Incidence, prevalence and mortality of chronic liver diseases in Sweden between 2005 and 2019.

BACKGROUND: Updated data on the incidence, prevalence, and regional differences of chronic liver disease are missing from many countries. In this study, we aimed to describe time trends, incidence, prevalence, and mortality of a wide range of chronic liver diseases in Sweden. METHODS: In this register-based, nationwide observational study, patients with a register-based diagnosis of chronic liver disease, during 2005-2019, were retrieved from the Swedish National Board of Health and Welfare. Annual age-standardized incidence and mortality rates, and prevalence per 100,000 inhabitants was calculated and stratified on age, sex, and geographical region. RESULTS: The incidence of alcohol-related cirrhosis increased by 47% (2.6% annually), reaching an incidence rate of 13.1/100,000 inhabitants. The incidence rate of non-alcoholic fatty liver disease and unspecified liver cirrhosis increased by 217% and 87% (8.0 and 4.3% annually), respectively, reaching an incidence rate of 15.2 and 18.7/100,000 inhabitants, and a prevalence of 24.7 and 44.8/100,000 inhabitants. Furthermore, incidence rates of chronic hepatitis C declined steeply, but liver malignancies have become more common. The most common causes of liver-related mortality were alcohol-related liver disease and unspecified liver disease. CONCLUSION: The incidence rates of diagnosed non-alcoholic fatty liver disease, alcohol-related cirrhosis, unspecified liver cirrhosis, and liver malignancies have increased during the last 15 years. Worryingly, mortality in several liver diseases increased, likely reflecting increasing incidences of cirrhosis in spite of a decreasing rate of hepatitis C. Significant disparities exist across sex and geographical regions, which need to be considered when allocating healthcare resources.

Risk of Fractures and Subsequent Mortality in Alcohol-Related Cirrhosis: A Nationwide Population-Based Cohort Study.

BACKGROUND AND AIMS: Alcohol-related cirrhosis is linked to increased risk of fractures, but this has seldom been quantified nationally or compared against control subjects without cirrhosis. Here, we determined the rate and risk of fractures and postfracture mortality in patients with alcohol-related cirrhosis compared with individuals from the general population. METHODS: In this nationwide population-based cohort study, data were retrieved from the Swedish National Patient Registry on 25,090 patients with alcohol-related cirrhosis from 1969-2016. Patients were matched for sex, age, and municipality with 239,458 control subjects from the Swedish Total Population Registry. Cox regression models were fitted to investigate the rates of fractures and postfracture mortality. The cumulative incidence of fractures was calculated while accounting for competing risks (death or liver transplantation). RESULTS: A total of 48,635 fractures occurred during 3,468,860 person-years of follow-up. Patients with alcohol-related cirrhosis had a higher fracture rate per 1000 person-years (38.7) than control subjects (13.3; adjusted hazard ratio, 3.8; 95% confidence interval, 3.6-3.9). The cumulative incidence of fractures was elevated for patients the first 19 years of follow-up, with a 5-year risk of 9.6% compared with 4.5% for control subjects. Patients with alcohol-related cirrhosis had a higher postfracture mortality rate compared with control subjects who also experienced a fracture, at both 30 days (adjusted hazard ratio, 1.6; 95% confidence interval, 1.4-1.8) and 1 year (adjusted hazard ratio, 1.8; 95% confidence interval, 1.7-2.0). CONCLUSIONS: Alcohol-related cirrhosis is associated with an almost 4-fold increased fracture rate, a higher risk of fractures the first 2 decades after initial diagnosis, and higher postfracture mortality. Preventive interventions to reduce modifiable fracture risk factors in this population are justified.

Prediction of survival in patients with colorectal liver metastases- development and validation of a prognostic score model.

