Granulomatous skin involvement in a patient with an unusual NOD2 mutation

Blau syndrome is a rare disorder that is classically characterised by granulomatous arthritis, skin eruptions and uveitis, which occur in the absence of lung involvement. Blau syndrome has been linked to encoding mutations in the NOD‐2 gene and is inherited in an autosomal dominant form. The most commonly observed mutations are missense substitutions affecting the arginine residue at position 334. The rare E600A mutation has been described as causing uveitis without skin involvement. Our patient is a 54‐year‐old man with an unusual heterozygous c.1799A>C(E600A) mutation, who was seen for bilateral lower extremity swelling and pain. On physical examination, he was found to have lower leg oedema with decreased hair growth on the affected area. Biopsy showed non‐caseating micro‐granulomas consistent with a diagnosis of Blau syndrome. The patient had excellent response to colchicine, but this was stopped because he developed elevated transaminases. Thus, we present an unusual genetic form of a rare condition and we demonstrate skin involvement in a subtype where cutaneous involvement has not hitherto been reported. In addition, the type and presentation of the skin involvement is different from that normally found in classic Blau syndrome. Finally, we report his response to colchicine, although it was ultimately not tolerated by this patient.     

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%.     

CGRP induces migraine-like symptoms in mice during both the active and inactive phases

BackgroundCircadian patterns of migraine attacks have been reported by patients but remain understudied. In animal models, circadian phases are generally not taken into consideration. In particular, rodents are nocturnal animals, yet they are most often tested during their inactive phase during the day. This study aims to test the validity of CGRP-induced behavioral changes in mice by comparing responses during the active and inactive phases.MethodsMale and female mice of the outbred CD1 strain were administered vehicle (PBS) or CGRP (0.1 mg/kg, i.p.) to induce migraine-like symptoms. Animals were tested for activity (homecage movement and voluntary wheel running), light aversive behavior, and spontaneous pain at different times of the day and night.ResultsPeripheral administration of CGRP decreased the activity of mice during the first hour after administration, induced light aversive behavior, and spontaneous pain during that same period of time. Both phenotypes were observed no matter what time of the day or night they were assessed.ConclusionsA decrease in wheel activity is an additional clinically relevant phenotype observed in this model, which is reminiscent of the reduction in normal physical activity observed in migraine patients. The ability of peripheral CGRP to induce migraine-like symptoms in mice is independent of the phase of the circadian cycle. Therefore, preclinical assessment of migraine-like phenotypes can likely be done during the more convenient inactive phase of mice.Supplementary InformationThe online version contains supplementary material available at 10.1186/s10194-021-01277-9.     

The impact of COVID-19 on anaesthesia and critical care services in the UK: a serial service evaluation*

Between October 2020 and January 2021, we conducted three national surveys to track anaesthetic, surgical and critical care activity during the second COVID-19 pandemic wave in the UK. We surveyed all NHS hospitals where surgery is undertaken. Response rates, by round, were 64%, 56% and 51%. Despite important regional variations, the surveys showed increasing systemic pressure on anaesthetic and peri-operative services due to the need to support critical care pandemic demands. During Rounds 1 and 2, approximately one in eight anaesthetic staff were not available for anaesthetic work. Approximately one in five operating theatres were closed and activity fell in those that were open. Some mitigation was achieved by relocation of surgical activity to other locations. Approximately one-quarter of all surgical activity was lost, with paediatric and non-cancer surgery most impacted. During January 2021, the system was largely overwhelmed. Almost one-third of anaesthesia staff were unavailable, 42% of operating theatres were closed, national surgical activity reduced to less than half, including reduced cancer and emergency surgery. Redeployed anaesthesia staff increased the critical care workforce by 125%. Three-quarters of critical care units were so expanded that planned surgery could not be safely resumed. At all times, the greatest resource limitation was staff. Due to lower response rates from the most pressed regions and hospitals, these results may underestimate the true impact. These findings have important implications for understanding what has happened during the COVID-19 pandemic, planning recovery and building a system that will better respond to future waves or new epidemics.     

Hydroxyurea effectiveness in children and adolescents with sickle cell anemia: A large retrospective,population‐based cohort

The clinical efficacy of hydroxyurea in patients with sickle cell anemia (SCA) has been well established. However, data about its clinical effectiveness in practice is limited. We evaluated the clinical effectiveness of hydroxyurea in a large pediatric population using a retrospective cohort, pre‐post treatment study design to control for disease severity selection bias. The cohort included children with SCA (SS, Sβ⁰thalassemia) who received care at Children's Healthcare of Atlanta (CHOA) and who initiated hydroxyurea in 2009‐2011. Children on chronic transfusions, or children with inadequate follow up data and/or children who had taken hydroxyurea in the 3 years prior were excluded. For each patient healthcare utilization, laboratory values, and clinical outcomes for the 2‐year period prior to hydroxyurea initiation were compared to those 2 years after initiation. Of 211 children with SCA who initiated hydroxyurea in 2009–2011, 134 met eligibility criteria. After initiation of hydroxyurea, rates of hospitalizations, pain encounters, and emergency department visits were reduced by 47% (<0.0001), 36% (P = 0.0001) and 43% (P < 0.0001), respectively. Average hemoglobin levels increased by 0.7 g/dl (P < 0.0001). Hydroxyurea effectiveness was similar across gender, insurance types and age, although there was a slightly greater reduction in hospitalizations in younger children. Am. J. Hematol. 92:77–81, 2017. © 2016 Wiley Periodicals, Inc.