Interactions of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand (TRAIL) with the Immune System: Implications for Inflammation and Cancer

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL has historically been distinct from the Fas ligand and TNFα in terms of selective apoptosis induction in tumor cells and has a nearly non-existent systemic toxicity. Consequently, in the search for an ideal drug for tumor therapy, TRAIL rapidly drew interest, promising effective tumor control with minimal side effects. However, euphoria gave way to disillusionment as it turned out that carcinoma cells possess or can acquire resistance to TRAIL-induced apoptosis. Additionally, studies on models of inflammation and autoimmunity revealed that TRAIL can influence immune cells in many different ways. While TRAIL was initially found to be an important player in tumor defense by natural killer cells or cytotoxic T cells, additional effects of TRAIL on regulatory T cells and effector T cells, as well as on neutrophilic granulocytes and antigen-presenting cells, became focuses of interest. The tumor-promoting effects of these interactions become particularly important for consideration in cases where tumors are resistant to TRAIL-induced apoptosis. Consequently, murine models have shown that TRAIL can impair the tumor microenvironment toward a more immunosuppressive type, thereby promoting tumor growth. This review summarizes the current state of knowledge on TRAIL’s interactions with the immune system in the context of cancer

A literature review to understand health literacy in men with prostate cancer on active surveillance

Background and Objective: Active surveillance (AS) has been established as an important treatment option for patients with localised prostate cancer (PCa). Current evidence suggests that health literacy is an important facilitator or barrier to choosing and adhering to AS. We aim to understand how the level of health literacy has an impact on choosing and adhering to AS for PCa patients. Methods: We performed a narrative literature review in accordance with the Narrative Review guidelines through the MEDLINE online database via PubMed using two different search strategies to identify the relevant literature. We looked at literature until August 2022. A narrative synthesis was performed to identify if there is any evidence on how studies report health literacy as an outcome in the AS population and if there are any interventions targeting health literacy. Key Content and Findings: We identified 18 studies which looked at health literacy in the PCa context. Health literacy was measured in the context of comprehension of information of patients across PCa stages, decision making across PCa stages and quality of life (QoL) across PCa stages. Lower health literacy had a negative impact on the identified themes. Nine of the identified studies used validated health literacy measures. Interventions targeting health literacy have been used to improve health literacy with a positive impact across the patient journey. Conclusions: Health literacy plays an important role in enabling men to take an active part in their treatment journey. In this review, we presented how health literacy is measured and which interventions targeting health literacy are implemented across PCa. These examples of interventions targeting health literacy should be studied further and translated into the AS setting to improve treatment decision making and adherence to AS.</p

First successful treatment of Clostridium perfringens-associated emphysematous hepatitis: a case report

Emphysematous diseases of the abdomen are rare with an often inconspicuous presentation of symptoms and rapid lethal outcome if untreated. We report the first successfully treated case of Clostridium perfringens-associated emphysematous hepatitis. In the emergency room, a 79-year-old man presented with shortness of breath and deteriorated general condition since the morning of admission. Initial CT scans showed a small but rapidly expanding gas collection in liver segment 6. Emergency surgery with atypical liver resection was performed immediately. With early resection and prolonged administration of antibiotics in the presence of sepsis, the patient recovered successfully and was discharged 37 days after admission. As in our case, prompt diagnosis with early surgical treatment is crucial for the management of emphysematous hepatitis

Comparing the Ligand Behavior of N-Heterocyclic Phosphenium and Nitrosyl Units in Iron and Chromium Complexes

