Angiogenic miRNAs, the angiopoietin axis and related TIE2-expressing monocytes affect outcomes in cholangiocarcinoma

Background: Tumour angiogenesis is modulated on both an epigenetic and protein level and has potential implications for immune cell responses. However, the importance of related angiogenic biomarkers in cholangiocarcinoma (CCA) is unknown. This study assessed human CCA samples for the expression of angiogenesisassociated microRNAs, angiopoietins (Angs) and monocytes expressing the Angreceptor, TIE2, with regards to prognostic significance after liver resection. Methods: Angiogenic miRNAs were analysed in frozen samples of intrahepatic CCA (iCC; n = 43) and hilar CCA (HC; n = 45). Ang-1 and Ang-2, as well as TIE2- expressing monocytes (TEMs), were detected in paraffin-embedded iCC sections (n = 88). MiRNA expression and the abundance of TEMs and Angs were correlated with clinicopathological characteristics and survival. Results: MiR-126 was downregulated in 76.7% of all CCA samples, with high relative expression associated with smaller tumours and reduced lymph node metastasis. High Ang-1 expression was associated with less lymphangiosis carcinomatosa and better histological grading (all p < 0.05). The absence of TEMs in iCC correlated with elevated CA19-9 levels. High relative miR-126 and low miR-128 levels were associated with improved survival in iCC and HC, respectively (all p < 0.05). High miR-126, low miR-128 and TEMs were independent prognostic factors for recurrence-free and overall survival (all p < 0.05). Conclusions: These results suggest that angiogenic miRNAs, Angs and TEMs are of prognostic value in CCA. In addition to the possible functional links between angiogenic miRNA expression profiles, Angs and immune-cell responses by TEMs, these data have clinical implications as novel diagnostic tools

Telehealth interventions in outpatient psychotherapy practices (TIpp)

Based on epidemiological studies, the number of mental illnesses in Germany is steadily increasing. While 15,6 million people were affected by mental illness in 1998, this figure will rise to almost 18 million in 2022 (Wittich et al., 2001). The care of mentally ill people represents a complex challenge for the entire healthcare system. The need for people who require psychotherapeutic help is therefore continuously increasing. The existing structural supply problem is primarily characterized by a low number of outpatient and inpatient therapy places (Gerhardinger, 2022). If the waiting time nationwide in 2018 for a therapy place was already 22 weeks, there are significantly fewer treatment places available due to the effects related to the Corona pandemic, so that waiting times can be up to 9 months (Deutsches Ärzteblatt, 2021; Bundespsychotherapeuten Kammer, 2021). Due to the low level of care in rural areas, people there have to wait even longer for therapeutic treatment than in large cities (Walendzik et al., 2014). A large proportion of people with mental illness have no access to therapeutic help due to insufficient care options (Landespsychotherapeutenkammer Rheinland-Pfalz, 2022). This raises the question of what therapeutic interventions and services can be used to counteract the underuse of people with mental illness? Since 2019, when the Digital Health Care Act comes into force, digital health applications may be prescribed as a health insurance benefit (Bundesministerium für Gesundheit, 2020). Through telemedical offers in psychotherapy, patients can be treated with the help of digital communication media independent of location and time (Marx et al., 2021). The possibility of telemedical, cross-sector care for patients can minimize existing deficits within the care structure and enable better patient care (Weitzel et al., 2021). In the wake of the Covid-19 pandemic and the associated contact restrictions that went into effect to contain the pandemic in the spring of 2020, digital consultations, such as video consultations, were used by many outpatient psychotherapists in Germany to maintain outpatient care for people with mental illnesses (Beck-Hiestermann et al.,2021). Digital therapy interventions in some cases completely replaced the traditional face-to-face setting in psychotherapy and thus became the focus of psychotherapists' daily work (Richter et al., 2020). The Covid-19 Pandemic can thus be described as a catalyst for digital psychotherapy interventions in Germany. The focus of previous studies (during the Covid-19 pandemic) was only on the usage behavior and satisfaction of medical-therapeutic staff (physicians, psychiatrists and therapists) with video consultation (Oberman, 2020). Representative results from patients, who were equally affected by the changeover to digital therapy settings, are completely missing, as are study results from the group of psychotherapists working in outpatient settings on general satisfaction with digital interventions in Germany, combined with the survey of change requests (usability) with regard to digital interventions in psychotherapy. Digital psychotherapy applications enable psychotherapeutic interventions for a variety of disorders independent of time and place. However, the usage behavior and acceptance of these digital applications by therapists in private practice have not yet been sufficiently investigated. Therefore, the aim of the TIpP study is to evaluate the usage behavior of therapists and patients of telemedical interventions in psychotherapy, the satisfaction with digital offers and the interest in the integration of digital applications in the therapeutic everyday life

Internet-based cognitive behavioral therapy in children and adolescents with obsessive-compulsive disorder: A randomized controlled trial

