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The aim of this study was to analyse the clinical characteristics of acute pancreatitis (AP) in a prospectively collected, large, multicentre cohort and to validate the major recommendations in the IAP/APA evidence-based guidelines for the management of AP. Eighty-six different clinical parameters were collected using an electronic clinical research form designed by the Hungarian Pancreatic Study Group. 600 adult patients diagnosed with AP were prospectively enrolled from 17 Hungarian centres over a two-year period from 1 January 2013. With respect to aetiology, biliary and alcoholic pancreatitis represented the two most common forms of AP. The prevalence of biliary AP was higher in women, whereas alcoholic AP was more common in men. Hyperlipidaemia was a risk factor for severity, lack of serum enzyme elevation posed a risk for severe AP, and lack of abdominal pain at admission demonstrated a risk for mortality. Abdominal tenderness developed in all the patients with severe AP, while lack of abdominal tenderness was a favourable sign for mortality. Importantly, lung injury at admission was associated with mortality. With regard to laboratory parameters, white blood cell count and CRP were the two most sensitive indicators for severe AP. The most common local complication was peripancreatic fluid, whereas the most common distant organ failure in severe AP was lung injury. Deviation from the recommendations in the IAP/APA evidence-based guidelines on fluid replacement, enteral nutrition and timing of interventions increased severity and mortality. Analysis of a large, nationwide, prospective cohort of AP cases allowed for the identification of important determinants of severity and mortality. Evidence-based guidelines should be observed rigorously to improve outcomes in AP.

Irritable bowel syndrome (IBS) and functional digestive tract disorders, e.g. functional bloating, carbohydrate maldigestion and intolerances, are very common disorders frequently causing significant symptoms that challenge health care systems. A low Fermentable Oligosaccharides, Disaccharides, Monosaccharides and Polyols (FODMAP) diet is one of the possible therapeutic approaches for decreasing abdominal symptoms and improving quality of life. We aimed to meta-analyze data on the therapeutic effect of a low-FODMAP diet on symptoms of IBS and quality of life and compare its effectiveness to a regular, standard IBS diet with high FODMAP content, using a common scoring system, the IBS Symptom Severity Score (IBS-SSS). A systematic literature search was conducted in PubMed, EMBASE and the Cochrane Library as well as in the references in a recent meta-analysis. Adult patients diagnosed with IBS according to the Rome II, Rome III, Rome IV or NICE criteria were included in the analysis. Mean differences with 95% confidence intervals were calculated from studies that contained means, standard deviation (SD) or mean differences and SD of differences and p-values. A random effect model was used because of the heterogeneity (Q test (χ2) and I2 indicator). A p-value of less than 0.05 was chosen to indicate a significant difference. The literature search yielded 902 publications, but only 10 were eligible for our meta-analysis. Both regular and low-FODMAP diets proved to be effective in IBS, but post-diet IBS-SSS values were significantly lower (p = 0.002) in the low-FODMAP group. The low-FODMAP diet showed a correlation with the improvement of general symptoms (by IBS-SSS) in patients with IBS. This meta-analysis provides high-grade evidence of an improved general symptom score among patients with irritable bowel syndrome who have maintained a low-FODMAP diet compared to those on a traditional IBS diet, therefore showing its superiority to regular IBS dietary therapy. These data suggest that a low-FODMAP diet with dietitian control can be a candidate for first-line therapeutic modality in IBS. Because of a lack of data, well-planned randomized controlled studies are needed to ascertain the correlation between improvement of separate key IBS symptoms and the effect of a low-FODMAP diet.

Pancreatic cysts have various potential for malignant transformation. Differentiating mucinous from non-mucinous cysts is crucial to make the right decision about further management, since mucinous cysts carry the risk of malignancy. Using endoscopic ultrasound (EUS) guided fine needle aspiration to determine intracystic carcinoembryonic antigen (CEA) levels is the recommended method for identifying mucinous cysts, although intracystic glucose assessment has also proved to be an effective tool. This study aims to compare the diagnostic performance of intracystic glucose and CEA in distinguishing between mucinous and non-mucinous pancreatic cystic lesions. In this single center study, we prospectively collected and analyzed the data of 91 consecutive patients who underwent endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) with cytological analysis and measurement of intracystic CEA and glucose levels. The cyst type was classified based on radiological and EUS morphology, string sign, CEA, cytological and histological findings in resected cases. The diagnosis was established retrospectively by three experienced gastroenterologists blinded for glucose level in cases without definitive cytology or histology. We calculated the sensitivity, specificity, the positive- and negative predictive value of glucose and CEA respectively, and compared the two methods. The sensitivity of intracystic glucose versus CEA proved to be 96.2% vs. 69.2% in identifying mucinous cysts, while the specificity of glucose was shown to be 79.5%, compared to 100% for CEA. Intracystic glucose is a sensitive, easily accessible biomarker in identifying mucinous pancreatic cysts, however, the specificity is lower compared to CEA. The measurement of intracystic glucose level could help in decision-making in daily clinical practice, however the diagnostic performance of the method remains inferior to \"through-the-needle\" techniques, such as confocal laser endomicroscopy and Moray forceps biopsy.

