Pulmonary lesions in early response assessment in pediatric Hodgkin lymphoma: prevalence and possible implications for initial staging.

BACKGROUND: Disseminated pulmonary involvement in pediatric Hodgkin lymphoma (pHL) is indicative of Ann Arbor stage IV disease. During staging, it is necessary to assess for coexistence of non-malignant lung lesions due to infection representing background noise to avoid erroneously upstaging with therapy intensification. OBJECTIVE: This study attempts to describe new lung lesions detected on interim staging computed tomography (CT) scans after two cycles of vincristine, etoposide, prednisolone, doxorubicin in a prospective clinical trial. Based on the hypothesis that these new lung lesions are not part of the underlying malignancy but are epiphenomena, the aim is to analyze their size, number, and pattern to help distinguish true lung metastases from benign lung lesions on initial staging. MATERIALS AND METHODS: A retrospective analysis of the EuroNet-PHL-C1 trial re-evaluated the staging and interim lung CT scans of 1,300 pediatric patients with HL. Newly developed lung lesions during chemotherapy were classified according to the current Fleischner glossary of terms for thoracic imaging. Patients with new lung lesions found at early response assessment (ERA) were additionally assessed and compared to response seen in hilar and mediastinal lymph nodes. RESULTS: Of 1,300 patients at ERA, 119 (9.2%) had new pulmonary lesions not originally detectable at diagnosis. The phenomenon occurred regardless of initial lung involvement or whether a patient relapsed. In the latter group, new lung lesions on ERA regressed by the time of relapse staging. New lung lesions on ERA in patients without relapse were detected in 102 (7.8%) patients. Pulmonary nodules were recorded in 72 (5.5%) patients, the majority (97%) being<10 mm. Consolidations, ground-glass opacities, and parenchymal bands were less common. CONCLUSION: New nodules on interim staging are common, mostly measure less than 10 mm in diameter and usually require no further action because they are most likely non-malignant. Since it must be assumed that benign and malignant lung lesions coexist on initial staging, this benign background noise needs to be distinguished from lung metastases to avoid upstaging to stage IV disease. Raising the cut-off size for lung nodules to ≥ 10 mm might achieve the reduction of overtreatment but needs to be further evaluated with survival data. In contrast to the staging criteria of EuroNet-PHL-C1 and C2, our data suggest that the number of lesions present at initial staging may be less important.

Covert hepatic encephalopathy and spontaneous portosystemic shunts increase the risk of developing overt hepatic encephalopathy.

AIM: The aim of the study was to evaluate the presence of covert hepatic encephalopathy (cHE) and its characteristics according to the presence of spontaneous portosystemic shunts (SPSS) and their influence on the development of overt hepatic encephalopathy. METHODS: Secondary analysis of a multicentre study, which evaluated the association between SPSS and complications of cirrhosis. The present study population includes those patients who also underwent cHE diagnostic evaluation. Presence of SPSS was evaluated by cross-sectional imaging and quantified by total SPSS-area. Logistic and Cox-regression competing risk analyses were performed. RESULTS: About 65 patients were included of age 58 (IQR 50-66), MELD 15 (IQR 10-20), with alcoholic liver disease 63%. Thirty-two patients (49%) had cHE, had higher MELD [16 (IQR 12-24) vs 13 (IQR 9-17), P = .027], a greater proportion of SPSS [n = 18 (56%) vs n = 8 (24%); P = .008] and a higher total cross-sectional SPSS-area [28.3 (0-94.2) vs 0 (0-14.1); P = .005]. On multivariate analysis MELD [OR 1.11 (95% CI 1.01-1.21)] and presence of SPSS [OR 3.95 (95% CI 1.22-12.80)] were independently associated to cHE at baseline. During follow-up cHE was an independent predictor of oHE [cHE: HR 6.93 (95% CI 2.64-18.20). The effect of cHE on the development of oHE was greater in patients with SPSS [only cHE: HR 5.66 (95% CI 1.82-17.62), cHE and SPSS: HR 8.63 (95% CI 3.15-23.65)]. CONCLUSIONS: cHE is independently associated to the presence of SPSS (and total cross-sectional SPSS-area) and MELD. Furthermore, the presence of SPSS seems to increase the risk of cHE of developing of overt hepatic encephalopathy.

Development and evaluation of a software system for medical students to teach and practice anamnestic interviews with virtual patient avatars.

