Effect of a new squalene synthase inhibitor on an ApoE-/- mouse model of atherosclerosis.

Ηypercholesterolemia/hyperlipidemia in conjunction with oxidative stress and inflammatory processes contribute synergistically to the pathogenesis of atherosclerosis. We hereby evaluated the antiatherosclerotic effect of the multi-target derivative 4-methyl-2-(10H-phenothiazin-3-yl)morpholin-2-ol hydrobromide 1 in apoE-/- mice; compound 1 is a potent antihyperlipidemic agent acting through Squalene Synthase inhibition, while it has exhibited an outstanding antioxidant and anti-inflammatory activity in various experimental animal models. The new analogue was evaluated in terms of its antiatherosclerotic/antioxidant effect in the ApoE-/- transgenic mouse model. Its toxicity profile was also assessed by measuring the levels of four sensitive indicators of liver toxicity. Prolonged administration of 1 in ApoE-/- mice fed with a western-type (wt) diet efficiently reduced the aortic atheromatic lesions, an effect that took place through a cholesterol lowering independent manner. In addition, 1 displayed a significant reduction not only of glucose but also of oxidative stress levels, while it did not cause any toxicity. To the best of our knowledge this is the first time that the antiatherosclerotic effect of a Squalene Synthase inhibitor is studied in this specific atherosclerosis mouse model. As a result, compound 1 may serve as a promising starting point towards developing new bioactive analogues against the onset and subsequent development of atherosclerosis.

Markers of endothelial dysfunction and arterial stiffness in patients with early-stage autosomal dominant polycystic kidney disease: A meta-analysis.

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is characterised by increased rates of cardiovascular complications leading to significant morbidity and mortality. This meta-analysis aims to evaluate whether the disease is linked to endothelial dysfunction and arterial stiffness during its early stages. METHODS: Medline, Scopus, CENTRAL, Web of Science, Clinicaltrials.gov and Google Scholar databases comparing ADPKD patients with preserved renal function to healthy controls were included. The outcomes of interest were brachial flow-mediated dilatation, carotid-femoral pulse wave velocity, augmentation index, carotid intima-media thickness and central systolic blood pressure, plasma ADMA or homocysteine levels. Standardised mean differences (SMDs) were estimated by a random-effects model in R-3.6.3. RESULTS: A total of 27 studies were included, comprising 1967 individuals. ADPKD was linked to significantly lower flow-mediated dilatation (SMD: -1.44, 95% CI: [-2.35, -0.53]) and higher pulse wave velocity (SMD: 1.44, 95% CI: [0.22, 2.66]) and carotid intima-media thickness (SMD: 1.02, 95% CI: [0.57, 1.47]). No significant associations were noted regarding augmentation index (SMD: 0.62, 95% CI: [-0.19, 1.43]) and central systolic blood pressure (SMD: 1.84, 95% CI: [-0.12, 3.80]). Plasma homocysteine was significantly higher in ADPKD (SMD: 0.81, 95% CI: [0.16, 1.45]), while no difference was calculated for ADMA levels (SMD: 1.14, 95% CI: [-0.25, 2.53]). CONCLUSIONS: Early-stage ADPKD patients present increased vascular stiffness and endothelial dysfunction, as reflected by low flow-mediated dilatation and elevated values of pulse wave velocity, carotid intima-media thickness and plasma homocysteine. The exact effects of early arterial stiffness on long-term outcomes remain to be elucidated.

The Effect of TISSEELTM on Confined Bowel Perforation: An Experimental Study.