BACKGROUND: Metastatic spread of colorectal cancer to the liver impacts prognosis. Advances in chemotherapy have resulted in increased resectability rates and thereby improved survival in patients with colorectal liver metastases (CRLM). However, criteria are needed to ensure that patients selected for hepatic resection benefit from the invasive therapy. The study aimed to construct a predictive model for overall survival (OS) in patients with CRLM, based on preoperatively available information. METHODS: The retrospective cohort study reviewed all patients with CRLM discussed at multidisciplinary team conference at Karolinska University Hospital, Stockholm, Sweden, 2013-2018. Independent prognostic factors for OS were identified, based on which a score model was generated. The model was validated on patients treated for CRLM at Hôpital Universitaire Paul Brousse, Villejuif, France, 2007-2018. Calibration and discrimination methods were used for internal and external validation. RESULTS: The Swedish development cohort included 1013 patients, the French validation cohort 391 patients. Poor OS was significantly associated with age>60years (hazard ratio (HR) 3.57 (95%CI 2.18-9.94)), number of CRLM (HR 4.59 (2.83-12.20)), diameter of largest CRLM>5 cm (HR 2.59 (1.74-5.03)), right-sided primary tumour (HR 2.98 (2.00-5.80)), extrahepatic disease (HR 4.14 (2.38-15.87)) and non-resectability (HR 0.77 (0.66-0.90)). The C-statistic for prediction of OS was .74, in the development cohort and 0.69 in the validation cohort. CONCLUSION: The presented predictive score model can adequately predict OS for patients at the initial diagnosis of CRLM. The prognostic model could be of clinical value in the management of all patients with CRLM, by predicting individualized survival and thereby facilitating treatment recommendations.

Population-Based Cohort Study from a Prospective National Registry: Better Long-Term Survival in Esophageal Cancer After Minimally Invasive Compared with Open Transthoracic Esophagectomy.

BACKGROUND: Recent research indicates long-term survival benefits of minimally invasive esophagectomy (MIE) compared with open esophagectomy (OE) for patients with esophageal and gastroesophageal junction (GEJ) cancers, but there is a need for more population-based studies. METHODS: We conducted a prospective population-based nationwide cohort study including all patients in Sweden diagnosed with esophageal or junctional cancer who underwent a transthoracic esophagectomy with intrathoracic anastomosis. Data were collected from the Swedish National Register for Esophageal and Gastric Cancer in 2006-2019. Patients were grouped into OE and MIE including hybrid MIE (HMIE) and totally MIE (TMIE). Overall survival and short-term postoperative outcomes were compared using Cox regression and logistic regression models, respectively. All models were adjusted for age, sex, American Society of Anesthesiologists (ASA) score, clinical T and N stage, neoadjuvant therapy, year of surgery, and hospital volume. RESULTS: Among 1404 patients, 998 (71.1%) underwent OE and 406 (28.9%) underwent MIE. Compared with OE, overall survival was better following MIE (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.55-0.94), TMIE (HR 0.67, 95% CI 0.47-0.94), and possibly also after HMIE (HR 0.76, 95% CI 0.56-1.02). MIE was associated with shorter operation time, less intraoperative bleeding, higher number of resected lymph nodes, and shorter hospital stay compared with OE. MIE was also associated with fewer overall complications (odds ratio [OR] 0.70, 95% CI 0.47-1.03) as well as non-surgical complications (OR 0.64, 95% CI 0.40-1.00). CONCLUSIONS: MIE seems to offer better survival and similar or improved short-term postoperative outcomes in esophageal and GEJ cancers compared with OE in this unselected population-based cohort.

High prevalence of gastrointestinal symptoms in patients with primary Sjögren's syndrome cannot be attributed to pancreatic exocrine insufficiency.

INTRODUCTION: Pancreatic exocrine insufficiency (PEI) results in maldigestion of fat, leading to steatorrhea, malabsorption and weight loss. Sjögren's syndrome (SS) is a chronic autoimmune rheumatic disease with unknown etiology. The exocrine pancreas and the salivary glands are functionally and histologically comparable, and pancreatic dysfunction in SS has been hypothesized. METHODS: Patients were recruited from the Department for Rheumatology at the Karolinska University Hospital in Stockholm, Sweden, between June and December 2019. PEI was assessed by fecal elastase-1 (FE-1) and 13C-mixed triglyceride breath test (13C-MTG-BT). The presence and severity of gastrointestinal symptoms were assessed by a well-established and validated survey based on a seven-point Likert scale. RESULTS: Fifty-seven patients with primary SS were included in the study, comprising 92% females with a median age of 63 years. In total, 87% of SS patients were tested for FE-1 and all had normal results. All patients who underwent a 13C-MTG-BT had a normal cumulative 13C-exhalation. Compared to the control group, significantly more patients suffered from gastrointestinal (GI) symptoms (p < .01). The same number of patients noted moderate to severe loose bowel movements or constipation (38%). Eleven GI symptom parameters were compared to controls and the highest odd ratios were noted for the following moderate to severe symptoms: bloating, feeling of incompletely emptied bowel after defecation and abdominal pain relieved by bowel action. CONCLUSION: In our study, most SS patients suffered from irritable bowel syndrome (IBS)-like GI symptoms that could not be attributed to PEI.

