Optimal anesthetic conduct regarding immediate and short-term outcomes after liver transplantation - Systematic review of the literature and expert panel recommendations.

BACKGROUND: In the era of enhanced recovery after surgery, there is significant discussion regarding the impact of intraoperative anesthetic management on short-term outcomes following liver transplantation (LT), with no clear consensus in the literature. OBJECTIVES: To identify whether or not intraoperative anesthetic management affects short-term outcomes after liver transplantation. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: A systematic review following PRISMA guidelines was undertaken. The systematic review was registered on PROSPERO (CRD42021239758). An international expert panel made recommendations for clinical practice using the GRADE approach. RESULTS: After screening, 14 studies were eligible for inclusion in this systematic review. Six were prospective randomized clinical trials, three were prospective nonrandomized clinical trials, and five were retrospective studies. These manuscripts were reviewed to look at five questions regarding anesthetic care and its impact on short term outcomes following liver transplant. After review of the literature, the quality of evidence according to the following outcomes was as follows: intraoperative and postoperative morbidity and mortality (low), early allograft dysfunction (low), and hospital and ICU length of stay (moderate). CONCLUSIONS: For optimal short term outcomes after liver transplantation, the panel recommends the use of volatile anesthetics in preference to total intravenous anesthesia (TIVA) (Level of Evidence: Very low; Strength of Recommendation: Weak) and minimum alveolar concentration (MAC) versus bispectral index (BIS) for depth of anesthesia monitoring (Level of Evidence: Very low; Strength of Recommendation: Weak). Regarding ventilation and oxygenation, the panel recommends a restrictive oxygenation strategy targeting a PaO2 of 70-120 mmHg (10-14 kPa), a tidal volume of 6-8 ml/kg ideal body weight (IBW), administration of positive end expiratory pressure (PEEP) tailored to patient intraoperative physiology, and recruitment maneuvers. (Level of evidence: Very low; Strength of Recommendation: Strong). Finally, the panel recommends the routine use of antiemetic prophylaxis. (Level of evidence: low; Strength of Recommendation: Strong).

Mainstreaming adult ADHD into primary care in the UK: guidance, practice, and best practice recommendations.

BACKGROUND: ADHD in adults is a common and debilitating neurodevelopmental mental health condition. Yet, diagnosis, clinical management and monitoring are frequently constrained by scarce resources, low capacity in specialist services and limited awareness or training in both primary and secondary care. As a result, many people with ADHD experience serious barriers in accessing the care they need. METHODS: Professionals across primary, secondary, and tertiary care met to discuss adult ADHD clinical care in the United Kingdom. Discussions identified constraints in service provision, and service delivery models with potential to improve healthcare access and delivery. The group aimed to provide a roadmap for improving access to ADHD treatment, identifying avenues for improving provision under current constraints, and innovating provision in the longer-term. National Institute for Health and Care Excellence (NICE) guidelines were used as a benchmark in discussions. RESULTS: The group identified three interrelated constraints. First, inconsistent interpretation of what constitutes a 'specialist' in the context of delivering ADHD care. Second, restriction of service delivery to limited capacity secondary or tertiary care services. Third, financial limitations or conflicts which reduce capacity and render transfer of care between healthcare sectors difficult. The group recommended the development of ADHD specialism within primary care, along with the transfer of routine and straightforward treatment monitoring to primary care services. Longer term, ADHD care pathways should be brought into line with those for other common mental health disorders, including treatment initiation by appropriately qualified clinicians in primary care, and referral to secondary mental health or tertiary services for more complex cases. Long-term plans in the NHS for more joined up and flexible provision, using a primary care network approach, could invest in developing shared ADHD specialist resources. CONCLUSIONS: The relegation of adult ADHD diagnosis, treatment and monitoring to specialist tertiary and secondary services is at odds with its high prevalence and chronic course. To enable the cost-effective and at-scale access to ADHD treatment that is needed, general adult mental health and primary care must be empowered to play a key role in the delivery of quality services for adults with ADHD.

A Switchable Palladium(II) Trefoil Entangled Tetrahedron with Temperature Dependence and Concentration Independence.

Self-assembly makes metallo-interlocked architectures attractive targets, but being in equilibrium with smaller species means that they can suffer from dilution effects. We show that a junctioned system gives rise to a [Pd4 (L)2 ]8+ trefoil entangled tetrahedron irrespective of concentration. Heating the sample reversibly shifts the equilibrium from the knot to an isomeric non-interlocked dual metallo-cycle, demonstrating that thermodynamic equilibria can still be exploited for switching even in the absence of concentration effects.

Investigative study into whether an insect repellent has virucidal activity against SARS-CoV-2.

A small-scale study with Mosi-guard Natural spray, an insect repellent containing Citriodiol, was performed to determine if it has virucidal activity against SARS-CoV-2. A liquid test examined the activity of the insect repellent and the individual components for virucidal activity. A surface contact test looked at the activity of the insect repellent when impregnated on a latex surface as a synthetic skin for potential topical prophylactic application. Both Mosi-guard Natural spray and Citriodiol, as well as other components of the repellent, had virucidal activity in the liquid contact test. On a latex surface used to simulate treated skin, the titre of SARS-CoV-2 was less over time on the Mosi-guard Natural-treated surface but virus was still recovered.

Redefining Cirrhotic Cardiomyopathy for the Modern Era.

Cirrhotic cardiomyopathy (CCM) is cardiac dysfunction in patients with end-stage liver disease in the absence of prior heart disease. First defined in 2005 during the World Congress of Gastroenterology, CCM criteria consisted of echocardiographic parameters to identify subclinical cardiac dysfunction in the absence of overt structural abnormalities. Significant advancements in cardiovascular imaging over the past 14 years, including the integration of myocardial deformation imaging into routine clinical practice to identify subclinical cardiovascular dysfunction, have rendered the 2005 CCM criteria obsolete. Therefore, new criteria based on contemporary cardiovascular imaging parameters are needed. In this guidance document, assembled by a group of multidisciplinary experts in the field, new core criteria based on contemporary cardiovascular imaging parameters are proposed for the assessment of CCM. This document provides a critical assessment of the diagnosis of CCM and ongoing assessment aimed at improving clinical outcomes, particularly surrounding liver transplantation. Key points and practice-based recommendations for the diagnosis of CCM are provided to offer guidance for clinicians and identify gaps in knowledge for future investigations.

The perioperative management of simultaneous bilateral nephrectomy with renal transplantation: a case series.

PURPOSE: Bilateral nephrectomy is performed at times with renal transplantation. Though surgical indications and timing of these two procedures have been described, there are no large case series describing the anesthetic management of these cases. We sought to describe our experience. METHODS: We performed a historical cohort study on 54 consecutive cases of simultaneous bilateral nephrectomy with renal transplantation at a single, tertiary-care medical centre. Descriptive statistics were used. RESULTS: The most common etiology of kidney disease involved was autosomal dominant polycystic kidney disease at 52/54 (96%) cases. All patients received grafts from living donors. An arterial line was placed in 44 (81%) and a central venous catheter in 16 (30%) subjects. At least one vasopressor infusion was used in 44 (81%) cases and 37 (69%) patients required admission to the intensive care unit (ICU). Of this subset, 30 (81%) were admitted for ongoing vasopressor support and six (16%) for hemodynamic monitoring. All patients were extubated in the operating room upon completion of the procedure. Median [interquartile range (IQR)] ICU length of stay (LOS) was 0.9 [0.7-1.4] days and total hospital LOS was 4.4 [4.3-5.4] days. There were no cases of mortality at 30 days or of postoperative dialysis. CONCLUSIONS: Adult patients undergoing simultaneous bilateral nephrectomy with renal transplantation often developed perioperative hypotension requiring vasopressor infusions and postoperative transfer to the ICU. This is possibly due to a temporary loss of the renin-angiotensin system. Despite this, patients most commonly were transferred to the floor on postoperative day 1 and had successful outcomes with no mortality at 30 days.

