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Background: After pylorus-resecting pancreatoduodenectomy (PrPD), delayed gastric emptying (DGE) might partially be attributed to biliary reflux. We investigated whether the incidence of primary DGE is reduced after Roux-en-Y instead of Billroth-II reconstruction. Methods: Patients undergoing PrPD from 2016 to 2019 at a high-volume center were identified. Excluding causes of secondary DGE, we matched patients with Roux-en-Y and Billroth-II reconstruction in a 1:2 ratio and compared primary DGE. Results: In 24 vs. 48 (Roux-en-Y vs. Billroth-II) patients, DGE (grade B/C) incidence (20.8 % vs. 18.8 %; P = 1.000), nasogastric tube requirement (median 2 vs. 2 days; P = 0.844) and time to solid food intake (7 vs. 7 days; P = 0.933) were comparable. Univariable logistic regression showed no association between DGE and Roux-en-Y reconstruction (OR 1.47; P = 0.524), in contrast to age (1.08; P = 0.030) and pancreatic biochemical leak (4.98; P = 0.007). Conclusions: Primary DGE did not differ between Roux-en-Y and Billroth-II reconstruction after PrPD. Instead, age and postoperative pancreatic biochemical leak were associated with higher DGE risk.

IntroductionCancer frequently leads to psychological challenges, among them emotion regulation problems. These can be alleviated with the help of mindfulness therapies or neurofeedback (NF) interventions. Possible intervention effects on emotion procession can be detected in clinical EEG studies by exploring event-related potentials, e.g., early posterior negativity (EPN), which recently has been established to investigate emotional processing and represents very early attention to affective stimuli. Therefore, this clinical-experimental study investigated the efficacy of mindfulness and NF (10 sessions each) on the EPN in oncology patients.MethodThe study enrolled 42 cancer patients (age: 31–73 years; gender: 28 female, 14 male). The study design was an RCT with a parallel group [NF (n = 21) versus mindfulness (n = 21)] waitlist paradigm. EEG recordings in an oddball task with neutral, rare positive and negative valence and high and low arousal stimuli were performed at three measurement time points (T0 = before waitlist, T1 = before intervention, T2 = after intervention). Following preprocessing, data from electrodes O1, Oz and O2 were analyzed for EPN amplitudes.ResultsResponse time did not differ across groups and conditions. Comparing EPN at T1 and T2, there was a significant interaction of time, valence, and intervention (p = 0.042). Descriptive statistics showed increased EPN for negative stimuli after the NF intervention (T1 to T2), while EPN for positive stimuli only slightly increased. For mindfulness, positive stimuli evoked stronger amplitudes after the intervention, while EPN for negative stimuli increased from T1 to T2.ConclusionDistinct effects were observed for the EPN for pictures with negative valence. Here, it is presumed that mindfulness treatment led to a refocusing of attention with a focus on positive valence, whereas NF seems to entail a different processing of images with negative valence and is therefore to be seen more in the sense of a confrontational approach. Our results suggest that both interventions are suitable for modulating EPN. However, it is not clear to what extent the effects are due to the interventions alone and how other factors might have affected the amplitudes, which highlights the need for further research in this area.

Most patients with non-alcoholic steatohepatitis (NASH) have insulin resistance, and there is a near-universal association between NASH and insulin resistance. Insulin resistance induces lipid accumulation in the liver, leading to the development of metabolic syndrome. However, most NASH rodent models fail to develop metabolic syndrome. LEW.1WR1 rats that are 23 weeks old showed increased body mass, epididymal fat, and liver mass, suggesting obesity-driven metabolic dysfunction. We have characterized steatosis, inflammation, Mallory–Denk body formation with hematoxylin and eosin (H&E), and fibrosis with Trichome blue staining. The presence of hepatic fibrosis with other features of NASH described above is one of the major strengths of this model since most of the currently available NASH models do not develop microvesicular steatosis or fibrosis. Together with the other important features of NASH described above, we confirm that male LEW.1WR1 rats develop NASH and insulin resistance with a standard diet.

Abstract Introduction The assessment of bone density has gained significance in recent years due to the aging population. Accurate assessment of bone density is crucial when deciding on the appropriate treatment plan for spinal stabilization surgery. The objective of this work was to determine the trabecular bone density values of the subaxial cervical, thoracic and lumbar spine using Hounsfield units. Material and methods Data from 200 patients who underwent contrast-enhanced polytrauma computed tomography at a maximum care hospital over a two-year period were retrospectively analyzed. HUs were measured with an elliptical measurement field in three different locations within the vertebral body: below the upper plate, in the middle of the vertebral body, and above the base plate. The measured Hounsfield units were converted into bone density values using a validated formula. Results The mean age of the patient collective was 47.05 years. Mean spinal bone density values decreased from cranial to caudal (C3: 231.79 mg/cm3; L5: 155.13 mg/cm3; p < 0.001), with the highest values in the upper cervical spine. Bone density values generally decreased with age in all spinal segments. There was a clear decrease in values after age 50 years (p < 0.001). Conclusions In our study, bone density decreased from cranial to caudal with higher values in the cervical spine. These data from the individual spinal segments may be helpful to comprehensively evaluate the status of the spine and to design a better preoperative plan before instrumentation.