Impact of obesity on the outcomes after gastrectomy for gastric cancer: A meta-analysis.

The impact of body mass index (BMI) on surgical outcomes has previously been studied in relation to several oncological procedures. Regarding gastric cancer surgery, published results have been contradicting in terms of degree of technical difficulty, risk of postoperative complications and survival. In an attempt to clarify these issues, we performed a meta-analysis to evaluate the impact of obesity (defined as BMI ≥ 30 kg/m2) on outcomes after gastrectomy for gastric cancer. The meta-analysis was performed according to the PRISMA guidelines. Eligible studies were identified through search of PubMed, EMBASE, Web of Science and Cochrane Library databases. Quality assessment was performed using the Newcastle-Ottawa scale. The meta-analysis was conducted using random-effects modeling. A total of 11 studies with 13 538 patients were eligible for analysis. Obesity was associated with a significantly longer operation time (WMD = 19.38 min, 95% CI 12.72-26.04; p < 0.001), increased risk of overall complications (RR = 1.23, 95% CI 1.06-1.42; p = 0.005) and pulmonary complications (RR = 3.81, 95% CI 2.24-6.46; p < 0.001). These findings remained irrespective type of surgery (laparoscopic vs. open) and type of gastrectomy. No differences were found regarding blood loss, number of resected lymph nodes, anastomotic leakage, hospital stay, 30-day mortality and 5-year overall survival. The conclusion of the current meta-analysis is that high BMI in gastric cancer patients is associated with longer operative time and more frequent overall postoperative complications. However, it has no negative impact on survival, indicating that gastrectomy is a safe procedure for this group of patients.

External validation of the Toronto hepatocellular carcinoma risk index in a Swedish population.

BACKGROUND & AIMS: The Toronto hepatocellular carcinoma (HCC) risk index (THRI) is a predictive model to determine the risk of HCC in patients with cirrhosis. This study aimed to externally validate the THRI in a Swedish setting to investigate whether it could identify patients not requiring HCC surveillance. METHODS: From 2004-2017, 2,491 patients with cirrhosis at the Karolinska University Hospital were evaluated. Patients were classified into low-, intermediate- and high-risk groups for future HCC according to the THRI. Harrell's C-index, calibration-in-the-large, calibration slope and goodness-of-fit estimates were calculated to assess model discrimination and calibration. Cox proportional hazards regression was used to determine the risk of HCC. RESULTS: Most patients were male (n = 1,638, 66%). The most common etiologies of cirrhosis were steatohepatitis (n = 1,182, 48%) followed by viral hepatitis (n = 987, 40%). In all, 131 patients (5.3%) were designated as low risk for HCC. Harrell's C-index was 0.69. Calibration-in-the-large (0.11), calibration slope (1.24, not different from 1, p = 0.66) and goodness-of-fit showed good model calibration. Patients in the high-risk group had a 7.1-fold (95% CI 2.9-17.2) higher risk of HCC and patients in the intermediate-risk group had a 2.5-fold (95% CI 1.0-6.3) higher risk compared to the low-risk group. CONCLUSIONS: In a Swedish setting, the THRI could differentiate between low- and high-risk of HCC development. However, because the low-risk group was relatively small (5.3%), the clinical applicability of the THRI could be limited. LAY SUMMARY: The Toronto hepatocellular carcinoma (HCC) risk index (THRI) is a novel prediction model used to stratify patients with cirrhosis based on future risk of HCC. In this study, the THRI was validated in an external cohort using the TRIPOD guidance. Few patients were identified as low-risk, and the THRI had a modest discriminative ability, limiting its clinical applicability.

Postoperative hiatal herniation after open vs. minimally invasive esophagectomy; a systematic review and meta-analysis.

