The 1000IBD project: multi-omics data of 1000 inflammatory bowel disease patients; data release 1.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic complex disease of the gastrointestinal tract. Patients with IBD can experience a wide range of symptoms, but the pathophysiological mechanisms that cause these individual differences in clinical presentation remain largely unknown. In consequence, IBD is currently classified into subtypes using clinical characteristics. If we are to develop a more targeted treatment approach, molecular subtypes of IBD need to be discovered that can be used as new drug targets. To achieve this, we need multiple layers of molecular data generated from the same IBD patients. CONSTRUCTION AND CONTENT: We initiated the 1000IBD project ( https://1000ibd.org ) to prospectively follow more than 1000 IBD patients from the Northern provinces of the Netherlands. For these patients, we have collected a uniquely large number of phenotypes and generated multi-omics profiles. To date, 1215 participants have been enrolled in the project and enrolment is on-going. Phenotype data collected for these participants includes information on dietary and environmental factors, drug responses and adverse drug events. Genome information has been generated using genotyping (ImmunoChip, Global Screening Array and HumanExomeChip) and sequencing (whole exome sequencing and targeted resequencing of IBD susceptibility loci), transcriptome information generated using RNA-sequencing of intestinal biopsies and microbiome information generated using both sequencing of the 16S rRNA gene and whole genome shotgun metagenomic sequencing. UTILITY AND DISCUSSION: All molecular data generated within the 1000IBD project will be shared on the European Genome-Phenome Archive ( https://ega-archive.org , accession no: EGAS00001002702). The first data release, detailed in this announcement and released simultaneously with this publication, will contain basic phenotypes for 1215 participants, genotypes of 314 participants and gut microbiome data from stool samples (315 participants) and biopsies (107 participants) generated by tag sequencing the 16S gene. Future releases will comprise many more additional phenotypes and -omics data layers. 1000IBD data can be used by other researchers as a replication cohort, a dataset to test new software tools, or a dataset for applying new statistical models. CONCLUSIONS: We report on the establishment and future development of the 1000IBD project: the first comprehensive multi-omics dataset aimed at discovering IBD biomarker profiles and treatment targets.

Correction to: The 1000IBD project: multi-omics data of 1000 inflammatory bowel disease patients; data release 1.

Following publication of the original article [1], the authors.

Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial.

A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)- to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6-144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized (2:1) to abrupt conversion (<24 h) from CNI to SRL (n = 393) or CNI continuation for up to 6 years (n = 214). Between-group changes in baseline-adjusted mean Cockcroft-Gault GFR at month 12 (primary efficacy end point) were not significant. The primary safety end point, noninferiority of cumulative rate of graft loss or death at 12 months, was not met (6.6% vs. 5.6% in the SRL and CNI groups, respectively). Rates of death at 12 months were not significantly different, and no true graft losses (e.g. liver transplantation) were observed during the 12-month period. At 52 weeks, SRL conversion was associated with higher rates of biopsy-confirmed acute rejection (p = 0.02) and discontinuations (p < 0.001), primarily for adverse events. Adverse events were consistent with known safety profiles. In conclusion, liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI- to SRL-based immunosuppression.

Ecologic correlates of cancer mortality patterns in an industrialized urban population.

Cancer mortality data for the period 1968-80 were analyzed to examine whether the high cancer burden for the city of Philadelphia was "evenly" distributed spatially and, if not, whether this distribution could be associated with socioeconomic variables and air pollution. Areas with significantly higher-than-expected rates tended to cluster; lung cancer and non-lung cancers showed distinctive cluster patterns, which were evident only for males; female rates for any cancer or groups of cancers were almost uniformly distributed over the neighborhoods. Both the high lung cancer and the high non-lung cancer clusters were characterized by low socioeconomic status, but only the high lung cancer clusters exhibited high levels of air pollution. These neighborhood characteristics suggested that socioeconomic variables explain non-lung cancer mortality patterns; socioeconomic variables, together with air pollution, could be responsible for the observed lung cancer patterns. The uniform distribution of female lung cancer rates suggested that air pollution by itself cannot be a prominent factor in lung cancer mortality.

