Currently, axillary surgery for breast cancer is considered only as staging procedure, since the risk of developing metastasis depends on the biological behavior of the primary. The postsurgical therapy should be considered on the basis of biologic tumor characteristics rather than nodal involvement. Improvements in systemic treatments for breast cancer have increased the rates of pathologic complete response (pCR) in patients receiving neoadjuvant systemic therapy (NAST), offering the opportunity to de-escalate surgery in patients who have a pCR. European Breast Cancer Research Association of Surgical Trialists (EUBREAST)-01 is a clinical trial in which only patients with the highest likelihood of having a pCR after NAST (triple-negative or HER2-positive breast cancer) will be included and type of surgery will be defined according to the response to NAST rather than on the classical T (for tumor size in the breast) and N (for axillary lymph node involvement) status. In the discussed trial, axillary surgery will be eliminated completely (no axillary sentinel lymph node biopsy) for initially clinical node-negative (cN0) patients with radiologic complete remission and a breast pCR in the lumpectomy specimen. The trial design is a multicenter single-arm study with a limited number of patients (n = 267), which might give practice-changing results in a short period of time, sparing the time and the costs of a randomized comparison.

Little is known about the molecular and biological aspects of the epidemiological association between smoking and pancreatic pathology, such as chronic pancreatitis and pancreatic cancer. Recently, we reported that tobacco smoke exposure induced morphological alterations in the rat pancreas. Here, we have investigated the alterations in the expression of genes associated with exocrine pancreatic function and cellular differentiation upon exposure to cigarette smoke. Female rats were exposed to environmental smoke inhalation for 2 d/wk (70 min/d) for 12 weeks. The expression profiles of trypsinogen, pancreas-specific trypsin inhibitor, cholecystokinin A receptor, cystic fibrosis transmembrane conductance regulator (CFTR), carbonic anhydrase, and Muc1 and Muc4 mucins transcripts were analyzed by RNA slot blot analysis. Muc4 expression was also examined by immunohistochemistry. Our data revealed that the ratio of trypsinogen to that of the protective pancreas-specific trypsin inhibitor was elevated upon cigarette smoke exposure. The expression of carbonic anhydrase and CFTR remained unaltered when inflammatory signs were not detected in histological examinations. On the other hand, when pancreatic inflammation was present, the levels of CFTR and carbonic anhydrase were increased, indicating ductal and/or centroacinar cell involvement. No changes in the expression of Muc1 and Muc4 mucins were observed. Our data show that cigarette smoke exposure leads to an increased vulnerability to pancreatic self-digestion. Moreover, the concomitant involvement of pancreatic ducts occurs only when focal pancreatic inflammation is present.

Autoimmune diseases are disorders caused by an immune response directed against the body's own organs, tissues and cells. In practice more than 80 clinically distinct diseases, among them systemic lupus erythematosus and rheumatoid arthritis, are classified as autoimmune diseases. Although their etiology is unclear these diseases share certain similarities at the molecular level i.e. susceptibility regions on the chromosomes or the involvement of common genes. To gain an overview of these related diseases it is not feasible to do a literary review but it requires methods of automated analyses of the more than 500,000 Medline documents related to autoimmune disorders. In this paper we present the first version of the Autoimmune Disease Database which to our knowledge is the first comprehensive literature-based database covering all known or suspected autoimmune diseases. This dynamically compiled database allows researchers to link autoimmune diseases to the candidate genes or proteins through the use of named entity recognition which identifies genes/proteins in the corresponding Medline abstracts. The Autoimmune Disease Database covers 103 autoimmune disease concepts. This list was expanded to include synonyms and spelling variants yielding a list of over 1,200 disease names. The current version of the database provides links to 541,690 abstracts and over 5,000 unique genes/proteins. The Autoimmune Disease Database provides the researcher with a tool to navigate potential gene-disease relationships in Medline abstracts in the context of autoimmune diseases.

The aim of the study was to investigate the accuracy of ultrasound-derived estimated fetal weight (EFW) and to determine its impact on management and outcome of delivery. In this single-center cohort analysis, women with a singleton term pregnancy in the beginning stages of labor were included. Women with immediately antepartum EFW (N = 492) were compared to women without ultrasound (N = 515). EFW was correct (deviation from birth weight ≤ 10%) in 72.2% (355/492) of patients with fetal biometry; 19.7% (97/492) were underestimated, and 8.1% (40/492) were overestimated. Newborns with a lower birth weight were more frequently overestimated, and newborns with higher birth weight were more frequently underestimated. The mean difference between EFW and real birth weight was − 114.5 g (standard deviation ±313 g, 95% confidence interval 87.1–142.0). The rate of non-reassuring fetal heart tracing (9.8% vs. 1.9%, P < 0.001) and of caesarean delivery (9.1% vs. 5.0%, P = 0.013) was higher in women with EFW. Overestimation was associated with an increased risk for delivery by caesarean section (odds ratio 2.80; 95% confidence interval 1.2–6.5, P = 0.017). After adjustment, EFW remained associated with increased non-reassuring fetal heart tracing (odds ratio 4.73; 95% confidence interval 2.3–9.6) and caesarean delivery (odds ratio 1.86; 95% confidence interval 1.1–3.1). The incidence of perineal tears of grade 3/4, shoulder dystocia, postnatal depression and neonatal acidosis did not differ between groups. Antepartum ultrasound-derived EFW does not improve maternal and fetal outcome and is therefore not recommended.

Background: Reduced temporal muscle thickness (TMT) has been discussed as a prognostic marker in IDH-wildtype glioblastoma. This retrospective multicenter study was designed to investigate whether TMT is an independent prognostic marker in newly diagnosed glioblastoma. Methods: TMT was retrospectively measured in 335 patients with newly diagnosed glioblastoma between 1 January 2014 and 31 December 2019 at the University Hospitals of Leipzig and Rostock. The cohort was dichotomized by TMT and tested for association with overall survival (OS) after 12 months by multivariate proportional hazard calculation. Results: TMT of 7.0 mm or more was associated with increased OS (46.3 ± 3.9% versus 36.6 ± 3.9%, p > 0.001). However, the sub-groups showed significant epidemiological differences. In multivariate proportional hazard calculation, patient age (HR 1.01; p = 0.004), MGMT promoter status (HR 0.76; p = 0.002), EOR (HR 0.61), adjuvant irradiation (HR 0.24) and adjuvant chemotherapy (HR 0.40; all p < 0.001) were independent prognostic markers for OS. However, KPS (HR 1.00, p = 0.31), BMI (HR 0.98, p = 0.11) and TMT (HR 1.06; p = 0.07) were not significantly associated with OS. Conclusion: TMT has not appeared as a statistically independent prognostic marker in this cohort of patients with newly diagnosed IDH-wildtype glioblastoma.

The projection predictive variable selection is a decision-theoretically justified Bayesian variable selection approach achieving an outstanding trade-off between predictive performance and sparsity. Its projection problem is not easy to solve in general because it is based on the Kullback–Leibler divergence from a restricted posterior predictive distribution of the so-called reference model to the parameter-conditional predictive distribution of a candidate model. Previous work showed how this projection problem can be solved for response families employed in generalized linear models and how an approximate latent-space approach can be used for many other response families. Here, we present an exact projection method for all response families with discrete and finite support, called the augmented-data projection. A simulation study for an ordinal response family shows that the proposed method performs better than or similarly to the previously proposed approximate latent-space projection. The cost of the slightly better performance of the augmented-data projection is a substantial increase in runtime. Thus, if the augmented-data projection’s runtime is too high, we recommend the latent projection in the early phase of the model-building workflow and the augmented-data projection for final results. The ordinal response family from our simulation study is supported by both projection methods, but we also include a real-world cancer subtyping example with a nominal response family, a case that is not supported by the latent projection.