A Large Cluster of New Onset Autoimmune Myositis in the Yorkshire Region Following SARS-CoV-2 Vaccination.

BACKGROUND: The novel SARS-CoV-2 vaccines partially exploit intrinsic DNA or RNA adjuvanticity, with dysregulation in the metabolism of both these nucleic acids independently linked to triggering experimental autoimmune diseases, including lupus and myositis. METHODS: Herein, we present 15 new onset autoimmune myositis temporally associated with SARS-CoV-2 RNA or DNA-based vaccines that occurred between February 2021 and April 2022. Musculoskeletal, pulmonary, cutaneous and cardiac manifestations, laboratory and imaging data were collected. RESULTS: In total, 15 cases of new onset myositis (11 polymyositis/necrotizing/overlap myositis; 4 dermatomyositis) were identified in the Yorkshire region of approximately 5.6 million people, between February 2021 and April 2022 (10 females/5 men; mean age was 66.1 years; range 37-83). New onset disease occurred after first vaccination (5 cases), second vaccination (7 cases) or after the third dose (3 cases), which was often a different vaccine. Of the cases, 6 had systemic complications including skin (3 cases), lung (3 cases), heart (2 cases) and 10/15 had myositis associated autoantibodies. All but 1 case had good therapy responses. Adverse event following immunization (AEFI) could not be explained based on the underlying disease/co-morbidities. CONCLUSION: Compared with our usual regional Rheumatology clinical experience, a surprisingly large number of new onset myositis cases presented during the period of observation. Given that antigen release inevitably follows muscle injury and given the role of nucleic acid adjuvanticity in autoimmunity and muscle disease, further longitudinal studies are required to explore potential links between novel coronavirus vaccines and myositis in comparison with more traditional vaccine methods.

Proposed Therapeutic Range of Treosulfan in Reduced Toxicity Pediatric Allogeneic Hematopoietic Stem Cell Transplant Conditioning: Results From a Prospective Trial.

Treosulfan is given off-label in pediatric allogeneic hematopoietic stem cell transplant. This study investigated treosulfan's pharmacokinetics (PKs), efficacy, and safety in a prospective trial. Pediatric patients (n = 87) receiving treosulfan-fludarabine conditioning were followed for at least 1 year posttransplant. PKs were described with a two-compartment model. During follow-up, 11 of 87 patients died and 12 of 87 patients had low engraftment (≤ 20% myeloid chimerism). For each increase in treosulfan area under the curve from zero to infinity (AUC(0-∞) ) of 1,000 mg hour/L the hazard ratio (95% confidence interval) for mortality increase was 1.46 (1.23-1.74), and the hazard ratio for low engraftment was 0.61 (0.36-1.04). A cumulative AUC(0-∞) of 4,800 mg hour/L maximized the probability of success (> 20% engraftment and no mortality) at 82%. Probability of success with AUC(0-∞) between 80% and 125% of this target were 78% and 79%. Measuring PK at the first dose and individualizing the third dose may be required in nonmalignant disease.

Adequacy of antenatal steroids, rather than place of birth, determines survival to discharge in extreme prematurity in North Queensland.

AIM: The Townsville Hospital cares for babies in a large geographical area, many of who are outborn, are of Aboriginal or Torres Strait Islander origin and have families who reside in areas of deprivation. This study examined the outcomes of babies born at all locations in North Queensland to assess the predictors of poor outcomes. METHODS: A retrospective observational study examined the survival of 313 babies born from 22 completed weeks gestation to 27 + 6 weeks gestation in North Queensland between January 2010 and December 2016. Additional analyses were performed for the 300 non-syndromal babies whose mothers usually resided in North Queensland, studying demographics of gestation, gender, birthweight, Indigenous status, regionality of maternal residence and adequacy of antenatal steroids. Short-term morbidities of intraventricular haemorrhage/periventricular leukomalacia (IVH/PVL), surgical necrotizing enterocolitis, retinopathy of prematurity requiring treatment and chronic lung disease and death were studied in relation to demographic factors and clinical treatment. RESULTS: Adequacy of steroids was significantly associated with a decreased mortality odds ratio of 2.872 (95% confidence interval 1.228-6.715), whilst no difference in outcome was seen by retrieval status or ethnic origin. Babies from remote locations were at increased risk for IVH/PVL, 2.334 (1.037-5.255). Male babies suffered more chronic lung disease, 1.608 (1.010-2.561), and IVH/PVL, 2.572 (1.215-5.445). Aboriginal and Torres Strait Islander babies were at lower risk of IVH/PVL. CONCLUSIONS: Steroids should be administered wherever there is any possibility of the provision of intensive care for periviable babies. Place of birth and ethnicity of mother should not unduly influence antenatal counselling.