Statin-associated immune-mediated necrotizing myositis in Native Americans.

OBJECTIVES: Statin-associated immune-mediated necrotizing myopathy (IMNM) and idiopathic inflammatory myositis (IIM) are myopathies with overlapping features. This study compared the manifestations of IMNM to IIM in Native Americans. METHOD: Twenty-one Native American patients with inflammatory myopathy (IM) were characterized as to diabetes mellitus, hyperlipidaemia, statin exposure, myopathy diagnosis, muscle histology, autoimmune and myositis-specific autoantibodies, therapy and outcome. RESULTS: IM consisted of 52.4% IMNM, 42.9% IIM and 4.8% metabolic myopathy. IMNM vs IIM patients were older [61.6 years (s.d. 9.8) vs 39.8 (14.3)], diabetes mellitus (100% vs 55.6%), hyperlipidaemia (100% vs 33.3%), statin-exposure (100% vs 22.2%), creatine kinase [CK; 11 780 IU (s.d. 7064) vs 1707 (1658)], anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) antibodies (85.7% vs 11.1%) and necrotizing IM (81.8% vs 11.1%), but shorter disease duration [26.2 months (s.d. 395) vs 78.4 (47.9)], RP (9.1% vs 55.6%), cutaneous manifestations (0% vs 55.6%), ANA (18.2% vs 66.7%) or any autoantibody (18.2% vs 88.9%) (all P < 0.05). MRI abnormalities, histologic IM, myositis-specific autoantibodies, pulmonary hypertension, oesophageal dysfunction, interstitial lung disease, disability and persistently elevated CK were similar. IMNM vs IIM was treated more with IVIG (72.7% vs 11.1%; P = 0.009) and less with antimetabolites (45.5% vs 88.9%; P = 0.05) and rituximab (18.2% vs 55.6%; P = 0.09). CONCLUSIONS: IMNM may occur in Native Americans and is associated with diabetes mellitus, hyperlipidaemia, statin use and older age and is characterized by marked CK elevation, necrotizing myopathy and anti-HMGCR antibodies with few cutaneous or vascular manifestations.

Clinical and histological features of immune-mediated necrotising myopathy: A multi-centre South Australian cohort study.

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 myonecrosis 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 autoantibodies 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.

Statin-associated immune-mediated necrotising myopathy: a New Zealand case series showing possible overrepresentation in Pacific Islanders.

BACKGROUND: Statin-associated immmune-mediated necrotising myopathy (IMNM) is an emerging entity. Being an uncommon condition, our knowledge and understanding is largely based on case series. AIM: To review incident cases of statin-associated IMNM associated with anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) antibodies in a single New Zealand centre over a 2-year period. METHODS: Four incident cases of statin-associated IMNM were seen between 2014 and 2016. Their presentation, investigation, treatment and current response to treatment are summarised. Two of the four patients were Pacific Islanders despite a small Pacific Island population in the southern district health board. A literature search was performed focusing on the presentation, investigation and treatment of statin-associated IMNM and also genetic associations with this entity to determine whether Pacific Islanders may be at increased risk RESULTS: All four patients presented with profound weakness and recent exposure to atorvastatin. All proceeded to muscle biopsy. Two biopsies showed typical IMNM. One biopsy had mild changes, reported as possibly being compatible with anti-HMGCR antibodies. The final biopsy had features consistent with IMNM, with some features suggestive of polymyositis. Two recent studies have shown an association between anti-HMGCR antibodies and the HLA-DRB1*11:01 haplotype. Interestingly, HLA-DRB1 alleles (including HLA-DRB1*11:01) were observed to be among the most frequent alleles in a Pacific Island population study. CONCLUSION: This is the first case series of statin-associated IMNM with a focus on Pacific Islanders and raises the possibility that Pacific Islanders exposed to statins may be at increased risk of developing an immune-mediated myopathy.

Risk factors for complications following immediate tissue expander based breast reconstruction in Taiwanese population.

BACKGROUND/PURPOSE: Breast cancer patients in Asia show considerable disparities from Caucasian patients, such as younger age of onset and lower rates of smoking, obesity, and diabetes. Findings of prior studies regarding risk factors associated with complications in tissue expander may not hold for Asian populations, since most of these studies involved Caucasian patients. In this study, we surveyed risk factors in the Taiwanese population, providing additional evidence about the important differences and discuss the implications for clinical practice. METHODS: Patients who underwent immediate, two-stage, tissue expander breast reconstruction from December 2008 to August 2014 in the National Taiwan University Hospital, Taipei, Taiwan were included. Follow-up observations of all patients were conducted until December 2014. Complications occurring during the tissue expander stage were evaluated. Multivariate regression modeling was used to identify risk factors for complications. RESULTS: A total of 246 consecutive, immediate, smooth round tissue expander placements were performed for breast reconstruction. The most common complication was skin necrosis (4.9%), followed by wound dehiscence (4.1%). In the multivariate model, body mass index (BMI) ≥ 24 kg/m2 was the only risk factor that reached statistical significance (odds ratio: 2.41, 95% confidence interval: 1.17-4.96). CONCLUSION: We provided evidence that racial disparities have an impact on the risk factors for complications associated with tissue expander breast reconstruction. BMI≥24 kg/m2 was the only risk factor significantly associated with complications. Clinically, BMI≥24 kg/m2, rather than the standard definition of obesity (BMI > 30 kg/m2), may be a more suitable cutoff point for risk in patients of Asian ethnicity.

Association of genetic polymorphisms with histological grading of necroinflammation, staging of fibrosis, and liver function in Mexicans with chronic hepatitis C virus infection.