OBJECTIVE: During the last decades, surgeons of several specialties presenting different levels of expertise in colon handling have been involved in laparoscopic procedures. The aim of the present experimental study was to investigate the feasibility of TISSEELTM versus the conventional suture placement technique on confined bowel lesions in rats. METHODS: Twenty-four Sprague-Dawley rats underwent confined bowel perforation and were divided into three groups: the SUTURE group (sutures were used), the SUTURE + TISSEELTM group (sutures and TISSEELTM were utilized), and the TISSEELTM group (only TISSEELTM was used). Blinded histopathologic analysis followed animal sacrifice. RESULTS: The median weight of the rats was 526 ± 50 g. A single animal had hematochezia on the first postoperative day. Cessation of bleeding at the perforation margin was indicated intraoperatively after TISSEELTM application. Animals in the TISSEELTM group presented less intraperitoneal adhesions and lower hemorrhagic infiltration compared to animals of the two other groups. In addition, animals in the TISSEELTM group showed thrombus formation at the bowel perforation site compared to animals of the two other groups (p = 0.042). Histopathologic analysis demonstrated reduced inflammatory reaction (p = 0.003), diminished fibrosis (p = 0.001), and better tissue regeneration (p = 0.000) in the TISSEELTM group compared to the other two groups. CONCLUSION: Application of TISSEELTM at the perforation site was associated with increased regeneration of the intestinal wall and less inflammatory and fibrotic reaction compared to suture placement. However, more experimental and clinical studies should be conducted before implementation in humans.

Efficacy and safety of colistin loading dose: a meta-analysis.

OBJECTIVES: Colistin represents a polypeptide used for the treatment of MDR microorganisms, although the optimal dosing strategy is under investigation. The present meta-analysis aims to determine whether the administration of a colistin loading dose in patients receiving high-dose maintenance regimens changes the rates of treatment success and the risk of nephrotoxicity. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from inception to 18 November 2019. Studies were considered eligible if they reported clinical outcomes among patients receiving high-dose colistin therapy with and without the administration of a loading dose. Meta-analysis was performed by fitting a random-effects model. RESULTS: Eight (three prospective and five retrospective cohort) studies were included, comprising 1115 patients. The administration of a colistin loading dose was associated with significantly higher microbiological [risk ratio (RR) = 1.23, 95% CI = 1.10-1.39] but not clinical (RR = 1.04, 95% CI = 0.87-1.24) success. No significant associations were calculated for nephrotoxicity (RR = 1.31, 95% CI = 0.90-1.91) and mortality (RR = 1.03, 95% CI = 0.82-1.29) risk. The results remained stable after adjustments for small sample size, credibility ceilings, publication bias and risk of bias. CONCLUSIONS: Observational evidence suggests that the administration of a colistin loading dose in patients receiving high maintenance dosage regimens is significantly associated with higher rates of microbiological response, but does not change clinical cure, mortality or nephrotoxicity risk. The dosing regimen that would provide the optimal balance between treatment efficacy and safety needs to be determined by future randomized controlled trials.

Predictors of tolvaptan short-term response in patients with refractory ascites: A meta-analysis.

BACKGROUND AND AIM: Tolvaptan represents an oral V2 -receptor antagonist, which has been suggested as a promising add-on diuretic treatment for refractory ascites. The present meta-analysis aims to accumulate current evidence and identify which clinical and laboratory factors are linked to short-term response to tolvaptan therapy. METHODS: Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception. All observational studies reporting the correlation of patients' characteristics with tolvaptan response were selected. RESULTS: Tolvaptan response was associated with significantly higher baseline body weight (mean difference: 4.59 kg, 95% confidence interval [CI]: [3.58, 5.61]), presence of hepatitis C (odds ratio: 1.59 95% CI: [1.18, 2.14]), lower blood urea nitrogen (BUN) (mean difference: -6.88 mg/dL, 95% CI: [-8.13, -5.63]), lower serum creatinine (mean difference: -0.17 mg/dL, 95% CI: [-0.30, -0.05]), lower C-reactive protein (mean difference: -1.43 mg/dL, 95% CI: [-2.52, -0.35]), and higher sodium levels (mean difference: 1.00 mEq/L, 95% CI: [0.45, 1.55]). The outcomes of bodyweight, hepatitis C, BUN, and C-reactive protein remain significant independently of response definition and risk of bias. CONCLUSIONS: The present findings suggest bodyweight, BUN, C-reactive protein, and hepatitis C as potential predictive factors of tolvaptan short-term response in patients with refractory ascites. Future studies are needed to introduce cut-off values and construct an optimal combined screening model.