Abstract Background Despite recent advances in locoregional, systemic, and novel checkpoint inhibitor treatment, hepatocellular carcinoma (HCC) is still associated with poor prognosis. The feasibility of potentially curative liver resection (LR) and transplantation (LT) is limited by the underlying liver disease and a shortage of organ donors. Especially after LR, high recurrence rates present a problem and circulating tumor cells are a major cause of extrahepatic recurrence. Tigecycline, a commonly used glycylcycline antibiotic, has been shown to have antitumorigenic effects and could be used as a perioperative and adjuvant therapeutic strategy to target circulating tumor cells. We aimed to investigate the effect of tigecycline on HCC cell lines and its mechanisms of action. Methods Huh7, HepG2, Hep3B, and immortalized hepatocytes underwent incubation with clinically relevant tigecycline concentrations, and the influence on proliferation, migration, and invasion was assessed in two- and three-dimensional in vitro assays, respectively. Bioinformatic analysis was used to identify specific targets of tigecycline. The expression of RAC1 was detected using western blot, RT-PCR and RNA sequencing. ELISA and flow cytometry were utilized to measure reactive oxygen species (ROS) generation upon tigecycline treatment and flow cytometry to detect alterations in cell cycle. Changes in mitochondrial function were detected via seahorse analysis. RNA sequencing was performed to examine involved pathways. Results Tigecycline treatment resulted in a significant reduction of mitochondrial function with concomitantly preserved mitochondrial size, which preceded the observed decrease in HCC cell viability. The sensitivity of HCC cells to tigecycline treatment was higher than that of immortalized non-cancerous THLE-2 hepatocytes. Tigecycline inhibited both migratory and invasive properties. Tigecycline application led to an increase of detected ROS and an S-phase cell cycle arrest. Bioinformatic analysis identified RAC1 as a likely target for tigecycline and the expression of this molecule was increased in HCC cells as a result of tigecycline treatment. Conclusion Our study provides evidence for the antiproliferative effect of tigecycline in HCC. We show for the first time that this effect, likely to be mediated by reduced mitochondrial function, is associated with increased expression of RAC1. The reported effects of tigecycline with clinically relevant and achievable doses on HCC cells lay the groundwork for a conceivable use of this agent in cancer treatment.

Background: Patients affected by lumbar spinal stenosis (LSS) suffer from a multifactorial degeneration of the lumbar spine resulting in narrowing of the neuroforamina and spinal canal, leading to various functional limitations. It remains unclear whether LSS patients after surgery would benefit from early post-operative rehabilitation, or if a delayed rehabilitation would be more advantageous. The purpose of this partially randomized patient preference trial is to evaluate the impact of post-operative rehabilitation timing as well as surgical intervention type on psychometric properties and functional outcomes in patients with LSS. Methods: Data for this patient preference trial are collected before and after surgical (decompression only or decompression and fusion) and rehabilitative interventions as well as six, 12 and 24 months after completing rehabilitation. The study participants are patients diagnosed with LSS who are at least 18 years old. After a medical check-up, participants will complete patient-reported outcome measures (PAREMO-20, SIBAR, FREM-8, SF-12, SFI, ODI) and different functional assessments (functional reach test, loaded reach test, handgrip strength, standing balance control, 6-min walk test). Ethics and dissemination: The results of this study will be published through peer-reviewed publications and scientific contributions at national and international conferences. This research has been approved by the Institutional Review Board of Martin Luther University Halle-Wittenberg (reference number: 2022-128).

Abstract Background The sole presence of deep submucosal invasion is shown to be associated with a limited risk of lymph node metastasis. This justifies a local excision of suspected deep submucosal invasive colon carcinomas (T1 CCs) as a first step treatment strategy. Recently Colonoscopy-Assisted Laparoscopic Wedge Resection (CAL-WR) has been shown to be able to resect pT1 CRCs with a high R0 resection rate, but the long term outcomes are lacking. The aim of this study is to evaluate the safety, effectiveness and long-term oncological outcomes of CAL-WR as primary treatment for patients with suspected superficial and also deeply-invasive T1 CCs. Methods In this prospective multicenter clinical trial, patients with a macroscopic and/or histologically suspected T1 CCs will receive CAL-WR as primary treatment in order to prevent unnecessary major surgery for low-risk T1 CCs. To make a CAL-WR technically feasible, the tumor may not include > 50% of the circumference and has to be localized at least 25 cm proximal from the anus. Also, there should be sufficient distance to the ileocecal valve to place a linear stapler. Before inclusion, all eligible patients will be assessed by an expert panel to confirm suspicion of T1 CC, estimate invasion depth and subsequent advise which local resection techniques are possible for removal of the lesion. The primary outcome of this study is the proportion of patients with pT1 CC that is curatively treated with CAL-WR only and in whom thus organ-preservation could be achieved. Secondary outcomes are 1) CAL-WR’s technical success and R0 resection rate for T1 CC, 2) procedure-related morbidity and mortality, 3) 5-year overall and disease free survival, 4) 3-year metastasis free survival, 5) procedure-related costs and 6) impact on quality of life. A sample size of 143 patients was calculated. Discussion CAL-WR is a full-thickness local resection technique that could also be effective in removing pT1 colon cancer. With the lack of current endoscopic local resection techniques for > 15 mm pT1 CCs with deep submucosal invasion, CAL-WR could fill the gap between endoscopy and major oncologic surgery. The present study is the first to provide insight in the long-term oncological outcomes of CAL-WR. Trial registration CCMO register (ToetsingOnline), NL81497.075.22, protocol version 2.3 (October 2022).

