Leveraging Lymphatic System Targeting in Systemic Lupus Erythematosus for Improved Clinical Outcomes.

The role of advanced drug delivery strategies in drug repositioning and minimizing drug attrition rates, when applied early in drug discovery, is poised to increase the translational impact of various therapeutic strategies in disease prevention and treatment. In this context, drug delivery to the lymphatic system is gaining prominence not only to improve the systemic bioavailability of various pharmaceutical drugs but also to target certain specific diseases associated with the lymphatic system. Although the role of the lymphatic system in lupus is known, very little is done to target drugs to yield improved clinical benefits. In this review, we discuss recent advances in drug delivery strategies to treat lupus, the various routes of drug administration leading to improved lymph node bioavailability, and the available technologies applied in other areas that can be adapted to lupus treatment. Moreover, this review also presents some recent findings that demonstrate the promise of lymphatic targeting in a preclinical setting, offering renewed hope for certain pharmaceutical drugs that are limited by efficacy in their conventional dosage forms. These findings underscore the potential and feasibility of such lymphatic drug-targeting approaches to enhance therapeutic efficacy in lupus and minimize off-target effects of the pharmaceutical drugs. SIGNIFICANCE STATEMENT: The World Health Organization estimates that there are currently 5 million humans living with some form of lupus. With limited success in lupus drug discovery, turning to effective delivery strategies with existing drug molecules, as well as those in the early stage of discovery, could lead to better clinical outcomes. After all, effective delivery strategies have been proven to improve treatment outcomes.

The incidence of potentially serious complications during non-obstetric anaesthetic practice in the United Kingdom: an analysis from the 7th National Audit Project (NAP7) activity survey.

Complications and critical incidents arising during anaesthesia due to patient, surgical or anaesthetic factors, may cause harm themselves or progress to more severe events, including cardiac arrest or death. As part of the 7th National Audit Project of the Royal College of Anaesthetists, we studied a prospective national cohort of unselected patients. Anaesthetists recorded anonymous details of all cases undertaken over 4 days at their site through an online survey. Of 416 hospital sites invited to participate, 352 (85%) completed the survey. Among 24,172 cases, 1922 discrete potentially serious complications were reported during 1337 (6%) cases. Obstetric cases had a high reported major haemorrhage rate and were excluded from further analysis. Of 20,996 non-obstetric cases, 1705 complications were reported during 1150 (5%) cases. Circulatory events accounted for most complications (616, 36%), followed by airway (418, 25%), metabolic (264, 15%), breathing (259, 15%), and neurological (41, 2%) events. A single complication was reported in 851 (4%) cases, two complications in 166 (1%) cases and three or more complications in 133 (1%) cases. In non-obstetric elective surgery, all complications were 'uncommon' (10-100 per 10,000 cases). Emergency (urgent and immediate priority) surgery accounted for 3454 (16%) of non-obstetric cases but 714 (42%) of complications with severe hypotension, major haemorrhage, severe arrhythmias, septic shock, significant acidosis and electrolyte disturbances all being 'common' (100-1000 per 10,000 cases). Based on univariate analysis, complications were associated with: younger age; higher ASA physical status; male sex; increased frailty; urgency and extent of surgery; day of the week; and time of day. These data represent the rates of potentially serious complications during routine anaesthesia care and may be valuable for risk assessment and patient consent.

Peri-operative cardiac arrest: management and outcomes of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. We report the results of the 12-month registry phase, from 16 June 2021 to 15 June 2022, focusing on management and outcomes. Among 881 cases of peri-operative cardiac arrest, the initial rhythm was non-shockable in 723 (82%) cases, most commonly pulseless electrical activity. There were 665 (75%) patients who survived the initial event and 384 (52%) who survived to hospital discharge. A favourable functional outcome (based on modified Rankin Scale score) was reported for 249 (88%) survivors. Outcomes varied according to arrest rhythm. The highest rates of survival were seen for bradycardic cardiac arrests with 111 (86%) patients surviving the initial event and 77 (60%) patients surviving the hospital episode. The lowest survival rates were seen for patients with pulseless electrical activity, with 312 (68%) surviving the initial episode and 156 (34%) surviving to hospital discharge. Survival to hospital discharge was worse in patients at the extremes of age with 76 (40%) patients aged > 75 y and 9 (45%) neonates surviving. Hospital survival was also associated with surgical priority, with 175 (88%) elective patients and 176 (37%) non-elective patients surviving to discharge. Outcomes varied with the cause of cardiac arrest, with lower initial survival rates for pulmonary embolism (5, 31%) and bone cement implantation syndrome (9, 45%), and hospital survival of < 25% for pulmonary embolism (0), septic shock (13, 24%) and significant hyperkalaemia (1, 20%). Overall care was rated good in 464 (53%) cases, and 18 (2%) cases had overall care rated as poor. Poor care elements were present in a further 245 (28%) cases. Care before cardiac arrest was the phase most frequently rated as poor (92, 11%) with elements of poor care identified in another 186 (21%) cases. These results describe the management and outcomes of peri-operative cardiac arrest in UK practice for the first time.

