Induction of labor and nulliparity: A nationwide clinical practice pilot evaluation.

IntroductionInduction of labor has become an increasingly common obstetric procedure, but in nulliparous women or women with a previous cesarean section, it can pose a clinical challenge. Despite an overall expansion of medical indications for labor induction, there is little international consensus regarding the criteria for induction, or for the recommended methods among nulliparous women. In this light, we assessed variations in the practice of induction of labor among 21 birth units in a nationwide cohort of women with no prior vaginal birth.Material and methodsWe carried out a prospective observational pilot study of women with induced labor and no prior vaginal birth, across 21 Norwegian birth units. We registered induction indications, methods and outcomes from 1 September to 31 December 2018 using a web-based case record form. Women were grouped into "Nulliparous term cephalic", "Previous cesarean section" and "Other Robson" (Robson groups 6, 7, 8 or 10).ResultsMore than 98% of eligible women (n=1818) were included and a wide variety of methods was used for induction of labor. In nulliparous term cephalic pregnancies, cesarean section rates ranged from 11.1% to 40.6% between birth units, whereas in the previous cesarean section group, rates ranged from 22.7% to 67.5%. The indications "large fetus" and "other fetal" indications were associated with the highest cesarean rates. Failed inductions and failure to progress in labor contributed most to the cesarean rates. Uterine rupture occurred in two women (0.11%), both in the previous cesarean section group. In neonates, 1.6% had Apgar ConclusionsCesarean rates and applied methods for induction of labor varied widely in this nationwide cohort of women without a prior vaginal birth. Neonatal outcomes were similar to those of normal birth populations. Results could indicate the need to move towards more standardized induction protocols associated with optimal outcomes for mother and baby

Transverse Incision for Pancreatoduodenectomy Reduces Wound Complications: A Single-Center Analysis of 399 Patients

Background: Even if the minimally invasive approach is advancing in pancreatic surgery, the open approach is still the standard for a pancreatoduodenectomy. There are two types of incisions used: the midline incision (MI) and transverse incision (TI). The aim of this study was to compare these two incision types, especially regarding wound complications. Methods: A retrospective review of 399 patients who underwent a pancreatoduodenectomy at the University Hospital Erlangen between 2012 and 2021 was performed. A total of 169 patients with MIs were compared with 230 patients with TIs, with a focus on postoperative fascial dehiscence, postoperative superficial surgical site infection (SSSI) and the occurrence of incisional hernias during follow-up. Results: Postoperative fascial dehiscence, postoperative SSSI and incisional hernias occurred in 3%, 8% and 5% of patients, respectively. Postoperative SSSI and incisional hernias were significantly less frequent in the TI group (SSI: 5% vs. 12%, p = 0.024; incisional hernia: 2% vs. 8%, p = 0.041). A multivariate analysis confirmed the TI type as an independent protective factor for the occurrence of SSSI and incisional hernias (HR 0.45 (95% CI = 0.20–0.99), p = 0.046 and HR 0.18 (95% CI = 0.04–0.92), p = 0.039, respectively). Conclusion: Our data suggest that the transverse incision for pancreatoduodenectomy is associated with reduced wound complications. This finding should be confirmed by a randomized controlled trial

Time to Surgery Does Not Affect Overall or Disease-Free Survival of Patients with Primary Resectable PDAC

(1) Background: Delay in therapy for pancreatic ductal adenocarcinoma (PDAC) may contribute to a worse outcome. The aim of this study was to investigate the prognostic value of time from diagnosis to surgery in patients undergoing upfront surgery for primarily resectable pancreatic carcinoma. (2) Methods: This retrospective single-center study included 214 patients who underwent primary resection of PDAC from January 2000 to December 2018 at University Hospital Erlangen. Using a minimum p-value approach, patients were stratified according to time to surgery (TtS) into two groups: TtS ≤ 23 days and TtS > 23 days. Postoperative outcome and long-term survival were compared. (3) Results: Median TtS was 25 days. The best cut-off for TtS was determined as 23 days. There were no differences regarding postoperative outcome or overall survival (OS) and disease-free survival (DFS) (OS: 23.8 vs. 20.4 months, p = 0.210, respectively, and DFS: 15.8 vs. 13.6 months, p = 0.187). Multivariate analysis revealed age, lymph node metastasis, tumor differentiation and resection status as significant independent prognostic predictors for OS and DFS. (4) Conclusions: A delay of surgery > 23 days after first diagnosis does not affect overall or disease-free survival of patients with primary resectable PDAC. However, the psychological impact of a delay to patients waiting for surgery should not be underestimated

Upregulation of CD20 Positive B-Cells and B-Cell Aggregates in the Tumor Infiltration Zone is Associated with Better Survival of Patients with Pancreatic Ductal Adenocarcinoma

Patients with pancreatic ductal adenocarcinoma (PDAC) normally have a poor long-term prognosis. However, some rare cases of long-term survivors have been reported. The tumor microenvironment, consisting of cellular and stromal components, possibly plays an important role and might influence prognosis. In this context, the role of tumor-infiltrating B-cells and its impact on the survival in patients with PDAC remains controversial. We therefore aimed to assess the prognostic value of CD20-positive B-cells and CD20-positive B-cell aggregates as well as CD138, IgM, Pax5, and Ki67 on the survival of patients with PDAC using immunohistochemistry of FFPE pancreatectomy tissue sections from patients that underwent primary surgery for pT3- and R0-pancreatic adenocarcinoma between 1995 and 2016. Patients with PDAC were matched and grouped in 16 long-term-survivors (LTS, median overall survival (OS): 96 months [range: 61–177 months]) and 16 short-term-survivors (STS, median OS: 16 months [range: 7–32 months]). CD20-positive B-cells and B-cell aggregates in the tumor infiltration zone were significantly upregulated in the LTS-group compared to the STS-group (p = 0.0499 respectively p = 0.0432). Regarding the entire patient cohort (n = 32) CD20 positive B-cell aggregates in the tumor infiltration zone were an independent prognostic marker for overall survival in multivariate analysis (HR 9.2, CI 1.6–51.4, p = 0.012). These results underline the importance of tumor-associated B-cells for prognosis of patients with PDAC. The detailed role of B cells in the pathomechanism of PDAC should be further investigated for predicting outcome, identifying appropriate treatment regimens, and developing novel therapeutic option

A genetically modified minipig model for Alzheimer's disease with SORL1 haploinsufficiency

The established causal genes in Alzheimer’s disease (AD), APP, PSEN1, and PSEN2, are functionally characterized using biomarkers, capturing an in vivo profile reflecting the disease’s initial preclinical phase. Mutations in SORL1, encoding the endosome recycling receptor SORLA, are found in 2%–3% of individuals with early-onset AD, and SORL1 haploinsufficiency appears to be causal for AD. To test whether SORL1 can function as an AD causal gene, we use CRISPR-Cas9-based gene editing to develop a model of SORL1 haploinsufficiency in Göttingen minipigs, taking advantage of porcine models for biomarker investigations. SORL1 haploinsufficiency in young adult minipigs is found to phenocopy the preclinical in vivo profile of AD observed with APP, PSEN1, and PSEN2, resulting in elevated levels of β-amyloid (Aβ) and tau preceding amyloid plaque formation and neurodegeneration, as observed in humans. Our study provides functional support for the theory that SORL1 haploinsufficiency leads to endosome cytopathology with biofluid hallmarks of autosomal dominant AD

Pleural Resident Macrophages and Pleural IRA B Cells Promote Efficient Immunity Against Pneumonia by Inducing Early Pleural Space Inflammation

Airway infection is a major cause of mortality worldwide. The identification of new mechanisms aiding in effective host immune response is therefore required. Here, we show that the specific depletion of the pleural immune cell compartment during bacterial pneumonia resulted in a reduced pulmonary immune response and increased mortality in mice. Bacterial airway infection provoked early pleural space (PS) inflammation characterized by innate response activator (IRA) B cell development and pleural large resident macrophage (LRM) necroptosis, the repopulation of LRMs being driven by cellular proliferation in situ. Necroptotic LRMs amplified PS inflammation by stimulating pleural Mincle-expressing macrophages whereas IRA B cells contributed partially to GM-CSF-induced PS inflammation. Upon pulmonary infection, the induction of PS inflammation resulted in reduced bacterial burden whereas the specific depletion of pleural resident macrophages led to increased mortality and bacterial burden and reduced pulmonary immunity. Moreover, mice in which B cells were unable to produce GM-CSF exhibited reduced CD103+ dendritic cells and reduced CD4+ T cell numbers in the draining lymph node. Altogether, our results describe a previously unrecognized mechanism of pleural space inflammation necessary for effective protection against bacterial airway infection

General population normative scores for interpreting the BODY-Q

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The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure