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Summer School Emergency Medicine : wichtige Praxiserfahrungen für ukrainische Medizinstudierende
(2023)
Mit viel Engagement und dank finanzieller Mittel des Goethe-Ukraine-Fonds haben Prof. Miriam Rüsseler und ihr Team vom Frankfurter Institut für Notfallmedizin und Simulationstraining (FIneST) eine Summer School Emergency Medicine ins Leben gerufen. Das Ziel: Ukrainischen Medizinstudierenden wichtige Praxiserfahrungen zu ermöglichen, die sie aufgrund des russischen Angriffskriegs nicht an ihrer Universität in der Ukraine sammeln können. Die Beteiligten vom Fachbereich Medizin begeistert vor allem die außergewöhnliche Einsatz- und Lernbereitschaft der Studierenden.
SUMO : glue or solvent for phase-separated ribonucleoprotein complexes and molecular condensates?
(2021)
Spatial organization of cellular processes in membranous or membrane-less organelles (MLOs, alias molecular condensates) is a key concept for compartmentalizing biochemical pathways. Prime examples of MLOs are the nucleolus, PML nuclear bodies, nuclear splicing speckles or cytosolic stress granules. They all represent distinct sub- cellular structures typically enriched in intrinsically disordered proteins and/or RNA and are formed in a process driven by liquid-liquid phase separation. Several MLOs are critically involved in proteostasis and their formation, disassembly and composition are highly sensitive to proteotoxic insults. Changes in the dynamics of MLOs are a major driver of cell dysfunction and disease. There is growing evidence that post-translational modifications are critically involved in controlling the dynamics and composition of MLOs and recent evidence supports an important role of the ubiquitin-like SUMO system in regulating both the assembly and disassembly of these structures. Here we will review our current understanding of SUMO function in MLO dynamics under both normal and pathological conditions.
Heyn, Jens Michael ; Bräuninger, Susanne Barbara ; Dimova-Dobreva, Miryana ; Mathieson, Nicola ; Koptelova, Natalia V. ; Kolpakova, Anna ; Seidl, Christian ; Reinhardt, Peter ; Tsamadou, Chrysanthi ; Schrezenmeier, Hubert ; Nakov, Roumen ; Seifried, Erhard ; Bönig, Halvard-Björn
Background: Safety, tolerability and efficacy of granulocyte colony-stimulating factor (G-CSF) for mobilization of hematopoietic stem and progenitor cells (HSPCs) from healthy donors have been conclusively demonstrated. This explicitly includes, albeit for smaller cohorts and shorter observation periods, biosimilar G-CSFs. HSPC donation is non-remunerated, its sole reward being “warm glow”, hence harm to donors must be avoided with maximal certitude. To ascertain, therefore, long-term physical and mental health effects of HSPC donation, a cohort of G-CSF mobilized donors was followed longitudinally.
Methods: We enrolled 245 healthy volunteers in this bi-centric long-term surveillance study. 244 healthy volunteers began mobilization with twice-daily Sandoz biosimilar filgrastim and 242 underwent apheresis after G-CSF mobilization. Physical and mental health were followed up over a period of 5-years using the validated SF-12 health questionnaire.
Results: Baseline physical and mental health of HSPC donors was markedly better than in a healthy reference population matched for ethnicity, sex and age. Physical, but not mental health was sharply diminished at the time of apheresis, likely due to side effects of biosimilar G-CSF, however had returned to pre-apheresis values by the next follow-up appointment after 6 months. Physical and mental health slightly deteriorated over time with kinetics reflecting the known effects of aging. Hence, superior physical and mental health compared to the general healthy non-donor population was maintained over time.
Conclusions: HSPC donors are of better overall physical and mental health than the average healthy non-donor. Superior well-being is maintained over time, supporting the favorable risk–benefit assessment of volunteer HSPC donation.
Trial registration National Clinical Trial NCT01766934
Generation of reactive oxygen species (ROS) is increasingly recognized as an important cellular process involved in numerous physiological and pathophysiological processes. Complex I (NADH:ubiquinone oxidoreductase) is considered as one of the major sources of ROS within mitochondria. Yet, the exact site and mechanism of superoxide production by this large membrane-bound multiprotein complex has remained controversial. Here we show that isolated complex I from Yarrowia lipolytica forms superoxide at a rate of 0.15% of the rate measured for catalytic turnover. Superoxide production is not inhibited by ubiquinone analogous inhibitors. Because mutant complex I lacking a detectable iron-sulfur cluster N2 exhibited the same rate of ROS production, this terminal redox center could be excluded as a source of electrons. From the effect of different ubiquinone derivatives and pH on this side reaction of complex I we concluded that oxygen accepts electrons from FMNH or FMN semiquinone either directly or via more hydrophilic ubiquinone derivatives.