Peri-operative cardiac arrest: epidemiology and clinical features of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. Here we report the results of the 12-month registry, from 16 June 2021 to 15 June 2022, focusing on epidemiology and clinical features. We reviewed 881 cases of peri-operative cardiac arrest, giving an incidence of 3 in 10,000 anaesthetics (95%CI 3.0-3.5 per 10,000). Incidence varied with patient and surgical factors. Compared with denominator survey activity, patients with cardiac arrest: included more males (56% vs. 42%); were older (median (IQR) age 60.5 (40.5-80.5) vs. 50.5 (30.5-70.5) y), although the age distribution was bimodal, with infants and patients aged > 66 y overrepresented; and were notably more comorbid (73% ASA physical status 3-5 vs. 27% ASA physical status 1-2). The surgical case-mix included more weekend (14% vs. 11%), out-of-hours (19% vs. 10%), non-elective (65% vs. 30%) and major/complex cases (60% vs. 28%). Cardiac arrest was most prevalent in orthopaedic trauma (12%), lower gastrointestinal surgery (10%), cardiac surgery (9%), vascular surgery (8%) and interventional cardiology (6%). Specialities with the highest proportion of cases relative to denominator activity were: cardiac surgery (9% vs. 1%); cardiology (8% vs. 1%); and vascular surgery (8% vs. 2%). The most common causes of cardiac arrest were: major haemorrhage (17%); bradyarrhythmia (9%); and cardiac ischaemia (7%). Patient factors were judged a key cause of cardiac arrest in 82% of cases, anaesthesia in 40% and surgery in 35%.

Major haemorrhage: past, present and future.

Major haemorrhage is a leading cause of morbidity and mortality worldwide. Successful treatment requires early recognition, planned responses, readily available resources (such as blood products) and rapid access to surgery or interventional radiology. Major haemorrhage is often accompanied by volume loss, haemodilution, acidaemia, hypothermia and coagulopathy (factor consumption and fibrinolysis). Management of major haemorrhage over the past decade has evolved to now deliver a 'package' of haemostatic resuscitation including: surgical or radiological control of bleeding; regular monitoring of haemostasis; advanced critical care support; and avoidance of the lethal triad of hypothermia, acidaemia and coagulopathy. Recent trial data advocate for a more personalised approach depending on the clinical scenario. Fresh frozen plasma should be given as early as possible in major trauma in a 1:1 ratio with red blood cells until the results of coagulation tests are available. Tranexamic acid is a cheap, life-saving drug and is advocated in major trauma, postpartum haemorrhage and surgery, but not in patients with gastrointestinal bleeding. Fibrinogen levels should be maintained > 2 g.l-1 in postpartum haemorrhage and > 1.5 g.l-1 in other haemorrhage. Improving outcomes after major traumatic haemorrhage is now driving research to include extending blood-product resuscitation into prehospital care.

The 7th National Audit Project (NAP7) baseline survey of individual anaesthetists: preparedness for and experiences of peri-operative cardiac arrest.

The Royal College of Anaesthetists' 7th National Audit Project baseline survey assessed knowledge, attitudes, practices and experiences of peri-operative cardiac arrests among UK anaesthetists and Anaesthesia Associates. We received 10,746 responses, representing a 71% response rate. In-date training in adult and paediatric advanced life support was reported by 9646 (90%) and 7125 (66%) anaesthetists, respectively. There were 8994 (84%) respondents who were confident in leading a peri-operative cardiac arrest, with males more confident than females, but only 5985 (56%) were confident in leading a debrief and 7340 (68%) communicating with next of kin. In the previous two years, 4806 (46%) respondents had managed at least one peri-operative cardiac arrest, of which 321 (7%) and 189 (4%) of these events involved a child or an obstetric patient, respectively. Respondents estimated the most common causes of peri-operative cardiac arrest to be hypovolaemia, hypoxaemia and cardiac ischaemia, with haemorrhage coming fifth. However, the most common reported causes for the most recently attended peri-operative cardiac arrest were haemorrhage; (927, 20%); anaphylaxis (474, 10%); and cardiac ischaemia (397, 9%). Operating lists or shifts were paused or stopped after 1330 (39%) cardiac arrests and 1693 (38%) respondents attended a debrief, with 'hot' debriefs most common. Informal wellbeing support was relatively common (2458, 56%) and formal support was uncommon (472, 11%). An impact on future care delivery was reported by 196 (4%) anaesthetists, most commonly a negative psychological impact. Management of a peri-operative cardiac arrest during their career was reported by 8654 (85%) respondents. The overall impact on professional life was more often judged positive (2630, 30%) than negative (1961, 23%), but impact on personal life was more often negative.

Organisation of UK hospitals and anaesthetic departments in the treatment of peri-operative cardiac arrest: an analysis from the 7th National Audit Project (NAP7) local co-ordinator baseline survey.

We report the results of the Royal College of Anaesthetists' 7th National Audit Project organisational baseline survey sent to every NHS anaesthetic department in the UK to assess preparedness for treating peri-operative cardiac arrest. We received 199 responses from 277 UK anaesthetic departments, representing a 72% response rate. Adult and paediatric anaesthetic care was provided by 188 (95%) and 165 (84%) hospitals, respectively. There was no paediatric intensive care unit on-site in 144 (87%) hospitals caring for children, meaning transfer of critically ill children is required. Remote site anaesthesia is provided in 182 (92%) departments. There was a departmental resuscitation lead in 113 (58%) departments, wellbeing lead in 106 (54%) and departmental staff wellbeing policy in 81 (42%). A defibrillator was present in every operating theatre suite and in all paediatric anaesthesia locations in 193 (99%) and 149 (97%) departments, respectively. Advanced airway equipment was not available in: every theatre suite in 13 (7%) departments; all remote locations in 103 (57%) departments; and all paediatric anaesthesia locations in 23 (15%) departments. Anaesthetic rooms were the default location for induction of anaesthesia in adults and children in 148 (79%) and 121 (79%) departments, respectively. Annual updates in chest compressions and in defibrillation were available in 149 (76%) and 130 (67%) departments, respectively. Following a peri-operative cardiac arrest, debriefing and peer support programmes were available in 154 (79%) and 57 (29%) departments, respectively. While it is likely many UK hospitals are very well prepared to treat anaesthetic emergencies including cardiac arrest, the survey suggests this is not universal.

Patient characteristics, anaesthetic workload and techniques in the UK: an analysis from the 7th National Audit Project (NAP7) activity survey.

Detailed contemporary knowledge of the characteristics of the surgical population, national anaesthetic workload, anaesthetic techniques and behaviours are essential to monitor productivity, inform policy and direct research themes. Every 3-4 years, the Royal College of Anaesthetists, as part of its National Audit Projects (NAP), performs a snapshot activity survey in all UK hospitals delivering anaesthesia, collecting patient-level encounter data from all cases under the care of an anaesthetist. During November 2021, as part of NAP7, anaesthetists recorded details of all cases undertaken over 4 days at their site through an online survey capturing anonymous patient characteristics and anaesthetic details. Of 416 hospital sites invited to participate, 352 (85%) completed the activity survey. From these, 24,177 reports were returned, of which 24,172 (99%) were included in the final dataset. The work patterns by day of the week, time of day and surgical specialty were similar to previous NAP activity surveys. However, in non-obstetric patients, between NAP5 (2013) and NAP7 (2021) activity surveys, the estimated median age of patients increased by 2.3 years from median (IQR) of 50.5 (28.4-69.1) to 52.8 (32.1-69.2) years. The median (IQR) BMI increased from 24.9 (21.5-29.5) to 26.7 (22.3-31.7) kg.m-2 . The proportion of patients who scored as ASA physical status 1 decreased from 37% in NAP5 to 24% in NAP7. The use of total intravenous anaesthesia increased from 8% of general anaesthesia cases to 26% between NAP5 and NAP7. Some changes may reflect the impact of the COVID-19 pandemic on the anaesthetic population, though patients with confirmed COVID-19 accounted for only 149 (1%) cases. These data show a rising burden of age, obesity and comorbidity in patients requiring anaesthesia care, likely to impact UK peri-operative services significantly.

