Relapse after cessation of weekly tocilizumab for giant cell arteritis: a multicentre service evaluation in England.

OBJECTIVES: The National Health Service in England funds 12 months of weekly subcutaneous tocilizumab (qwTCZ) for patients with relapsing or refractory giant cell arteritis (GCA). During the COVID-19 pandemic, some patients were allowed longer treatment. We sought to describe what happened to patients after cessation of qwTCZ. METHODS: Multicentre service evaluation of relapse after stopping qwTCZ for GCA. The log-rank test was used to identify significant differences in time to relapse. RESULTS: 336 GCA patients were analysed from 40 centres, treated with qwTCZ for a median (interquartile range, IQR) of 12 (12-17) months. At time of stopping qwTCZ, median (IQR) prednisolone dose was 2 (0-5) mg/day. By 6, 12 and 24 months after stopping qwTCZ, 21.4%, 35.4% and 48.6% respectively had relapsed, requiring an increase in prednisolone dose to a median (IQR) of 20 (10-40) mg/day. 33.6% of relapsers had a major relapse as defined by EULAR. Time to relapse was shorter in those that had previously also relapsed during qwTCZ treatment (P = 0.0017); in those not in remission at qwTCZ cessation (P = 0.0036); and in those with large vessel involvement on imaging (P = 0.0296). Age ≥65, gender, GCA-related sight loss, qwTCZ treatment duration, TCZ taper, prednisolone dosing, and conventional synthetic DMARD use were not associated with time to relapse. CONCLUSION: Up to half our patients with GCA relapsed after stopping qwTCZ, often requiring a substantial increase in prednisolone dose. One third of relapsers had a major relapse. Extended use of TCZ or repeat treatment for relapse should be considered for these patients.

Outcomes of patients with subarachnoid haemorrhage admitted to Australian and New Zealand intensive care units following a cardiac arrest.

OBJECTIVES: To describe the characteristics and outcomes of adults with a subarachnoid haemorrhage (SAH) admitted to Australian and New Zealand intensive care units (ICUs) with a cardiac arrest in the preceding 24 hours. DESIGN: Retrospective cohort study. SETTING: Study data from 144 Australian and New Zealand ICUs were obtained from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database. PARTICIPANTS: A total of 439 of 11 047 (3.9%) patients admitted to an ICU with a SAH had a documented cardiac arrest in the 24 hours preceding their ICU admission. The mean age of patients with SAH and a preceding cardiac arrest was 55.3 years (SD, 13.7) and 251 of 439 (57.2%) were female. MAIN OUTCOME MEASURES: The primary outcome of interest was in-hospital mortality. Key secondary outcomes were ICU mortality, ICU and hospital lengths of stay, the proportion of patients discharged home. RESULTS: SAH patients with a history of cardiac arrest preceding ICU admission had a higher mortality rate (81.5% v 23.3%; P < 0.0001) and a lower rate of discharge home (4.6% v 37.0%; P < 0.0001) compared with patients with SAH who did not have a cardiac arrest. Among patients with SAH who had a cardiac arrest and survived, 20 of 81 (24.7%) were discharged home. In SAH patients with cardiac arrest, having a GCS of 3, the Australian and New Zealand Risk of Death score, and being admitted to ICU for palliative care or organ donation were significant predictors of in-hospital death. CONCLUSIONS: Almost one in five SAH patients who had a documented cardiac arrest in the 24 hours preceding ICU admission to an Australian and New Zealand ICU survived to hospital discharge, with around a quarter of these survivors discharged home. The neurological outcomes of these patients are uncertain, and understanding the burden of disability in survivors is an important area for further research.

Ventriculoperitoneal Shunt Malfunction Due to a Fibrous Capsule Obstructing the Peritoneal Catheter.

Ventriculoperitoneal shunt obstruction is a common neurosurgical condition. Obstruction of the peritoneal catheter is less common than other sites of blockage in the system. We present a case of a ventriculoperitoneal shunt blockage caused by a sheath of hyalinised fibrous tissue that had encased the distal side slits of the peritoneal catheter resulting in sub-total blockage. The patient made a complete recovery following the removal of this fibrous tissue from the distal peritoneal catheter without the need to revise the entire shunt.

A tolerogenic role for Toll-like receptor 9 is revealed by B-cell interaction with DNA complexes expressed on apoptotic cells.

Intracellular protein complexes containing nucleic acids are common targets of autoantibodies in many autoimmune diseases. Central tolerance to these antigens is incomplete, yet nucleosomal DNA is expressed on the surface of cells dying by apoptosis. It is commonly believed that autoimmunity is prevented by the rapid uptake of apoptotic cells (ACs) by neighbors or professional phagocytes to which they deliver anti-inflammatory signals. Self-reactive, innate-like B cells contact and are selected by intracellular antigens expressed on ACs; however, how self-tolerance is maintained is not well understood. Here we report that IL-10 production by B cells, stimulated by contact with ACs, results from the engagement of Toll-like receptor 9 (TLR9) within the B cell after recognition of DNA-containing complexes on the surface of ACs. Until now, TLR9 ligation has been considered an inflammatory signal, but we have confirmed a hitherto unexpected immunoregulatory role by demonstrating the absence of the protective effect of ACs during experimental autoimmune encephalitis (EAE) in TLR9-deficient mice. Human circulating CD27(+) B cells also respond to DNA-bearing ACs, but not to DNase-treated cells, by secreting IL-10. Chronic autoimmune disease may arise if this tolerance mechanism is not reimposed after episodes of inflammation, or if the regulatory B-cell response is subverted.