BACKGROUND AND OBJECTIVES: Taking a medical history is a core competence of the diagnostic process. At the beginning of their study medical students need to learn and practice the necessary techniques, initially focusing on good structuring and completeness. For this purpose, an interactive software system (ViPATalk) was developed in which the student can train to pose questions to virtual patient avatars in free conversation. At the end, the student receives feedback on the completeness of the questioning and an explanation of the essential items. The use of this software was compared to the traditional format of student role play in a randomized trial. METHODS: The central component of ViPATalk is a chatbot based on the AI language AIML, which generates an appropriate answer based on keywords in the student's question. To enable a realistic use, the student can enter the question via microphone (speech-to-text) and the answer generated by the chatbot is presented as a short video sequence, where the avatar is generated from a real image. Here, the transition between the sequences is seamless, resulting in a continuous movement of the avatar during the conversation. RESULTS: The learning success by practicing with ViPATalk was tested in an anamnestic interview with actors as simulated patients. The completeness of the conversation was evaluated with regard to numerous aspects and also certain behaviors during the conversation. These results were compared with those after practicing using peer role play. CONCLUSIONS: It was found that practicing with ViPATalk was mostly equivalent to the students' role play. In the subsequent survey of the students, the wish was expressed that the ViPATalk software should also be used as an online tool for self-study and that there should be more cases for practicing.

Empowerment for the Digital Transformation: Results of a Structured Blended-Learning On-the-Job Training for Practicing Physicians in Germany.

(1) Background: Practicing physicians have not been in the focus of structured qualifications in basic digital competences so far. However, they are the current gatekeepers to implement digital technologies and need empowerment to proactively take part in the ongoing digital transformation process. The present study investigates if a structured blended-learning training for practicing physicians in Germany enhances both physicians' knowledge about central aspects of the digital transformation (including awareness of personal possibilities to act) and their attitudes towards a more digitally empowered mindset. (2) Methods: Participants (n = 32) self-assessed their knowledge (19 items, 10-point Likert-scale) and attitudes (6 items, 5-point Likert-scale) towards the digital transformation at the beginning and at the end of the training. MANCOVAs were conducted. (3) Results: Participants reported an increase in every knowledge domain, representing large effects (Hedges' g 1.06 to 2.82). Attitudes were partly shifted towards a more empowered mindset with decreased insecurity towards technological, legal, and ethical aspects of the digital transformation (Hedges' g -0.82 to -1.40). However, preparedness for the digital transformation remained low. (4) Conclusions: Generally, the hypotheses were confirmed. The presented on-the-job training had the desired effects on practicing physicians' knowledge and attitudes. Nevertheless, additional empowerment and support are essential.

Telephone-based communication training in the era of COVID-19.

Introduction: In the wake of the COVID-19 pandemic, alternatives to established and proven formats had to be found in university teaching within a very short time. In the case of the SkillsLab at the Dorothea Erxleben Lernzentrum Halle (Saale) at the Martin Luther University Halle (Saale)-Wittenberg, this meant in relation to the communication courses that a considerable proportion of the simulation participants of advanced age or with pre-existing conditions were suddenly no longer available for conversation simulations in teaching. Project description: In the course of the seminar "Conversation with relatives - dealing with relatives" in the 8th semester, the conversation simulation was therefore adapted at short notice and converted into a telephone conversation. Thus, the simulation subjects were able to participate remotely and the students had the opportunity to test their doctor-patient conversation skills with regard to telephone calls in a safe environment. Results: The focus on nonverbal techniques and the departure from the usual face-to-face setting was perceived by students and simulation subjects alike as a positive stimulus and particularly challenging. The lack of visual impressions had made empathic conversation more difficult. Discussion and Conclusions: The positive experiences from this project should be used to expand the communication curriculum in the future to include telephone-based conversations with simulation subjects. Ideally, it would then be possible for the simulation persons to be present in the future after the conversation for feedback mediation and group discussion.

["Halle surgery week": how a teaching format awakens medical students' interest in surgery]. / "Hallesche OP-Wochen": Wie ein Lehrformat das Interesse von Medizinstudierenden an der Chirurgie weckt.

