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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.
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.