External Validation of COVID-19 Risk Scores during Three Waves of Pandemic in a German Cohort-A Retrospective Study.

Several risk scores were developed during the COVID-19 pandemic to identify patients at risk for critical illness as a basic step to personalizing medicine even in pandemic circumstances. However, the generalizability of these scores with regard to different populations, clinical settings, healthcare systems, and new epidemiological circumstances is unknown. The aim of our study was to compare the predictive validity of qSOFA, CRB65, NEWS, COVID-GRAM, and 4C-Mortality score. In a monocentric retrospective cohort, consecutively hospitalized adults with COVID-19 from February 2020 to June 2021 were included; risk scores at admission were calculated. The area under the receiver operating characteristic curve and the area under the precision-recall curve were compared using DeLong's method and a bootstrapping approach. A total of 347 patients were included; 23.6% were admitted to the ICU, and 9.2% died in a hospital. NEWS and 4C-Score performed best for the outcomes ICU admission and in-hospital mortality. The easy-to-use bedside score NEWS has proven to identify patients at risk for critical illness, whereas the more complex COVID-19-specific scores 4C and COVID-GRAM were not superior. Decreasing mortality and ICU-admission rates affected the discriminatory ability of all scores. A further evaluation of risk assessment is needed in view of new and rapidly changing epidemiological evolution.

Real-Time Detection of Tumor Cells during Capture on a Filter Element Significantly Enhancing Detection Rate.

Circulating tumor cells (CTCs) that enter the bloodstream play an important role in the formation of metastases. The prognostic significance of CTCs as biomarkers obtained from liquid biopsies is intensively investigated and requires accurate methods for quantification. The purpose of this study was the capture of CTCs on an optically accessible surface for real-time quantification. A filtration device was fabricated from a transparent material so that capturing of cells could be observed microscopically. Blood samples were spiked with stained tumor cells and the sample was filtrated using a porous structure with pore sizes of 7.4 µm. The possible removal of lysed erythrocytes and the retention of CTCs were assessed. The filtration process was observed in real-time using fluorescence microscopy, whereby arriving cells were counted in order to determine the number of CTCs present in the blood. Through optimization of the microfluidic channel design, the cell retention rate could be increased by 13% (from 76% ± 7% to 89% ± 5%). Providing the possibility for real-time detection significantly improved quantification efficiency even for the smallest cells evaluated. While end-point evaluation resulted in a detection rate of 63% ± 3% of the spiked cells, real-time evaluation led to an increase of 21% to 84% ± 4%. The established protocol provides an advantageous and efficient method for integration of fully automated sample preparation and CTC quantification into a lab-on-a-chip system.

Impact of implementing a non-restrictive antibiotic stewardship program in an emergency department: a four-year quasi-experimental prospective study.

Antibiotic resistance is increasing worldwide. The implementation of antibiotic stewardship programmes (ASPs) is of utmost importance to optimize antibiotic use in order to prevent resistance development without harming patients. The emergency department (ED), cornerstone between hospital and community, represents a crucial setting for addressing ASP implementation; however, evidence data on ASP in ED are poor. In this study, a 4-year, non-restrictive, multi-faceted ASP was implemented in a general ED with the aim to evaluate its impact on antibiotic use and costs. Secondly, the study focused on assessing the impact on length of hospital stay (LOS), Clostridioides difficile infection (CDI) incidence rate, and mortality in the patients' group admitted from ED to medical wards. The ASP implementation was associated with a reduction of antibiotic use and costs. A mild but sustained LOS decrease in all medical wards and a significant downward trend of CDI incidence rate were observed, while mortality did not significantly change. In conclusion, the implementation of our ED-based ASP has demonstrated to be feasible and safe and might clinically benefit the hospital admitted patients' group. Further research is needed to identify the most suitable ASP design for ED and the key outcome measures to reliably assess its effectiveness.

Three different ways of training ultrasound student-tutors yield significant gains in tutee's scanning-skills.

Aim: Many medical universities rely these days on trained student tutors to enable faculty-wide undergraduate ultrasound training. However, there is neither consensus on an optimal method nor any developed and agreed standard in the training of these student tutors. Usually internships and courses are employed which have both a specific set of advantages and disadvantages. We conducted a prospective quasi-randomized study of assess the effects of three types of tutor training on the resulting improvement in scanning skills of their tutees. Methods: Three batches of student tutors were trained by a course only (C-group), by an internship only (I-group) or by a course and an internship (CI-group). The respective gains in ultrasound scanning skills of the tutees were measured prospectively. A total 75 of the 124 5th year medical students (60.5%) who attended the mandatory ultrasound course completed both pre- and post-exams on a voluntary basis. Within a limit of eight minutes and three images, they were asked to depict and label a maximum of 14 anatomical structures. Two blinded raters independently awarded two points for each label with an identifiable structure and one point for each label with a possibly identifiable structure. Results: In all three groups, the tutees improved significantly by more than doubling their pre-score results and comparably (Gains: C-group 9.19±5.73 points, p<.0001, I-group 9.77±4.81 points, p<.0001, CI-group 8.97±5.49 points, p<.0001). Conclusion: Student tutors, who were trained with a course or an internship or a course and an internship could teach scanning skills to 5th year medical students very effectively and with similar success.

