The status of transgender persons in civil law

The status of transgender persons in civil law Abstract The thesis focuses on the legal regulation of gender reassignment in the Czech Republic, both in terms of civil law and constitutional law. The thesis initially focuses mainly on the correct definition of important terms and their essential meaning. Attention is paid not only to transsexuality itself and its forms, but also to related conditions such as intersexuality and transvestitism. After discussing the human rights foundations of gender reassignment, the thesis briefly discusses the historical genesis of the legal regulation of gender reassignment. This is followed by a description of the currently effective legislation, including its shortcomings with regard not only to domestic law but also to the Czech Republic's international obligations under international human rights treaties. In this area, the greatest emphasis is then placed on the decision-making of the European Court of Human Rights, which is more advanced than Czech national courts in this area. Apart from transsexuality and the process of gender reassignment, the thesis also focuses on the opposite phenomenon, namely detransition. This topic is often neglected, even though it is a topic essentially inseparable from gender reassignment and offers many interesting legal issues. The...Postavení transgender osob v civilním právu Abstrakt Diplomová práce se zaměřuje na právní úpravu změny pohlaví v České republice, a to jak v rovině civilněprávní, tak ústavněprávní. Práce se zprvu soustřeďuje zejména na správnou definici významných pojmů a na jejich základní obsah. Pozornost je věnována nejen samotné transsexualitě a jejím formám, ale také souvisejícím stavům jako je intersexualita a transvestitismus. Po rozebrání lidskoprávních základů změny pohlaví se práce stručně zaobírá historickou genezí zákonné právní úpravy změny pohlaví. Následuje popis aktuálně účinné právní úpravy včetně jejích nedostatků s ohledem nejen na vnitrostátní právo, ale také na mezinárodní závazky České republiky plynoucí z mezinárodních smluv o lidských právech. V této oblasti je pak největší důraz kladen na rozhodovací činnost Evropského soudu pro lidská práva, který je v této oblasti pokrokovější než vnitrostátní soudy. Kromě samotné transsexuality a procesu změny pohlaví se práce věnuje také v podstatě opačnému jevu, a to detranzici. Toto téma je často opomíjeno, ačkoliv se jedná o téma od změny pohlaví v podstatě neoddělitelné a nabízející spoustu zajímavých právních otázek. Předmětem posledních dvou obsahových částí této diplomové práce je pak vnitrostátní i zahraniční judikatura. Rozhodovací činnost českých...Department of Civil LawKatedra občanského právaFaculty of LawPrávnická fakult

Lis1 is an initiation factor for dynein-driven organelle transport

The molecular motor cytoplasmic dynein is responsible for most minus-end–directed, microtubule-based transport in eukaryotic cells. It is especially important in neurons, where defects in microtubule-based motility have been linked to neurological diseases. For example, lissencephaly is caused by mutations in the dynein-associated protein Lis1. In this paper, using the long, highly polarized hyphae of the filamentous fungus Aspergillus nidulans, we show that three morphologically and functionally distinct dynein cargos showed transport defects in the genetic absence of Lis1/nudF, raising the possibility that Lis1 is ubiquitously used for dynein-based transport. Surprisingly, both dynein and its cargo moved at normal speeds in the absence of Lis1 but with reduced frequency. Moreover, Lis1, unlike dynein and dynactin, was absent from moving dynein cargos, further suggesting that Lis1 is not required for dynein-based cargo motility once it has commenced. Based on these observations, we propose that Lis1 has a general role in initiating dynein-driven motility

Combination of Immunotherapy and Radiotherapy-The Next Magic Step in the Management of Lung Cancer?

none4sinoneHendriks L.E.L.; Menis J.; De Ruysscher D.K.M.; Reck M.Hendriks, L. E. L.; Menis, J.; De Ruysscher, D. K. M.; Reck, M

Avelumab Versus Platinum-Based Doublet Chemotherapy as First-Line Treatment for Patients With High-Expression Programmed Death-Ligand 1–Positive Metastatic NSCLC: Primary Analysis From the Phase 3 JAVELIN Lung 100 Trial

