Prognostic Significance of Erythropoietin in Pancreatic Adenocarcinoma

BACKGROUND: Erythropoietin (Epo) administration has been reported to have tumor-promoting effects in anemic cancer patients. We investigated the prognostic impact of endogenous Epo in patients with pancreatic ductal adenocarcinoma (PDAC). METHODOLOGY: The clinico-pathological relevance of hemoglobin (Hb, n = 150), serum Epo (sEpo, n = 87) and tissue expression of Epo/Epo receptor (EpoR, n = 104) was analyzed in patients with PDAC. Epo/EpoR expression, signaling, growth, invasion and chemoresistance were studied in Epo-exposed PDAC cell lines. RESULTS: Compared to donors, median preoperative Hb levels were reduced by 15% in both chronic pancreatitis (CP, p<0.05) and PDAC (p<0.001), reaching anemic grade in one third of patients. While inversely correlating to Hb (r = -0.46), 95% of sEPO values lay within the normal range. The individual levels of compensation were adequate in CP (observed to predicted ratio, O/P = 0.99) but not in PDAC (O/P = 0.85). Strikingly, lower sEPO values yielding inadequate Epo responses were prominent in non-metastatic M0-patients, whereas these parameters were restored in metastatic M1-group (8 vs. 13 mU/mL; O/P = 0.82 vs. 0.96; p<0.01)--although Hb levels and the prevalence of anemia were comparable. Higher sEpo values (upper quartile ≥ 16 mU/ml) were not significantly different in M0 (20%) and M1 (30%) groups, but were an independent prognostic factor for shorter survival (HR 2.20, 10 vs. 17 months, p<0.05). The pattern of Epo expression in pancreas and liver suggested ectopic release of Epo by capillaries/vasa vasorum and hepatocytes, regulated by but not emanating from tumor cells. Epo could initiate PI3K/Akt signaling via EpoR in PDAC cells but failed to alter their functions, probably due to co-expression of the soluble EpoR isoform, known to antagonize Epo. CONCLUSION/SIGNIFICANCE: Higher sEPO levels counteract anemia but worsen outcome in PDAC patients. Further trials are required to clarify how overcoming a sEPO threshold ≥16 mU/ml by endogenous or exogenous means may predispose to or promote metastatic progression

Lessons learned from a multimodal sensor-based eHealth approach for treating pediatric obsessive-compulsive disorder

IntroductionThe present study investigates the feasibility and usability of a sensor-based eHealth treatment in psychotherapy for pediatric obsessive-compulsive disorder (OCD), and explores the promises and pitfalls of this novel approach. With eHealth interventions, therapy can be delivered in a patient's home environment, leading to a more ecologically valid symptom assessment and access to experts even in rural areas. Furthermore, sensors can help indicate a patient's emotional and physical state during treatment. Finally, using sensors during exposure with response prevention (E/RP) can help individualize therapy and prevent avoidance behavior.MethodsIn this study, we developed and subsequently evaluated a multimodal sensor-based eHealth intervention during 14 video sessions of cognitive-behavioral therapy (CBT) in 20 patients with OCD aged 12-18. During E/RP, we recorded eye movements and gaze direction via eye trackers, and an ECG chest strap captured heart rate (HR) to identify stress responses. Additionally, motion sensors detected approach and avoidance behavior.ResultsThe results indicate a promising application of sensor-supported therapy for pediatric OCD, such that the technology was well-accepted by the participants, and the therapeutic relationship was successfully established in the context of internet-based treatment. Patients, their parents, and the therapists all showed high levels of satisfaction with this form of therapy and rated the wearable approach in the home environment as helpful, with fewer OCD symptoms perceived at the end of the treatment.DiscussionThe goal of this study was to gain a better understanding of the psychological and physiological processes that occur in pediatric patients during exposure-based online treatment. In addition, 10 key considerations in preparing and conducting sensor-supported CBT for children and adolescents with OCD are explored at the end of the article. This approach has the potential to overcome limitations in eHealth interventions by allowing the real-time transmission of objective data to therapists, once challenges regarding technical support and hardware and software usability are addressed. Clinical Trial Registrationwww.ClinicalTrials.gov, identifier (NCT05291611)

The global geology of Rhea: preliminary implications from the Cassini ISS data

With a mean diameter of 1528 km, Rhea is the second-largest satellite of Saturn. The low average density of 1.233 g cm-3 and water ice absorption bands imply that Rhea's interior and its surface are dominated by water ice. Rhea was imaged by the cameras aboard the Cassini Orbiter at spatial resolutions up 10 m/pxl. Rhea's surface is charaterized by densely cratered plains dating back to a period of at least 4.2 billion years ago. Oldest features in the cratered plains are impact basins several 100 km in diameter. Cassini ISS has revealed tectonic features indicative of extensional, compressional and shear stresses which possibly were active prior to 3 billion years ago. One of the youngest features found on Rhea is a bright crater, about 48 km in diameter, with an extended system of bright rays. The butterfly wing pattern of these ejecta suggest an oblique impact from the east

Geomorphology of Saturn's satellite Rhea: preliminary implications from the Cassini ISS data

With a mean diameter of 1528 km, Rhea is Saturn's second-largest satellite. The cameras aboard the Cassini Orbiter have imaged Rhea at resolutions up to 10 m/pxl. At regional image scale (e.g. 350 m/pxl), the densely cratered plains show little variation in terms of albedo and morphology. Large craters and impact stuctures (basins) are abundant. The cratered plains date back to a time of about 4.2 billion years. Ring structures have only one or two rings. Tectonic features provide evidence of extensional, compressive and shear stresses which also appear to have been active at earliest times, possibly at least 3 billion years ago or more

Tectonic features on Saturn's satellites Dione and Rhea: Morphology and stratigraphy derived from Cassini ISS images

Cassini ISS images were used to derive a stratigraphic sequence of tectonic features on the two mid-sized Saturnian satellites Dione and Rhe