Paediatric aortic valve replacement: a meta-analysis and microsimulation study.

AIMS: To support decision-making in children undergoing aortic valve replacement (AVR), by providing a comprehensive overview of published outcomes after paediatric AVR, and microsimulation-based age-specific estimates of outcome with different valve substitutes. METHODS AND RESULTS: A systematic review of published literature reporting clinical outcome after paediatric AVR (mean age <18 years) published between 1/1/1990 and 11/08/2021 was conducted. Publications reporting outcome after paediatric Ross procedure, mechanical AVR (mAVR), homograft AVR (hAVR), and/or bioprosthetic AVR were considered for inclusion. Early risks (<30d), late event rates (>30d) and time-to-event data were pooled and entered into a microsimulation model. Sixty-eight studies, of which one prospective and 67 retrospective cohort studies, were included, encompassing a total of 5259 patients (37 435 patient-years; median follow-up: 5.9 years; range 1-21 years). Pooled mean age for the Ross procedure, mAVR, and hAVR was 9.2 ± 5.6, 13.0 ± 3.4, and 8.4 ± 5.4 years, respectively. Pooled early mortality for the Ross procedure, mAVR, and hAVR was 3.7% (95% CI, 3.0%-4.7%), 7.0% (5.1%-9.6%), and 10.6% (6.6%-17.0%), respectively, and late mortality rate was 0.5%/year (0.4%-0.7%/year), 1.0%/year (0.6%-1.5%/year), and 1.4%/year (0.8%-2.5%/year), respectively. Microsimulation-based mean life-expectancy in the first 20 years was 18.9 years (18.6-19.1 years) after Ross (relative life-expectancy: 94.8%) and 17.0 years (16.5-17.6 years) after mAVR (relative life-expectancy: 86.3%). Microsimulation-based 20-year risk of aortic valve reintervention was 42.0% (95% CI: 39.6%-44.6%) after Ross and 17.8% (95% CI: 17.0%-19.4%) after mAVR. CONCLUSION: Results of paediatric AVR are currently suboptimal with substantial mortality especially in the very young with considerable reintervention hazards for all valve substitutes, but the Ross procedure provides a survival benefit over mAVR. Pros and cons of substitutes should be carefully weighed during paediatric valve selection.

Quantum Non-Gaussianity of Multiphonon States of a Single Atom.

Quantum non-Gaussian mechanical states are already required in a range of applications. The discrete building blocks of such states are the energy eigenstates-Fock states. Despite progress in their preparation, the remaining imperfections can still invisibly cause loss of the aspects critical for their applications. We derive and apply the most challenging hierarchy of quantum non-Gaussian criteria on the characterization of single trapped-ion oscillator mechanical Fock states with up to 10 phonons. We analyze the depth of these quantum non-Gaussian features under intrinsic mechanical heating and predict their requirement for reaching quantum advantage in the sensing of a mechanical force.

Slowing Quantum Decoherence by Squeezing in Phase Space.

Non-Gaussian states, and specifically the paradigmatic cat state, are well known to be very sensitive to losses. When propagating through damping channels, these states quickly lose their nonclassical features and the associated negative oscillations of their Wigner function. However, by squeezing the superposition states, the decoherence process can be qualitatively changed and substantially slowed down. Here, as a first example, we experimentally observe the reduced decoherence of squeezed optical coherent-state superpositions through a lossy channel. To quantify the robustness of states, we introduce a combination of a decaying value and a rate of decay of the Wigner function negativity. This work, which uses squeezing as an ancillary Gaussian resource, opens new possibilities to protect and manipulate quantum superpositions in phase space.

Nonclassical Light from Large Ensembles of Trapped Ions.

The vast majority of physical objects we are dealing with are almost exclusively made of atoms. Because of their discrete level structure, single atoms have proved to be emitters of light, which is incompatible with the classical description of electromagnetic waves. We demonstrate this incompatibility for atomic fluorescence when scaling up the size of the source ensemble, which consists of trapped atomic ions, by several orders of magnitude. The presented measurements of nonclassical statistics on light unconditionally emitted from ensembles containing up to more than a thousand ions promise further scalability to much larger emitter numbers. The methodology can be applied to a broad range of experimental platforms focusing on the bare nonclassical character of single isolated emitters.

Deterministic nonclassicality from thermal states.

