Bacterial Adherence and its Importance in Pathogenesis of Oral Lichen Ruber

Oralni lihen ruber (OLR) je kronična, mukokutana, autoimuna bolest. Etiologija te oralne bolesti još nije potpuno razjašnjena. Pretpostavlja se da još uvijek nepoznati strani antigeni adheriraju na površinu keratinocita i tako mijenjaju njihovu antigenu strukturu potičući nastanak autoimune reakcije. Svrha ovoga istraživanja bila je ustanoviti povezanost pretpostavljene hipteze i patogenskoga mehanizma kod OLR-a. Uzeti su citološki ubrisci (N = 30) s lezija OLR a (predhodno klinički i patohistološki potvređene dijagnoze) prije i poslije antibiotske terapije te uspoređeni s nalazima kontrolne skupine (N = 30) zdravih osoba. Uzorci su obojeni po Gramu te očitani nalazi ustanovljeni svjetlosnim mikroskopom. Dobiveni su rezultati pokazali znatno manji broj, za površinu keratinocita, adheriranih streptococa i drugih mikroorganizama nakon provedene antibiotske terapije te su uspoređeni s kontrolnom skupinom. Klinički nalaz također je bio bolji nakon provedene terapije. Ti rezultati pokazuju da bi mehanizam i uloga bakterijske adherencije na površini keratinocita oralne sluznice mogli biti ključna karika u patogenetskom mehanizmu kod oralnoga lihen rubera.Oral lichen ruber (OLR) is a chronic, mucocutaneous autoimmune disease. The etiology of this oral disease is still not clear. It is assumed that some uncharacteristic antigens adher to keratinocyte surfaces and in that way change antigenic structure of keratinocytes, which can influence autoimmunity reaction. The aim of this investigation was to detect how much that hypothesis can be included in classical pathogenesis of OLR. We took cytological smears (N = 30) of OLR lesions (clinical and pathohistologically confirmed) before and after antibiotic therapy and comparedthem with the control group (N =30) of healthy subjects. Detection of that observation was done by Gramm and light microscopy method. Results showed a significant lower number of streptococcus and other bacterial microorganisms, which adhered to keratinocytes surfaces, after antibiotic therapy and compared with the control group. The clinical status was also better. These results can be a key step in the pathogenesis of OLR, and the mechanism and role of bacterial adherence to oral keratinocytes can be considered

Bacterial Adherence and its Importance in Pathogenesis of Oral Lichen Ruber

Oralni lihen ruber (OLR) je kronična, mukokutana, autoimuna bolest. Etiologija te oralne bolesti još nije potpuno razjašnjena. Pretpostavlja se da još uvijek nepoznati strani antigeni adheriraju na površinu keratinocita i tako mijenjaju njihovu antigenu strukturu potičući nastanak autoimune reakcije. Svrha ovoga istraživanja bila je ustanoviti povezanost pretpostavljene hipteze i patogenskoga mehanizma kod OLR-a. Uzeti su citološki ubrisci (N = 30) s lezija OLR a (predhodno klinički i patohistološki potvređene dijagnoze) prije i poslije antibiotske terapije te uspoređeni s nalazima kontrolne skupine (N = 30) zdravih osoba. Uzorci su obojeni po Gramu te očitani nalazi ustanovljeni svjetlosnim mikroskopom. Dobiveni su rezultati pokazali znatno manji broj, za površinu keratinocita, adheriranih streptococa i drugih mikroorganizama nakon provedene antibiotske terapije te su uspoređeni s kontrolnom skupinom. Klinički nalaz također je bio bolji nakon provedene terapije. Ti rezultati pokazuju da bi mehanizam i uloga bakterijske adherencije na površini keratinocita oralne sluznice mogli biti ključna karika u patogenetskom mehanizmu kod oralnoga lihen rubera.Oral lichen ruber (OLR) is a chronic, mucocutaneous autoimmune disease. The etiology of this oral disease is still not clear. It is assumed that some uncharacteristic antigens adher to keratinocyte surfaces and in that way change antigenic structure of keratinocytes, which can influence autoimmunity reaction. The aim of this investigation was to detect how much that hypothesis can be included in classical pathogenesis of OLR. We took cytological smears (N = 30) of OLR lesions (clinical and pathohistologically confirmed) before and after antibiotic therapy and comparedthem with the control group (N =30) of healthy subjects. Detection of that observation was done by Gramm and light microscopy method. Results showed a significant lower number of streptococcus and other bacterial microorganisms, which adhered to keratinocytes surfaces, after antibiotic therapy and compared with the control group. The clinical status was also better. These results can be a key step in the pathogenesis of OLR, and the mechanism and role of bacterial adherence to oral keratinocytes can be considered

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

Background: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. Objectives: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. Methods: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was 13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with Pinteraction = 0.43. Conclusions: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402

Effects of alirocumab on cardiovascular and metabolic outcomes after acute coronary syndrome in patients with or without diabetes: a prespecified analysis of the ODYSSEY OUTCOMES randomised controlled trial

Background: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4–1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. Methods: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1–12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65–1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)—defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose—and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. Findings: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20–2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25–2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78–2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65–2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, −0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89–1·11). HRs were 0·97 (95% CI 0·87–1·09) for patients with prediabetes and 1·30 (95% CI 0·93–1·81) for those with normoglycaemia (pinteraction=0·11). Interpretation: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65–1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes. Funding: Sanofi and Regeneron Pharmaceuticals