Improved Durability to SARS-CoV-2 Vaccine Immunity following Coimmunization with Molecular Adjuvant Adenosine Deaminase-1.

Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have demonstrated strong immunogenicity and protection against severe disease, concerns about the duration and breadth of these responses remain. In this study, we show that codelivery of plasmid-encoded adenosine deaminase-1 (pADA) with SARS-CoV-2 spike glycoprotein DNA enhances immune memory and durability in vivo. Coimmunized mice displayed increased spike-specific IgG of higher affinity and neutralizing capacity as compared with plasmid-encoded spike-only-immunized animals. Importantly, pADA significantly improved the longevity of these enhanced responses in vivo. This coincided with durable increases in frequencies of plasmablasts, receptor-binding domain-specific memory B cells, and SARS-CoV-2-specific T follicular helper cells. Increased spike-specific T cell polyfunctionality was also observed. Notably, animals coimmunized with pADA had significantly reduced viral loads compared with their nonadjuvanted counterparts in a SARS-CoV-2 infection model. These data suggest that pADA enhances immune memory and durability and supports further translational studies.

Deep learning-based facial analysis for predicting difficult videolaryngoscopy: a feasibility study.

While videolaryngoscopy has resulted in better overall success rates of tracheal intubation, airway assessment is still an important prerequisite for safe airway management. This study aimed to create an artificial intelligence model to identify difficult videolaryngoscopy using a neural network. Baseline characteristics, medical history, bedside examination and seven facial images were included as predictor variables. ResNet-18 was introduced to recognise images and extract features. Different machine learning algorithms were utilised to develop predictive models. A videolaryngoscopy view of Cormack-Lehane grade of 1 or 2 was classified as 'non-difficult', while grade 3 or 4 was classified as 'difficult'. A total of 5849 patients were included, of whom 5335 had non-difficult and 514 had difficult videolaryngoscopy. The facial model (only including facial images) using the Light Gradient Boosting Machine algorithm showed the highest area under the curve (95%CI) of 0.779 (0.733-0.825) with a sensitivity (95%CI) of 0.757 (0.650-0.845) and specificity (95%CI) of 0.721 (0.626-0.794) in the test set. Compared with bedside examination and multivariate scores (El-Ganzouri and Wilson), the facial model had significantly higher predictive performance (p < 0.001). Artificial intelligence-based facial analysis is a feasible technique for predicting difficulty during videolaryngoscopy, and the model developed using neural networks has higher predictive performance than traditional methods.

The Foundation to Advance Brain Rehabilitation: Organization, History, and Collaborative Database.

OBJECTIVE: To describe the history, organization, goals, and data management procedures of the Foundation to Advance Brain Rehabilitation (FABR). SETTING: Postacute brain injury rehabilitation following acute inpatient care. KEY POINTS: FABR was incorporated in 2019 with a primary mission to advance brain rehabilitation through scientific and strategic analysis of industry-wide data. Contributing FABR member organizations include Bancroft NeuroRehab, Collage Rehabilitation Partners, On With Life, Pate NeuroRehabilitation, and Shepherd Center. These organizations contribute demographic, admission, discharge, and follow-up data on persons served in 5 types of intensive posthospital brain injury rehabilitation programs (neurobehavioral residential, neurorehabilitation residential, home and community neurorehabilitation, day treatment, and outpatient) and 3 types of supported living programs (neurobehavioral residential, residential, and community-based) to a collaborative database managed by Inventive Software Solutions. Inventive Software Solutions provides FABR researchers with a dataset that is de-identified both for participant and organizational identifying information.

Outcomes of Six Specific Types of Post-Hospital Brain Injury Rehabilitation Programs.

