Background
New oral anticoagulants (NOACs) offer an alternative to warfarin for preventing stroke in patients with atrial fibrillation. NOACs are expected to replace warfarin and other vitamin K ...antagonists for most of their indications in the future. Knowledge of the use of NOACs in the perioperative period is important for optimal care.
Methods
Studies that reported on the use of NOACs were identified, focusing on evidence‐based guidance relating to the perioperative period. PubMed was searched for relevant articles published between January 2000 and January 2014.
Results
The anticipated expanded clinical use of NOACs such as rivaroxaban (Xarelto™), apixaban (Eliquis™) and dabigatran (Pradaxa™) has the potential to simplify perioperative anticoagulant management because of fewer drug–drug interactions, rapid onset of action, predictable pharmacokinetics and relatively short half‐lives. However, coagulation status cannot be monitored by international normalized ratio and no antidotes are currently available. In elective surgery, it is important to discontinue the use of NOACs, with special consideration of renal function as route of elimination. Guidelines for the management of bleeding complications in patients on NOACs are provided, and may be considered for trauma and emergency surgery. Haemodialysis could be considered for bleeding with use of dabigatran. Better options for reversal of the effects of NOACs when bleeding occurs may follow with novel drugs.
Conclusion
Management of NOACs in elective and emergency conditions requires knowledge of time of last intake of drug, current renal function and the planned procedure in order to assess the overall risk of bleeding. Currently no antidote exists to reverse the effects of these drugs.
Increasing use, no antidote available
The retinal pigment epithelium (RPE)-choriocapillaris (CC) complex in the eye is compromised in age-related macular degeneration (AMD) and related macular dystrophies (MDs), yet in vitro models of ...RPE-CC complex that enable investigation of AMD/MD pathophysiology are lacking. By incorporating iPSC-derived cells into a hydrogel-based extracellular matrix, we developed a 3D RPE-CC model that recapitulates key features of both healthy and AMD/MD eyes and provides modular control over RPE and CC layers. Using this 3D RPE-CC model, we demonstrated that both RPE- and mesenchyme-secreted factors are necessary for the formation of fenestrated CC-like vasculature. Our data show that choroidal neovascularization (CNV) and CC atrophy occur in the absence of endothelial cell dysfunction and are not necessarily secondary to drusen deposits underneath RPE cells, and CC atrophy and/or CNV can be initiated systemically by patient serum or locally by mutant RPE-secreted factors. Finally, we identify FGF2 and matrix metalloproteinases as potential therapeutic targets for AMD/MDs.
Display omitted
•First patient-derived 3D RPE-CC model•Captures hallmarks of RPE-CC morphogenesis and AMD•Insight into cellular, soluble, and systemic factors that initiate AMD pathology•Pharmacological targeting of AMD pathology in a physiological iPSC model
We developed a patient-derived in vitro model of the retinal pigment epithelium (RPE)-choriocapillaris (CC) complex to investigate local and systemic factors underlying age-related macular degeneration (AMD) and similar maculopathies. The model captures hallmarks of RPE-CC morphogenesis and AMD, provides insight into factors that induce dysfunction, and leads to the identification of therapeutic targets.
The alternating shielding gas technique is a method of achieving transient arc characteristics during arc welding; however the complex flow that occurs through its use has not been investigated ...previously. A schlieren system was used to image density gradients that arise when alternating argon and helium shield gases, under varying flow parameters, with gas tungsten arc welding (GTAW). A theoretical analysis was carried out to determine the conditions under which the technique facilitates arc pulsing, in particular to avoid mixing of the shield gases in the delivery pipe prior to the welding nozzle. At appropriate pulsing frequency and flow rates, a stable horizontal region of helium was observed in the weld region, maintained in position by the denser argon from the preceding pulse. This higher than average mass fraction of helium when applying the shielding gases alternately, compared to a premixed gas with the same volume of argon and helium, increased the weld penetration by 13% on average, suggesting a modest improvement in heat transfer.
Display omitted
•High-speed schlieren imaging facilitates observation of transient flow features during GTAW.•High pulse rates and low flow rates resulted in the shielding gases being delivered premixed.•Low pulse rates and higher flow rates showed more efficient use of the helium.•Alternating instead of premixing the gases increased the weld penetration by 13% on average.
This study considered the effect of shielding gas parameters (composition, supply method and flow rate) on the post-weld thermal properties (thermal expansion, specific heat capacity, thermal ...diffusivity and thermal conductivity) of the weld metal in gas metal arc welding. This is of importance as the thermal properties influence the temperature distribution and therefore the residual stresses and distortion present within the final structure. Due to the lack of accurate thermal data, computational modelling techniques (such as FEA and CFD) used for modelling the welding process generally make assumptions regarding the material thermal properties, and it is often the case that the parent material thermal properties are extended to the weld metal, introducing errors to the simulation. It was determined that the weld metal posses considerably different thermal properties to the DH36 grade steel parent material and that the shielding gas parameters significantly alter key thermal properties of the solidified weld metal. A lower shielding gas flow rate exhibited beneficial properties including a lower thermal expansion and higher specific heat capacity and thermal conductivity than a higher shielding gas flow rate.
The transient variation of the shielding gas present in the alternating shielding gas process produces a dynamic action within the liquid weld metal. Flow vectors opposite in direction have been ...reported due to the various forces acting on the weld metal when argon and helium are present; however, no data have been provided to substantiate this claim. This part of the study evaluates the various forces acting on the liquid weld metal when using argon and helium, and their effects are discussed. It was determined that argon produces a greater vertically downward force in the central region than does helium for both the arc force and Lorentz force. However, helium produces a greater radially outward force at the pool surface than does argon due to plasma shear stress and Marangoni convection. In addition, the buoyancy force, i.e. the vertically upward force in the central portion of the weld metal, was greater for helium.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A series of experimental trials have been conducted to investigate the effects of reducing the shielding gas consumption in gas metal arc welding (GMAW). A number of claims have been made as to ...potential shielding gas savings in the GMAW process when using gas-saving devices such as commercially available self-regulating valves. However, the literature and data available on weld quality obtained as a result of reducing the shielding gas flow rate is not readily available, so the thrust of this study is to present a new body of data to report on the technical and economic merits of controlling the shielding gas flow rate using (a) a conventional flow meter and (b) a ‘new to market’ self-regulating gas-saving device. It has been determined that, in a draft-free environment, the shielding gas flow rate can be reduced to 6 L/min without diminishing weld quality, although a lower flow rate was more susceptible to the effects of cross-drafts, and the weld quality level was compromised. In addition to the economic savings associated with reducing the shielding gas flow rate, there are several weld aspects that have been found to be influenced by the shielding gas flow rate including penetration, leg length, distortion and peak temperature, thus suggesting that the heat transfer efficiency is affected by the shielding gas flow rate. This significant finding supports the view that there is scope to increase the travel speed when implementing a lower flow rate and, consequently, enhance productivity.
This study compared the mechanical and microstructural properties produced during friction stir welding of S275 structural steel in air and underwater. Post-weld tests assessed the tensile strength, ...microhardness, distortion, Charpy impact toughness and fatigue performance in each case. The study showed that there was no significant difference in the strength, hardness or fatigue life of the air and underwater specimens. However, Charpy impact toughness was shown to decrease for the underwater specimens and was attributed to the presence of a slightly less angular grain structure than the samples welded in air. Reduced angular and longitudinal distortion was observed in the underwater welded plate compared to the plate welded in air.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Liver transplantation (LT) can significantly improve mortality for severe alcoholic hepatitis (AH). However, this practice remains controversial. Our aim is to report the findings from our ...institution regarding outcomes for LT in severe AH and to discuss the results of a pilot program for discharging selected patients with close follow-up, in order to demonstrate sustained outpatient sobriety before listing.
Patient records were reviewed retrospectively from January 1, 2015 to January 17, 2018. The primary outcomes were patient and graft survival after LT. Secondary outcomes included relapse rates after LT, survival for those not transplanted, and reasons for denial among those not approved for transplant listing.
A total of 18 patients with severe AH were considered for LT, of which 10 were transplanted and 8 were either denied transplantation or died before completing the evaluation. Patient and graft survival rates were 100% among those transplanted, and only 1 of the 10 patients (10%) returned to harmful drinking. In comparison, 6 of 8 (75%) of patients not transplanted died. Among the 10 patients transplanted, 4 were initially not approved for listing and were discharged with close follow-up, to demonstrate outpatient sobriety. All 4 of those patients demonstrated short-term abstinence and ultimately underwent transplantation, with no instances of relapse post-LT.
Liver transplantation for AH can achieve excellent outcomes with low rates of relapse. Carefully selected patients can be discharged with close monitoring to demonstrate commitment to outpatient sobriety prior to transplant listing.
•The decision to join the list for a liver transplant may be delayed in carefully selected patients.•There are no specific characteristics most indicative of increased relapse risk.•We demonstrate a protocol for patients to demonstrate short-term abstinence.•All patients in the program were successfully transplanted with no relapse events.
PDF
