Grundlagenbeitrag: Inhaltsanalysen inklusive Medienanalysen

Der Grundlagenbeitrag fokussiert auf die Methode der Inhaltsanalyse inkl. Medienanalyse und reflektiert den Einsatz dieser im Bereich der Evaluation von Wissenschaftskommunikation. Nachdem einleitend deren Relevanz reflektiert wird, wird diese vorgestellt, indem Untersuchungsgegenstände, Analyseprozesse und Ziele der quantitativen/standardisierten und qualitativen Inhaltsanalyse erläutert werden. Herausgearbeitet werden dann die Analyseschwerpunkte der Inhalts- und Medienanalysen im Bereich der Evaluation von Wissenschaftskommunikation und ihrer Begleitforschung. Diese sind u. a. (1) Modi der Wissenschaftskommunikation, (2) die Genauigkeit der Berichterstattung, (3) die Darstellung, das Framing und die Bewertung von Wissenschaft und wissenschaftlichen Erkenntnissen, und (4) Dialogizität und Funktionalität der Wissenschaftskommunikation bzw. Funktionen der Öffentlichkeitsarbeit. Im letzten Punkt wird ein Ausblick gegeben und relevante Forschungslücken werden herausgestellt

Neonatal outcomes associated with time from a high fetal blood lactate concentration to operative delivery

Introduction: Adjunctive technologies to cardiotocography intend to increase the specificity of the diagnosis of fetal hypoxia. If correctly diagnosed, time to delivery could affect neonatal outcome. In the present study, we aimed to investigate the effect of time from when fetal distress is indicated by a high fetal blood sample (FBS) lactate concentration to operative delivery on the risk of adverse neonatal outcomes. Material and methods: We conducted a prospective observational study. Deliveries with a singleton fetus in cephalic presentation at 36+0weeks of gestation or later were included. Adverse neonatal outcomes, related to decision-to-delivery interval (DDI), were investigated in operative deliveries indicated by an FBS lactate concentration of at least 4.8 mmol/L. We applied logistic regression to estimate crude and adjusted odds ratios (aOR) of various adverse neonatal outcomes, with associated 95% confidence intervals (CI), for a DDI exceeding 20 minutes, compared with a DDI of 20 minutes or less. ClinicalTrials.gov Identifier: NCT04779294. Results: The main analysis included 228 women with an operative delivery indicated by an FBS lactate concentration of 4.8 mmol/L or greater. The risk of all adverse neonatal outcomes was significantly increased for both DDI groups compared with the reference group (deliveries with an FBS lactate below 4.2 mmol/L within 60 minutes before delivery). In operative deliveries indicated by an FBS lactate concentration of 4.8 mmol/L or more, there was a significantly increased risk of a 5-minute Apgar score less than 7 if the DDI exceeded 20 minutes, compared with a DDI of 20 minutes or less (aOR 8.1, 95% CI 1.1–60.9). We found no statistically significant effect on other short-term outcomes for deliveries with DDI longer than 20 minutes, compared with those with DDI of 20 minutes or less (pH ≤7.10: aOR 2.0, 95% CI 0.5–8.4; transfer to the neonatal intensive care unit: aOR 1.1, 95% CI 0.4–3.5). Conclusions: After a high FBS lactate measurement, the increased risk of adverse neonatal outcome is further augmented if the DDI exceeds 20 minutes. These findings give support to current Norwegian guidelines for intervention in cases of fetal distress.publishedVersio

Cytoplasmic colocalization of RXRα and PPARγ as an independent negative prognosticator for breast cancer patients

Retinoid X receptor α (RXRα) is a nuclear receptor (NR) which functions as the primary heterodimeric partner of other NRs including the peroxisome proliferator-activated receptor γ (PPARγ). We previously reported that, in breast cancers (BC), the subcellular localization of these two receptors was strongly associated with patient prognosis. In the present work, we investigated the prognosis value of the combined cytoplasmic expression of RXRα and PPARγ using a retrospective cohort of 250 BC samples. Patients with tumors expressing both NRs in tumor cell cytoplasm exhibited a significant shorter overall (OS) and disease-free survival (DFS). This was also observed for patients with stage 1 tumors. Cox univariate analysis indicated that patients with tumors coexpressing RXRα and PPARγ in the cytoplasm of tumor cells have a decreased 5 y OS rate. Cytoplasmic co-expression of the two NRs significantly correlated with HER2 positivity and with NCAD and CD133, two markers of tumor aggressiveness. Finally, in Cox multivariate analysis, the co-expression of RXRα and PPARγ in the cytoplasm appeared as an independent OS prognosticator. Altogether, this study demonstrates that the cytoplasmic co-expression of RXRα and PPARγ could be of relevance for clinicians by identifying high-risk BC patients, especially amongst those with early and node-negative disease

Prognostic relevance of nuclear receptors in relation to peritumoral inflammation and tumor infiltration by lymphocytes in breast cancer

The prognostic impact of tumor-infiltrating lymphocytes (TILs) is intensively investigated in breast cancer (BC). It is already known that triple-negative breast cancer (TNBC), the most aggressive type of BC, has the highest percentage of TILs. In addition, there is an influence of steroid hormone receptor expression (type I nuclear receptors) on TIL subpopulations in breast cancer tissue. The link between type II nuclear receptors and the level of TILs is unclear. Therefore, the aim of this study was to quantify TILs in a panel of 264 sporadic breast cancers and investigate the correlation of TIL levels with type I and II nuclear receptors expression. TIL levels were significantly increased in the subgroup of TNBC. By contrast, they decreased in estrogen (ER)- or progesterone receptor (PR)-positive cases. Moreover, TIL levels were correlated with type II nuclear receptors, including PPARγ, with a significant inverse correlation of the nuclear form (r = −0.727, p 15% showed a significantly decreased overall survival. In addition, peritumoral inflammation was also quantified in BC tissue samples. In our cohort, although the level of peritumoral inflammation was not correlated with OS, it determined the prognostic value of ER, PR, and PPARγ in BC. Altogether, the present study provides a differentiated overview of the relations between nuclear receptor expression, TIL levels, peritumoral inflammation, and prognosis in BC

Adapted Bacteriophages for Treating Urinary Tract Infections

Urinary tract infections (UTIs) are among the most widespread microbial diseases and their economic impact on the society is substantial. The continuing increase of antibiotic resistance worldwide is worrying. As a consequence, well-tolerated, highly effective therapeutic alternatives are without delay needed. Although it has been demonstrated that bacteriophage therapy may be effective and safe for treating UTIs, the number of studied patients is low and there is a lack of randomized controlled trials (RCTs). The present study has been designed as a two-phase prospective investigation: (1) bacteriophage adaptation, (2) treatment with the commercially available but adapted Pyo bacteriophage. The aim was to evaluate feasibility, tolerability, safety, and clinical/microbiological outcomes in a case series as a pilot for a double-blind RCT. In the first phase, patients planned for transurethral resection of the prostate were screened (n = 130) for UTIs and enrolled (n = 118) in the study when the titer of predefined uropathogens (Staphylococcus aureus, E. coli, Streptococcus spp., Pseudomonas aeruginosa, Proteus mirabilis) in the urine culture was ≥104 colony forming units/mL. In vitro analysis showed a sensitivity for uropathogenic bacteria to Pyo bacteriophage of 41% (48/118) and adaptation cycles of Pyo bacteriophage enhanced its sensitivity to 75% (88/118). In the second phase, nine patients were treated with adapted Pyo bacteriophage and bacteria titer decreased (between 1 and 5 log) in six of the nine patients (67%). No bacteriophage-associated adverse events have been detected. The findings of our prospective two-phase study suggest that adapted bacteriophage therapy might be effective and safe for treating UTIs. Thus, well-designed RCTs are highly warranted to further define the role of this potentially revolutionizing treatment option

Hereditary thrombotic thrombocytopenic purpura and COVID-19: Impacts of vaccination and infection in this rare disease.

