Prediction of hematocrit decline and the impact of peri-operative fluid use in lumbar spinal fusion surgery.

PURPOSE: Peri-operative blood loss unaccounted for and post-operative hematocrit decline could have a significant impact on the outcome of elective spinal surgery patients. The study assesses the accuracy of predictive models of hematocrit decline and blood loss in spinal surgery and determines the impact of peri-operative fluid administration on hematocrit levels of patients undergoing first-time single level lumbar fusion surgery for degenerative spine disease and the trend thereof in the first 24 h post-operatively. METHODS: Clinical and biochemical parameters were prospectively collected in patients undergoing single level lumbar spinal surgery. Predictive models were applied to assess their accuracy in intra-operative blood loss and post-operative hematocrit decline. RESULTS: High correlation (0.98 Pearson correlation coefficient) occurred between calculated (predicted) and recorded hematocrit from hours 2 to 6 post-operatively. Predictive accuracy declined thereafter yet remained moderate. Patients received an average intra-operative fluid volume of 545.45 ml per hour (47% of estimated total blood volume). A significant hematocrit decline occurred post-induction (43.47-39.78%, p < 0.001) with total fluid volume received being the significant contributing variable (p < 0.001). Hypertensive patients were the only subgroup to drop below the safe hematocrit threshold of 30%. CONCLUSION: Iatrogenic hemodilution can accurately be predicted for the first six hours post-operatively, with high risk patients identifiable. Fluid therapy should be goal directed rather than generic, and good communication between the surgeon and anesthesiologist remains the cornerstone to manage physiological changes secondary to blood loss. Although helpful, predictive formulas are not universally applicable to all phenotypes.

Cardiovascular events among recipients of hematopoietic stem cell transplantation-A systematic review and meta-analysis.

Cardiovascular diseases are an emerging cause of mortality and morbidity in survivors of hematopoietic stem cell transplantation (HSCT); however, the incidence of cardiovascular events (CVEs) in this population is not well described. This systematic review summarizes the evidence on the incidence of CVEs in HSCT recipients. Medline and Embase were searched from inception to December 2020. Inclusion criteria were cohort studies and phase 3 randomized controlled trials that reported CVEs among adults who underwent HSCT for hematological malignancies. After reviewing 8386 citations, 57 studies were included. The incidence of CVEs at 100 days was 0.19 (95% CI: 0.17-0.21) per 100 person-days after autologous HSCT and 0.06 (95% CI: 0.05-0.07) per 100 person-days after allogeneic HSCT. This higher incidence after autologous HSCT was driven by reports of arrhythmia from one population-based study in patients with multiple myeloma. The incidence of long-term CVEs was 3.98 (95% CI; 3.44-4.63) per 1000 person-years in survivors of autologous HSCT and 3.06 (95% CI; 2.69-3.48) per 1000 person-years in survivors of allogeneic HSCT. CVEs remain an important but under-reported cause of morbidity and mortality in recipients of HSCT. Future studies are required to better understand the incidence and risk factors for CVEs in HSCT recipients.

Hemostats in Spine Surgery: Literature Review and Expert Panel Recommendations.

Bleeding in spine surgery is a common occurrence but when bleeding is uncontrolled the consequences can be severe due to the potential for spinal cord compression and damage to the central nervous system. There are many factors that influence bleeding during spine surgery including patient factors and those related to the type of surgery and the surgical approach to bleeding. There are a range of methods that can be employed to both reduce the risk of bleeding and achieve hemostasis, one of which is the adjunct use of hemostatic agents. Hemostatic agents are available in a variety of forms and materials and with considerable variation in cost, but specific evidence to support their use in spine surgery is sparse. A literature review was conducted to identify the pre-, peri-, and postsurgical considerations around bleeding in spine surgery. The review generated a set of recommendations that were discussed and ratified by a wider expert group of spine surgeons. The results are intended to provide a practical guide to the selection of hemostats for specific bleeding situations that may be encountered in spine surgery.

An international multidisciplinary peer-driven consensus on the optimal use of hemostatic powders in surgical practice.