Coupling an oscillator to a single two-level system is one of the most fundamental interactions in quantum physics. We report on a dynamical effect during which a thermal state of an oscillator is unconditionally transformed to a highly nonclassical state with negative Wigner function values by mere absorbtion by a single uncontrolled two-level system. This complements the traditional test of Rabi oscillations and it serves as a simply measurable witness that the process in question is highly nonclassical. The process is experimentally feasible with possible experimental implementation in a number of experimental platforms with intrinsic Jaynes-Cummings interaction and it has the potential of enabling deterministic generation of nonclassical quantum states.

Heralded source of bright multi-mode mesoscopic sub-Poissonian light.

In a direct detection scheme, we observed 7.8 dB of twin-beam squeezing for multi-mode two-color squeezed vacuum generated via parametric downconversion. Applying post-selection, we conditionally prepared a sub-Poissonian state of light containing 6.3·105 photons per pulse on the average with the Fano factor 0.63±0.01. The scheme can be considered as the heralded preparation of pulses with the mean energy varying between tens and hundreds of fJ and the uncertainty considerably below the shot-noise level. Such pulses can be used in metrology (for instance, for radiometer calibration), as well as for probing multi-mode nonlinear optical effects.

Decarboxylative Fluorination of Aliphatic Carboxylic Acids via Photoredox Catalysis.

The direct conversion of aliphatic carboxylic acids to the corresponding alkyl fluorides has been achieved via visible light-promoted photoredox catalysis. This operationally simple, redox-neutral fluorination method is amenable to a wide variety of carboxylic acids. Photon-induced oxidation of carboxylates leads to the formation of carboxyl radicals, which upon rapid CO2-extrusion and F(•) transfer from a fluorinating reagent yield the desired fluoroalkanes with high efficiency. Experimental evidence indicates that an oxidative quenching pathway is operable in this broadly applicable fluorination protocol.

Selective Radical-Radical Cross-Couplings: Design of a Formal ß-Mannich Reaction.

A direct ß-coupling of cyclic ketones with imines has been accomplished via the synergistic combination of photoredox catalysis and organocatalysis. Transient ß-enaminyl radicals derived from ketones via enamine and oxidative photoredox catalysis readily combine with persistent α-amino radicals in a highly selective hetero radical-radical coupling. This novel pathway to γ-aminoketones is predicated upon the use of DABCO as both a base and an electron transfer agent. This protocol also formally allows for the direct synthesis of ß-Mannich products via a chemoselective three-component coupling of aryl aldehydes, amines, and ketones.

Optical Synthesis of Large-Amplitude Squeezed Coherent-State Superpositions with Minimal Resources.

We propose and experimentally realize a novel versatile protocol that allows the quantum state engineering of heralded optical coherent-state superpositions. This scheme relies on a two-mode squeezed state, linear mixing, and a n-photon detection. It is optimally using expensive non-Gaussian resources to build up only the key non-Gaussian part of the targeted state. In the experimental case of a two-photon detection based on high-efficiency superconducting nanowire single-photon detectors, the freely propagating state exhibits a 67% fidelity with a squeezed even coherent-state superposition with a size |α|(2)=3. The demonstrated procedure and the achieved rate will facilitate the use of such superpositions in subsequent protocols, including fundamental tests and optical hybrid quantum information implementations.

Retrograde flush is more protective than heparin in the uncontrolled donation after circulatory death lung donor.

BACKGROUND: Formation of microthrombi after circulatory arrest is a concern for the development of reperfusion injury in lung recipients from donation after circulatory death (DCD) donors. In this isolated lung reperfusion study, we compared the effect of postmortem heparinization with preharvest retrograde pulmonary flush or both. METHODS: Domestic pigs (n = 6/group) were sacrificed by ventricular fibrillation and left at room temperature for 1 h. This was followed by 2.5 h of topical cooling. In control group [C], no heparin and no pulmonary flush were administered. In group [R], lungs were flushed with Perfadex in a retrograde way before explantation. In group [H], heparin (300 IU/kg) was administered 10 min after cardiac arrest followed by closed chest massage for 2 min. In the combined group, animals were heparinized and the lungs were explanted after retrograde flush [HR]. The left lung was assessed for 60 min in an ex vivo reperfusion model. RESULTS: Pulmonary vascular resistance at 50 and 55 min was significantly lower in [R] and [HR] groups compared with [C] and [H] groups (P < 0.01 and P < 0.001) and at 60 min in [R], [H], and [HR] groups compared with [C] group (P < 0.001). Oxygenation, compliance, and plateau airway pressure were more stable in [R] and [HR] groups. Plateau airway pressure was significantly lower in [R] group compared with the [H] group at 60 min (P < 0.05). No significant differences in wet-dry weight ratio were observed between the groups. CONCLUSIONS: This study suggests that preharvest retrograde flush is more protective than postmortem heparinization to prevent reperfusion injury in lungs recovered from donation after circulatory death donors.

