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To reduce sleep-related infant deaths, the American Academy of Pediatrics (AAP) has identified safe infant sleep recommendations; however, it is unclear which training strategies to teach safe infant sleep practices are most effective. Since the AAP released updated safe sleep recommendations in 2016, no analysis of the safe infant sleep training literature has been conducted. The purpose of the present review was to evaluate the safe infant sleep training literature of relevant populations such as caregivers and medical personnel, and provide recommendations for future research. The overall efficacy of training strategies was found to be positive or mixed where experiments most commonly implemented an educational session, followed by use of instructional materials, distribution of safe materials, and hospital-wide policy change. Methodological limitations were also identified.

Both Legionella pneumophila and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause pneumonia. L. pneumophila is acquired from water sources, sometimes in healthcare settings. We report 2 fatal cases of L. pneumophila and SARS-CoV-2 co-infection in England. Clinicians should be aware of possible L. pneumophila infections among SARS-CoV-2 patients.

Immune-mediated necrotising myopathy (IMNM) is a recently described entity. We describe a cohort of South Australian IMNM patients in order to define the spectrum of disease, characterise features that distinguish IMNM from other idiopathic inflammatory myopathy (IIM) subtypes and identify factors associated with clinically severe disease. Subjects were identified from the South Australian Myositis Database(SAMD), a histologically defined registry. Consecutive muscle sections from patients with IMNM (n=62), other forms of IIM (n=60) and histologically normal muscle (n=17) were stained using immunohistochemistry and graded. Clinical information was collected from the SAMD and through retrospective chart review. IMNM patients displayed clinical and histological heterogeneity. While most (67%) were profoundly weak at presentation, 24% exhibited mild to moderate weakness and 9% had normal power. Histological myonecros is ranged from minor to florid. The amount of myofibre complement deposition was closely associated with clinical severity. Patients of Aboriginal and Torres Strait Islander heritage and those with anti-SRP auto antibodies present with a severe phenotype. Despite intense immunotherapy,few IMNM patients recovered full power at one year follow up. The identification of clinical, serological and histological features which are associated with severe forms of the disease may have diagnostic and therapeutic utility. Refereed/Peer-reviewed

Immune-mediated necrotising myopathy (IMNM)is a relatively recently described form of idiopathic inflammatory myopathy (IIM)that is characterised by progressive proximal weakness and few extra-muscular manifestations. Prominent myonecrosis, muscle fibre regeneration and a relative paucity of intramuscular lymphocytes are seen histologically. Immunological mechanisms are believed to underpin the pathogenesis, and intense immunotherapy is frequently required. Disease is often severe and neuromuscular recovery may be poor. Recently there has been an impressive international research effort to understand and characterise this emerging condition, although much remains unknown. Significant advances in the field include the discovery of specific autoantibodies, increased understanding of the risk factors, clinical characteristics and treatment options owing to a wealth of observational studies, and the development of novel classification criteria. Herein we review the current evidence regarding the pathophysiology, clinical presentation, histological features and serological profiles associated with this condition. Diagnostic approaches are discussed, including the role of muscle MRI and antibodies targeting 3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR)and signal-recognition peptide (SRP), and a review of current treatment recommendations is provided Refereed/Peer-reviewed

Objective To externally validate the European League Against Rheumatism/American College of Rheumatism (EULAR/ACR) classification criteria for idiopathic inflammatory myositis (IIM) and determine the optimal cut points for Australian patients. To determine the level of agreement with traditional criteria and assess the effect of including magnetic resonance imaging (MRI) and an extended myositis antibody panel as well as extending histological criteria to include myofiber invasion. Methods Data were collected on adult patients referred for muscle biopsy to two Australian teaching hospitals. Patients were scored for "risk of IIM" according to EULAR/ACR criteria, using clinician diagnosis as the gold standard. Results Overall, 87 of 204 patients had IIM. For patients with muscle biopsy, the optimal cut point of 5.25 (sensitivity 90%, specificity 89%) was lower than the EULAR/ACR cut point of 6.7, which in our cohort showed reduced sensitivity (71% vs 93%) but comparable specificity (89% vs 88%). We found moderate agreement between the EULAR/ACR criteria and Bohan and Peter (κ = 0.45, 95% confidence interval [CI] = 0.28, 0.62, P < 0.001) and Targoff (κ = 0.40, 95% CI = 0.23, 0.57, P < 0.001). Inclusion of MRI (area under curve [AUC] = 0.86, 95% CI = 0.79, 0.93) or non-Jo1 antibodies (AUC = 0.84, 95% CI = 0.77, 0.91) as covariates improved the probability of IIM diagnosis (AUC = 0.80, 95% CI = 0.75, 0.86). Extending histologic criteria to include myofiber invasion slightly improved sensitivity (75% vs 71%) with the same level of specificity (89% vs 89%). Conclusion Application of the EULAR/ACR criteria to an Australian cohort showed comparable specificity but lower sensitivity, and a lower optimal cut point. Inclusion of MRI or non-Jo1 antibodies as covariates may improve the accuracy of determining the probability of IIM diagnoses. Extending the histologic criteria to include myofiber invasion did not reduce specificity.

Objective Recent advances in cardiac MRI (CMR) and other diagnostic techniques have made it easier to identify subclinical cardiac inflammation and dysfunction in the idiopathic inflammatory myopathies (IIM). Herein, we systematically review the literature regarding cardiac involvement in IIM. Methods We searched Medline and EMBASE from 1990 to 2020 using keywords related to IIM and cardiac disease. We included English language studies in adults with any immune-mediated, inflammatory muscle pathology. Results We identified 10 425 potentially relevant abstracts, of which 29 were included. Most frequently these included patients with PM or DM without symptomatic myocarditis. Five categories of cardiac investigation were used in these patients: cardiac enzyme testing, ECG, transthoracic echocardiography, CMR and nuclear medicine testing. Patients with clinical myocarditis had universally abnormal cardiac troponin levels and ECG. Elevated cardiac troponin T was more common than cardiac troponin I and may correlate with disease activity, whereas cardiac troponin I was more specific for cardiac involvement. Non-specific ECG changes were common. The major finding on transthoracic echocardiography was abnormal ejection fraction. Gross systolic dysfunction was unusual, but subclinical systolic dysfunction was reported in several studies. Abnormal diastolic function was common and may be associated with disease duration. Late gadolinium enhancement (reflecting regional necrosis or scarring) and abnormal myocardial mapping parameters (reflecting myocardial inflammation, fibrosis and oedema) were frequently identified on CMR, suggesting significant subclinical myocardial pathology (despite typically normal ejection fraction). Conclusion Abnormal cardiac investigations are commonly found in asymptomatic IIM patients, which has potential prognostic and treatment implications.

This study evaluated the effectiveness of an adaptive, computer-based staff training software program called Train-to-Code (TTC) to teach the administration of a social skills intervention. The software program actively trained participants to identify whether video models illustrated each step of the procedure effectively or ineffectively. Multiple exemplars of each step of the social skills task analysis were represented. Most-to-least prompting as well as feedback and error correction were embedded into the software program and prompts were faded through seven levels as the participant reached criterion accuracy. A multiple-probe across participants design was used to evaluate the effectiveness of this program by comparing pre- and post-training in vivo probes conducted with a confederate learner. All participant scores increased from pre-training to post-training, indicating that Train-to-Code was effective at teaching administration of the social skills intervention. These results have implications for training staff in applied community settings. Due to Train-to-Code’s ability to be internet-based and to measure actual viewing performance, it has the potential for “distance training” deliveries.

Natural killer (NK) cells are a specialised population of innate lymphoid cells (ILCs) that help control local immune responses. Through natural cytotoxicity, production of cytokines and chemokines, and migratory capacity, NK cells play a vital immunoregulatory role in the initiation and chronicity of inflammatory and autoimmune responses. Our understanding of their functional differences and contributions in disease settings is evolving owing to new genetic and functional murine proof‐of‐concept studies. Here, we summarise current understanding of NK cells in several classic autoimmune disorders, particularly in rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE) and type 1 diabetes mellitus (T1DM), but also less understood diseases such as idiopathic inflammatory myopathies (IIMs). A better understanding of how NK cells contribute to these autoimmune disorders may pave the way for NK cell‐targeted therapeutics., In this review, we summarise current understanding of NK cells in several classic autoimmune disorders, particularly in rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE) and type 1 diabetes mellitus (T1DM), but also less understood diseases such as idiopathic inflammatory myopathies. We also discuss how a better understanding of the contribution of NK cells to these autoimmune disorders may pave the way for NK cell‐targeted therapeutics.

