Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging.

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. A total of 917 coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22 to 50] vs 29 [21 to 41], p <0.001) was significantly higher and QFR (0.92 [0.78 to 0.99] vs 0.97 [0.91 to 0.99], p <0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (area under the curve of receiver operating characteristic [AUCROC] 0.632 [95% confidence interval [CI] 0.589 to 0.674], p <0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669 to 0.784], p <0.0001, p Value for AUCROC comparison = 0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p Value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

Prognostic role of discordance between quantitative flow ratio and visual estimation in revascularization guidance.

Aims: Revascularization guided by functional severity has presented improved outcomes compared with visual angiographic guidance. Quantitative flow ratio (QFR) is a reliable angiography-based method for functional assessment. We sought to investigate the prognostic value of discordance between QFR and visual estimation in coronary revascularization guidance. Methods and results: We performed offline QFR analysis on all-comers undergoing coronary angiography. Vessels with calculated QFR were divided into four groups based on the decision to perform or defer percutaneous coronary intervention (PCI) and on the QFR result, i.e.: Group A (PCI-, QFR > 0.8); Group B (PCI+, QFR ≤ 0.8); Group C (PCI+, QFR > 0.8); Group D (PCI-, QFR ≤ 0.8). Patients with at least one vessel falling within the disagreement groups formed the discordance group, whereas the remaining patients formed the concordance group. The primary endpoint was the composite endpoint of cardiovascular death, myocardial infarction, and ischaemia-driven revascularization. Overall, 546 patients were included in the study. Discordance between QFR and visual estimation was found in 26.2% of patients. After a median follow-up period of 2.5 years, the discordance group had a significantly higher rate of the composite outcome (hazard ratio: 3.34, 95% confidence interval 1.99-5.60, P < 0.001). Both disagreement vessel Groups C and D were associated with increased cardiovascular risk compared with agreement Groups A and B. Conclusion: Discordance between QFR and visual estimation in revascularization guidance was associated with a worse long-term prognosis. Our results highlight the importance of proper patient selection for intervention and the need to avoid improper stent implantations when not dictated by a comprehensive functional assessment.

Diagnostic performance of quantitative flow ratio in non-ST elevation acute coronary syndromes in comparison to non-hyperemic pressure ratios: a prospective study.

Quantitative flow ratio (QFR) is a new angiography-based coronary physiology tool aimed to evaluate functional relevance of intermediate coronary lesions. Aim of the study is to assess diagnostic performance of QFR in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) in comparison to currently used non-hyperaemic pressure ratios (NHPRs). In this prospective, single-centre study, coronary physiology of intermediate coronary stenoses of non-culprit vessels in patients presenting with NSTE-ACS was evaluated using NHPRs (iFR, DFR or RFR). Subsequently, QFR was computed offline by a QFR analyst blinded to the NHPR results. Diagnostic performance of QFR was assessed in comparison to NHPRs as reference standard. A total of 60 vessels with intermediate coronary stenoses was investigated. The NHPRs were used as follows: RFR 38%, DFR 47% and iFR 15% of the cases. The NHPR result was positive, showing significant lesion, in 19 cases. A significant correlation was found between NHPR and QFR (r = 0.84, p < 0.001). Classification agreement of the two methods (95%) and diagnostic performance of QFR in comparison to NHPR (AUC: 0.962 [0.914-1.00]) were both high. Sensitivity, specificity, positive and negative predictive value of QFR in comparison to NHPR were 84.2%, 100%, 100% and 93.2% respectively. QFR has high diagnostic performance in detecting functionally significant lesions of non-culprit arteries in patients with NSTE-ACS and multivessel disease. Due to its high negative predictive value, it can be used to safely avoid unnecessary invasive physiological assessment of these lesions.

Prognostic Value of Post-PCI Angiography-Derived Fractional Flow Reserve: A Systematic Review and Meta-Analysis of Cohort Studies.

The post-percutaneous coronary intervention (post-PCI) fractional flow reserve (FFR) can detect suboptimal PCI or residual ischemia and potentially lead to fewer adverse clinical outcomes. We sought to investigate the predictive value of the angiography-derived FFR for adverse cardiovascular events in patients after PCI. We conducted a comprehensive search of electronic databases, MEDLINE, EMBASE, and the Cochrane Library, for studies published until March 2023 that investigated the prognostic role of angiography-derived fractional flow reserve values after PCI. We investigated the best predictive ability of the post-PCI angiography-derived FFR and relative risk (RR) estimates with 95% confidence intervals (CIs) between post-PCI angiography-derived FFR values and adverse events. Thirteen cohort studies involving 6961 patients (9719 vascular lesions; mean follow-up: 2.2 years) were included in this meta-analysis. The pooled HR of the studies using specific cut-off points for post-PCI angiography-derived FFR was 4.13 (95% CI, 2.92-5.82) for total cardiovascular events, while the pooled HRs for target vessel revascularization, cardiac death, target vessel myocardial infarction, and target lesion revascularization were 6.87 (95% CI, 4.93-9.56), 6.17 (95% CI, 3.52-10.80), 3.98 (95% CI, 2.37-6.66) and 6.27 (95% CI, 3.08-12.79), respectively. In a sensitivity analysis of three studies with 1789 patients assessing the predictive role of the post-PCI angiography-derived FFR as a continuous variable, we found a 58% risk reduction for future adverse events per 0.1 increase in the post-PCI angiography-derived FFR value. In conclusion, post-PCI angiography-derived FFR is an effective tool for predicting adverse cardiovascular events and could be potentially used in decision making, both during PCI and in the long-term follow-up.

Echocardiographic and Cardiac Magnetic Resonance Imaging-Derived Strains in Relation to Late Gadolinium Enhancement in Hypertrophic Cardiomyopathy.

We compared speckle tracking echocardiography (STE) and feature tracking cardiovascular magnetic resonance (FT-CMR) in patients with hypertrophic cardiomyopathy (HC) with a varying extent of fibrosis as defined by late gadolinium enhancement to look at the level of agreement between methods and their ability to relate those to myocardial fibrosis. At 2 reference centers, 79 patients with HC and 16 volunteers (the control group) underwent STE and CMR with late gadolinium enhancement and FT-CMR. Patients were classified into 3 categories: no detectable, limited, and extensive fibrosis. Global longitudinal strain (GLS) and global radial strain (GRS) were derived using FT-CMR and STE. STE-derived GRS was decreased in all HC categories compared with the control group (p <0.001), whereas FT-CMR GRS was reduced only in patients with HC with fibrosis (p <0.05). Reduced STE-derived GLS was associated with extensive fibrosis (p <0.05) and a value less than -15.2% identified those with extensive fibrosis (sensitivity 79%, specificity 92%, area under the curve 0.863, 95% confidence interval [CI] 0.76 to 0.97, p <0.001). Inter-modality agreement was moderate for STE versus CMR-GLS (overall population intra-class correlation coefficient = 0.615, 95% CI 0.42 to 0.75, p <0.001; patients with HC 0.63, 0.42 to 0.76, p <0.001) and GRS (overall population intra-class correlation coefficient = 0.601, 95% CI 0.397 to 0.735, p <0.001). A low level of agreement for GRS was seen between methods in patients with HC. In conclusion, strain indexes measured using echocardiography and CMR are reduced in patients with HC compared with the control group and correlate well with the burden of myocardial fibrosis. Reduced STE-GLS can identify patients with extensive fibrosis, but whether there is an added value for risk stratification for sudden cardiac death remains to be determined.

Laparoscopic distal gastric and D1 resection for large perforated duodenal bulb peptic ulcer, with intracorporeal antecolic gastrojejunal anastomosis.

BACKGROUND: Peptic ulcer perforation is a common surgical emergency and a major cause of death especially in elderly patients, despite the fact of the presence of effective drug treatments and an increased understanding of its etiology. Giant duodenal perforations, in particular, pose a significant challenge and there is scarce data regarding their optimal management. Laparoscopic surgery is advocated in the surgical treatment of perforated duodenal ulcer disease, in experienced hands. METHODS: Herein we present an 84-year-old man with past medical history of type II diabetes mellitus and hypertension who was admitted to our Department due to epigastric pain and diffuse peritonitis. CT scan revealed the presence of a significant amount of free air and fluid in the upper abdomen secondary to a duodenal perforation. RESULTS: The patient was taken immediately to the theater for an urgent laparoscopy. Methylene blue via the NG tube better defined the extent of the duodenal perforation which was not amenable to a primary repair. Consequently, a decision was made for a laparoscopic pancreas-sparing, ampulla preserving gastroduodenectomy with intracorporeal Billroth II gastrojejunal anastomosis. The postoperative period was uneventful and the patient was discharged on the 13th postoperative day. Histopathology revealed a large benign duodenal ulcer. CONCLUSIONS: Although the incidence of peptic ulcer disease is decreasing, it appears that the incidence of complications is rising. Laparoscopic approach, especially when performed by laparoscopic surgery experts, could be a treatment option for difficult duodenal ulcer perforations with less pain, shorter hospital stay and reduced morbidity.