Won, Sae-Yeon ; Dubinski, Daniel ; Behmanesh, Bedjan ; Bernstock, Joshua D. ; Keil, Fee ; Freiman, Thomas Michael ; Konczalla, Jürgen ; Seifert, Volker ; Geßler, Florian
Background: Research on chronic subdural hematoma (cSDH) management has primarily focused on potential recurrence after surgical evacuation. Herein, we present a novel postoperative/non-invasive treatment that includes a supervised Valsalva maneuver (SVM), which may serve to reduce SDH recurrence. Accordingly, the aims of the study were to investigate the effects of SVM on SDH recurrence rates and functional outcomes.
Methods: A prospective study was conducted from December 2016 until December 2019 at the Goethe University Hospital Frankfurt. Of the 204 adult patients with surgically treated cSDH who had subdural drains placed, 94 patients were assigned to the SVM group and 82 patients were assigned to the control group. The SVM was performed by having patients blow into a self-made SVM device at least two times/h for 12 h/day. The primary end-point was SDH recurrence rate, while secondary outcomes were morbidity and functional outcomes at 3 months of follow-up.
Results: SDH recurrence was observed in 16 of 94 patients (17%) in the SVM group, which was a significant reduction as compared with the control group, which had 24 of 82 patients (29.3%; p = 0.05) develop recurrent SDHs. Further, the infection rate (e.g., pneumonia) was significantly lower in the SVM group (1.1%) than in the control group (13.4%; p < 0.001; odds ratio [OR] 0.1). At the 3-month follow-up, 85 of 94 patients (90.4%) achieved favorable outcomes in the SVM group compared with 62 of 82 patients (75.6%) in the control group (p = 0.008; OR 3.0). Independent predictors for favorable outcome at follow-up were age (OR 0.9) and infection (OR 0.2).
Conclusion: SVM appears to be safe and effective in the post-operative management of cSDHs, reducing both recurrence rates and infections after surgical evacuation, thereby resulting in favorable outcomes at follow-up.
Jansen, Leontien ; De Burghgraeve, Tine ; Akker, Marjan van den ; Buntinx, Frank ; Schoenmakers, Birgitte
Background: Increasingly, informal caregivers in Belgium care in group for an older patient. This study aimed to decrease the caregiver burden and to increase the well-being of caregivers and patients by supporting the needs of informal care groups of older patients (≥70 years).
Method: Through an online self-management tool, the groups were supported to make informed choices concerning the care for the older patient, taking into account the standards, values, concerns and needs of every caregiver and patient. A pre-post study was performed.
Results: Although patients and caregivers considered the self-management tool as useful and supportive, no clear evidence for decreased caregiver burden was found. There was a positive trend in group characteristics such as the distribution of tasks, communication and prevalence of conflicts. Caregivers also stated that they took more time for themselves, had less feelings of guilt and experienced less barriers to ask help.
Conclusion: Tailor-made support of informal care groups starts with facilitating and guiding a process to achieve consent within the group to optimise the care for the patient and also for the caregivers. With a shared vision and supported decisions, caregivers can enter into conversations with the professional caregiver to coordinate adjusted support regarding the care needs.