OBJECTIVE: Evaluate outcomes of intensive posthospital brain injury rehabilitation programs compared to supported living (SL) programs; explore variations in outcome by diagnostic category (traumatic brain injury, stroke, and other acquired brain injury [ABI]) and specific program type. SETTING: Data were obtained from Residential Neurobehavioral, Residential Neurorehabilitation, Home and Community Neurorehabilitation, Day Treatment, Outpatient Neurorehabilitation, and SL programs serving individuals with ABI. PARTICIPANTS: A total of 2120 individuals with traumatic brain injury, stroke, or other ABI participated in this study. MAIN MEASURES: The main measures are sex, age, time since injury, and Mayo-Portland Adaptability Inventory (4th edition; MPAI-4). DESIGN: Retrospective analyses of demographic variables and MPAI-4 Total, index, and subscale Rasch-derived T-scores on admission and discharge. RESULTS: Gains on MPAI-4  Total T-scores were significantly greater for the intensive rehabilitation (IR) group in comparison to stable functioning in the SL group (F = 236.69, P < .001, partial η2 = .101) while controlling for admission/time 1 scores; similar results were found for MPAI-4 indices and subscales. For the IR cohort, discharge scores differed by diagnostic category after controlling for admission scores for the Total MPAI-4 T-score (F = 22.65, P < .001, partial η2 = .025), as well as all indices and subscales. A statistically significant interaction between program type and diagnostic group on discharge MPAI-4 Total T-scores (F = 2.55, P = .018, partial η2 = .01) after controlling for admission scores indicated that differing outcomes across diagnoses also varied by program type. Varying significant main effects and interactions were apparent for MPAI-4 indices and subscales with generally small effect sizes. CONCLUSIONS: Significant gains on MPAI-4 variables across IR program types compared to no change over a comparable period of time for SL programs supports the effectiveness of posthospital brain injury rehabilitation. This finding in the presence of small effect sizes on outcome variables for program type and for significant interactions between program type and diagnostic category suggests that participants generally were appropriately matched to program type and benefited from interventions provided through specific program types.

Evaluation of Posthospital Brain Injury Rehabilitation Outcomes With Quasi-Experimental Controls.

OBJECTIVE: To further evaluate, using quasi-experimental methodologies, posthospital brain injury rehabilitation outcomes described in an accompanying report of a large observational study (n = 2120). SETTING: Data from Intensive Rehabilitation (IR: Residential Neurobehavioral, Residential Neurorehabilitation, Home and Community Neurorehabilitation, Day Treatment, Outpatient Neurorehabilitation) and Supported Living (SL) programs serving individuals with acquired brain injury (ABI). PARTICIPANTS: Two hundred twenty-eight individuals with traumatic brain injury, stroke, or other ABI in propensity score analysis; 1344 in analysis by extent of recommended treatment completed (TC) rating. MAIN MEASURES: Sex, age, time since injury, Mayo-Portland Adaptability Inventory-4th edition (MPAI-4) Rasch-derived T-scores, and TC rating. DESIGN: Analyses of covariance (1) of discharge MPAI-4 Total, index, and subscale T-scores on propensity score-matched samples of IR and SL participants controlling for admission scores and (2) of MPAI-4 T-scores by TC rating and diagnostic category. RESULTS: Propensity score-matched groups showed superior outcomes for IR participants compared to SL participants on MPAI-4 Total T-score (F = 77.21, P < .001; partial η2 = 0.257) and all MPAI-4 index and subscale T-scores controlling for sex, age, and baseline scores. Participants with traumatic brain injury and stroke who completed the recommended course of rehabilitation had superior outcomes on all MPAI-4 T-scores compared to those who completed less than or much less than the recommended treatment. No additional benefit was apparent for those who completed more than the recommended course. The association between TC rating and outcome was not significant for the other ABI group. CONCLUSIONS: These analyses using quasi-experimental controls provide more scientifically rigorous evidence of the benefit of IR provided through posthospital brain injury rehabilitation programs after acute inpatient care, consistent with the results of numerous observational studies. However, improved internal validity limits external validity and generalization. The absence of a significant association between TC rating and outcomes for the other ABI group most likely reflects the difficulty prescribing rehabilitation for this highly heterogeneous group.

Role and Outcomes of Supported Community Living Programs in Post-Hospital Brain Injury Rehabilitation Programs.

OBJECTIVES: (1) To determine the proportion of participants admitted to supported community living (SCL) programs over the course of 5 years who improve, decline, or maintain functioning and community integration and (2) to examine the associations of time since injury, time in program, and age to their functional trajectory. SETTING: Data from SCL programs serving individuals with acquired brain injury (ABI). PARTICIPANTS: 104 individuals with traumatic brain injury (TBI), stroke, or other ABI. MAIN MEASURES: Sex, age, time since injury, Mayo-Portland Adaptability Inventory (4th edition; MPAI-4). DESIGN: Retrospective analyses of MPAI-4 total and MPAI-4 indices using Linear Mixed Models (LMM) of Rasch-derived T-scores from admission to 5 years into service delivery. RESULTS: MPAI-4 total, index, and subscale scores for yearly intervals of SCL services from admission to 5 years showed a high degree of stability in function (defined using the standard error of measurement (SEM) for the MPAI-4, defined as change ≥3 T-score points) with all intervals showing at least 89% of patients with improved scores or no change. The rate of change over time did not significantly vary by time since injury, time in the program, or age. CONCLUSIONS: The expectations for services in the SCL portion of the care continuum for ABI are unique. Unlike intensive rehabilitation programs which focus on improvement often earlier in the course of recovery, the goal of SCL services is sustained functioning over the long term. Analyses reported here indicate this can be achieved for at least 5 years, potentially mitigating the increased risk for rehospitalization and increased care needs in the ABI population. This study highlights a key finding of MPAI-4 stability within these understudied brain injury service lines. Additional exploration of comorbidities and more nuanced delineation of diagnostic information could further clarify factors influencing outcome stability over time.

Distinguishing Characteristics of Admissions to Various Types of Posthospital Brain Injury Rehabilitation Programs.

OBJECTIVE: Describe and compare the demographic characteristics and disability profiles of individuals admitted to 6 types of posthospital brain injury rehabilitation (PHBIR) programs. SETTING: Data from Residential Neurobehavioral, Residential Neurorehabilitation, Home and Community Neurorehabilitation, Day Treatment, Outpatient Neurorehabilitation, and Supported Living programs serving individuals with acquired brain injury (ABI). PARTICIPANTS: Two thousand twenty-eight individuals with traumatic brain injury (TBI), stroke, or other ABI. MAIN MEASURES: Sex, age, time since injury, and Mayo-Portland Adaptability Inventory, 4th edition (MPAI-4). DESIGN: Retrospective analyses of demographic variables and MPAI-4 Total, Index, and subscale Rasch-derived T-scores on admission comparing diagnostic categories and program types within diagnostic categories. RESULTS: Participants with TBI were predominantly male, and those with stroke were generally older. Admissions to more intensive and supervised programs (residential neurobehavioral and residential neurorehabilitation) generally showed greater disability than admissions to home and community programs who were more disabled than participants in day treatment and outpatient programs. Residential neurobehavioral and supported living program participants generally were male and had TBI. Home and community admissions tended to be more delayed than residential neurorehabilitation admissions. The majority of those with other ABI were admitted to outpatient rather than more intensive programs. Additional analyses demonstrated significant differences in MPAI-4 profiles among the various program types. CONCLUSIONS: Admissions with TBI, stroke, and other ABI to PHBIR differ in demographic factors and disability profiles. When examined within each diagnostic category, demographic features and disability profiles also distinguish among admissions to the various program types. Results provide insights about decision-making in referral patterns to various types of PHBIR programs, although other factors not available for analysis (eg, participant/family preference, program, and funding availability) likely also contribute to admission patterns.

Alternatives to remifentanil for the analgesic component of total intravenous anaesthesia: a narrative review.

Propfol-remifentanil-based total intravenous anaesthesia has dominated recent clinical practice due to its favourable pharmacokinetic profile. Interruption in remifentanil supply has presented an opportunity to diversify or even avoid the use of opioids and consider adjuncts to propofol-based total intravenous anaesthesia. Propofol, while a potent hypnotic, is not an effective analgesic. The administration of opioids, along with other adjuncts such as α-2 adrenoceptor agonists, magnesium, lidocaine, ketamine and nitrous oxide provide surgical anaesthesia and avoids large doses of propofol being required. We provide an overview of both target-control and manual infusion regimes for the alternative opioids: alfentanil, sufentanil and fentanyl. The optimal combination of hypnotic-opioid dose, titration sequence and anticipated additional postoperative analgesia required depend on the chosen combination. In addition, we include a brief discussion on the role of non-opioid adjuncts in total intravenous anaesthesia, suggested doses and expected reduction in propofol dose.

Aerosol generation with the use of positive pressure ventilation via supraglottic airway devices: an observational study.

The amount of aerosol generation associated with the use of positive pressure ventilation via a supraglottic airway device has not been quantified. We conducted a two-group, two-centre, prospective cohort study in which we recruited 21 low-risk adult patients scheduled for elective surgery under general anaesthesia with second-generation supraglottic airway devices. An optical particle sizer and an isokinetic sampling probe were used to record particle concentrations per second at different size distributions (0.3-10 µm) during use as well as baseline levels during two common activities (conversation and coughing). There was a median (IQR [range]) peak increase of 2.8 (1.5-4.5 [1-28.1]) and 4.1 (2.0-7.1 [1-18.2]) times background concentrations during SAD insertion and removal. Most of the particles generated during supraglottic airway insertion (85.0%) and removal (85.3%) were < 3 µm diameter. Median (IQR [range]) aerosol concentration generated by insertion (1.1 (0.6-5.1 [0.2-22.3]) particles.cm-3 ) and removal (2.1 (0.5-3.0 [0.1-18.9]) particles.cm-3 ) of SADs were significantly lower than those produced during continuous talking (44.5 (28.3-70.5 [2.0-134.5]) particles.cm-3 ) and coughing (141.0 (98.3-202.8 [4.0-296.5]) particles.cm-3 ) (p < 0.001). The aerosol levels produced were similar with the two devices. The proportion of easily inhaled and small particles (<1 µm) produced during insertion (57.5%) and removal (57.5%) was much lower than during talking (99.1%) and coughing (99.6%). These results suggest that the use of supraglottic airway devices in low-risk patients, even with positive pressure ventilation, generates fewer aerosols than speaking and coughing in awake patients.

Postoperative pulmonary complications in older patients undergoing elective surgery with a supraglottic airway device or tracheal intubation.

The two most commonly used airway management techniques during general anaesthesia are supraglottic airway devices and tracheal tubes. In older patients undergoing elective non-cardiothoracic surgery under general anaesthesia with positive pressure ventilation, we hypothesised that a composite measure of in-hospital postoperative pulmonary complications would be less frequent when a supraglottic airway device was used compared with a tracheal tube. We studied patients aged ≥ 70 years in 17 clinical centres. Patients were allocated randomly to airway management with a supraglottic airway device or a tracheal tube. Between August 2016 and April 2020, 2900 patients were studied, of whom 2751 were included in the primary analysis (1387 with supraglottic airway device and 1364 with a tracheal tube). Pre-operatively, 2431 (88.4%) patients were estimated to have a postoperative pulmonary complication risk index of 1-2. Postoperative pulmonary complications, mostly coughing, occurred in 270 of 1387 patients (19.5%) allocated to a supraglottic airway device and 342 of 1364 patients (25.1%) assigned to a tracheal tube (absolute difference -5.6% (95%CI -8.7 to -2.5), risk ratio 0.78 (95%CI 0.67-0.89); p < 0.001). Among otherwise healthy older patients undergoing elective surgery under general anaesthesia with intra-operative positive pressure ventilation of their lungs, there were fewer postoperative pulmonary complications when the airway was managed with a supraglottic airway device compared with a tracheal tube.

Liver function from Y to Z: The guidance of William Jakoby.

