Successful management of bleeding complications in patients supported with extracorporeal membrane oxygenation with primary respiratory failure.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a lifesaving procedure in patients with severe respiratory insufficiency failing conventional support. Bleeding complications are common due to the necessity for anticoagulation and circuit-related factors. METHODS: A retrospective review was conducted in patients requiring ECMO for respiratory failure from 7/2010 to 6/2011 to identify episodes of major bleeding, bleeding management and outcomes. RESULTS: Twenty-one patients were supported with ECMO during the study although five experienced massive bleeding related to chest tube insertion, jejunal arterio-venous malformations, distal perfusion cannula dislodgement and ventricular rupture. Patients required aggressive resuscitation or endoscopic or operative intervention, totaling 28 procedures. There were no instances of dehiscence, infection or sepsis related to interventions. Anticoagulation was stopped six hours before and restarted 24 hours after major interventions, with no thrombotic or neurologic complications. All patients weaned off ECMO were discharged. CONCLUSIONS: ECMO bleeding complications can be managed successfully via surgical and endoscopic approaches in this high-risk population.

Experimental achievement and signatures of ignition at the National Ignition Facility.

An inertial fusion implosion on the National Ignition Facility, conducted on August 8, 2021 (N210808), recently produced more than a megajoule of fusion yield and passed Lawson's criterion for ignition [Phys. Rev. Lett. 129, 075001 (2022)10.1103/PhysRevLett.129.075001]. We describe the experimental improvements that enabled N210808 and present the first experimental measurements from an igniting plasma in the laboratory. Ignition metrics like the product of hot-spot energy and pressure squared, in the absence of self-heating, increased by ∼35%, leading to record values and an enhancement from previous experiments in the hot-spot energy (∼3×), pressure (∼2×), and mass (∼2×). These results are consistent with self-heating dominating other power balance terms. The burn rate increases by an order of magnitude after peak compression, and the hot-spot conditions show clear evidence for burn propagation into the dense fuel surrounding the hot spot. These novel dynamics and thermodynamic properties have never been observed on prior inertial fusion experiments.

Design of an inertial fusion experiment exceeding the Lawson criterion for ignition.

We present the design of the first igniting fusion plasma in the laboratory by Lawson's criterion that produced 1.37 MJ of fusion energy, Hybrid-E experiment N210808 (August 8, 2021) [Phys. Rev. Lett. 129, 075001 (2022)10.1103/PhysRevLett.129.075001]. This design uses the indirect drive inertial confinement fusion approach to heat and compress a central "hot spot" of deuterium-tritium (DT) fuel using a surrounding dense DT fuel piston. Ignition occurs when the heating from absorption of α particles created in the fusion process overcomes the loss mechanisms in the system for a duration of time. This letter describes key design changes which enabled a ∼3-6× increase in an ignition figure of merit (generalized Lawson criterion) [Phys. Plasmas 28, 022704 (2021)1070-664X10.1063/5.0035583, Phys. Plasmas 25, 122704 (2018)1070-664X10.1063/1.5049595]) and an eightfold increase in fusion energy output compared to predecessor experiments. We present simulations of the hot-spot conditions for experiment N210808 that show fundamentally different behavior compared to predecessor experiments and simulated metrics that are consistent with N210808 reaching for the first time in the laboratory "ignition."

Hybrid endovascular treatment of an aberrant right subclavian artery with Kommerell aneurysm.

Aberrant right subclavian artery is a rare anatomical finding of abnormal embryologic development of the dorsal aorta and right subclavian artery. An associated aortic outpouching, or Kommerell diverticulum, may develop at the origin of the aberrant right subclavian artery. Given historically high rates of aneurysm rupture and mortality, early repair is indicated. Successful aneurysm exclusion can be accomplished with thoracic endovascular stent grafting following open carotid-subclavian bypass, maintaining upper extremities perfusion. Such hybrid techniques offer a decrease in mortality and complication rates. Herein, we describe a successful repair of a symptomatic (dysphagia, weight loss) aberrant right subclavian artery with Kommerell diverticulum using this hybrid open-endovascular approach.

Obesity and mobility disability in the older adult.

Mobility disability is becoming prevalent in the obese older population (> or = 60 years of age). We included a total of 13 cross-sectional and 15 longitudinal studies based on actual physical assessments of mobility in the obese older population in this review. We systematically examined existing evidence of which adiposity estimate best predicted mobility disability. Cross-sectional studies (82-4000 participants) showed poorer lower extremity mobility with increasing obesity severity in both men and women. All longitudinal studies (1-22 years) except for one, reported relationships between adiposity and declining mobility. While different physical tests made interpretation challenging, a consistent finding was that walking, stair climbing and chair rise ability were compromised with obesity, especially if the body mass index (BMI) exceeded 35 kg m(-2). More studies found that obese women were at an increased risk for mobility impairment than men. Existing evidence suggests that BMI and waist circumference are emerging as the more consistent predictors of the onset or worsening of mobility disability. Limited interventional evidence shows that weight loss is related with increased mobility and lower extremity function. Additional longitudinal studies are warranted that address overall body composition fat and muscle mass or change on future disability.

Somite chondrogenesis in vitro: 1. Alterations in proteoglycan synthesis.

During embryonic development, somites undergo chondrogenic differentiation when stimulated by notochord or spinal cord. The present study shows that, when cultured in suitable medium, explanted somites incorporated radioactive sulfate into cartilage-specific proteoglycans and the synthetic rate increased when notochord was included with somites. With increased culture time, explanted somites also synthesized proteoglycan monomers which were larger in size along with a larger proportion that were capable of interacting with exogenous hyaluronic acid. Interaction with notochord also resulted in increased synthesis of chondroitin 4-sulfate. Gel electrophoretic analysis showed that proteoglycans from unstimulated somites did not contain link protein (required for stable aggregate formation), even on day 9, while notochord-induced somites showed link protein as early as day 3, increasing 3-fold by day 9.

Somite chondrogenesis in vitro: 2. Changes in the hyaluronic acid synthesis.

The role of hyaluronic acid in limb morphogenesis (chondrogenesis) has been well defined. In the present study, we found that hyaluronic acid synthesis in somite explants steadily increased until day 6, then decreased, and inclusion of notochord did not accelerate the rate of synthesis. Analysis of hyaluronidase activity in the somite explants indicated an increase in the enzyme level in day-6 cultures. Again, inclusion of notochord did not alter this pattern. The decrease in hyaluronic acid after day 6 and the increase in sulfated proteoglycan synthesis from day 6 resemble the pattern described during limb development. Subsequent studies showed that, with time, the size of the hyaluronic acid synthesized by somites increased and, again, inclusion of notochord did not influence this pattern. The results indicate that unstimulated somites are capable of synthesizing cartilage-specific proteoglycans in a relatively restricted manner, and the inclusion of notochord resulted in accelerated synthesis of stable proteoglycan aggregates typical of differentiated chondrocytes. Metabolic events in somites related to hyaluronic acid are not influenced by the notochord.

Forskolin- and dibutyryl cyclic AMP-mediated inhibition of chondrogenesis.

The regulatory role of cyclic AMP in various cellular activities is well known. It has been documented that both the notochord and extracellular matrix materials (ECM) induce somite chrondrogenesis. We believe that the ECM modulates the intracellular cAMP level during chondrogenic differentiation. The studies indicated that notochordal induction, which resulted in somite chondrogenesis (reflected by increased sulfated glycosaminoglycan synthesis) reduced the intracellular cAMP level in somites. Addition of forskolin and dibutyryl cAMP resulted in increased intracellular cAMP levels and decreased synthesis of sulfated glycosaminoglycans (decreased chondrogenesis). In the case of dibutyryl cAMP, the inhibition of sulfated glycosaminoglycan synthesis was related to the length of exposure time. Thus, the inverse relationship between cAMP content and enhanced chondrogenesis supports the theory that, in somites, a decrease in the intracellular cAMP level may be necessary to trigger chondrogenic differentiation.

Somite chondrogenesis: alterations in cyclic AMP levels and proteoglycan synthesis.

Cyclic AMP (cAMP) levels have been shown to have a positive influence on chondrogenesis in limb buds and pelvic cartilage. In the present study the level of cAMP was measured during somite chondrogenesis in vitro and found to decrease from 1.38 pmol/micrograms DNA on day 0 to 0.9 pmol/micrograms DNA on day 6. Inclusion of notochord with somites caused a marked reduction, with levels decreasing from 1.41 pmol/micrograms DNA on day 0 to 0.36 pmol/micrograms DNA on day 6. Concurrently, the incorporation of radioactive sulfate into sulfated glycosaminoglycans increased from day 3 to day 6 by 38% in somite and 77% in somite-notochord explants. The aggregation of proteoglycans was analyzed by gel chromatography and found to increase with a corresponding decrease in cAMP levels. The results indicate that a decrease in cAMP levels may be necessary for chondrogenic expression in somites.