Cardiovascular autonomic nervous system responses and orthostatic intolerance in astronauts and their relevance in daily medicine

Neurological Sciences - The harsh environmental conditions during space travel, particularly weightlessness, impose a major burden on the human body including the cardiovascular system. Given its...     

Impact of Modified Frozen Elephant Trunk Procedure on Downstream Aorta Remodeling in Acute Aortic Dissection: CT Scan Follow-Up

World Journal of Surgery - The aim was to evaluate the impact of a modified frozen elephant trunk procedure (mFET) on remodeling of the downstream aorta following acute aortic dissections. Over a...     

One-stage double free flap arteriovenous loop reconstruction of a massive abdominothoracic defect following necrotizing fasciitis: A case report

We report the case of a 67-year old male with necrotizing fasciitis after injection of the glenohumeral joint. After extensive debridement a massive defect from the left hip joint to the left upper arm, exposing ribs, scapula, axillary vessels and brachial plexus (45 × 40 cm) was present. Reconstruction was performed with a conjoined right myocutaneous tensor fasciae lata/vastus lateralis flap and a left myocutaneous vastus lateralis flap in combination with an arteriovenous loop originating from the axillary vessels using the greater saphenous vein. Revisional surgeries were necessary including ribs resection and flap re-advancements. Due to multiorganic failure invasive ventilation, renal replacement- and extensive transfusion therapy was required. After 241 days the patient was discharged for rehabilitation. At the 12 months follow-up wounds were sufficiently closed without the need for further intervention. This case illustrates that immediate diagnosis followed by an aggressive multidisciplinary treatment approach is crucial for the patient survival.     

Intravenous immunoglobulin significantly reduces exposure of concomitantly administered anti‐C5 monoclonal antibody tesidolumab

Awareness of drug‐drug interactions is critical in organ transplant recipient management. However, biologic agents interfering with monoclonal antibodies is not widely considered. We report the effect of high‐dose intravenous immunoglobulin (IVIg) on safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of the human anti‐C5 monoclonal antibody tesidolumab (LFG316) in end‐stage renal disease patients awaiting kidney transplant. In this single‐center, phase 1, open‐label, parallel‐group study, 8 patients were assigned to receive either single‐dose tesidolumab + IVIg or tesidolumab alone, with 56‐day follow‐up. Within‐group PK parameters were consistent. Mean tesidolumab exposure decreased 34%, clearance increased 63%, and half‐life decreased 41% comparing tesidolumab + IVIg to tesidolumab alone. IVIg influence on tesidolumab elimination was most evident in the first 3 weeks. Complete suppression of both total and alternative complement activities was maintained for 4 weeks in the tesidolumab alone group and for 2 weeks in the tesidolumab + IVIg group. Tesidolumab was well tolerated. IVIg infused before tesidolumab affected tesidolumab PK and PD, resulting in a shortened period of full complement activity inhibition. These findings suggest a clinically relevant impact of IVIg on monoclonal antibody clearance and indirectly hint at an IVIg mechanism of action in treating autoimmune diseases and allosensitization by accelerating pathogenic IgG antibody degradation. Trial registration number: NCT02878616.