Avelumab; Chemotherapy; Non–small cell lung cancerAvelumab; Quimioteràpia; Càncer de pulmó de cèl·lules no petitesAvelumab; Quimioterapia; Cáncer de pulmón de células no pequeñasIntroduction We report the primary analysis from JAVELIN Lung 100, a phase 3 trial comparing avelumab (anti⁠–programmed death-ligand 1 [PD-L1]) versus platinum-based doublet chemotherapy as first-line treatment for PD-L1–positive (+) advanced NSCLC. Methods Adults with PD-L1+ (≥1% of tumor cells; PD-L1 immunohistochemistry 73-10 pharmDx), EGFR and ALK wild-type, previously untreated, stage IV NSCLC were randomized to avelumab 10 mg/kg every 2 weeks (Q2W), avelumab 10 mg/kg once weekly (QW) for 12 weeks and Q2W thereafter, or platinum-based doublet chemotherapy every 3 weeks. Primary end points were overall survival (OS) and progression-free survival (PFS) per independent review committee. The primary analysis population was patients with high-expression PD-L1+ tumors (≥80% of tumor cells). Results A total of 1214 patients were randomized to avelumab Q2W (n = 366), avelumab QW (n = 322), or chemotherapy (n = 526). In the primary analysis population, hazard ratios (HRs) for OS and PFS with avelumab Q2W (n = 151) versus chemotherapy (n = 216) were 0.85 (95% confidence interval [CI]: 0.67–1.09; one-sided p = 0.1032; median OS, 20.1 versus 14.9 mo) and 0.71 (95% CI: 0.54–0.93; one-sided p = 0.0070; median PFS, 8.4 versus 5.6 mo), respectively. With avelumab QW (n = 130) versus chemotherapy (n = 129), HRs were 0.79 (95% CI: 0.59–1.07; one-sided p = 0.0630; median OS, 19.3 versus 15.3 mo) and 0.72 (95% CI: 0.52–0.98; one-sided p = 0.0196; median PFS, 7.5 versus 5.6 mo), respectively. No new safety signals were observed. Conclusions Longer median OS and PFS were observed with avelumab versus platinum-based doublet chemotherapy in advanced NSCLC, but differences in OS and PFS were not statistically significant, and the trial did not meet its primary objective. ClinicalTrials.gov Identifier: NCT02576574

Beurteilung des Therapieerfolgs – konventionelle versus neue Methoden

New ways of evaluating treatment success among thoracic tumour patients are increasingly being used alongside more conventional methods. These new approaches include tumour regression grading, CAD volumetry (computer-assisted volumetry), determination of the tumour density and tumour perfusion as well as the use of positron emission tomography (PET) using (18)F-FDG (fluorodeoxyglucose) or other tracers. Increasingly, endpoints that impact directly on the patient's quality of life and tumour-related symptoms are becoming more relevant factors together with the objectively measurable parameters used for assessing treatment response. This contribution describes the potential value of new methods and end-points from the point of view of a pathologist, radiologist, nuclear medicine specialist, radiotherapist, thoracic surgeon, medical and pneumology oncologist, and general practitioner

HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor–Mutated Non–Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy

Non-small-cell lung cancer; Mutation; Epidermal growth factorCáncer de pulmón de células no pequeñas; Mutación; Factor de crecimiento epidérmicoCàncer de pulmó de cèl·lules no petites; Mutació; Factor de creixement epidèrmicPURPOSE Patritumab deruxtecan, or HER3-DXd, is an antibody-drug conjugate consisting of a fully human monoclonal antibody to human epidermal growth factor receptor 3 (HER3) attached to a topoisomerase I inhibitor payload via a stable tetrapeptide-based cleavable linker. We assessed the efficacy and safety of HER3-DXd in patients with epidermal growth factor receptor (EGFR)–mutated non–small-cell lung cancer (NSCLC). METHODS This phase II study (ClinicalTrials.gov identifier: NCT04619004) was designed to evaluate HER3-DXd in patients with advanced EGFR-mutated NSCLC previously treated with EGFR tyrosine kinase inhibitor (TKI) therapy and platinum-based chemotherapy (PBC). Patients received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks or an uptitration regimen (3.2 → 4.8 → 6.4 mg/kg). The primary end point was confirmed objective response rate (ORR; RECIST 1.1) by blinded independent central review (BICR), with a null hypothesis of 26.4% on the basis of historical data. RESULTS Enrollment into the uptitration arm closed early on the basis of a prespecified benefit-risk assessment of data from the phase I U31402-A-U102 trial. In total, 225 patients received HER3-DXd 5.6 mg/kg once every 3 weeks. As of May 18, 2023, median study duration was 18.9 (range, 14.9-27.5) months. Confirmed ORR by BICR was 29.8% (95% CI, 23.9 to 36.2); median duration of response, 6.4 months; median progression-free survival, 5.5 months; and median overall survival, 11.9 months. The subgroup of patients with previous osimertinib and PBC had similar outcomes. Efficacy was observed across a broad range of pretreatment tumor HER3 membrane expression levels and across diverse mechanisms of EGFR TKI resistance. In patients with nonirradiated brain metastases at baseline (n = 30), the confirmed CNS ORR by BICR per CNS RECIST was 33.3% (95% CI, 17.3 to 52.8). The safety profile (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) was manageable and tolerable, consistent with previous observations. CONCLUSION After tumor progression with EGFR TKI therapy and PBC in patients with EGFR-mutated NSCLC, HER3-DXd once every 3 weeks demonstrated clinically meaningful efficacy with durable responses, including in CNS metastases. A phase III trial in EGFR-mutated NSCLC after progression on an EGFR TKI is ongoing (HERTHENA-Lung02; ClinicalTrials.gov identifier: NCT05338970)