Association of postoperative fluid overload with adverse outcomes after congenital heart surgery: a systematic review and dose-response meta-analysis.

BACKGROUND: Pediatric cardiac surgery is commonly associated with acute kidney injury (AKI) and significant fluid retention, which complicate postoperative management and lead to increased rates of morbidity. This meta-analysis aimed to accumulate current literature evidence and evaluate the correlation of fluid overload degree with adverse outcome in patients undergoing congenital heart surgery. METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov, and Google Scholar were systematically searched from inception. All studies reporting the effects of fluid overload on postoperative clinical outcomes were selected. A dose-response meta-analytic method using restricted cubic splines was implemented in R-3.6.1. RESULTS: Twelve studies were included, with a total of 3111 pediatric patients. Qualitative synthesis indicated that fluid overload was linked to significantly higher risk of mortality, AKI, prolonged hospital, and intensive care unit (ICU) stay, as well as with increased duration of mechanical ventilation, inotrope need, and infection rate. Meta-analysis demonstrated a linear correlation between fluid overload and the risk of mortality (χ2 = 6.22, p value = 0.01) and AKI (χ2 = 35.84, p value < 0.001), while a positive curvilinear relationship was estimated for the outcomes of hospital (χ2 = 18.84, p value = 0.0001) and ICU stay (χ2 = 63.69, p value = 0.0001). CONCLUSIONS: The present meta-analysis supports that postoperative fluid overload is significantly linked to elevated risk of prolonged hospital stay, AKI development, and mortality in pediatric patients undergoing cardiac surgery. These findings warrant replication by future prospective studies, which should define the optimal cutoff values and assess the effectiveness of therapeutic strategies to limit fluid overload in the postoperative setting.

Paraoxonase-1 and Symptomatic Status in Carotid Artery Disease.

BACKGROUND: Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL)-associated hydrolase that appears to have a protective action against atherosclerosis. The aim of our study is to identify whether PON-1 levels may be associated with the manifestation of symptoms in patients with carotid artery stenosis. METHODS: We studied all patients who underwent carotid endarterectomy in the Vascular Surgery Department of Laikon Hospital, Athens, Greece, from July 2012 to July 2014. Medical history was recorded and PON-1 glucose, total cholesterol, HDL cholesterol, low-density lipoprotein cholesterol, and triglycerides levels were measured. Variables were compared between symptomatic and asymptomatic patients. A receiver operating characteristic (ROC) curve was constructed to evaluate the accuracy of PON-1 to predict symptoms. RESULTS: A total of 74 patients were included, 41 were asymptomatic and the mean age was 68.5 years. The 2 groups appear to differ significantly with regards to the PON-1 levels, with the symptomatic group showing lower levels (5.3 ± 1.19 vs. 4.6 ± 1.36 ng/mL; P = 0.025). ROC analysis demonstrated an area under the curve of 0.654 (P = 0.023). CONCLUSIONS: Reduced PON-1 levels showed a significant association with symptomatic status, which was independent of other traditional cardiovascular factors. Further studies are required to prospectively assess the role of PON-1 in predicting cerebrovascular events in patients with carotid artery disease.

The Effect of Cyclosporine and the Consequences in Hepatic and Renal Function Following Ischemic Stroke in a Rats' Model.