RéSUMé: OBJECTIF: La néphrectomie bilatérale est parfois réalisée en même temps qu'une transplantation rénale. Bien que les indications chirurgicales et le moment de ces deux interventions aient été décrits, il n'existe aucune grande série de cas décrivant la prise en charge anesthésique de ces procédures. Notre objectif était de décrire notre expérience. MéTHODE: Nous avons réalisé une étude de cohorte historique sur 54 cas consécutifs de néphrectomie bilatérale avec transplantation rénale simultanée dans un seul centre médical de soins tertiaires. Des statistiques descriptives ont été utilisées. RéSULTATS: La maladie polykystique des reins autosomique dominante constituait l'étiologie de la maladie rénale la plus fréquente, représentant 52/54 (96 %) des cas. Tous les patients ont reçu des greffes de donneurs vivants. Une ligne artérielle a été installée chez 44 (81 %) patients et un cathéter veineux central chez 16 (30 %) patients. Au moins une perfusion de vasopresseurs a été utilisée chez 44 (81 %) patients, et 37 (69 %) patients ont dû être admis à l'unité de soins intensifs (USI). De ce sous-ensemble, 30 (81 %) patients ont été admis pour recevoir un soutien continu de vasopresseurs et six (16 %) pour un monitorage hémodynamique. Tous les patients ont été extubés en salle d'opération à la fin de l'intervention. La durée médiane [écart interquartile (ÉIQ)] de séjour aux soins intensifs était de 0,9 [0,7 à 1,4] jour, et la durée totale de séjour à l'hôpital était de 4,4 [4,3 à 5,4] jours. Il n'y a eu aucun cas de mortalité à 30 jours ou de dialyse postopératoire. CONCLUSION: Les patients adultes subissant une néphrectomie bilatérale et une transplantation rénale simultanées ont souvent souffert d'hypotension périopératoire exigeant des perfusions de vasopresseurs et un transfert postopératoire aux soins intensifs. Ceci est probablement dû à une perte temporaire du système rénine-angiotensine. Malgré cela, les patients étaient en général transférés à l'étage au jour postopératoire 1 et ont eu des devenirs favorables sans mortalité à 30 jours.

Anesthetic considerations for combined heart--liver transplantation in patients with Fontan-associated liver disease.

PURPOSE OF REVIEW: The success of the Fontan procedure has led to increased survival of patients born with certain congenital heart disease to the point that new sequlae, as a result of Fontan circulation, are being discovered. Included among these is Fontan-associated liver disease (FALD). The purpose of this review is to present available literature on the perioperative management of the combined heart--liver transplantation (CHLT) in patients with FALD. RECENT FINDINGS: The perioperative management of a combined heart-liver transplant in a patient with Fontan circulation is complex. The patient is at risk for hemodynamic disturbances, significant blood loss, coagulopathies, and metabolic derangements. The maintenance of an appropriate transpulmonary pressure gradient is paramount to success. Postoperative management should be accomplished by a multidisciplinary care team. Limited series have demonstrated good outcomes in patients who have undergone CHLT. SUMMARY: The perioperative management of CHLT in patients with FALD is complex and available literature is limited. Future studies are needed to further assess proper perioperative management of patients with FALD who undergo CHLT.

A Reduced-Symmetry Heterobimetallic [PdPtL4 ]4+ Cage: Assembly, Guest Binding, and Stimulus-Induced Switching.