Aortic Valve Embryology, Mechanobiology, and Second Messenger Pathways: Implications for Clinical Practice.

During the Renaissance, Leonardo Da Vinci was the first person to successfully detail the anatomy of the aortic root and its adjacent structures. Ever since, novel insights into morphology, function, and their interplay have accumulated, resulting in advanced knowledge on the complex functional characteristics of the aortic valve (AV) and root. This has shifted our vision from the AV as being a static structure towards that of a dynamic interconnected apparatus within the aortic root as a functional unit, exhibiting a complex interplay with adjacent structures via both humoral and mechanical stimuli. This paradigm shift has stimulated surgical treatment strategies of valvular disease that seek to recapitulate healthy AV function, whereby AV disease can no longer be seen as an isolated morphological pathology which needs to be replaced. As prostheses still cannot reproduce the complexity of human nature, treatment of diseased AVs, whether stenotic or insufficient, has tremendously evolved, with a similar shift towards treatments options that are more hemodynamically centered, such as the Ross procedure and valve-conserving surgery. Native AV and root components allow for an efficient Venturi effect over the valve to allow for optimal opening during the cardiac cycle, while also alleviating the left ventricle. Next to that, several receptors are present on native AV leaflets, enabling messenger pathways based on their interaction with blood and other shear-stress-related stimuli. Many of these physiological and hemodynamical processes are under-acknowledged but may hold important clues for innovative treatment strategies, or as potential novel targets for therapeutic agents that halt or reverse the process of valve degeneration. A structured overview of these pathways and their implications for cardiothoracic surgeons and cardiologists is lacking. As such, we provide an overview on embryology, hemodynamics, and messenger pathways of the healthy and diseased AV and its implications for clinical practice, by relating this knowledge to current treatment alternatives and clinical decision making.

Direct ß-functionalization of cyclic ketones with aryl ketones via the merger of photoredox and organocatalysis.

The direct ß-coupling of cyclic ketones with aryl ketones has been achieved via the synergistic combination of photoredox catalysis and organocatalysis. Diaryl oxymethyl or aryl-alkyl oxymethyl radicals, transiently generated via single-electron reduction of ketone precursors, readily merge with ß-enaminyl radical species, generated by photon-induced enamine oxidation, to produce γ-hydroxyketone adducts. Experimental evidence indicates that two discrete reaction pathways can be operable in this process depending upon the nature of the ketyl radical precursor and the photocatalyst.

Total synthesis of (±)-cycloclavine and (±)-5-epi-cycloclavine.

Novel routes to the naturally occurring indole alkaloid cycloclavine and its unnatural C(5)-epimer are described. Key features include the rapid construction of the heterocyclic core segments by two Diels-Alder reactions. An indole annulation was accomplished by a late-stage intramolecular Diels-Alder furan cycloaddition, and a methylenecyclopropane dienophile was used for a stereoselective intramolecular [4 + 2] cycloaddition to give the cyclopropa[c]indoline building block present in cycloclavine.

Off-label use of stretchable polytetrafluoroethylene: overexpansion of synthetic shunts.

PURPOSE: To describe our experience with balloon dilatation and stenting of modified systemic-to-pulmonary artery (PA) shunts in relation to an assessment and interpretation of the mechanical properties of thin-walled expandable polytetrafluoroethylene (ePTFE) stretch vascular grafts. METHODS: Our pediatric cardiology/cardiac surgery database was reviewed to identify all infants and children with a modified systemic-to-PA shunt who underwent cardiac catheterization. Reports and images were reviewed. Thin-walled stretchable and regular Gore-Tex vascular grafts were mechanically compared using tensiometry. RESULTS: 11 patients underwent dilatation or stenting procedures of a systemic-to-PA shunt. No major complications occurred and none of our patients died during or due to this intervention. High pressures in balloons and stents with diameters larger than the graft were used. Shunt diameters and oxygen saturation levels increased from 2.05 +/- 1.25 mm to 4.75 +/- 0.88 mm and with 12 +/- 6.8%, respectively. In 6 patients re-catheterizations were performed. Four patients died, all with patent shunts. The fail-stress and the fail-strain in the circumferential direction of the stretchable graft were significantly higher than in the non-stretchable graft. CONCLUSIONS: Dilatation and stenting of stenosed modified systemic-to-PA shunts is feasible and safe. Dilatation and stenting of these shunts to calibers larger than those provided by the manufacturer is possible. Results of our technical study posit a great advantage for the use of the thin-walled stretch configuration of ePTFE.