Case Report of Primary Synovial Sarcoma of the Thyroid Gland: An Unusual Histology at Atypical Location.

Primary synovial sarcoma of the thyroid gland is extremely rare, aggressive, and has a dismal prognosis. We report the case of a 15-year-old male who presented with a progressively increasing neck mass, which was excised and the histopathological and immunohistochemical study suggested biphasic synovial sarcoma of the thyroid gland which was confirmed by synovial sarcoma translocation. There are 14 cases of primary synovial sarcoma of the thyroid reported in the literature so far. This study aimed to document the occurrence of synovial sarcoma histology at an unusual anatomical location with a review of the literature on this rare entity.

Gap Statistics for Confined Particles with Power-Law Interactions.

We consider the N particle classical Riesz gas confined in a one-dimensional external harmonic potential with power-law interaction of the form 1/r^{k}, where r is the separation between particles. As special limits it contains several systems such as Dyson's log-gas (k→0^{+}), the Calogero-Moser model (k=2), the 1D one-component plasma (k=-1), and the hard-rod gas (k→∞). Despite its growing importance, only large-N field theory and average density profile are known for general k. In this Letter, we study the fluctuations in the system by looking at the statistics of the gap between successive particles. This quantity is analogous to the well-known level-spacing statistics which is ubiquitous in several branches of physics. We show that the variance goes as N^{-b_{k}} and we find the k dependence of b_{k} via direct Monte Carlo simulations. We provide supporting arguments based on microscopic Hessian calculation and a quadratic field theory approach. We compute the gap distribution and study its system size scaling. Except in the range -1-2 with both Gaussian and non-Gaussian scaling forms.

CaSR expression in normal parathyroid and PHPT: new insights into pathogenesis from an autopsy-based study.

PURPOSE: Calcium sensing receptor (CaSR), on the surface of normal parathyroid cells, is essential for maintaining serum calcium levels. The normal pattern of CaSR immunostaining remains undefined and is presumptively circumferential. Given the physiological variation in serum calcium, we postulated that CaSR expression could not be uniformly circumferential. Also, cytoplasmic expression has not been evaluated either in normal or pathological tissues. We studied normal parathyroid tissues derived from forensic autopsies and those rimming parathyroid adenomas for membranous and cytoplasmic CaSR immunoexpression. Results were compared with primary hyperparathyroidism (PHPT) to look for any pathogenetic implications. MATERIALS AND METHODS: We evaluated 34 normal parathyroid tissues from 11 autopsies, 30 normal rims, 45 parathyroid adenoma, 10 hyperplasia, and 7 carcinoma cases. Membranous expression was categorized complete/incomplete and weak/moderate/strong; scored using Her2/Neu and Histo-scores; predominant pattern noted. Cytoplasmic expression was categorized negative/weak/moderate/strong; predominant intensity noted. RESULTS: Normal autopsy-derived parathyroid tissues were Her2/Neu 3 + , but incomplete membranous staining predominated in 85%. Their immune-scores were significantly more than the cases (p < < 0.05). The mean histo-score of normal rims was intermediate between the two (p < < 0.05). Cytoplasmic expression was strong in all autopsy-derived tissues, weak/negative in hyperplasia (100%), moderate in 16% adenomas, and 43% carcinomas. CONCLUSIONS: Normal autopsy-derived parathyroid tissues showed strong but predominantly incomplete membranous expression. Surface CaSR expression decreased in PHPT and is probably an early event in parathyroid adenoma, seen even in normal rims. Whether there is a defect in CaSR trafficking from the cytoplasm to the cell surface in adenoma and carcinoma needs further evaluation.

Position statement from the Editors of Anaesthesia on equity, diversity and inclusion.

There is a need to prioritise equity, diversity and inclusion within anaesthesia and medicine as a whole. This position statement outlines the Anaesthesia Editors' current policies and practices aiming to achieve equity, represent the diversity of our specialty and actively include people engaged with this journal and beyond. We will define, promote and embed principles of equity, diversity and inclusion across all our work. We will monitor and report author and editor characteristics and ensure recruitment practices are transparent and adhere to our principles on equity, diversity and inclusion. We will attempt to remove systemic barriers restricting those from under-represented groups from progressing into leadership roles within anaesthesia. We will respond to threats and barriers to the principles and practices we set. With these principles and specific actions we undertake, we aim to be pro-active rather than reactive. We commit to embracing and embedding equity, diversity and inclusion in all our practices and regularly reviewing, improving and updating our policies and practices.

