The assessment of impaired liver function and prognosis in hepatocellular carcinoma.

Introduction: The impairment of liver function strongly limits the therapeutic options for hepatocellular carcinoma (HCC), and the assessment of liver function is key to finding the appropriate therapy for patients suffering from this disease. Furthermore, preexisting liver dysfunction has a negative impact on the prognosis of patients in addition to the malignant potential of HCC. Hence, defining the optimal treatment of patients with HCC requires a comprehensive examination with liver function being a crucial part of it.

Introducing ProsperNN-a Python package for forecasting with neural networks.

We present the package prosper_nn, that provides four neural network architectures dedicated to time series forecasting, implemented in PyTorch. In addition, prosper_nn contains the first sensitivity analysis suitable for recurrent neural networks (RNN) and a heatmap to visualize forecasting uncertainty, which was previously only available in Java. These models and methods have successfully been in use in industry for two decades and were used and referenced in several scientific publications.

Economic Evidence on Cost Sharing and Alternative Insurance Designs to Address Moral and Behavioral Hazards in High-Income Health Care Systems: A Systematic Review.

In health insurance, "moral hazard" describes the concept that coverage without an out-of-pocket cost to consumers could result in health care utilization beyond economically efficient levels. In response, payers in the United States (US) have designed pharmaceutical benefit plans with significant cost exposure (e.g.

Primary percutaneous metal stenting above the ampulla in resectable perihilar cholangiocarcinoma.

Introduction: We present a case of a patient with resectable perihilar cholangiocarcinoma (pCCA) who underwent primary metal stenting above the ampulla, followed by a successful surgical resection. Biliary drainage is a crucial step in the preoperative management of pCCA, yet there is no consensus on the optimal approach. Traditional drainage methods involve passing through the ampulla and/or the skin barrier, thereby increasing the risk of bacterial contamination of the biliary tree and secondary cholangitis.

Sleeve-gastrectomy results in improved metabolism and a massive stress response of the liver proteome in a mouse model of metabolic dysfunction-associated steatohepatitis.

Background: Bariatric surgery has been shown to improve the histopathological findings in patients with obesity and metabolic dysfunction-associated steatohepatitis, but there are also reports about non-responders or progressive disease after bariatric interventions. Therefore, it is of utmost importance to understand the pathophysiological processes in the liver after bariatric surgery.

Materials And Methods: In the present study, 4 weeks old male C57/Bl6 mice were fed a Western Diet to induce metabolic dysfunction-associated steatohepatitis and sleeve-gastrectomy (SG), or sham operation in the pair-fed and ad libitum control group were performed.

Failure to Rescue After Resection of Perhilar Cholangiocarcinoma in an International Multicenter Cohort.

Background: Failure to rescue (FTR) is defined as the inability to prevent death after the development of a complication. FTR is a parameter in evaluating multidisciplinary postoperative complication management. The aim of this study was to evaluate FTR rates after major liver resection for perihilar cholangiocarcinoma (pCCA) and analyze factors associated with FTR.

Public sector replacement of privately funded pharmaceutical R&D: cost and efficiency considerations.

Aims: Economic studies have found that public support of basic medical research provides important long-term benefits. In response to suggestions that private pharmaceutical research and development (R&D) funding could be totally replaced by public funding, we investigate the economic implications of such a substitution in funding roles that maintain the recent pace of pharmaceutical innovation.

Materials And Methods: Total lifecycle R&D costs were estimated using the latest available R&D expenditures per novel molecule entering clinical trials, likelihood of approval, pre-clinical and post-approval expenditures, using a published survey and a review of publicly available financial accounts from US-listed multinational developers.

Preoperative nonalcoholic steatohepatitis and resolution of metabolic comorbidities after bariatric surgery.

Background: Most patients undergoing bariatric surgery demonstrate elements of the metabolic syndrome (MetS) and can therefore be diagnosed with metabolically unhealthy obesity (MUO). Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) as hepatic manifestations of the MetS occur in many patients with obesity, but their leverage on postoperative improvement to Metabolic Health (MH), defined as absence of any metabolic comorbidity, remains unclear.

Objectives: The aim of this study was to assess the influence of liver health status, operative procedure, and sex on postoperative switch from a MUO to an MH phenotype.

Combined portal and hepatic vein embolisation in perihilar cholangiocarcinoma.

Background: Major hepatectomy in perihilar cholangiocarcinoma (pCCA) patients with a small future liver remnant (FLR) risks posthepatectomy liver failure (PHLF). This study examines combined portal and hepatic vein embolisation (PVE/HVE) to increase preoperative FLR volume and potentially decrease PHLF rates.

Methods: In this retrospective, multicentre, observational study, data was collected from centres affiliated with the DRAGON Trials Collaborative and the EuroLVD registry.

Temporal Trends in Acute Adrenal Insufficiency Events in Children With Congenital Adrenal Hyperplasia During 2019-2022.

Background: It is unclear whether targeted monitoring of acute adrenal insufficiency (AI) related adverse events (AE) such as sick day episodes (SDEs) and hospitalization rate in congenital adrenal hyperplasia (CAH) is associated with a change in the occurrence of these events.