BACKGROUND: A practical education in surgery is difficult to conduct in a student-centered manner and is thus often inadequate. New teaching concepts are required to provide students with insights into surgery and make the field more appealing. METHODS: As part of a two-week facultative event, medical students followed eight live surgical procedures from different disciplines from an auditorium. In the auditorium, the procedures were simultaneously moderated by an experienced surgeon. Before and after every procedure, questionnaires were used to analyze whether the teaching event was suited to improve an understanding and interest for the field of surgery. RESULTS: A total of 709 completed questionnaires (pre and post) from 381 students were collected. The self-reported learning effect was evaluated as good or very good by students. In many of the presented disciplines, experiencing a live surgical procedure was associated with significant positive changes in attitude regarding each discipline in general, a potential clinical traineeship in the discipline and choosing the discipline as a later specialization. CONCLUSION: The high attendance as well as the evaluation results suggest a high acceptance for the teaching event. The teaching format is suited to improve the understanding of surgical procedures and had a positive effect on medical students' attitude towards surgical disciplines.

Wild and Domestic Differences in Plant Development and Responses to Water Deficit in Cicer.

There is growing interest in widening the genetic diversity of domestic crops using wild relatives to break linkage drag and/or introduce new adaptive traits, particularly in narrow crops such as chickpea. To this end, it is important to understand wild and domestic adaptive differences to develop greater insight into how wild traits can be exploited for crop improvement. Here, we study wild and domestic Cicer development and water-use over the lifecycle, measuring responses to reproductive water deficit, a key Mediterranean selection pressure, using mini-lysimeters (33 L round pots) in common gardens under contrasting water regimes. Wild and domestic Cicer were consistently separated by later phenology, greater water extraction and lower water use efficiency (WUE) and harvest index in the former, and much greater yield-responsiveness in the latter. Throughout the lifecycle, there was greater vegetative investment in wild, and greater reproductive investment in domestic Cicer, reflected in root and harvest indices, rates of leaf area, and pod growth. Domestic WUE was consistently greater than wild, suggesting differences in water-use regulation and partitioning. Large wild-domestic differences revealed in this study are indicative of evolution under contrasting selection pressures. Cicer domestication has selected for early phenology, greater early vigor, and reproductive efficiency, attributes well-suited to a time-delimited production system, where the crop is protected from grazing, disease, and competition, circumstances that do not pertain in the wild. Wild Cicer attributes are more competitive: higher peak rates of leaf area growth, greater ad libitum water-use, and extraction under terminal drought associated with greater vegetative dry matter allocation, leading to a lower reproductive capacity and efficiency than in domestic chickpea. These traits strengthen competitive capacity throughout the growing season and are likely to facilitate recovery from grazing, two significant selection pressures faced by wild, rather than domesticated Cicer. While increased water extraction may be useful for improving chickpea drought tolerance, this trait must be evaluated independently of the other associated wild traits. To this end, the wild-domestic populations have been developed.

Application of telepresence systems in teaching - transfer of an interprofessional teaching module on digital aided communication into the block training "internal medicine" during the Covid-19 pandemic.

Objective: The contact restrictions caused by the Covid-19 pandemic fundamentally limit patient-centered teaching. To realize a patient-oriented education in the block training "Internal Medicine" at the University Hospital Halle (Saale) despite the challenges, the already established teaching module "Interprofessional Teleconsultation" was adapted. The short article outlines the interprofessional teaching module including first evaluation results and describes the adapted block training. Method: In the "Internal Medicine" block training, students in a lecture hall navigated a telepresence system, which was accompanied by a physician across the ward and conducted an anamnesis via video and audio transmission without actual patient contact. Results: Students, physicians, and patients were open-minded about this form of communication during the Covid-19 pandemic and quickly got accustomed to the use of the telepresence system. To be able to react to technical challenges (e.g. unstable connection between the communication partners), a careful preparation of the lecturers is necessary. Conclusion: In using a telepresence system, patient-oriented teaching of students in the block training "Internal Medicine" can be ensured with low-threshold technical effort during the Covid-19 pandemic. The telepresence system allows for the involvement of patients into teaching while adhering to the necessary hygiene measures. Despite technical challenges, the teaching format based on telepresence is suitable as an alternative to face-to-face teaching if actual patient contact is not possible.

Dienogest for Treatment of Endometriosis in Chinese Women: A Placebo-Controlled, Randomized, Double-Blind Phase 3 Study.