INTRODUCTION: Recent studies have indicated that the damaging effects of stroke are not only limited to the brain. We sought to examine the changes of liver and renal enzymes in the acute phase of ischemic stroke and to investigate possible explanations and therapeutic options, concerning in particular the functional alterations of peripheral organs after administration of an anti-inflammatory agent. MATERIAL/METHODS: Twelve-week-old Wistar male rats were randomly divided into control and Cyclosporine groups (n = 10 each). Cyclosporine was given orally by gavage for 5 days prior to cerebral ischemia at a total volume of 15 mg/kg/day. All animals were subjected to 60 minutes focal ischemia by filament occlusion of the middle cerebral artery. Serum concentrations of Creatinine, Urea, SGOT, SGPT, and γGT were determined at the time before surgery and after 60 minutes brain ischemia. RESULTS: Comparing data of 2 time-points, in both groups the serum liver enzyme levels increased progressively during the ischemic period. The liver enzymes and Urea were significantly lower in the Cyclosporine group than in the control group and the levels of Creatinine were slightly higher in the Cyclosporine group, in both time-points. CONCLUSIONS: The detection of high liver enzyme serum levels in the acute phase of ischemic stroke implies the secondary effect of cerebral infraction on the peripheral organs and particularly on the liver function. Cyclosporine seems to exhibit a protective activity and to affect both liver and renal function after ischemic stroke.

Behavioral and Neurochemical Effects of Extra Virgin Olive Oil Total Phenolic Content and Sideritis Extract in Female Mice.

The aim of this study was to determine the cognitive and behavioral effects of extra virgin olive oil total phenolic content (TPC) and Sideritis (SID) extracts in female mice, and identify the associated neurochemical changes in the hippocampus and the prefrontal cortex. All animals received intraperitoneal low or high doses of TPC, SID or vehicle treatment for 7 days and were subjected to the Open Field (OF), Novel Object Recognition (NOR) and Tail Suspension Test (TST). The prefrontal cortex and hippocampus were dissected for analysis of neurotransmitters and aminoacids with high performance liquid chromatography with electrochemical detection (HPLC-ED). Both TPC doses enhanced vertical activity and center entries in the OF, which could indicate an anxiolytic-like effect. In addition, TPC enhanced non-spatial working memory and, in high doses, exerted antidepressant effects. On the other hand, high SID doses remarkably decreased the animals' overall activity. Locomotor and exploratory activities were closely associated with cortical increases in serotonin turnover induced by both treatments. Cognitive performance was linked to glutamate level changes. Furthermore, TPC reduced cortical taurine levels, while SID reduced cortical aspartate levels. TPC seems to have promising cognitive, anxiolytic and antidepressant effects, whereas SID has sedative effects in high doses. Both extracts act in the brain, but their specific actions and properties merit further exploration.

Allopurinol Administration for the Prevention of Contrast-Induced Nephropathy: A Network Meta-analysis With Trial Sequential Analysis.

Contrast-induced nephropathy represents a major source of morbidity in patients undergoing coronary angiography. Various preventive measures have been proposed, although the optimal one remains still unknown. The aim of the present meta-analysis is to accumulate current literature knowledge and evaluate the renoprotective effects of allopurinol administration before contrast medium exposure. To achieve this, MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception to November 8, 2018. Statistical meta-analysis was conducted with Review Manager 5.3, TSA 0.9.5.5 and R-3.4.3. Six studies were included with a total of 918 patients. Quantitative synthesis revealed that allopurinol leads to significantly reduced incidence of contrast-induced nephropathy compared with hydration alone [odds ratio: 0.29, 95% confidence interval: (0.09-0.90)]. Trial sequential analysis suggested that Z-curve crossed the O'Brien-Fleming significance boundaries, although required information size was not reached. Network meta-analysis indicated that allopurinol had the highest probability (81.2%) to rank as the most effective intervention compared with hydration and N-acetyl cysteine; however, significant overlap with the rest treatments was noted. In conclusion, the present meta-analysis suggests that allopurinol may represent a promising measure for the prevention of acute kidney injury after coronary angiography. Future large-scale randomized controlled trials should verify this finding, while combinations of allopurinol with other novel interventions should be evaluated to define the most effective strategy to be implemented in the clinical setting.

A single center's experience with total arterial revascularization and spiral aneurysmorrhaphy for ischemic cardiac disease.

