Tissue engineering for the diaphragm and its various therapeutic possibilities - a systematic review

Diaphragmatic impairments exhibit high morbidity as well as mortality while current treatment options remain unsatisfactory. Tissue engineering (TE) approaches have explored the generation of an optimal biocompatible scaffold for diaphragmatic repair through tissue decellularization or de novo construction, with or without the addition of cells. We conducted a systematic review on the current state of the art in diaphragmatic tissue engineering (DTE) and found 24 articles eligible for final synthesis. The included approaches studied decellularization-based graft generation (9) and de novo bioscaffold construction (9). Three studies focused on in vitro host-scaffold interaction with synthesized, recellularized grafts (2) and decellularized extracellular matrix scaffolds (1). Another three studies investigated evaluation tools for decellularization efficacy. Among all studies, recellularization was performed in both decellularization-based (4) and de novo generated scaffolds (4). De novo constructed biocomposites as well as decellularized and recellularized scaffolds induced pro-regenerative remodeling and recovery of diaphragmatic function in all examined animal models. Potential therapeutic applications comprise substance defects requiring patch repair, such as congenital diaphragmatic hernia, and functional diseases demanding an entire organ transplant, like muscular dystrophies or dysfunction after prolonged artificial respiration

Low-Level Waste Overview of the Nevada Test Site

This paper provides an overview and the impacts of new policies, processes, and opportunities at the Nevada Test Site. Operational changes have been implemented, such as larger trench sizes and more efficient soil management as have administrative processes to address U.S. Department of Energy and U.S. Code of Federal Regulation analyses. Some adverse conditions have prompted changes in transportation and mixed low-level waste polices, and a new funding mechanism was developed. This year has seen many changes to the Nevada Test Site disposal family

NAD+ protects against EAE by regulating CD4+ T-cell differentiation

CD4+ T cells are involved in the development of autoimmunity, including multiple sclerosis (MS). Here we show that nicotinamide adenine dinucleotide (NAD+) blocks experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, by inducing immune homeostasis through CD4+IFNγ+IL-10+ T cells and reverses disease progression by restoring tissue integrity via remyelination and neuroregeneration. We show that NAD+ regulates CD4+ T-cell differentiation through tryptophan hydroxylase-1 (Tph1), independently of well-established transcription factors. In the presence of NAD+, the frequency of T-bet−/− CD4+IFNγ+ T cells was twofold higher than wild-type CD4+ T cells cultured in conventional T helper 1 polarizing conditions. Our findings unravel a new pathway orchestrating CD4+ T-cell differentiation and demonstrate that NAD+ may serve as a powerful therapeutic agent for the treatment of autoimmune and other diseases

FIRE-9 - PORT / AIO-KRK-0418: a prospective, randomized, open, multicenter Phase III trial to investigate the efficacy of adjuvant/additive chemotherapy in patients with definitely-treated metastatic colorectal cancer

BACKGROUND: Additive/adjuvant chemotherapy as concept after local treatment of colorectal metastases has not been proven to be successful by phase III trials. Accordingly, a standard of care to improve relapse rates and long-term survival is not established and adjuvant chemotherapy cannot be recommended as a standard therapy due to limited evidence in literature. The PORT trial aims to generate evidence that post-resection/ablation/radiation chemotherapy improves the survival in patients with metastatic colorectal cancer. METHODS: Patients to be included into this trial must have synchronous or metachronous metastases of colorectal cancer-either resected (R0 or R1) and/or effectively treated by ablation or radiation within 3-10 weeks before randomization-and have the primary tumor resected, without radiographic evidence of active metastatic disease at study entry. The primary endpoint of the trial is progression-free survival after 24 months, secondary endpoints include overall survival, safety, quality of life, treatments (including efficacy) beyond study participation, translational endpoints, and others. One arm of the study comprising 2/3 of the population will be treated for 6 months with modified FOLFOXIRI or modified FOLFOX6 (investigator´s choice, depending on the performance status of the patients but determined before randomization), while the other arm (1/3 of the population) will be observed and undergo scheduled follow-up computed tomography scans according to the interventional arm. DISCUSSION: Optimal oncological management after removal of colorectal metastases is unclear. The PORT trial aims to generate evidence that additive/adjuvant chemotherapy after definitive treatment of colorectal metastases improves progression free and overall survival in patients with colorectal cancer. TRIAL REGISTRATION: This study is registered with clinicaltrials.gov ( NCT05008809 ) and EudraCT (2020-006,144-18)

Mittelfristige Ergebnisse der Behandlung von Aneurysmen der Aorta descendens mit endovaskulären Prothesen unter Einschluss von Hochrisikopatienten

Methods: 21 patients (17 men, 4 women; mean age 66.1 years, range 29-90 years) with 15 true aneurysms, and 6 type B-dissections were treated by implantation of a TalentTM Endoluminal Stentgraft System from February 2000 to July 2003. In 3 cases it was necessary to overstent the left subclavian artery, in 1 case to overstent the left common carotid.Results: 2 patients (9.5%) died during the first 30 days (1 myocardial infarction, 1 pneumonia). Two patients (9.5%) suffered from cerebral ischemia and needed revascularisation. No paraplegia, no stroke occurred. One endoleak required additional stenting. No patient needed conversion. Follow-up, average 25.4 months (range 0-39), was 100% complete. During this another two patients died of myocardial infarction i.e. 9.5% (the above mentioned endoleak, but no late migration were detected in the remaining patients). In all cases the graft lumen stayed patent.Conclusions: Treatment of descending thoracic aortic aneurysm with an endovascular approach has acceptable mortality and morbidity-rates even in high risk patients. Procedural overstenting of the subclavian artery requires subclavian revascularisation in a minority of cases.Methoden: 21 Patienten (17 Männer, 4 Frauen, Altersdurchschnitt 66,1 Jahre, Bereich 29-90 Jahren) mit 15 echten Aortenaneurysmen und 6 B-Typ Dissektionen wurde eine TalentTM Endoluminal Prothese eingesetzt im Zeitraum Februar 2000 - Juli 2003. In 3 Fällen war ein Überstenten der linken A. subclavia, in einem weiteren Fall der linken A. carotis communis notwendig. Resultate: 2 Patienten (9,5%) verstarben innerhalb der ersten 30 Tage (ein Myokardinfarkt, eine Pneumonie). 2 Patienten erlitten eine Hirnischämie, welche eine Revaskularisierung erforderlich machte. Weder Paraplegien noch Schlaganfälle traten auf. Eine Endoleckage erforderte zusätzliches Stenten. Keiner der Patienten benötigte Konversion. Die Nachsorgephase, im Durchschnitt 25,4 Monate, -spanne: 0-39 Monate, wurde zu 100% durchgeführt. Währenddessen verstarben zwei weitere Patienten an einem Myokardinfarkt (9,5%). Die oben erwähnte Endoleckage, aber keine Spätstadienmigration wurde in den verbleibenden Patienten festgestellt. In allen Fällen blieb der Durchmesser der Gefäßendoprothese offen.Schlussfolgerung: Die Aneurysmabehandlung im Bereich der absteigenden Aorta thoracica mit endovaskulären Prothesen weist akzeptable Mortalitäts- und Morbiditätsraten auf, auch bei Hochrisikopatienten. Das Überstenten der A. subclavia während der Prothesenimplantation erfordert bei einer Minderheit der Fälle eine Revaskularisierung