Ifversen, Marianne ; Meisel, Roland ; Sedlacek, Petr ; Kalwak, Krzysztof ; Sisinni, Luisa ; Hutt, Daphna ; Lehrnbecher, Thomas ; Balduzzi, Adriana ; Diesch, Tamara ; Jarisch, Andrea ; Güngör, Tayfun ; Stein, Jerry ; Yaniv, Isaac ; Bönig, Halvard-Björn ; Kuhlen, Michaela ; Ansari, Marc ; Nava, Tiago ; Dalle, Jean-Hugues ; Diaz-de-Heredia, Cristina ; Trigoso, Eugenia ; Falkenberg, Ulrike ; Hartmann, Mihaela ; Deiana, Marco ; Canesi, Marta ; Broggi, Chiara ; Bertaina, Alice ; Gibson, Brenda ; Krivan, Gergely ; Vettenranta, Kim ; Matic, Toni ; Büchner, Jochen ; Lawitschka, Anita ; Peters, Christina ; Yesilipek, Akif ; Yalçin, Koray ; Lucchini, Giovanna ; Bakhtiar, Shahrzad ; Turkiewicz, Dominik ; Niinimäki, Riitta ; Wachowiak, Jacek ; Cesaro, Simone ; Dalissier, Arnaud ; Corbacioglu, Selim ; Willasch, Andre Manfred ; Bader, Peter
Specific protocols define eligibility, conditioning, donor selection, graft composition and prophylaxis of graft vs. host disease for children and young adults undergoing hematopoietic stem cell transplant (HSCT). However, international protocols rarely, if ever, detail supportive care, including pharmaceutical infection prophylaxis, physical protection with face masks and cohort isolation or food restrictions. Supportive care suffers from a lack of scientific evidence and implementation of practices in the transplant centers brings extensive restrictions to the child's and family's daily life after HSCT. Therefore, the Board of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) held a series of dedicated workshops since 2017 with the aim of initiating the production of a set of minimal recommendations. The present paper describes the consensus reached within the field of infection prophylaxis.
Kowanetz, Katarzyna ; Crosetto, Nicola ; Haglund, Kaisa ; Schmidt, Mirko Hans Heinrich ; Heldin, Carl-Henrik ; Đikić, Ivan
The ubiquitin (Ub) ligase Cbl plays a critical role in attenuation of receptor tyrosine kinase (RTK) signaling by inducing ubiquitination of RTKs and promoting their sorting for endosomal degradation. Herein, we describe the identification of two novel Cbl-interacting proteins, p70 and Clip4 (recently assigned the names Sts-1 and Sts-2, respectively), that inhibit endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor. Sts-1 and Sts-2 contain SH3 domains that interacted with Cbl, Ub-associated domains, which bound directly to mono-Ub or to the EGFR/Ub chimera as well as phosphoglycerate mutase domains that mediated oligomerization of Sts-1/2. Ligand-induced recruitment of Sts-1/Sts-2 into activated EGFR complexes led to inhibition of receptor internalization, reduction in the number of EGFR-containing endocytic vesicles, and subsequent block of receptor degradation followed by prolonged activation of mitogenic signaling pathways. On the other hand, interference with Sts-1/Sts-2 functions diminished ligand-induced receptor degradation, cell proliferation, and oncogenic transformation in cultured fibroblasts. We suggest that Sts-1 and Sts-2 represent a novel class of Ub-binding proteins that regulate RTK endocytosis and control growth factor-induced cellular functions.
Purpose of Review: To provide an overview of current surgical peri-implantitis treatment options.
Recent Findings: Surgical procedures for peri-implantitis treatment include two main approaches: non-augmentative and augmentative therapy. Open flap debridement (OFD) and resective treatment are non-augmentative techniques that are indicated in the presence of horizontal bone loss in aesthetically nondemanding areas. Implantoplasty performed adjunctively at supracrestally and buccally exposed rough implant surfaces has been shown to efficiently attenuate soft tissue inflammation compared to control sites. However, this was followed by more pronounced soft tissue recession. Adjunctive augmentative measures are recommended at peri-implantitis sites exhibiting intrabony defects with a minimum depth of 3 mm and in the presence of keratinized mucosa. In more advanced cases with combined defect configurations, a combination of augmentative therapy and implantoplasty at exposed rough implant surfaces beyond the bony envelope is feasible.
Summary: For the time being, no particular surgical protocol or material can be considered as superior in terms of long-term peri-implant tissue stability.
Banys-Paluchowski, Maggie ; Gasparri, Maria Luisa ; de Boniface, Jana ; Gentilini, Oreste ; Stickeler, Elmar ; Hartmann, Steffi ; Thill, Marc ; Rubio, Isabel T. ; Di Micco, Rosa ; Bonci, Eduard-Alexandru ; Niinikoski, Laura ; Kontos, Michalis ; Cakmak, Guldeniz Karadeniz ; Hauptmann, Michael ; Peintinger, Florentia ; Pinto, David ; Matrai, Zoltan ; Murawa, Dawid ; Kadayaprath, Geeta ; Dostalek, Lukas ; Nina, Helidon ; Krivorotko, Petr ; Classe, Jean-Marc ; Schlichting, Ellen ; Appelgren, Matilda ; Paluchowski, Peter ; Solbach, Christine ; Blohmer, Jens-Uwe ; Kühn, Thorsten
Simple Summary: Currently, it is unclear which kind of axillary staging surgery breast cancer patients with lymph node metastasis should receive after neoadjuvant chemotherapy. For decades, these patients have been treated with a full axillary lymph node dissection, even if they converted to clinical node negativity. However, the removal of a large number of lymph nodes during the procedure can increase arm morbidity and impact quality of life. Therefore, several studies investigated less radical surgical strategies in this setting, such as sentinel lymph node biopsy or targeted axillary dissection, i.e., removal of a previously marked node combined with sentinel node removal. In this review, we summarize current evidence on the different surgical techniques and compare national and international recommendations. We show that many questions regarding oncological safety of different surgery types and the optimal marking technique remain unanswered and present the multinational prospective cohort study AXSANA that will address these open issues.