Bleeding is a consequence of insufficient hemostasis and excessive bleeding at a surgical site is associated with an increased risk of post-operative infection, transfusion and re-operation, in addition to increased hospital length of stay and costs. Surgeons employ a range of methods to achieve hemostasis, including topical hemostatic agents of differing composition and properties. Hemostatic powders are a sub-group of topical hemostats, which can be used in helping as adjuncts to manage troublesome bleeding in a variety of situations. As this technology is relatively new and potentially not well known by the broad surgical community, no specific guidelines or recommendations for the optimal use of hemostatic powders in surgery currently exist. A steering group throughout Europe of multidisciplinary surgeons, expert in hemostasis and hemostatics, identified from literature and from personal experience, five key topics. When to use hemostatic powder, the evidence for use, benefits of use, safety remarks and considerations in various surgical specialties. Thirty-seven statements were subsequently drawn from these five key topics. An online survey was sent to 128 high-volume surgeons working in breast surgery, gynaecological and obstetric surgery, general and emergency surgery, thoracic surgery and urological surgery in Europe to assess agreement (consensus) with these statements. Consensus was defined as high if ≥ 75% and very high if ≥ 90% of respondents agreed with a statement. A total of 79 responses were received and consensus among the surgical experts was very high in 27 (73%) statements, high in 8 (22%) statements and was not achieved in 2 (5%) statements. Based on the consensus scores, the steering group produced 16 key recommendations which they considered could improve patient outcomes by reducing post-operative bleeding and its associated complications using hemostatic powder.

Guideline on the peri-operative management of patients with sickle cell disease: Guideline from the Association of Anaesthetists.

Sickle cell disease is a multisystem disease characterised by chronic haemolytic anaemia, painful vaso-occlusive crises and acute and chronic end-organ damage. It is one of the most common serious inherited single gene conditions worldwide and has a major impact on the health of affected individuals. Peri-operative complications are higher in patients with sickle cell disease compared with the general population and may be sickle or non-sickle-related. Complications may be reduced by meticulous peri-operative care and transfusion, but unnecessary transfusion should be avoided, particularly to reduce the risk of allo-immunisation. Planned surgery and anaesthesia for patients with sickle cell disease should ideally be undertaken in centres with experience in caring for these patients. In an emergency, advice should be sought from specialists with experience in sickle cell disease through the haemoglobinopathy network arrangements. Emerging data suggest that patients with sickle cell disease are at increased risk of COVID-19 infection but may have a relatively mild clinical course. Outcomes are determined by pre-existing comorbidities, as for the general population.

Multiple deprivation and other risk factors for maternal obesity in Portsmouth, UK.

BACKGROUND: Maternal obesity is known to be associated with a range of adverse outcomes, both for the mothers and their children. It may be more prevalent in areas with higher deprivation as measured by the Index of Multiple Deprivation (IMD), but this has not been demonstrated consistently. This study focused primarily on the relationship between maternal obesity and deprivation in a setting where areas of significant deprivation are surrounded by the overall affluent South East England. METHODS: The study used the records of 3830 women who delivered under the care of a Portsmouth hospital from 1 April 2013 to 31 March 2014. Logistic regression was used to analyse the association between national IMD quintiles and maternal obesity, accounting for the potential confounders of age, ethnic origin, smoking status and parity. RESULTS: Following adjustment, women in the most deprived IMD quintile were 1.60 (95% CI: 1.13, 2.26) times more likely to be obese compared to those in the least deprived quintile. Maternal obesity was also found to be associated with ethnicity and parity, but not with age or smoking status. CONCLUSIONS: Maternal obesity increased with increasing deprivation. IMD may be a useful group-level indicator when planning interventions aimed at tackling maternal obesity.

A mixed-methods evaluation of the Association of Anaesthetists of Great Britain and Ireland Uganda Fellowship Scheme.

The Association of Anaesthetists of Great Britain and Ireland and the then Uganda Society of Anaesthesia established the Uganda Fellowship Scheme in 2006, to provide scholarships to encourage doctors to train in anaesthesia in Uganda. We conducted an evaluation of this programme using online questionnaires and face-to-face semi-structured interviews with trainees who received scholarships, as well as with senior surgeons and anaesthetists. Focus group discussions were held to assess changes in attitudes towards anaesthesia over the last 10 years. Interviews were recorded, transcribed and analysed using the constant comparative method. A total of 54 Ugandan doctors have received anaesthesia scholarships since 2006 (median funding per trainee (IQR [range]) £5520 (£5520-£6750 [£765-£9000]). There has been a four-fold increase in the number of physician anaesthetists in Uganda during this time. All those who received funding remain in the region. The speciality of anaesthesia is undergoing a dramatic transformation led by this group of motivated young anaesthetists. There is increased access to intensive care, and this has allowed surgical specialities to develop. There is greater understanding and visibility of anaesthesia, and the quality of education in anaesthesia throughout the country has improved. The Uganda Fellowship Scheme provided a relatively small financial incentive to encourage doctors to train as anaesthetists. Evaluation of the project shows a wide-ranging impact that extends beyond the initial goal of simply improving human resource capacity. Financial incentives combined with strong 'north-south' links between professional organisations can play an important role in tackling the shortage of anaesthesia providers in a low-income country and in improving access to safe surgery and anaesthesia.