Aim: Study temporal trends of AI related AE in the I-CAH Registry.

Methods: In 2022, data on the occurrence of AI-related AE in children aged <18 years with 21-hydroxylase deficiency CAH were compared to data collected in 2019.

β-Glucan-binding proteins are key modulators of immunity and symbiosis in mutualistic plant-microbe interactions.

In order to discriminate between detrimental, commensal, and beneficial microbes, plants rely on polysaccharides such as β-glucans, which are integral components of microbial and plant cell walls. The conversion of cell wall-associated β-glucan polymers into a specific outcome that affects plant-microbe interactions is mediated by hydrolytic and non-hydrolytic β-glucan-binding proteins. These proteins play crucial roles during microbial colonization: they influence the composition and resilience of host and microbial cell walls, regulate the homeostasis of apoplastic concentrations of β-glucan oligomers, and mediate β-glucan perception and signaling.

Satisfaction with a new patient education program for children, adolescents, and young adults with differences of sex development (DSD) and their parents.

Objective: Evaluation of the participant satisfaction with a newly developed interdisciplinary, modular education program for children, adolescents, and young adults with differences of sex development (DSD) and their parents.

Methods: The two-day program including tailored medical information, peer consultation and psychological support aimed to improve diagnosis-specific knowledge and empowerment. Post-training satisfaction was measured using an adapted ZUF-8 questionnaire, scoring from 5 (worst) to a maximum of 26 (best) for persons aged 6-17 and from 10 to 40 points for adults, including 2 open-ended questions.

Amphicarpic development in Cardamine chenopodiifolia.

Amphicarpy is an unusual trait where two fruit types develop on the same plant: one above and the other belowground. This trait is not found in conventional model species. Therefore, its development and molecular genetics remain under-studied.

GAL3ST1 Deficiency Reduces Epithelial-Mesenchymal Transition and Tumorigenic Capacity in a Cholangiocarcinoma Cell Line.

Cholangiocarcinoma (CCA), or bile duct cancer, is the second most common liver malignancy, with an increasing incidence in Western countries. The lack of effective treatments associated with the absence of early symptoms highlights the need to search for new therapeutic targets for CCA. Sulfatides (STs), a type of sulfoglycosphingolipids, have been found in the biliary tract, with increased levels in CCA and other types of cancer.

A quantitative modeling framework to understand the physiology of the hypothalamic-pituitary-adrenal axis and interaction with cortisol replacement therapy.

Congenital adrenal hyperplasia (CAH) is characterized by impaired adrenal cortisol production. Hydrocortisone (synthetic cortisol) is the drug-of-choice for cortisol replacement therapy, aiming to mimic physiological cortisol circadian rhythm. The hypothalamic-pituitary-adrenal (HPA) axis controls cortisol production through the pituitary adrenocorticotropic hormone (ACTH) and feedback mechanisms.

Clinical features and prediction of long-term survival after surgery for perihilar cholangiocarcinoma.

Introduction: The treatment of perihilar Cholangiocarcinoma (pCCA) poses specific challenges not only due to its high perioperative complication rates but also due its dismal long-term prognosis with only a few long-term survivors (LTS) among the patients. Therefore, in this analysis characteristics and predictors of LTS in pCCA patients are investigated.

Material And Methods: In this single center analysis, patients undergoing curative-intent liver resection for pCCA between 2010 and 2022 were categorized into long-term and short-term survivors (STS) excluding perioperative mortality.

Partial liver resection alters the bile salt-FGF19 axis in patients with perihilar cholangiocarcinoma: Implications for liver regeneration.

Background: Extended liver resection is the only treatment option for perihilar cholangiocarcinoma (pCCA). Bile salts and the gut hormone FGF19, both promoters of liver regeneration (LR), have not been investigated in patients undergoing resection for pCCA. We aimed to evaluate the bile salt-FGF19 axis perioperatively in pCCA and study its effects on LR.

Inflammation-associated intramyocellular lipid alterations in human pancreatic cancer cachexia.

Background: Cancer cachexia is a multifactorial metabolic syndrome characterized by systemic inflammation and ongoing skeletal muscle loss resulting in weakness, poor quality of life, and decreased survival. Whereas lipid accumulation in skeletal muscle is associated with cancer cachexia as well as the prognosis of cancer patients, surprisingly little is known about the nature of the lipids that accumulate in the muscle during cachexia, and whether this is related to inflammation. We aimed to identify the types and distributions of intramyocellular lipids in patients with and without cancer cachexia.

Preoperative three-dimensional lung volumetry predicts respiratory complications in patients undergoing major liver resection for colorectal metastases.

Colorectal liver metastases (CRLM) are the predominant factor limiting survival in patients with colorectal cancer and liver resection with complete tumor removal is the best treatment option for these patients. This study examines the predictive ability of three-dimensional lung volumetry (3DLV) based on preoperative computerized tomography (CT), to predict postoperative pulmonary complications in patients undergoing major liver resection for CRLM. Patients undergoing major curative liver resection for CRLM between 2010 and 2021 with a preoperative CT scan of the thorax within 6 weeks of surgery, were included.