Co-expression patterns of cancer associated fibroblast markers reveal distinct subgroups related to patient survival in oropharyngeal squamous cell carcinoma

Background: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) is rapidly increasing in high income countries due to its association with persistent high-risk human papilloma virus (HPV) infection. Recent scientific advances have highlighted the importance of the tumor microenvironment in OPSCC. In this study, including 216 OPSCC patients, we analyze the composition of four established markers of cancer associated fibroblasts (CAFs) in the context of intratumoral CD8 T-cell infiltration.Methods: Immunohistochemical staining for fibroblast activation protein (FAP), platelet-derived growth factor receptor beta (PDGFRb), periostin, alpha smooth muscle actin (α-SMA) and CD8 were analyzed digitally and their association with survival, tumor- and patient characteristics was assessed.Results: Co-expression of CAF markers was frequent but not associated with HPV status. FAPhigh and PDGFRbhigh expression were associated with increased CD8 T-cell infiltration. Low expression of PDGFRb improved patient survival in female patients but not in male patients. We identified PDGFRblow periostinlow α-SMAlow status as an independent predictor of improved survival (hazard ratio 0.377, p = 0.006).Conclusion: These findings elucidate the co-expression of four established CAF markers in OPSCC and underscore their association with T-cell infiltration and patient survival. Future analyses of CAF subgroups in OPSCC may enable the development of individualized therapies

Providing practical skills in curricular teaching—effect of SkillsLab and flipped classroom

