsszedés javította a műtét eredményességét. A reoperációk eredményessége elmaradt a primer operációétól. Következtetések: Megfigyeléseink alapján elmondható, hogy a centrumunkban alkalmazott fundoplicatiók eredményessége megfelel a nemzetközi eredményeknek, a szorongásos-depressziós pszichiátriai társbetegségek okozta rosszabb posztoperatív eredmények (tünetjavulási arány) feltehetően kivédhetők vagy mérsékelhetők megfelelően beállított antidepresszáns kezeléssel, de ebben a kérdésben további tanulmányok szükségesek. Orv Hetil. 2018; 159(25): 1013–1023. | Abstract: Introduction: Gastroesophageal reflux disease is one of the most common gastrointestinal diseases in developed countries. Besides the conservative modalities, surgery plays an increasing role in the treatment of the disease. Aim: Our aim was to investigate and compare the surgical and 6-month follow-up data of patients to the literature (quality control), who underwent Nissen fundoplication in the Medical Centre of Pécs between 2007 and 2014, and to assess the factors (especially psychiatric comorbidity and antidepressants) influencing the success. Method: In summary, data of 183 fundoplications of 166 patients were collected from the medical database of the University of Pécs. Statistical analysis: For data analysis, descriptive statistical methods (relative frequency) and odds ratio with 95% confidence interval were used. Results: The most frequent indication of fundoplications was hiatal hernia combined with the failure of conservative (proton-pump inhibitor, PPI) treatment (54%). Reoperation rate (8%) was similar to literature data (5–10%). 62% of the patients had postoperative complaints, which, except bloating, were more common among women. 93.67% experienced certain grade of improvement of reflux symptoms. Postoperative PPI treatment was necessary in 37% of patients and in 9% postoperative interventions had to be performed. Female gender and psychiatric comorbidity worsened, antidepressant medication improved the success rate. The results of reoperations were inferior compared to primary operations. Conclusions: Our results suggest that the success rate of fundoplications in our centre fits to the literature data and adequate antidepressant medication may improve the worse results of psychiatric patients postoperatively, however, more randomized clinical studies are needed in this issue. Orv Hetil. 2018; 159(25): 1013–1023

Relative performance of various biomaterials used for maxillary sinus augmentation. A Bayesian network meta-analysis.

To assess the histomorphometric outcomes obtained in randomized clinical trials (RCTs) with different biomaterials used for maxillary sinus augmentation (MSA).A search of the existing medical literature until October 1, 2019 was performed. Inclusion criteria were (1) RCTs assessing a two-stage MSA from the lateral approach using autologous bone or biomaterials for grafting, (2) reported histomorphometric outcomes based on crestal bone core biopsy samples. The Bayesian method was used to perform pairwise meta-analyses and network meta-analysis (NMA). The primary outcome, the new bone percentage (NB%), was calculated as mean differences with 95% credible intervals. The interventions were ranked by their posterior probability by calculating the Surface Under the Cumulative Ranking curve values.Thirty-four RCTs (842 MSAs) were included in the analysis with a normal healing period (5-8 months). All comparisons were presented in a league table. On the basis of the ranking probability, the most effective bone grafting material for NB% was bovine xenograft + bone marrow concentrate (BMC) (81%), followed by bovine xenograft + platelet-rich plasma (PRP) (77%), bioactive glass ceramic + autologous bone 1:1 (70 %), nanocrystalline hydroxyapatite in silica gel (70%), and bioactive glass ceramic (70%). Autologous bone graft alone took the twelfth position with 57%.Within the limitations of the present NMA, the analysis did not confirm autologous bone alone as the gold standard for MSA and showed superiority of composite grafts such as bovine xenograft + BMC after 5-8 months of healing

Risk of chronic pancreatitis in carriers of loss-of-function CTRC variants: A meta-analysis

The digestive protease chymotrypsin C (CTRC) protects the pancreas against pancreatitis by degrading potentially harmful trypsinogen. Loss-of-function genetic variants in CTRC increase risk for chronic pancreatitis (CP) with variable effect size, as judged by the reported odds ratio (OR) values. Here, we performed a meta-analysis of published studies on four variants that alter the CTRC amino-acid sequence, are clinically relatively common (global carrier frequency in CP >1%), reproducibly showed association with CP and their loss of function phenotype was verified experimentally. We found strong enrichment of CTRC variants p.A73T, p.V235I, p.K247_R254del, and p.R245W in CP cases versus controls, yielding OR values of 6.5 (95% confidence interval (CI) 2.4-17.8), 4.5 (CI 2.2-9.1), 5.4 (CI 2.6-11.0), and 2.6 (CI 1.6-4.2), respectively. Subgroup analysis demonstrated disease association of variants p.K247_R254del and p.R245W in alcoholic CP with similar effect sizes as seen in the overall CP group. Homozygosity or compound heterozygosity were rare and seemed to be associated with higher risk. We also identified a so far unreported linkage disequilibrium between variant p.K247_R254del and the common c.180C>T (p.G60 =) haplotype. Taken together, the results indicate that heterozygous loss-of-function CTRC variants increase the risk for CP approximately 3-7-fold. This meta-analysis confirms the clinical significance of CTRC variants and provides further justification for the genetic screening of CP patients

Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19 : a systematic review and meta-analysis

Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMDALC = - 0.35 × 109/L [CI - 0.43, - 0.27], p < 0.001, I2 = 94.2%; < 0.8 × 109/L, ORALC = 3.74 [CI 1.77, 7.92], p = 0.001, I2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention

EASY-APP: An artificial intelligence model and application for early and easy prediction of severity in acute pancreatitis

Acute pancreatitis; Artificial intelligence; Severity predictionPancreatitis aguda; Inteligencia artificial; Predicción de gravedadPancreatitis aguda; Intel·ligència artificial; Predicció de la gravetatBackground Acute pancreatitis (AP) is a potentially severe or even fatal inflammation of the pancreas. Early identification of patients at high risk for developing a severe course of the disease is crucial for preventing organ failure and death. Most of the former predictive scores require many parameters or at least 24 h to predict the severity; therefore, the early therapeutic window is often missed. Methods The early achievable severity index (EASY) is a multicentre, multinational, prospective and observational study (ISRCTN10525246). The predictions were made using machine learning models. We used the scikit-learn, xgboost and catboost Python packages for modelling. We evaluated our models using fourfold cross-validation, and the receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), and accuracy metrics were calculated on the union of the test sets of the cross-validation. The most critical factors and their contribution to the prediction were identified using a modern tool of explainable artificial intelligence called SHapley Additive exPlanations (SHAP). Results The prediction model was based on an international cohort of 1184 patients and a validation cohort of 3543 patients. The best performing model was an XGBoost classifier with an average AUC score of 0.81 ± 0.033 and an accuracy of 89.1%, and the model improved with experience. The six most influential features were the respiratory rate, body temperature, abdominal muscular reflex, gender, age and glucose level. Using the XGBoost machine learning algorithm for prediction, the SHAP values for the explanation and the bootstrapping method to estimate confidence, we developed a free and easy-to-use web application in the Streamlit Python-based framework (http://easy-app.org/). Conclusions The EASY prediction score is a practical tool for identifying patients at high risk for severe AP within hours of hospital admission. The web application is available for clinicians and contributes to the improvement of the model.University of Pécs Medical School Research Fund. Grant Number: 300909. National Research, Development and Innovation Office Research Fund. Grant Numbers: K131996, FK131864, K128222, FK12463

Exosomes as prognostic biomarkers in pancreatic ductal adenocarcinoma—a systematic review and meta-analysis

Extensive research is focused on the role of liquid biopsy in pancreatic cancer since reliable diagnostic and follow-up biomarkers represent an unmet need for this highly lethal malignancy. We performed a systematic review and meta-analysis on the prognostic value of exosomal biomarkers in pancreatic ductal adenocarcinoma (PDAC). MEDLINE, Embase, Scopus, Web of Science, and CENTRAL were systematically searched on the 18th of January, 2021 for studies reporting on the differences in overall (OS) and progression-free survival (PFS) in PDAC patients with positive versus negative exosomal biomarkers isolated from blood. The random-effects model estimated pooled multivariate-adjusted (AHR) and univariate hazard ratios (UHRs) with 95% confidence intervals (CIs). Eleven studies comprising 634 patients were eligible for meta-analysis. Detection of positive exosomal biomarkers indicated increased risk of mortality (UHR=2.81, CI:1.31-6,00, I2=88.7%, p<0.001), and progression (UHR=3.33, CI: 2.33-4.77, I2=0, p=0.879) across various disease stages. Positive exosomal biomarkers identified preoperatively revealed a higher risk of mortality in resectable stages (UHR=5.55, CI: 3.24-9.49, I2=0, p=0.898). The risk of mortality in unresectable stages was not significantly increased with positive exosomal biomarkers (UHR=2.51, CI: 0.55-11.43, I2=90.3%, p<0.001). Detectable exosomal micro ribonucleic acids were associated with a decreased OS (UHR=4.08, CI: 2.16-7.69, I2=46.9%, p=0.152) across various stages. Our results reflect the potential of exosomal biomarkers for prognosis evaluation in PDAC. The associated heterogeneity reflects the variability of study methods and need for their uniformization before transition to clinical use