Multidrug-resistant tuberculosis treatment programmes insufficiently consider comorbid mental disorders.

The successful treatment of multidrug-resistant tuberculosis (MDR-TB) is a global health priority and a key pillar of the World Health Organization's (WHO's) End TB strategy. There has been significant global investment in diagnostic capabilities in recent years. However, we argue that the mental distress of those with MDR-TB and their families continues to be overlooked by TB programmes. Priorities in the End TB Strategy of 'patient-centred care' and 'patient support' are still to be delivered in practice in many low-income settings, and in particular consideration of mental distress. Our experience of undertaking MDR-TB operational research in China, Pakistan, Bangladesh, Nepal and Swaziland has given us detailed insight into the challenges facing patients, their families, health professionals and wider health systems. We are increasingly concerned that psychosocial support, and particularly support focused on mental health, is being insufficiently addressed in national MDR-TB programmes. We suggest that the presence of comorbid mental disorders reduces treatment adherence. We recommend the trialling within TB programmes of brief screening tools for common mental disorders and the incorporation of principles from the WHO Mental Health Gap Action Programme programme into TB programme treatment guidance. Our work in Nepal also suggests that brief psychological counselling delivered by non-specialist counsellors may be feasible.

Implementation of the WHO Surgical Safety Checklist and surgical swab and instrument counts at a regional referral hospital in Uganda - a quality improvement project.

The World Health Organization (WHO) Surgical Safety Checklist is a cost-effective tool that has been shown to improve patient safety. We explored the applicability and effectiveness of quality improvement methodology to implement the WHO checklist and surgical counts at Mbarara Regional Referral Hospital in Uganda between October 2012 and September 2013. Compliance rates were evaluated prospectively and monthly structured feedback sessions were held. Checklist and surgical count compliance rates increased from a baseline median (IQR [range]) of 29.5% (0-63.5 [0-67.0]) to 85.0% (82.8-87.5 [79.0-93.0]) and from 25.5% (0-52.5 [0-60.0]) to 83.0% (80.8-85.5 [69.0-89.0]), respectively. The mean all-or-none completion rate of the checklist was 69.3% (SD 7.7, 95% CI [64.8-73.9]). Use of the checklist was associated with performance of surgical counts (p value < 0.001; r(2) = 0.91). Pareto analysis showed that understaffing, malfunctioning and lack of equipment were the main challenges. A carefully designed quality improvement project, including stepwise incremental change and standardisation of practice, can be an effective way of improving clinical practice in low-income settings.

The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer.

BACKGROUND: The management of NSCLC has been transformed by stratified medicine. The National Lung Matrix Trial (NLMT) is a UK-wide study exploring the activity of rationally selected biomarker/targeted therapy combinations. PATIENTS AND METHODS: The Cancer Research UK (CRUK) Stratified Medicine Programme 2 is undertaking the large volume national molecular pre-screening which integrates with the NLMT. At study initiation, there are eight drugs being used to target 18 molecular cohorts. The aim is to determine whether there is sufficient signal of activity in any drug-biomarker combination to warrant further investigation. A Bayesian adaptive design that gives a more realistic approach to decision making and flexibility to make conclusions without fixing the sample size was chosen. The screening platform is an adaptable 28-gene Nextera next-generation sequencing platform designed by Illumina, covering the range of molecular abnormalities being targeted. The adaptive design allows new biomarker-drug combination cohorts to be incorporated by substantial amendment. The pre-clinical justification for each biomarker-drug combination has been rigorously assessed creating molecular exclusion rules and a trumping strategy in patients harbouring concomitant actionable genetic abnormalities. Discrete routes of pathway activation or inactivation determined by cancer genome aberrations are treated as separate cohorts. Key translational analyses include the deep genomic analysis of pre- and post-treatment biopsies, the establishment of patient-derived xenograft models and longitudinal ctDNA collection, in order to define predictive biomarkers, mechanisms of resistance and early markers of response and relapse. CONCLUSION: The SMP2 platform will provide large scale genetic screening to inform entry into the NLMT, a trial explicitly aimed at discovering novel actionable cohorts in NSCLC. CLINICAL TRIAL ISRCTN: 38344105.