[Gastrointestinal complications of the new immune checkpoint inhibitor therapies]. / Gastroenterologische Komplikationen der neuen Immuncheckpoint-Inhibitor-Therapien.

In recent years, immune checkpoint inhibitors (ICPI) have become established as an integral part of drug tumor therapy. They belong to a group of monoclonal antibodies that promote anti-cancer cell immune response. Inhibitory signaling pathways are interrupted by binding to CTLA-4 and PD-1 or PD-L1, which increases the activity of cytotoxic T lymphocytes and reduces the immunological tolerance to tumor cells.Diarrhea - a symptom of enterocolitis - is the most common side effect of ICPI therapy after dermatological phenomena. A combined CTLA-4 and PD-1 blockade may affect up to 44 % of patients. The symptoms of ICPI-associated colitis are similar to the clinical appearance of inflammatory bowel disease.The treatment of affected patients should follow a standardized approach. Both the European and American Oncology Societies offer specific recommendations for the diagnosis and treatment of ICPI-associated adverse reactions. Rapid immunosuppressant treatments, to include steroids and biologics, are necessary to reduce morbidity once differential diagnoses are excluded. It may then be possible to subsequently resume ICPI therapy.Immune-mediated hepatitis is a potential side effect which occurs about 6 to 14 weeks after initiation of therapy. It is usually asymptomatic and characterized by an increase in serum transaminases. Lipasemia, without clinical signs of acute pancreatitis, is a common laboratory finding, which usually has no therapeutic consequence.

Electronic Patient-Reported Outcome Measures in Radiation Oncology: Initial Experience After Workflow Implementation.

BACKGROUND: Mobile health (mHealth) technologies are increasingly used in various medical fields. However, the potential of mHealth to improve patient care in radiotherapy by acquiring electronic patient reported outcome measures (ePROMs) during treatment has been poorly studied so far. OBJECTIVE: The aim of this study was to develop and implement a novel Web app (PROMetheus) for patients undergoing radiotherapy. Herein, we have reported our experience with a focus on feasibility, patient acceptance, and a correlation of ePROMs with the clinical course of the patients. METHODS: In the period between January and June 2018, 21 patients used PROMetheus to score side effects, symptoms, and quality of life-related parameters during and after their treatment. Items of the Patient Reported Outcome version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) were chosen based on the primary site of disease, 27 items for head and neck tumors, 21 items for thoracic tumors, and 24 items for pelvic tumors. RESULTS: In total, 17 out of the 21 patients (81%) regularly submitted ePROMs and more than 2500 data points were acquired. An average of 5.2, 3.5, and 3.3 min was required to complete the head and neck, thorax, and pelvis questionnaires, respectively. ePROMS were able to detect the occurrence of both expected and unexpected side effects during the treatment. In addition, a gradual increase in the severity of side effects over the course the treatment and their remission afterward could be observed with ePROMs. In total, 9 out of the 17 patients (53%), mostly those with head and neck and thoracic cancers, reported PRO-CTCAE grade III or IV fatigue with severe impairments of activities of daily life. CONCLUSIONS: This study shows the successful implementation of an ePROM system and a high patient acceptance. ePROMs have a great potential to improve patient care in radiotherapy by providing a comprehensive documentation of symptoms and side effects, especially of ones that are otherwise underreported.

Outcomes of three different ways to train medical students as ultrasound tutors.

BACKGROUND: In order to provide faculty-wide undergraduate ultrasound training in times of scarce resources, many medical faculties employ trained peer-student tutors to oversee the hands-on training. However, data to guide the training of ultrasound peer-student tutors are scarce. We conducted a prospective quasi-randomized study to assess the gain in theoretical knowledge and practical scanning skills of peer-student tutors who were trained with a course only, an internship only, or the combination of a course and an internship. METHODS: A total of 44 peer-student tutors were trained by a one-week course only (C-Group, n = 21), by an internship only (I-Group, n = 10) or by a course and an internship (CI-Group, n = 13). Prior to and after the completion of the training the peer-student tutors completed an MC-test (theoretical knowledge) and an OSCE (practical scanning skills). RESULTS: With all three education concepts, the peer-student tutors had significant and comparable gains in theoretical knowledge (C-group + 90%, I-group + 61.5%, CI-group + 114.0%) and practical scanning skills (C-group + 112.0%, I-group + 155.0% and CI-group + 123.5%), all p < 0.001. CONCLUSION: Peer-student tutors, who were trained with a course or an internship or a course and internship improved their theoretical knowledge and their practical scanning skills significantly and to a comparable degree.

