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Aim: To assess outcomes in patients with advanced adenocarcinoma non-small-cell lung cancer who received nintedanib plus docetaxel after progression on prior chemotherapy followed by immune checkpoint inhibitor (ICI) therapy. Patients & methods: VARGADO is a prospective, noninterventional study. We describe initial data from a cohort of 22 patients who received nintedanib plus docetaxel after chemotherapy and ICI therapy. Results: Median progression-free survival with nintedanib plus docetaxel was 5.5 months (95% CI: 1.9–8.7 months). The objective response rate was 7/12 (58%) and the disease control rate was 10/12 (83%). Data for overall survival rate 12 months after the start of treatment (primary end point) are not yet mature and are not reported. Of 22 patients, 73% experienced drug-related adverse events; adverse events led to treatment discontinuation in 32% of patients. Conclusion: These data highlight the potential clinical benefit of nintedanib plus docetaxel in patients who failed prior ICI therapy.
Trial registration number: NCT02392455
Aims: Balloon pulmonary angioplasty (BPA) is an interventional treatment modality for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Therapy monitoring, based on non-invasive biomarkers, is a clinical challenge. This post-hoc study aimed to assess dynamics of high-sensitivity cardiac troponin T (hs-cTnT) as a marker for myocardial damage and its relation to N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels as a marker for cardiac wall stress.
Methods and results: This study included 51 consecutive patients who underwent BPA treatment and completed a 6-month follow-up (6-MFU) between 3/2014 and 3/2017. Biomarker measurement was performed consecutively prior to each BPA and at 6-MFU.
In total, the 51 patients underwent an average of 5 BPA procedures. The 6-month survival rate was 96.1%. The baseline (BL) meanPAP (39.5±12.1mmHg) and PVR (515.8±219.2dyn×sec×cm-5) decreased significantly within the 6-MFU (meanPAP: 32.6±12.6mmHg, P<0.001; PVR: 396.9±182.6dyn×sec×cm-5, P<0.001). At BL, the median hs-cTnT level was 11 (IQR 6–16) ng/L and the median NT-proBNP level was 820 (IQR 153–1872) ng/L. The levels of both biomarkers decreased steadily after every BPA, showing the first significant difference after the first procedure. Within the 6-MFU, hs-cTnT levels (7 [IQR 5–12] ng/L; P<0.001) and NT-proBNP levels (159 [IQR 84–464] ng/l; P<0.001) continued to decrease. The hs-cTnT levels correlated with the PVR (rrs = 0.42; p = 0.005), the meanPAP (rrs = 0.32; p = 0.029) and the NT-proBNP (rrs = 0.51; p<0.001) levels at BL.
Conclusion: Non-invasive biomarker measurement provides valuable evidence for the decreasing impairment of myocardial function and structure during BPA therapy. Changes in hs-cTNT levels are suggestive for a reduction in ongoing myocardial damage.
Seit über zehn Jahren werden am Institut für Sportwissenschaften die Auswirkungen von Vibrationen auf die Bewegungssteuerung des Menschen erforscht. Das Team um Dr. Christian Haas und Prof. Dietmar Schmidtbleicher fand dabei ein weites Funktionsspektrum mit physiologisch positiven, aber auch negativen Effekten. So können gleichförmige hochfrequente Vibrationen zu Wahrnehmungsstörungen führen oder einen Verlust der Reflextätigkeit bewirken. Andererseits verbessert ein Training mit variablen Vibrationsreizen, so genannten »Stochastischen Resonanzen«, die Koordination. Diese ständig wechselnden Reize trainieren das Zusammenspiel zwischen Sensoren, Gehirn und Muskulatur und bewirken effizientere, an die jeweilige Anforderungssituation angepasste Bewegungsabläufe. Interessanterweise zeigen sich diese Effekte sowohl bei Hochleistungsathleten als auch bei Patienten mit Bewegungsstörungen.