Incidence of hypoxia and related events detected by pulse oximeters provided by the Lifebox Foundation in the maternity unit at Sylvanus Olympio University Teaching Hospital, Togo.

In recent decades anesthesia safety has not been improved in low-income countries. This prospective audit describes the incidence of hypoxia and related events detected among a cohort of patients undergoing surgery in the maternity unit at Sylvanus Olympio University Teaching Hospital, Togo, West Africa, by using pulse oximeters donated by the Lifebox Foundation. The Lifebox oximeter enables early detection of hypoxia for patients undergoing surgery before irreversible damage occurs. Pulse oximetry is cost-effective intervention and should be more accessible in all operating rooms of this type.

Murine, but not human, ephrin-B2 can be efficiently cleaved by the serine protease kallikrein-4: implications for xenograft models of human prostate cancer.

BACKGROUND: Ephrin-B2 is the sole physiologically-relevant ligand of the receptor tyrosine kinase EphB4, which is over-expressed in many epithelial cancers, including 66% of prostate cancers, and contributes to cancer cell survival, invasion and migration. Crucially, however, the cancer-promoting EphB4 signalling pathways are independent of interaction with its ligand ephrin-B2, as activation of ligand-dependent signalling causes tumour suppression. Ephrin-B2, however, is often found on the surface of endothelial cells of the tumour vasculature, where it can regulate angiogenesis to support tumour growth. Proteolytic cleavage of endothelial cell ephrin-B2 has previously been suggested as one mechanism whereby the interaction between tumour cell-expressed EphB4 and endothelial cell ephrin-B2 is regulated to support both cancer promotion and angiogenesis. METHODS: An in silico approach was used to search accessible surfaces of 3D protein models for cleavage sites for the key prostate cancer serine protease, KLK4, and this identified murine ephrin-B2 as a potential KLK4 substrate. Mouse ephrin-B2 was then confirmed as a KLK4 substrate by in vitro incubation of recombinant mouse ephrin-B2 with active recombinant human KLK4. Cleavage products were visualised by SDS-PAGE, silver staining and Western blot and confirmed by N-terminal sequencing. RESULTS: At low molar ratios, KLK4 cleaved murine ephrin-B2 but other prostate-specific KLK family members (KLK2 and KLK3/PSA) were less efficient, suggesting cleavage was KLK4-selective. The primary KLK4 cleavage site in murine ephrin-B2 was verified and shown to correspond to one of the in silico predicted sites between extracellular domain residues arginine 178 and asparagine 179. Surprisingly, the highly homologous human ephrin-B2 was poorly cleaved by KLK4 at these low molar ratios, likely due to the 3 amino acid differences at this primary cleavage site. CONCLUSION: These data suggest that in in vivo mouse xenograft models, endogenous mouse ephrin-B2, but not human tumour ephrin-B2, may be a downstream target of cancer cell secreted human KLK4. This is a critical consideration when interpreting data from murine explants of human EphB4+/KLK4+ cancer cells, such as prostate cancer cells, where differential effects may be seen in mouse models as opposed to human clinical situations.

Inhibiting Eph kinase activity may not be "Eph"ective for cancer treatment.

Several Eph receptor tyrosine kinases (RTKs) are commonly over-expressed in epithelial and mesenchymal cancers and are recognized as promising therapeutic targets. Although normal interaction between Eph receptors and their ephrin ligands stimulates kinase activity and is generally tumor suppressive, significant Eph over-expression allows activation of ligand- and/or kinase-independent signaling pathways that promote oncogenesis. Single-agent kinase inhibitors are widely used to target RTK-driven tumors but acquired and de novo resistance to such agents is a major limitation to effective clinical use. Accumulating evidence suggests that Ephs can be inhibited by "leaky" or low-specificity kinase inhibitors targeted at other RTKs. Such off-target effects may therefore inadvertently promote ligand- and/or kinase-independent oncogenic Eph signaling, thereby providing a new mechanism by which resistance to the RTK inhibitors can emerge. We propose that combining specific, non-leaky kinase inhibitors with tumor-suppressive stimulators of Eph signaling may provide more effective treatment options for overcoming treatment-induced resistance and clinical failure.