A strategy is presented that enables the quantitative assembly of a heterobimetallic [PdPtL4 ]4+ cage. The presence of two different metal ions (PdII and PtII ) with differing labilities enables the cage to be opened and closed selectively at one end upon treatment with suitable stimuli. Combining an inert PtII tetrapyridylaldehyde complex with a suitably substituted pyridylamine and PdII ions led to the assembly of the cage. 1 H and DOSY NMR spectroscopy and ESI mass spectrometry data were consistent with the quantitative formation of the cage, and the heterobimetallic structure was confirmed using single-crystal X-ray crystallography. The structure of the host-guest adduct with a 2,6-diaminoanthraquinone guest molecule was determined. Addition of N,N'-dimethylaminopyridine (DMAP) resulted in the formation of the open-cage [PtL4 ]2+ compound and [Pd(DMAP)4 ]2+ complex. This process could then be reversed, with the reformation of the cage, upon addition of p-toluenesulfonic acid (TsOH).

Metallosupramolecular Architectures Formed with Ferrocene-Linked Bis-Bidentate Ligands: Synthesis, Structures, and Electrochemical Studies.

The self-assembly of ligands of different geometries with metal ions gives rise to metallosupramolecular architectures of differing structural types. The rotational flexibility of ferrocene allows for conformational diversity, and, as such, self-assembly processes with 1,1'-disubstituted ferrocene ligands could lead to a variety of interesting architectures. Herein, we report a small family of three bis-bidentate 1,1'-disubstituted ferrocene ligands, functionalized with either 2,2'-bipyridine or 2-pyridyl-1,2,3-triazole chelating units. The self-assembly of these ligands with the (usually) four-coordinate, diamagnetic metal ions Cu(I), Ag(I), and Pd(II) was examined using a range of techniques including 1H and DOSY NMR spectroscopies, high-resolution electrospray ionization mass spectrometry, X-ray crystallography, and density functional theory calculations. Additionally, the electrochemical properties of these redox-active metallosupramolecular assemblies were examined using cyclic voltammetry and differential pulse voltammetry. The copper(I) complexes of the 1,1'-disubstituted ferrocene ligands were found to be coordination polymers, while the silver(I) and palladium(II) complexes formed discrete [1 + 1] or [2 + 2] metallomacrocyclic architectures.

Synthesis and Light-Induced Actuation of Photo-Labile 2-Pyridyl-1,2,3-Triazole Ru(bis-bipyridyl) Appended Ferrocene Rotors.

To realise useful control over molecular motion in the future an extensive toolbox of both actionable molecules and stimuli-responsive units must be developed. Previously, our laboratory has reported 1,1'-disubstituted ferrocene (Fc) rotor units which assume a contracted/π-stacked conformation until complexation of cationic metal ions causes rotation about the Ferrocene (Fc) molecular 'ball-bearing'. Herein, we explore the potential of using the photochemical ejection of [Ru(2,2'-bipyridyl)2]2+ units as a stimulus for the rotational contraction of new ferrocene rotor units. Fc rotors with both 'regular' and 'inverse' 2-pyridyl-1,2,3-triazole binding pockets and their corresponding [Ru(2,2'-bipyridyl)2]2+ complexes were synthesised. The rotors and complexes were characterised using nuclear magnetic resonance (NMR) and ultraviolet (UV)-visible spectroscopies, Electro-Spray Ionisation Mass Spectrometry (ESI⁻MS), and electrochemistry. The 1,1'-disubstituted Fc ligands were shown to π-stack both in solution and solid state. Density Functional Theory (DFT) calculations (CAM-B3LYP/6-31G(d)) support the notion that complexation to [Ru(2,2'-bipyridyl)2]2+ caused a rotation from the syn- to the anti-conformation. Upon photo-irradiation with UV light (254 nm), photo-ejection of the [Ru(2,2'-bipyridyl)2(CH3CN)2]2+ units in acetonitrile was observed. The re-complexation of the [Ru(2,2'-bipyridyl)2]2+ units could be achieved using acetone as the reaction solvent. However, the process was exceedingly slowly. Additionally, the Fc ligands slowly decomposed when exposed to UV irradiation meaning that only one extension and contraction cycle could be completed.