N-Heterocyclic phosphenium (NHP) and nitro-sonium (NO+) ligands are often viewed as isolobal analogues that share the capability to switch between different charge states and thus display redox "noninnocent" behavior. We report here on mixed complexes [(NHP)M(CO)(n)(NO)] (M = Fe, Cr; n = 2, 3), which permit evaluating the donor/acceptor properties of both types of ligands and their interplay in a single complex. The crystalline target compounds were obtained from reactions of N-heterocyclic phosphenium triflates with PPN[Fe(CO)(3)(NO)] or PPN[Cr(CO)(4)-(NO)], respectively, and fully characterized (PPN = nitride-bistriphenylphosphonium cation). The structural and spectroscopic (IR, UV-vis) data support the presence of carbene-analogue NHP ligands with an overall positive charge state and pi-acceptor character. Even if the structural features of the M-NO unit were in all but one product blurred by crystallographic CO/NO disorder, spectroscopic studies and the structural data of the remaining compound suggest that the NO units exhibit nitroxide (NO-) character. This assignment was validated by computational studies, which reveal also that the electronic structure of iron NHP/ NO complexes is closely akin to that of the Hieber anion, [Fe(CO)(3)(NO)](-). The electrophilic character of the NHP units is further reflected in the chemical behavior of the mixed complexes. Cyclic voltammetry and IR-SEC studies revealed that complex [(NHP)Fe(CO)(2) (NO)] (4) undergoes chemically reversible one-electron reduction. Computational studies indicate that the NHP unit in the resulting product carries significant radical character, and the reduction may thus be classified as predominantly ligand-centered. Reaction of 4 with sodium azide proceeded likewise under nucleophilic attack at phosphorus and decomplexation, while super hydride and methyl lithium reacted with all chromium and iron complexes via transfer of a hydride or methyl anion to the NHP unit to afford anionic phosphine complexes. Some of these species were isolated after cation exchange or trapped with electrophiles (H+, SnPh3(+)) to afford neutral complexes representing the products of a formal hydrogenation or hydrostannylation of the original M=P double bond.Peer reviewe

Impact of myopenia and myosteatosis on postoperative outcome and recurrence in Crohn’s disease

PURPOSE: Myopenia and myosteatosis have been proposed to be prognostic factors of surgical outcomes for various diseases, but their exact role in Crohn’s disease (CD) is unknown. The aim of this study is to evaluate their impact on anastomotic leakage, CD recurrence, and postoperative complications after ileocecal resection in patients with CD. METHODS: A retrospective analysis of CD patients undergoing ileocecal resection at our tertiary referral center was performed. To assess myopenia, skeletal muscle index (skeletal muscle area normalized for body height) was measured using an established image analysis method at third lumbar vertebra level on MRI cross-sectional images. Muscle signal intensity was measured to assess myosteatosis index. RESULTS: A total of 347 patients were retrospectively analyzed. An adequate abdominal MRI scan within 12 months prior to surgery was available for 223 patients with median follow-up time of 48.8 months (IQR: 20.0–82.9). Anastomotic leakage rate was not associated with myopenia (SMI: p = 0.363) or myosteatosis index (p = 0.821). Patients with Crohn’s recurrence had a significantly lower SMI (p = 0.047) in univariable analysis, but SMI was not an independent factor for recurrent anastomotic stenosis in multivariable analysis (OR 0.951, 95% CI 0.840–1.078; p = 0.434). Postoperative complications were not associated with myopenia or myosteatosis. CONCLUSION: Based on the largest cohort of its kind with a long follow-up time, we could provide some data that MRI parameters for myopenia and myosteatosis may not be reliable predictors of postoperative outcome or recurrence in patients with Crohn’s disease undergoing ileocecal resection

Evaluation of Open Surgical and Endovascular Treatment Options for Visceral Artery Erosions after Pancreatitis and Pancreatic Surgery