In the 1960s, my lab was interested in understanding how bilirubin and other organic anions are transferred from the plasma through the liver cell and into the bile. We performed gel filtration of liver supernatants and identified two protein fractions, designated Y and Z, which bound organic anions including bilirubin, and thus we proposed that they were involved in hepatic uptake of organic anions from plasma. Subsequently, the Y and Z proteins responsible for this binding activity were purified, cloned, and sequenced. With Bill Jakoby, we identified Y protein as a member of the glutathione S-transferase (GST) protein family. In separate studies, Z was found to be a member of the fatty acid-binding protein (FABP) family. These proteins have since been shown to have additional surprising roles, but understanding of their full role in physiology and disease has not yet been achieved. In the 1960s, bilirubin metabolism was a "hot" topic. Along with other groups, my lab was studying various forms of inheritable jaundice in an effort to dissect the mechanism of bilirubin's transfer from plasma into the hepatocyte and its role in intracellular metabolism and biliary secretion. These processes were eventually identified and found to be related to the basic mechanisms whereby the liver handles many anionic drugs, metabolites, and hormones. Because the mechanism of hepatic uptake of bilirubin was unknown, A.J. Levi, Z. Gatmaitan, and I took advantage of advances in gel permeation chromatography to study this process. In 1969, we described two hepatic cytoplasmic protein fractions, designated Y and Z, that bound bilirubin and various organic anionic dyes in vivo and in vitro and, based on tissue distribution, abundance, and effects of genetic and pharmacologic models, were proposed to participate in organic anion uptake (Levi et al., 1969) [1]. In the decades since then, the Y and Z proteins have been identified as members of large protein families that were cloned and sequenced. Several surprising functions emerged, whereas others are proposed based on binding properties. Many challenges remain in understanding the full role of these proteins in physiology and disease.

Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review.

Various techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long- and short-acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non-steroidal anti-inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non-steroidal anti-inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose-dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.

Peri-operative neurological monitoring with electroencephalography and cerebral oximetry: a narrative review.

Surgery and anaesthesia subject the brain to considerable stress in the peri-operative period. This may be caused by potentially neurotoxic anaesthetic drugs, impaired cerebral perfusion and reperfusion injury related to surgery or thromboembolic events. Patient monitoring using electroencephalogram and cerebral oximetry can assist in optimising depth of anaesthesia and assessment of cerebral metabolic activity. However, research findings have been contradictory as to whether these monitors can help ameliorate peri-operative neurocognitive complications. In this narrative review, we will discuss recent evidence in the use of electroencephalography and cerebral oximetry and the underlying scientific principles. It is important to appreciate the raw electroencephalographic changes under anaesthesia and those associated with ageing, in order to interpret depth of anaesthesia indices correctly. Cerebral oximetry is useful not only for the detection of cerebral desaturation but also to identify those patients who are particularly vulnerable to injury, for better risk stratification. An algorithm-based approach may be most effective in managing the episodes of cerebral desaturation.

Peri-operative management of patients with Parkinson's disease.

Patients with Parkinson's disease are at higher risk of peri-operative medical and surgical complications. Multidisciplinary management, early recognition of potential complications, specialised care of medications and intra-operative protection of the vulnerable brain are all important aspects of the peri-operative management of patients with Parkinson's disease. Advances in continuous dopaminergic treatment, development of a peri-operative Parkinson's disease pathway and application of telemedicine are starting to play a role in improving peri-operative care. Management of patients with advanced Parkinson's disease is also evolving, with potential for incorporation of integrated care and changes in the anaesthetic management for deep brain stimulation surgery. There are new methods for localisation of target nuclei and increasing insight on the effects of anaesthetic drugs on microelectrode recordings and clinical outcomes. Parkinson's disease is a progressive disease, but management is improving with better peri-operative care for patients.

Altered Env conformational dynamics as a mechanism of resistance to peptide-triazole HIV-1 inactivators.

BACKGROUND: We previously developed drug-like peptide triazoles (PTs) that target HIV-1 Envelope (Env) gp120, potently inhibit viral entry, and irreversibly inactivate virions. Here, we investigated potential mechanisms of viral escape from this promising class of HIV-1 entry inhibitors. RESULTS: HIV-1 resistance to cyclic (AAR029b) and linear (KR13) PTs was obtained by dose escalation in viral passaging experiments. High-level resistance for both inhibitors developed slowly (relative to escape from gp41-targeted C-peptide inhibitor C37) by acquiring mutations in gp120 both within (Val255) and distant to (Ser143) the putative PT binding site. The similarity in the resistance profiles for AAR029b and KR13 suggests that the shared IXW pharmacophore provided the primary pressure for HIV-1 escape. In single-round infectivity studies employing recombinant virus, V255I/S143N double escape mutants reduced PT antiviral potency by 150- to 3900-fold. Curiously, the combined mutations had a much smaller impact on PT binding affinity for monomeric gp120 (four to ninefold). This binding disruption was entirely due to the V255I mutation, which generated few steric clashes with PT in molecular docking. However, this minor effect on PT affinity belied large, offsetting changes to association enthalpy and entropy. The escape mutations had negligible effect on CD4 binding and utilization during entry, but significantly altered both binding thermodynamics and inhibitory potency of the conformationally-specific, anti-CD4i antibody 17b. Moreover, the escape mutations substantially decreased gp120 shedding induced by either soluble CD4 or AAR029b. CONCLUSIONS: Together, the data suggest that the escape mutations significantly modified the energetic landscape of Env's prefusogenic state, altering conformational dynamics to hinder PT-induced irreversible inactivation of Env. This work therein reveals a unique mode of virus escape for HIV-1, namely, resistance by altering the intrinsic conformational dynamics of the Env trimer.

Effect of Stent Strut Interval on Neointima Formation After Venous Stenting in an Ovine Model.

OBJECTIVE: The impact of stent design on venous patency is not well studied. The purpose of this study was to investigate the effect of stent material burden on endothelial coverage of stented venous segments, which may contribute to vessel healing and patency. METHODS: Segmented self expanding bare nitinol stents (18 × 50 mm) comprising 5 mm long attached metallic rings separated by 2, 5, or 8 mm gaps were implanted in the inferior vena cava (IVC) of 10 sheep. These stents were designed and manufactured for the purposes of this study. At six, 12, and 24 weeks after implantation the animals were euthanised and the stented vessels harvested for histomorphometric analysis. Three sections from the metallic part as well as the gaps between the struts were reviewed for quantification of endothelialisation after six, 12, and 24 weeks. The intimal thickness over and between the stent struts was measured. The endothelialisation score (graded from 1 for complete luminal endothelialisation to 5 for absence of endothelial cells) was determined. RESULTS: All stents were successfully deployed and all 10 sheep survived until the time of harvesting. Macroscopic inspection after 24 weeks showed only partial endothelialisation over stents with 2 mm and 5 mm skipped segments, whereas the stents with 8 mm skipped segments were totally incorporated into the vein wall. After 24 weeks, the mean (SD) neointimal thicknesses over stent struts with 2 mm, 5 mm, and 8 mm skipped segments were 254.0 (51.6), 182.2 (98.1), and 194.6 (101.1) µm, respectively. Comparison of endothelialisation scores of stents over time showed statistically significantly better endothelialisation over stents with 8 mm gaps after 12 and 24 weeks. CONCLUSION: Stent designs providing structural support to veins with larger gaps between the scaffold material appear to lead to faster and more complete endothelialisation as well as a thinner intimal layer.

Iliocaval Skip Stent Reconstruction Technique for Chronic Bilateral Iliocaval Venous Occlusion.

