Selbstwert und allgemeine Selbstwirksamkeitserwartung bei MigränepatientInnen

Theoretischer Hintergrund: Der Selbstwert sowie die allgemeine Selbstwirksamkeitserwartung können getreu der Theorie der „core evaluations“ als fundamentale Kernbewertungen des Selbst betrachtet werden. In Bezug zu transaktionalen Modellen chronischen Schmerzes könnten diese psychischen Ressourcen eine entscheidende Rolle im Schmerzerleben und der schmerzbedingten emotionalen Belastung spielen. Bezüglich des Kopfschmerzes erwies sich bisher der Selbstwert als wichtiger Prädiktor der Kopfschmerzhäufigkeit in jugendlichen Stichproben, für die kopfschmerzspezifische Selbstwirksamkeit sind Zusammenhänge mit der Dauer und Intensität von Kopfschmerzen belegt. Beeinträchtigungen des Selbstwertes im Vergleich zu gesunden Personen konnten darüber hinaus bei chronischen Schmerzpatienten gefunden werden. Zielsetzung: Ziel der Studie war daher a) ein Vergleich der Kernselbstbewertungen sowie der spezifischen Selbstwertfacetten zwischen Migränepatienten und einer Kontrollgruppe, b) die Überprüfung des Zusammenhangs zwischen Selbstbewertungen und migränespezifischen Schmerzparametern sowie c) die Vorhersage der Depressivität von Migränepatienten mittels der Selbstbewertungen. Methoden: Teilnehmer waren 111 Migränepatienten sowie 111 Kontrollpersonen, die die Multidimensionale Selbstwertskala, die Skala zur Allgemeinen Selbstwirksamkeit sowie das Depressions-Inventar von Beck ausfüllten. Die Kopfschmerzdiagnose, Komorbiditäten und die Migräneparameter wurden vorab in einem Interview erfragt. Ergebnisse und Schlussfolgerung: Die Ergebnisse der GLMs zeigen, dass Migränepatienten einen signifikant geringeren Selbstwert aufweisen, die allgemeine Selbstwirksamkeit sowie die Selbstwertschätzung im emotionalen, sozialen und leistungsbezogenen Bereich unterscheiden sich jedoch nicht bei Berücksichtigung der Depressivität als Kovariate. Die Selbstbewertungen weisen keine signifikanten Zusammenhänge mit den schmerzspezifischen Parametern auf, der globale Selbstwert stellt jedoch einen signifikanten Prädiktor der Depressivität bei Migränepatienten dar. Die Ergebnisse legen für die psychologische Behandlung von Migränepatienten eine Förderung des Selbstwertes als Ressource gegen die Depressivität nahe.Theoretical Background: According to the core evaluations approach, self-esteem and general self-efficacy can be considered as fundamental core self-evaluations. With regard to transactional models of chronic pain, these psychological resources could be assumed to be associated with pain experience and pain emotions. Relating to headache, self-esteem has been shown to be a significant predictor of headache frequency in adolescent samples while headache-specific self-efficacy exhibits a meaningful association with headache intensity and duration. In comparison with healthy persons, a diminished self-esteem has been reported in pain patients. Objective: Objective of this study was therefore the examination of a) the two core self-evaluations as well as specific self-esteem facets in migraine patients compared to a healthy reference group, b) the association between self-evaluations and pain parameters and c) self-esteem and general self-efficacy as predictors of depressive mood in migraine patients. Methods: Participants were 111 migraine patients and 111 control subjects which completed the multidimensional self-esteem scale, the general self-efficacy scale as well as the Beck-depression-inventory. Headache diagnosis, comorbidity, pain parameters etc. were raised in a preceding interview. Results and Conclusion: Results of the GLMs reveal a significantly lower general self-esteem in migraine patients, while general self-efficacy and emotional, social and performance based self-esteem did not show significant differences when depression was considered as a covariate. None of the self-evaluations was significantly associated with migraine-specific pain parameters, but the general self-esteem turned out to be a highly relevant predictor of depression in migraine patients. These findings may contribute to the treatment of migraine patients by paying attention to the advancement of self-esteem, which in turn will be beneficial for depressive mood in migraine patients

Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19

LKB1 Somatic Mutations in Sporadic Tumors

Germline mutations of LKB1/Peutz-Jeghers syndrome gene predispose carriers to hamartomatous polyposis of the gastrointestinal tract as well as to cancer of different organ systems. Although Peutz-Jeghers syndrome patients frequently present with neoplasms of the colon, stomach, small intestine, pancreas, breast, ovaries, and cervix, somatic mutations appear to be rare in the sporadic tumor types thus far studied (colorectal, gastric, testicular, and breast cancers). To evaluate whether somatic mutations of LKB1 contribute to the tumorigenesis of yet unstudied tumor types, we screened 14 cell lines and 129 tumor specimens from different cancers for a genetic defect in LKB1. Six melanoma and eight myeloma cell lines were scrutinized for LKB1 somatic mutations by genomic sequencing. No changes were found in the coding LKB1 sequence and exon/intron boundaries. Next, we analyzed 12 pancreatic, 8 gastric, 12 ovarian granulosa cell, 26 cervical, 28 lung, 24 soft tissue, and 19 renal tumors by single-strand conformational polymorphism analysis. Three changes in LKB1 coding nucleotide sequence were identified. One base pair deletion at A957 and G958 substitution by T occurred in a cervical adenocarcinoma sample, resulting in a frameshift and premature stop codon at position 335. Substitution of A581 by T occurred in a lung adenocarcinoma sample, resulting in the change of aspartic acid at position 194 to valine. A loss of another allele was detected in this sample. One silent change, C1257T, was found in a pancreatic carcinoma sample. The changes were not present in the matched normal tissue DNA samples. Our results suggest that mutational inactivation of LKB1 is a rare event in most sporadic tumor types

Effects of COVID-19 Lockdown on Melanoma Diagnosis in Switzerland: Increased Tumor Thickness in Elderly Females and Shift towards Stage IV Melanoma during Lockdown

At the early stages of the COVID-19 outbreak in 2020, Switzerland was among the countries with the highest number of SARS-CoV2-infections per capita in the world. Lockdowns had a remarkable impact on primary care access and resulted in postponed cancer screenings. The aim of this study was to investigate the effects of the COVID-19 lockdown on the diagnosis of melanomas and stage of melanomas at diagnosis. In this retrospective, exploratory cohort study, 1240 patients with a new diagnosis of melanoma were analyzed at five tertiary care hospitals in German-speaking Switzerland over a period of two years and three months. We compared the pre-lockdown (01/FEB/19–15/MAR/20, n = 655) with the lockdown (16/MAR/20–22/JUN/20, n = 148) and post-lock-down period (23/JUN/20–30/APR/21, n = 437) by evaluating patients’ demographics and prognostic features using Breslow thickness, ulceration, subtype, and stages. We observed a short-term, two-week rise in melanoma diagnoses after the major lift of social lockdown restrictions. The difference of mean Breslow thicknesses was significantly greater in older females during the lockdown compared to the pre-lockdown (1.9 ± 1.3 mm, p = 0.03) and post-lockdown period (1.9 ± 1.3 mm, p = 0.048). Thickness increase was driven by nodular melanomas (2.9 ± 1.3 mm, p = 0.0021; resp. 2.6 ± 1.3 mm, p = 0.008). A proportional rise of advanced melanomas was observed during lockdown (p = 0.047). The findings provide clinically relevant insights into lockdown-related gender-and age-dependent effects on melanoma diagnosis. Our data highlight a stable course in new melanomas with a lower-than-expected increase in the post-lockdown period. The lockdown period led to a greater thickness in elderly women driven by nodular melanomas and a proportional shift towards stage IV melanoma. We intend to raise awareness for individual cancer care in future pandemic management strategies.ISSN:2072-669

Effects of COVID-19 Lockdown on Melanoma Diagnosis in Switzerland: Increased Tumor Thickness in Elderly Females and Shift towards Stage IV Melanoma during Lockdown