Purpose: To report and compare the results of endovascular and open surgical treatment for erosion bleeding of visceral arteries following pancreatitis and pancreatic surgery. Materials and Methods: This retrospective study included 65 consecutive patients (46 males, mean age 63 +/- 14 years) presenting with visceral artery erosions between January 2011 and December 2020. Endpoints were technical success, freedom from reintervention, stent-graft-related complications, and 30-day and one-year mortality. Results: The causes of erosion bleeding included complications of surgical treatment for the pancreas and upper gastrointestinal tract (75%), pancreatitis (19%), and spontaneous bleeding (6%). Pancreatectomy was performed in 34 (52%) patients, representing 2% of all pancreatectomy procedures (n = 1645) performed in our hospital during the study period. A total of 37 (57%) patients underwent endovascular treatment (EVT), and 28 (43%) patients had open surgery (OS) as a primary treatment. Eight of 37 (22%) patients in the EVT group underwent stent-graft treatment of the eroded vessels and 28 (78%) coil embolization. Six (9%) patients underwent reintervention with no significant differences between EVT and OS groups (11% vs. 7%, p = 0.692). Postoperative morbidity and complications in 52% of all patients were higher in the OS group than in the EVT group (41% vs. 68%, p = 0.029). The in-hospital 30-days mortality rate for all patients was 25%, and it was higher in the OS group than in the EVT group (14% vs. 39%, p = 0.017). Conclusions: An endovascular-first strategy for treating visceral arteries erosions may be preferred to reduce the complications associated with open surgery if patients are hemodynamically stable and have no anastomotic insufficiency. Endovascular treatment may be associated with better in-hospital survival when compared to primary open surgery. Further studies are required to identify the optimal approach

Scoping review protocol : is there a role for physical activity interventions in the treatment pathway of bladder cancer?

Introduction Patients with bladder cancer (BC) have been found to have worse experiences than those with other cancers which may partly be due to impact on quality of life. Currently, little is known about the impact of physical activity (PA) on BC outcomes. This scoping review aims to identify what interventions are available, their reported efficacy and feasibility, and a description of potential underlying biological mechanisms for their effects. Methods and analysis Preferred Reporting Items for Systematic Reviews and Meta-Analyses Scoping Review (ScR) guidelines and the Levac methodology framework will be followed/used. Electronic databases will be searched (MEDLINE, EMBASE, the Cochrane Library, PsycInfo and Health, OpenGray). Two independent reviewers will screen all abstracts and titles and during a second stage and full-text publications for inclusion. All studies describing PA (as an existing lifestyle or as part of an intervention programme) during BC management will be included. Study characteristics will be recorded; qualitative data will be extracted and evaluated using the Donabedian framework. Quantitative data will be extracted and summarised. A further consultation step will be carried out with patients, their family members and healthcare professionals

The Immune Checkpoint Landscape in Tumor Cells of Pancreatic Ductal Adenocarcinoma

Immune checkpoint therapy (ICT) has shown promising potential in the treatment of multiple solid tumors. However, the role of ICT in pancreatic ductal adenocarcinoma (PDAC) remains limited. Patterns of immune checkpoints (ICs) in PDAC represent the basis for establishing a potent ICT. The aim of this study is to create a profile of IC expression and its prognostic relevance in cancer cells of PDAC. Therefore, tumor cells from peripheral and central tissue microarray (TMA) spots from histologically confirmed PDAC of 68 patients after tumor resection were investigated in terms of expressions of TIM3, IDO, B7H4, LAG3, VISTA, and PD-L1 using immunohistochemistry. The presence of the respective ICs was compared to overall survival (OS). The presence of VISTA and PD-L1 significantly correlates with shorter OS (median OS: 22 months vs. 7 months and 22 months vs. 11 months, respectively, p 0.05). The analysis of OS of combined subgroups for VISTA and PD-L1 (VISTA and PD-L1 neg., VISTA pos. and PD-L1 neg., VISTA neg. and PD-L1 pos., and VISTA and PD-L1 pos.) yielded overall statistical significance difference (p = 0.02). These results suggest that the presence of VISTA and PD-L1 is of prognostic relevance and potentially qualifies them as targets for ICT

Perfusion Visualization during Ileal J-Pouch Formation—A Proposal for the Standardization of Intraoperative Imaging with Indocyanine Green Near-Infrared Fluorescence and a Postoperative Follow-Up in IBD Surgery