Introduction: Primary dedifferentiated liposarcomas of the spine mark a rare tumor entity. Research question and case description: We present a rare case of a primary dedifferentiated liposarcoma of the thoracic spine. A 36-year-old previously completely healthy woman presented with a sudden ascending paresthesia of both legs, persistently increasing over the course of two days before initial presentation. Case report: Computed tomography and magnetic resonance imaging revealed an expansively growing tumor mass extending from T5 to T6 and absolutely compressing the dural sac and spinal cord. The patient's neurological function completely recovered after emergency posterior decompression via laminectomy with intralesional tumor debulking. The tumor was histologically classified as primary grade 2 dedifferentiated liposarcoma (DDLPS) of the spine and after referral to a sarcoma center, the patient was treated with three courses of polychemotherapy (doxorubicin plus ifosfamide). Chemotherapy was followed by aggressive resection by en-bloc spondylectomy in cooperation with a spine tumor center. Subsequently, the patient also underwent radiation therapy. Results: The patient still undergoes structured tumor aftercare and is tumor- and metastasis-free 53 months after tumor resection. Discussion and conclusion: DDLPS rarely occur in the spine, with definitive resection of the tumor being the treatment of choice. Surgery should be accompanied by other (radio-) oncological treatment options in cases where only subtotal resection is possible. Also, referral of patients with primary sarcomas of the spine to specialized sarcoma centers is essential, so they can be provided with individual treatment options and structured interdisciplinary aftercare, that ensure the best possible outcome.

Introduction: Predicting the pre-morbid sagittal profile of the spine or segmental angles could enhance the process of planning the extent of fracture reduction. There is evidence that spinopelvic parameters may be suitable for this purpose. Research question: Is it possible to determine the inflection point and the mono- and bi-segmental endplate angles (EPA) in the thoracolumbar transition (from Th9 to L2) based on age, gender, spinopelvic parameters, and the adjacent EPA in the supine position? Material and methods: Based on Polytrauma CT scans in the supine position, the following spinopelvic parameters were measured using non-fractured spines: pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), and the apex of the LL. Results: In this study, a total of 287 patients with a mean age of 42±16 years were included. Age-related changes were observed, where LL, thoracic kyphosis (TK), and PI increase with age. Gender-related comparisons showed that females had a more pronounced LL and reduced TK. Significant correlations between IP and spinopelvic parameters, with the apex of LL providing the best prediction, were found. However, the overall model quality remained low. Predicting mEPA and bEPA showed positive correlations. The prediction for mEPA L2/3 demonstrated the highest correlation. For bisegmental angles, the most caudal bEPA (L2) exhibited the highest correlation, albeit with some notable absolute differences in the values between measured and predicted values. Discussion and conclusion: While this study highlights the complexity of the relationship between the pelvis and thoracolumbar parameters, finding a predictive tool for thoracolumbar reduction and stabilization was not possible.

Background: EEG biofeedback (NF) is an established therapy to enable individuals to influence their own cognitive-emotional state by addressing changes in brainwaves. Psycho-oncological approaches of NF in cancer patients are rare and effects are hardly studied. Objective: The aim of this explorative, randomized controlled trial was to test the effectiveness of an alpha and theta NF training protocol, compared to mindfulness based therapy as an established psycho-oncological treatment. Methods: Of initially 62 screened patients, 56 were included (inclusion criteria were cancer independent of tumor stage, age >18 years, German speaking; exclusion criteria suicidal ideation, brain tumor). Randomization and stratification (tumor stage) was conducted by a computer system. Participants got 10 sessions over 5 weeks, in (a) an NF intervention (n = 21; 13 female, 8 male; MAge = 52.95(10 519); range = 31 to 73 years)) or (b) a mindfulness group therapy as control condition (CG; n = 21; ie, 15 female, 6 male; MAge = 50.33(8708); range = 32 to 67 years)). Outcome parameters included self-reported cognitive impairment (PCI) as primary outcome, and secondary outcomes of emotional distress (DT, PHQ-8, GAD-7), fatigue (MFI-20), rumination (RSQ), quality of life (QoL, EORTC-30 QoL), self-efficacy (GSE), and changes in EEG alpha, and theta-beta band performance in the NF condition. Results: No changes in cognitive impairment were found ( P = .079), neither in NF nor CG. High affective distress was evident, with 70.7% showing elevated distress and 34.1% showing severe depressive symptoms. Affective symptoms of distress ( P ≤ .01), depression ( P ≤ .05) and generalized anxiety ( P ≤ .05) decreased significantly over time. No differences between NF and CG were found. There was a significant increase of the alpha band ( P ≤ .05; N = 15) over the NF sessions. Self-efficacy predicted QoL increase in NF with P ≤ .001 and an explained variance of 48.2%. Conclusion: This is the first study to investigate NF technique with regard to basic mechanisms of effectiveness in a sample of cancer patients, compared to an established psycho-oncological intervention in this field. Though there were no changes in cognitive impairment, present data show that NF improves affective symptoms comparably to mindfulness-based therapy and even more pronounced in QoL and self-efficacy. Trial registration: ID: DRKS00015773

