Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Nasomaxillary frame translocation in medial maxillectomy

Medial maxillectomy is the standard operation for en bloc resection of the lateral nasal wall with portions of the maxillary and ethmoid sinuses. Although most reports comment on good to excellent cosmetic results, nasal collapse is a possible complication of the procedure and is best explained by the loss of lateral nasal wall support. To overcome this problem, we describe a technique with temporary mobilization of a bone frame around the ipsilateral pyriform aperture, including one nasal bone, and fixing it to its original position at the end of the operation

High-resolution computed tomographic evaluation of the cochlear capsule in otosclerosis: Relationship between densitometry and sensorineural hearing loss

Otosclerotic cochlear involvement is a rather frequent disease that has not been clearly understood in terms of diagnosis and management. Objective evaluation methods are needed to confirm the clinical diagnosis, investigate the relationship with hearing impairment, and validate the results of treatment. In this study two ear groups with bone conduction hearing loss (BCHL) were investigated with audiometry and high-resolution computed tomography (HRCT). In the first group (n = 22) the diagnosis of fenestral otosclerosis was confirmed at operation; the second group (n = 9) was composed of ears clinically suspicious for purely cochlear involvement. Additionally, a control group (n = 14) of otologically normal ears was also studied. Foci of demineralization were demonstrated in 58% of the ears in the two groups; the sensorineural hearing loss (SNHL) in those ears was significantly worse than in those with normal radiologic findings. Three methods of MCT densitometry were used to determine the abnormal regions in the cochlear capsule; the results suggested that hypodense regions were consistent with a greater degree of SNHL, in contrast to the hyperdense ones in ears with better cochlear reserves. Agreement was found between the location of the density change and the frequency topography of the SNHL; densitometric values were correlated with the bone conduction thresholds for certain frequencies. It is concluded that the spongiotic foci are responsible for the SNHL, since there was a correlation between their location and the SNHL frequency. The determination of better hearing in those ears with sclerotic foci supports the hypothesis that the sclerotic phase may not be a healing process following the spongiotic phase, and that it can be the first stage of the disease

MANAGEMENT OF PARAPHARYNGEAL SPACE CYSTS

Parapharyngeal space cysts, besides salivary gland origin may be derived from the first and dorsal portions of the second pharyngeal pouches. They are mucosal or epethelial lined structures with no external or visceral opening and always present on the lateral aspects of the nasopharyngeal wall

SPONTANEOUS REGRESSION OF A SYMPTOMATIC LARYNGOPYOCOELE

A laryngopyocoele is a rarely encountered neck mass which may cause respiratory obstruction. Spontaneous regression of an established symptomatic laryngopyocoele is an even more unusual situation, since most of the reported cases require immediate intervention for impending airway obstruction. A case of a laryngopyocoele showing spontaneous regression after antibiotic therapy is presented and the clinical aspects are reviewed

TEOAE monitoring of Cisplatin induced ototoxicity in guinea pigs: the protective effect of vitamin B treatment

Objective: To evaluate Cisplatin (CP) induced ototoxicity and the effects of vitamin B treatment on ototoxicity in guinea pigs by using the Transient Evoked Otoacoustic Emission (TEOAE) technique. Methods: Eleven guinea pigs were divided into two groups and they were tested by TEOAE before and after the experiment. A TEOAE response was regarded as positive when all of the following criteria were met: 1. The mean amplitude of the cochlear response in dB pe SPL should be greater than that of the noise in the external auditory canal; 2. The reproducibility rate of the response should be greater than 50%; 3. The stimulus stability rate should be greater than 65%; 4. The signal to noise ratio of the response in 1, 2, 3, 4 and 5 kHz band frequencies should be greater than 3 dB pe SPL in at least two bands. The first group included five animals that had only CP injections. Six animals in the second group received additional 0.2 ml/kg combined vitamin B preparations for 7 consecutive days. Thereafter, the right and left ears of all animals in both groups were tested by TEOAE. Results: TEOAE responses recorded from 22 ears of 11 guinea pigs before drug administrations showed that the responses with maximum amplitude were originated from the mid-frequency legion. Positive TEOAE responses were significantly reduced after CP administrations in both groups when compared with their respective pretreatment results (P < 0.01). However, vitamin B injections, in addition to a single large dose of CP, resulted in significantly better TEOAE responses than those obtained after only CP injections (P < 0.05). Conclusions: The routine use of TEOAE monitoring is recommended in clinical CP treatment protocols for the early detection and follow up of ototoxicity. Also, prospective clinical trials are needed in order to validate the protective effects of vitamin B treatment against ototoxicity. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved