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Nicoletta Machin, Margaret V Ragni Department of Medicine, University of Pittsburgh, Hemophilia Center of Western Pennsylvania, Pittsburgh, PA, USA Abstract: Fitusiran is an RNA interference therapeutic that targets antithrombin (AT) in the liver and interferes with AT translation by binding and degrading messenger RNA-AT, thereby silencing AT gene expression and preventing AT synthesis. In both preclinical and clinical studies, AT knockdown results in dose-dependent AT lowering when fitusiran is given weekly or monthly subcutaneously. In clinical trials, fitusiran dose escalation has resulted in improved thrombin generation and clinical hemostasis as measured by reduction in annualized bleed rate. Unlike currently licensed drugs, this improvement was not only in patients with hemophilia A but in also those with hemophilia B, with or without inhibitors. In dental and surgical procedures, fitusiran also provided perioperative hemostasis in association with AT lowering. Fitusiran is well tolerated, with minor local injection site reactions, but in one subject with severe hemophilia A, the concomitant use of daily high-dose factor VIII, inconsistent with trial guidance to avoid high, repeat doses of clotting factor, was associated with fatal thrombosis, suggesting the need for caution when using hemostatic agents in conjunction with fitusiran. Preclinical in vitro and in silico studies indicate improvement in thrombin generation in rare bleeding disorder plasmas, including in plasmas from patients with severe factors V, VII, and X deficiency, suggesting potential therapeutic benefit. Keywords: congenital bleeding disorder, clotting factor, fitusiran, mRNA, novel bypass

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We report the case of an elderly woman with primary Sjogren's syndrome and abnormal liver function tests indicative of primary biliary cirrhosis. She was found to have a raised serum angiotensin converting enzyme activity. We proceeded to study 21 further cases of Sjogren's syndrome to discover whether raised levels of this enzyme were a feature of Sjogren's syndrome. None of them had any features to suggested associated primary biliary cirrhosis. The cases included 12 with associated rheumatoid arthritis, two with systemic sclerosis, three with systemic lupus erythematosus and four with primary Sjogren's syndrome. In only two of these 21 patients was a raised serum angiotensin converting enzyme obtained, the elevation being modest. We conclude that a raised activity of the enzyme is not usually associated with primary or secondary Sjogren's syndrome, and that discovery of such an abnormality should prompt a search for an associated condition. [ABSTRACT FROM PUBLISHER]

Surveillance for Middle East Respiratory Syndrome (MERS) has been undertaken in the UK since September 2012. This study describes the surveillance outcomes in England from 2012 to 2018. This was a descriptive study using surveillance data. Local health protection teams in England report possible MERS cases to the National Infection Service with clinical and laboratory data. A total of 1301 possible MERS cases were identified in the study period. Five cases were laboratory-confirmed MERS. The majority of cases had travelled to Saudi Arabia (56.7%) and United Arab Emirates (25.9%). Fifty-four percent of cases were men and 43.7% were women. The majority of cases (65.1%) were aged 45 years or older. The number of tests increased in the period after Hajj each year. Laboratory-confirmed alternative diagnoses were available for 513 (39.4%) cases; influenza was the most common virus detected (n = 255, 52.4%). Our study highlights the importance of differential diagnosis of influenza and other respiratory pathogens and early influenza antiviral treatment. • Routine surveillance for Middle East Respiratory Syndrome has been carried out. • In total, 1301 possible cases were identified including five laboratory-confirmed cases. • Influenza was the most common pathogen detected for differential diagnosis. [ABSTRACT FROM AUTHOR]