Prospectively investigating the impact of AI onshared decision-making in post kidney transplant care (PRIMA-AI): protocol for a longitudinal qualitative study among patients, their support persons and treating physicians at a tertiary care centre.

Introduction: As healthcare is shifting from a paternalistic to a patient-centred approach, medical decision making becomes more collaborative involving patients, their support persons (SPs) and physicians. Implementing shared decision-making (SDM) into clinical practice can be challenging and becomes even more complex with the introduction of artificial intelligence (AI) as a potential actant in the communicative network. Although there is more empirical research on patients' and physicians' perceptions of AI, little is known about the impact of AI on SDM.

Bayesian modelling of time series data (BayModTS)-a FAIR workflow to process sparse and highly variable data.

Motivation: Systems biology aims to better understand living systems through mathematical modelling of experimental and clinical data. A pervasive challenge in quantitative dynamical modelling is the integration of time series measurements, which often have high variability and low sampling resolution. Approaches are required to utilize such information while consistently handling uncertainties.

Quantifying fat zonation in liver lobules: an integrated multiscale in silico model combining disturbed microperfusion and fat metabolism via a continuum biomechanical bi-scale, tri-phasic approach.

Metabolic zonation refers to the spatial separation of metabolic functions along the sinusoidal axes of the liver. This phenomenon forms the foundation for adjusting hepatic metabolism to physiological requirements in health and disease (e.g.

Future Directions in the Diagnosis and Treatment of APDS and IEI: a Survey of German IEI Centers.

Introduction: The diagnosis and treatment of inborn errors of immunity (IEI) is a major challenge as the individual conditions are rare and often characterized by a variety of symptoms, which are often non disease-specific. Ideally, patients are treated in dedicated centers by physicians who specialize in the management of primary immune disorders. In this study, we used the example of Activated PI3Kδ syndrome (APDS), a rare IEI with an estimated prevalence of 1:1,000,000.

Comparison of uniportal robotic-assisted thoracic surgery pulmonary anatomic resections with multiport robotic-assisted thoracic surgery: a multicenter study of the European experience.

Background: Robotic-assisted thoracic surgery (RATS) has seen increasing interest in the last few years, with most procedures primarily being performed in the conventional multiport manner. Our team has developed a new approach that has the potential to convert surgeons from uniportal video-assisted thoracic surgery (VATS) or open surgery to robotic-assisted surgery, uniportal-RATS (U-RATS). We aimed to evaluate the outcomes of one single incision, uniportal robotic-assisted thoracic surgery (U-RATS) against standard multiport RATS (M-RATS) with regards to safety, feasibility, surgical technique, immediate oncological result, postoperative recovery, and 30-day follow-up morbidity and mortality.

Periportal steatosis in mice affects distinct parameters of pericentral drug metabolism.

Little is known about the impact of morphological disorders in distinct zones on metabolic zonation. It was described recently that periportal fibrosis did affect the expression of CYP proteins, a set of pericentrally located drug-metabolizing enzymes. Here, we investigated whether periportal steatosis might have a similar effect.

The single-cell transcriptional landscape of lung carcinoid tumors.

Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread. Several recent single-cell studies have provided detailed insights into the cellular heterogeneity of more common lung cancers, such as adeno- and squamous cell carcinoma.

Prediction of Survival After Partial Hepatectomy Using a Physiologically Based Pharmacokinetic Model of Indocyanine Green Liver Function Tests.

The evaluation of hepatic function and functional capacity of the liver are essential tasks in hepatology as well as in hepatobiliary surgery. Indocyanine green (ICG) is a widely applied test compound that is used in clinical routine to evaluate hepatic function. Important questions for the functional evaluation with ICG in the context of hepatectomy are how liver disease such as cirrhosis alters ICG elimination, and if postoperative survival can be predicted from preoperative ICG measurements.

Hepatectomy-Induced Alterations in Hepatic Perfusion and Function - Toward Multi-Scale Computational Modeling for a Better Prediction of Post-hepatectomy Liver Function.

Liver resection causes marked perfusion alterations in the liver remnant both on the organ scale (vascular anatomy) and on the microscale (sinusoidal blood flow on tissue level). These changes in perfusion affect hepatic functions via direct alterations in blood supply and drainage, followed by indirect changes of biomechanical tissue properties and cellular function. Changes in blood flow impose compression, tension and shear forces on the liver tissue.

Surgical Ventricular Reconstruction Eligible for Late Assist Device Implantation.

In patients with ischemic cardiomyopathy and left ventricular aneurysm formation who are symptomatic despite optimal medical therapy, it is challenging to determine whether surgical ventricular reconstruction, heart transplantation, or left ventricular assist device (LVAD) implantation is the treatment of choice. This report describes the concept of surgical ventricular reconstruction with a specially prepared LVAD fixation ring to facilitate subsequent LVAD implantation if required. In the patient reported in this case, endoventricular circular LVAD ring plasty sufficiently reduced the ventricular volume, normalized the left ventricular geometry, and subsequently led to an improvement of left ventricular ejection fraction.

Single-cell RNA sequencing reveals distinct tumor microenvironmental patterns in lung adenocarcinoma.

Recent developments in immuno-oncology demonstrate that not only cancer cells, but also the tumor microenvironment can guide precision medicine. A comprehensive and in-depth characterization of the tumor microenvironment is challenging since its cell populations are diverse and can be important even if scarce. To identify clinically relevant microenvironmental and cancer features, we applied single-cell RNA sequencing to ten human lung adenocarcinomas and ten normal control tissues.

Neutrophil Gelatinase-Associated Lipocalin Protects from ANCA-Induced GN by Inhibiting T17 Immunity.

Background: Neutrophil gelatinase-associated lipocalin (NGAL) is a diagnostic marker of intrinsic kidney injury produced by damaged renal cells and by neutrophils. ANCA-associated vasculitis features necrotizing crescentic GN (NCGN), and ANCA-activated neutrophils contribute to NCGN. Whether NGAL plays a mechanistic role in ANCA-associated vasculitis is unknown.

Metformin plus megestrol acetate compared with megestrol acetate alone as fertility-sparing treatment in patients with atypical endometrial hyperplasia and well-differentiated endometrial cancer: a randomised controlled trial.

Objective: To assess the efficacy of metformin in megestrol acetate (MA)-based fertility-sparing treatment for patients with atypical endometrial hyperplasia (AEH) and endometrioid endometrial cancer (EEC).

Design: A randomised, single-centre, open-label, controlled trial conducted between October 2013 and December 2017.

Setting: Shanghai OBGYN Hospital of Fudan University, China.

Perspectives of the International Society for Cell & Gene Therapy Gastrointestinal Scientific Committee on the Intravenous Use of Mesenchymal Stromal Cells in Inflammatory Bowel Disease (PeMeGi).

Inflammatory bowel disease (IBD), namely, Crohn's disease and ulcerative colitis, remains a grievous and recalcitrant problem incurring significant human and health care costs, even in consideration of the growing incidence. Initial goals of care aimed to achieve the induction and maintenance of clinical remission. The advent of novel treat-to-target approaches using patient stratification, early introduction of immunosuppressants and rapid escalation to biologics or early use of combination therapy has refocused the goals of care toward the achievement of mucosal healing.

A novel approach reveals that HLA class 1 single antigen bead-signatures provide a means of high-accuracy pre-transplant risk assessment of acute cellular rejection in renal transplantation.

Background: Acute cellular rejection (ACR) is associated with complications after kidney transplantation, such as graft dysfunction and graft loss. Early risk assessment is therefore critical for the improvement of transplantation outcomes. In this work, we retrospectively analyzed a pre-transplant HLA antigen bead assay data set that was acquired by the e:KID consortium as part of a systems medicine approach.

Mucosal Autoimmunity to Cell-Bound GP2 Isoforms Is a Sensitive Marker in PSC and Associated With the Clinical Phenotype.