Abstract: In the last two decades, surgical methods for axillary staging in breast cancer patients have become less extensive, and full axillary lymph node dissection (ALND) is confined to selected patients. In initially node-positive patients undergoing neoadjuvant chemotherapy, however, the optimal management remains unclear. Current guidelines vary widely, endorsing different strategies. We performed a literature review on axillary staging strategies and their place in international recommendations. This overview defines knowledge gaps associated with specific procedures, summarizes currently ongoing clinical trials that address these unsolved issues, and provides the rationale for further research. While some guidelines have already implemented surgical de-escalation, replacing ALND with, e.g., sentinel lymph node biopsy (SLNB) or targeted axillary dissection (TAD) in cN+ patients converting to clinical node negativity, others recommend ALND. Numerous techniques are in use for tagging lymph node metastasis, but many questions regarding the marking technique, i.e., the optimal time for marker placement and the number of marked nodes, remain unanswered. The optimal number of SLNs to be excised also remains a matter of debate. Data on oncological safety and quality of life following different staging procedures are lacking. These results provide the rationale for the multinational prospective cohort study AXSANA initiated by EUBREAST, which started enrollment in June 2020 and aims at recruiting 3000 patients in 20 countries (NCT04373655; Funded by AGO-B, Claudia von Schilling Foundation for Breast Cancer Research, AWOgyn, EndoMag, Mammotome, and MeritMedical).
Widera, Marek ; Mühlemann, Barbara ; Corman, Victor Max ; Toptan, Tuna ; Beheim-Schwarzbach, Jörn ; Kohmer, Niko ; Schneider, Julia ; Berger, Annemarie ; Veith, Talitha ; Pallas, Christiane ; Bleicker, Tobias ; Götsch, Udo ; Tesch, Julia ; Gottschalk, René ; Jones, Terry C. ; Ciesek, Sandra ; Drosten, Christian
Background: International travel is a major driver of the introduction and spread of SARS- CoV-2. Aim: To investigate SARS-CoV-2 genetic diversity in the region of a major transport hub in Germany, we characterized the viral sequence diversity of the SARS-CoV-2 variants circulating in Frankfurt am Main, the city with the largest airport in Germany, from the end of October to the end of December 2020. Methods: In total, we recovered 136 SARS-CoV-2 genomes from nasopharyngeal swab samples. We isolated 104 isolates that were grown in cell culture and RNA from the recovered viruses and subjected them to full-genome sequence analysis. In addition, 32 nasopharyngeal swab samples were directly sequenced. Results and conclusion: We found 28 different lineages of SARS- CoV-2 circulating during the study period, including the variant of concern B.1.1.7 (∆69/70, N501Y). Six of the lineages had not previously been observed in Germany. We detected the spike protein (S) deletion ∆69/∆70 in 15% of all sequences, a four base pair (bp) deletion (in 2.9% of sequences) and a single bp deletion (in 0.7% of sequences) in ORF3a, leading to ORF3a truncations. In four sequences (2.9%), an amino acid deletion at position 210 in S was identified. In a single sample (0.7%), both a 9 bp deletion in ORF1ab and a 7 bp deletion in ORF7a were identified. One sequence in lineage B.1.1.70 had an N501Y substitution while lacking the ∆69/70 in S. The high diversity of sequences observed over two months in Frankfurt am Main highlights the persisting need for continuous SARS-CoV-2 surveillance using full-genome sequencing, particularly in cities with international airport connections.