OBJECTIVES: Obsessive-compulsive disorder (OCD) in childhood and adolescence often leads to significant impairment in various areas of life and has a high risk of becoming chronic. Cognitive behavioral therapy (CBT) is the recommended first-line treatment, but it is too rarely implemented in accordance with guidelines and is often not available close to the patient’s home. Importantly, internet-based CBT could help to reduce this gap in care. Having previously successfully demonstrated the feasibility of an internet-based CBT approach, we aimed to assess its effectiveness in a waiting list controlled randomized trial. METHODS: Children and adolescents aged 6–18 years with a principal diagnosis of OCD received 14 sessions of therapist-delivered CBT via videoconference distributed over 16 weeks. After inclusion, participants were randomly assigned to either the treatment or waiting list group. Participants in the treatment group began treatment immediately after baseline diagnostics, and participants in the waiting list group began treatment after a 16-week waiting period. The primary outcome was a pre-post comparison of OCD symptoms as measured with the Children’s Yale-Brown Obsessive Compulsive Scale (CY-BOCS). Additionally, remission was an important outcome measure. Follow-up assessments were conducted for all measures 16 and 32 weeks after completion of treatment. RESULTS: A total of 60 children and adolescents were included into the analyses. Over the course of the treatment, OCD symptoms according to the CY-BOCS significantly decreased in the treatment group compared to the waiting-list control group. Cohen’s d between groups was 1.63. After the patients in the waiting list group also received the treatment, the OCD symptoms decreased significantly in this group as well. This improvement of symptoms increased over the course of the follow-up assessments. Remission rate peaked at the 32-week follow-up, with 68% in the treatment group and 79% in the waiting list group. Importantly, patient satisfaction with treatment was high to very high. CONCLUSION: In our study, OCD symptoms decreased significantly and remission rate was high after internet-based CBT. Those effects were comparable to those found in studies of face-to-face treatment. Although further evidence is needed, these are early indications that our approach may be a viable way to provide access to adequate treatment for children and adolescents affected by OCD. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [NCT05037344]

The SSTeP-KiZ System&mdash;Secure Real-Time Communication Based on Open Web Standards for Multimodal Sensor-Assisted Tele-Psychotherapy

In this manuscript, we describe the soft- and hardware architecture as well as the implementation of a modern Internet of Medical Things (IoMT) system for sensor-assisted telepsychotherapy. It enables telepsychotherapy sessions in which the patient exercises therapy-relevant behaviors in their home environment under the remote supervision of the therapist. Wearable sensor information (electrocardiogram (ECG), movement sensors, and eye tracking) is streamed in real time to the therapist to deliver objective information about specific behavior-triggering situations and the stress level of the patients. We describe the IT infrastructure of the system which uses open standards such as WebRTC and OpenID Connect (OIDC). We also describe the system&rsquo;s security concept, its container-based deployment, and demonstrate performance analyses. The system is used in the ongoing study SSTeP-KiZ (smart sensor technology in telepsychotherapy for children and adolescents with obsessive-compulsive disorder) and shows sufficient technical performance

High rate of Ki-67 increase in entero-pancreatic NET relapses after surgery with curative intent.

Neuroendocrine neoplasms (NENs) present with advanced disease at diagnosis in up to 28% of cases, precluding the possibility of curative-intent surgery. Histopathological heterogeneity of this disease can be observed inter-individually as well as intra-individually during disease course. The present study aimed to assess the frequency of Ki-67 change after radical surgery, in a series of patients with radically resected entero-pancreatic neuroendocrine tumors (EP-NETs). We present the analysis of a multicenter, retrospective, series of EP-NETs G1-G2 recurring after radical resection and with histological re-evaluation at disease recurrence (DR). The primary endpoint was the description of Ki-67 change at DR compared to time of surgery. The secondary endpoint was assessment of recurrence-free survival (RFS) rates. In total, 47 patients had a second histological evaluation and could be included in the present study. Median Ki-67 at surgery was 3% (range 1-15%) but, at DR, a significant increase in the value was observed (7%, range 1-30%; p < .01) and involved 66.0% of cases, with a corresponding increase in tumor grading in 34.0% (p = .05). Median RFS of the overall population was 40 months, and was worse when Ki-67 increased at DR vs. stable Ki-67 value (36 vs. 61 months, respectively; p = .02). In conclusion, in more than half of the cases with relapse after radical surgery, a higher proliferative index with a potentially more aggressive potential was observed. Therefore, histological reassessment should be considered on DR because tailored therapeutic strategies may be required for these patients

Urinary Biomarkers α-GST and π-GST for Evaluation and Monitoring in Living and Deceased Donor Kidney Grafts

The aim of this study was to analyze the value of urine α- and π-GST in monitoring and predicting kidney graft function following transplantation. In addition, urine samples from corresponding organ donors was analyzed and compared with graft function after organ donation from brain-dead and living donors. Urine samples from brain-dead (n = 30) and living related (n = 50) donors and their corresponding recipients were analyzed before and after kidney transplantation. Urine α- and π-GST values were measured. Kidney recipients were grouped into patients with acute graft rejection (AGR), calcineurin inhibitor toxicity (CNI), and delayed graft function (DGF), and compared to those with unimpaired graft function. Urinary π-GST revealed significant differences in deceased kidney donor recipients with episodes of AGR or DGF at day one after transplantation (p = 0.0023 and p = 0.036, respectively). High π-GST values at postoperative day 1 (cutoff: >21.4 ng/mg urine creatinine (uCrea) or >18.3 ng/mg uCrea for AGR or DGF, respectively) distinguished between rejection and no rejection (sensitivity, 100%; specificity, 66.6%) as well as between DGF and normal-functioning grafts (sensitivity, 100%; specificity, 62.6%). In living donor recipients, urine levels of α- and π-GST were about 10 times lower than in deceased donor recipients. In deceased donors with impaired graft function in corresponding recipients, urinary α- and π-GST were elevated. α-GST values >33.97 ng/mg uCrea were indicative of AGR with a sensitivity and specificity of 77.7% and 100%, respectively. In deceased donor kidney transplantation, evaluation of urinary α- and π-GST seems to predict different events that deteriorate graft function. To elucidate the potential advantages of such biomarkers, further analysis is warranted