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Polycythemia Vera (PV) is a myeloproliferative neoplasm driven by activating mutations in JAK2 that result in unrestrained erythrocyte production, increasing patients’ hematocrit and hemoglobin concentration, placing them at risk of life-threatening thrombotic events. Our GWAS of 440 PV cases and 403,351 controls utilising UK Biobank data found that SNPs in HFE known to cause hemochromatosis are highly associated with PV diagnosis, linking iron regulation to PV. Analysis of the FinnGen dataset independently confirmed over-representation of homozygous HFE mutations in PV patients. HFE influences expression of hepcidin, the master regulator of systemic iron homeostasis. Through genetic dissection of PV mouse models, we show that the PV erythroid phenotype is directly linked to hepcidin expression: endogenous hepcidin upregulation alleviates erythroid disease whereas hepcidin ablation worsens it. Further, we demonstrate that in PV, hepcidin is not regulated by expanded erythropoiesis but is likely governed by inflammatory cytokines signalling via GP130 coupled receptors. These findings have important implications for understanding the pathophysiology of PV and offer new therapeutic strategies for this disease.

Iron is a highly important metal ion cofactor within the human body, necessary for haemoglobin synthesis, and required by a wide range of enzymes for essential metabolic processes. Iron deficiency and overload both pose significant health concerns and are relatively common world-wide health hazards. Effective measurement of total iron stores is a primary tool for both identifying abnormal iron levels and tracking changes in clinical settings. Population based data is also essential for tracking nutritional trends. This review article provides an overview of the strengths and limitations associated with current techniques for diagnosing iron status, which sets a basis to discuss the potential of a new serum marker – ferritin-bound iron – and the improvement it could offer to iron assessment.

BACKGROUND Bone marrow biopsy (BMB) is an accepted investigation in fever of unknown origin (FUO) to uncover haematological malignancies, such as lymphoma, and sometimes infections. With the advance in imaging modalities, such as 18-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to identify the focus of lymphoma, BMB may not contribute to the diagnosis when there are no other clinical features to suggest an underlying haematological disease. AIM To investigate the utility of BMB in determining the cause of FUO, when there are no other indications for BMB. METHODS Medical records of adult patients who had BMB performed for FUO or febrile illness from 1 January 2005 to 31 December 2014 in four metropolitan tertiary hospitals in Melbourne, Australia were reviewed. Patients with other concurrent indications for BMB, known human immunodeficiency virus infection and previously diagnosed connective tissue diseases were excluded. RESULTS Seventy-three patients were included in the study. Fifty-one patients had a final diagnosis for fever (systemic inflammatory diseases, infective, malignancy or other) while 22 patients had no diagnoses. In only 10 patients (13.7%) did BMB contribute to the diagnosis, finding either malignancy or granulomata. However, all these diagnoses could have been made without BMB. Two patients with diffuse large B-cell lymphoma had normal BMB. FDG-PET was helpful in making a diagnosis in eight (25%) out of 32 patients. CONCLUSION Performing BMB in patients with FUO and no other haematological abnormalities is of very limited value, and other investigations, such as FDG-PET, may be more likely to help establish a definitive diagnosis.

Prevalence of skin sores and scabies in remote Australian Aboriginal communities remains unacceptably high, with Group AStreptococcus(GAS) the dominant pathogen. We aim to better understand the drivers of GAS transmission using mathematical models. To estimate the force of infection, we quantified the age of first skin sores and scabies infection by pooling historical data from three studies conducted across five remote Aboriginal communities for children born between 2001 and 2005. We estimated the age of the first infection using the Kaplan–Meier estimator; parametric exponential mixture model; and Cox proportional hazards. For skin sores, the mean age of the first infection was approximately 10 months and the median was 7 months, with some heterogeneity in median observed by the community. For scabies, the mean age of the first infection was approximately 9 months and the median was 8 months, with significant heterogeneity by the community and an enhanced risk for children born between October and December. The young age of the first infection with skin sores and scabies reflects the high disease burden in these communities.

Objective To quantify the childhood infectious disease burden and antibiotic use in the Northern Territory's East Arnhem region through synthesis and analysis of historical data resources. Methods We combined primary health clinic data originally reported in three separate publications stemming from the East Arnhem Healthy Skin Project (Jan-01 to Sep-07). Common statistical techniques were used to explore the prevalence of infectious conditions and the seasonality of infections, and to measure rates of antibiotic use. Results There was a high monthly prevalence of respiratory (mean: 32% [95% confidence interval (CI): 20%, 34%]) and skin (mean: 20% [95%CI: 19%, 22%]) infectious syndromes, with upper respiratory tract infections (mean: 29% [95%CI: 27%, 31%]) and skin sores (mean: 15% [95%CI: 14%, 17%]) the most common conditions. Antibiotics were frequently prescribed with 95% (95%CI: 91%, 97%) of children having received at least one antibiotic prescription by their first birthday, and 47% having received six antibiotic prescriptions; skin sores being a key driver. Conclusions Early life infections drive high antibiotic prescribing rates in remote Aboriginal communities. Implications for public health: Eliminating skin disease could reduce antibiotic use by almost 20% in children under five years of age in this population.

Neurolymphomatosis (NL) is a rare presentation of lymphoma or leukemic infiltration of cranial or peripheral nerves. It is distinct from subarachnoid seeding of lymphoma as well as perineural tumour seen in epidural lymphoma. This rare condition has been reported mainly in oncology literature. Imaging features of solitary nerve involvement mimics, among others, peripheral nerve sheath tumours. We present the MRI and (18) fluorodeoxyglucose positron emission tomography ((18) FDG-PET) features of three cases of NL. MRI demonstrated variable appearances: infiltrative mass displacing neural fascicles, diffuse thickening and enhancement, and thickening of individual neural fascicles. (18) FDG-PET demonstrated avid uptake in all cases, two of which revealed skip lesions of the same nerve. The diagnosis of NL was confirmed by uncomplicated CT-guided biopsy of the affected sciatic nerve in one patient.

Background: The most common skin infections affecting children in remote Aboriginal communities are scabies and impetigo. Group A streptococcal skin infections are linked to the high rates of heart and renal disease occurring in Aboriginal Australians. Methods: A retrospective review of medical records was conducted in a primary health care centre in the East Arnhem region of the Northern Territory. Data was collected from all presentations to the clinic in the first 2 years of life for 99 children born between 2001 and 2005 as a component of the East Arnhem Regional Healthy Skin Project. Results: The median number of presentations to the clinic in the first 2 years of life was 32. Skin disease was recorded in 22% of all presentations. By 1 year of age 82% of children had presented to the clinic with their first episode of impetigo and 68% with their first episode of scabies. Antibiotics were administered to 49% of children with impetigo. Conclusion: Skin infections are a major reason for presentation to primary health clinics and contribute to the high disease burden experienced by children in the first 2 years of life. This high frequency of presentation provides multiple opportunities for intervention and monitoring.

