Prostate cancer is one of the most common cancers in men and the global burden of
this disease is rising. Lifestyle modifications like smoking cessation, exercise and
weight control offer opportunities to decrease the risk of developing prostate cancer.
Early detection of prostate cancer by PSA screening remains controversial; yet, changes in
PSA threshold, frequency of screening, and addition of other biomarkers have potential to
minimise overdiagnosis associated with PSA screening. Several new biomarkers appear
promising in individuals with elevated PSA levels or those diagnosed with prostate cancer,
these are likely to guide in separating individuals who can be spared of aggressive
treatment from those who need it. Several pharmacological agents like 5α-reductase
inhibitors, aspirin etc. have a potential to prevent development of prostate cancer. In
this review, we discuss the current evidence and research questions regarding prevention,
early detection of prostate cancer and management of men either at high risk of prostate
cancer or diagnosed with low-grade prostate cancer.
Objective
Autoantibodies recognizing 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) are associated with statin exposure, the HLA allele DRB1*11:01, and necrotizing muscle biopsies in adult myositis patients. The aim of this study was to characterize the features of pediatric anti-HMGCR-positive myositis patients.
Methods
The sera of 440 juvenile myositis patients were screened for anti-HMGCR autoantibodies. Demographic and clinical features, responses to therapy, and HLA alleles were assessed. The features of anti-HMGCR-positive patients were compared to those of previously described adult patients with this autoantibody and to children with other myositis-specific autoantibodies (MSAs).
Results
Five (1.1%) of 440 patients were anti-HMGCR-positive; none had taken statin medications. Three patients had rashes characteristic of juvenile dermatomyositis and two patients had immune-mediated necrotizing myopathies. The median highest creatine kinase (CK) level of anti-HMGCR-positive subjects was 17,000 IU/L. All patients had severe proximal muscle weakness, distal weakness, muscle atrophy, joint contractures, and arthralgias, which were all more prevalent in HMGCR-positive subjects compared to MSA-negative patients or those with other MSAs. Anti-HMGCR-positive patients had only partial responses to multiple immunosuppressive medications and often a chronic course. The DRB1*07:01allele was present in all 5 patients compared to 26.25% of healthy controls (Pcorrected=0.01); none of the 5 pediatric patients had DRB1*11:01.
Conclusions
Compared to children with other MSAs, muscle disease appeared to be more severe in those with anti-HMGCR autoantibodies. Like adults, children with anti-HMGCR autoantibodies have severe weakness and high CK levels. In contrast to adults, anti-HMGCR-positive children have a strong association with HLA DRB1*07:01.
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