Metalloproteinase expression after desflurane preconditioning in hepatectomies: A randomized clinical trial

BACKGROUNDHepatectomy with inflow occlusion results in ischemia-reperfusion injury; however, pharmacological preconditioning can prevent such injury and optimize the postoperative recovery of hepatectomized patients. The normal inflammatory response after a hepatectomy involves increased expression of metalloproteinases, which may signal pathologic hepatic tissue reformation. AIMTo investigate the effect of desflurane preconditioning on these inflammatory indices in patients with inflow occlusion undergoing hepatectomy.METHODSThis is a single-center, prospective, randomized controlled trial conducted at the 4^th Department of Surgery of the Medical School of Aristotle University of Thessaloniki, between August 2016 and December 2017. Forty-six patients were randomized to either the desflurane treatment group for pharmacological preconditioning (by replacement of propofol with desflurane, administered 30 min before induction of ischemia) or the control group for standard intravenous propofol. The primary endpoint of expression levels of matrix metalloproteinases and their inhibitors was determined preoperatively and at 30 min posthepatic reperfusion. The secondary endpoints of neutrophil infiltration, coagulation profile, activity of antithrombin III (AT III), protein C (PC), protein S and biochemical markers of liver function were determined for 5 d postoperatively and compared between the groups.RESULTSThe desflurane treatment group showed significantly increased levels of tissue inhibitor of metalloproteinases 1 and 2, significantly decreased levels of matrix metalloproteinases 2 and 9, decreased neutrophil infiltration, and less profound changes in the coagulation profile.  During the 5-d postoperative period, all patients showed significantly decreased activity of AT III, PC and protein S (vs baseline values, P < 0.05). The activity of AT III and PC differed significantly between the two groups from postoperative day 1 to postoperative day 5 (P < 0.05), showing a moderate drop in activity of AT III and PC in the desflurane treatment group and a dramatic drop in the control group. Compared to the control group, the desflurane treatment group also had significantly lower international normalized ratio values on all postoperative days (P < 0.005) and lower serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase values on postoperative days 2 and 3 (P < 0.05).   Total length of stay was significantly less in the desflurane group (P = 0.009).CONCLUSIONDesflurane preconditioning can lessen the inflammatory response related to ischemia-reperfusion injury and may shorten length of hospitalization.     

Lipidomics in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disorder in Western countries, comprises steatosis to nonalcoholic steatohepatitis (NASH), with the latter having the potential to progress to cirrhosis. The transition from isolated steatosis to NASH is still poorly understood, but lipidomics approach revealed that the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis and these alterations correlate with disease progression. Recent data suggest that both quantity and quality of the accumulated lipids are involved in pathogenesis of NAFLD. Changes in glycerophospholipid, sphingolipid, and fatty acid composition have been described in both liver biopsies and plasma of patients with NAFLD, implicating that specific lipid species are involved in oxidative stress, inflammation, and cell death. In this article, we summarize the findings of main human lipidomics studies in NAFLD and delineate the currently available information on the pathogenetic role of each lipid class in lipotoxicity and disease progression.     

Akt1 and Akt2 protein kinases differentially contribute to macrophage polarization

Activated macrophages are described as classically activated or M1 type and alternatively activated or M2 type, depending on their response to proinflammatory stimuli and the expression of genetic markers including iNOS, arginase1, Ym1, and Fizz1. Here we report that Akt kinases differentially contribute to macrophage polarization, with Akt1 ablation giving rise to an M1 and Akt2 ablation resulting in an M2 phenotype. Accordingly, Akt2(-/-) mice were more resistant to LPS-induced endotoxin shock and to dextran sulfate sodium (DSS)-induced colitis than wild-type mice, whereas Akt1(-/-) mice were more sensitive. Cell depletion and reconstitution experiments in a DSS-induced colitis model confirmed that the effect was macrophage-dependent. Gene-silencing studies showed that the M2 phenotype of Akt2(-/-) macrophages was cell autonomous. The microRNA miR-155, whose expression was repressed in naive and in LPS-stimulated Akt2(-/-) macrophages, and its target C/EBPβ appear to play a key role in this process. C/EBPβ, a hallmark of M2 macrophages that regulates Arg1, was up-regulated upon Akt2 ablation or silencing. Overexpression or silencing of miR-155 confirmed its central role in Akt isoform-dependent M1/M2 polarization of macrophages.     

Noninvasive diagnostic techniques for coronary disease in women

Significant advances in medical treatment, medical technology, and the focus on sex-specific research have contributed to a reduction in cardiovascular mortality in women. Despite these advances, coronary artery disease (CAD) is the leading cause of cardiovascular death of women in the Western world. In the past 2 decades, the focused research on women at risk for CAD has helped to clarify our understanding of some of the sex-specific factors that are important in the detection of CAD. In women, the detection and evaluation of physiologically significant CAD can be challenging. Many of the traditional tests that are designed to detect focal areas of coronary artery stenosis are less sensitive and specific in female patients, who have a greater burden of symptoms, higher atherosclerotic burden, and lower prevalence of obstructive coronary disease. In this article, we review the available evidence on the role of contemporary noninvasive diagnostic techniques in the evaluation of women with symptoms of CAD. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Tooth wear in the deciduous dentition of 5–7-year-old children: risk factors

This study was conducted to investigate the distribution and severity of tooth wear in deciduous dentition and its relationship with possible risk factors. A stratified cluster sample of 243 5-7-year-old children was examined using the tooth wear index of Smith and Knight, and their exposure to intrinsic and extrinsic risk factors was retrospectively investigated through a structured questionnaire. The severity of wear was quantitatively estimated by the number of surfaces with affected dentine and by the cumulative score of the sextants, based on the Basic Erosive Wear Examination scoring system. Only 1.6% of the children were tooth wear free, whereas 45.6% had moderate to severe wear involving dentine. Maxillary canines were the most affected teeth (83.2%), and occlusal/incisal the most affected surfaces (52.7%). The likelihood of tooth wear involving dentine was greater in boys than girls (OR = 1.72), in immigrants than in Greeks (OR = 1.93), and in 6- and 7-year olds than in 5-year olds (OR = 2.78 to 2.93). After adjustment for age, gender, and nationality, exposure to several dietary factors and especially to soft drinks was found to significantly affect the prevalence (OR = 1.27) and the severity of tooth wear. Every additional serving/week of consumption of soft drinks increases the number of surfaces with dentine affected by 0.03 per year (p < 0.05) and the cumulative score of sextants by 0.04 (p < 0.05). The cluster of children with the higher prevalence and severity of tooth wear had an average exposure to soft drinks of 10 servings/week for a duration of 4 years. The cumulative score of sextants was better predicted by the assessed risk factors, in comparison with the number of surfaces with affected dentine. Tooth wear is a common condition in children, related both to the physiological process of aging of dentition and to the erosive effect of dietary factors. Strategies to reduce the intake of soft drinks in children are expected to have multiple benefits preventing tooth wear in childhood and in later life, as well as many other general and oral health diseases.     

Long-term impact of multifactorial treatment on new-onset diabetes and related cardiovascular events in metabolic syndrome: a post hoc ATTEMPT analysis

This post hoc analysis of the Assessing The Treatment Effect in Metabolic Syndrome Without Perceptible diabeTes (ATTEMPT) study assesses the 3? year incidence of new-onset diabetes (NOD) and related cardiovascular disease (CVD) events in patients with metabolic syndrome (MetS), after multifactorial (lifestyle and drug, including atorvastatin) intervention. Patients were randomized to group A (low-density lipoprotein cholesterol [LDL-C] target < 100 mg/dL) and group B (< 130 mg/dL). The incidence of NOD during the 42-month follow-up was very low, 0.83 to 1.00/100 patient-years in patients with MetS and MetS with impaired fasting glucose, respectively. Older age, increased waist circumference, and persistent MetS were determinants of NOD. One CVD nonfatal event occurred in the 28 patients with NOD. Our findings suggest that treating the characteristics of MetS is achievable and beneficial. New-onset diabetes incidence and CVD events were negligible and not different from what is expected in the general population.     

Autograft and pulmonary allograft performance in the second post-operative decade after the Ross procedure: insights from the Rotterdam Prospective Cohort Study

Aims The objective of the present study was to report our ongoing prospective cohort of autograft recipients with up to 21 years of follow-up. Methods and results All consecutive patients (n = 161), operated between 1988 and 2010, were analysed. Mixed-effects models were used to assess changes in echocardiographic measurements (n = 1023) over time in both the autograft and the pulmonary allograft. The mean patient age was 20.9 years (range 0.05-52.7)-66.5% were male. Early mortality was 2.5% (n = 4), and eight additional patients died during a mean follow-up of 11.6 ± 5.7 years (range 0-21.5). Patient survival was 90% [95% confidence interval (CI), 78-95] up to 18 years. During the follow-up, 57 patients required a re-intervention related to the Ross operation. Freedom from autograft reoperation and allograft re-intervention was 51% (95% CI 38-63) and 82% (95% CI 71-89) after 18 years, respectively. No major changes were observed over time in autograft gradient, and allograft gradient and regurgitation. An initial increase of sinotubular junction and aortic anulus diameter was observed in the first 5 years after surgery. The only factor associated with an increased autograft reoperation rate was pre-operative pure aortic regurgitation (AR) (hazard ratio 1.88; 95% CI 1.04-3.39; P= 0.037). Conclusion We observed good late survival in patients undergoing autograft procedure without reinforcement techniques. However, over half of the autografts failed prior to the end of the second decade. The reoperation rate and the results of echocardiographic measurements over time underline the importance of careful monitoring especially in the second decade after the initial autograft operation and in particular in patients with pre-operative AR.     

Inflammatory markers and plaque morphology: an optical coherence tomography study

Background

OCT with its unique image resolution is the ideal method to detect culprit lesion characteristics in different clinical presentations. The identification of inflammatory markers related to plaque characteristics may be of clinical importance.

Methods

Thirty-two patients with acute coronary syndromes (ACS) and fourteen patients with stable angina pectoris (SAP) were enrolled in this study. Culprit lesion morphology was assessed by optical coherence tomography (OCT) in patients with ACS and SAP. The possible relations between serum levels of high sensitivity-C reactive protein (hs-CRP) and interleukin-18 (IL-18) with plaque characteristics were investigated in those patients.

Results

Plaque rupture and thin-cap fibroatheroma (TCFA) were detected more frequently in ACS patients compared with SAP patients, (78.6% vs. 14.3%, p < 0.001, 92.9% vs. 14.3%, p < 0.001, respectively). Higher levels of serum hs-CRP and IL-18 were found in patients with plaque rupture vs. those with no plaque rupture (median value: 19.2 mg/L vs. 1.6 mg/L, p < 0.001 and 219.5 pg/ml vs. 127.5 pg/ml, p = 0.001 respectively), and TCFA vs. those without TCFA (median value: 15.2 mg/L vs. 1.6 mg/L, p = 0.004 and 209.0 pg/ml vs.153.2 pg/ml, p = 0.03 respectively). Serum hs-CRP was the only independent predictor of plaque rupture (p = 0.02, odds ratio 1.1, 95% confidence interval 1.0 to 1.2). A cut-off value of hs-CRP > 4.5 mg/L could detect ruptured plaque with a sensitivity of 91.7% and a specificity of 77.8%.

Conclusions

OCT detected plaque rupture and TCFA more frequent in ACS patients compared with SAP. Elevated hs-CRP and IL-18 were positively related to plaque instability and rupture.     

Comparative effects of sevoflurane and propofol based general anaesthesia for elective surgery on memory

Introduction

Unconscious processing of words during general anaesthesia has been suggested. We used the process dissociation procedure (PDP) to test memory performance during sevoflurane and propofol anaesthesia in relation to hypnotic depth.

Material and methods

One hundred participants anaesthetised for elective surgery (50 with propofol and 50 with sevoflurane) and 50 non-anaesthetized listened to a list of words. The bispectral index (BIS) of the anaesthetised patients was recorded. Within 36 h after word presentation, memory was assessed using a word stem completion task, based on Buchner''s model applied on the PDP.

Results

There was evidence of memory for words presented during light (BIS 61-80) (p = 0.001) and adequate (BIS 41-60) (p = 0.008) but not deep anaesthesia (BIS 21-40) (p = 0.09). The PDP showed a significant implicit but not explicit memory contribution (mean total explicit memory scores: 0.04 ±0.07 in all BIS categories; mean implicit memory scores: 0.01 ±0.04, 0.1 ±0.08, and 0.05 ±0.09 at BIS = 21-40, 41-60, and 61-80, respectively). There was a statistically significant difference between the mean implicit memory score (I) of the propofol and sevoflurane group in the BIS category 41-60 in general (p = 0.016), and after incision (I_A.I.) (p = 0.005) in particular, with propofol depressing I more than sevoflurane in both cases. Memory performance of nonanaesthetized participants was better, with a higher contribution of explicit and a comparable contribution of implicit memory.

Conclusions

During general anaesthesia, implicit memory persists even in adequate hypnotic states. Sevoflurane affects the implicit memory of adequately anaesthetised subjects less than propofol.     

Statins and cardiovascular outcomes in elderly and younger patients with coronary artery disease: a post hoc analysis of the GREACE study

Introduction

The effect of cardiovascular disease (CVD) prevention measures aimed at elderly patients requires further evidence. We investigated the effect of statin treatment (targeted to achieve guideline goals) on CVD outcomes in different age groups to determine whether statins are more beneficial in the elderly.

Material and methods

The primary endpoint of this post hoc analysis of the GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study (n = 1,600 patients with established coronary heart disease (CHD), mean follow-up 3 years) was the absolute and relative CVD event (a composite of death, myocardial infarction, revascularization, unstable angina, heart failure and stroke) risk reduction in age quartiles (each n = 200). Patients on “structured care” with atorvastatin (n = 800) followed up by the university clinic and treated to lipid goal were compared with the corresponding quartiles on “usual care” (n = 800) followed up by specialists or general practitioners of the patient''s choice outside the hospital.

Results

In the elderly (mean age 69 ±4 and 70 ±3 years in the “structured” and “usual care”, respectively) the absolute CVD event reduction between “structured” and “usual care” was 16.5% (p < 0.0001), while in the younger patients (mean age 51 ±3 years and 52 ±3 years in the “structured” and “usual care”, respectively) this was 8.5% (p = 0.016); relative risk reduction (RRR) 60% (p < 0.0001) vs. 42% respectively (p = 0.001). The elderly had higher rates of chronic kidney disease and higher uric acid levels, plus an increased prevalence of diabetes, metabolic syndrome and non-alcoholic fatty liver disease. These factors might contribute to the increased CVD risk in older patients.

Conclusions

All age groups benefited from statin treatment, but the elderly on “structured care” had a greater absolute and relative CVD risk reduction than the younger patients when compared with the corresponding patients assigned to “usual care”. These findings suggest that we should not deprive older patients of CVD prevention treatment and lipid target achievement.