BACKGROUND/AIM: The aim of this work was to establish an association between the single-nucleotide polymorphisms (SNPs) of TGFB1 (rs1800471), AT (rs3789679), MMP-1 (rs17886084), MMP-3 (rs35068180), and PAI-1 (rs1799889) and the histological grading of necroinflammation, staging of hepatic fibrosis, and liver function in Mexican patients with advanced liver fibrosis due to chronic hepatitis C virus infection. METHODS: AT, MMP-1, MMP-3, and PAI-1 gene polymorphisms were analyzed by polymerase chain reaction in real time, whereas TGFB1 polymorphism was detected by polymerase chain reaction-based restriction fragment length polymorphism in 38 patients with established advanced liver fibrosis and 50 subjects from the general population. Grading of necroinflammation and staging of liver fibrosis were assessed by liver biopsy and graded according to modified histological activity index Ishak score. RESULTS: Regarding TGFB1 SNP, significant differences were found between G/G and G/C genotypes of patients with hepatic necroinflammation (P = 0.05) and hepatic fibrosis (P = 0.002). There were also significant differences among genotypes of patients with the AT SNP in hepatic necroinflammation (P = 0.01). The albumin-globulin ratio between genotypes of patients with the MMP-3 SNP gene showed significant differences (P = 0.02). CONCLUSION: Our findings demonstrate that a specific combination of genotypes associated with biochemical values and a histological high score determine more severe liver disease. The presence of the G/G genotype of TGFB1 SNP in patients was significantly associated with severity of liver necroinflammation and fibrosis. Patients with the G/G genotype of AT SNP were associated with severe necroinflammation. The albumin-globulin ratio was increased in patients with the 6A allele of MMP-3 SNP. These results might contribute to diagnosis and further establishment of liver disease treatment.

Influence of platelet reactivity and inflammation on peri-procedural myonecrosis in East Asian patients undergoing elective percutaneous coronary intervention.

BACKGROUND AND OBJECTIVES: The contribution of multiple risk factors to peri-procedural myocardial infarction (PMI) in East Asians remains controversial. To assess the influence of clinical or laboratory covariates on PMI in these patients. METHODS: Stable patients (n=341) undergoing elective percutaneous coronary intervention (PCI) were enrolled. Platelet reactivity was measured by conventional aggregometry and VerifyNow. Inflammation markers and lipid profile were determined by standard methods. PMI was defined according to Universal definition (troponin I or CK-MB ≥ 3 times the 99th percentile of the upper reference limit). RESULTS: PMI (defined by troponin I and CK-MB) occurred in 47 (13.8%) and 30 (8.8%) patients, respectively. There was no significant difference in ADP-induced platelet reactivity between patients with vs. without PMI. Patients with PMI (troponin I) had higher levels of 6 µg/mL collagen-induced platelet aggregation (PA) and VerifyNow 'BASE' compared with those without PMI. The combination of '6 µg/mL collagen-induced PA>40%'+'BASE>318' (odds ratio, 14.08; 95% confidence intervals, 1.68 to 111.11; p=0.015) or 'WBC>6550/mm(3)'+'C-reactive protein>2.3mg/L' (odds ratio, 7.75; 95% confidence intervals, 2.49 to 24.39; p<0.001) was associated with an increased risk of PMI (troponin I). The greatest likelihood ratio was observed when cholesterol, inflammation marker and platelet function were combined together. CONCLUSION: This is the first study to demonstrate that heightened platelet responsiveness to collagen and thrombin may be a risk factor for myonecrosis in patients undergoing elective PCI. The utility of the combining measures of platelet function, inflammation and cholesterol to enhance risk stratification and thus facilitate personalized therapy deserves further study.

More advanced hepatic fibrosis in hispanics with chronic hepatitis C infection: role of patient demographics, hepatic necroinflammation, and steatosis.

BACKGROUND AND AIMS: We sought to assess whether Hispanics have more advanced hepatitis C virus (HCV)-related liver disease than non-Hispanic whites (NHW) and to identify contributory factors. PATIENTS AND METHODS: Patients were recruited from the Los Angeles county hepatitis clinic. Liver fibrosis and necroinflammation (NI) were assessed by the Ishak scoring system. Hepatic steatosis was graded as 0-4. RESULTS: A total of 232 patients were evaluated, 63 NHW and 169 Hispanic. Hispanics were older and had a higher prevalence of blood transfusion (40%vs 21%), obesity (body mass index > 30) (47%vs 21%), diabetes mellitus (DM) (16%vs 5%), and hepatic steatosis (79%vs 47%), p < 0.02. Independent predictors of hepatic steatosis were Hispanic ethnicity (odds ratio [OR] 3.8, 95% CI 1.7-8.7, p= 0.001) and obesity (OR 5.7, 95% CI 2.3-14.1, p= 0.0002). Compared with NHW, Hispanics also had higher fibrosis stage (3.3 +/- 2 vs 2.3 +/- 6.9, p= 0.001), NI grade (6.4 +/- 1.8 vs 5.6 +/- 1.6, p= 0.002), and faster fibrosis progression/yr (0.14 +/- 0.09 vs 0.09 +/- 0.07, p= 0.0002). Presence of DM (OR 2.9, p= 0.02), grade 1-2 hepatic steatosis (OR 2.3, p= 0.03), AST/ALT > 1 (OR 4.3, p= 0.01), NI grade (OR 1.7, p < 0.0001), age at biopsy (OR 1.1, p < 0.0001), and serum bilirubin (OR 5.4, p < 0.0001) were independent predictors of fibrosis stage > or =4. CONCLUSION: This study confirms that Hispanics have more advanced hepatic fibrosis than NHW. This is related to older age, higher NI grade, and greater prevalence of hepatic steatosis and DM.