Orthopädische Praxis

Positron emission tomography (PET) of the brain using [18F]fluorodeoxyglucose (FDG) is becoming increasingly important for the diagnosis and differential diagnosis of atypical parkinsonian syndrome such as multiple system atrophy (MSA), which is characterized by hypometabolism of the putamen, pons, and cerebellum. We report on a patient with clinically established MSA based on a rapidly progressive, poorly levodopa-responsive parkinsonian syndrome, multidomain autonomic failure, and imaging findings where hereditary spastic paraplegia was discussed as a differential diagnosis. PET images revealed a well-preserved glucose metabolism in the striatum, specifically in the putamen, while metabolism in the cerebellum was significantly reduced. This pattern of glucose metabolism might indicate a distinct subtype of synucleinopathy as proven by seed-amplification assay and should be taken into account when diagnosing patients with MSA.

To identify predictors of treatment changes and to evaluate the effectiveness and patient-reported outcomes (PROs) in patients with rheumatoid arthritis (RA) initiating tofacitinib in a real-world setting. The non-interventional study ESCALATE-RA included 1518 patients with RA from Germany. RA treatment, including all changes in therapy, was documented for 24 months starting from the initial intake of tofacitinib. All patients started with tofacitinib therapy, either as monotherapy or in combination with methotrexate (MTX). The impact of several factors of interest on the number and timing of treatment changes was assessed as primary outcome using Cox proportional hazards models. Further outcomes were tofacitinib drug survival and the use of follow-up disease-modifying antirheumatic drugs after first treatment change. We also assessed the effectiveness, concomitant glucocorticoid (GC) use, PROs (such as functional ability, patient satisfaction, pain and quality of life) and safety. Analyses were based on observed data. 'Lack of efficacy' (HR 3.30) and 'intolerance' (HR 4.43) leading to termination of tofacitinib were key factors favouring therapy changes. Higher patient satisfaction was significantly associated with a reduced likelihood of treatment changes (HR 0.82). Increasing GC doses were associated with a higher probability of step-up/switch changes (HR 1.21). The estimated tofacitinib drug survival was 48% at the end of study. Proportions of patients achieving low disease activity (both Simplified Disease Activity Index (SDAI) and Clinical Disease Activity Index (CDAI) Δ62%) and remission (SDAI Δ25%, CDAI Δ28%) increased from baseline under tofacitinib and were comparable between monotherapy and combination therapy with MTX. Mean concomitant GC dose decreased (2 mg/day). PROs indicated reduced pain and fatigue, while functional ability and quality of life improved. 63.9% of the patients experienced a treatment-emergent adverse event (AE), 8.8% a treatment-emergent AE of special interest and deaths occurred in 0.5%. Key factors for therapy changes in patients with RA treated with tofacitinib were lack of efficacy and intolerance. Higher patient satisfaction was associated with a reduced probability of treatment changes, while increased GC doses led to a higher likelihood of step-ups/switches. Patients demonstrated a marked reduction in disease activity for up to 24 months, along with improvements in functional ability, pain and quality of life. Observed AEs were consistent with the known safety profile of tofacitinib. NCT03387423.

IntroductionAn emerging challenge in early breast cancer (eBC) is improving risk assessment through the use of biomarkers. Clinical guidelines have recommended urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 for risk evaluation. This study aimed to validate the prognostic and predictive impact of uPA/PAI-1.Patients and methodsFrom a prospective cohort of 1270 patients (PiA-study, Prognostic assessment in routine Application, NCT01592825), concentrations of uPA and PAI-1 were determined in fresh tumour tissue (n = 813) by ELISA (FEMTELLE®; LOXO Diagnostics). The uPA/PAI-1 status was defined as low if both uPA and PAI-1 levels were low and as high if one or both were elevated. Primary objectives were the distribution of the uPA/PAI-1 status and its association with clinical/histopathological parameters. Secondary objectives were the association of the uPA/PAI-1 status with recurrence-free interval (RFI), overall survival (OS), and benefit from adjuvant chemotherapy.ResultsA low uPA/PAI-1 status was observed in 37.6% (306 of 813) of the entire cohort and in 47.9% (181 of 378) of those classified as intermediate-risk patients (≥ 35yrs, ≤ pN1, G2, sHR positive/HER2 negative). A low uPA/PAI-1 status was associated with parameters that predict a favourable prognosis. Overall, 96.7% (95% CI 94.5–98.9) of patients with a low uPA/PAI-1-status remained recurrence-free at five years and 87.2% (95% CI 84.1–90.3) with a high uPA/PAI-1 status even after adjustment to tumour size, nodal status, grading, steroid hormone receptor (sHR) status and HER2 status (adjusted HR 2.6, 95% CI 1.29–5.23). Among intermediate-risk patients without chemotherapy (n = 197), the prognostic value was even more pronounced (HR 10.10, 95% CI 1.13–16.12). Similar results were observed for OS. Only patients with a high uPA/PAI-1 status appeared to benefit from chemotherapy (adjusted HR 0.28, 95% CI 0.07-1.12, p = 0.07).ConclusionThis prospective analysis confirms the uPA/PAI-1 status as an independent prognostic factor and suggests a predictive impact considering benefit from chemotherapy.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10549-025-07850-z.