Natural History of a Traumatic Olecranon Loss Resulting in a "Reversed Elbow": A Case Report.

Case description: A 58-year-old woman suffered an open displaced olecranon fracture with extensive soft tissue damage when she was involved in a car accident in Africa. Local doctors performed a debridement of the elbow. Later, she presented in our centre for further treatment. There was a possibility of active infection, for which antibiotics were given and a debridement was performed. We then applied dynamic external fixation to minimize infection risk. Physiotherapy started soon after. External fixation was removed after 2 months. On follow-up, the patient reported no pain and no signs of major instability were present. Therefore, we agreed not to perform additional surgery. Annual follow-up radiographs showed progressive remodelling of the joint. Eleven years after the initial trauma, a reversed elbow has formed. It is a fully functional neo-articulation that is shaped by osteophyte formation and erosion of ulna, radius and humerus. The patient is free of pain and shows intact flexion and supination, while extension and pronation are limited. She has regained good elbow function and can perform most of her daily activities. Conclusion: Invasive reconstructive surgery with implantation of foreign material should be avoided or postponed in heavily contaminated fractures to avoid infection. It could be valuable to consider a watchful waiting strategy, which sometimes results in a good functional end result. Nature can be kind, which has been proven in our case. How to cite this article: Hendrikx FR, Heusdens CHW, Van Dyck P, et al. Natural History of a Traumatic Olecranon Loss Resulting in a "Reversed Elbow": A Case Report. Strategies Trauma Limb Reconstr 2020;15(2):126-129.

Retrograde flush following warm ischemia in the non-heart-beating donor results in superior graft performance at reperfusion.

BACKGROUND: The use of non-heart-beating donors (NHBD) has been propagated as an alternative to overcome the scarcity of pulmonary grafts. The presence of postmortem thrombi, however, is a concern for the development of primary graft dysfunction. In this isolated lung reperfusion study, we looked at the need and the best route of preharvest pulmonary flush. METHODS: Domestic pigs were sacrificed by ventricular fibrillation and divided in 3 groups (n = 6 per group). After 1 h of in situ warm ischemia, lungs in group I were retrieved unflushed (NF). In group II, lungs were explanted after an anterograde flush (AF) through the pulmonary artery. Finally, in group III, lungs were explanted after a retrograde flush (RF) via the left atrium. After 3 h of cold storage, the left lung was assessed for 60 min in our ex vivo reperfusion model. Wet-to-dry weight ratio (W/D) was calculated after reperfusion. RESULTS: Pulmonary vascular resistance (dynes x sec x cm(-5)) was 1145 +/- 56 (RF) versus 1560 +/- 123 (AF) and 1435 +/- 95 (NF) at 60 min of reperfusion (P < 0.05). Oxygenation and compliance were higher and plateau airway pressure was lower in RF versus AF and NF, although the difference did not reach statistical significance. No differences in W/D were observed between groups after reperfusion. Histological examination revealed fewer microthrombi in the left lung in RF compared with AF and NF. CONCLUSION: RF of lungs from NHBD improves graft function by elimination of microthrombi from the pulmonary vasculature, resulting in lower pulmonary vascular resistance upon reperfusion.

Prevalence of ergot derivatives in natural ryegrass pastures: detection and pathogenicity in the horse.

In the present study, we determined the incidence and effects of season and weather on clinical manifestations of endophyte-infected ryegrass toxicity, performed chemical detection and pharmacological bioassays on ryegrass extracts, and conducted trials on: (i) effects of domperidone or metochlopramide on ovarian inactivity induced by endophyte-infected ryegrass; (ii) efficacy of buspirone or dihydrochloro phenyl piperazine (m-CPP) for preventing suppressed milk production induced by endophyte-infected ryegrass; and (iii) efficacy of domperidone to induce ovulation during winter anestrus. Mares with toxicosis had prolonged gestation, embryonic losses, dystocia, poor mammary gland development, low milk production, prolonged uterine involution, and suppressed ovarian activity. Foals had respiratory failure, abnormalities of the skin, umbilicus, bone, and muscle, failure to thrive, blindness, testicular atrophy, and decreased serum total immunoglobulin concentrations. Endophyte-infected ryegrass and the incidence of toxicosis were correlated (r=0.861, P=0.03). Ergot alkaloids were not detected in extracts of endophyte-infected ryegrass by either thin-layer chromatography or spectrophotometry, but their presence was inferred in bioassays of extracts (dose-related increases in the contractile response of rat uterus). Mares given metoclopropamide (0.6 mg/kg/d), given orally every 8h for up to 7d) ovulated earlier (4-7d vs. 15-18d, P<0.001) than those given domperidone (1.1mg/kg/d) orally for up to 18d). Although both metoclopropamide and domperidone induced milk production, the latter did not induce ovarian cyclicity in healthy mares during seasonal anestrus. Based on these findings, we inferred that endophyte-infected ryegrass is associated with ergot alkaloid intoxication in horse.

