[Prevention of progression of allergic bronchial asthma as an occupational disease]. / Prävention eines Progresses des allergischen Asthma bronchiale als Berufskrankheit.

Since January 1st, 2021, termination of a harmful activity as a requirement for its recognition as an occupational disease (OD) has been abolished in Germany. This also includes the OD No. 4301 in accordance with Appendix 1 of the Occupational Diseases Ordinance (ODO) (obstructive respiratory diseases caused by allergenic substances). There has already been a significant increase in the number of diseases recognized under this OD. In this article, we present two patients with allergic (in the second case report mixed-form) bronchial asthma, in whom a medically easily preventable disease progression occurred as a result of continued occupational exposure to allergens as a farmer. According to § 3 (1) ODO, if there is a "risk that an occupational disease will develop, recur or worsen", the statutory accident insurance institutions are obliged to "counteract this danger with all suitable means". These individual preventive measures are compulsory by law and medically sensible, even under circumstances where only the risk of the genesis of an OD is given. Nonetheless, they are likely to be indicated and offered more frequently in the future due to an increased recognition of ODs. Unfavorable clinical courses such as those described in the two case reports presented here should therefore occur less frequently in the future.

GERNERMED++: Semantic annotation in German medical NLP through transfer-learning, translation and word alignment.

We present a statistical model, GERNERMED++, for German medical natural language processing trained for named entity recognition (NER) as an open, publicly available model. We demonstrate the effectiveness of combining multiple techniques in order to achieve strong results in entity recognition performance by the means of transfer-learning on pre-trained deep language models (LM), word-alignment and neural machine translation, outperforming a pre-existing baseline model on several datasets. Due to the sparse situation of open, public medical entity recognition models for German texts, this work offers benefits to the German research community on medical NLP as a baseline model. The work serves as a refined successor to our first GERNERMED model. Similar to our previous work, our trained model is publicly available to other researchers. The sample code and the statistical model is available at: https://github.com/frankkramer-lab/GERNERMED-pp.

[Occupational obstructive airway diseases: How can early diagnosis be made to avoid chronic courses?] / Obstruktive Atemwegserkrankungen im Beruf: Wie gelingt eine frühe Diagnostik zur Vermeidung chronischer Verläufe?

Since abolishing the obligation to terminate the harmful professional activity from January 1st, 2021 onwards for some occupational diseases including obstructive respiratory diseases in Germany, the recognition of occupational diseases coded under 4301, 4302 and 1315 according the Occupational Diseases Ordinance has increased significantly. By the time these diseasese are recognized, they are usually already at an advanced stage. Therefore, early detection will play a greater role in the future, as the statutory accident insurance can offer individual preventive measures in order to minimize the consequences of illness and thus also the socio-economic burden. However, precursors of such obstructive airway diseases are often overlooked. For optimizing early detection, the statutory accident insurance worked out an early notification procedure for the respiratory tract - comparable to the already well-established dermatological procedure. "Early cases" from the pilot regions can be reported there; to qualify for being reported as early cases, patients must persue insured professional activity with potential effects on the respiratory tract and suffer from a disease of the upper or lower respiratory tract according to the ICD-10 code (e.g. J31.0 chronic rhinitis).

Heat Shock Protein 90 as a Prognostic Marker and Therapeutic Target for Adrenocortical Carcinoma.

Background: Adrenocortical carcinoma (ACC) is a rare tumor entity with restricted therapeutic opportunities. HSP90 (Heat Shock Protein 90) chaperone activity is fundamental for cell survival and contributes to different oncogenic signaling pathways. Indeed, agents targeting HSP90 function have shown therapeutic efficacy in several cancer types. We have examined the expression of HSP90 in different adrenal tumors and evaluated the use of HSP90 inhibitors in vitro as possible therapy for ACC. Methods: Immunohistochemical expression of HSP90 isoforms was investigated in different adrenocortical tumors and associated with clinical features. Additionally, a panel of N-terminal (17-allylamino-17-demethoxygeldanamycin (17-AAG), luminespib, and ganetespib) and C-terminal (novobiocin and silibinin) HSP90 inhibitors were tested on various ACC cell lines. Results: Within adrenocortical tumors, ACC samples exhibited the highest expression of HSP90ß. Within a cohort of ACC patients, HSP90ß expression levels were inversely correlated with recurrence-free and overall survival. In functional assays, among five different compounds tested luminespib and ganetespib induced a significant decrease in cell viability in single as well as in combined treatments with compounds of the clinically used EDP-M scheme (etoposide, doxorubicin, cisplatin, mitotane). Inhibition of cell viability correlated furthermore with a decrease in proliferation, in cell migration and an increase in apoptosis. Moreover, analysis of cancer pathways indicated a modulation of the ERK1/2-and AKT-pathways by luminespib and ganetespib treatment. Conclusions: Our findings emphasize HSP90 as a marker with prognostic impact and promising target with N-terminal HSP90 inhibitors as drugs with potential therapeutic efficacy toward ACC.