BACKGROUND: Dienogest is a progestin with demonstrated efficacy in the treatment of endometriosis in European women. The objective of this study was to evaluate the efficacy and safety of dienogest in Chinese women. PATIENTS AND METHODS: This 24-week, randomized, double-blind, placebo-controlled multicenter (n = 23) study evaluated the efficacy and safety of 2 mg dienogest once daily in 255 Chinese women aged 18-45 years with laparoscopically diagnosed endometriosis and an endometriosis-associated pelvic pain (EAPP) score ≥30 mm on a 0-100 mm visual analog scale. The primary efficacy variable was absolute change in EAPP from baseline to week 24. Secondary efficacy variables included proportions of responders and intake of supportive analgesic medication. Safety variables included adverse events (AEs), laboratory parameters, and bleeding patterns. Bone mineral density (BMD) was evaluated in a subset of 140 women. RESULTS: After 24 weeks of treatment, the difference between treatment arms for mean reduction in EAPP was statistically significant in favor of dienogest (-24.54 mm; 95% CI -29.93 to -19.15; p < 0.0001). Secondary efficacy analyses supported the significant superiority of dienogest over placebo. Dienogest was well tolerated, with few AEs associated with therapy. Dienogest had no effect on BMD levels after 24 weeks of treatment. CONCLUSIONS: Dienogest 2 mg once daily for 24 weeks was superior to placebo in reducing EAPP and was safe and well tolerated in Chinese women with endometriosis. The results are consistent with studies previously conducted in European women.

Reproductive Strategies in Mediterranean Legumes: Trade-Offs between Phenology, Seed Size and Vigor within and between Wild and Domesticated Lupinus Species Collected along Aridity Gradients.

To investigate wild and domesticated Mediterranean annual reproductive strategies, common garden comparisons of Old World lupins collected along aridity gradients were initiated. These are excellent candidates for ecophysiology, being widely distributed across contrasting environments, having distinct domestication histories, from ancient Lupinus albus to recently domesticated Lupinus angustifolius and Lupinus luteus, facilitating the study of both natural and human selection. Strong trade-offs between seed size, early vigor and phenology were observed: vigor increasing, and flowering becoming earlier with increasing seed size. Despite large specific differences in all these traits, natural and human selection have operated in very similar ways in all 3 species. In wild material, as collection environments became drier and hotter, phenology became earlier, while seed size, early vigor and reproductive investment increased. Wild and domesticated germplasm separated along similar lines. Within similar habitats, domesticated material was consistently earlier, with larger seeds, greater early vigor and higher reproductive investment than wild, suggesting selection for both early establishment and timely maturity/drought escape in both domesticated and wild low rainfall ecotypes. Species differences reflected their distribution. Small and soft-seeded, low vigor L. luteus had a late, rainfall-responsive phenology specifically adapted to long season environments, and a narrow coastal distribution. L. angustifolius was much more conservative; more hard-seeded, flowering and maturing much earlier, with a wide Mediterranean distribution. L. albus flowered earlier but matured much later, with longer reproductive phases supporting much larger seed sizes and early vigor than either L. luteus or L. angustifolius. This ruderal/competitive combination appears to give L. albus a broad adaptive capacity, reflected in its relatively wider Mediterranean/North African distribution.

Osmotic adjustment in chickpea (Cicer arietinum L.) results in no yield benefit under terminal drought.

Variation in osmotic adjustment (OA) among chickpea (Cicer arietinum L.) cultivars has been observed when exposed to terminal drought, but some studies suggest that this benefits yield while others suggest it does not benefit yield in water-limited environments. In the present study, parents differing in OA were crossed and a set of advanced breeding lines (ABLs) developed for yield testing. The variation in OA during podding was measured under terminal drought in the F(2), F(3), F(7), and F(8) progeny and in the parents by either rehydrating the leaves before sampling for osmotic potential (OP) or by measuring the relative water content (RWC) and OP on adjacent leaves for the calculation of the OP at full turgor. Yields were measured in the F(8) progeny under terminal drought in Australia and India. While differences in OA were measured in the chickpea lines and parents, OA varied from year to year and did not consistently benefit yield when measured in the field under terminal drought. In Australia, differences in OA were not associated with any yield benefit in any year, while in India early flowering resulted in higher yields at three of the four sites, and OA had an inconsistent effect on seed yields. A comparison of OP at full turgor measured after rehydration and from measurements of RWC and OP showed that the rehydration technique underestimated OA. The lack of contribution of OA to yield of chickpea is discussed.