Zusammenfassung Hintergrund Im Zuge der Neustrukturierung des Medizinstudiums werden erstmalig auch praktische Kompetenzen als Lernziele klar definiert. Zur effektiven Nutzung der kurzen Präsenzzeit, die im Fach HNO-Heilkunde zur Verfügung steht, war das Ziel dieser Studie die Verzahnung der Vermittlung praktischer Fertigkeiten unter Zuhilfenahme von „flipped classroom“, digitaler Lehre und einem neu errichteten SkillsLab zu evaluieren. Material und Methoden Im Rahmen des HNO-Praktikums wurden die Studierenden in 2 Gruppen unterteilt: Gruppe A = 93 Studierende (männlich n  = 42, weiblich n  = 51), Gruppe B = 113 Studierende (männlich n  = 42, weiblich n  = 71). Sie bearbeiteten zunächst digital zur Verfügung gestelltes Material, welches einzelne HNO-Untersuchungen erläuterte. Anschließend erfolgte der Präsenzunterricht in Kleingruppen, welcher eine Hospitation und Übungen der Untersuchungstechniken beinhaltete. Während Gruppe A diese dozentengeführt an Modellen absolvierte und sich gegenseitig untersuchte, erhielt Gruppe B den Unterricht anhand strukturierter Arbeitsstationen im hierfür neu errichteten HNO-SkillsLab. Die Effekte auf die Motivation und subjektiven Kompetenzen wurden anhand eines eigens für diese Studie entwickelten Fragebogens gemessen. Ergebnisse Nach Bearbeitung des digitalen Materials zeigte sich in beiden Gruppen ein hohes Level an Motivation und Kompetenz. Im Verlauf des Präsenztags zeigte sich ein Zugewinn an Motivation und Kompetenz, welcher nur in der SkillsLab-Gruppe statistisch signifikant war ( p  < 0,001). Obwohl die SkillsLab-Gruppe vor dem Präsenztag in ihrer subjektiven Kompetenz unterlegen war, zeigte sie sich nach dem Präsenztag der anderen Gruppe hierin sogar überlegen. Schlussfolgerung Die Kombination eines digitalen „flipped classroom“ mit strukturierten Arbeitsstationen im Rahmen eines SkillsLabs ermöglicht eine effektivere Vermittlung praktischer Kompetenzen, welche sich in der statistisch signifikanten Steigerung von Motivation und Selbsteinschätzung der Gruppe B widerspiegelt. Dabei erleichtert insbesondere die digitale Befunderhebung die Überprüfung der individuellen Lernerfolge und regt die Diskussion an.Abstract Background In the course of the restructuring of medical studies, practical competencies are clearly defined as learning objectives for the first time. In order to make most effective use of the short attendance time available in otolaryngology, the aim of this study was to teach practical skills with the help of flipped classroom, digital teaching, and a newly established SkillsLab. Materials and methods During their ENT internship, two groups of students—group A = 93 students (male n  = 42, female n  = 51) and group B = 113 students (male n  = 42, female n  = 71)—first worked through material provided online, which explained the individual examinations. This was followed by face-to-face teaching, which consisted of observation and practical exercise of the different examination techniques. While group A practiced on each other or on dummies, group B used structured workstations in the ENT SkillsLab, which was newly built for this purpose. The effects on motivation and subjective competence were measured using a questionnaire developed for this study. Results After working through the online material, both groups showed a high level of motivation and competence. On the day of face-to-face teaching, there was a gain in motivation and competence, which was statistically significant only in the SkillsLab group ( p  < 0.001). Although the SkillsLab group was inferior in terms of its subjective competence at the beginning, it was superior to the other group after the face-to-face teaching. Conclusion Combination of digitized teaching in the flipped classroom with structured workstations in the setting of a SkillsLab enables more effective teaching of practical skills, which was reflected by increases in motivation and subjective competence in group B. In particular, the presentation of all collected findings on monitors allows verification of learning success and stimulates discussion.Zusammenfassung Hintergrund Im Zuge der Neustrukturierung des Medizinstudiums werden erstmalig auch praktische Kompetenzen als Lernziele klar definiert. Zur effektiven Nutzung der kurzen Präsenzzeit, die im Fach HNO-Heilkunde zur Verfügung steht, war das Ziel dieser Studie die Verzahnung der Vermittlung praktischer Fertigkeiten unter Zuhilfenahme von „flipped classroom“, digitaler Lehre und einem neu errichteten SkillsLab zu evaluieren. Material und Methoden Im Rahmen des HNO-Praktikums wurden die Studierenden in 2 Gruppen unterteilt: Gruppe A = 93 Studierende (männlich n  = 42, weiblich n  = 51), Gruppe B = 113 Studierende (männlich n  = 42, weiblich n  = 71). Sie bearbeiteten zunächst digital zur Verfügung gestelltes Material, welches einzelne HNO-Untersuchungen erläuterte. Anschließend erfolgte der Präsenzunterricht in Kleingruppen, welcher eine Hospitation und Übungen der Untersuchungstechniken beinhaltete. Während Gruppe A diese dozentengeführt an Modellen absolvierte und sich gegenseitig untersuchte, erhielt Gruppe B den Unterricht anhand strukturierter Arbeitsstationen im hierfür neu errichteten HNO-SkillsLab. Die Effekte auf die Motivation und subjektiven Kompetenzen wurden anhand eines eigens für diese Studie entwickelten Fragebogens gemessen. Ergebnisse Nach Bearbeitung des digitalen Materials zeigte sich in beiden Gruppen ein hohes Level an Motivation und Kompetenz. Im Verlauf des Präsenztags zeigte sich ein Zugewinn an Motivation und Kompetenz, welcher nur in der SkillsLab-Gruppe statistisch signifikant war ( p  < 0,001). Obwohl die SkillsLab-Gruppe vor dem Präsenztag in ihrer subjektiven Kompetenz unterlegen war, zeigte sie sich nach dem Präsenztag der anderen Gruppe hierin sogar überlegen. Schlussfolgerung Die Kombination eines digitalen „flipped classroom“ mit strukturierten Arbeitsstationen im Rahmen eines SkillsLabs ermöglicht eine effektivere Vermittlung praktischer Kompetenzen, welche sich in der statistisch signifikanten Steigerung von Motivation und Selbsteinschätzung der Gruppe B widerspiegelt. Dabei erleichtert insbesondere die digitale Befunderhebung die Überprüfung der individuellen Lernerfolge und regt die Diskussion an.Abstract Background In the course of the restructuring of medical studies, practical competencies are clearly defined as learning objectives for the first time. In order to make most effective use of the short attendance time available in otolaryngology, the aim of this study was to teach practical skills with the help of flipped classroom, digital teaching, and a newly established SkillsLab. Materials and methods During their ENT internship, two groups of students—group A = 93 students (male n  = 42, female n  = 51) and group B = 113 students (male n  = 42, female n  = 71)—first worked through material provided online, which explained the individual examinations. This was followed by face-to-face teaching, which consisted of observation and practical exercise of the different examination techniques. While group A practiced on each other or on dummies, group B used structured workstations in the ENT SkillsLab, which was newly built for this purpose. The effects on motivation and subjective competence were measured using a questionnaire developed for this study. Results After working through the online material, both groups showed a high level of motivation and competence. On the day of face-to-face teaching, there was a gain in motivation and competence, which was statistically significant only in the SkillsLab group ( p  < 0.001). Although the SkillsLab group was inferior in terms of its subjective competence at the beginning, it was superior to the other group after the face-to-face teaching. Conclusion Combination of digitized teaching in the flipped classroom with structured workstations in the setting of a SkillsLab enables more effective teaching of practical skills, which was reflected by increases in motivation and subjective competence in group B. In particular, the presentation of all collected findings on monitors allows verification of learning success and stimulates discussion