Lawson McLean, Aaron ; Lawson McLean, Anna Cecilia ; Maurer, Stefanie ; Nistor-Gallo, Dorothea ; Moritz, Ina ; Tourbier, Meriem
The Ethics of Waiting lists and Rationing access to care (Ethics Parallel Session), September 26, 2023, 4:50 PM - 6:20 PM
Background: There has been a fivefold increase of neurosurgeons over the last three decades in Germany, despite a lesser increase in operations. Currently, there are approximately 1000 neurosurgical residents employed at training hospitals. Little is known about the overall training experience and career opportunities for these trainees.
Methods: In our role as resident representatives, we implemented a mailing list for interested German neurosurgical trainees. Thereafter, we created a survey including 25 items to assess the trainees’ satisfaction with their training and their perceived career prospects, which we then distributed through the mailing list. The survey was open from 1st April until 31st May 2021.
Results: 90 trainees were enrolled in the mailing list and we received 81 completed responses to our survey. Overall, 47% of trainees were very dissatisfied or dissatisfied with their training. 62% of trainees reported a lack of surgical training. 58% of trainees found it difficult to attend courses or classes and only 16% had consistent mentoring. There was an expressed desire for a more structured training programme and mentoring projects. In addition, 88% of trainees were willing to relocate for fellowships outside their current hospitals.
Conclusions: Half of the responders were dissatisfied with their neurosurgical training. There are various aspects that require improvement, such as the training curriculum, the lack of structured mentoring and the amount of administrative work. We propose the implementation of a modernized structured curriculum, which addresses the mentioned aspects, in order to improve neurosurgical training and, consecutively, patient care.
Koch, Christine ; Bambey, Cornelia ; Filmann, Sonja Natalie ; Stanke, Marc ; Waidmann, Oliver ; Husmann, Gabriele ; Bojunga, Jörg
Introduction: Scarce data exist for therapy regimens other than somatostatin analogues (SSA) and peptide receptor radiotherapy (PRRT) for siNET. We analyzed real world data for differences in survival according to therapy. Patients and methods: Analysis of 145 patients, diagnosed between 1993 and 2018 at a single institution, divided in treatment groups. Group (gr.) 0: no treatment (n = 10), gr 1: TACE and/or PRRT (n = 26), gr. 2: SSA (n = 32), gr. 3: SSA/PRRT (n = 8), gr. 4: chemotherapy (n = 8), gr. 5: not metastasized (at diagnosis), surgery only (n = 53), gr. 6 = metastasized (at diagnosis), surgery only (n = 10). Results: 45.5% female, median age 60 years (range, 27–84). A total of 125/145 patients with a resection of the primary tumor. For all patients, 1-year OS (%) was 93.8 (95%-CI: 90–98), 3-year OS = 84.3 (CI: 78–90) and 5-year OS = 77.5 (CI: 70–85). For analysis of survival according to therapy, only stage IV patients (baseline) that received treatment were included. Compared with reference gr. 2 (SSA only), HR for OS was 1.49 (p = 0.47) for gr. 1, 0.72 (p = 0.69) for gr. 3, 2.34 (p = 0.19) for gr. 4. The 5 y OS rate of patients whose primary tumor was resected (n = 125) was 73.1%, and without PTR was 33.3% (HR: 4.31; p = 0.003). Individual patients are represented in swimmer plots. Conclusions: For stage IV patients in this analysis (limited by low patient numbers in co. 3/4), multimodal treatment did not significantly improve survival over SSA treatment alone. A resection of primary tumor significantly improves survival.
Chierigo, Francesco ; Borghesi, Marco ; Würnschimmel, Christoph ; Flammia, Rocco S. ; Horlemann, Benedikt ; Sorce, Gabriele ; Höh, Robert Benedikt ; Tian, Zhe ; Saad, Fred ; Graefen, Markus ; Gallucci, Michele ; Briganti, Alberto ; Montorsi, Francesco ; Chun, Felix ; Shariat, Shahrokh F. ; Mantica, Guglielmo ; Suardi, Nazareno ; Terrone, Carlo ; Karakiewicz, Pierre I.
Aim: To compare overall mortality (OM), cancer-specific mortality (CSM), and other cause mortality (OCM) rates between radical prostatectomy (RP) versus radiotherapy (RT) in clinical node-positive (cN1) prostate cancer (PCa).
Materials and Methods: Within Surveillance, Epidemiology, End Results (SEER) (2004–2016), we identified 4685 cN1 PCa patients, of whom 3589 (76.6%) versus 1096 (24.4%) were treated with RP versus RT. After 1:1 propensity score matching (PSM), Kaplan–Meier plots and Cox regression models tested the effect of RP versus RT on OM, while cumulative incidence plots and competing-risks regression (CRR) models addressed CSM and OCM between RP and RT patients. All analyses were repeated after the inverse probability of treatment weighting (IPTW). For CSM and OCM analyses, the propensity score was used as a covariate in the regression model.