Introduction: High Mobility Group Box Protein 1 (HMGB1) is a DNA-binding protein that exerts inflammatory or pro-repair effects upon translocation from the nucleus. We postulate aberrant HMGB1 expression in immune-mediated necrotising myopathy (IMNM). Methods: Herein, we compare HMGB1 expression (serological and sarcoplasmic) inpatients with IMNM with that of other myositis subtypes using immunohistochemistry and ELISA. Results: IMNM (n = 62) and inclusion body myositis (IBM, n = 14) patients had increased sarcoplasmic HMGB1 compared with other myositis patients (n = 46). Sarcoplasmic HMGB1 expression correlated with muscle weakness and histological myonecrosis,inflammation, regeneration and autophagy. Serum HMGB1 levels were elevated inpatients with IMNM, dermatomyositis and polymositis, and those myositis patients with extramuscular inflammatory features. Discussion: Aberrant HMGB1 expression occurs in myositis patients and correlates with weakness. A unique expression profile of elevated sarcoplasmic and serum HMGB1 was detected in IMNM. Refereed/Peer-reviewed

To determine the presence and genotypic macrolide susceptibility of Mycoplasma amphoriforme, and the presence of Ureaplasma spp. and Mycoplasma fermentans among clinical samples from England previously investigated for Mycoplasma pneumoniae.Quantitative and conventional PCR methods were used to retrospectively screen a collection of 160 clinical samples previously submitted to Public Health England (PHE) for the detection of M. pneumoniae between October 2016 and December 2017. Samples which were positive for M. amphoriforme DNA were further investigated for mutations associated with genotypic macrolide resistance by sequencing domain V of the 23s rRNA.M. amphoriforme was detected in 10/160 samples (6.3%), Ureaplasma parvum was detected in 4/160 samples (2.5%), and M. fermentans was not detected in any samples (0/160). Of the nine individuals (two samples were from the same patient) in which M. amphoriforme was detected, eight were male (age range 10-60 years) and one was female (age range 30-40 years). One individual with cystic fibrosis was positive for both M. amphoriforme and U. parvum. All M. amphoriforme DNA was genotypically susceptible to macrolides.Mycoplasma amphoriforme was found in clinical samples, including lower respiratory tract samples of patients with pneumonia. In the absence of other respiratory pathogens, these data suggest a potential role for this organism in human disease, with no evidence of acquired macrolide resistance. Ureaplasma parvum was detected in cerebrospinal fluid and respiratory tract samples. These data suggest that there is a need to consider these atypical respiratory pathogens in future diagnostic investigations.

Antiphospholipid syndrome is an autoimmune condition, characterised by the persistent presence of antiphospholipid antibodies and either thrombosis or obstetric morbidity. The cornerstone of therapy is long-term anticoagulation to reduce morbidity and mortality; however, better understanding of the immunological pathways may direct us to develop future therapeutic strategies. We provide an overview of the current understanding of the immunopathogenesis of this perplexing condition and its associated morbidities and current evidence for some of the immunotherapeutic strategies.