Background: Dentists are at a higher risk of suffering from musculoskeletal disorders (MSD) than the general population. However, the latest study investigating MSD in the dental profession in Germany was published about 20 years ago. Therefore, the aim of this study was to reveal the current prevalence of MSD in dentists and dental students in Germany. Methods: The final study size contained 450 (287 f/163 m) subjects of different areas of specialization. The age of the participants ranged from 23 to 75 years. The questionnaire consisted of a modified version of the Nordic Questionnaire, work-related questions from the latest questionnaire of German dentists, typical medical conditions and self-developed questions. Results: The overall prevalence showed that dentists suffered frequently from MSD (seven days: 65.6%, twelve months: 92%, lifetime: 95.8%). The most affected body regions included the neck (42.7%–70.9%–78.4%), shoulders (29.8%–55.6%–66.2%) and lower back (22.9%–45.8%–58.7%). Overall, female participants stated that they suffered from pain significantly more frequently, especially in the neck, shoulders and upper back. Conclusion: The prevalence of MSD among dentists, especially in the neck, shoulder and back area, was significantly higher than in the general population. In addition, women suffered more frequently from MSD than men in almost all body regions.
Background: Dental professionals are subjected to higher risks for musculoskeletal disorders (MSDs) than other professional groups, especially the hand region. This study aims to investigate the prevalence of hand complaints among dentists (Ds) and dental assistants (DAs) and examines applied therapies. Methods: For this purpose, an online questionnaire analysed 389 Ds (240female/149male) and 406 DAs (401female/5male) working in Germany. The self-reported data of the two occupational groups were compared with regard to the topics examined. The questionnaire was based on the Nordic Questionnaire (self-reported lifetime, 12-month and 7-day MSDs prevalence of the hand, the conducted therapy and its success), additional occupational and sociodemographic questions as well as questions about specific medical conditions. Results: 30.8% of Ds affirmed MSDs in the hand at any time in their lives, 20.3% in the last twelve months and 9.5% in the last seven days. Among DAs, 42.6% reported a prevalence of MSDs in the hand at any time in their lives, 31.8% in the last 12 months and 15.3% in the last seven days. 37.5% of the Ds and 28.3% of the DAs stated that they had certain treatments. For both, Ds and DAs, physiotherapy was the most frequently chosen form of therapy. 89.7% of Ds and 63.3% of DAs who received therapy reported an improvement of MSDs. Conclusion: Although the prevalence of MSDs on the hand is higher among DAs than among Ds, the use of therapeutic options and the success of therapy is lower for DAs compared to Ds.
Background: Dentists (Ds) and dental assistants (DAs) have a high lifetime prevalence of musculoskeletal disorders (MSDs). In this context, it is assumed that they have an increased intake of substances such as pain medication. Currently, there exist no data on the use of medication among Ds and DAs with MSDs in Germany. Methods: The online questionnaire (i.e., the Nordic Questionnaire) analysed the medical therapies used by 389 Ds (240 f/149 m) and 406 DAs (401 f/5 m) to treat their MSDs. Results: Ds (28.3–11.5%) and DAs (29.4–10.3%) with MSDs took medication depending on the affected body region. A trend between the Ds and DAs in the intake of drug therapy and the frequency was found for the neck region (Ds: 21.1%, DAs: 28.7%). A single medication was taken most frequently (Ds: 60.0–33.3%, DAs: 71.4–27.3%). The frequency of use varied greatly for both occupational groups depending on the region affected. Conclusion: Ds and DAs perceived the need for medical therapies because of their MSDs. Painkillers such as ibuprofen and systemic diclofenac were the medications most frequently taken by both occupational groups. The intake of pain killers, most notably for the neck, should prevent sick leave.
Background: dental professionals suffer frequently from musculoskeletal disorders (MSD). Dentists and dental assistants work closely with each other in a mutually dependent relationship. To date, MSD in dental assistants have only been marginally investigated and compared to their occurrence in dentists. Therefore, the aim of this study was to compare the prevalence of MSD between dentists and dental assistants by considering occupational factors, physical activity and gender. Methods: This was a cross-sectional observational study. A Germany-wide survey, using a modified version of the Nordic Questionnaire and work-related questions, was applied. In total, 2548 participants took part, of which 389 dentists (240 females and 149 males) and 322 dental assistants (320 females and 2 males) were included in the analysis. Data were collected between May 2018 and May 2019. Differences between the dentists and dental assistants were determined by using the Chi2 test for nominal and the Wilcoxon–Mann–Whitney U test for both ordinal and non-normally distributed metric data. Results: A greater number of dental assistants reported complaints than dentists in all queried body regions. Significant differences in the most affected body regions (neck, shoulders, wrist/hands, upper back, lower back and feet/ankles) were found for the lifetime prevalence, annual prevalence and weekly prevalence. Data from the occupational factors, physical activity and gender analyses revealed significant differences between dentists and dental assistants. Conclusions: Dental assistants appear to be particularly affected by MSD when compared to dentists. This circumstance can be explained only to a limited extent by differences in gender distribution and occupational habits between the occupations.