Results: Overall, RT patients were older, harbored higher prostate-specific antigen values, higher clinical T and higher Gleason grade groups. PSM resulted in two equally sized groups of 894 RP versus 894 RT patients. After PSM, 5-year OM, CSM, and OCM rates were, respectively, 15.4% versus 25%, 9.3% versus 17%, and 6.1% versus 8% for RP versus RT (all p < 0.001) and yielded respective multivariate hazard ratios (HRs) of 0.63 (0.52–0.78, p < 0.001), 0.66 (0.52–0.86, p < 0.001), 0.71 (0.5–1.0, p = 0.05), all favoring RP. After IPTW, Cox regression models yielded HR of 0.55 (95% confidence interval [CI] = 0.46–0.66) for OM, and CRR yielded HRs of 0.49 (0.34–0.70) and 0.54 (0.36–0.79) for, respectively, CSM and OCM, all favoring RP (all p < 0.001).
Conclusions: RP may hold a CSM advantage over RT in cN1 PCa patients.
Survival following relapse in children with Acute Myeloid leukemia: a report from AML-BFM and COG
(2021)
Rasche, Mareike ; Zimmermann, Martin ; Steidel, Emma ; Alonzo, Todd ; Aplenc, Richard ; Bourquin, Jean-Pierre ; Boztug, Heidrun ; Cooper, Todd ; Gamis, Alan S. ; Gerbing, Robert B. ; Janotova, Iveta ; Klusmann, Jan-Henning ; Lehrnbecher, Thomas ; Mühlegger, Nora ; Neuhoff, Nils von ; Niktoreh, Naghmeh ; Sramkova, Lucie ; Stary, Jan ; Waack, Katharina ; Walter, Christiane ; Creutzig, Ursula ; Dworzak, Michael ; Kaspers, Gertjan ; Kolb, Edward Anders ; Reinhardt, Dirk
Simple Summary: Acute myeloid leukemia in children remains a difficult disease to cure despite intensive therapies that push the limits of tolerability. Though the intent of initial therapy should be the prevention of relapse, about 30% of all patients experience a relapse. Hence, relapse therapy remains critically important for survival. This retrospective analysis of two large international study groups (COG and BFM) was undertaken to describe the current survival, response rates and clinical features that predict outcomes. We demonstrate that children with relapsed AML may be cured with cytotoxic therapy followed by HSCT. High-risk features at initial diagnosis and early relapse remain prognostic for post-relapse survival. Current response criteria are not aligned with the standards of care for children, nor are the count recovery thresholds meaningful for prognosis in children with relapsed AML. Our data provide a new baseline for future treatment planning and will allow an updated stratification in upcoming studies.
Abstract: Post-relapse therapy remains critical for survival in children with acute myeloid leukemia (AML). We evaluated survival, response and prognostic variables following relapse in independent cooperative group studies conducted by COG and the population-based AML-BFM study group. BFM included 197 patients who relapsed after closure of the last I-BFM relapse trial until 2017, while COG included 852 patients who relapsed on the last Phase 3 trials (AAML0531, AAML1031). Overall survival at 5 years (OS) was 42 ± 4% (BFM) and 35 ± 2% (COG). Initial high-risk features (BFM 32 ± 6%, COG 26 ± 4%) and short time to relapse (BFM 29 ± 4%, COG 25 ± 2%) predicted diminished survival. In the BFM dataset, there was no difference in OS for patients who had a complete remission with full hematopoietic recovery (CR) following post-relapse re-induction compared to those with partial neutrophil and platelet recovery (CRp and CRi) only (52 ± 7% vs. 63 ± 10%, p = 0.39). Among 90 patients alive at last follow-up, 87 had received a post-relapse hematopoietic stem cell transplant (HSCT). OS for patients with post-relapse HSCT was 54 ± 4%. In conclusion, initial high-risk features and early relapse remain prognostic. Response assessment with full hematopoietic recovery following initial relapse therapy does not predict survival. These data indicate the need for post-relapse risk stratification in future studies of relapse therapies.
Wenzel, Mike ; Collà Ruvolo, Claudia ; Würnschimmel, Christoph ; Nocera, Luigi ; Tian, Zhe ; Saad, Fred ; Briganti, Alberto ; Tilki, Derya ; Graefen, Markus ; Becker, Andreas ; Roos, Frederik ; Mandel, Philipp ; Chun, Felix ; Karakiewicz, Pierre I.