Abstract Background Molecular differences in colorectal cancer (CRC) are associated with the metastatic route. Patient survival is mainly driven by metastatic spread thus it is imperative to understand its key drivers to develop biomarkers for risk stratification, follow-up protocols and personalized therapy. Thus, this study aimed to identify genes associated with the metastatic route in CRC. Material and methods CRC patients resected at our clinic from 2005 to 2014 and with a minimum 5-year follow-up were included in this analysis and grouped into CRC with hepatic (HEP), peritoneal (PER) or without distant metastases (M0), and HEP/PER. Firstly, tumor RNA of 6 patients each was isolated by microdissection from formalin-fixed paraffin-embedded specimens and analyzed by a NanoString analysis. Subsequently, these results were validated with immunohistochemistry and correlated to clinicopathological parameters in a larger collective of CRC patients (HEP n = 51, PER n = 44, M0 n = 47, HEP/PER n = 28). Results Compared to M0, HEP tumors showed 20 differentially expressed genes associated with epithelial-mesenchymal transition (EMT) and angiogenesis. Compared to M0, PER tumors had 18 differentially expressed genes. The finding of different gene signatures was supported by the multidimensional principal component clustering analysis. Tumor perforation did not influence the metastatic route. CIB1 was homogenously and significantly overexpressed in HEP compared to M0 (p

Abstract Objectives Osteoporotic fractures of the pelvis (OFP) are an increasing issue in orthopedics. Current classification systems (CS) are mostly CT-based and complex and offer only moderate to substantial inter-rater reliability (interRR) and intra-rater reliability (intraRR). MRI is thus gaining importance as a complement. This study aimed to develop a simple and reliable CT- and MRI-based CS for OFP. Methods A structured iterative procedure was conducted to reach a consensus among German-speaking spinal and pelvic trauma experts over 5 years. As a result, the proposed OF-Pelvis CS was developed. To assess its reliability, 28 experienced trauma and orthopedic surgeons categorized 25 anonymized cases using X-ray, CT, and MRI scans twice via online surveys. A period of 4 weeks separated the completion of the first from the second survey, and the cases were presented in an altered order. While 13 of the raters were also involved in developing the CS (developing raters (DR)), 15 user raters (UR) were not deeply involved in the development process. To assess the interRR of the OF-Pelvis categories, Fleiss’ kappa (κF) was calculated for each survey. The intraRR for both surveys was calculated for each rater using Kendall’s tau (τK). The presence of a modifier was calculated with κF for interRR and Cohen’s kappa (κC) for intraRR. Results The OF-Pelvis consists of five subgroups and three modifiers. Instability increases from subgroups 1 (OF1) to 5 (OF5) and by a given modifier. The three modifiers can be assigned alone or in combination. In both surveys, the interRR for subgroups was substantial: κF = 0.764 (Survey 1) and κF = 0.790 (Survey 2). The interRR of the DR and UR was nearly on par (κF Survey 1/Survey 2: DR 0.776/0.813; UR 0.748/0.766). The agreement for each of the five subgroups was also strong (κF min.–max. Survey 1/Survey 2: 0.708–0.827/0.747–0.852). The existence of at least one modifier was rated with substantial agreement (κF Survey 1/Survey 2: 0.646/0.629). The intraRR for subgroups showed almost perfect agreement (τK = 0.894, DR: τK = 0.901, UR: τK = 0.889). The modifier had an intraRR of κC = 0.684 (DR: κC = 0.723, UR: κC = 0.651), which is also considered substantial. Conclusion The OF-Pelvis is a reliable tool to categorize OFP with substantial interRR and almost perfect intraRR. The similar reliabilities between experienced DRs and URs demonstrate that the training status of the user is not important. However, it may be a reliable basis for an indication of the treatment score.

