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%.

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.

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.

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.

Identification of the Language Network from Resting-State fMRI in Patients with Brain Tumors: How Accurate Are Experts?

BACKGROUND AND PURPOSE: Resting-state fMRI helps identify neural networks in presurgical patients who may be limited in their ability to undergo task-fMRI. The purpose of this study was to determine the accuracy of identifying the language network from resting-state-fMRI independent component analysis (ICA) maps. MATERIALS AND METHODS: Through retrospective analysis, patients who underwent both resting-state-fMRI and task-fMRI were compared by identifying the language network from the resting-state-fMRI data by 3 reviewers. Blinded to task-fMRI maps, these investigators independently reviewed resting-state-fMRI ICA maps to potentially identify the language network. Reviewers ranked up to 3 top choices for the candidate resting-state-fMRI language map. We evaluated associations between the probability of correct identification of the language network and some potential factors. RESULTS: Patients included 29 men and 14 women with a mean age of 41 years. Reviewer 1 (with 17 years' experience) demonstrated the highest overall accuracy with 72%; reviewers 2 and 3 (with 2 and 7 years' experience, respectively) had a similar percentage of correct responses (50% and 55%). The highest accuracy used ICA50 and the top 3 choices (81%, 65%, and 60% for reviewers 1, 2, and 3, respectively). The lowest accuracy used ICA50, limiting each reviewer to the top choice (58%, 35%, and 42%). CONCLUSIONS: We demonstrate variability in the accuracy of blinded identification of resting-state-fMRI language networks across reviewers with different years of experience.

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.

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.

Esophageal Melanosis: An Unknown Entity.

Esophageal melanosis is the proliferation of melanocytes in the squamous epithelium of the esophagus and the accumulation of melanin in the walls of the esophagus. Normal esophageal mucosa does not contain melanocytes. It is a rare disease of the digestive system, and its significance has yet to be fully understood. Various studies have attributed it to gastroesophageal reflux disease, but hard evidence supporting such a claim is lacking. Some studies also point towards it being a pre-malignant condition, and further evaluation is warranted for earlier detection and treatment. We hereby present a case of chronic iron deficiency anemia incidentally found to have esophageal melanosis, confirmed with histopathological examination.

Can dual staining with p16 and Ki67 be biomarkers of epithelial dysplasia in oral lesions?

Background: Oral carcinogenesis is a multistage process with epithelial dysplasia as a premalignant condition. There is a significant inter-observer variation in diagnosing and grading the oral epithelial dysplasia. As human papillomavirus (HPV) is believed to have à strong relationship with oral carcinogenesis, using P16 as a biomarker may help in identifying the cells which may be undergoing the malignant transformation. However, due to the low specificity of P16, dual staining test P16INK4/Ki67 might be a better promising marker for identifying the transformed cells. This study was designed to evaluate the dual expression of P16 and Ki67 as a promising biomarker for dysplasia and their correlation with clinicopathological factors. Materials and Methods: Immunohistochemical analysis for p16 and ki67 was performed on 30 premalignant oral lesions and 36 oral squamous cell carcinoma (OSCC) by dual staining using the CINtec PLUS kit. Results: CINtec positivity was observed only in leukoplakia with dysplasia (46.7%) and squamous cell carcinoma (25%). None of the cases of leukoplakia without dysplasia or oral submucosal fibrosis stained positive for CINtec plus staining. In leukoplakia with dysplasia, there was no significant association with any of the clinicopathological parameters studied. In OSCC cases, alcohol intake showed statistically significant association with CINtec positivity. Conclusion: P16INK4/Ki67 assessment by dual staining is a promising biomarker for identifying dysplasia in cases with diagnostic dilemmas.

A Case of Type 2 Protein S Deficiency Presenting as Cerebral Venous Thrombosis (CVT) in an 18-Year-Old Female.

Here, we report a case of cerebral venous thrombosis in an 18-year-old female. On evaluation, she was found to have type 2 protein S deficiency, which is the rarest form of protein S deficiency and is also known as a qualitative defect. Protein S is primarily synthesized by hepatocytes and undergoes vitamin K-dependent gamma-carboxylation. Mature protein S circulates in two states: free and bound to the complement component C4b-binding protein (C4b-BP). The free form of protein S acts as a cofactor for activated protein C. This case is unique as here, there is a qualitative effect that is responsible for the manifestations.