Background: The survival benefit of primary external beam radiation therapy (EBRT) has never been formally tested in elderly men who were newly diagnosed with metastatic prostate cancer (mPCa). We hypothesized that elderly patients may not benefit of EBRT to the extent as younger newly diagnosed mPCa patients, due to shorter life expectancy.
Methods: We relied on Surveillance, Epidemiology and End Results (2004–2016) to identify elderly newly diagnosed mPCa patients, aged >75 years. Kaplan–Meier, univariable and multivariable Cox regression models, as well as Competing Risks Regression models tested the effect of EBRT versus no EBRT on overall mortality (OM) and cancer-specific mortality (CSM).
Results: Of 6556 patients, 1105 received EBRT (16.9%). M1b stage was predominant in both EBRT (n = 823; 74.5%) and no EBRT (n = 3908; 71.7%, p = 0.06) groups, followed by M1c (n = 211; 19.1% vs. n = 1042; 19.1%, p = 1) and M1a (n = 29; 2.6% vs. n = 268; 4.9%, p < 0.01). Median overall survival (OS) was 23 months for EBRT and 23 months for no EBRT (hazard ratio [HR]: 0.97, p = 0.6). Similarly, median cancer-specific survival (CSS) was 29 months for EBRT versus 30 months for no EBRT (HR: 1.04, p = 0.4). After additional multivariable adjustment, EBRT was not associated with lower OM or lower CSM in the entire cohort, as well as after stratification for M1b and M1c substages.
Conclusions: In elderly men who were newly diagnosed with mPCa, EBRT does not affect OS or CSS. In consequence, our findings question the added value of local EBRT in elderly newly diagnosed mPCa patients.
Maurer-Grubinger, Christian ; Adjami, Frederic ; Avaniadi, Ioanna ; Christian, Wolfgang ; Doerry, Charlotte ; Fay, Viola Nathalie ; Fisch, Vanessa ; Gerez, Ali ; Goecke, Julian ; Kaya, Ugur ; Keller, Julia ; Krüger, Kai-Dominik ; Pflaum, Julia ; Porsch, Laurin ; Wischnewski, Christina ; Scharnweber, Benjamin ; Sosnov, Polyna ; Oremek, Gerhard ; Groneberg, Jan David Alexander ; Ohlendorf, Daniela Maren
Objectives: Symmetrical dental occlusion blocking is used in dentistry as a quick diagnostic tool to test for potential influences of the craniomandibular system on body sway and weight distribution. This study presents the changes of body sway and pressure distribution in healthy subjects, free of a temporomandibular dysfunction (TMD). Immediate effects between occlusal blocking and rest position on body sway and body weight distribution in general, as well as for both genders and for four age decades will be evaluated.
Materials and methods: 725 (396f/329 m) subjects (neither subjective signs of TMD nor acute/chronic complaints in the musculoskeletal system) volunteered (21 to 60 years) while both genders were divided into four age groups according to decades. A pressure measuring platform was used. Body sway and weight distribution were recorded in two dental occlusion conditions (a) in rest position and (b) symmetrical blocking (bicuspid region) by cotton rolls.
Results: Both, the frontal sway and the sagittal sway reduced by 0.67 mm (t(724) = − 3.9 (p < 0.001)) and by 0.33 mm (t(724) = − 3.4 (p < 0.001)). The relative pressure under the left forefoot increased by 0.33% (t(724) = 2.88 (p < 0.001)) and the relative pressure overall under the forefoot increased by 0.67% (t(724) = − 3.4 (p < 0.001)). Gender-specific, age-specific and BMI-specific reactions could not be identified.
Conclusions: Subjects, free of any TMD and with no complaints of the musculoskeletal system, show small changes of the body sway and weight distribution when biting symmetrically on a cotton roll. These changes are independent of age, gender or body mass index (BMI). Due to the relative large sample size, the presented results can also be seen as norm values when body sway is used as an additional assessment of a TMD.