Semliki Forest virus and Sindbis virus, but not vaccinia virus, require glycolysis for optimal replication.

Viruses are obligate intracellular pathogens which rely on the cell's machinery to produce the energy and macromolecules required for replication. Infection is associated with a modified metabolic profile and one pathway which can be modified is glycolysis. In this study, we investigated if the glycolysis pathway is required for alphavirus replication. Pre-treatment of Vero cells with three different glycolysis inhibitors (2-deoxyglucose, lonidamine and oxamate) resulted in a significant reduction (but not abrogation) of Semliki Forest virus and Sindbis virus replication, but not of the unrelated virus, vaccinia virus. Reduced virus yield was not associated with any significant cytotoxic effect and delayed treatment up to 3 h post-infection still resulted in a significant reduction. This suggested that glycolysis is required for optimal replication of alphaviruses by supporting post-entry life cycle steps.

Changes in transfusion practice over time in adult patients undergoing liver transplantation.

OBJECTIVE: The aim of this study was to investigate changes in transfusion practice over time in liver transplantation surgery and to evaluate potential causes for changes in practice and report associated perioperative morbidity and mortality. DESIGN: A retrospective cohort study. SETTING: A single tertiary referral academic hospital. PARTICIPANTS: Two cohorts of 100 sequential adult primary liver transplant recipients: Early practice (1990-1991) and recent practice (2005-2006). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Perioperative transfusion and hemoglobin data were recorded. Mortality and postoperative complications were identified up to 30 days postoperatively. Appropriate intergroup statistical comparisons were made; p ≤ 0.05 was considered statistically significant. Compared with the early group, the recent group had significantly fewer perioperative allogeneic red blood cell transfusions, intraoperative autotransfusions, and transfusions of other blood products. No change in perioperative transfusion triggers was identified. There were no significant alterations in perioperative morbidity or mortality. CONCLUSIONS: When compared with patients in the early group, recent cohort patients received significantly fewer blood transfusions. The authors attribute this observation to changes in surgical technique rather than a significant alteration in transfusion triggers over the studied time period.

Anesthesia and Critical Care for the Prediction and Prevention for Small-for-size Syndrome: Guidelines from the ILTS-iLDLT-LTSI Consensus Conference.

BACKGROUND: During the perioperative period of living donor liver transplantation, anesthesiologists and intensivists may encounter patients in receipt of small grafts that puts them at risk of developing small for size syndrome (SFSS). METHODS: A scientific committee (106 members from 21 countries) performed an extensive literature review on aspects of SFSS with proposed recommendations. Recommendations underwent a blinded review by an independent expert panel and discussion/voting on the recommendations occurred at a consensus conference organized by the International Liver Transplantation Society, International Living Donor Liver Transplantation Group, and Liver Transplantation Society of India. RESULTS: It was determined that centers with experience in living donor liver transplantation should utilize potential small for size grafts. Higher risk recipients with sarcopenia, cardiopulmonary, and renal dysfunction should receive small for size grafts with caution. In the intraoperative phase, a restrictive fluid strategy should be considered along with routine use of cardiac output monitoring, as well as use of pharmacologic portal flow modulation when appropriate. Postoperatively, these patients can be considered for enhanced recovery and should receive proactive monitoring for SFSS, nutrition optimization, infection prevention, and consideration for early renal replacement therapy for avoidance of graft congestion. CONCLUSIONS: Our recommendations provide a framework for the optimal anesthetic and critical care management in the perioperative period for patients with grafts that put them at risk of developing SFSS. There is a significant limitation in the level of evidence for most recommendations. This statement aims to provide guidance for future research in the perioperative management of SFSS.

Roles of Metal Ions in Foldamers and Other Conformationally Flexible Supramolecular Systems.