Vermittlung praktischer Fähigkeiten in der curricularen Lehre

$\bf Hintergrund:$ Im Zuge der Neustrukturierung des Medizinstudiums werden erstmalig auch praktische Kompetenzen als Lernziele klar definiert. Zur effektiven Nutzung der kurzen Präsenzzeit, die im Fach HNO-Heilkunde zur Verfügung steht, war das Ziel dieser Studie die Verzahnung der Vermittlung praktischer Fertigkeiten unter Zuhilfenahme von "flipped classroom", digitaler Lehre und einem neu errichteten SkillsLab zu evaluieren. $\textbf {Material und Methoden:}$ Im Rahmen des HNO-Praktikums wurden die Studierenden in 2 Gruppen unterteilt: Gruppe A = 93 Studierende (männlich $\it n$ = 42, weiblich $\it n$ = 51), Gruppe B = 113 Studierende (männlich $\it n$ = 42, weiblich $\it n$ = 71). Sie bearbeiteten zunächst digital zur Verfügung gestelltes Material, welches einzelne HNO-Untersuchungen erläuterte. Anschließend erfolgte der Präsenzunterricht in Kleingruppen, welcher eine Hospitation und Übungen der Untersuchungstechniken beinhaltete. Während Gruppe A diese dozentengeführt an Modellen absolvierte und sich gegenseitig untersuchte, erhielt Gruppe B den Unterricht anhand strukturierter Arbeitsstationen im hierfür neu errichteten HNO-SkillsLab. Die Effekte auf die Motivation und subjektiven Kompetenzen wurden anhand eines eigens für diese Studie entwickelten Fragebogens gemessen. $\bf Ergebnisse:$ Nach Bearbeitung des digitalen Materials zeigte sich in beiden Gruppen ein hohes Level an Motivation und Kompetenz. Im Verlauf des Präsenztags zeigte sich ein Zugewinn an Motivation und Kompetenz, welcher nur in der SkillsLab-Gruppe statistisch signifikant war ($\it p$ < 0,001). Obwohl die SkillsLab-Gruppe vor dem Präsenztag in ihrer subjektiven Kompetenz unterlegen war, zeigte sie sich nach dem Präsenztag der anderen Gruppe hierin sogar überlegen. $\bf Schlussfolgerung:$ Die Kombination eines digitalen "flipped classroom" mit strukturierten Arbeitsstationen im Rahmen eines SkillsLabs ermöglicht eine effektivere Vermittlung praktischer Kompetenzen, welche sich in der statistisch signifikanten Steigerung von Motivation und Selbsteinschätzung der Gruppe B widerspiegelt. Dabei erleichtert insbesondere die digitale Befunderhebung die Überprüfung der individuellen Lernerfolge und regt die Diskussion an

Sex-specific aspects in patients with oropharyngeal squamous cell carcinoma: a bicentric cohort study

Background Oropharyngeal squamous cell carcinoma (OPSCC) is the only subgroup of head neck cancer that presents with an increased incidence. Gender-specific studies in other cancer entities have revealed differences in treatment response and prognosis. However, only limited data in OPSCC according to gender and human papillomavirus (HPV) status exist. Therefore, we aimed to investigate sex-specific differences in OPSCC and how these may be distributed in relation to HPV and other risk factors. Methods This retrospective, bicentric study included 1629 patients with OPSCC diagnosed between 1992 and 2020. We formed subgroups based on TNM status, American Joint Cancer Committee 8th edition (AJCC8), HPV status, treatment modality (surgery (± radio(chemo)therapy (RCT) vs. definitive RCT) and patient-related risk factors and investigated gender differences and their impact on patients survival via descriptive-,uni- and multivariate analysis. Results With the exception of alcohol abuse, no significant differences were found in risk factors between men and women. Females presented with better OS than males in the subgroup T1-2, N + , independent of risk factors (p = 0.008). Males demonstrated significant stratification through all AJCC8 stages (all p < 0.050). In contrast, women were lacking significance between stage II and III (p = 0.992). With regard to therapy (surgery (± R(C)T) – vs. definitive RCT) women treated with surgery had better OS than men in the whole cohort (p = 0.008). Similar results were detected in the HPV-negative OPSCC sub-cohort (p = 0.042) and in high-risk groups (AJCC8 stage III and IV with M0, p = 0.003). Conclusion Sex-specific differences in OPSCC represent a health disparity, particularly according to staging and treatment, which need to be addressed in future studies

Prospective studies on the routine use of a novel multivariant enzyme-linked immunosorbent assay for the diagnosis of autoimmune bullous diseases.