Angiography-based estimation of coronary physiology: A frame is worth a thousand words.

Cumulative evidence has shown that coronary revascularization should be guided by functional significance of coronary lesions. Fractional flow reserve (FFR) is the gold standard for assessment of hemodynamic significance of coronary stenosis and FFR-guided percutaneous coronary intervention has improved clinical outcomes in patients with coronary artery disease. However, limitations of FFR such as increased operational time and cost, requirement of pressure wire and adenosine and technical difficulties have led to significant underutilization of the method in clinical practice. In the last few years, several methods of FFR estimation based on coronary angiography images have emerged to overcome invasive FFR limitations. The common elements of the novel indices include a 3D anatomical reconstruction of coronary vessels by angiographic projections and various approaches to fluid dynamics computation. Angiography-derived FFR methods have shown high diagnostic accuracy compared to invasive FFR. Although there are promising results regarding their prognostic role, large randomized trials evaluating clinical outcomes are lacking. The aim of this review is to present currently available angiography-derived FFR indices and highlight their differences, advantages, disadvantages and potential clinical implications.

Irreversible Electroporation (IRE) Combined With Chemotherapy Increases Survival in Locally Advanced Pancreatic Cancer (LAPC).

OBJECTIVES: Locally advanced pancreatic cancer (LAPC) is found in about 40% of patients with pancreatic cancer. Irreversible electroporation (IRE) is a nonthermal ablative technique that provides an alternative in patients with LAPC and can be safely combined with chemotherapy. MATERIALS AND METHODS: From 2015 until October of 2019, we performed laparotomic IRE in a total of 40 patients with stage III LAPC. The median age of these patients was 65.2 years (range: 46 to 81 y), and the median tumor size was 3.8 cm (range: 2 to 5.2 cm). 33 of 40 patients were treated preoperatively with FOLFIRINOX or nab-paclitaxel plus gemcitabine and in case of disease control, IRE was performed, whereas in 7 patients, IRE was performed without previous chemotherapy. RESULTS: All patients were treated successfully with IRE as the tumor evaluation showed no disease progression after the completion of induction chemotherapy. No IRE-related deaths occurred. Two major grade III complications were reported: pancreatic fistula grade A in 8 patients and 3 patients diagnosed with delayed gastric emptying. Up to October 31, 2019, the median overall survival (OS) of all patients was 24.2 months (range: 6 to 36 mo), and the median progression-free survival was 10.3 months (range: 3 to 24 mo). After the completion of IRE, 30 patients (75%) continued with adjuvant chemotherapy. Fifteen patients (37%) have >24 months OS and 3 patients (8%) have reached 36 months OS and are still alive. CONCLUSION: The combination of chemotherapy with IRE, which is a safe and effective procedure, may result in a survival benefit for patients with LAPC.

Exercise tolerance and quality of life in patients with known or suspected coronary artery disease.

BACKGROUND: Coronary artery disease (CAD) is known to impact on patients' physical and mental health. The relationship between performance on treadmill exercise tolerance test (ETT) and health-related quality of life (HRQL)has never been specifically investigated in the setting of CAD. METHODS: Consecutive patients undergoing an ETT with the Bruce protocol during a diagnostic workup for CAD (n = 1,631, age 55 ± 12 years) were evaluated. Exercise-related indices were recorded. Detailed information on cardiovascular risk factors and past medical history were obtained. HRQLwas assessed with the use of the validated 36-Item Short Form Survey (SF-36) questionnaire. RESULTS: Increasing age and the presence of cardiovascular risk factors and comorbidities correlated with lower scores on the physical and mental health component of SF-36(all P < 0.05). Subjects with arrhythmias during exercise and slow recovery of systolic blood pressure had lower scores on the physical health indices or the Social Role Functioning component (P < 0.05). Achieved target heart rate and good exercise tolerance were independently associated with better scores of the physical and mental health domains of SF-36 and overall HRQLscores (ß = 0.05 for target HR and PCS-36, ß = 1.86 and ß = 1.66 per increasing stage of exercise tolerance and PCS-36 and MCS-36, respectively, P < 0.001 for all associations). Ischemic ECG changes were associated with worse scores on Physical Functioning (ß = - 3.2, P = 0.02) and Bodily Pain (ß = - 4.55, P = 0.026). CONCLUSION: ETT parameters are associated with HRQL indices in patients evaluated for possible CAD. Physical conditioning may increase patient well-being and could serve as a complementary target in conjunction with cardiovascular drug therapy.

A Bayesian meta-analysis on early tobacco exposure and vascular health: From childhood to early adulthood.

BACKGROUND: Smoking has been consistently associated with increased cardiovascular risk in adults. Although exposure to tobacco products often starts in early life, evidence for the possible adverse effects on the cardiovascular system of the young is scarce. We sought to derive pooled estimates of smoking effects on indices of early vascular damage in children and adolescents. DESIGN AND METHODS: We performed a systematic review and meta-analysis of clinical studies involving young individuals up to 21 years old that provided data on smoking exposure (active or passive) and flow-mediated dilatation, carotid to femoral pulse wave velocity and maximum carotid intima-media thickness. We employed three distinct methodologies of random-effects data synthesis, including the Sidik-Jonkman estimator, the Hartung and Knapp correction and a Bayesian method with a well-informed prior on the level of between-study variance. RESULTS: In 12 studies and 5279 individuals in total, smoking exposure was related to deterioration in all three outcomes (mean adjusted flow-mediated dilatation decrease: -0.77%, 95% confidence interval -1.38--0.15, mean adjusted pulse wave velocity increase: 0.1 m/s, 95% confidence interval 0.02-0.17 and mean adjusted carotid intima-media thickness increase: 0.35 mm, 95% confidence interval 0.16-0.55, for the Sidik-Jonkman estimator). No difference was established between active and passive smoking on associations with arterial damage. CONCLUSIONS: Exposure to tobacco products is associated with subclinical vascular damage early in life, even from childhood. Public health initiatives should target these very young age groups to prevent early smoking exposure and associated arterial damage and its sequelae.

Diabetic Polyneuropathy Is Associated With Pathomorphological Changes in Human Dorsal Root Ganglia: A Study Using 3T MR Neurography.

Diabetic neuropathy (DPN) is one of the most severe and yet most poorly understood complications of diabetes mellitus. In vivo imaging of dorsal root ganglia (DRG), a key structure for the understanding of DPN, has been restricted to animal studies. These have shown a correlation of decreased DRG volume with neuropathic symptom severity. Our objective was to investigate correlations of DRG morphology and signal characteristics at 3 Tesla (3T) magnetic resonance neurography (MRN) with clinical and serological data in diabetic patients with and without DPN. In this cross-sectional study, participants underwent 3T MRN of both L5 DRG using an isotropic 3D T2-weighted, fat-suppressed sequence with subsequent segmentation of DRG volume and analysis of normalized signal properties. Overall, 55 diabetes patients (66 ± 9 years; 32 men; 30 with DPN) took part in this study. DRG volume was smaller in patients with severe DPN when compared to patients with mild or moderate DPN (134.7 ± 21.86 vs 170.1 ± 49.22; p = 0.040). In DPN patients, DRG volume was negatively correlated with the neuropathy disability score (r = -0.43; 95%CI = -0.66 to -0.14; p = 0.02), a measure of neuropathy severity. DRG volume showed negative correlations with triglycerides (r = -0.40; 95%CI = -0.57 to -0.19; p = 0.006), and LDL cholesterol (r = -0.33; 95%CI = -0.51 to -0.11; p = 0.04). There was a strong positive correlation of normalized MR signal intensity (SI) with the neuropathy symptom score in the subgroup of patients with painful DPN (r = 0.80; 95%CI = 0.46 to 0.93; p = 0.005). DRG SI was positively correlated with HbA1c levels (r = 0.30; 95%CI = 0.09 to 0.50; p = 0.03) and the triglyceride/HDL ratio (r = 0.40; 95%CI = 0.19 to 0.57; p = 0.007). In this first in vivo study, we found DRG morphological degeneration and signal increase in correlation with neuropathy severity. This elucidates the potential importance of MR-based DRG assessments in studying structural and functional changes in DPN.

The efficacy and safety of the open approach irreversible electroporation in the treatment of pancreatic cancer: A systematic review.

BACKGROUND: Irreversible Electroporation (IRE) is a novel non-thermal ablation technique used in patients with locally advanced pancreatic cancer (LAPC), in the proximity of sensitive structures such as vessels, intestinal wall and the bile duct. Currently, it is only used in the setting of clinical trials. This systematic review aimed to tackle the knowledge gap in the literature, in relation to the safety and efficacy of the open approach IRE. METHODS: MEDLINE, EMBASE and Cochrane libraries were searched for English language articles published from January 2000 to December 2019. Data related to safety and efficacy were extracted. RESULTS: Nine studies involving 460 patients with LAPC were included. Open approach IRE was associated with high morbidity (29.4%) but with a survival benefit compared to traditional treatment. Median overall survival (OS) was at 17.15 months. Major morbidity was at 10.2% and mortality at 3.4%. CONCLUSIONS: Despite the paucity of literature and the low quality of evidence, the results regarding safety and efficacy appear to be encouraging. The high morbidity seems to be mitigated by a demonstrated improvement in OS. The potential of this technique is more evident when mortality and major morbidity are considered, since they are at acceptable levels. The limitations of this review have made it difficult to extract definitive conclusions. Higher quality evidence is needed in the form of large-scale multicentre randomized controlled trials. It remains to be elucidated whether the rate of adverse events decreases as our experience with this technique increases.

Impaired dexamethasone resorption in two patients with pseudo-Cushing after bariatric surgery: Implications for immunosuppressive treatment.

Two cases of middle-aged female patients treated by gastric bypass surgery for weight loss presented to our clinic for a follow-up examination 3-6 months after the surgical procedure (a mini gastric bypass and a modified single anastomosis sleeve-ileostomy). In both patients increased ACTH levels and either high serum cortisol or an increased urinary cortisol excretion was apparent and triggered further endocrine testing. Serum cortisol could not be suppressed adequately by 2 and 4 mg dexamethasone in the standardized oral overnight suppression test while midnight salivary cortisol dropped well below the desired cut-off. This led to the hypothesis of an impaired dexamethasone resorption and could be further substantiated by suppression of serum cortisol below the cut-off by an intravenous dexamethasone application. The data presented point to an impairment of enteral synthetic corticosteroid resorption in patients after gastric bypass surgery and could be of importance for individuals in need for immunosuppressive treatment. In view of the growing number of bariatric procedures, pharmacokinetics of corticosteroids and other drugs should be tested in clinical trials.

Open Interphalangeal Dislocation of the Great Toe in an Amateur Football Player: A Rare Case Report.

INTRODUCTION: Open interphalangeal (IP) dislocations are completely uncommon. Up to now, different patterns of dislocation have been described. The combination of axial loading and hyperdorsiflexion forces, leading to plantar dislocation of the distal phalanx, is a rare type of injury, which has yet not been reported. CASE REPORT: A rare case of traumatic open dislocation of the left great toe IP joint in a highly active, overweighted, male, amateur football player is presented. The possible underlying mechanism was impact of the left great toe against the ground and subsequent hyperdorsiflexion. The distal phalanx was dislocated plantarly, whereas the proximal phalanx was protruding out the dorsal skin of the toe. Open exploration and reduction led to excellent clinical results 6 months after surgery. CONCLUSION: Open traumatic IP dislocation of the great toe due to low force activity is a very rare mode of injury, which requires adequate treatment including immediate purification of the exposed joint, control of the sesamoids' position, exclusion of intra-articular fractures, joint's reduction, soft-tissue repair, and proper stabilization.

Snare Technique for Transcatheter Aortic Valve Implantation in a Difficult Anatomy With Calcified Aortic Valve.

Crossing the aortic annulus with a prosthetic valve was impossible due to severe calcification. A snare catheter technique was used to centralize the entire system with the aortic orifice.

Vascular acrosyndromes in young adult population. Definition of clinical symptoms and connections to joint hypermobility.

OBJECTIVES: Clinical recognition of vascular acrosyndromes is often challenging. The term Raynaud's phenomenon (RP) is commonly overused to describe any form of cold-related disorder. This study aims to formally evaluate peripheral vascular symptoms affecting the population, aged ≤ 40 years, and identify any correlations to joint hypermobility (JH). PATIENTS AND METHODS: Fifty patients (31 males, 19 females) with vasomotor symptoms enrolled in this five-year prospective observational study. Clinical examination by a rheumatologist and a vascular surgeon was performed along with cardiology, echocardiographic and Doppler evaluation. Patients underwent blood cell count, biochemistry, thyroid and selectively immunologic testing. Twenty-four (48%) of them performed nailfold capillaroscopy. The SPSS for Windows, v.17.0, Chicago, USA, was used for the statistical analyses. RESULTS: Twenty-eight patients (56%) presented with erythromelalgia (EM), 6 (12%) with acrocyanosis (AC) and 9 (18%) as a combination of the above disorder. RP diagnosed in five (10%) while two patients (4%) presented as a mix of EM-RP. There was no correlation with abnormal laboratory tests. Increased incidence of JH was found in EM and AC patients. Among those who were tested with nailfold capillaroscopy, 75% had abnormalities ranged from mild to autoimmune-like diseases. CONCLUSIONS: Erythromelalgia is the commonest functional vasculopathy in young population followed by acrocyanosis and a combination of these conditions. Joint hypermobility is markedly increased, indicating that dysautonomy may be considered the causative factor following a trigger event. Overall, RP was observed in 14% of patients. Clinical recognition of these disorders avoids unnecessary investigation. Key Points • Vascular acrosyndromes in young adults are commonly functional disorders resembling vascular algodystrophy induced by thermic stress. • Dysautonomy of joint hypermobility is the co-factor influencing the appearance of the vascular disorders. • Raynaud's phenomenon accounts to approximately 14% of vascular acrosyndromes presented in the young adult population.

The Role of Arterial Hypertension in Mitral Valve Regurgitation.

PURPOSE OF REVIEW: To review medical literature for evidence of association between hypertension and mitral regurgitation (MR) and summarize potential favorable effects of antihypertensive drugs on MR natural history and treatment. RECENT FINDINGS: Hypertension and MR are common diseases affecting a large proportion of the general population. Contemporary evidence suggests that hypertension may worsen the progression and prognosis of MR through augmented mechanical stress and increased regurgitation volume. Renin-angiotensin axis inhibitors, beta-blockers, and vasodilators have been tested in order to prevent or decrease primary or secondary MR. Although antihypertensive agents may improve hemodynamic parameters and left ventricular remodeling in primary MR, there is no strong evidence of benefit on clinical outcomes. On the other hand, a beneficial effect of these drugs on secondary MR is better established. Moreover, there are no studies evaluating a possible benefit of lower blood pressure targets in MR. Randomized controlled trials are warranted to elucidate the precise role of antihypertensive therapy on treatment of MR.

Methylglyoxal and Advanced Glycation End Products in Patients with Diabetes - What We Know so Far and the Missing Links.

Hyperglycemia explains the development of late diabetic complications in patients with diabetes type 1 and type 2 only partially. Most therapeutic efforts relying on intensive glucose control failed to decrease the absolute risk for complications by more than 10%, especially in patients with diabetes type 2. Therefore, alternative pathophysiological pathways have to be examined, in order to develop more individualized treatment options for patients with diabetes in the future. One such pathway might be the metabolism of dicarbonyls, among them methylglyoxal and the accumulation of advanced glycation end products. Here we review currently available epidemiological data on dicarbonyls and AGEs in association with human diabetes type 1 and type 2.

Pleiotropic Effect of Lipoprotein-Apheresis on the Soluble Form of Activated Leukocyte Cell Adhesion Molecule (sALCAM) in Familial Hypercholesterolaemia.

INTRODUCTION/BACKGROUND: Atherosclerosis is an inflammatory disorder in which several converging immune responses modulate and induce lipid accumulation in macrophages. Activated leukocyte cell adhesion molecule (ALCAM) has been described as a structural homologue of HDL-receptor and functions as a pattern recognition receptor (PRR), while its soluble form sALCAM is involved in ALCAM-dependent and -independent immune mechanisms. The aim of this study was to investigate the effect of aggressive removal of low density lipoprotein-cholesterol (LDL-C) and lipoprotein(a) (Lp [a]) by lipoprotein-apheresis (LA) on sALCAM and blood viscosity as well as to evaluate its association with lipoproteins and serum markers of inflammation.