BACKGROUND: Post-esophagectomy hiatal hernia (PEHH) is a known, but relatively uncommon, complication after esophagectomies. The incidence of PEHH seems to be increasing since the introduction of minimally invasive esophagectomy. This systematic review and meta-analysis aimed to determine the pooled incidence of PEHH after esophagectomy, and to evaluate if minimally invasive technique is associated with increased risk for PEHH compared to open esophagectomy. METHODS: A systematic search of PubMed, Medline via Ovid and Web of Science was performed. Retrospective and prospective studies in English language describing the incidence or risk factors for PEHH were included. Weighted incidence of PEHH after all types of esophagectomy, and after open or minimally invasive technique was calculated. RESULTS: A total of 7943 esophagectomy patients were included in the analysis. In total, 310 patients (3.9%) were diagnosed with PEHH. The estimated weighted incidence rate for PEHH after open esophagectomy was 0.024 (95% confidence interval: 0.012-0.045) compared to 0.065 (95% confidence interval: 0.040-0.106) after minimally invasive esophagectomy. Odds ratio for PEHH after minimally invasive esophagectomy compared to open esophagectomy was 2.76 (95% confidence interval: 1.49-5.11). CONCLUSION: The risk for post-esophagectomy hiatal hernia was significantly higher after minimally invasive esophagectomy compared to open technique. Heterogeneity and retrospective designs of the included studies were important limitations of the analysis. Future studies should investigate preventive measures to reduce PEHH after minimally invasive esophagectomy.

Short-course compared to long-course palliative radiotherapy for oesophageal cancer: a single centre observational cohort study.

BACKGROUND: Common symptoms of oesophageal cancer are dysphagia, pain, and bleeding. These symptoms can be relieved with palliative radiotherapy. The aim of this study was to analyse the outcome of two different palliative radiotherapy schedules. METHODS: We conducted a retrospective cohort study on palliative radiotherapy for oesophageal cancer given at Karolinska University Hospital. Patients included were treated with either short-course (20 Gy in 4 Gy fractions daily, 5 consecutive workdays) or long-course (30-39 Gy in 3 Gy fractions, 10-13 consecutive workdays) palliative external beam radiotherapy between January 2009 and December 2013. The primary endpoint was dysphagia relief and secondary endpoints were adverse events, re-interventions, and overall survival. Cox regression analyses were used to estimate the effect of treatment schedule on survival. RESULTS: A total of 128 patients received external beam radiotherapy under the study period, of these 75 (58.6%) received short-course radiotherapy and 53 (41.4%) long-course radiotherapy. Sixteen (30.8%) patients experienced dysphagia relief after short-course radiotherapy and 9 (22.0%) patients after long-course radiotherapy (p = 0.341). Acute toxicity was less frequent after short-course radiotherapy than after long-course radiotherapy, particularly oesophagitis (35.4% vs. 56.0%, p = 0.027) and nausea/emesis (18.5% vs. 36.0% p = 0.034). Re-interventions tended to be more common after short-course radiotherapy (32.0%) than after long-course radiotherapy (18.9%) (p = 0.098). There was no difference in overall survival between the two groups. CONCLUSIONS: Short- and long-course palliative radiotherapy for oesophageal cancer were equally effective to relieve dysphagia and no difference was seen in overall survival. Acute toxicity was, however, more frequent and more severe after long-course radiotherapy. Our results suggest that short-course radiotherapy is better tolerated with equal palliative effects as long-course radiotherapy.

Interobserver agreement of a gastric adenocarcinoma tumor regression grading system that incorporates assessment of lymph nodes.

Perioperative chemotherapy is increasingly used in combination with surgery for the treatment of patients with locally advanced, resectable gastric cancer. Histologic tumor regression grade (TRG) has emerged as an important prognostic factor; however, a common standard for its evaluation is lacking. Moreover, the clinical significance of regressive changes in metastatic lymph nodes (LNs) remains unclear. We conducted an international study to examine the interobserver agreement of a TRG system that is based on the Becker system for the primary tumors and additionally incorporates regression grading in LNs. Twenty observers at different levels of experience evaluated the TRG in 60 histologic slides (30 primary tumors and 30 LNs) based on the following criteria: for primary tumors, grade 1 represented complete response (no residual tumor), grade 2 represented <10%, grade 3 represented 10-50%, and grade 4 represented >50% residual tumor, as described by Becker et al. For LNs, grade "a" represented complete, grade "b" represented partial, and grade "c" represented no regression. The interobserver agreement was estimated using the Kendall's coefficient of concordance (W). Regarding primary tumors, agreement was good irrespective of the level of experience, reaching a W-value of 0.70 overall, 0.71 among subspecialized, and 0.71 among nonsubspecialized observers. Regarding LNs, interobserver agreement was moderate to good, with W-values of 0.52 overall, 0.64 among subspecialized, and 0.45 among nonsubspecialized observers. These findings indicate that the combination of the Becker TRG system with a three-tiered grading of regression in LNs generates a system that is reproducible. Future studies should investigate whether the additional information of TRG in LNs adds to the prognostic value of histologic regression grading in gastric cancer specimens.

