Retrosternal Percutaneous Tracheostomy: An Approach for Predictably Impossible Classic Tracheostomy

Percutaneous tracheostomy is a routine procedure in intensive care units. In cases of very low position of the larynx, cervical spine deformation, morbid obesity, or neck tumor, performance of the classic tracheostomy is inapplicable. Retrosternal approach to tracheostomy in such 20 patients is herein reported. After preoperative neck computerized tomography to define the neck anatomy, a small suprasternal incision followed by a short retrosternal tissue dissection to expose the trachea was done; the trachea was then catheterized at the level of the 2nd ring in the usual tracheostomy manner. The immediate and late (≥6 months) outcomes were similar to that of the standard tracheostomy. Thus, percutaneous retrosternal tracheostomy is safe in patients with abnormal positioning of the trachea or neck constitution. It is a bedside applicable technique, that, however, requires caution to avoid hazardous vascular complications

IST-2000-30148 I-METRA: D3.2 Implementation of relevant algorithms

This deliverable provides a high level description of the software developed within the I-METRA project following the selection reported in D3.1 "Design, Analysis and Selection of Suitable Algorithms".Preprin

IST-2000-30148 I-METRA: D3.1 Design, analysis and selection of suitable algorithms

This deliverable contains a description of the space-time coding algorithms to be simulated within the I-METRA project. Different families of algorithms have been selected and described in this document with the objective of evaluating their performance. One of the main objectives of the I-METRA project is to impact into the current standardisation efforts related to the introduction of Multiple Input Multiple Output (MIMO) configurations into the High Speed Downlink and Uplink Packet Access concepts of UMTS (HSDPA and HSUPA). This required a review of the current specifications for these systems and the analysis of the impact of the potential incorporation of the selected MIMO schemes.Preprin

NOX4 inhibition potentiates immunotherapy by overcoming cancer-associated fibroblast-mediated CD8 T-cell exclusion from tumours

Determining mechanisms of resistance to PD-1/PD-L1 immune checkpoint immunotherapy is key to developing new treatment strategies. Cancer-associated fibroblasts (CAF) have many tumor-promoting functions and promote immune evasion through multiple mechanisms, but as yet, there are no CAF-specific inhibitors clinically available. Here we generated CAF-rich murine tumor models (TC1, MC38, 4T1) to investigate how CAF influence the immune microenvironment and affect response to different immunotherapy modalities (anti-cancer vaccination; TC1, [HPV E7 DNA vaccine];PD-1, MC38) and found that CAFs broadly suppressed response by specifically excluding CD8+ T-cells from tumors (not CD4+ T-cells or macrophages); CD8+ T-cell exclusion was similarly present in CAF-rich human tumors. RNA sequencing of CD8+ T-cells from CAF-rich murine tumors and immunochemistry analysis of human tumors identified significant upregulation of CTLA-4 in the absence of other exhaustion markers; inhibiting CTLA-4 with a non-depleting antibody overcame the CD8+ T-cell exclusion effect without affecting T-regs. We then examined the potential for CAF targeting, focusing on the ROS-producing enzyme NOX4, which is upregulated by CAF in many human cancers, and compared this to TGF-062;1 inhibition, a key regulator of the CAF phenotype. siRNA knockdown or pharmacological inhibition (GKT137831 [Setanaxib]) of NOX4 'normalized' CAF to a quiescent phenotype and promoted intratumoral CD8+T-cell infiltration, overcoming the exclusion effect; TGF-062;1 inhibition could prevent, but not reverse, CAF differentiation. Finally, NOX4 inhibition restored immunotherapy response in CAF-rich tumors. These findings demonstrate that CAF-mediated immunotherapy resistance can be effectively overcome through NOX4 inhibition, and could improve outcome in a broad range of cancers

Evil and Exile

A series of interviews between Wiesel and French journalist Phillipe de Saint-Cheron, Evil and Exile probes some of the issues which confront humankind today. Having survived the evil of the holocaust, Wiesel remained silent for ten years before dedicating his life to the memory of this tragedy, witnessing tirelessly to remind an often indifferent world of its potential for self-destruction. Wiesel offers counsel in this volume concerning evil and suffering, life and death, chance and circumstance. Moreover, the dialogue evokes candid and often surprising responses by Wiesel on the Palestinian problem, Judeo-Christian relations, recent changes in the Soviet Union as well as insights into writers such as Kafka, Malraux, Mauriac and Unamuno.https://corescholar.libraries.wright.edu/dlpp_all/1246/thumbnail.jp

Impact of setanaxib on quality of life outcomes in primary biliary cholangitis in a phase 2 randomized controlled trial

There is a real unmet need for primary biliary cholangitis (PBC) treatments that can improve quality of life impacting symptoms. In this post hoc analysis, we evaluated potential effects of the NADP oxidase 1/4 inhibitor, setanaxib, on patient-reported quality of life from a phase 2 trial in PBC. The underpinning double-blind, randomized, placebo-controlled trial (NCT03226067) recruited 111 patients with PBC and inadequate response/intolerance to ursodeoxycholic acid. Patients self-administered oral placebo (n=37), setanaxib 400 mg once daily (OD; n=38), or setanaxib 400 mg twice daily (BID; n=36), in addition to ursodeoxycholic acid for 24 weeks. Quality of life outcomes were assessed using the validated PBC-40 questionnaire. Patients were stratified post hoc by baseline fatigue severity. At week 24, patients treated with setanaxib 400 mg BID reported greater mean (SE) absolute reductions from baseline in PBC-40 fatigue domain score [-3.6 (1.3)] versus those receiving setanaxib 400 mg OD [-0.8 (1.0)]) or placebo [0.6 (0.9)]. Similar observations were made across all PBC-40 domains except itch. In the setanaxib 400 mg BID arm, patients with moderate-to-severe fatigue at baseline had a greater reduction in mean fatigue score at week 24 [-5.8 (2.1)] versus those with mild fatigue [-0.6 (0.9)]; results were similar across all domains. Reduced fatigue was correlated with emotional, social, symptom, and cognitive improvements. These results support further investigation of setanaxib as a treatment for patients with PBC, particularly for those with clinically significant fatigue