BACKGROUND Serologic diagnosis of autoimmune blistering disease (AIBD) usually follows a sophisticated multistep algorithm. OBJECTIVE We sought validation of a multivariant enzyme-linked immunosorbent assay (ELISA) in the routine diagnosis of AIBD. METHODS The multivariant ELISA comprising 6 recombinant immunodominant forms of major AIBD target antigens, ie, desmoglein 1, desmoglein 3, envoplakin, BP180, BP230, and type VII collagen was applied in: (1) a cohort of well-characterized AIBD (n = 173) and control sera (n = 130), (2) a prospective multicenter study with 204 sera from patients with newly diagnosed AIBD with positive direct immunofluorescence microscopy, and (3) a prospective monocenter study with 292 consecutive sera from patients with clinical suspicion of AIBD in comparison with the conventional multistep diagnostic algorithm. RESULTS Concordant results in the multivariant ELISA compared with direct immunofluorescence microscopy were seen in 94% of patients with pemphigus and 71% of patients with pemphigoid (Cohen κ value, 0.95 and 0.66) and with the conventional multistep diagnostic approach in 91% of patients with pemphigus and 88% of patients with bullous pemphigoid and 93% of autoantibody-negative sera (Cohen κ, 0.95, 0.84, and 0.78). LIMITATIONS IgA autoantibodies and less common target antigens were not analyzed. CONCLUSIONS The multivariant ELISA is a practical, highly standardized, and widely available novel diagnostic tool for the routine diagnosis of AIBD

Autoantibodies to Cytosolic 5′-Nucleotidase 1A in Primary Sjögren’s Syndrome and Systemic Lupus Erythematosus

IntroductionAutoantibodies to cytosolic 5′-nucleotidase 1A (cN-1A; NT5C1A) have a high specificity when differentiating sporadic inclusion body myositis from polymyositis and dermatomyositis. In primary Sjögren’s syndrome (pSS) and systemic lupus erythematosus (SLE) anti-cN-1A autoantibodies can be detected as well. However, various frequencies of anti-cN-1A reactivity have been reported in SLE and pSS, which may at least in part be explained by the different assays used. Here, we determined the occurrence of anti-cN-1A reactivity in a large number of patients with pSS and SLE using one standardized ELISA.MethodsSera from pSS (n = 193) and SLE patients (n = 252) were collected in five European centers. Anti-cN-1A, anti-Ro52, anti-nucleosome, and anti-dsDNA reactivities were tested by ELISA (Euroimmun AG) in a single laboratory. Correlations of anti-cN-1A reactivity with demographic data and clinical data (duration of disease at the moment of serum sampling, autoimmune comorbidity and presence of muscular symptoms) were analyzed using SPSS software.ResultsAnti-cN-1A autoantibodies were found on average in 12% of pSS patients, with varying frequencies among the different cohorts (range: 7–19%). In SLE patients, the anti-cN-1A positivity on average was 10% (range: 6–21%). No relationship was found between anti-cN-1A reactivity and the presence or absence of anti-Ro52, anti-nucleosome, and anti-dsDNA reactivity in both pSS and SLE. No relationship between anti-cN-1A reactivity and duration of disease at the moment of serum sampling and the duration of serum storage was observed. The frequency of muscular symptoms or viral infections did not differ between anti-cN-1A-positive and -negative patients. In both disease groups anti-cN-1A-positive patients suffered more often from other autoimmune diseases than the anti-cN-1A-negative patients (15 versus 5% (p = 0.05) in pSS and 50 versus 30% (p = 0.02) in SLE).ConclusionOur results confirm the relatively frequent occurrence of anti-cN-1A in pSS and SLE patients and the variation in anti-cN-1A reactivity between independent groups of these patients. The explanation for this variation remains elusive. The correlation between anti-cN-1A reactivity and polyautoimmunity should be evaluated in future studies. We conclude that anti-cN-1A should be classified as a myositis-associated-, not as a myositis-specific-autoantibody based on its frequent presence in SLE and pSS

Reforming Moldovan social assistance: Poor Laws for the European fringe?

The small south-eastern European Republic of Moldova is often referred to as 'the poorhouse of the continent'. During its transition from a communist to a market economy, inequality and poverty rose exponentially - with the latter reaching a peak of 70% in 1999. Thus, a new social contract between state and society had to be fabricated. The Soviet social protection system, designed around the needs of the workforce and specific groups, was unable to meet the challenges posed by transition. A reform seemed inevitable, re-targeting resources at the most needy. However, Western means-tested models could not be simply transferred; path-dependencies along with donor interventions shaped and altered the policy process