Background Skin sores caused by Group A streptococcus (GAS) infection are a major public health problem in remote Aboriginal communities. Skin sores are often associated with scabies, which is evident in scabies intervention programs where a significant reduction of skin sores is seen after focusing solely on scabies control. Our study quantifies the strength of association between skin sores and scabies among Aboriginal children from the East Arnhem region in the Northern Territory. Methods and results Pre-existing datasets from three published studies, which were conducted as part of the East Arnhem Healthy Skin Project (EAHSP), were analysed. Aboriginal children were followed from birth up to 4.5 years of age. Self-controlled case series design was used to determine the risks, within individuals, of developing skin sores when infected with scabies versus when there was no scabies infection. Participants were 11.9 times more likely to develop skin sores when infected with scabies compared with times when no scabies infection was evident (Incidence Rate Ratio (IRR) 11.9; 95% CI 10.3–13.7; p1 year (IRR 0.8; 95% CI 0.7–0.9). Conclusion The association between scabies and skin sores is highly significant and indicates a causal relationship. The public health importance of scabies in northern Australia is underappreciated and a concerted approach is required to recognise and eliminate scabies as an important precursor of skin sores., Author summary Skin sores, also known as impetigo, are highly contagious bacterial skin infections, which are found commonly in school children and occasionally in adults. Skin sores are prevalent in disadvantaged or resource-poor settings. In Australia, about two thirds of Aboriginal children suffer from skin sores by their first birthday. If untreated or treated poorly, skin sores can eventually cause heart and kidney problems. It is also believed that scabies, another common skin infection in Aboriginal children, can increase the risk of developing skin sores by allowing the bacteria to enter the skin more easily through breaks in the skin. Our research explored the following: if scabies is a risk factor for skin sores then what is the strength of the association between the two conditions.

We describe the case of a 35-year-old man presenting with thrombotic microangiopathy (TMA) and renal impairment following, as he later disclosed, intravenous injection of oral formulation tamper-resistant extended-release oxycodone hydrochloride (Oxycontin). Recurrent misuse of this agent was associated with relapsing TMA despite treatment with terminal complement inhibitor eculizumab. Cases of TMA have been reported in the USA in association with intravenous misuse of extended-release oxymorphone (Opana ER) after the introduction of a new non-crushable formulation in 2012. There are two reported accounts of TMA associated with tamper-resistant Oxycontin, which became available in Australia in 2014. This is the first documented case in which eculizumab was used. This case illustrates the practical diagnostic challenges in identifying TMA disorders, and the importance of a detailed drug history. It also highlights the need to clarify what role, if any, eculizumab therapy has in cases of drug-associated TMA.

Resumen Carga de morbilidad y visitas a consultorios entre los ninos pequenos en comunidades aborigenes remotas del norte de Australia Objetivo Determinar la frecuencia de visitas y la carga de morbilidad infecciosa en los servicios de atencion primaria (AP) entre los ninos pequenos en dos comunidades aborigenes remotas de zonas tropicales del norte de Australia.Metodos Se estudio a una poblacion de ninos que habian nacido despues del 1 de enero de 2001 y residian en la zona al 30 de septiembre de 2005, tras obtener el consentimiento informado oportuno. Se examinaron los datos clinicos correspondientes a todas las visitas realizadas entre el 1 de enero de 2002 y el 30 de septiembre de 2005. Entre los datos recopilados figuraban el motivo de la visita (si era un proceso infeccioso), la prescripcion de antibioticos y la posible derivacion a un hospital.Resultados Se consideraron en total 7273 visitas a consultorios de 174 ninos de 0 a 4,75 anos, el 55% de los cuales eran varones. La tasa mediana de visitas por nino y ano fue de 16 (23 en el primer ano de vida). Las infecciones de las vias respiratorias superiores (32%) y las infecciones cutaneas (18%) fueron las causas infecciosas mas frecuentes de visita al consultorio. Las primeras visitas por sarna o heridas cutaneas presentaban un pico a la edad de dos meses. Al ano de edad, el 63% y el 69% de los ninos habian acudido con sarna y heridas cutaneas, respectivamente.Conclusion Los ninos aborigenes estudiados hicieron como promedio unas dos visitas al mes a los centros de atencion primaria durante su primer ano de vida. Esa elevada tasa refleja la carga de morbilidad existente, la voluntad de la poblacion aborigen de usar los servicios de salud y el gran volumen de trabajo a que deben hacer frente esos servicios. La sarna y las heridas cutaneas siguen siendo problemas sanitarios importantes en esa poblacion, y el estudio pone de relieve por primera vez que esas afecciones suponen una carga ya en los primeros meses de vida, de modo que, para conseguir reducir la alta morbilidad infecciosa en esa poblacion, las estrategias de prevencion y tratamiento deben abarcar el periodo neonatal.