Abstract The heterozygous human Klotho KL-VS haplotype has been associated with improved cognitive performance but results are inconsistent. Here we assessed Klotho KL-VS haplotype and cognition using data from the third examination of the population-based Heinz Nixdorf Recall Study. We analyzed cognition tests (immediate and delayed word list, Trail-Making Test [TMT] part A and B, Maze test, interference condition of the Stroop color-word test, verbal fluency) and their associations with Klotho KL-VS haplotype. The Klotho KL-VS haplotype is classified by the V-allele at SNP rs9536314 (F352V) and the S-allele at SNP rs9527025 (C370S). Heterozygotes for the KL-VS haplotype were compared with non-carriers. Analyses were performed in 1812 subjects (55–87 years). We found consistent but only slightly lower performance in heterozygous carriers of the KL-VS haplotype in all tasks with Z-scores ranging between Z = − 0.042 (verbal fluency) and − 0.17 (TMT part A). Differences between carriers and non-carriers were similar for men and women for all tests but TMT part B (interaction contrast = 8.4 s (95% CI − 2.3; 19.1)). While cognition declined with age, we found an effect modification by age (55–65 years, 66–75 years, > 75 years). In the 66–75 years KL-VS heterozygous age group, lower performance was seen in memory, visual attention and motor speed. Contrary to our hypothesis, heterozygous carriers of the KL-VS haplotype did not show enhanced performance in cognitive tests in our study.

Abstract Background Inguinal hernia repair, gallbladder removal, and knee- and hip replacements are the most commonly performed surgical procedures, but all are subject to practice variation and variable patient-reported outcomes. Shared decision-making (SDM) has the potential to reduce surgery rates and increase patient satisfaction. This study aims to evaluate the effectiveness of an SDM strategy with online decision aids for surgical and orthopaedic practice in terms of impact on surgery rates, patient-reported outcomes, and cost-effectiveness. Methods The E-valuAID-study is designed as a multicentre, non-randomized stepped-wedge study in patients with an inguinal hernia, gallstones, knee or hip osteoarthritis in six surgical and six orthopaedic departments. The primary outcome is the surgery rate before and after implementation of the SDM strategy. Secondary outcomes are patient-reported outcomes and cost-effectiveness. Patients in the usual care cluster prior to implementation of the SDM strategy will be treated in accordance with the best available clinical evidence, physician’s knowledge and preference and the patient’s preference. The intervention consists of the implementation of the SDM strategy and provision of disease-specific online decision aids. Decision aids will be provided to the patients before the consultation in which treatment decision is made. During this consultation, treatment preferences are discussed, and the final treatment decision is confirmed. Surgery rates will be extracted from hospital files. Secondary outcomes will be evaluated using questionnaires, at baseline, 3 and 6 months. Discussion The E-valuAID-study will examine the cost-effectiveness of an SDM strategy with online decision aids in patients with an inguinal hernia, gallstones, knee or hip osteoarthritis. This study will show whether decision aids reduce operation rates while improving patient-reported outcomes. We hypothesize that the SDM strategy will lead to lower surgery rates, better patient-reported outcomes, and be cost-effective. Trial registration: The Netherlands Trial Register, Trial NL8318, registered 22 January 2020. URL: https://www.trialregister.nl/trial/8318 .

Abstract Background Cognitive models of psychosis postulate an important role of Theory of mind (ToM) in the formation and maintenance of delusions, but research on this plausible conjecture has gathered conflicting findings. In addition, it is still an open question whether problems in emotion recognition (ER) are associated with delusions. We examined the association of problems in ToM and ER with different aspects of delusions in a large sample of patients with psychosis enrolled in a therapy trial. This also enabled us to explore the possible impact of ToM and ER on one part of patients’ social life: the quality of their therapeutic relationship. Methods Patients with psychotic disorders and delusions and/or hallucinations (n = 185) and healthy controls (n = 48) completed a ToM picture sequencing task and an ER task. Subsequently, patients were enrolled in a randomized-controlled Cognitive Behavior Therapy (CBT) trial (ISRCTN29242879). Patients and therapists rated the quality of the therapeutic relationship during the first five sessions of therapy. Results In comparison to controls, patients were impaired in both ToM and ER. Patients with deficits in ER experienced more severe delusional distress, whereas ToM problems were not related to delusions. In addition, deficits in ER predicted a less favorable therapeutic relationship and interactional problems viewed by the therapist. Impaired ER also moderated (increased) the negative influence of delusions on the therapeutic relationship and interactional difficulties viewed by the therapist. Conclusions Cognitive models on the formation and maintenance of delusions should consider ER as a potential candidate that might be related to the formation and maintenance of delusional distress, whereas problems in ToM might not be directly related to delusions and secondary dimensions of delusions. In addition, problems in ER in patients with psychosis might have an impact on the quality of the therapeutic relationship and patients with problems in ER are more likely to be viewed as problematic by their therapists. Nevertheless, training ER might be a way to improve the quality of the therapeutic relationship and potentially the effectiveness of CBT or other interventions for patients with psychosis.

Acetylcholine regulates intestinal epithelial secretion via muscarinic Gq-coupled receptors but its role in cell differentiation is unclear. Here, the authors show that Prox1-positive endocrine cells are sensors for the cholinergic intestinal niche and can trigger increased differentiation of enteroendocrine DCLK1-positive tuft cells.

