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Treatment concepts for patients with localized and locally advanced non-small cell lung cancer (NSCLC) are based on local treatment, surgery and/or radiotherapy, with curative intent. An adjuvant systemic treatment is added after primary resection of an operable NSCLC primarily to reduce the systemic risk of relapse. Locally advanced stages with mediastinal lymph node involvement carry a substantial risk of local and distant recurrence and require multimodal treatment strategies in an interdisciplinary approach. Recently, immunotherapy with programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) checkpoint inhibitors is increasingly being integrated into adjuvant, neoadjuvant or perioperative treatment concepts.Within a few years the introduction of immune checkpoint inhibitors (ICI) fundamentally changed the treatment landscape of patients with metastatic non-small cell lung cancer (NSCLC) and improved survival for a relevant proportion of patients. Immune monotherapies are highly efficient in cancers showing a PD-L1 overexpression ≥ 50% of tumor cells, all others with a lower level and independent from the PD-L1 expression can be treated with various treatment combinations. In a curative setting all PD-L1 positive patients (≥ 1%) who underwent chemoradiotherapy to reduce disease relapse and subsequently to improve survival should undergo an ICI maintenance treatment. Furthermore, positive results from phase III studies are also available for adjuvant treatment of patients with resectable NSCLC, whereby an EMA approval is currently pending. The treatment with ICIs has given rise to a new class of immune-mediated adverse side effects, which occur in approximately one third of the patients and range from easily substituted endocrinopathies to life-threatening organ toxicity. An anticipatory monitoring as well as interdisciplinary treatment are therefore the keys to avoiding progression of higher grade potentially fatal toxicities.

Patients with an unclear diagnosis and suspected rare disease pose special challenges to physicians, among others.

The ZSE-DUO project aims to establish whether patient care under the joint supervision of asomatic expert and amental health expert can improve diagnostic efficacy and precision, as well as shorten the time to diagnosis.

ZSE-DUO has successfully recruited more than 1000patients at eleven national centres for rare diseases in acontrol and an intervention group. The findings are being analysed by three evaluating institutions.

The study is currently in its final phase. The results will be published in further papers.

The study is currently in its final phase. The results will be published in further papers.Monitoring of vitamin K antagonist treatment with the international normalized ratio (INR) is obligatory, whereas this only applies to direct oral anticoagulants (DOAC) or low molecular weight heparin in the context of selected clinical scenarios. For DOAC the focus is on the determination of trough and peak plasma levels of the drug but for low molecular weight heparins the focus is on anti-Xa activity. The timing of blood sampling in relation to drug intake is essential for the interpretation of the results. A new-onset thrombocytopenia during hospitalization is common. The cause can frequently be identified based on the classification of the underlying disease, the day of onset and documentation of the dynamics of thrombocytopenia as well as the medication history. The importance of thrombophilia testing following a venous thromboembolism has decreased in the absence of clear therapeutic consequences; however, antiphospholipid antibody syndrome must not be overlooked as both the duration of treatment and the choice of anticoagulant depend on this.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumoral overproduction of FGF-23. Due to local recurrence, we describe the long-term efficacy and safety profile of burosumab, an anti-FGF-23 monoclonal antibody, in a TIO patient after three unsuccessfully surgical attempts.

TIO is a rare paraneoplastic syndrome caused by tumoral overproduction of fibroblast growth factor 23 (FGF23), resulting in hyperphospaturia, hypophosphatemia, and osteomalacia. Surgery is the only definitive treatment, but tumor can locally recur, even after years from primary surgery. Furthermore, some tumors cannot be removed by surgery due to their location.

We describe the case of a 54-year-old woman affected by recurrent TIO who, after three unsuccessful surgical attempts of tumor removal, was treated with burosumab, an anti-FGF-23 monoclonal antibody.

The patient was referred to our Bone Unit after experiencing several fractures in different sites, both traumatic and non-traumatic. At the time of affected by TIO treated with burosumab for more than 2years. Burosumab is a promising therapy in the medical treatment of TIO refractory or not eligible for definitive surgery, with good efficacy and safety profile.

To our knowledge, this is the first European patient affected by TIO treated with burosumab for more than 2 years. Burosumab is a promising therapy in the medical treatment of TIO refractory or not eligible for definitive surgery, with good efficacy and safety profile.

In this retrospective study, the effectiveness of short-term teriparatide with denosumab in reducing fragility fracture risk was determined in comparison with denosumab monotherapy. Administration of sequential teriparatide with denosumab showed excellent outcomes in suppressing the risk for fragility fractures compared with denosumab monotherapy.

To determine the effectiveness of short-term teriparatide with denosumab in reducing the risk of fragility fractures in comparison to denosumab monotherapy.