Platelets in chronic liver disease, from bench to bedside.

In the last decade, numerous studies revealed physiologic and pathophysiologic roles of platelets beyond haemostasis, a process to prevent and stop bleeding. These include the activation of the immune system and the promotion of inflammation, infection and cancer. Hence, the emerging view on the role of platelets has shifted - platelets are now seen as alert "sentinels" of the immune compartment, rather than passive bystanders. Herein, we review well-established and newly discovered features of platelets that define their natural role in maintaining blood haemostasis, but also their functional relationship with other cells of the immune system. We focus on recent studies underlining functional involvement of platelets in chronic liver diseases and cancer, as well as the effects of anti-platelet therapy in these contexts. Finally, we illustrate the potential of platelets as possible diagnostic and therapeutic tools in liver disease based on recently developed methodologies.

[Surveillance after Treatment of Gastrointestinal Cancer]. / Besonderheiten in der Nachsorge von gastrointestinalen Tumoren.

Treatment for gastrointestinal malignancies has evolved over the past two decades. Long-term outcomes have considerably improved, however a high rate of recurrence persists. With the exception of colon cancer, clear consensus strategies with regards to post-treatment surveillance are lacking. Current surveillance practices in non-colon cancer cases are inadequately based on retrospective case analyses and expert recommendations which are not uniformly consistent.This article presents the key follow-up aspects such as recurrence frequency, timing, localization, and therapeutic efficacy for the most common gastrointestinal tumors, and summarizes current recommendations for early detection of recurrence. In particular, we compare and contrast the recommendations of the German S3 guideline, the European Society for Medical Oncology (ESMO) and the American National Comprehensive Cancer Network (NCCN).

Doxycycline regulation in a single retroviral vector by an autoregulatory loop facilitates controlled gene expression in liver cells.

The tetracycline system has limitations in liver cells, such as toxic effects and low controllability. We generated different retroviral vectors for controlled gene expression in liver cells, in which the regulatory elements were arranged in different patterns. Only the organization of the tetracycline system in an autoregulatory loop in the sense orientation results in high retroviral titres and in tight regulation of gene expression in highly differentiated hepatoma cells. Because of the toxicity of the transactivator tTA, it was impossible to establish doxycycline-dependent stable HepG2 cell lines. To avoid sequelching-related toxicity in liver cells, we replaced tTA with new non-toxic transactivators. By using tTA2, tTA3 and tTA4, we observed tight doxycycline-dependent gene expression in 23, 49 and 45% of the isolated clones. The tTA4 vector was used to transduce hepatocytes of mice in vivo. Tight doxycycline-controllable gene regulation was also observed in the liver of mice, confirming our hypothesis that retroviral vectors with autoregulatory loops of the tetracycline system facilitate inducible gene expression in the liver in vivo. Our new retroviral vector system allows rapid isolation of controllable clones in a very high yield and should make the tetracycline system more applicable to liver-derived cells and in liver gene therapy in vivo.

Caspase 8 small interfering RNA prevents acute liver failure in mice.

A major concern in therapy of acute liver failure is protection of hepatocytes to prevent apoptosis and maintain liver function. Small interfering RNA (siRNA) is a powerful tool to silence gene expression in mammalian cells. To evaluate the therapeutic efficacy of siRNA in vivo we used different mouse models of acute liver failure. We directed 21-nt siRNAs against caspase 8, which is a key enzyme in death receptor-mediated apoptosis. Systemic application of caspase 8 siRNA results in inhibition of caspase 8 gene expression in the liver, thereby preventing Fas (CD95)-mediated apoptosis. Protection of hepatocytes by caspase 8 siRNA significantly attenuated acute liver damage induced by agonistic Fas (CD95) antibody (Jo2) or by adenovirus expressing Fas ligand (AdFasL). However, in a clinical situation the siRNAs most likely would be applied after the onset of acute liver failure. Therefore we injected caspase 8 siRNA at a time point during AdFasL- and adenovirus wild type (Adwt)-mediated liver failure with already elevated liver transaminases. Improvement of survival due to RNA interference was significant even when caspase 8 siRNA was applied during ongoing acute liver failure. In addition, it is of particular interest that caspase 8 siRNA treatment was successful not only in acute liver failure mediated by specific Fas agonistic agents (Jo2 and AdFasL) but also in acute liver failure mediated by Adwt, which is an animal model reflecting multiple molecular mechanisms involved in human acute viral hepatitis. Consequently, our data raise hope for future successful application of siRNA in patients with acute liver failure.