The restoration of left ventricular (LV) geometry in combination with coronary artery bypass grafting for the treatment of ischemic cardiac disease remains controversial. We hereby present the experience of our center with total arterial myocardial revascularization (TAMR) and spiral aneurysmorrhaphy for ischemic heart disease. A retrospective analysis of 101 patients with advanced cardiovascular disease who underwent TAMR and spiral aneurysmorrhaphy was performed. Spiral aneurysmorrhaphy is a modification of the linear aneurysmorrhaphy and was applied to patients who had a LV aneurysm with a diameter of less than 5 cm. Peri-operative and in-hospital data were retrieved. The majority of the patients were male (87.13%) with a mean age of 63.1 years. Mean pre-operative ejection fraction (EF) was 35.7% ranging between 20 and 65%. An average of 3.23 grafts was required per patient. Early mortality was 6.93% (one intra-operative and six in-hospital deaths). Addition of concomitant valve surgery was associated with prolonged total operative, cardiopulmonary bypass and cross-clamp time (p < 0.001), increased need for blood (p = 0.012) and plasma (p = 0.038), longer intensive care unit (ICU) stay (p = 0.045) and higher rate of post-operative cerebrovascular accident (p = 0.011). Furthermore, patients with a pre-operative EF between 30 and 50% had a shorter ICU stay (p = 0.045) and LoS (p = 0.029) compared with patients with EF <30%. Early mortality and post-operative complication rates following this combined procedure are in consistency with the relevant available data suggesting its feasibility regardless of the EF or addition of concomitant surgeries. Data from the follow-up of these patients are required to examine the long-term efficacy of this surgical modality.

Pharmacological interventions for the prevention of acute kidney injury after pediatric cardiac surgery: a network meta-analysis.

BACKGROUND: Acute kidney injury constitutes a major complication of cardiac surgery in pediatric patients. The present meta-analysis aims to accumulate current literature and assess the efficacy of pharmacological interventions in preventing postoperative renal dysfunction after congenital heart surgery. METHODS: Literature search was conducted using Medline (1966-2018), Scopus (2004-2018), Cochrane Central Register of Controlled Trials CENTRAL (1999-2018), Clinicaltrials.gov (2008-2018), and Google Scholar (2004-2018) databases. Statistical analysis was performed with Review Manager 5.3 and R 3.4.3. RESULTS: Meta-analysis included 14 studies, with a total of 2,625 patients. AKI incidence was significantly lower in the dexmedetomidine (OR 0.49, 95% CI [0.28-0.87]) and acetaminophen (OR 0.43, 94% CI [0.28-0.67]) groups, while no difference was present in patients receiving corticosteroid (OR 1.16, 95% CI [0.69-1.95]), fenoldopam (OR 0.47, 95% CI [0.22-1.02]), or aminophylline (OR 0.98, 95% CI [0.29-3.34]). Network meta-analysis proposed that dexmedetomidine had the greatest probability (44.5%) to rank first, although significant overlap with the other treatments was observed. CONCLUSIONS: The present meta-analysis suggests that no firm evidence exists about the protective role of pharmacological interventions in the pediatric population. Future randomized controlled trials should clarify the effectiveness of dexmedetomidine and acetaminophen and indicate the optimal protocol to be applied, to protect renal function in the perioperative setting.

Expression of S100B Protein in Ischemia/Reperfusion-Induced Brain Injury After Cyclosporine Therapy: A Biochemical Serum Marker with Prognostic Value?