Conformational control is a key prerequisite for much molecular function. As chemists seek to create complex molecules that have applications beyond the academic laboratory, correct spatial positioning is critical. This is particularly true of flexible systems. Conformationally flexible molecules show potential because they resemble in many cases naturally occurring analogues such as the secondary structures found in proteins and peptides such as α-helices and ß-sheets. One of the ways in which conformation can be controlled in these molecules is through interaction with or coordination to metal ions. This review explores how secondary structure (i.e., controlled local conformation) in foldamers and other conformationally flexible systems can be enforced or modified through coordination to metal ions. We hope to provide examples that illustrate the power of metal ions to influence this structure toward multiple different outcomes.

Heteroleptic Tripalladium(II) Cages.

There is a concerted attempt to develop self-assembled metallo-cages of greater structural complexity, and heteroleptic PdII cages are emerging as prime candidates in these efforts. Most of these are dinuclear: few examples of higher nuclearity have been reported. We demonstrate here a robust method for the formation of tripalladium(II) cages from the 2 : 3 : 3 combination of a tritopic ligand, PdII , and a selection of ditopic ligands of the correct size and geometry.

Histopathological and Immunological Findings in the Common Marmoset Following Exposure to Aerosolized SARS-CoV-2.

There is an enduring requirement to develop animal models of COVID-19 to assess the efficacy of vaccines and therapeutics that can be used to treat the disease in humans. In this study, six marmosets were exposed to a small particle aerosol (1-3 µm) of SARS-CoV-2 VIC01 that delivered the virus directly to the lower respiratory tract. Following the challenge, marmosets did not develop clinical signs, although a disruption to the normal diurnal temperature rhythm was observed in three out of six animals. Early weight loss and changes to respiratory pattern and activity were also observed, yet there was limited evidence of viral replication or lung pathology associated with infection. There was a robust innate immunological response to infection, which included an early increase in circulating neutrophils and monocytes and a reduction in the proportion of circulating T-cells. Expression of the ACE2 receptor in respiratory tissues was almost absent, but there was ubiquitous expression of TMPRSS2. The results of this study indicate that exposure of marmosets to high concentrations of aerosolised SARS-CoV-2 did not result in the development of clear, reproducible signs of COVID-19.

Critical care issues in patients after liver transplantation.

The majority of patients who undergo liver transplantation (LT) spend some time in the intensive care unit during the postoperative period. For some, this is an expected part of the immediate posttransplant recovery period, whereas for others, the stay is more prolonged because of preexisting conditions, intraoperative events, or postoperative complications. In this review, 4 topics that are particularly relevant to the postoperative intensive care of LT recipients are discussed, with an emphasis on current knowledge specific to this patient group. Infectious complications are the most common causes of early posttransplant morbidity and mortality. The common patterns of infection seen in patients after LT and their management are discussed. Acute kidney injury and renal failure are common in post-LT patients. Kidney injury identification, etiologies, and risk factors and approaches to management are reviewed. The majority of patients will require weaning from mechanical ventilation in the immediate postoperative period; the approach to this is discussed along with the approach for those patients who require a prolonged period of mechanical ventilation. A poorly functioning graft requires prompt identification and appropriate management if the outcomes are to be optimized. The causes of poor graft function are systematically reviewed, and the management of these grafts is discussed.

Critical care of the end-stage liver disease patient awaiting liver transplantation.

Patients with end-stage liver disease awaiting liver transplantation frequently require intensive care admission and management due to either complications of liver failure or to intercurrent illness, particularly infection. Mortality in such patients is high and the development of an illness necessitating intensive care unit management can influence transplant candidacy. Specialized support frequently requires hemodynamic support, mechanical ventilation, and renal support. In this review, areas of management of particular importance to patients with end-stage liver disease in the intensive care unit are discussed. These areas are hepatic encephalopathy, infectious diseases, cardiovascular support, mechanical ventilation, renal support and combined transplantation, and decisions regarding delisting. Current knowledge specific to these patients, when available, is discussed, current practice is described, and areas of uncertainty in the evidence are discussed.