Maurer-Grubinger, Christian ; Avaniadi, Ioanna ; Adjami, Frederic ; Christian, Wolfgang ; Doerry, Charlotte ; Fay, Viola Nathalie ; Fisch, Vanessa ; Gerez, Ali ; Goecke, Julian ; Kaya, Ugur ; Keller, Julia ; Krüger, Kai-Dominik ; Pflaum, Julia ; Porsch, Laurin ; Wischnewski, Christina ; Scharnweber, Benjamin ; Sosnov, Polyna ; Oremek, Gerhard ; Groneberg, Jan David Alexander ; Ohlendorf, Daniela Maren
Background: Temporary occlusal changes and their influence on the upper body statics are still controversially discussed. Furthermore, concrete statements on whether age- or gender-specific differences in neurophysiological reactions exist are missing. Therefore, it is the aim of this study to evaluate the immediate effects of a symmetrical occlusion blocking on the upper body posture. These effects shall be investigated for both genders and for a larger age range.
Methods: In this study, 800 (407f/393 m) subjects volunteered aged from 21 to 60 years. Both genders were divided into four age groups according to decades. The three-dimensional upper body posture was measured by using the rasterstereography (ABW-Bodymapper). The habitual static posture was measured in two dental occlusion conditions (a) in rest position and (b) symmetrical blocking in the bicuspid region by cotton rolls.
Results: A significant reduction of the trunk length (0.72 mm; p < 0.001), an increase of the lumbar (0.30°; p < 0.001) and the thoracic bending angle (0.14°; p = 0.001), a reduction of the spinal forward decline (0.16°; p < 0.001) and a reduction of the scapular distance (0.36 mm; p = 0.001) was found. Gender-specific reactions can only be recorded in scapular distance, in that regard men reduce this distance while over all age groups women did not show a significant change.
Discussion: Slight gender- and age-independent reactions due to a symmetric occlusion blockade are shown: A gender independent reaction of the spinal related variables in the sagittal plane (thoracic and lumbar flexion angle, trunk length, spinal forward decline). In addition, a gender specific change of the shoulder blade distance could be observed, where men reduced the distance while female did not show a change. However, since these reactions are of a minimum amount, it can be concluded that neurophysiological compensation mechanisms work equally well regardless of age and sex, and the upper body posture of healthy people changes only very slightly due to a temporarily symmetrical altered bite position.
Koch, Vitali ; Abt, Julia Anna Walburga ; Grünewald, Leon David ; Eichler, Katrin ; D’Angelo, Tommaso ; Martin, Simon S. ; Albrecht, Moritz Hans Ernst ; Thalhammer, Axel ; Booz, Christian ; Yel, Ibrahim ; Bernatz, Simon ; Mahmoudi, Scherwin ; Harth, Marc ; Derwich, Wojciech ; Vogl, Thomas J. ; Gray, Daphne ; Gruber-Rouh, Tatjana ; Jung, Georg
Highlights
• MRI and ultrasound provided significant correlations between findings suggestive of vasculitis and the final diagnosis.
• Careful selection of available imaging techniques is warranted considering the time course, location, and clinical history.
• Considering its moderate diagnostic power to distinguish tracer uptake, a holistic view of PET/CT findings is essential.
Abstract
Purpose: To assess the diagnostic value of different imaging modalities in distinguishing systemic vasculitis from other internal and immunological diseases.
Methods: This retrospective study included 134 patients with suspected vasculitis who underwent ultrasound, magnetic resonance imaging (MRI), or 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) between 01/2010 and 01/2019, finally consisting of 70 individuals with vasculitis. The main study parameter was the confirmation of the diagnosis using one of the three different imaging modalities, with the adjudicated clinical and histopathological diagnosis as the gold standard. A secondary parameter was the morphological appearance of the vessel affected by vasculitis.
Results: Patients with systemic vasculitis had myriad clinical manifestations with joint pain as the most common symptom. We found significant correlations between different imaging findings suggestive of vasculitis and the final adjudicated clinical diagnosis. In this context, on MRI, vessel wall thickening, edema, and diameter differed significantly between vasculitis and non-vasculitis groups (p < 0.05). Ultrasound revealed different findings that may serve as red flags in identifying patients with vasculitis, such as vascular occlusion or halo sign (p = 0.02 vs. non-vasculitis group). Interestingly, comparing maximal standardized uptake values from PET/CT examinations with vessel wall thickening or vessel diameter did not result in significant differences (p > 0.05).
Conclusions: We observed significant correlations between different imaging findings suggestive of vasculitis on ultrasound or MRI and the final adjudicated diagnosis. While ultrasound and MRI were considered suitable imaging methods for detecting and discriminating typical vascular changes, 18F-FDG PET/CT requires careful timing and patient selection given its moderate diagnostic accuracy.