BACKGROUND Accumulating evidence has indicated that S100B protein may be involved in the pathophysiology of ischemia-reperfusion brain injury. Cyclosporine has been shown to have neuroprotective functions. This study investigated the effect of cyclosporine on S100B serum levels and the severity of brain tissue damage in a rat model of cerebral ischemia-reperfusion (I/R). MATERIAL AND METHODS Twelve-week-old Wistar male rats were randomly divided into Control I/R and Cyclosporine I/R groups (n=10 each). Cyclosporine was given orally by gavage for 5 days prior to cerebral I/R, at a total volume of 15 mg/kg/day. The Control group received an equal volume of saline. Body weight was measured and all animals were subjected to 60-min focal ischemia by filament occlusion of the middle cerebral artery. ELISA was used to assess the concentrations of serum S100B and development of brain infarct size and neurological outcomes were determined at 2 and 24 h after occlusion withdrawal. RESULTS Cyclosporine improved the neurological deficit score and decreased the cerebral infarct size and body weight. S100B serum levels were significantly elevated in Cyclosporine-treated rats compared with untreated Control rats during the reperfusion phase. Total infarct size was positively associated with S100B serum levels in the Control I/R group, but no significant correlation was observed in the Cyclosporine I/R group. CONCLUSIONS Cyclosporine seems to affect both ischemia-reperfusion brain tissue damage and S100B protein serum levels. S100B serum level appears to be a state marker for the severity of the cerebral ischemia-reperfusion, rather than a trait marker for Cyclosporine responsiveness.

The Role of Tolvaptan Administration After Cardiac Surgery: A Meta-Analysis.

OBJECTIVE: To evaluate the efficacy and safety of tolvaptan in fluid management after cardiac surgery compared with conventional diuretic treatment. DESIGN: Systematic review of the literature with meta-analyses. SETTING: The Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were searched from inception to July 30, 2018. PARTICIPANTS: The study comprised 759 patients undergoing cardiac surgery. INTERVENTIONS: Tolvaptan administration (n = 397) or standard diuretic therapy (n = 398). MEASUREMENTS AND MAIN RESULTS: Ten studies were included in the present meta-analysis. Tolvaptan administration was associated with a significantly faster return to preoperative body weight (mean difference [MD)] -1.48 d, 95% confidence interval [CI] -1.92 to 1.03), shorter duration of hospital stay (MD -2.58 d, 95% CI -5.09 to -0.07), lower incidence of acute kidney injury (odds ratio 0.34, 95% CI 0.16-0.69), and greater urine output (MD 0.47 L/d, 95% CI 0.25-0.69) and sodium levels (MD 2.85 mEq/L, 95% CI 1.90-3.80). No significant differences were present regarding duration of intensive care unit stay (MD -0.09 d, 95% CI -0.33 to 0.15), arrhythmia incidence (odds ratio 0.58, 95% CI 0.33-1.02), and serum creatinine values (MD -0.08 mg/dL, 95% CI -0.20 to 0.04). CONCLUSIONS: The outcomes of the present meta-analysis suggest the promising role of tolvaptan administration in the management of fluid retention in patients after cardiac surgery. Future large-scale clinical trials should be conducted to fully elucidate its efficacy and to assess the optimal treatment protocol to be applied in the clinical setting.

Expression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 in Human Epicardial and Intramyocardial Coronary Arteries of Male Patients Undergoing Coronary Artery Bypass Grafting.

OBJECTIVES: Atherosclerosis is almost absent in intramyocardial coronary arteries, while epicardial coronary arteries may show extensive occlusive disease. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression has been implicated in atherogenesis. We aimed to investigate differences in arterial wall LOX-1 expression between human epicardial and intramyocardial coronary arteries. METHODS: Epicardial and intramyocardial total artery wall specimens were obtained from 13 male patients (aged 61.9 ± 10.3 years) undergoing coronary artery bypass graft surgery due to 3-vessel coronary artery disease. LOX-1 expression was examined by reverse transcription-polymerase chain reaction. RESULTS: LOX-1 expression was significantly higher in the arterial wall of epicardial coronary arteries compared to intramyocardial coronary arteries. The LOX-1/GAPDH ratio was 0.48 ± 0.07 vs. 0.35 ± 0.03 (p < 0.001). CONCLUSIONS: Our findings may partially explain the atheroprotective effect of the intramyocardial course since arterial wall LOX-1 expression was lower in intramyocardial arteries and higher in epicardial coronary arteries.

Apolipoprotein J as a predictive biomarker for restenosis after carotid endarterectomy: a retrospective study.

Carotid endarterectomy (CEA) is an effective surgical option for stroke prophylaxis in most patients. Restenosis after CEA can lead to re-intervention and adverse events, but the factors predicting restenosis are poorly understood. Apolipoprotein J (ApoJ) is considered to be a novel predictive factor of vascular restenosis and is associated with a large number of processes related to atherosclerosis and cell-cycle phases. The aim of this study was to elucidate the predictive value of Apo J in internal carotid artery (ICA) restenosis following CEA. This retrospective study examined all prospectively collected data for patients who underwent CEA at our surgical department over a 2-year period. The serum ApoJ levels of 100 patients were examined; 56 patients who underwent CEA comprised the vascular group (VG), and 44 patients who underwent minor surgery comprised the control group (CG). ApoJ samples were obtained preoperatively, 24 h after the surgical procedure and at 1, 6 and 12 months thereafter during the follow-up. The preoperative difference in ApoJ levels between the CG and VG was statistically signifcant; the mean values were 39.11±14.16 and 83.03±35.35 µg/mL, respectively. In the VG, the serum ApoJ levels were 112.09±54.40, 71.20±23.70, 69.92±25.76 and 62.25±19.17 µg/mL at postoperative day 1 and at 1, 6 and 12 months post-operatively, respectively, while the ApoJ concentrations of patients in the CG remained unchanged. Further subdivision of the VG into patients with or without restenosis revealed that restenosis patients presented signifcantly higher mean ApoJ values than non-restenosis VG patients. In summary, ApoJ seems to be an important predictor for carotid restenosis at 6 and 12 months postoperatively.

Neutrophil gelatinase-associated lipocalin as predictor of acute kidney injury in neonates with perinatal asphyxia: a systematic review and meta-analysis.

There is growing evidence that neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury. The objective of this meta-analysis is to determine the accuracy of serum and urinary NGAL in the detection of acute kidney injury in neonates with perinatal asphyxia. Medline (1966-2018), Scopus (2004-2018), EMBASE (1980-2018), Clinicaltrials.gov (2008-2018), and Google Scholar (2004-2018) databases, along with the reference lists of the electronically retrieved articles, were systematically searched. Eleven studies were included, with a total number of 652 neonates. The summary sensitivity of serum NGAL was 0.818 (95% CI [0.668, 0.909]), the specificity 0.870 (95% CI [0.754, 0.936]), and the area under the curve 0.912. Regarding urinary NGAL, pooled sensitivity was calculated at 0.897 (95% CI [0.829, 0.940]), specificity at 0.729 (95% CI [0.561, 0.850]), and area under the curve at 0.899. CONCLUSION: Serum and urinary NGAL represent candidate biomarkers with high performance in the prediction of acute kidney injury in newborns with perinatal asphyxia. Before NGAL can be widely used in clinical practice, future large prospective studies are needed to define the optimal cutoffs and accurately determine which levels are suggestive of post-asphyxial acute kidney injury. What is Known: • Acute kidney injury is a major cause of morbidity and mortality in perinatal asphyxia. • Current markers are insufficient in predicting post-asphyxial acute kidney injury. What is New: • Area under the curve for serum and urinary neutrophil gelatinase-associated lipocalin is 0.818 and 0.899, respectively. • Neutrophil gelatinase-associated lipocalin is a useful marker for detecting asphyxiated neonates at risk of developing acute kidney injury.

The diagnostic accuracy of presepsin in neonatal sepsis: a meta-analysis.

