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With increasing recognition of the high burden and impact of psoriatic arthritis (PsA) and the growing number of therapeutic options, there has been an intensifying focus on treatment strategy in recent years. In 2015, the Tight Control of Psoriatic Arthritis study confirmed the clinical benefit of using a treat-to-target approach in PsA. This randomised controlled trial found benefits in both arthritis and psoriasis disease activity as well as lower disease impact reported by patients, although participants allocated to tight control experienced a higher rate of serious adverse events. European and international recommendations support the use of a treat-to-target approach in PsA and have offered specific advice on how to do this using outcomes such as the minimal disease activity criteria. However, implementation of this approach in routine practice is low, with real-world data highlighting undertreatment as a result. Recent qualitative work with physicians in the UK has helped researchers to understand the barriers to implementation of treat-to-target in PsA. We now need to address these barriers, provide education and support to non-specialist clinicians in routine practice, and aid the translation of optimal care to the clinic.

Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of potentially life-threatening complications that occur after solid organ and bone marrow transplantation. Risk factors for acquiring PTLD are type of organ transplanted, age, intensity of immunosuppression, viral infections such as Epstein-Barr virus (EBV) and time after transplantation. Due to a dearth of well designed prospective trials, treatment for PTLD is often empirical, with reduction in immunosuppression accepted as the first step. Rituximab, a monoclonal antibody directed against the CD20 antigen of immature B cells, is often used as monotherapy after reduction in immunosuppression, although this is associated with a high risk of relapse if patients have at least one of the following risk factors: age greater than 60 years, elevated lactate dehydrogenase levels and Eastern Cooperative Oncology Group Score between 2 and 4. For such patients, rituximab should be considered in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), particularly if high-grade PTLD is present. Although widely prescribed, the use of ganciclovir for PTLD remains controversial as EBV-transformed cells lack the thymidine kinase necessary for ganciclovir activation. Newer antivirals that combine ganciclovir with activators of cellular thymidine kinase have shown promising results in preclinical studies. In the absence of controlled trials, surgery may be indicated for localized disease and radiotherapy for patients with impending spinal cord compression or disease localized to the central nervous system or orbit. Future interventions may include adoptive immunotherapy, intravenous immunoglobulin, mammalian target of rapamycin inhibitors, monoclonal antibodies to interleukin-6 and galectin-1, and even EBV vaccination. Although several trials are in progress, it is necessary to wait for the long-term outcome of these studies on risk of PTLD relapse. [PUBLICATION ABSTRACT]

Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of potentially life-threatening complications that occur after solid organ and bone marrow transplantation. Risk factors for acquiring PTLD are type of organ transplanted, age, intensity of immunosuppression, viral infections such as Epstein-Barr virus (EBV) and time after transplantation. Due to a dearth of well designed prospective trials, treatment for PTLD is often empirical, with reduction in immunosuppression accepted as the first step. Rituximab, a monoclonal antibody directed against the CD20 antigen of immature B cells, is often used as monotherapy after reduction in immunosuppression, although this is associated with a high risk of relapse if patients have at least one of the following risk factors: age greater than 60 years, elevated lactate dehydrogenase levels and Eastern Cooperative Oncology Group Score between 2 and 4. For such patients, rituximab should be considered in combination with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), particularly if high-grade PTLD is present. Although widely prescribed, the use of ganciclovir for PTLD remains controversial as EBV-transformed cells lack the thymidine kinase necessary for ganciclovir activation. Newer antivirals that combine ganciclovir with activators of cellular thymidine kinase have shown promising results in preclinical studies. In the absence of controlled trials, surgery may be indicated for localized disease and radiotherapy for patients with impending spinal cord compression or disease localized to the central nervous system or orbit. Future interventions may include adoptive immunotherapy, intravenous immunoglobulin, mammalian target of rapamycin inhibitors, monoclonal antibodies to interleukin-6 and galectin-1, and even EBV vaccination. Although several trials are in progress, it is necessary to wait for the long-term outcome of these studies on risk of PTLD relapse.

Sequential pattern mining is a technique of data mining whose objective is to identify statistically relevant patterns within a database with timerelated data. It has a wide range of applications in variety of domains like education, healthcare, bioinformatics, web usage mining, telecommunications, intrusion detection etc. At present, most of the real sequence databases are incremental in nature. So there is a need to explore incremental and distributed pattern mining algorithms. Periodic pattern mining is a technique to discover periodic pattern which may be a pattern that repeats itself after a specific time interval. It has a wide range of applications in weather prediction, stock market analysis, web usage recommendation etc. Moreover, uncertain frequent pattern mining has become a popular research domain among researchers, as many reallife databases at present consist of uncertain and incomplete data. In this paper, a novel attempt is made to incorporate a systematic literature review of stateoftheart techniques of sequential pattern mining which ranges from incremental pattern mining, periodic pattern mining and uncertain frequent pattern mining. Researchers in the field of pattern mining will find it very useful to get the information about various algorithms of different types of pattern mining.