PURPOSE: To report safety and efficacy of a skip stent technique using nitinol stents in patients with chronic bilateral iliocaval venous occlusions. MATERIALS AND METHODS: A retrospective analysis of 48 consecutive patients (32 men; mean age, 40.7 years; age range, 18-68 years) with chronic bilateral iliocaval obstructions treated using a nonoverlapping stent technique was conducted at a single center. None of the patients had May-Thurner syndrome. Iliocaval confluence was treated by deploying a nitinol stent in inferior vena cava (IVC) and a nitinol stent in each common iliac vein close to the caval stent. Patency of stents was assessed by duplex US at 2 weeks, 3 months, and 6 months and yearly thereafter. RESULTS: Recanalization and stent reconstruction was technically successful in 47 (98%) patients. The sinus-XL venous stent was used to treat IVC (95 [100%]). Common iliac and external iliac veins were treated with sinus-Venous and VENOVO stents (80 [83%] and 16 [17%] limbs, respectively). External iliac and common femoral veins were treated with sinus-Venous and VENOVO stents (83 [92%] and 7 [18%] limbs, respectively). Early thrombosis (< 30 days) of the iliac vein with stent occurred in 2 limbs. Cumulative primary, assisted primary, and secondary patency rates at 30 months were 74%, 83%, and 97%. CONCLUSIONS: Findings of this study suggest that leaving a skipped lesion at the level of iliocaval confluence may not adversely affect stent patency. Patency rates were comparable with other reported techniques of stent reconstruction at the level of iliocaval confluence.

Influence of propofol-based total intravenous anaesthesia on peri-operative outcome measures: a narrative review.

Propofol-based total intravenous anaesthesia is well known for its smooth, clear-headed recovery and anti-emetic properties, but there are also many lesser known beneficial properties that can potentially influence surgical outcome. We will discuss the anti-oxidant, anti-inflammatory and immunomodulatory effects of propofol and their roles in pain, organ protection and immunity. We will also discuss the use of propofol in cancer surgery, neurosurgery and older patients.

An international multidisciplinary consensus statement on fasting before procedural sedation in adults and children.

The multidisciplinary International Committee for the Advancement of Procedural Sedation presents the first fasting and aspiration prevention recommendations specific to procedural sedation, based on an extensive review of the literature. These were developed using Delphi methodology and assessment of the robustness of the available evidence. The literature evidence is clear that fasting, as currently practiced, often substantially exceeds recommended time thresholds and has known adverse consequences, for example, irritability, dehydration and hypoglycaemia. Fasting does not guarantee an empty stomach, and there is no observed association between aspiration and compliance with common fasting guidelines. The probability of clinically important aspiration during procedural sedation is negligible. In the post-1984 literature there are no published reports of aspiration-associated mortality in children, no reports of death in healthy adults (ASA physical status 1 or 2) and just nine reported deaths in adults of ASA physical status 3 or above. Current concerns about aspiration are out of proportion to the actual risk. Given the lower observed frequency of aspiration and mortality than during general anaesthesia, and the theoretical basis for assuming a lesser risk, fasting strategies in procedural sedation can reasonably be less restrictive. We present a consensus-derived algorithm in which each patient is first risk-stratified during their pre-sedation assessment, using evidence-based factors relating to patient characteristics, comorbidities, the nature of the procedure and the nature of the anticipated sedation technique. Graded fasting precautions for liquids and solids are then recommended for elective procedures based upon this categorisation of negligible, mild or moderate aspiration risk. This consensus statement can serve as a resource to practitioners and policymakers who perform and oversee procedural sedation in patients of all ages, worldwide.

Labour analgesia: update and literature review.

Pain relief is an important component of modern obstetric care and can be produced by neuraxial, systemic, or inhalational analgesia or various physical techniques. We review the most recent evidence on the efficacy and safety of these techniques. Over the past decade, the availability of safer local anaesthetics, ultra-short acting opioids, combined spinal-epidural needles, patient-controlled analgesic devices, and ultrasound have revolutionised obstetric regional analgesia. Recent meta-analyses have supported epidural analgesia as the most efficacious technique, as it leads to higher maternal satisfaction and good maternal and fetal safety profiles. We examine the controversies and myths concerning the initiation, maintenance, and discontinuation of epidural analgesia. Recent evidence will also be reviewed to address concerns about the effects of epidural analgesia on the rates of instrumental and operative delivery, lower back pain, and breastfeeding. New developments in labour analgesia are also discussed.