Aktuelle Entwicklungen und Perspektiven zielgerichteter Therapien

Current Developments and Perspectives in Targeted Therapies Many different approaches for improving the prognosis of patients with advanced non-small-cell lung cancer (NSCLC) are currently being investigated. This article discusses the significance of maintenance therapy after primary chemotherapy and reviews study data on second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), inhibitors of insulin-like growth factor receptors (IGFR), vascular-disrupting agents (VDAs) and multi-TKIs of vascular endothelial growth factor receptors (VEGFR). The article also looks at the future prospects of using genetic markers in the field of NSCLC

TROPION-Lung08: phase III study of datopotamab deruxtecan plus pembrolizumab as first-line therapy for advanced NSCLC

Antibody–drug conjugate; Immuno-oncology; Non-small-cell lung cancerConjugado anticuerpo-fármaco; Inmuno-oncología; Cáncer de pulmón de células no pequeñasConjugat anticòs-fàrmac; Immuno-oncologia; Càncer de pulmó de cèl·lules no petitesPembrolizumab monotherapy is a standard first-line treatment for PD-L1–high advanced non-small-cell lung cancer (NSCLC) without actionable genomic alterations (AGA). However, few patients experience long-term disease control, highlighting the need for more effective therapies. Datopotamab deruxtecan (Dato-DXd), a novel trophoblast cell-surface antigen 2-directed antibody–drug conjugate, showed encouraging safety and antitumor activity with pembrolizumab in advanced NSCLC. We describe the rationale and design of TROPION-Lung08, a phase III study evaluating safety and efficacy of first-line Dato-DXd plus pembrolizumab versus pembrolizumab monotherapy in patients with advanced/metastatic NSCLC without AGAs and with PD-L1 tumor proportion score ≥50%. Primary end points are progression-free survival and overall survival; secondary end points include objective response rate, duration of response, safety and presence of antidrug antibodies.This study is sponsored by Daiichi Sankyo, Inc. In July 2020, Daiichi Sankyo entered into a global development and commercialization collaboration agreement with AstraZeneca for datopotamab deruxtecan (Dato-DXd). Pembrolizumab is being provided under agreement by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD). BP Levy received consulting fees from Amgen, AstraZeneca, Daiichi Sankyo, Eli Lilly, Janssen, Mirati, Novartis, Pfizer, and Roche/Genentech. E Felip received consulting fees and/or honoraria from Amgen, AstraZeneca, Bayer, BerGenBio, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Roche, GSK, Janssen, Medical Trends, Medscape, Merck Serono, MSD, Novartis, PeerVoice, Peptomyc, Pfizer, Sanofi, Takeda, and touchONCOLOGY and grant funding to her institution from Merck KGaA and Fundación Merck Salud. E Felip is an independent member of the Grífols Board of Directors. M Reck received consulting fees, honoraria, and support for attending meetings from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, GSK, Mirati, Merck, MSD, Novartis, Pfizer, Sanofi, Roche, and Regeneron and served on data safety monitoring boards for Daiichi Sankyo and Sanofi. JCH Yang received consulting or advisory fees from Ono Pharmaceuticals and Pfizer, grant funding to his institution from AstraZeneca and advisory or consulting fees to his institution from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Gilead, GSK, Johnson & Johnson, Merck KGaA, MSD, Novartis, Puma Technology, Roche/Genentech, Takeda and Yuhan Pharmaceuticals. F Cappuzzo received consulting fees from AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Janssen, Merck, MSD, Novartis, Pfizer, PharmaMar, Roche, and Takeda. C Zhou received consulting fees and/or honoraria from Amoy Diagnostics, AnHeart Therapeutics, Boehringer Ingelheim, CStone Pharmaceuticals, Luye Pharma Group, Eli Lilly China, Jiangsu Hengrui Pharmaceuticals, Innovent Biologics, MSD, Qilu Pharmaceutical, Roche, Sanofi, and TopAlliance Biosciences. S Rawat is an employee of and owns stock and/or stock options in Daiichi Sankyo. P Basak and J Xie are employees of Daiichi Sankyo. L Xu was an employee at MSD at the time this study was designed and is a current employee of AstraZeneca. J Sands received consulting fees from AstraZeneca, Curadev, Daiichi Sankyo, Guardant Health, Jazz Pharmaceuticals, Medtronic, PharmaMar, Sanofi, and Takeda and is the treasurer of the Rescue Lung Society. Y Yoneshima declares no potential conflicts. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed