Erectile dysfunction as a predictor of two-year prognosis in acute myocardial infarction

  Background: Erectile dysfunction (ED) is a predictor or marker of coronary artery disease in patients at high risk of cardiovascular diseases. The aim of this study was to investigate the prevalence of ED in patients with acute myocardial infarction (AMI) and after 2 years of follow-up, and to determine the association between ED and the concentrations of the markers of inflammation, endothelial dysfunction and oxidative stress which were measured on the third day after hospital admission. Methods: The study included 80 patients aged 62.25 ± 10.47 years. The primary endpoints of interest were re-hospitalization due to cardiovascular causes and death during the 2 year period after hospital­ization. The Sexual Health Inventory for Men (SHIM) was assessed at the point of hospital discharge and 24 months thereafter. Results: 40.1% of patients had some degree of ED. The percentage of patients without ED increased (13.2%), while the percentage of patients with severe ED significantly decreased (14.7%) after 2 years. Patients with ED had significantly higher B-type natriuretic peptide (BNP) levels and decreased levels of nitric-oxide. During the 2 years of follow-up, 9 patients died (6.5% without ED, 68.6% with ED) (c2 = 7.19, p = 0.015). During the same time period, 22 (27.5%) patients were re-hospitalized due to cardiovascular causes, of whom 59.1% had ED at hospital admission (p < 0.05). Conclusions: Low levels of nitric-oxide were the best predictors of ED during AMI and after 2 years. ED predicted the worst outcomes of AMI: death and re-hospitalization. Lifestyle changes and nitric- -oxide donors could assist in the treatment of ED and in the improvement of long-term prognosis for AMI. (Cardiol J 2017; 24, 4: 393–402

Influence of peanut matrix on stability of allergens in gastric-simulated digesta: 2S albumins are main contributors to the IgE reactivity of short digestion-resistant peptides

Background: Most food allergens sensitizing via the gastrointestinal tract are stable proteins that are resistant to pepsin digestion, in particular major peanut allergens, Ara h 2 and Ara h 6. Survival of their large fragments is essential for sensitizing capacity. However, the immunoreactive proteins/peptides to which the immune system of the gastrointestinal tract is exposed during digestion of peanut proteins are unknown. Particularly, the IgE reactivity of short digestion-resistant peptides (SDRPs; lt 10 kDa) released by gastric digestion under standardized and physiologically relevant in vitro conditions has not been investigated. Objective: The aim of this study was to investigate and identify digestion products of major peanut allergens and in particular to examine IgE reactivity of SDRPs released by pepsin digestion of whole peanut grains. Methods: Two-dimensional gel-based proteomics and shotgun peptidomics, immunoblotting with allergen-specific antibodies from peanut-sensitized patients, enzyme-linked immunosorbent inhibition assay and ImmunoCAP tests, including far ultraviolet-circular dichroism spectroscopy were used to identify and characterize peanut digesta. Results: Ara h 2 and Ara h 6 remained mostly intact, and SDRPs from Ara h 2 were more potent in inhibiting IgE binding than Ara h 1 and Ara 3. Ara h 1 and Ara h 3 exhibited sequential digestion into a series of digestion-resistant peptides with preserved allergenic capacity. A high number of identified SDRPs from Ara h 1, Ara h 2 and Ara h 3 were part of short continuous epitope sequences and possessed substantial allergenic potential. Conclusion and Clinical Relevance: Peanut grain digestion by oral and gastric phase enzymes generates mixture of products, where the major peanut allergens remain intact and their digested peptides have preserved allergenic capacity highlighting their important roles in allergic reactions to peanut.This is the peer-reviewed version of the following article: Prodić, I.; Stanić-Vučinić, D.; Apostolović, D.; Mihailović, J.; Radibratović, M.; Radosavljević, J.; Burazer, L.; Milcić, M.; Smiljanić, K.; van Hage, M.; Ćirković-Veličković, T. Influence of Peanut Matrix on Stability of Allergens in Gastric-Simulated Digesta: 2S Albumins Are Main Contributors to the IgE Reactivity of Short Digestion-Resistant Peptides. Clinical and Experimental Allergy 2018, 48 (6), 731–740. [https://doi.org/10.1111/cea.13113]

Subpollen particles are rich carriers of major short ragweed allergens and NADH dehydrogenases: quantitative proteomic and allergomic study

Background: Short ragweed (Ambrosia artemisiifolia) allergies affect more than 36 million people annually. Ragweed pollen grains release subpollen particles (SPP) of respirable size upon hydration or a change in air electrical conditions. The aim of this study was to characterize the proteomes and allergomes of short ragweed SPP and total pollen protein extract (TOT), and compare their effects with those of standard aqueous pollen protein extract (APE) using sera from short ragweed pollen-sensitized patients. Methods: Quantitative 2D gel-based and shotgun proteomics, 1D and 2D immunoblotting, and quantitative ELISA were applied. Novel SPP extraction and preparation protocols enabled appropriate sample preparation and further downstream analysis by quantitative proteomics. Results: The SPP fraction contained the highest proportion (94%) of the allergome, with the largest quantities of the minor Amb a 4 and major Amb a 1 allergens, and as unique, NADH dehydrogenases. APE was the richest in Amb a 6, Amb a 5 and Amb a 3, and TOT fraction was the richest in the Amb a 8 allergens (89% and 83% of allergome, respectively). Allergenic potency correlated well among the three fractions tested, with 1D immunoblots demonstrating a slight predominance of IgE reactivity to SPP compared to TOT and APE. However, the strongest IgE binding in ELISA was noted against APE. New allergenic candidates, phosphoglycerate mutase and phosphoglucomutase, were identified in all the three pollen fractions. Enolase, UTP-glucose-1-phosphate uridylyltransferase and polygalacturonase were observed in SPP and TOT fractions as novel allergens of the short ragweed pollen, as previously described. Conclusion and Clinical Relevance: We demonstrated that the complete major (Amb a 1 and 11) and almost all minor (Amb a 3, 4, 5, 6, 8 and 9) short ragweed pollen allergen repertoire as well as NADH oxidases are present in SPP, highlighting an important role for SPP in allergic sensitization to short ragweed.This is the peer‐reviewed version of the article: Smiljanic, K.; Apostolovic, D.; Trifunovic, S.; Ognjenovic, J.; Perusko, M.; Mihajlovic, L.; Burazer, L.; Hage, M. van; Velickovic, T. C. Subpollen Particles Are Rich Carriers of Major Short Ragweed Allergens and NADH Dehydrogenases: Quantitative Proteomic and Allergomic Study. Clinical & Experimental Allergy 2017, 47 (6), 815–828.[https://doi.org/10.1111/cea.12874

A review of the risk and precipitating factors for spontaneous coronary artery dissection

IntroductionSpontaneous coronary artery dissection (SCAD) accounts for 1%–4% of cases of acute coronary syndrome (ACS). SCAD is caused by separation occurring within or between any of the three tunics of the coronary artery wall. This leads to intramural hematoma and/or formation of false lumen in the artery, which leads to ischemic changes or infarction of the myocardium. The incidence of SCAD is higher in women than in men, with a ratio of approximately 9:1. It is estimated that SCAD is responsible for 35% of ACS cases in women under the age of 60. The high frequency is particularly observed during pregnancy and in the peripartum period (first week). Traditional risk factors are rare in patients with SCAD, except for hypertension. Patients diagnosed with SCAD have different combinations of risk factors compared with patients who have atherosclerotic changes in their coronary arteries. We presented the most common so-called “non-traditional” risk factors associated with SCAD patients.Risk factors and precipitating disorders which are associated with SCADIn the literature, there are few diseases frequently associated with SCAD, and they are identified as predisposing factors. The predominant cause is fibromuscular dysplasia, followed by inherited connective tissue disorders, systemic inflammatory diseases, pregnancy, use of sex hormones or steroids, use of cocaine or amphetamines, thyroid disorders, migraine, and tinnitus. In recent years, the genetic predisposition for SCAD is also recognized as a predisposing factor. The precipitating factors are also different in women (emotional stress) compared with those in men (physical stress). Women experiencing SCAD frequently describe symptoms of anxiety and depression. These conditions could increase shear stress on the arterial wall and dissection of the coronary artery wall. Despite the advancement of SCAD, we can find significant differences in the clinical presentation between women and men.ConclusionWhen evaluating patients with chest pain or other ACS symptoms who have a low cardiovascular risk, particularly female patients, it is important to consider the possibility of ACS due to SCAD, particularly in conditions often associated with SCAD. This will increase the recognition of SCAD and the timely treatment of affected patients

Drugs for spontaneous coronary dissection: a few untrusted options

Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome that is often overlooked, misdiagnosed, and maltreated. Medical treatment poses a significant challenge because of the lack of randomized studies to guide treatment. The initial clinical presentation should guide medical and interventional management. Fibrinolytic agents and anticoagulants should be avoided because they could favor hematoma propagation. In patients with SCAD, antiplatelet therapy should be prescribed especially dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel, whereas potent P2Y12 inhibitors, e.g., ticagrelor and prasugrel, should be avoided. If a stent was used, DAPT should be continued for 12 months. Aspirin only can be an option for patients without “high-risk” angiographic features—thrombus burden, critical stenosis, and decreased coronary flow. Beta-blocking (BB) agents should be used to prevent recurrence of SCAD. There is a general agreement that angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, mineralocorticoid antagonists, and loop diuretics should be used in patients with SCAD experiencing the symptoms of heart failure and a decrease in left ventricular ejection fraction below 50%. Although without firm evidence, statins can be used in SCAD due to their pleiotropic properties. The results of a randomized trial on the use of BB and statins are awaited. Aggregation of data from national registries might point out truly beneficial medications for patients with SCAD

Surgical versus non-surgical interventions for treating patellar dislocation

Background: Patellar dislocation occurs when the patella disengages completely from the trochlear (femoral) groove. Following reduction of the dislocation, conservative (non-surgical) rehabilitation with physiotherapy may be used. Since recurrence of dislocation is common, some surgeons have advocated surgical intervention rather than non-surgical interventions. This is an update of a Cochrane review first published in 2011. Objectives: To assess the effects (benefits and harms) of surgical versus non-surgical interventions for treating people with primary or recurrent patellar dislocation. Search methods: We searched the Cochrane Bone, Joint and Muscle Trauma Group's Specialised Register, the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE, EMBASE, AMED, CINAHL, ZETOC, Physiotherapy Evidence Database (PEDro) and a variety of other literature databases and trial registries. Corresponding authors were contacted to identify additional studies. The last search was carried out in October 2014. Selection criteria: We included randomised and quasi-randomised controlled clinical trials evaluating surgical versus non-surgical interventions for treating lateral patellar dislocation. Data collection and analysis: Two review authors independently examined titles and abstracts of each identified study to assess study eligibility, extract data and assess risk of bias. The primary outcomes we assessed were the frequency of recurrent dislocation, and validated patient-rated knee or physical function scores. We calculated risk ratios (RR) for dichotomous outcomes and mean differences MD) for continuous outcomes. When appropriate, we pooled data. Main results: We included five randomised studies and one quasi-randomised study. These recruited a total of 344 people with primary (first-time) patellar dislocation. The mean ages in the individual studies ranged from 19.3 to 25.7 years, with four studies including children, mainly adolescents, as well as adults. Follow-up for the full study populations ranged from two to nine years across the six studies. The quality of the evidence is very low as assessed by GRADE (Grading of Recommendations