Background: An anastomotic leak (AL) after a restorative proctocolectomy and an ileal J-pouch increases morbidity and the risk of pouch failure. Thus, a perfusion assessment during J-pouch formation is crucial. While indocyanine green near-infrared fluorescence (ICG-NIRF) has shown potential to reduce ALs, its suitability in a restorative proctocolectomy remains unclear. We aimed to develop a standardized approach for investigating ICG-NIRF and ALs in pouch surgery. Methods: Patients undergoing a restorative proctocolectomy with an ileal J-pouch for ulcerative colitis at an IBD-referral-center were included in a prospective study in which an AL within 30 postoperative days was the primary outcome. Intraoperatively, standardized perfusion visualization with ICG-NIRF was performed and video recorded for postoperative analysis at three time points. Quantitative clinical and technical variables (secondary outcome) were correlated with the primary outcome by descriptive analysis and logistic regression. A novel definition and grading of AL of the J-pouch was applied. A postoperative pouchoscopy was routinely performed to screen for AL. Results: Intraoperative ICG-NIRF-visualization and its postoperative visual analysis in 25 patients did not indicate an AL. The anastomotic site after pouch formation appeared completely fluorescent with a strong fluorescence signal (category 2) in all cases of ALs (4 of 25). Anastomotic site was not changed. ICG-NIRF visualization was reproducible and standardized. Logistic regression identified a two-stage approach vs. a three-stage approach (Odds ratio (OR) = 20.00, 95% confidence interval [CI] = 1.37-580.18, p = 0.029) as a risk factor for ALs. Conclusion: We present a standardized, comparable approach of ICG-NIRF visualization in pouch surgery. Our data indicate that the visual interpretation of ICG-NIRF alone may not detect ALs of the pouch in all cases-quantifiable, objective methods of interpretation may be required in the future

Regulierende Ökosystemleistungen in Fruchtfolgen mit Ackerbohnen (Vicia faba) und Erbsen (Pisum sativum): Quantifizierung, Bewertung und Realisierung (Verbundvorhaben)

Das hier beschriebene Verbundvorhaben umfasst folgende Teilprojekte: FKZ 15EPS016, FKZ 15EPS060 und FKZ 15EPS061. Die kombinierten Wirkungen diversifizierter Fruchtfolgen mit Körnerleguminosen in konventionellen Anbausystemen sind wenig untersucht. Wir haben die Effekte des Anbaus von Ackerbohnen (Vicia faba) auf die Vielfalt und Abundanz von Bestäubern und Raubarthropoden, die biologische Schädlingskontrolle und die Kulturpflanzenbestäubung untersucht. Zudem wurden Vorfrucht- und Nachbarschaftseffekte analysiert. Ökonomische und agronomische Daten wurden anhand von Betriebsbefragungen erhoben. Die Ergebnisse zeigen, dass v. a. Hummeln vom Ackerbohnenanbau profitieren, andere Wildbienen aber von blütenreichen, naturnahen Lebensräumen in der Agrarlandschaft abhängen. Insektenbestäubung ist ein wichtiger Parameter für die Ertragsbildung bei Ackerbohnen und Raps. Es zeigte sich ein positiver Nachbarschaftseffekt der Ackerbohne auf vegetationsbewohnende Nützlinge. Zudem waren die Aktivitätsdichten von Spinnen in Landschaften mit Ackerbohne höher als in Landschaften ohne Ackerbohne. Ackerbohnen können in einzelnen Jahren unter Einbezug des monetären Vorfruchtwerts eine wirtschaftlich konkurrenzfähige Alternative zu den übrigen Hauptkulturen sein, die allerdings stark von den gegebenen Standort- und Witterungsbedingungen beeinflusst wird. Der Anbau von Ackerbohnen bringt landwirtschaftlichen Betrieben agronomische Vorteile. Allerdings zeigte sich auch eine Volatilität in der Wirtschaftlichkeit des Ackerbohnenanbaus. Hinsichtlich der ökologischen Wirkungen sollte der Ackerbohnenanbau mit anderen Maßnahmen (v. a. die Wiederherstellung und der Erhalt von halbnatürlichen Habitaten) kombiniert werden, die auch für die Bereitstellung von Ökosystemleistungen wie biologische Schädlingskontrolle oder Bestäubung von Relevanz sind