Wide-field endoscopic submucosal dissection for the treatment of Barrett's esophagus neoplasia.

Background and study aims Implementation of endoscopic submucosal dissection (ESD) for the treatment of Barrett's esophagus neoplasia (BEN) has been hampered by high rates of positive margins and complications. Dissection with wider margins was proposed to overcome these problems, but was never tested. We aim to compare Wide-Field ESD (WF-ESD) with conventional ESD (C-ESD) for treatment of BEN. Patients and methods This was a cohort study of all ESDs performed in our center during 2011 to 2018. C-ESD was the only technique used before 2014, with WF-ESD used beginning in 2014. In WF-ESD marking was performed 10 mm from the tumor margin compared to 5 mm with C-E. Results ESD was performed in 90 cases, corresponding to 74 patients, 84 % male, median age 69. Of these, 22 were C-ESD (24 %) and 68 were WF-ESD (76 %). The en bloc resection rate was 95 vs 100 % (ns), the positive lateral margin rate was 23 % vs 3 % ( P  < 0.01), the R0 rate was 73 % vs 90 %, and the curative resection rate was 59 % vs 76 % in the C-ESD and WF-ESD groups, respectively, (both P  > 0.05). The procedure speed was 4.4 and 2.3 (min/mm) in the C-ESD and WF-ESD groups ( P  < 0.01), respectively. WF-ESD was associated with less post-operative strictures, 6 % vs 27 % ( P  = 0.01), with no local recurrence but no significantly reduced risk of metachronous recurrence (Hazard Ratio = 0.46, 95 %CI = 0.14-1.46), during a follow-up of 13.4 and 9.4 months in the C-ESD and WF-ESD cohorts, respectively. Conclusions WF-ESD is associated with a reduction in positive lateral margins, faster dissection, and lower stricture rates. Further prospective, multicenter studies are warranted to evaluate its role in clinical practice.

Morbidity, risk of cancer and mortality in 3645 HFE mutations carriers.

BACKGROUND & AIMS: Mutations in the HFE gene can lead to hereditary haemochromatosis (HH) and have been suggested to increase the risk of extra-hepatic diseases, especially breast and colorectal cancer. Here we investigated long-term outcomes of Swedish patients with HFE mutations. METHODS: We identified 3645 patients with a homozygous p.C282Y (62%) or a compound heterozygous p.C282Y/p.H63D (38%) mutation from eight centres in Sweden between 1997 and 2017. These were matched 1:10 by age, sex and county of residence to reference individuals from the general population. We ascertained incident outcomes until the end of 2017 by linkage to national registers. Studied outcomes were HH, cirrhosis, hepatocellular carcinoma (HCC), breast cancer (in women), colorectal cancer, type 1 and 2 diabetes, hypothyroidism, Parkinson's disease and mortality. Cox proportional hazards regression was used to estimate hazard ratios for these outcomes. RESULTS: Median age at diagnosis was 52 years, 44% were females. During a mean follow-up of 7.9 years, we found an increased risk for HCC, HH, cirrhosis, type 2 diabetes, osteoarthritis and death. Excess mortality was only seen in men. No increased risk was seen for colorectal or breast cancer. Liver-related outcomes were rare, with a cumulative incidence of <1%. CONCLUSIONS: Individuals found to be HFE mutation carriers in a university hospital setting had an increased risk for mortality in men, along with increased risks of cirrhosis, HCC, diabetes type 2, and osteoarthritis. In general, the absolute risk for adverse outcomes was low and no increased risk for colon or breast cancer was observed.

Gastric Microbiota in a Low-Helicobacter pylori Prevalence General Population and Their Associations With Gastric Lesions.