Assessment, Development and Evaluation Working Group) criteria, with all studies being at high risk of performance and detection biases, relating to the lack of blinding. There was very low quality but consistent evidence that participants managed surgically had a significantly lower risk of recurrent dislocation following primary patellar dislocation at two to five years follow-up (21/162 versus 32/136; RR 0.53 favouring surgery, 95% confidence interval (CI) 0.33 to 0.87; five studies, 294 participants). Based on an illustrative risk of recurrent dislocation in 222 people per 1000 in the non-surgical group, these data equate to 104 fewer (95% CI 149 fewer to 28 fewer) people per 1000 having recurrent dislocation after surgery. Similarly, there is evidence of a lower risk of recurrent dislocation after surgery at six to nine years (RR 0.67 favouring surgery, 95% CI 0.42 to 1.08; two studies, 165 participants), but a small increase cannot be ruled out. Based on an illustrative risk of recurrent dislocation in 336 people per 1000 in the non-surgical group, these data equate to 110 fewer (95% CI 195 fewer to 27 more) people per 1000 having recurrent dislocation after surgery. The very low quality evidence available from single trials only for four validated patient-rated knee and physical function scores (the Tegner activity scale, KOOS, Lysholm and Hughston VAS (visual analogue scale) score) did not show significant differences between the two treatment groups. The results for the Kujala patellofemoral disorders score (0 to 100: best outcome) differed in direction of effect at two to five years follow-up, which favoured the surgery group (MD 13.93 points higher, 95% CI 5.33 points higher to 22.53 points higher; four studies, 171 participants) and the six to nine years follow-up, which favoured the non-surgical treatment group (MD 3.25 points lower, 95% CI 10.61 points lower to 4.11 points higher; two studies, 167 participants). However, only the two to five years follow-up included the clear possibility of a clinically important effect (putative minimal clinically important difference for this outcome is 10 points). Adverse effects of treatment were reported in one trial only; all four major complications were attributed to the surgical treatment group. Slightly more people in the surgery group had subsequent surgery six to nine years after their primary dislocation (20/87 versus 16/78; RR 1.06, 95% CI 0.59 to 1.89, two studies, 165 participants). Based on an illustrative risk of subsequent surgery in 186 people per 1000 in the non-surgical group, these data equate to 11 more (95% CI 76 fewer to 171 more) people per 1000 having subsequent surgery after primary surgery. Authors' conclusions: Although there is some evidence to support surgical over non-surgical management of primary patellar dislocation in the short term, the quality of this evidence is very low because of the high risk of bias and the imprecision in the effect estimates. We are therefore very uncertain about the estimate of effect. No trials examined people with recurrent patellar dislocation. Adequately powered, multi-centre, randomised controlled trials, conducted and reported to contemporary standards, are needed. To inform the design and conduct of these trials, expert consensus should be achieved on the minimal description of both surgical and non-surgical interventions, and the anatomical or pathological variations that may be relevant to both choice of these interventions and the natural history of patellar instability. Furthermore, well-designed studies recording adverse events and long-term outcomes are needed

Incremental value of high-sensitive troponin T in addition to the revised cardiac index for peri-operative risk stratification in non-cardiac surgery