Introduction Severe COVID-19 is associated with an important increase of von Willebrand factor and mild lowering of ADAMTS13 activity that may, in the presence of a strong inflammatory reaction, increase the risk of acute thrombotic thrombocytopenic purpura (TTP). Although acute episodes of immune-mediated TTP associated with COVID-19 or SARS-CoV-2 vaccination have been reported, data about clinical evolution of hereditary TTP (hTTP) during the pandemic are scarce. Method We conducted a survey among adult patients of the International Hereditary TTP Registry about SARS-CoV-2 vaccination, COVID-19, and occurrence of acute hTTP episodes. Results Of 122 adult hTTP patients invited to participate, 86 (70.5%) responded. Sixty-five had been vaccinated (75.6%), of which 14 had received in addition a booster, resulting in 139 individual vaccine shots. Although vaccinations in patients on plasma prophylaxis were done within 1 week of the last plasma infusion, all 23 patients treated with plasma on demand were vaccinated without prior plasma infusions. One patient on uninterrupted weekly plasma infusions presented within 3 days from his second vaccination with neurological symptoms and computed tomography scan 9 days later showed subacute ischemic/hemorrhagic frontal lobe infarction. A second male patient developed acute myocarditis after his second dose of mRNA-1273 vaccine. Twelve (14%) patients had COVID-19, associated with an acute hTTP episode in three of them: one patient had a transient ischemic attack, one a stroke, and a pregnant woman was hospitalized to intensify plasma treatment. Discussion The risk of an acute episode triggered by COVID-19 seems higher than following vaccination in hTTP patients, who can be safely vaccinated against SARS-CoV-2

Diagnóstico pré-natal: avanços e perspectivas

OBJECTIVE: The development of laboratorial techniques for the prenatal diagnosis of genetic diseases was a great step for clinical genetics, changing reproductive perspectives of high risk families. At Hospital de Clínicas de Porto Alegre (HCPA), the prenatal diagnosis program is part of the Fetal Medicine Group, which includes several professionals of different areas. The main objective of this group is to study, evaluate, diagnose and advice high risk pregnant women. The aim of the present study is to review the main procedures for the prenatal diagnosis and to show the results of our sample regarding the laboratory analysis offer to the pregnant women. MATERIALS AND METHODS: From January 1989 to July 2001, karyotypes were performed for 613 pregnancies, metabolic studies were carried out in 86 pregnancies and molecular analysis was performed for four cases. Prenatal genetic counseling was given to 1,378 families. RESULTS: The prenatal diagnosis of genetic diseases accomplished at HCPA reached a culture growth rate of 98%, which is similar to the result of developed countries. CONCLUSIONS: The prenatal diagnosis is an important tool for the families that are likely to have fetal anomalities. New techniques of diagnosis are being introduced at HCPA, and they will contribute even more to the treatmento of these families. Future prospectives and ethical aspects for prenatal diagnosis are also discussed.OBJETIVO: O desenvolvimento de técnicas para diagnosticar as condições genéticas intra-útero foi um grande avanço na genética clínica, mudando a perspectiva reprodutiva de famílias de risco. No Hospital de Clínicas de Porto Alegre (HCPA), o programa de diagnóstico pré-natal (DPN) de anomalias congênitas faz parte do Grupo de Medicina Fetal, que é composto por uma equipe multidisciplinar, cuja meta principal é estudar, analisar, diagnosticar e aconselhar as gestantes de alto risco. O trabalho apresentado aqui tem como objetivos revisar os principais procedimentos de diagnóstico pré-natal, descrever a nossa amostra e os exames que são oferecidos às nossas gestantes. MATERIAIS E MÉTODOS: De janeiro de 1989 a julho de 2001, foram cariotipadas 613 gestações, realizadas investigações enzimáticas em 86 casos e em 4 foram realizados estudos moleculares em material fetal. Um total de 1.378 novos casos foram avaliados no ambulatório de DPN do HCPA, de julho de 1993 a julho de 2001, para aconselhamento genético reprodutivo. RESULTADOS: O diagnóstico pré-natal de cromossomopatias realizado no HCPA atingiu uma taxa de crescimento de culturas de 98%, índice semelhante ao dos paísesdesenvolvidos. CONCLUSÕES: O diagnóstico pré-natal é um importante recurso para as famílias com risco de anomalia fetal. Novas técnicas de diagnóstico estão em implantação no HCPA, e poderão contribuir ainda mais para o atendimento dessas famílias. Apresentamos também os aspectos éticos envolvidos e algumas perspectivas futuras na área do diagnóstico pré-natal de anormalidades congênitas