Timing of elective surgery and risk assessment after SARS-CoV-2 infection: an update: A multidisciplinary consensus statement on behalf of the Association of Anaesthetists, Centre for Perioperative Care, Federation of Surgical Specialty Associations, Royal College of Anaesthetists, Royal College of Surgeons of England

The impact of vaccination and new SARS-CoV-2 variants on peri-operative outcomes is unclear. We aimed to update previously published consensus recommendations on timing of elective surgery after SARS-CoV-2 infection to assist policymakers, administrative staff, clinicians and patients. The guidance remains that patients should avoid elective surgery within 7 weeks of infection, unless the benefits of doing so exceed the risk of waiting. We recommend individualised multidisciplinary risk assessment for patients requiring elective surgery within 7 weeks of SARS-CoV-2 infection. This should include baseline mortality risk calculation and assessment of risk modifiers (patient factors; SARS-CoV-2 infection; surgical factors). Asymptomatic SARS-CoV-2 infection with previous variants increased peri-operative mortality risk three-fold throughout the 6 weeks after infection, and assumptions that asymptomatic or mildly symptomatic omicron SARS-CoV-2 infection does not add risk are currently unfounded. Patients with persistent symptoms and those with moderate-to-severe COVID-19 may require a longer delay than 7 weeks. Elective surgery should not take place within 10 days of diagnosis of SARS-CoV-2 infection, predominantly because the patient may be infectious, which is a risk to surgical pathways, staff and other patients. We now emphasise that timing of surgery should include the assessment of baseline and increased risk, optimising vaccination and functional status, and shared decision-making. While these recommendations focus on the omicron variant and current evidence, the principles may also be of relevance to future variants. As further data emerge, these recommendations may be revised

SARS-CoV-2 infection, COVID-19 and timing of elective surgery: A multidisciplinary consensus statement on behalf of the Association of Anaesthetists, the Centre for Peri-operative Care, the Federation of Surgical Specialty Associations, the Royal College of Anaesthetists and the Royal College of Surgeons of England

The scale of the COVID-19 pandemic means that a significant number of patients who have previously been infected with SARS-CoV-2 will require surgery. Given the potential for multisystem involvement, timing of surgery needs to be carefully considered to plan for safe surgery. This consensus statement uses evidence from a systematic review and expert opinion to highlight key principles in the timing of surgery. Shared decision-making regarding timing of surgery after SARS-CoV-2 infection must account for severity of the initial infection; ongoing symptoms of COVID-19; comorbid and functional status; clinical priority and risk of disease progression; and complexity of surgery. For the protection of staff, other patients and the public, planned surgery should not be considered during the period that a patient may be infectious. Precautions should be undertaken to prevent pre- and peri-operative infection, especially in higher risk patients. Elective surgery should not be scheduled within 7 weeks of a diagnosis of SARS-CoV-2 infection unless the risks of deferring surgery outweigh the risk of postoperative morbidity or mortality associated with COVID-19. SARS-CoV-2 causes either transient or asymptomatic disease for most patients, who require no additional precautions beyond a 7-week delay, but those who have persistent symptoms or have been hospitalised require special attention. Patients with persistent symptoms of COVID-19 are at increased risk of postoperative morbidity and mortality even after 7 weeks. The time before surgery should be used for functional assessment, prehabilitation and multidisciplinary optimisation. Vaccination several weeks before surgery will reduce risk to patients and might lessen the risk of nosocomial SARS-CoV-2 infection of other patients and staff. National vaccine committees should consider whether such patients can be prioritised for vaccination. As further data emerge, these recommendations may need to be revised, but the principles presented should be considered to ensure safety of patients, the public and staff

Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction (HARP-2) trial : study protocol for a randomized controlled trial

Acute lung injury (ALI) is a common devastating clinical syndrome characterized by life-threatening respiratory failure requiring mechanical ventilation and multiple organ failure. There are in vitro, animal studies and pre-clinical data suggesting that statins may be beneficial in ALI. The Hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in Acute lung injury to Reduce Pulmonary dysfunction (HARP-2) trial is a multicenter, prospective, randomized, allocation concealed, double-blind, placebo-controlled clinical trial which aims to test the hypothesis that treatment with simvastatin will improve clinical outcomes in patients with ALI

Carbamazepine overdose after exposure to simethicone: a case report

<p>Abstract</p> <p>Introduction</p> <p>Carbamazepine is an anticonvulsant drug and is also used as a treatment for patients with manic-depressive illness, post-herpetic neuralgia or phantom limb pain. The drug itself has many drug interactions. Simethicone is an antifoaming agent and is reported to be an inert material with no known drug interaction with carbamazepine.</p> <p>Case presentation</p> <p>We present a case of a patient who was routinely using carbamazepine 400 mg three times per day and levetiracetam 500 mg twice daily, and experienced carbamazepine overdose after exposure to simethicone. After cessation of simethicone therapy normal drug levels of carbamazepine were obtained again with the standard dose of the drug. The mechanism of interaction is unknown but the risk of overdose should be considered when prescribing simethicone to a patient who is using carbamazepine.</p> <p>Conclusion</p> <p>Simethicone and carbamazepine, when taken together, may be a cause of carbamazepine toxicity. The risk of carbamazepine overdose should be considered when prescribing simethicone to a patient who is using carbamazepine.</p

FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function

Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail. Hence, this study aimed to investigate the role of FKBPL and SIRT-1 in pre-gestational (type 1 diabetes mellitus, T1D) and gestational diabetes mellitus (GDM). Placental protein expression of important angiogenesis proteins, FKBPL, SIRT-1, PlGF and VEGF-R1, was determined from pregnant women with GDM or T1D, and in the first trimester trophoblast cells exposed to high glucose (25 mM) and varying oxygen concentrations [21%, 6.5%, 2.5% (ACH-3Ps)]. Endothelial cell function was assessed in high glucose conditions (30 mM) and following FKBPL overexpression. Placental FKBPL protein expression was downregulated in T1D (FKBPL; p<0.05) whereas PlGF/VEGF-R1 were upregulated (p<0.05); correlations adjusted for gestational age were also significant. In the presence of GDM, only SIRT-1 was significantly downregulated (p<0.05) even when adjusted for gestational age (r=-0.92, p=0.001). Both FKBPL and SIRT-1 protein expression was reduced in ACH-3P cells in high glucose conditions associated with 6.5%/2.5% oxygen concentrations compared to experimental normoxia (21%; p<0.05). FKBPL overexpression in endothelial cells (HUVECs) exacerbated reduction in tubule formation compared to empty vector control, in high glucose conditions (junctions; p<0.01, branches; p<0.05). In conclusion, FKBPL and/or SIRT-1 downregulation in response to diabetic pregnancies may have a key role in the development of vascular dysfunction and associated complications affected by impaired placental angiogenesis

Effect of mechanical preconditioning on the electrical properties of knitted conductive textiles during cyclic loading

This paper presents, for the first time, the electrical response of knitted conductive fabrics to a considerable number of cycles of deformation in view of their use as wearable sensors. The changes in the electrical properties of four knitted conductive textiles, made of 20% stainless steel and 80% polyester fibers, were studied during unidirectional elongation in an Instron machine. Two tests sessions of 250 stretch–recovery cycles were conducted for each sample at two elongation rates (9.6 and 12 mm/s) and at three constant currents (1, 3 and 6 mA). The first session assessed the effects of an extended cyclic mechanical loading (preconditioning) on the electrical properties, especially on the electrical stabilization. The second session, which followed after a 5 minute interval under identical conditions, investigated whether the stabilization and repeatability of the electrical features were maintained after rest. The influence of current and elongation rate on the resistance measurements was also analyzed. In particular, the presence of a semiconducting behavior of the stainless steel fibers was proved by means of different test currents. Lastly, the article shows the time-dependence of the fabrics by means of hysteresis graphs and their non-linear behavior thanks to a time–frequency analysis. All knit patterns exhibited interesting changes in electrical properties as a result of mechanical preconditioning and extended use. For instance, the gauge factor, which indicates the sensitivity of the fabric sensor, varied considerably with the number of cycles, being up to 20 times smaller than that measured using low cycle number protocols