Methods of the 7th National Audit Project (NAP7) of the Royal College of Anaesthetists: peri-operative cardiac arrest.

Cardiac arrest in the peri-operative period is rare but associated with significant morbidity and mortality. Current reporting systems do not capture many such events, so there is an incomplete understanding of incidence and outcomes. As peri-operative cardiac arrest is rare, many hospitals may only see a small number of cases over long periods, and anaesthetists may not be involved in such cases for years. Therefore, a large-scale prospective cohort is needed to gain a deep understanding of events leading up to cardiac arrest, management of the arrest itself and patient outcomes. Consequently, the Royal College of Anaesthetists chose peri-operative cardiac arrest as the 7th National Audit Project topic. The study was open to all UK hospitals offering anaesthetic services and had a three-part design. First, baseline surveys of all anaesthetic departments and anaesthetists in the UK, examining respondents' prior peri-operative cardiac arrest experience, resuscitation training and local departmental preparedness. Second, an activity survey to record anonymised details of all anaesthetic activity in each site over 4 days, enabling national estimates of annual anaesthetic activity, complexity and complication rates. Third, a case registry of all instances of peri-operative cardiac arrest in the UK, reported confidentially and anonymously, over 1 year starting 16 June 2021, followed by expert review using a structured process to minimise bias. The definition of peri-operative cardiac arrest was the delivery of five or more chest compressions and/or defibrillation in a patient having a procedure under the care of an anaesthetist. The peri-operative period began with the World Health Organization 'sign-in' checklist or first hands-on contact with the patient and ended either 24 h after the patient handover (e.g. to the recovery room or intensive care unit) or at discharge if this occured earlier than 24 h. These components described the epidemiology of peri-operative cardiac arrest in the UK and provide a basis for developing guidelines and interventional studies.

Life-saving transfusion in autoimmune hemolytic anemia: a case report and procedure review of the dilution method.

A woman with autoimmune hemolytic anemia (AIHA) presented in the emergency department with life-threatening anemia (hemoglobin 3 g/dL). Exaggeration of preexisting chronic anemia to severe anemia after a recent red blood cell (RBC) transfusion led to suspicion of delayed hemolytic transfusion reaction. Given the urgency for transfusion along with a stronger suspicion for coexistence of an alloantibody, the dilution method proposed by Lawrence Petz and George Garratty was used to find an RBC unit for transfusion. An alloantibody with Fyb specificity was identified, which was masked by the coexistent autoantibody. This method is based on the assumption that the titers of an alloantibody are higher than that of autoantibody. Diluting the autoantibody would reveal the alloantibody and, for this purpose, a serial doubling dilution of serum is performed. This method has an important limitation of missing any alloantibodies with titers less than that of the autoantibody. In spite of this, this method may be of use at a resource-poor setting, where trained personnel and other reagents intended for advanced immunohematology methods are unavailable.

Use of indocyanine green fluorescence angiography during ileal J-pouch surgery requiring lengthening maneuvers.

BACKGROUND: The purpose of this study was to review whether routine usage of indocyanine green (ICG) perfusion assessment during complex ileal J-pouch surgery requiring lengthening maneuvers reduces ischemic complications. METHODS: Retrospective chart review of patients with ulcerative colitis (UC) or familial adenomatous polyposis (FAP) who underwent ileal pouch-anal anastomosis (IPAA) surgery with lengthening maneuvers and intraoperative ICG assessment between January 2015 and January 2021. All patients underwent a double stapled anastomosis and were temporarily diverted. All patients underwent laparoscopic and trans-anal ICG assessment of their J-pouch and anastomosis. All J-pouches were evaluated 6 weeks after surgery via contrast enema and pouchoscopy. RESULTS: One hundred fifty eight patients underwent ileal J-pouch surgery during the study period. Sixteen patients (10%) underwent lengthening maneuvers and intra-operative ICG assessment. Twelve patients underwent surgery for UC and 4 for FAP. Median age was 40.3 years and average body mass index was 24.9 kg/m2. Twelve patients underwent a two-stage procedure and the remaining underwent a three-stage procedure. 93.7% of cases were completed laparoscopically (15/16). All patients underwent scoring of the peritoneum and 43% (7/16) underwent division of the ileocolic or intermediate mesenteric vessels. There was no mortality or pouch ischemia and the leak rate was 12.5%. All patients underwent reversal after an average of 18 ± 7 weeks. CONCLUSION: ICG perfusion assessment appears to be of utility in complex IPAA surgery requiring lengthening maneuvers. Its application may be associated with reduced J-pouch ischemia and leak rate in this unique setting.