Introduction Partial pancreatoduodenectomy (PD) is the treatment of choice for various benign and malignant tumours of the pancreatic head or the periampullary region. For reconstruction of the gastrointestinal passage, two stomach-preserving PD variants exist: pylorus preservation PD (ppPD) or pylorus resection PD (prPD) with preservation of the stomach. In pancreatic surgery, delayed gastric emptying (DGE) remains a serious complication after PD with an incidence varying between 4.5% and 45%, potentially delaying hospital discharge or further treatment, for example, adjuvant chemotherapy. Evidence is lacking to assess, which variant of PD entails fewer postoperative DGE.Methods and analysis The protocol of a large-scale, multicentre, pragmatic, two-arm parallel-group, registry-based randomised controlled trial (rRCT) using a two-stage group-sequential design is presented. This patient-blind rRCT aims to demonstrate the superiority of prPD over ppPD with respect to the overall incidence of DGE within 30 days after index surgery in a German real-world setting. A total of 984 adults undergoing elective PD for any indication will be randomised in a 1:1 ratio. Patients will be recruited at about 30 hospitals being members of the StuDoQ|Pancreas registry established by the German Society of General and Visceral Surgery. The postoperative follow-up for each patient will be 30 days. The primary analysis will follow an intention-to-treat approach and applies a binary logistic random intercepts model. Secondary perioperative outcomes include overall severe morbidity (Clavien-Dindo classification), blood loss, 30-day all-cause mortality, postoperative hospital stay and operation time. Complication rates and adverse events will be closely monitored.Ethics and dissemination This protocol was approved by the leading ethics committee of the Medical Faculty of the Ludwig-Maximilians-Universität, Munich (reference number 19-221). The results will be published in a peer-reviewed journal and presented at international conferences. Study findings will also be disseminated via the website (http://www.dgav.de/studoq/pylorespres/).Trial registration number DRKS-ID: DRKS00018842.

Abstract Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with a broad variety of hematological and solid malignancies. The two main drivers behind this success are checkpoint inhibitors (CPIs) and chimeric antigen receptor (CAR) T cells. This review summarizes seminal findings from clinical and translational studies recently presented or published at important meetings or in top-tier journals, respectively. For checkpoint blockade, current studies focus on combinational approaches, perioperative use, new tumor entities, response prediction, toxicity management and use in special patient populations. Regarding cellular immunotherapy, recent studies confirmed safety and efficacy of CAR T cells in larger cohorts of patients with acute lymphoblastic leukemia or diffuse large B cell lymphoma. Different strategies to translate the striking success of CAR T cells in B cell malignancies to other hematological and solid cancer types are currently under clinical investigation. Regarding the regional distribution of registered clinical immunotherapy trials a shift from PD-1 / PD-L1 trials (mainly performed in the US and Europe) to CAR T cell trials (majority of trials performed in the US and China) can be noted.

Vector-borne diseases play a major role in human and veterinary medicine worldwide. A previous study detected asymptomatic vector-borne pathogens in military working dogs stationed at a military base in eastern Austria, and a follow-up survey of potential arthropod vectors was conducted in spring 2019 and 2020 in the vicinity of the base to evaluate the presence of vectors and their carrier status for a range of canine and zoonotic pathogens. A total of 1324 ticks (nymphs and adults of Ixodes ricinus, comprising 92.9% of the collected specimens, and adults of Haemaphysalis inermis, a tick previously only rarely described in Austria, Haemaphysalis concinna, and Dermacentor reticulatus) were collected by flagging. In 44.1% (125/284) of all pools (n = 284), one infectious agent was found; in 27.8% (79/284) and in 1.1% (3/284), two and three different agents, respectively, could be identified. Overall, 72.9% of the pools contained at least one pathogen (Borrelia spp., Rickettsia spp., Bartonella spp., and Babesia microti). Borrelia mijamotoi, B. lustinaniae, and B. microti were previously only described in single cases in Austria. Mosquitoes were collected with BG-Sentinel traps monthly during the summer of 2019. A total of 71 individuals from 11 species were collected. No filarioid DNA was detected in the mosquito sample pools, although Dirofilaria repens had been present in the dogs from the military site. In conclusion, vector surveillance should be combined with the surveillance of an exposed population whenever possible to estimate the infection risks for dogs and their handlers.

Background: The amygdala and the hippocampus are two limbic structures that play a critical role in cognition and behavior, however their manual segmentation and that of their smaller nuclei/subfields in multicenter datasets is time consuming and difficult due to the low contrast of standard MRI. Here, we assessed the reliability of the automated segmentation of amygdalar nuclei and hippocampal subfields across sites and vendors using FreeSurfer in two independent cohorts of older and younger healthy adults. Methods: Sixty-five healthy older (cohort 1) and 68 younger subjects (cohort 2), from the PharmaCog and CoRR consortia, underwent repeated 3D-T1 MRI (interval 1–90 days). Segmentation was performed using FreeSurfer v6.0. Reliability was assessed using volume reproducibility error (ε) and spatial overlapping coefficient (DICE) between test and retest session. Results: Significant MRI site and vendor effects (p ​0.43, p ​ ​0.80). Conclusion: Our results support the use of volumetric measures of larger amygdalar nuclei and hippocampal subfields in multisite MRI studies. These measures could be useful for disease tracking and assessment of efficacy in drug trials.