Zymogen granule glycoprotein 2 (GP2) was demonstrated as first autoimmune mucosal target in primary sclerosing cholangitis (PSC) associated with disease severity. Autoantibodies to four GP2 isoforms (aGP2) were found in patients with inflammatory bowel diseases but reactivity against specific GP2 epitopes has not been investigated in PSC yet. Hence, the prevalence of aGP2 and their association with the PSC phenotype for risk prediction were examined.

HEPATOKIN1 is a biochemistry-based model of liver metabolism for applications in medicine and pharmacology.

The epidemic increase of non-alcoholic fatty liver diseases (NAFLD) requires a deeper understanding of the regulatory circuits controlling the response of liver metabolism to nutritional challenges, medical drugs, and genetic enzyme variants. As in vivo studies of human liver metabolism are encumbered with serious ethical and technical issues, we developed a comprehensive biochemistry-based kinetic model of the central liver metabolism including the regulation of enzyme activities by their reactants, allosteric effectors, and hormone-dependent phosphorylation. The utility of the model for basic research and applications in medicine and pharmacology is illustrated by simulating diurnal variations of the metabolic state of the liver at various perturbations caused by nutritional challenges (alcohol), drugs (valproate), and inherited enzyme disorders (galactosemia).

Long-term Efficacy and Safety of Stem Cell Therapy (Cx601) for Complex Perianal Fistulas in Patients With Crohn's Disease.

Background & Aims: Therapies for perianal fistulas in patients with Crohn's disease are often ineffective in producing long-term healing. We performed a randomized placebo-controlled trial to determine the long-term efficacy and safety of a single local administration of allogeneic expanded adipose-derived stem cells (Cx601) in patients with Crohn's disease and perianal fistulas.

Methods: We performed a double-blind study at 49 hospitals in Europe and Israel, comprising 212 patients with Crohn's disease and treatment-refractory, draining, complex perianal fistulas.

Computational Modeling in Liver Surgery.

The need for extended liver resection is increasing due to the growing incidence of liver tumors in aging societies. Individualized surgical planning is the key for identifying the optimal resection strategy and to minimize the risk of postoperative liver failure and tumor recurrence. Current computational tools provide virtual planning of liver resection by taking into account the spatial relationship between the tumor and the hepatic vascular trees, as well as the size of the future liver remnant.

Evaluation of adherence and tolerability of prolonged-release tacrolimus (Advagraf™) in kidney transplant patients in Germany: A multicenter, noninterventional study.

This study assessed adherence to prolonged-release tacrolimus (PR-T)-based immunosuppression during routine maintenance of renal transplant recipients in Germany. Patients had received PR-T for ≥1 month at inclusion. Data were collected during four visits (V): baseline (V1), 6 (V2), 12 (V3), and 18 (V4) months.

Liver Preservation by Aortic Perfusion Alone Compared With Preservation by Aortic Perfusion and Additional Arterial Ex Situ Back-Table Perfusion With Histidine-Tryptophan-Ketoglutarate Solution: A Prospective, Randomized, Controlled, Multicenter Study.

Background: Arterial ex situ back-table perfusion (BP reportedly reduces ischemic-type biliary lesion after liver transplantation. We aimed to verify these findings in a prospective investigation.

Methods: Our prospective, randomized, controlled, multicenter study involved livers retrieved from patients in 2 German regions, and compared the outcomes of standard aortic perfusion to those of aortic perfusion combined with arterial ex situ BP.

Chimeric PD-1:28 Receptor Upgrades Low-Avidity T cells and Restores Effector Function of Tumor-Infiltrating Lymphocytes for Adoptive Cell Therapy.

Inherent intermediate- to low-affinity T-cell receptors (TCR) that develop during the natural course of immune responses may not allow sufficient activation for tumor elimination, making the majority of T cells suboptimal for adoptive T-cell therapy (ATT). TCR affinity enhancement has been implemented to provide stronger T-cell activity but carries the risk of creating undesired cross-reactivity leading to potential serious adverse effects in clinical application. We demonstrate here that engineering of low-avidity T cells recognizing a naturally processed and presented tumor-associated antigen with a chimeric PD-1:28 receptor increases effector function to levels seen with high-avidity T cells of identical specificity.