Background and Aims: The prevalence of hepatitis C virus (HCV) antibodies in Germany has been estimated to be in the range of 0.4–0.63%. Screening for HCV is recommended in patients with elevated ALT levels or significant risk factors for HCV transmission only. However, 15–30% of patients report no risk factors and ALT levels can be normal in up to 20–30% of patients with chronic HCV infection. The aim of this study was to assess the HCV seroprevalence in patients visiting two tertiary care emergency departments in Berlin and Frankfurt, respectively.
Methods: Between May 2008 and March 2010, a total of 28,809 consecutive patients were screened for the presence of anti-HCV antibodies. Anti-HCV positive sera were subsequently tested for HCV-RNA.
Results: The overall HCV seroprevalence was 2.6% (95% CI: 2.4–2.8; 2.4% in Berlin and 3.5% in Frankfurt). HCV-RNA was detectable in 68% of anti-HCV positive cases. Thus, the prevalence of chronic HCV infection in the overall study population was 1.6% (95% CI 1.5–1.8). The most commonly reported risk factor was former/current injection drug use (IDU; 31.2%) and those with IDU as the main risk factor were significantly younger than patients without IDU (p<0.001) and the male-to-female ratio was 72% (121 vs. 46 patients; p<0.001). Finally, 18.8% of contacted HCV-RNA positive patients had not been diagnosed previously.
Conclusions: The HCV seroprevalence was more than four times higher compared to current estimates and almost one fifth of contacted HCV-RNA positive patients had not been diagnosed previously.
The occupation of dental assistants (DAs) involves many health risks of the musculoskeletal system due to static and prolonged work, which can lead to musculoskeletal disorders (MSDs). The aim of the study was to investigate the prevalence of MSDs in DAs in Germany. Methods: For this purpose, an online questionnaire analyzed 406 (401 female participants and 5 male participants, 401w/5m) DAs. It was based on the Nordic Questionnaire (lifetime, 12-month, and seven-day MSDs’ prevalence separated into neck, shoulder, elbow, wrist, upper back, lower back, hip, knee, and ankle), and occupational and sociodemographic questions as well as questions about specific medical conditions. Results: 98.5% of the participants reported complaints of at least one body region in their lives, 97.5% reported at least one complaint in the last 12 months and 86.9% affirmed at least one complaint in the last seven days. For lifetime, 12-month and seven-day prevalence, the neck was the region that was most affected followed by the shoulder, the upper back and the lower back. Conclusion: The prevalence of MSDs among German (female) DAs was very high. The most affected area is the neck, followed by the shoulder, the lower back, and the upper back. It, therefore, seems necessary to devote more attention to ergonomics at the working practice of DAs as well in education and in dental work.
Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) has been identified as high-risk subgroup of acute T-lymphoblastic leukemia (T-ALL) with a high rate of FLT3-mutations in adults. To unravel the underlying pathomechanisms and the clinical course we assessed molecular alterations and clinical characteristics in a large cohort of ETP-ALL (n = 68) in comparison to non-ETP T-ALL adult patients. Interestingly, we found a high rate of FLT3-mutations in ETP-ALL samples (n = 24, 35%). Furthermore, FLT3 mutated ETP-ALL was characterized by a specific immunophenotype (CD2+/CD5-/CD13+/CD33-), a distinct gene expression pattern (aberrant expression of IGFBP7, WT1, GATA3) and mutational status (absence of NOTCH1 mutations and a low frequency, 21%, of clonal TCR rearrangements). The observed low GATA3 expression and high WT1 expression in combination with lack of NOTCH1 mutations and a low rate of TCR rearrangements point to a leukemic transformation at the pluripotent prothymocyte stage in FLT3 mutated ETP-ALL. The clinical outcome in ETP-ALL patients was poor, but encouraging in those patients with allogeneic stem cell transplantation (3-year OS: 74%). To further explore the efficacy of targeted therapies, we demonstrate that T-ALL cell lines transfected with FLT3 expression constructs were particularly sensitive to tyrosine kinase inhibitors. In conclusion, FLT3 mutated ETP-ALL defines a molecular distinct stem cell like leukemic subtype. These data warrant clinical studies with the implementation of FLT3 inhibitors in addition to early allogeneic stem cell transplantation for this high risk subgroup.