Surgical safety checklists: do they improve outcomes?

The concept of using a checklist in surgical and anaesthetic practice was energized by publication of the WHO Surgical Safety Checklist in 2008. It was believed that by routinely checking common safety issues, and by better team communication and dynamics, perioperative morbidity and mortality could be improved. The magnitude of improvement demonstrated by the WHO pilot studies was surprising. These initial results have been confirmed by further detailed work demonstrating that surgical checklists, when properly implemented, can make a substantial difference to patient safety. However, introducing surgical checklists is not as straightforward as it seems, and requires leadership, flexibility, and teamwork in a different way to that which is currently practiced. Future work should be aimed at ensuring effective implementation of the WHO Surgical Safety Checklist, which will benefit our patients on a global scale.

Improving surgical safety globally: pulse oximetry and the WHO Guidelines for Safe Surgery.

Access to safe surgery should be considered as part of the basic human right for health, but unfortunately, this ideal is far from being reached in many low-income countries. Pulse oximetry is recommended as a minimum standard of monitoring by all anesthesia organizations that have set standards, yet around 78,000 operating theaters worldwide lack this essential monitor. The WHO Safe Surgery Saves Lives Program has identified evidence-based guidelines for safe surgery that are applicable in any setting, and the Global Pulse Oximetry Program will help improve access to pulse oximetry in countries where it is not available. However, these initiatives are just a start; capacity, infrastructure, trained healthcare providers and access to essential drugs, and equipment for anesthesia and surgery need to become a public health priority in many low-income countries.

Global oximetry: an international anaesthesia quality improvement project.

Pulse oximetry is mandatory during anaesthesia in many countries, a standard endorsed by the World Health Organization 'Safe Surgery Saves Lives' initiative. The Association of Anaesthetists of Great Britain and Ireland, the World Federation of Societies of Anaesthesiologists and GE Healthcare collaborated in a quality improvement project over a 15-month period to investigate pulse oximetry in four pilot sites in Uganda, Vietnam, India and the Philippines, using 84 donated pulse oximeters. A substantial gap in oximeter provision was demonstrated at the start of the project. Formal training was essential for oximeter-naïve practitioners. After introduction of oximeters, logbook data were collected from over 8000 anaesthetics, and responses to desaturation were judged appropriate. Anaesthesia providers believed pulse oximeters were essential for patient safety and defined characteristics of the ideal oximeter for their setting. Robust systems for supply and maintenance of low-cost oximeters are required for sustained uptake of pulse oximetry in low- and middle-income countries.

Orthopaedic surgery in haemophilia patients with inhibitors: a practical guide to haemostatic, surgical and rehabilitative care.

All but essential surgery is generally avoided in haemophilia patients with inhibitor antibodies, because of concern about the reliability with which haemostasis can be achieved and maintained in such patients. Orthopaedic surgical procedures which are not required to preserve life fall under this category. As a result, patients with inhibitors may be denied operations, which could greatly enhance their quality of life, and which are routinely offered to other haemophilia patients. While caution is appropriate in recommending surgery in any circumstance, we believe that the threshold for offering validated surgical procedures to patients with inhibitors should be re-evaluated in the light of current surgical and rehabilitative techniques, and the long experience with safe and effective factor VIII inhibitor bypassing agents, namely activated prothrombin complex concentrates and recombinant activated factor FVII. In this article, we review the haematological, surgical and rehabilitative considerations relevant to orthopaedic surgery in haemophilia patients with inhibitors, and provide recommendations for carrying out such procedures.

Cardiac surgery in patients with haemophilia B: a case report and review of the literature.

Cardiac surgery for coronary heart disease, and for calcific and degenerative valvular heart disease, will likely become more frequent with an ageing haemophilia population. Our report describes the successful management of an individual with mild haemophilia B undergoing elective aortic valve replacement using a continuous infusion of recombinant factor IX. Emphasis is placed on the multidisciplinary coordination of care required across three hospital sites to ensure an uncomplicated peri- and postoperative course. We also provide a review of the current literature on cardiac surgery in patients with haemophilia B.