Extracellular vesicles (EV) are considered as a promising diagnostic tool for pancreatic ductal adenocarcinoma (PDAC), a disease with a poor 5-year survival that has not improved in the past years. PDAC patient-derived 3D organoids maintain the intratumoral cellular heterogeneity, characteristic for the tumor in vivo.Thus, they represent an ideal in vitro model system to study human cancers. Here we show that the miRNA cargo of EVs from PDAC organoids largely differs among patients. However, we detected a common set of EV miRNAs that were present in matched organoids and blood plasma samples of individual patients. Importantly, the levels of EV miR-21 and miR-195 were higher in PDAC blood EV preparations than in healthy controls, albeit we found no difference compared to chronic pancreatitis (CP) samples. In addition, here we report that the accumulation of collagen I, a characteristic change in the extracellular matrix (ECM) in both CP and PDAC, largely increases EV release from pancreatic ductal organoids. This provides a possible explanation why both CP and PDAC patient-derived plasma samples have an elevated amount of CD63 + EVs. Collectively, we show that PDAC patient-derived organoids represent a highly relevant model to analyze the cargo of tumor cell-derived EVs. Furthermore, we provide evidence that not only driver mutations, but also changes in the ECM may critically modify EV release from pancreatic ductal cells.

Background and Aims: Pancreatic ductal adenocarcinoma has one of the worst prognosis of all malignancies. This investigated the relationship between the preoperative serum carbohydrate antigen 19-9 and surgical resectability. Methods: A systematic search was performed in three databases (MEDLINE, EMBASE, and Web of Science) to compare the surgical resectability of pancreatic ductal adenocarcinoma in patients with high and low preoperative serum carbohydrate antigen 19-9 values. The receiving operating characteristic curves were constructed and the weighted mean differences for preoperative serum carbohydrate antigen 19-9 levels of resectable and unresectable groups of patients were calculated. The PROSPERO registration number is CRD42019132522. Results: Results showed that there was a significant difference in resectability between the low and high carbohydrate antigen 19-9 groups. Six out of the eight studies utilised receiver operating characteristic curves in order to find the cut-off preoperative carbohydrate antigen 19-9 levels marking unresectability. The overall result from the pooled area under curve values from the receiver operating characteristic curves was 0.794 (CI: 0.694–0.893), showing that the preoperative carbohydrate antigen 19-9 level is a “fair” marker of resectability. The result of the pooled weighted mean differences was 964 U/ml ( p < 0.001) showing that there is a significant carbohydrate antigen 19-9 difference between the resectable and unresectable groups. Based on the results of the I-squared test, the result was 87.4%, accounting for “considerable” heterogeneity within the population. Conclusion: Carbohydrate antigen 19-9 is not a reliable marker of unresectability, it should not be used on its own in surgical decision-making.

Chronic pancreatitis is an inflammatory disease associated with structural and functional damage to the pancreas, causing pain, maldigestion and weight loss and thus worsening the quality of life. Our aim was to find correlations from a multicentre database representing the epidemiological traits, diagnosis and treatment of the disease in Hungary. The Hungarian Pancreatic Study Group collected data prospectively from 2012 to 2014 on patients suffering from chronic pancreatitis. Statistical analysis was performed on different questions. Data on 229 patients (74% male and 26% female) were uploaded from 14 centres. Daily alcohol consumption was present in the aetiology of 56% of the patients. 66% of the patients were previously treated for acute exacerbation. One third of the patients had had previous endoscopic or surgical interventions. Pain was present in 69% of the cases, endocrine insufficiency in 33%, diarrhoea in 13% and weight loss in 39%. Diagnosis was confirmed with US (80%), CT scan (52%), MRI-MRCP (6%), ERCP (39%), and EUS (7,4%). A functional test was carried out in 5% of the patients. In 31% of the cases, an endoscopic intervention was performed with the need for re-intervention in 5%. Further elective surgical intervention was necessitated in 44% of endoscopies. 20% of the registered patients were primarily treated with surgery. The biliary complication rate for surgery was significantly smaller (2%) than endoscopy (27%); however, pancreatic complications were higher in the patients treated with surgery. Patients who smoked regularly needed significantly more surgical intervention following endoscopy (66.7% vs. 26.9%, p = 0.002) than non-smokers, and the ratio of surgical intervention alone was also significantly higher (27.3% vs. 10.8%, p = 0.004). The ratio of surgery in patients who smoked and drank was significantly higher (30.09% vs. 12.5%, p = 0.012) than in abstinent and non-smoking patients, similarly to the need for further surgical intervention after endoscopic treatment (71.43% vs. 27.78%, p = 0.004). According to the data analysed, the epidemiological data and the aetiological factors in our cohort differ little from European trends. The study highlighted the overuse of ERCP as a diagnostic modality and the low ratio of use of endoscopic ultrasonography. The results proved that alcohol consumption and smoking represent risk factors for the increased need for surgical intervention. Chronic pancreatitis should be treated by multidisciplinary consensus grounded in evidence-based medicine.