Ovine models for chronic heart failure.

PURPOSE: Testing and optimizing of surgical therapies for chronic heart failure (CHF) requires large animal models. CHF has been induced in several large animal species. Sheep have modest body mass increase and demonstrate docile behavior and are therefore a preferred species in research on surgical therapies for CHF METHODS: A literature search for existing ovine CHF models was performed, using search terms "sheep" and "heart failure". Relevant secondary references were traced. RESULTS: Rapid ventricular pacing produces rapid-onset CHFE Its severity ranges from moderate left ventricular failure to severe biventricular failure, depending on length and frequency of pacing. Its counterpart in human CHF is tachycardia-induced HF since it is reversible upon cessation of pacing. Myocardial damage models include CHF induced by cardiototoxic drugs and ischemia. Ischemia-based models include coronary microembolization, occlusion and ischemia/reperfusion models. The microembolization model is relevant to diabetic cardiomyopathy. Coronary occlusion models exhibit variable functional impairment, some with aneurysm formation, and some with mitral valve regurgitation, depending on occlusion localization. They are relevant to CHF following non-reperfused myocardial infarction. Coronary occlusion/reperfusion models are relevant to the occurrence of human ãã despite coronary artery recanalization. Pressure overload of left and right ventricle is induced by aortic and pulmonary artery banding, respectively. Hypertrophy precedes CHF as in patients with valve stenosis and hypertension. Volume overload is induced by valve damage or shunt creation. Atrioventricular valve regurgitation is the most important clinical counterpart. CONCLUSION: Several ovine CHF models exist. Since they exhibit important cardiac pathology differences, the choice of model should be based on the specific experimental question.

The absorption, tissue distribution and excretion of enteraly administered alpha-ketoglutarate in rats.

The absorption, tissue distribution and excretion of enteral alpha-ketoglutarate (AKG) was studied in four experiments. Six male Sprague Dawley rats were used to investigate the excretion of AKG in urine and faeces. Thirty rats, randomly assigned to five groups, were used to investigate the distribution of AKG in body tissues. They were gavaged with AKG enriched with 3 muCi/kg BW of (14)C uniformly marked AKG. Fourteen male Sprague Dawley rats were used to study the absorption of AKG (duodenum vs. ileum). Intestinal recovery of NaAKG vs. CaAKG was investigated in 36 rats. There was no significant excretion of non-metabolized AKG in the urine and faeces. There was no significant difference in the systemic levels of AKG when comparing the proximal to distal small intestine infusion. Up to 50%, 30% and 20% of gastrically delivered AKG was recovered in the stomach, 0.5, 1 and 2 h after gavage; the jejunal recovery achieved a maximum of 3%, 30 min after gavage, and was not detectable 2 h later. There was a relatively high distribution of (14)C-AKG in the tissues (e.g. liver, brain, bones, skin, muscles), 3 h after gavage, up to 70% of the administered dose. In conclusion, the high rate of retention of the carbon from AKG allows the postulation that there is a non-energetic mode of metabolism of intragastrically administered AKG. After conversion to final metabolites, AKG penetrates into all tissues and organs of rats, including the bone tissue. Intestinal absorption of AKG does not depend on the type of AKG salt administered.

Valgus instability of the elbow: acute and chronic form.

There has been an increase in thrower-specific elbow injuries in recent years. High valgus stresses during the late cocking and acceleration phases of throwing need to be compensated by the flexor pronator muscles as these can exceed the tensile strength of the medial collateral ligament complex. Prevention of injuries is the priority, with a focus on strengthening, reducing throwing frequency, decreasing force, and promoting a technique. The spectrum of thrower injuries ranges from a simple sprain to complete failure of the valgus stabilizing factors. The medial collateral ligament can stretch, leading to posteromedial impingement and radiocapitellar compression forces. This in turn can result in arthrosis and the formation of osteophytes. Ligament failure may eventually occur, making it impossible for the athlete to continue their throwing activities. The outcome of conservative treatment with strengthening, improvement of technique, and relative rest is often disappointing. Direct repair may no longer be possible in these acute-on-chronic injuries and a reconstruction with a tendon graft may be necessary.