Effect of aging on tensile mechanical properties of the rabbit distal femoral growth plate.

Tensile tests to failure were performed on the distal femoral growth plate of rabbits. The measured tensile forces, together with animal weight and dimensional measurements of the femur, were used to develop a noninvasive method of predicting growth failure loads and to examine the effects of age on the tensile strength of the growth plate. Growth plate failure load correlated with rabbit weight, (r = 0.93), femoral length, (r = 0.91), and contoured growth plate surface area, (r = 0.74). Regression analysis for these relationships allowed for failure load prediction if animal weight, femoral length, or growth plate surface area was known. Nominal stress (failure load/surface area) was calculated and correlated with animal weight (age) for each distal femoral growth plate utilizing two surface area estimating techniques: growth plate surface contour and growth plate cross-sectional enlargement. A strong association was found with either technique. The growth and maturation of growth plate cartilage is of major importance in pediatric orthopaedics. This study demonstrate that the age-dependent increases in tensile mechanical properties of the growth plate do not result merely from growth plate enlrgement or conformational changes. The changing tensile mechanical properties of the growth plate may explain why transphyseal distraction used clinically has produced varied and somewhat unpredictable results. Our study suggests that dose-response investigations are needed to define safe and optimal transphyseal distraction tensions before further clinical application is pursued.

A comparison of high-dose continuous and split-course irradiation in non-oat-cell carcinoma of the lung.

From 1969 through 1979, 171 patients with localized but inoperable or unresectable non-oat-cell carcinoma (NOCC) of the lung completed high-dose definitive irradiation. One hundred fifteen received continuous course irradiation to 6000-6500 rad at 180-200 rad/day. Fifty-six received split-course irradiation to 5500 rad at 250-300 rad/day, which included a 2-week break. The two groups were similar with respect to all measured variables. There were no differences in the response rates, failure patterns, survival, or complication rates between the two regimens. The 5-year survival was 6%, with 25.8% dying with infield failure alone and 54.7% with metastases. The incidence of complications was 8.2%, predominantly acute radiation pneumonitis. A review of the most comparable literature reveals no significant improvement in the cure rate of definitively irradiated NOCC with increasing tumor dose, split-course irradiation, or other modifications of radiotherapeutic technique over the past 25 years. The problems of frequent local recurrences and distant metastases, and the poor response of NOCC to presently available systemic therapy, requires that more effective and broadly applicable local and systemic therapies be developed before substantial improvements in the cure rate of NOCC can be expected.

Patterns of mortality from selected causes in an urban population.

Mortality data for selected non-cancer causes for the period 1974-1980 were analyzed for the City of Philadelphia to examine spatial patterns. Four categories of conditions--ischemic heart disease (including acute myocardial infarction), chronic liver disease and cirrhosis, cerebrovascular disease, and external causes--demonstrated significant variation in death rates. Moreover, neighborhoods with high levels of mortality for these conditions appeared in significant clusters. With the exception of ischemic heart disease, neighborhoods with high levels of mortality were characterized by below average levels of SES. A group of predominantly black neighborhoods in the central part of the city had extremely high rates for five or more of the nine causes investigated in this paper. In an earlier analysis, all but one of these neighborhoods were found to have the highest level of overall cancer mortality. These findings support the hypothesis that there are social and behavioral factors that are associated with a wide range of disease conditions, and many of these factors are associated with socioeconomic status.

Phase II study of low-dose mitomycin in patients with ovarian cancer previously treated with chemotherapy.

Forty-three evaluable patients with ovarian cancer who had failed one or more chemotherapy regimens were treated with mitomycin iv at 28-day intervals. Thirty-six patients with good bone marrow reserve received 10 mg/m2 and seven patients with poor bone marrow reserve received 6.7 mg/m2 initially. Ten patients (23%) responded. Patients with an Eastern Cooperative Oncology Group performance status of 0-1 had better response rates and survivals as compared to patients with a performance status of 2-4 (44% vs 8%; median survival, 8 vs 4 months). The acute hematologic and gastrointestinal toxicity was minimal. No patients developed pulmonary, renal, cardiovascular, or local tissue toxicity.