The potential advantages of hydroxyapatite (HA)-coated cementless total knee arthroplasty (TKA) implants are bone stock preservation and biological fixation. Studies comparing the outcomes of HA-coated cementless, non HA-coated cementless (uncemented) and cemented TKA implants reported contradictory data. Our aim was to provide a comparison of the effects of HA coating of tibial stem on the stability and functionality of TKA implants. A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the CENTRAL databases up to May 31st, 2019. The primary outcome was Maximum Total Point Motion (MTPM) of the tibial stem. This parameter is determined by radiosterometric analysis and refers to the migration pattern of the prosthesis stems. The clinical outcomes of the implanted joints were evaluated by the Knee Society Knee Score (KSS) and the Knee Society Function Score (KFS). Weighted mean difference (WMD) with 95% confidence interval (CI) were calculated with the random-effects model. Altogether, 11 randomized controlled trials (RCTs) with 902 patients for primary TKA implants were included. There was a statistically significant difference in the MTPM values with the use of HA-coated and uncoated uncemented implants (WMD = +0.28, CI: +0.01 to +0.56, P<0.001). However, HA-coated stems showed significantly higher migration when compared with the cemented prostheses (WMD = -0.29, CI: -0.41 to -0.16, P<0.001). The KSS values of HA-coated implants were significantly higher than those for the uncemented implants; moreover, KSS and KFS outcome scores were statistically not different between the HA-coated and cemented prosthesis cases. HA-coating yields better stability than other, uncemented prostheses. More importantly, the HA-coating is not outperformed by cemented prosthesis in providing good functional outcome.

Background Spectral imaging via photon-counting detector CT (PCD-CT) scanners allows the generation of spectral attenuation curves. Our study aimed to test the feasibility of spectral attenuation curve analysis for differentiating mucinous from non-mucinous cyst fluids of pancreatic cystic lesions (PCL). Methods Our study included 74 patients with PCLs. The classic morphological features were evaluated by an expert radiologist. The spectral attenuation curves were generated from the pancreatic-phase scans. The average CT values were measured on the 70 keV (HU 70keV ) and 40 keV (HU 40keV ) virtual monoenergetic images (VMIs), and the differences were calculated (HU Δ40−70keV ). The cases were divided into training (53 mucinous vs. 19 non-mucinous PCLs) and test (10 mucinous vs. 10 non-mucinous PCLs) datasets. The receiver operating characteristic (ROC) curve analysis assessed the discrimination performance. The intra- and interobserver reproducibilities were evaluated by the intraclass correlation coefficient (ICC). Results On 70 keV VMIs, no significant differences were found between the average CT values of mucinous and non-mucinous PCLs, however, the difference was significant in HU Δ40−70keV values ( p  < 0.0001). The diagnostic performance of HU Δ40−70keV in differentiating between mucinous vs. non-mucinous PCL had AUCs of 0.92 and 0.92 on the training and test datasets, respectively, with a good interobserver (ICC = 0.82) and excellent intraobserver reproducibility (ICC = 0.94). The conventional clinical-radiological model achieved AUCs of 0.85 and 0.86, and with the addition of HU Δ40−70keV values its performance increased significantly to 0.98 and 0.94 on the training and test datasets, respectively. Conclusions Spectral attenuation curve assessment of cyst fluids could be a useful additional measurement to facilitate the noninvasive differential diagnosis of PCLs.

Experimental data suggest that the HLA-DQ2 gene dose has a strong quantitative effect on clinical outcomes and severity of celiac disease (CD). We aimed to conduct a meta-analysis with systematic review to investigate the association between HLA-DQB1*02 gene doses and the characteristics of CD. We searched seven medical databases for studies discussing HLA-DQB1 gene dose in CD and various disease characteristics, such as clinical presentation, histology, age at diagnosis, and comorbidities. Odds ratios (OR, for categorical variables) and weighted mean differences (for age) were calculated to compare patients with a double dose of HLA-DQB1*02 versus those with single and zero doses. Heterogeneity was tested with I2-statistics and explored by study subgroups (children and adults). Twenty-four publications were eligible for meta-analysis. Classical CD was more frequent with a double versus single dose of the HLA-DQB1*02 allele (OR = 1.758, 95%CI: 1.148-2.692, I2 = 0.0%). In pediatric studies, gene dose effect was more prominent (OR = 2.082, 95%CI: 1.189-3.646, I2 = 0.0% and OR = 3.139, 95%CI: 1.142-8.630, I2 = 0.0% for the comparisons of double versus single and double versus zero dose, respectively). Atrophic histology was more prevalent with a double versus zero dose (OR = 2.626, CI: 1.060-6.505, I2 = 21.3%). We observed no gene dose effect regarding diarrhea, age at diagnosis, the severity of villous atrophy, and the association with type 1 diabetes mellitus. A double dose of HLA-DQB1*02 gene seems to predispose patients to developing classical CD and villous atrophy. Risk stratification by HLA-DQB1*02 gene dose requires further clarification due to the limited available evidence.