Aims We aimed to evaluate the incremental value of high-sensitive troponin T (hsTnT) for risk prediction prior to non-cardiac surgery in comparison with the established revised cardiac index. Methods and results In this prospective, international multicentre observational study, 979 patients prior to non-cardiac surgery were enrolled. The endpoints were in-hospital mortality, the combination of death, acute myocardial infarction, cardiac arrest, cardio-pulmonary resuscitation, and acute decompensated heart failure. Twenty-five patients (2.6%) deceased and 36 (3.7%) of the patients experienced the combined endpoint. Cardiac markers were elevated in those patients who died when compared with survivors (hsTnT: 21 ng/L vs. 7 ng/L; P < 0.001; NT-proBNP: 576 pg/mL vs. 166 pg/mL; P < 0.001). Applying a cut-off for hsTnT of 14 ng/L and for NT-proBNP of 300 pg/mL, those patients with elevated hsTnT had a mortality of 6.9 vs. 1.2% (P < 0.001) and with elevated NT-proBNP 4.8 vs. 1.4% (P = 0.002). The highest AUC of the ROC curve was found for hsTnT as a predictor for mortality of 0.809. In a multivariate Cox regression analyses, hsTnT was the strongest independent predictor for the combined endpoint [HR 2.6 (95% CI: 1.3-5.3); P = 0.01]. Conclusion High-sensitive troponin T provides strong prognostic information in patients undergoing non-cardiac surgery incremental to the widely accepted revised cardiac inde

Purification and Characterization of Naturally Occurring Post-Translationally Cleaved Ara h 6, an Allergen That Contributes Substantially to the Allergenic Potency of Peanut

The 2S albumin Ara h 6 is one of the most important peanut allergens. A post-translationally cleaved Ara h 6 (pAra h 6) was purified from Virginia type peanuts, and the cleavage site was mapped using high-resolution mass spectrometry. Compared to intact Ara h 6, pAra h 6 lacks a 5-amino acid stretch, resembling amino acids 43−47 (UniProt accession number Q647G9) in the nonstructured loop. Consequently, pAra h 6 consists of two chains: an N-terminal chain of approximately 5 kDa and a C-terminal chain of approximately 9 kDa, held together by disulfide bonds. Intermediate post-translationally cleaved products, in which this stretch is cleaved yet still attached to one of the subunits, are also present. The secondary structure and immunoglobulin E (IgE) binding of pAra h 6 resembles that of intact Ara h 6, indicating that the loss of the nonstructured loop is not critical for maintaining the protein structure. Commercially available monoclonal and polyclonal immunoglobulin G (IgG) antibodies directed to Ara h 6 react with both intact Ara h 6 and pAra h 6, suggesting that the involved epitopes are not located in the area that is post-translationally cleaved. No differences between intact Ara h 6 and pAra h 6 in terms of IgE binding were found, suggesting that the area that is post-translationally cleaved is not involved in IgE epitopes either. For all main cultivars Runner, Virginia, Valencia, and Spanish, intact Ara h 6 and pAra h 6 occur in peanut at similar levels, indicating that pAra h 6 is a consistent and important contributor to the allergenic potency of peanut

Peptidomics of an in vitro digested α-Gal carrying protein revealed IgE-reactive peptides

The mammalian carbohydrate galactose-alpha 1,3-galactose (alpha-Gal) causes a novel form of food allergy, red meat allergy, where patients experience severe allergic reactions several hours after red meat consumption. Here we explored gastric digestion of alpha-Gal glycoproteins using an in vitro model. Bovine thyroglobulin (BTG), a typical alpha-Gal carrying glycoprotein, was digested with pepsin. The resulting peptides were characterised by SDS PAGE, immunoblot and ImmunoCAP using sera from 20 red meat allergic patients. During pepsinolysis of BTG, a wide range of peptide bands was observed of which 14 to 17 kDa peptides remained stable throughout the gastric phase. The presence of the alpha-Gal epitope on the obtained peptides was demonstrated by an anti-alpha-Gal antibody and IgE from red meat allergic patients. The alpha-Gal digests were able to inhibit up to 86% of IgE reactivity to BTG. Importantly, basophil activation test demonstrated that the allergenic activity of BTG was retained after digestion in all four tested patients. Mass spectrometry-based peptidomics revealed that these peptides represent mostly internal and C-terminal parts of the protein, where the most potent IgE-binding alpha-Gal residues were identified at Asn(1756), Asn(1850) and Asn(2231). Thus allergenic a-Gal epitopes are stable to pepsinolysis, reinforcing their role as clinically relevant food allergens