Background:Autoantibodies targeting a muscle-specific autoantigen, four-and-a-half-LIM-domain 1 (FHL1), have been previously identified in patients with idiopathic inflammatory myopathies (IIM) (1).Objectives:The aim of this project was to determine the prevalence and associations of anti-FHL antibody in South Australian patients with histologically-confirmed IIM and in an autoimmune disease control (systemic sclerosis (SSc)).Methods:Sera from patients with IIM (n=267) from the South Australian Myositis Database (SAMD), and SSc (n=174) from the Australian Scleroderma Cohort Study (ASCS) followed at the Royal Adelaide Hospital, and healthy controls (HC, n=100) were analyzed for anti-FHL1 autoantibodies by Enzyme-Linked ImmunoSorbent Assay (ELISA). Clinical, serological and histological details were retrieved from the SAMD and the ASCS.Results:Autoantibodies to FHL1 were more frequent in patients with IIM (55/267, 20.5%) compared with SSc (18/174, 10%) (p+ patients compared with anti-FHL1- (p+ patients with inclusion body myositis (IBM) and immune-mediated necrotizing myopathy (IMNM). In 35/54 anti-FHL1+ patients, there were no other myositis-specific autoantibodies present. Anti-FHL1 autoantibodies in patients with SSc were associated with gastric antral vascular ectasia.Conclusion:Anti-FHL1 autoantibodies were detected in 20.5% of IIM patients. In IBM and IMNM, the presence of anti-FHL1-autoantibodies was associated with a severe myopathy as suggested by presence of dysphagia and muscle atrophy.References:[1]Albrecht I, Wick C, Hallgren A, Tjarnlund A, Nagaraju K, Andrade F, et al. Development of autoantibodies against muscle-specific FHL1 in severe inflammatory myopathies. J Clin Invest. 2015;125(12):4612-24.Disclosure of Interests:Angeles Shunashy Galindo-Feria: None declared, Begum Horuluoglu: None declared, Jessica Day: None declared, Catia Cerqueira: None declared, Susanna Proudman: None declared, Ingrid E. Lundberg Consultant of: Consulting fees from Corbus Pharmaceuticals, Inc, Grant/research support from: Research grants from Bristol Myers Squibb and Astra Zeneca, Vidya Limaye Consultant of: Scientific adviser for Actelion and Boehringer-Ingelheim, Grant/research support from: PI for clinical trials for Bayer, Boehringer-Ingelheim, Corbus, and CSL

We have read with great interest the article published by Jinnin et al , which was an external validation of sensitivity and specificity of the EULAR/ACR (European League Against Rheumatism / American College of Rheumatology) classification criteria for idiopathic inflammatory myopathies with a Japanese cohort. The title and article claim that this is the first external validation study. While this may be true for a Japanese cohort, our intention is to alert the readers to the earlier published validation studies that preceded this and help highlight the complete body of evidence that should be considered. The idiopathic inflammatory myopathies (IIMs) are a group of uncommon disorders with a potential for significant mortality and morbidity. Progress in the understanding and management of these disorders has been …

The Museums Victoria (NMV) Vertebrate Palaeontology Collection holds more than 130,000 specimens, including the single largest collection of vertebrate fossils from the state of Victoria, Australia. Accessioned specimens make up around one third of the collection; however, few of the other, unaccessioned specimens have been catalogued. Vertebrate fossil accession at NMV is carried out in three stages: registration under a permanent specimen number, entry into the database software catalogue Axiell EMu, and barcode-based location tracking using a handheld device linked to an online application (http://mvwise.museum.vic.gov.au). In the past, unregistered specimens have been catalogued or location- tracked only infrequently, and the scale of legacy subcollections makes full registration an impractical goal for unaccessioned specimens. Accurate knowledge of unaccessioned specimens is essential to estimate collection size and composition, and predict future resource needs. Where such knowledge is held by staff but not documented, there is a persistent risk of dissociation or loss. Further, having accessible digital records greatly enhances data discoverability for research and exhibition users. We describe an EMu-based workflow for unaccessioned specimens in the NMV Vertebrate Palaeontology Collection, which newly documents and tracks specimens without the time burden of prior accession protocols. Minimum-data EMu catalogue records are generated from a handheld MVWISE scanner (based on Apple mobile hardware), with photographs that include the specimen along with any existing metadata or context. These records are immediately linked to trackable barcodes associated with storage locations. Subsequently, relevant taxonomic, stratigraphic or historical information can be cross-referenced to catalogue records en masse, either directly or using import functions. This metadata is accessed efficiently from within Axiell EMu via the specimen photographs, rather than requiring a subsequent physical search. The risks mitigable by this project are discussed, as are reasons commonly cited for not accessioning specimens, and dilemmas and consequences arising from the new approach. We also provide guidance on the rates of data generation, the required and recommended resources to be used, and forecast practical benefits in discovery and use for the collection.