There is growing evidence that presepsin is a promising biomarker in the diagnosis of sepsis in adults. The objective of our study is to investigate current evidence related to the diagnostic accuracy of presepsin in neonatal sepsis. To accomplish this, we searched the Medline (1966-2017), Scopus (2004-2017), Clinicaltrials.gov (2008-2017), EMBASE (1980-2017), Cochrane Central Register of Controlled Trials CENTRAL (1999-2017), and Google Scholar (2004-2017) databases. Eleven studies were included in the present meta-analysis, with a total number of 783 neonates. The pooled sensitivity of serum presepsin for the prediction of neonatal sepsis was 0.91 (95% CI [0.87-0.93]) and the pooled specificity was 0.91 (95% CI [0.88-0.94]). The diagnostic odds ratio was 170.28 (95% CI [51.13-567.11]) and the area under the curve (AUC) was 0.9751 (SE 0.0117). Head-to-head comparison with AUC values of C-reactive protein (0.9748 vs. 0.8580) and procalcitonin (0.9596 vs. 0.7831) revealed that presepsin was more sensitive in detecting neonatal sepsis. CONCLUSION: Current evidence support the use of presepsin in the early neonatal period in high-risk populations as its diagnostic accuracy seems to be high in detecting neonatal sepsis. What is known: • Neonatal sepsis is a leading cause of morbidity and mortality. • Current laboratory tests cannot accurately discriminate endangered neonates. What is new: • The diagnostic odds ratio of presepsin is 170.28 and the area under the curve is 0.9751. • According to our meta-analysis, presepsin is a useful protein that may help clinicians identify neonates at risk.

The impact of fast track protocols in upper gastrointestinal surgery: A meta-analysis of observational studies.

BACKGROUND: Fast track surgery has been implemented in colorectal procedures during the last decade and is accompanied by significant improvement in patient outcomes during the early postoperative period. However, to date, its adoption in upper gastrointestinal surgery remains a matter of debate. In this context, we aimed to summarize the existing evidence in the international literature. MATERIALS AND METHODS: We searched Medline, Scopus, ClinicalTrials.gov and Cochrane Central Register databases for published randomized controlled trials. The meta-analysis was performed with the RevMan 5.3.5 software. MAIN FINDINGS: Thirty studies were finally included in the present meta-analysis. The post-operative morbidity was not influenced by the implementation of fast track surgery (FTS) (OR 0.84, 95% CI 0.64-1.09). However, in cases treated with laparoscopic surgery fast track surgery seemed to reduce morbidity by 50% (p = .006). The overall mortality of patients was low in the majority of included studies and was not influenced by fast track surgery (OR 1.12, 95% CI 0.50-2.52). The duration of postoperative hospitalization was significantly reduced with the adoption of FTS (MD -2.24, 95% CI -2.63 to -1.85 days). Concurrently, the overall cost was significantly reduced in cases treated with FTS (MD -982.30, 95% CI -1367.68 to -596.91 U.S dollars). CONCLUSION: According to the findings of our meta-analysis suggest that FTS seems to be safe in patients undergoing upper gastrointestinal surgery and reduce both the days of postoperative hospitalization and the overall cost. This observation should be taken into account in future recommendations to enhance the implementation of FTS protocols in current clinical practice.

The diagnostic efficacy of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in ovarian cancer.

BACKGROUND: Platelet-to-lymphocyte (PLR) and Neutrophil-to-Lymphocyte (NLR) ratios have been extensively investigated in cancer. However, to date, actual guidelines concerning ovarian cancer are missing. The purpose of the present systematic review is to summarize the available evidence. METHODS: We systematically searched Medline (1966-2016), Scopus (2004-2016), ClinicalTrials.gov (2008-2016), and Cochrane Central Register of Controlled Trials CENTRAL (1999-2016) databases together with reference lists from included studies. RESULTS: Eighteen studies were included in the present systematic review that involved 3453 patients. According to the current data, both PLR and NLR values in ovarian cancer patients seem to deviate from healthy controls. Furthermore, they may also be indicative of the stage of the disease and of the response to chemotherapy. Nevertheless, their diagnostic accuracy remains limited as their sensitivity and specificity are moderate (detects 55-80% of ovarian cancer women). CONCLUSION: According to the findings of our study, both PLR and NLR seem to be promising screening and prognostic factors of epithelial ovarian cancer. The actual diagnostic cut-off values remain, however, undefined until now. Despite their limited sensitivity and specificity, they might be useful in the future as adjunct biomarkers for the detection and surveillance of the disease.