Exercise is recommended for the healthy population as it increases fitness and prevents diseases. Moreover, exercise is also applied as an adjunct therapy for patients with various chronic diseases including cancer. Childhood cancer is a rare, heterogeneous disease that differs from adult cancer. Improved therapeutic strategies have increased childhood cancer survival rates to above 80% in developed countries. Although this is higher than the average adult cancer survival rate of about 50%, therapy results often in substantial long-term side effects in childhood cancer survivors. Exercise in adult cancer patients has many beneficial effects and may slow down tumor progression and improve survival in some cancer types, suggesting that exercise may influence cancer cell behavior. In contrast to adults, there is not much data on general effects of exercise in children. Whilst it seems possible that exercise might delay cancer progression or improve survival in children as well, there is no reliable data yet to support this hypothesis. Depending on the type of cancer, animal studies of adult cancer types show that the exercise-induced increase of the catecholamines epinephrine and norepinephrine, have suppressive as well as promoting effects on cancer cells. The diverse effects of exercise in adult cancer patients require investigating whether these results can be achieved in children with cancer.

Myeloid-derived suppressor cells (MDSCs) are one of the main suppressive cell population of the immune system. They play a pivotal role in the establishment of the tumor microenvironment (TME). In the context of cancers or other pathological conditions, MDSCs can differentiate, expand, and migrate in large quantities during circulation, inhibiting the cytotoxic functions of T cells and NK cells. This process is regulated by ROS, iNOS/NO, arginase-1, and multiple soluble cytokines. The definition of MDSCs and their phenotypes in humans are not as well represented as in other organisms such as mice, owing to the absence of the cognate molecule. However, a comprehensive understanding of the differences between different species and subsets will be beneficial for clarifying the immunosuppressive properties and potential clinical values of these cells during tumor progression. Recently, experimental evidence and clinical investigations have demonstrated that MDSCs have a close relationship with poor prognosis and drug resistance, which is considered to be a leading marker for practical applications and therapeutic methods. In this review, we summarize the remarkable position of MDSCs in solid tumors, explain their classifications in different models, and introduce new treatment approaches to target MDSCs to better understand the advancement of new approaches to cancer treatment.

Abstract Background In patients with stage II colorectal cancer (CRC) the number of surgically retrieved lymph nodes (LNs) is associated with prognosis, resulting in a minimum of 10–12 retrieved LNs being recommended for this stage. Current guidelines do not provide a recommendation regarding LN yield in T1 CRC. Studies evaluating LN yield in T1 CRC suggest that such high LN yields are not feasible in this early stage, and a lower LN yield might be appropriate. We aimed to validate the cut-off of 10 retrieved LNs on risk for recurrent cancer and detection of LN metastasis (LNM) in T1 CRC, and explored whether this number is feasible in clinical practice. Methods Patients diagnosed with T1 CRC and treated with surgical resection between 2000 and 2014 in thirteen participating hospitals were selected from the Netherlands Cancer Registry. Medical records were reviewed to collect additional information. The association between LN yield and recurrence and LNM respectively were analyzed using 10 LNs as cut-off. Propensity score analysis using inverse probability weighting (IPW) was performed to adjust for clinical and histological confounding factors (i.e., age, sex, tumor location, size and morphology, presence of LNM, lymphovascular invasion, depth of submucosal invasion, and grade of differentiation). Results In total, 1017 patients with a median follow-up time of 49.0 months (IQR 19.6–81.5) were included. Four-hundred five patients (39.8%) had a LN yield ≥ 10. Forty-one patients (4.0%) developed recurrence. LN yield ≥ 10 was independently associated with a decreased risk for recurrence (IPW-adjusted HR 0.20; 95% CI 0.06–0.67; P = 0.009). LNM were detected in 84 patients (8.3%). LN yield ≥ 10 was independently associated with increased detection of LNM (IPW-adjusted OR 2.27; 95% CI 1.39–3.69; P = 0.001). Conclusions In this retrospective observational study, retrieving

We investigated the MMN at electrode Fz to 12% temporally predictable or unpredictable duration decrement deviant stimuli in 29 healthy controls and 31 schizophrenia patients. With a stimulus onset asynchronicity of 500 ms in the regular predictable condition, a deviant occurred every 4 s while it varied randomly in the unpredictable condition.Here we report detailed data tables and multivariate analysis of variance results (MANOVA) on MMN, P3a and standard ERP data including details on follow-up analyses. An extended figure shows MMN difference curves and averages to standard and deviant stimuli in both experimental conditions and subject groups. Keywords: Cognitive Neuroscience, Neurophysiology, Mismatch Negativity

During colorectal inflammation and cancer, myeloid cells accumulate in the spleen and suppress the host immunity response. In this study, the authors use a mouse model of colitis to demonstrate that upon vagus stimulation splenic memory T cells release TFF2, which suppresses the expansion of myeloid cells and cancer progression.