Zusammenfassung Einleitung Um im Leistungssport erfolgreich zu sein, spielen neben individuellen auch verschiedene umweltbedingte Faktoren eine zentrale Rolle. Dazu zählen auch organisationale Stressoren wie lange Reisezeiten, Konflikte im Team oder mit Trainer*innen sowie Schwierigkeiten mit dem benötigten Sportmaterial. Diese wurden bisher vor allem in qualitativen Studien untersucht. Obwohl international validierte Instrumente zur quantitativen Erfassung existieren, fehlt bislang eine entsprechende deutsche Version. Methode In dieser Studie wurde daher der Organizational Stressor Indicator for Sport Performers ins Deutsche übersetzt, adaptiert und im Online-Fragebogenformat an deutsche Bundeskader-Athlet*innen olympischer Sportarten verteilt. Insgesamt nahmen N = 347 Athlet*innen aus 64 Sportarten teil. Zur Evaluation der psychometrischen Eigenschaften wurden konfirmatorische und explorative Faktoranalysen durchgeführt. Zusätzlich wurde der Zusammenhang zu psychischen Belastungsfolgen, erfasst mit einem sportkontextuell angepassten Modul des Munich Employee Health Questionnaire , explorativ untersucht. Ergebnisse Die ursprüngliche 5‑Faktoren-Struktur des Originalfragebogens zeigte keinen zufriedenstellenden Modellfit. Explorative Analysen ergaben eine inhaltlich plausible 6‑faktorielle Struktur mit einem zusätzlichen Faktor („Long-term Logistics“), die einen verbesserten Modellfit (Comparative Fit Index (CFI) ≥ 0,91; Root Mean Square Error of Approximation (RMSEA) = 0,05, Standardized Root Mean Square Residual (SRMR) = 0,06) aufwies. In explorativen Analysen korrelierten die organisationalen Stressoren signifikant mit dem Modul der Belastungsfolgen ( r ≥ 0,50; p < 0,001). Diskussion Die adaptierte deutsche Version des Organizational Stressor Indicator for Sport Performers weist strukturelle Abweichungen zur Originalversion auf, die jedoch inhaltlich nachvollziehbar auf spezifische Adaptionen des Fragebogens zurückgeführt werden können. Die Ergebnisse der explorativen Analysen betonen die Bedeutung organisationaler Stressoren für die psychische Gesundheit von Athlet*innen. Zukünftige Forschung könnte dazu beitragen, diese Stressoren nicht nur besser zu identifizieren, sondern auch gezielt zu adressieren, um langfristig die Rahmenbedingungen im Leistungssport zu optimieren.