Hepcidin is the master regulator of systemic iron bioavailability in humans. This review examines primary research articles that assessed hepcidin during pregnancy and postpartum and report its relationship to maternal and infant iron status and birth outcomes; areas for future research are also discussed. A systematic search of the databases Medline and Cumulative Index to Nursing and Allied Health returned 16 primary research articles including 10 human and six animal studies. Collectively, the results indicate that hepcidin is lower during pregnancy than in a non-pregnant state, presumably to ensure greater iron bioavailability to the mother and fetus. Pregnant women with undetectable serum hepcidin transferred a greater quantity of maternally ingested iron to their fetus compared to women with detectable hepcidin, indicating that maternal hepcidin in part determines the iron bioavailability to the fetus. However, inflammatory states, including preeclampsia, malaria infection, and obesity were associated with higher hepcidin during pregnancy compared to healthy controls, suggesting that maternal and fetal iron bioavailability could be compromised in such conditions. Future studies should examine the relative contribution of maternal versus fetal hepcidin to the control of placental iron transfer as well as optimizing maternal and fetal iron bioavailability in pregnancies complicated by inflammation.

Magnetic resonance imaging (MRI) is an important tool in the evaluation of neuromuscular disorders. MRI accurately demonstrates muscle oedema, atrophy, subcutaneous pathology and fatty infiltration and also highlights the distribution of muscle involvement. This review examines the role of MRI in evaluation of the idiopathic inflammatory myopathies (IIMs), a heterogeneous group of autoimmune conditions characterised by muscle inflammation and a variety of extra-muscular manifestations. MRI has a clear role in aiding diagnosis of these conditions, guiding muscle biopsy, differentiating subtypes of IIM using a pattern-based approach, and monitoring disease activity in a longitudinal fashion. Whole body MRI is an emerging technique that offers several advantages over regional MRI, but is not currently widely available. We will also consider newer MRI techniques which provide detailed information regarding the metabolism, function and structure of muscle, although their use is restricted to research purposes at present. Refereed/Peer-reviewed

Refereed/Peer-reviewed

To the Editor: Legionella species are significant pathogens with most infections being caused by Legionella pneumoniae and presenting as Legionnaire disease or Pontiac fever1. Extrapulmonary legionellosis is uncommon and is often thought to arise from hematogenous spread after primary pulmonary infection2. To date, the extrapulmonary sites of infections that have been reported in the literature include spleen, kidneys, liver3, infective endocarditis4, myositis5, cellulitis, and cutaneous abscesses5. The majority of extrapulmonary Legionella infections have been described in immunocompromised patients. A 69-year-old female florist presented to hospital with 1 week of worsening pain and swelling of the right hand, having been treated in the community for presumed seronegative arthritis for the preceding 6 months. Her presentation 6 months earlier was with pain and swelling in her right hand and mild, transient symptoms in the left hand. Clinical examination at that time found synovitis in multiple proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints and palmar tenosynovitis in the right hand. Otherwise, joint examination was normal. The tenosynovitis was confirmed on ultrasound (US). She was treated with ceftriaxone, but failed to improve. … Address correspondence to Dr. L. Chou, Department of Rheumatology, Royal Melbourne Hospital, 300 Grattan St., Parkville, Melbourne, Australia 3050. E-mail: louisa.chou{at}monash.edu

We report a 78-year-old man who presented with rapidly progressive cerebellar ataxia, dysarthria and vertigo. MRI of the brain showed no evidence of infiltrative pathology in the posterior fossa. Cerebrospinal fluid analysis revealed an elevated protein and pleocytosis. He was subsequently diagnosed with squamous cell carcinoma of the lung on bronchoscopy. Paraneoplastic cerebellar degeneration (PCD) was diagnosed. To our knowledge, there are only two previously reported patients with PCD associated with squamous cell carcinoma of the lung.