INTRODUCTION: Non-Helicobacter pylori microbiota might account for some cases with unexplained chronic gastritis that may in a minority eventually progress to gastric cancer through the Correa cascade. We characterized gastric microbiota by describing the normal stomach, compared it with early precancerous lesions and other disease states, and assessed whether H. pylori status affects bacterial diversity. METHODS: In a population-based study of those with and without gastrointestinal symptoms, cytology brush samples were collected during endoscopy from 316 individuals. Mucosal status was classified as normal mucosa (171), nonatrophic H. pylori gastritis (33), atrophic gastritis (12), or antral chemical gastritis (61). The 16S rRNA gene sequencing and analysis were performed to characterize the microbiota. RESULTS: Microbiota in atrophic gastritis and nonatrophic H. pylori gastritis stomachs were dysbiotic and differed from those in the normal stomach (P = 0.001). The normal stomach had the highest microbial diversity, followed by antral chemical gastritis. The atrophic gastritis and chronic H. pylori gastritis groups had the lowest diversity, a difference that was statistically significant (P = 0.01). Besides H. pylori, non-H. pylori bacteria accounted for group differences. Microbial network analysis showed that the normal group network was most highly connected, whereas the H. pylori gastritis group had the lowest connection. We found an increasing positive co-occurrence of oral bacteria in the stomach because samples deviated from the normal network, some of which were pathogens. The H. pylori-negative group had the highest microbial diversity (Shannon index) compared with the H. pylori-positive group (P = 0.001). DISCUSSION: In this low-H. pylori prevalence general population, the gastric mucosal microbiota of the normal stomach differed significantly from those with nonatrophic or atrophic gastritis. There was an increasing abundance of pathogenic bacteria from the normal state to early precancerous states.

Effects of Tumor Necrosis Factor Antagonists in Patients With Primary Sclerosing Cholangitis.

BACKGROUND & AIMS: Few patients with primary sclerosing cholangitis (PSC) and inflammatory bowel diseases (IBDs) are exposed to tumor necrosis factor (TNF) antagonists because of the often mild symptoms of IBD. We assessed the effects of anti-TNF agents on liver function in patients with PSC and IBD, and their efficacy in treatment of IBD. METHODS: We performed a retrospective analysis of 141 patients with PSC and IBD receiving treatment with anti-TNF agents (infliximab or adalimumab) at 20 sites (mostly tertiary-care centers) in Europe and North America. We collected data on the serum level of alkaline phosphatase (ALP). IBD response was defined as either endoscopic response or, if no endoscopic data were available, clinical response, as determined by the treating clinician or measurements of fecal calprotectin. Remission was defined more stringently as endoscopic mucosal healing. We used linear regression analysis to identify factors associated significantly with level of ALP during anti-TNF therapy. RESULTS: Anti-TNF treatment produced a response of IBD in 48% of patients and remission of IBD in 23%. There was no difference in PSC symptom frequency before or after drug exposure. The most common reasons for anti-TNF discontinuation were primary nonresponse of IBD (17%) and side effects (18%). At 3 months, infliximab-treated patients had a median reduction in serum level of ALP of 4% (interquartile range, reduction of 25% to increase of 19%) compared with a median 15% reduction in ALP in adalimumab-treated patients (interquartile range, reduction of 29% to reduction of 4%; P = .035). Factors associated with lower ALP were normal ALP at baseline (P < .01), treatment with adalimumab (P = .090), and treatment in Europe (P = .083). CONCLUSIONS: In a retrospective analysis of 141 patients with PSC and IBD, anti-TNF agents were moderately effective and were not associated with exacerbation of PSC symptoms or specific side effects. Prospective studies are needed to investigate the association between use of adalimumab and reduced serum levels of ALP further.

Stationary and portable sequencing-based approaches for tracing wastewater contamination in urban stormwater systems.

Urban sewer systems consist of wastewater and stormwater sewers, of which only wastewater is processed before being discharged. Occasionally, misconnections or damages in the network occur, resulting in untreated wastewater entering natural water bodies via the stormwater system. Cultivation of faecal indicator bacteria (e.g. Escherichia coli; E. coli) is the current standard for tracing wastewater contamination. This method is cheap but has limited specificity and mobility. Here, we compared the E. coli culturing approach with two sequencing-based methodologies (Illumina MiSeq 16S rRNA gene amplicon sequencing and Oxford Nanopore MinION shotgun metagenomic sequencing), analysing 73 stormwater samples collected in Stockholm. High correlations were obtained between E. coli culturing counts and frequencies of human gut microbiome amplicon sequences, indicating E. coli is indeed a good indicator of faecal contamination. However, the amplicon data further holds information on contamination source or alternatively how much time has elapsed since the faecal matter has entered the system. Shotgun metagenomic sequencing on a subset of the samples using a portable real-time sequencer, MinION, correlated well with the amplicon sequencing data. This study demonstrates the use of DNA sequencing to detect human faecal contamination in stormwater systems and the potential of tracing faecal contamination directly in the field.