Learning outcomes The learning outcomes are as follows: to understand entrepreneurial behaviour through the lens of Effectuation Theory and apply its relevance in early-stage ventures; analyse user feedback and the competition landscape to develop strategies that enhance user adoption; assess the completeness and coherence of a startup pitch using established criteria; evaluate the viability of target segment expansion and recommend strategic adjustments for new market inclusion; and develop a comprehensive growth strategy for a digital health startup by applying key concepts of innovation, market segmentation and strategic decision making. Case overview/synopsis Two female Indian entrepreneurs, Suchitra and Reva, are preparing to pitch their FemTech app, PinkCart, to an angel investor. They have spent two years developing the app, which aims to address a wide range of needs for women in India, including health, psychology, personal life, law, security, social networking and finance. They are focused on developing a compelling pitch highlighting PinkCart’s unique features, such as its user-friendly interface and comprehensive approach to women’s needs, to attract investment and secure the future of their innovative venture. Suchitra and Reva are well-versed in the technical aspects of their software, but they were unsure how to get their dream product from the prototype stage to commercialization. To begin, they would need a seed investment of INR 85m (approximately US$1m), and they would have to convince their investors that their product had the potential to be favourably received by the population they were targeting. Suchitra and Reva also conducted a market survey of the FemTech market to have a better understanding of the market. Their challenge was how to make a compelling presentation to investors and persuade them that their entrepreneurial efforts were worthwhile as this was their first step towards creating PinkCart, an acceptable FemTech app for Indian women. Complexity academic level This case can be used in MBA programs in courses on marketing or entrepreneurship. Supplementary material Teaching notes are available for educators only. Subject code CSS8: Marketing.

Heavy menstrual bleeding (HMB) is a common complication of anticoagulant therapy in menstruating women with venous thromboembolism (VTE). Direct oral anticoagulants (DOAC) used for VTE treatment may differ in their menstrual bleeding profiles. Therefore, the prospective multicenter noninterventional investigator-initiated HEMBLED registry (HE: avy M: enstrual BLE: eding in patients treated with D: OAC) was performed to analyze spontaneous menstrual bleeding in women treated with therapeutic DOAC doses.A modified pictorial blood assessment chart (PBAC) score was used to define the severity of menstrual bleeding. Patients were only included when they did not use hormonal or intrauterine contraception methods. The prospective follow-up was 4 months. The primary endpoint was the comparison of the PBAC scores between the individual DOAC groups.Overall, 73 patients with 213 monthly assessments of the PBAC scores were analyzed. Patients were on average 35 years old and were anticoagulated with apixaban (62%), rivaroxaban (26%), edoxaban (7%), or dabigatran (6%). The PBAC scores of the rivaroxaban group (mean: 145 points) were significantly increased by 54% compared with the apixaban group (mean: 93 points, p = 0.0193). HMB (PBAC score > 100 points) at least once was detected in 53% of the apixaban group compared with 79% of the rivaroxaban group (p = 0.0913). The duration of menstrual bleeding was numerically shorter in the apixaban group compared with the rivaroxaban group (p = 0.1894).DOAC differ in their influence on the intensity of spontaneous menstrual bleeding. This should be taken into account when advising young women with VTE who need an oral anticoagulant.

BackgroundThis epidemiologic cohort study documented clinical and serological data in MS patients over several vaccination cycles against severe respiratory syndrome coronavirus-2 (SARS-CoV-2) in a real-world setting.MethodsAdult patients with MS were included during a period of 26 months from July 2021 if SARS-CoV-2 vaccination was planned, or first dose was given, or vaccination was completed within the last 6 weeks, or vaccination was completed >6 weeks ago and a booster dose was planned within the next 90 days. Humoral immune response to authorized SARS-CoV-2 vaccines was investigated during each vaccination cycle at baseline and approximately 1 and 6 months after vaccination. Immune response was defined as an anti-SARS-CoV-2 spike protein IgG titer >100 BAU/ml above pre-vaccination level and, separately, by the presence of SARS-CoV-2 neutralizing antibodies (NAb) approximately 1 month after the last vaccination.ResultsOf 159 patients enrolled, 140 (88.1%) were being treated with a DMT. Most patients (67.9%, n = 108) entered the study after complete initial SARS-CoV-2 vaccination (up to two doses) and before the 1st booster dose. Approximately 1 month after the 1st booster vaccination, response was seen in 68.1% of the patients (n = 79/116) based on anti-S1-IgG increase and in 72.1% (n = 88/122) based on NAb seropositivity. Persisting immune response approximately 6 months after vaccination was observed in 71.8% (n = 51/71) and in 93.7% (n = 74/79) of the responders, respectively. Adequate humoral immune response and persistence of response was less frequent in patients on anti-CD20 antibodies or sphingosine-1-phosphate receptor (S1PR) modulators compared to patients on other DMTs or DMT-untreated patients. Breakthrough infections with the SARS-CoV-2 virus were reported in 58 patients (36.5%). Seven patients (4.4%) experienced an MS relapse during the study period.ConclusionsWith the exception of anti-CD20 antibodies and S1PR modulators, DMTs did not impair humoral response to any of the authorized SARS-CoV-2 vaccines. Persistence of humoral immune response was seen over a period of at least 3 months in the majority of initial responders but was decreased in the anti-CD20 antibodies/S1PR modulator subgroup.Clinical trial registrationThis epidemiological study is registered in the German Clinical Trials Register (DRKS00025893).

IntroductionThis study evaluates the efficacy and safety of faricimab in a real-world cohort of treatment-naïve patients with neovascular age-related macular degeneration (nAMD). Data were retrospectively collected from 130 eyes of 118 patients across 11 centers of the Swiss Retina Research Network, all treated with faricimab using a treat-and-extend regimen and followed for 12 months between May 2022 and October 2024.MethodsDemographic data, visual and anatomical outcomes, treatment intervals, and adverse events were extracted from the electronic medical records over a 12-month follow-up period. Main outcomes included change in best corrected visual acuity (BCVA), central retinal thickness (CRT), presence of intra- and subretinal fluid, retinal pigment epithelial detachment (PED), injection intervals, and safety. Data are presented as mean ± standard deviation.ResultsTwelve months after the initiation of faricimab therapy, mean BCVA improved from 64.6 ± 14.1 to 69.2 ± 20.3 ETDRS (Early Treatment of Diabetic Retinopathy Study) letters (p < 0.001), while mean CRT decreased from 386.3 ± 172.3 to 246.6 ± 90.4 μm (p < 0.001). An early anatomical response to faricimab was observed in 34.6% of eyes achieving complete retinal fluid resolution after the first injection and in 55.6% after 12 months. The mean treatment interval was extended to 10.5 ± 4.3 weeks, with 26.2% of eyes achieving intervals of 8–11 weeks and 39.2% achieving intervals of ≥ 12 weeks after 12 months. Intraocular inflammation occurred in 0.77% of eyes (n = 1, anterior uveitis); serious adverse events were not reported.ConclusionFaricimab demonstrates favorable anatomical and functional outcomes with extended treatment intervals in a majority of patients with treatment-naïve nAMD, offering the potential of reduced treatment burden and the absence of retinal fluid in more than half of the subjects during the first year, while maintaining safety in a real-world setting.

Zusammenfassung: Theoretischer Hintergrund: Der Einsatz Digitaler Gesundheitsanwendungen für psychische Erkrankungen (PsyDiGA) wird kontrovers diskutiert. Fragestellung: Für wen und in welchem Behandlungskontext sind PsyDiGA (nicht) geeignet? Methode: Bundesweit niedergelassene Psychotherapeut_innen erhielten einen Fragebogen, der stratifiziert nach Verschreibungserfahrung mit PsyDiGA ausgewertet wurde. Zusätzlich analysierten wir leitfadenbasierte Interviews mittels qualitativer Inhaltsanalyse. Ergebnisse: Es lagen 321 Fragebögen sowie 16 Interviews vor. PsyDiGA seien geeignet für Patient_innen mit eingeschränkter Mobilität und ungeeignet bei Personen älter als 65 Jahre. Die Befragten lehnten PsyDiGA als primäre Behandlungsmethode ab, während dem Einsatz zur Überbrückung von Wartezeiten mehrheitlich zugestimmt wurde. Psychotherapeut_innen mit und ohne Verschreibungserfahrung von PsyDiGA unterschieden sich zum Teil deutlich hinsichtlich ihres Antwortverhaltens. Aus den Interviews ergaben sich die Notwendigkeit von persönlichem Kontakt, die Berücksichtigung psychischer Belastung sowie Technikaffinität als Kriterien für (fehlende) Eignung. Schlussfolgerungen: Die Verschreibung von PsyDiGA scheint abhängig von der therapeutischen Orientierung sowie der Abwägung zwischen Notwendigkeit und Möglichkeiten zu persönlicher Kontaktaufnahme zu sein.