Clinicopathologic spectrum of newly diagnosed multiple myeloma presenting with renal impairment: A tertiary care center experience from north India.

Multiple myeloma (MM) is a hematologic malignancy, characterized by the neoplastic proliferation of plasma cells producing a monoclonal immunoglobulin. Patients presents with signs and symptoms related to the infiltration of plasma cells into the bone or other organs or to kidney damage from excess light chains. Renal involvement with various presentations may be the first manifestation of the disease. MATERIAL: All patients of MM presenting with renal dysfunction between July 2019 to June 2021 were included. Diagnosis of MM was made according to the 2014 guidelines of international myeloma working group. OBSERVATION: Out of total 144 cases of multiple myeloma renal involvement was present in 43 (29.8%). Mean age of study population was 55.49 years with 72% males. Most common clinical features were fatigue (59%), anorexia (47%) & edema (42%). Anemia was present in 79%, hypercalcemia in 16.2% and hyperuricemia in 20.9% patients. Renal failure was present in 72.1% with a mean eGFR 35.8 ml/min/1.73m2. Serum protein electrophoresis revealed M band in 81.4% and all except one patient had increased light chains in serum. Most common histological lesion were myeloma cast nephropathy (39.5%), primary amyloidosis (30.2%) & monoclonal immunoglobulin deposition disease (14%). Primary amyloidosis group had maximum 24-hour proteinuria and highest eGFR. CONCLUSION: The spectrum of renal involvement in multiple myeloma is heterogenous. It mainly affects middle and elderly age group. Typical clinical features might not be seen in all the cases and therefore a high index of suspicion in unexplained renal failure cases might help in early diagnosis and timely management.

Development of difficulty index for management of impacted maxillary canine: A CBCT-based study.

BACKGROUND: The aim of this study was to propose an Impacted Canine Treatment Difficulty Index using Cone-beam Computed Tomography (CBCT) imaging to assess difficulty anticipated during the alignment of impacted maxillary canine and further validate the index in clinical set up. METHODS: Pre-treatment CBCT of 15 patients with unilateral or bilateral impacted maxillary canine aged between 12 and 30 years were selected. All the following five factors were assessed on CBCT image: 1) angulation, 2) vertical position, 3) bucco-palatal position, 4) horizontal position and 5) rotation. Two orthodontists evaluated the pre-treatment CBCT for the selected five factors and allocated a total difficulty score. To validate the proposed difficulty index in clinical settings, a team of oral and maxillofacial surgeons were included in the study to grade the difficulty encountered during surgical procedure. RESULTS: The distribution of difficulty score recorded by observer 1 was significantly associated with the difficulty score recorded by observer 2 (P-value < 0.001), with relatively higher level of linearly weighted Cohen's kappa value of 0.610. The distribution of difficulty score recorded by oral and maxillofacial surgeon was significantly associated with the difficulty score recorded by observer 1 (P-value < 0.01), with relatively higher level of linearly weighted Cohen's kappa value of 0.667. The distribution of difficulty score recorded by orthodontist was significantly associated with the difficulty score recorded by observer 1 (P-value < 0.001), with relatively higher linearly weighted Cohen's kappa value of 0.819. CONCLUSION: Impacted Canine Treatment Difficulty Index using CBCT imaging could be used to assess the difficulty that would be anticipated during the alignment of impacted maxillary cuspid.

Anaemia in cardiac surgery - a retrospective review of a centre's experience with a pre-operative intravenous iron clinic.