At the early stages of the COVID-19 outbreak in 2020, Switzerland was among the countries with the highest number of SARS-CoV2-infections per capita in the world. Lockdowns had a remarkable impact on primary care access and resulted in postponed cancer screenings. The aim of this study was to investigate the effects of the COVID-19 lockdown on the diagnosis of melanomas and stage of melanomas at diagnosis. In this retrospective, exploratory cohort study, 1240 patients with a new diagnosis of melanoma were analyzed at five tertiary care hospitals in German-speaking Switzerland over a period of two years and three months. We compared the pre-lockdown (01/FEB/19–15/MAR/20, n = 655) with the lockdown (16/MAR/20–22/JUN/20, n = 148) and post-lockdown period (23/JUN/20–30/APR/21, n = 437) by evaluating patients’ demographics and prognostic features using Breslow thickness, ulceration, subtype, and stages. We observed a short-term, two-week rise in melanoma diagnoses after the major lift of social lockdown restrictions. The difference of mean Breslow thicknesses was significantly greater in older females during the lockdown compared to the pre-lockdown (1.9 ± 1.3 mm, p = 0.03) and post-lockdown period (1.9 ± 1.3 mm, p = 0.048). Thickness increase was driven by nodular melanomas (2.9 ± 1.3 mm, p = 0.0021; resp. 2.6 ± 1.3 mm, p = 0.008). A proportional rise of advanced melanomas was observed during lockdown (p = 0.047). The findings provide clinically relevant insights into lockdown-related gender- and age-dependent effects on melanoma diagnosis. Our data highlight a stable course in new melanomas with a lower-than-expected increase in the post-lockdown period. The lockdown period led to a greater thickness in elderly women driven by nodular melanomas and a proportional shift towards stage IV melanoma. We intend to raise awareness for individual cancer care in future pandemic management strategies

L'avenir des partis politiques en France et en Allemagne

De part et d’autre du Rhin, les partis politiques jouent un rôle central dans la formation de l’opinion publique. Les deux systèmes ont connu au départ un processus de concentration. Mais une bipolarisation a émergé en France, tandis qu’un système de compétition voyait le jour en Allemagne. Avec la faiblesse des partis de rassemblement allemands, il devient de plus en plus difficile de constituer des majorités structurelles. Ainsi, l’Allemagne se rapproche de la situation française, traditionnellement caractérisée par une tendance à la fragmentation. Dans les deux pays, les partis établis perdent en dynamisme, en termes de personnel comme de programme, et sont en concurrence pour un électorat qui ne cesse de fluctuer. Dans ce contexte, ils accordent une importance croissante à la professionnalisation de leurs campagnes électorales. De plus, à Paris comme à Berlin, la démocratie des médias transforme les règles de la compétition politique. Cet ouvrage s’articule en deux parties. La première livre une analyse comparative des systèmes partisans français et allemand et s’arrête en particulier sur leurs transformations récentes. La seconde partie se concentre sur le discours des partis, décryptant leurs positions sur les grandes questions politiques

Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer

BackgroundNeratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies.MethodsPatients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks (DE2). The primary endpoint was incidence of grade ≥3 diarrhea. Health-related quality of life (HRQoL) was assessed using FACT-B and EQ-5D-5L.Results563 patients were enrolled into six cohorts. All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%). Diarrhea-related discontinuations occurred early and were lowest in DE1 (DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%). More patients stayed on neratinib for the prescribed period versus historical controls. Prior pertuzumab use did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration. Early transient reductions in HRQoL scores were observed.ConclusionsThese complete results from CONTROL show improved neratinib tolerability with proactive management at the start of therapy. Two-week neratinib DE with loperamide as needed was particularly effective.ClinicaltrialsGov registration numberNCT02400476

Oxysterol Sensing through the Receptor GPR183 Promotes the Lymphoid-Tissue-Inducing Function of Innate Lymphoid Cells and Colonic Inflammation

International audienceGroup 3 innate lymphoid cells (ILC3s) sense environmental signals and are critical for tissue integrity in the intestine. Yet, which signals are sensed and what receptors control ILC3 function remain poorly understood. Here, we show that ILC3s with a lymphoid-tissue-inducer (LTi) phenotype expressed G-protein-coupled receptor 183 (GPR183) and migrated to its oxysterol ligand 7α,25-hydroxycholesterol (7α,25-OHC). In mice lacking Gpr183 or 7α,25-OHC, ILC3s failed to localize to cryptopatches (CPs) and isolated lymphoid follicles (ILFs). Gpr183 deficiency in ILC3s caused a defect in CP and ILF formation in the colon, but not in the small intestine. Localized oxysterol production by fibroblastic stromal cells provided an essential signal for colonic lymphoid tissue development, and inflammation-induced increased oxysterol production caused colitis through GPR183-mediated cell recruitment. Our findings show that GPR183 promotes lymphoid organ development and indicate that oxysterol-GPR183-dependent positioning within tissues controls ILC3 activity and intestinal homeostasis