Electrophysiological indices are sensitive to cognitive dysfunction in schizophrenia but have rarely been used to assess benefits of cognitive remediation. Our aim was to evaluate the effect of specific cognitive training approaches on event-related potentials. Forty-six patients with schizophrenia underwent either auditory (AUD) or visuo-spatial (VIS) cognitive training or treatment-as-usual (TAU). Cognitive training was computer-assisted and administered for 10 sessions within two weeks. Event-related potentials during an active odd-ball paradigm together with clinical and neuropsychological variables were assessed before and after training and again at a two-month follow-up. Compared to the TAU group both the AUD and VIS training groups showed decreased P2 latency following training. At follow-up, the P2-latency reduction was stable in the VIS group but the AUD group experienced a relapse. Training resulted in improved digit-span backward among neuropsychological variables. Increased P2 amplitude was related to more positive symptoms and lower social-occupational functioning and longer P2 latency was associated with greater severity of stereotyped thinking. The more general visuo-spatial training appears to have a longer-lasting effect on P2 latency than the specific auditory training. Alternatively, there may be specific auditory discrimination deficits in schizophrenia requiring more extensive training for a stable change.

The diagnosis of pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis, in particular, when patients present with unresectable disease. While significant progress has been made in understanding the biology of PDAC, this knowledge has not translated into a clear clinical benefit and current chemotherapeutic strategies only offer a modest improvement in overall survival. Accordingly, novel approaches are desperately needed. One hypothesis that could—at least in part—explain the desolate response of PDAC to chemotherapy is the so-called cancer stem cell (CSC) concept, which attributes specific traits, such as chemoresistance, metastatic potential and a distinct metabolism to a small cellular subpopulation of the whole tumor. At the same time, however, some of these attributes could make CSCs more permissive for novel therapeutic strategies with compounds that are already in clinical use. Most recently, several publications have tried to enlighten the field with the idea of repurposing established drugs for antineoplastic use. As such, recycling drugs could present an intriguing and fast-track method with new therapeutic paradigms in anti-cancer and anti-CSC treatments. Here, we aim to summarize important aspects and novel findings of this emerging field.

BACKGROUND: The Mismatch Negativity (MMN) is an event-related potential (ERP) sensitive to early auditory deviance detection and has been shown to be reduced in schizophrenia patients. Moreover, MMN amplitude reduction to duration deviant tones was found to be related to functional outcomes particularly, to neuropsychological (working memory and verbal domains) and psychosocial measures. While MMN amplitude is thought to be correlated with deficits of early sensory processing, the functional significance of MMN latency remains unclear so far. The present study focused on the investigation of MMN in relation to neuropsychological function in schizophrenia. METHOD: Forty schizophrenia patients and 16 healthy controls underwent a passive oddball paradigm (2400 binaural tones; 88% standards [1 kHz, 80 db, 80 ms], 11% frequency deviants [1.2 kHz], 11% duration deviants [40 ms]) and a neuropsychological test-battery. Patients were assessed with regard to clinical symptoms. RESULTS: Compared to healthy controls schizophrenia patients showed diminished MMN amplitude and shorter MMN latency to both deviants as well as an impaired neuropsychological test performance. Severity of positive symptoms was related to decreased MMN amplitude to duration deviants. Furthermore, enhanced verbal memory performance was associated with prolonged MMN latency to frequency deviants in patients. CONCLUSION: The present study corroborates previous results of a diminished MMN amplitude and its association with positive symptoms in schizophrenia patients. Both, the findings of a shorter latency to duration and frequency deviants and the relationship of the latter with verbal memory in patients, emphasize the relevance of the temporal aspect of early auditory discrimination processing in schizophrenia.

Men are traditionally thought to have more problems in understanding women compared to understanding other men, though evidence supporting this assumption remains sparse. Recently, it has been shown, however, that meńs problems in recognizing women's emotions could be linked to difficulties in extracting the relevant information from the eye region, which remain one of the richest sources of social information for the attribution of mental states to others. To determine possible differences in the neural correlates underlying emotion recognition from female, as compared to male eyes, a modified version of the Reading the Mind in the Eyes Test in combination with functional magnetic resonance imaging (fMRI) was applied to a sample of 22 participants. We found that men actually had twice as many problems in recognizing emotions from female as compared to male eyes, and that these problems were particularly associated with a lack of activation in limbic regions of the brain (including the hippocampus and the rostral anterior cingulate cortex). Moreover, men revealed heightened activation of the right amygdala to male stimuli regardless of condition (sex vs. emotion recognition). Thus, our findings highlight the function of the amygdala in the affective component of theory of mind (ToM) and in empathy, and provide further evidence that men are substantially less able to infer mental states expressed by women, which may be accompanied by sex-specific differences in amygdala activity.