Pre-operative anaemia is associated with higher rates of transfusion and worse outcomes, including prolonged hospital stay, morbidity and mortality. Iron deficiency is associated with significantly lower haemoglobin levels throughout the peri-operative period and more frequent blood transfusion. Correction of iron stores before surgery forms part of the first pillar of patient blood management. We established a pre-operative anaemia clinic to aid identification and treatment of patients with iron deficiency anaemia scheduled for elective cardiac surgery. We present a retrospective observational review of our experience from January 2017 to December 2019. One-hundred and ninety patients received treatment with intravenous iron, a median of 21 days before cardiac surgery. Of these, 179 had a formal laboratory haemoglobin level measured before surgery, demonstrating a median rise in haemoglobin of 8.0 g.l-1 . Patients treated with i.v. iron demonstrated a significantly higher incidence of transfusion (60%) compared with the non-anaemic cohort (22%) during the same time period, p < 0.001. Significantly higher rates of new requirement for renal replacement therapy (6.7% vs. 0.6%, p < 0.001) and of stroke (3.7% vs. 1.2%, p = 0.010) were also seen in this group compared with those without anaemia, although there was no significant difference in in-hospital mortality (1.6% vs. 0.8%, p = 0.230). In patients where the presenting haemoglobin was less than 130 g.l-1 , but there was no intervention or treatment, there was no difference in rates of transfusion or of complications compared with the anaemic group treated with iron. In patients with proven iron deficiency anaemia, supplementation with intravenous iron showed only a modest effect on haemoglobin and this group still had a significantly higher transfusion requirement than the non-anaemic cohort. Supplementation with intravenous iron did not improve outcomes compared with patients with anaemia who did not receive intravenous iron and did not reduce peri-operative risk to non-anaemic levels. Questions remain regarding identification of patients who will receive most benefit, the use of concomitant treatment with other agents, and the optimum time frames for treatment in order to produce benefit in the real-world setting.

The incidence and effect of resternotomy following cardiac surgery on morbidity and mortality: a 1-year national audit on behalf of the Association of Cardiothoracic Anaesthesia and Critical Care.

Over 30,000 adult cardiac operations are carried out in the UK annually. A small number of these patients need to return to theatre in the first few days after the initial surgery, but the exact proportion is unknown. The majority of these resternotomies are for bleeding or cardiac tamponade. The Association of Cardiothoracic Anaesthesia and Critical Care carried out a 1-year national audit of resternotomy in 2018. Twenty-three of the 35 centres that were eligible participated. The overall resternotomy rate (95%CI) within the period of admission for the initial operation in these centres was 3.6% (3.37-3.85). The rate varied between centres from 0.69% to 7.6%. Of the 849 patients who required resternotomy, 127 subsequently died, giving a mortality rate (95%CI) of 15.0% (12.7-17.5). In patients who underwent resternotomy, the median (IQR [range]) length of stay on ICU was 5 (2-10 [0-335]) days, and time to tracheal extubation was 20 (12-48 [0-2880]) hours. A total of 89.3% of patients who underwent resternotomy were transfused red cells, with a median (IQR [range]) of 4 (2-7 [1-1144]) units of red blood cells. The rate (95%CI) of needing renal replacement therapy was 23.4% (20.6-26.5). This UK-wide audit has demonstrated that resternotomy after cardiac surgery is associated with prolonged intensive care stay, high rates of blood transfusion, renal replacement therapy and very high mortality. Further research into this area is required to try to improve patient care and outcomes in patients who require resternotomy in the first 24 h after cardiac surgery.

A European consensus statement on the use of four-factor prothrombin complex concentrate for cardiac and non-cardiac surgical patients.

Modern four-factor prothrombin complex concentrate was designed originally for rapid targeted replacement of the coagulation factors II, VII, IX and X. Dosing strategies for the approved indication of vitamin K antagonist-related bleeding vary greatly. They include INR and bodyweight-related protocols as well as fixed dose regimens. Particularly in the massively bleeding trauma and cardiac surgery patient, four-factor prothrombin complex concentrate is used increasingly for haemostatic resuscitation. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology performed a systematic literature review on four-factor prothrombin complex concentrate. The available evidence has been summarised for dosing, efficacy, drug safety and monitoring strategies in different scenarios. Whereas there is evidence for the efficacy of four-factor prothrombin concentrate for a variety of bleeding scenarios, convincing safety data are clearly missing. In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg-1 . This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available. In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half-dose bolus (12.5 IU.kg-1 ) should be considered. A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue-factor-activated, factor VII-dependent and heparin insensitive point-of-care tests may be used for peri-operative monitoring and guiding of prothrombin complex concentrate therapy.