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

ContextPreeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.ObjectiveTo investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.Design and interventionFKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia. Trophoblast and endothelial cell function was assessed following mesenchymal stem cell (MSC) treatment and in the context of FKBPL signaling.Settings and participantsHuman samples prediagnosis (15 and 20 weeks of gestation; n ≥ 57), or postdiagnosis (n = 18 for plasma; n = 4 for placenta) of preeclampsia were used to determine FKBPL and CD44 levels, compared to healthy controls. Trophoblast or endothelial cells were exposed to low/high oxygen, and treated with MSC-conditioned media (MSC-CM) or a FKBPL overexpression plasmid.Main outcome measuresPreeclampsia risk stratification and diagnostic potential of FKBPL and CD44 were investigated. MSC treatment effects and FKBPL-CD44 signaling in trophoblast and endothelial cells were assessed.ResultsThe CD44/FKBPL ratio was reduced in placenta and plasma following clinical diagnosis of preeclampsia. At 20 weeks of gestation, a high plasma CD44/FKBPL ratio was independently associated with the 2.3-fold increased risk of preeclampsia (odds ratio = 2.3, 95% confidence interval [CI] 1.03-5.23, P = 0.04). In combination with high mean arterial blood pressure (>82.5 mmHg), the risk further increased to 3.9-fold (95% CI 1.30-11.84, P = 0.016). Both hypoxia and MSC-based therapy inhibited FKBPL-CD44 signaling, enhancing cell angiogenesis.ConclusionsThe FKBPL-CD44 pathway appears to have a central role in the pathogenesis of preeclampsia, showing promising utilities for early diagnostic and therapeutic purposes

Clinical diagnosis of Lewy body dementia

This is the final version. Available on open access from Cambridge University Press via the DOI in this recordBackground Lewy body dementia consisting of both dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) dementia (PDD) is considerably under-recognised clinically compared to its frequency in autopsy series. Aims This study investigated the clinical diagnostic pathways of patients with Lewy body dementia to assess if difficulties in diagnosis maybe contributing to these differences. Methods We reviewed the medical notes of 74 DLB and 72 non-DLB dementia cases matched for age, gender and cognitive performance, together with 38 PDD cases and 35 PD cases, matched for age and gender, from two geographically distinct UK regions. Results DLB cases took longer to reach a final diagnosis (1.2v0.6 years, p=0.003), underwent more scans (1.7v1.2, p=0.017) and had more alternative prior diagnoses (0.8v0.4, p=0.002), than non-DLB cases. Cases diagnosed in one region had significantly more core features (2.1v1.5, p=0.007) than in the other and were less likely to have dopamine transporter imaging (p<0.001). For PDD cases, more than 1.4 years prior to receiving a dementia diagnosis, 46% had documented impaired activities of daily living due to cognitive impairment, 57% had cognitive impairment in multiple domains, with 38% having both, and 39% already receiving anti-dementia drugs. 3 Conclusions Our results show the pathway to diagnosis of DLB is longer and more complex than nonDLB dementia. There were also marked differences between regions in the thresholds clinicians adopt for diagnosing DLB and also in the use of dopamine transporter imaging. Whilst for PDD, a diagnosis of dementia was delayed well beyond symptom onset and even treatment.National Institute for Health Research (NIHR

Unexpected differential metabolic responses of Campylobacter jejuni to the abundant presence of glutamate and fucose

Introduction: Campylobacter jejuni is the leading cause of foodborne bacterial enteritis in humans, and yet little is known in regard to how genetic diversity and metabolic capabilities among isolates affect their metabolic phenotype and pathogenicity. Objectives: For instance, the C. jejuni 11168 strain can utilize both l-fucose and l-glutamate as a carbon source, which provides the strain with a competitive advantage in some environments and in this study we set out to assess the metabolic response of C. jejuni 11168 to the presence of l-fucose and l-glutamate in the growth medium. Methods: To achieve this, untargeted hydrophilic liquid chromatography coupled to mass spectrometry was used to obtain metabolite profiles of supernatant extracts obtained at three different time points up to 24 h. Results: This study identified both the depletion and the production and subsequent release of a multitude of expected and unexpected metabolites during the growth of C. jejuni 11168 under three different conditions. A large set of standards allowed identification of a number of metabolites. Further mass spectrometry fragmentation analysis allowed the additional annotation of substrate-specific metabolites. The results show that C. jejuni 11168 upon l-fucose addition indeed produces degradation products of the fucose pathway. Furthermore, methionine was faster depleted from the medium, consistent with previously-observed methionine auxotrophy. Conclusions: Moreover, a multitude of not previously annotated metabolites in C. jejuni were found to be increased specifically upon l-fucose addition. These metabolites may well play a role in the pathogenicity of this C. jejuni strain.</p