The data of postmenopausal patients treated with denosumab for > 2years between August 2015 and October 2020 were retrospectively analyzed. One hundred sixty four postmenopausal women of a total 615 were excluded, since they did not undergo > 2 bone mineral density (BMD) tests, were lost to follow-up, or received long-term teriparatide therapy. Total 320 patients received denosumab monotherapy and 131 patients received teriparatide for ≥ 3months followed by denosumab. The number of osteoporotic fractpressing the risk of fragility fractures compared with denosumab monotherapy.

Short-term teriparatide use before denosumab showed excellent outcomes in suppressing the risk of fragility fractures compared with denosumab monotherapy.The diagnostics and treatment of pediatric urology patients in the clinical routine can be extremely challenging. In comparison to adult patients, congenital diseases, more time consuming examinations and limited options in addition to the parents' expectations must be taken into account in the diagnostic work up. In this first of two parts we will delve into ultrasound diagnostics as the cornerstone in the diagnostic pathway of children with hydronephrosis ans take a closer look on contrast enhanced ultrasound (CEUS). Conventional voiding cystourethrography still plays a major role in the diagnostic pathway of vesicoureteric reflux and will be treated in this article. Computed tomography should only be considered in pediatric patients in rare cases, always taking radiation into critical account. Magnetic resonance imaging provides an excellent anatomical overview without exposing the child to unnecessary radiation. This article provides an overview on the diagnostic imaging studies in pediatric urology and brings tips for the diagnostic evaluation.Molecular analysis of disseminated tumour cells (DTC) may aid in predicting the course of the disease and response to therapies in individual patients. It has been shown in bladder cancer and many other cancer types that the presence of disseminated tumour cells or occult micrometastases in bone marrow or lymph nodes is associated with shorter survival. This type of analysis is particularly important for patients who have been declared disease-free after postsurgery histopathological and clinical imaging analysis. However, comprehensive molecular analysis of disseminated tumour cells is challenging due to the low amount of material and great heterogeneity of the disease. Therefore, currently the routine molecular analysis of these cells is hardly possible in daily clinical practice. Nevertheless, we see daily advances in clinical utility of analysis of cellular or cell-free liquid biopsy analytes taken before, during or after surgery. TVB-3664 These advances will enable an integration of translational research workflows into clinical decision-making.

The treatment options for locally advanced and metastatic urothelial carcinoma (UC) are currently limited to established chemotherapy and immunotherapy protocols. Targeted treatment is so far restricted to a small subgroup of patients. Urothelial organoid systems could make a decisive contribution in establishing effective personalized treatment options by enabling drug response prediction through testing the sensitivity of individual patients. The aim of this article is to describe the state of the science of clinically applicable organoid systems for UC.

Asystematic literature search was conducted in several medical databases (Medline, Cochrane Library) and study registers (ClinicalTrials.gov, the EU Clinical Trials Register and the WHO International Clinical Trials Registry). The search terms and the search strategy were adapted to the databases used.

Overall, 7studies met the inclusion criteria on the topic of UC organoids. These studies describe the fundamental workflow in establishing organoid systems in patients with tumors of the urinary bladder or the renal pelvis. The success rates in generating organoids from non-muscle-invasive bladder cancer were 70-77% and for muscle-invasive bladder cancer 42%. For patient organoids systematic drug testing was carried out.

The generation of UC organoids is feasible and the ex vivo testing of individual treatment forms is possible. Due to the lack of a standardized methodology, their implementation remains experimental at the moment. The methodology has a high potential to provide a personalized treatment concept to patients with urothelial cancer.

The generation of UC organoids is feasible and the ex vivo testing of individual treatment forms is possible. Due to the lack of a standardized methodology, their implementation remains experimental at the moment. The methodology has a high potential to provide a personalized treatment concept to patients with urothelial cancer.

In view of continued development of new oncological approaches, there is ahigh demand for personalized tumor therapy. However, fast and effective functional platforms for the prediction of individual patient response to drug therapy are largely unavailable. Various promising approaches have already been described for three-dimensional cell culture models, which represent cellular complexity and almost identical structures of the original tumor tissue.

Based on acase report, we show the capability and results of anovel test system using patient-derived microtumors (PDMs) and autologous tumor-infiltrating lymphocytes (TILs) for the prediction of response to cancer therapy.

We established PDMs and TILs from primary tumor tissue of arenal cell carcinoma metastasis. Using immunohistochemistry and multiplex florescence-activated cell sorting (FACS ) analyses, the PDMs and TILs were characterized regarding to histology and immunophenotype. Tumor-specific cytotoxicity of standard of care and investigational compounds were assessed.

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