Abstract Case report - Introduction Since the discovery of aquaporin-4 antibody in 2004, the association between visual loss and auto-immune disease has become increasingly apparent. Certainly, neuro-myelitis optica spectrum disorders (NMOSD) can co-exist with connective tissue disease (CTD). The complexity comes in trying to differentiate the two diagnoses. NMOSD feels like the tip of an iceberg with regards to autoimmune eye disease. When no specific antibody can be found, the clinical syndrome can only be described. Case report - Case description A 22-year-old female, with a history of childhood ITP presented with 4 months of myalgia, arthralgia, raised inflammatory markers (ESR 81, CRP 49) and weight loss. She had no clinical features suggestive of CTD. PET-CT demonstrated abnormal uptake associated with large joints. Small joint musculoskeletal ultrasound was normal. Initial ANA was borderline positive. 3 months later she presented with right-sided retro-orbital pain of 3 weeks' duration, followed by abrupt onset total visual loss in the right eye. The visual acuity in the left eye was also reduced. Ophthalmological examination revealed brilliant white optic atrophy of the right disc, with only perception of light. On the left, the disc and acuity were normal. MRI coronal STIR images of the orbits demonstrated inflammatory change in the peri-optic structures and signal change in the optic nerve anteriorly. Post-contrast images confirmed abnormal enhancement affecting the right optic nerve sheath and surrounding fat, some intrinsic enhancement of the optic nerve and some ill-defined enhancement of the left optic nerve sheath. Saggital T2 imaging of the spine confirmed no cord lesions. All disease-specific antibodies were negative (rheumatoid factor, CCP, connective tissue disease screen, dsDNA, ENA panel, anti-phospholipid, centromere, MOG, Aquaporin-4). HLA-B27 was negative. Complements were normal. HIV, syphilis and Lyme serology were all negative. She was initially treated with oral prednisolone and hydroxychloroquine with poor recovery of vision in the right eye. 2 years later, she developed a small deep left thalamic infarct, and was switched to azathioprine. Following a further episode of right eye pain associated with a rise in ESR, treatment was changed to injectable methotrexate resulting in resolution of arthralgia and normalisation of inflammatory markers. Surveillance MRI this year has identified a subtle area of high FLAIR signal in the right pons, with further interval scan awaited. Case report - Discussion Inflammatory eye disease is a developing field, with the relatively recent identification of aquaporin-4 and MOG antibodies in the context of neuromyelitis optica spectrum disorders. Case report - Key learning points This patient initially presented with an inflammatory arthritis, and then went on to develop abrupt onset visual loss. The rheumatologist should remain vigilant for development of optic peri-neuritis in CTD, and consider investigation if eye pain or discomfort develops. In NMOSD, aquaporin-4 (AQP4) antibodies are directed against the AQP4 channels on astrocytes. It is possible that optic peri-neuritis in this case may be due to inflammation in the optic nerve sheath caused by an as-yet unidentified antigen/antibody-mediated process. In patients presenting with CTD who develop optic neuritis or peri-neuritis, further evaluation for NMOSD is essential. AQP4 and MOG antibodies are now readily available and easily checked in routine practice. There appears to be an emerging association between NMOSD and CTD, and the rheumatologist should remain vigilant for the presence of dual pathology.

INTRODUCTION:Herbal and dietary supplements (HDS) are an important cause of liver injury. EmergeR weight loss supplement is advertised as a product which burns fat and stimulates weight loss. We report a case of acute severe cholestatic hepatitis after consumption of EmergeR in a 32 year-old man. This case highlights a previously unreported and important association between this supplement and hepatotoxicity and the importance of obtaining a through medication history including HDS.CASE DESCRIPTION/METHODS:A 32-year-old male presented to hepatology clinic for evaluation of jaundice and elevated liver tests. He was well until 1 week ago when he developed flu-like symptoms, fatigue, jaundice, pruritus, dark urine and pale stools. He denied other symptoms, recent travel, reported rare alcohol use and did not take any other medications. However, he started a new weight loss supplement, EmergeR 3 weeks ago and had normal liver tests prior (Table 1). Exam was remarkable for a BMI of 35 and scleral icterus. Liver tests were elevated with AST 987 IU/L, ALT 2305 IU/L, total bilirubin 7.2 mg/dl and INR 1.1 (Table 1). Testing for other viral causes was negative. Abdominal ultrasound showed hepatic steatosis. The patient was advised to stop EmergeR immediately and undergo liver tests and INR weekly. 4 weeks later (7 weeks after starting EmergeR), patient was asymptomatic with resolution of prior symptoms.DISCUSSION:Despite the widespread use and potential severe side effects associated with weight loss supplements, HDS do not require FDA approval prior to marketing.3 This emphasizes the need for physicians to report potential side effects associated with weight loss products as continued use without awareness or proper monitoring can lead to severe liver injury. To our knowledge, this is the first reported case of acute cholestatic hepatitis from EmergeR use. The temporal relationship of acute liver injury with the use of Emerge, improvement after withdrawal and absence of other possible causes strongly suggested that liver injury was secondary to this supplement. As EmergeR contains a variety of ingredients which may also be contaminated by an unknown toxic botanical or synthetic chemical, it remains unclear which component of EmergeR caused liver injury.4 As patients may exhibit subtle symptoms such as fatigue and nausea at the time of presentation, a high index of suspicion is required for diagnosis of HDS induced liver injury along with a through HDS use history.