Association between poor oral health and gastric cancer: A prospective cohort study.

Poor oral health may be involved in the pathogenesis of gastric cancer, however, some aspects have not been explored. Further, for previously studied aspects, for example, tooth-loss, the findings are inconsistent. We conducted a prospective cohort study of 19,831 participants from Uppsala, Sweden, cancer-free at baseline in 1973-1974 and followed until 2012 through linkage to national registers. We found that individuals with fewest teeth at baseline had an increased risk of gastric cancer relative to subjects with all examined teeth present (p = 1.75e-2). Presence of denture-associated lesions was also associated with an increased risk of gastric cancer (p = 1.00e-4). However, these excess risks significantly varied with attained age; estimated hazard ratio (HR) at attained age 50 for tooth loss was 4.24 [95% confidence interval (CI) 1.83-9.80] and 5.91 (95% CI 2.76-12.63) for denture-associated lesions, decreasing at an estimated 4% and 6% per year respectively, resulting in HR of 1.54 (95% CI 0.90-2.64) for tooth loss and HR 1.29 (95% CI 0.90-1.85) for denture-associated lesions at attained age 75. No increased risk of gastric cancer was found for individuals with higher levels of dental plaque, or with Candida-related or tongue lesions. In conclusion, tooth-loss and denture-associated lesions are associated with increased risks of gastric cancer. Previous conflicting findings of tooth-loss and gastric cancer risk may partly be explained by the age-varying relative risk of gastric cancer.

Critical amino acid residues in proteins: a BioMart integration of Reactome protein annotations with PRIDE mass spectrometry data and COSMIC somatic mutations.

The reversible phosphorylation of serine, threonine and tyrosine hydroxyl groups is an especially prominent form of post-translational modification (PTM) of proteins. It plays critical roles in the regulation of diverse processes, and mutations that directly or indirectly affect these phosphorylation events have been associated with many cancers and other pathologies. Here, we describe the development of a new BioMart tool that gathers data from three different biological resources to provide the user with an integrated view of phosphorylation events associated with a human protein of interest, the complexes of which the protein (modified or not) is a part, the reactions in which the protein and its complexes participate and the somatic mutations that might be expected to perturb those functions. The three resources used are the Reactome, PRIDE and COSMIC databases. The Reactome knowledgebase contains annotations of phosphorylated human proteins linked to the reactions in which they are phosphorylated and dephosphorylated, to the complexes of which they are parts and to the reactions in which the phosphorylated proteins participate as substrates, catalysts and regulators. The PRIDE database holds extensive mass spectrometry data from which protein phosphorylation patterns can be inferred, and the COSMIC database holds records of somatic mutations found in human cancer cells. This tool supports both flexible, user-specified queries and standard ('canned') queries to retrieve frequently used combinations of data for user-specified proteins and reactions. We demonstrate using the Wnt signaling pathway and the human c-SRC protein how the tool can be used to place somatic mutation data into a functional perspective by changing critical residues involved in pathway modulation, and where available, check for mass spectrometry evidence in PRIDE supporting identification of the critical residue.

The Reactome BioMart.

Reactome is an open source, expert-authored, manually curated and peer-reviewed database of reactions, pathways and biological processes. We provide an intuitive web-based user interface to pathway knowledge and a suite of data analysis tools. The Reactome BioMart provides biologists and bioinformaticians with a single web interface for performing simple or elaborate queries of the Reactome database, aggregating data from different sources and providing an opportunity to integrate experimental and computational results with information relating to biological pathways. Database URL: http://www.reactome.org.

BioMart Central Portal: an open database network for the biological community.

BioMart Central Portal is a first of its kind, community-driven effort to provide unified access to dozens of biological databases spanning genomics, proteomics, model organisms, cancer data, ontology information and more. Anybody can contribute an independently maintained resource to the Central Portal, allowing it to be exposed to and shared with the research community, and linking it with the other resources in the portal. Users can take advantage of the common interface to quickly utilize different sources without learning a new system for each. The system also simplifies cross-database searches that might otherwise require several complicated steps. Several integrated tools streamline common tasks, such as converting between ID formats and retrieving sequences. The combination of a wide variety of databases, an easy-to-use interface, robust programmatic access and the array of tools make Central Portal a one-stop shop for biological data querying. Here, we describe the structure of Central Portal and show example queries to demonstrate its capabilities.